Bio 2A03 Intro Lecture

Physiology

Explains the physical and chemical factors for the origin and progression of life

Environmental Physiology

How physiological systems respond and adapt to changing environments

Comparative Physiology

Diversity of how physiology works in various organisms

Medical Physiology or Pathophysiolgy

Abnormal physiology as a result of disease

Hierarchal Organization of the body

Cells tissues Functional units organs organ systems organism
Cells

Muscle Cells
o Specialized for contraction for movement
o Subtypes include skeletal (limbs and skin), cardiac (heart), and smooth (blood
vessels)
Nerve Cells
o Generate and propagate electrical signals
Connective Tissue Cells
o Provide physical support to other structures
Epithelial Cells
o Function as barriers often involved in secretion and absorption

Tissues

Collection of similar cells performing similar functions

Functional Units

Subunits of an organ

Organs

Intact structure composed of 2 or more tissues

Organ systems

Collection of organs that function together

Homeostasis

The internal environment is very stable even when the external environment changes

Extracellular Fluid (ECF)

Is rapidly transported by the circulation and mixes between blood and tissues by moving
across capillary walls
It bathes the tissues and creates the internal environment of the body

Negative Feedback

Regulated variable changes (ex. body temperature) and the change is detected and
regulatory system responds to oppose the change and buffer the internal environment
Components of a negative feedback loop include:
1. Sensor
2. Integrating centre
3. Effector

Thermoregulation and Negative Feedback

1) The regulated variable changes (temperature) which is detected by the sensors

(thermoreceptors)
2) The thermoreceptors then signal the brain (integrating centre) which signals different
effectors (blood vessels, sweat glands etc.)
3) The effectors then cause compensatory responses to return the internal environment back
to the set point

Bio 2A03 Lecture 1

Carbohydrates

Monosaccharides (glucose)
Disaccharides (sucrose)
Polysaccharides (glycogen)

Nucleotides

Lipids

DNA: genetic information

RNA: protein translation
ATP, ADP - Energy transfer

Triglycerides: glycerol + 3 fatty acids

Phospholipids
o Hydrophobic tail (2 fatty acid chains)
o Hydrophilic head (phosphate containing group)
Steroids
o Ex cholesterol
o Structure involves 4 rings (3 hexagons + 1 pentagon)
Eicosanoids

Proteins

Amino acid polymers

o Made up of a central carbon attached to an amino group, a carboxyl group, and a
residual R group
Peptide bonds link amino acids to create polypeptides
o Via condensation reaction
Protein structure depends on its structure (primary, secondary, tertiary, quaternary)

Protein Function is Controlled by:

1) Protein amount
a. Is controlled by protein synthesis and degradation
2) Allosteric Modifiers
a. bind non-covalently to regulatory sites on the protein
b. affect protein function by changing its structure
3) Covalent modulation
a. Phosphorylation by kinases and dephosphorylation by phosphatases
b. Affect protein function by changing its structure
Metabolism

Sum of all chemical reactions in the cell

Types of Reactions

Hydrolysis or condensation (AB + H2O AOH + HB)

Phosphorylation or dephosphorylation (ADP + Pi ATP + H2O)
Oxidation or reduction (H2 2H+ + 2e-)

Principles of Chemical Equilibrium and Law of Mass Action

Dictate the direction of reversible reactions and the eventual concentrations of reactants
and products

Enzymes

Enzymes are protein catalysts that increase the rate of biochemical reactions by reducing
the activation energy (usually a factor of 105 to 1017)
Activation energy is the energy required to go through the transition state of a reaction
The rate of the chemical reaction is dictated by:
o Height of the activation barrier
o Temperature
o Concentration of reactants and products
Enzymes do not get altered by the chemical reaction
The reactant bound to the enzyme is called a substrate
o Enzymes will only bind to specific substrates (specificity)

Both the substrate and the product can bind to the active site of the enzyme allowing the
reaction to proceed in reverse

Rates of Enzyme Reactions

Rates of enzyme reactions (V) depend on:

Concentration of substrates [S] and products [P]

o The higher the concentration, the more enzyme-substrate complexes can be
formed and the rate of the reaction will increase

o
Enzymatic activity
o The rate at which the enzyme catalyzes the reaction (kcat)
Enzyme concentrations [E]
o The higher the concentration, the higher the rate
o Vmax = kcat[E]

o
The affinity of the enzyme for its substrate
o The higher the affinity, the lower the Km
o Vmax does not change when affinity changes

Temperature, pH and other physical factors

Allosteric Modulation

Regulatory site of the enzyme is different from the active site (the site at which the
substrate binds)

In order to activate or inactivate the enzyme activity, a modulator needs to bind to the
regulatory site
This bond changes the enzyme shape allowing its active site to either be activated or
inactivated

Covalent modification

Phosphorylation or dephosphorylation affects the activity of an enzyme

Energy Metabolism

Encompasses the pathways needed to convert the energy in food to ATP to power cellular
functions
Two processes involved in ATP production and ATP homeostasis are:
o Substrate-level phosphorylation
occurs in the absence of O2
ex. anaerobic glycolysis
o Oxidative phosphorylation
Depends on the supply of O2
Occurs in the mitochondria
Primary mode of ATP production

Glucose Oxidation

Involves the breakdown of glucose to produce energy

Processes include glycolysis linking step Krebs cycle oxidative phosphorylation
Complete oxidation of glucose yields ~34 ATP most of which come from oxidative
phosphorylation
In the absence of oxygen, glycolysis is followed by lactate production yielding only 2
ATP

Glycolysis and Linking step

Breaks down glucose and produces 2 molecules of pyruvate and occurs in the cytosol
Pyruvate enters the mitochondria where the linking step converts it to acetyl-coA
Result is acetyl-coA for the Krebs cycle, NADH for oxidative phosphorylation and ATP

Krebs Cycle (tricarboxylic acid cycle)

Acetyl-coA enters the Krebs cycle in the mitochondrial matrix

Results in:
o ATP
o Reducing equivalent (NADH and FADH2) which enter oxidative phosphorylation
o They are called reducing equivalents because they act as temporary electron
carriers

Oxidative Phosphorylation

NADH and FADH2 donate their electrons to electron acceptors in the ETC and are
oxidized to NAD+ and FAD
Electrons move through the ETC until they reduce O2 and H2O
The energy released during this process is used to pump protons out of the mitochondrial
matrix

Protons then move back into the matrix (down their concentration gradient) through the
ATP synthase to make ATP
Oxidative phosphorylation can metabolize carbohydrates, lipids, and proteins to make
ATP
o Healthy cells usually break down carbs and fats but in times of starvation or tissue
breakdown, they metabolize proteins

Bio 2A03 Lecture 2

Membranes

Are selective barriers

Transport proteins on the membranes dictate movement in or out of the cells or organelles
Membrane proteins can also be involved in detecting chemical messengers at the cell
surface
Transport across membranes is very important for maintaining intracellular and
extracellular homeostasis
Intracellular fluid mostly contains K+ while extracellular fluid mostly contains (Na+)

Transport Mechanisms across Membranes

Passive Transport

Do not require ATP

Simple diffusion through lipid bilayer
Carrier-mediated diffusion through transmembrane protein channels

Active Transport

Require ATP and transport proteins

Primary active transport
Secondary active transport

Simple Diffusion

Movement of molecules from one location to another due to random thermal motion
Concentration gradient provides a chemical driving force for diffusion
o Solute moves from regions of high concentration to lower concentration
(downhill) until uniformly distributed
Flux is the rate of solute movement per unit time
o Molecules move in all directions but the net flux ( = flux 1 flux 2) is in the
direction of lower concentration

Diffusive equilibrium
o Net flux is 0
o When movement in one direction is equal to the movement in the opposite
direction
Diffusion is only good for shorter distances because the rate of diffusion slows down with
increasing distance
o Diffusion times (t) are proportional to distance squared (x2)
Net diffusion flux rate is proportional to the concentration difference between two
locations (C)
o The higher the concentration gradient, the higher the flux rate
o Net diffusion flux rate across a membrane is also proportional to membrane
permeability
o Permeability describes the ease of passage of a substance across a membrane

Ficks Law

Net diffusion flux rate across a membrane (F) based on chemical driving forces

The permeability constant (KP) is affected by:

o Temperature
as temperature increases, diffusion increases
o Solubility in lipid bilayers (non-polar vs. polar)
O2, CO2, fatty acids and steroid hormones are non-polar and diffuse more
rapidly than charged/polar solutes
o Size and shape of the molecule
Smaller molecules diffuse faster

Electrical Driving Force

Net diffusion flux rate of a charged solute (ion) across a membrane depends on the
internal and external electrical charges
There is a membrane potential (voltage, Vm) across the cell membrane due to
maintenance of distinct ionic composition inside and outside cells
o Typically -50 to -100 mV inside
o Outside is positive
Magnitude of Vm and the valency (charge) of the ion dictates the electrical driving force
Electrical driving force of a positive ion increases with increasing Vm

Electrochemical driving force

The combined effect of chemical and electoral forces dictates the diffusion of ions across
the membrane
The equilibrium potential (Ek) for an ion is the Vm at which the electrical and chemical
forces are equal
If the electrical driving force and the chemical driving forces are equal, then
electrochemical driving force is 0
When Vm is not equal to the Ek for a particular ion, there is a electrochemical driving
force tending to cause diffusion

Nernst Equation

The equilibrium potential differs between ions, depending on:

o An ions concentration inside and outside the cell
o Its valency (charge)
Ek can be calculated with the Nernst equation

Carrier-Mediated Diffusion (Facilitated Diffusion)

Occurs through protein channel/carriers, often for substances with otherwise low
membrane permeability
Channels are selective for particular ion (based on size, charge, etc.) and can be regulated
to open/close
The rate of facilitated diffusion is dictated by the same factors as simple diffusion except
that the rate is saturable
o The rate reaches its maximum when a channels maximum capacity is reached

Primary Active Transport

Membrane proteins that carry out primary active transport must hydrolyze ATP directly to
harness energy, so they can transport ions against their electrochemical gradients
Membrane proteins involved are called ATPases and/or ion pumps
o Ex. Na+/K+ -ATPase
Primary active transport must constantly counteract passive ion leaks across membranes
to maintain the distinct ionic composition in the intracellular and extracellular
environments

Leak is regulated by channels in a manner that differs between ions

Ion pumping is one of the most ATP demanding processes in the cells

Na+ from ICF fills in the binding sites of the protein

When ATP is hydrolyzed to form ADP, the protein channel opens outwards releasing the
Na+ ions into the ECF
K+ ions from the ECF enter the binding sites of the protein
When the phosphate is removed from the protein, the channel opens inwards releasing the
K+ ions into the ECF

Secondary Active Transport

Is carried out by proteins that do not themselves hydrolyze ATP, but it relies upon ionic
gradients established by other ATPases
o For ex: many transporters use [Na+] gradient established by Na+/K+-ATPase to
co transport other substances against their electrochemical gradient

o
Transporters involved in secondary active transport can be co-transporters or countertransporters (aka antiporters)

o
Osmosis

Passive diffusion of water across membranes

Membranes are permeable to water due to its small size, even though it is a polar
molecule
Water diffusion occurs down its concentration gradient
o Water concentration depends on the osmolarity of the solution
o Osmolarity: total solute particle concentration
o The higher the osmolarity, the lower the water concentration
Osmosis occurs in the direction of higher omsolarity
1 mole of dissolved particles = 1 osmolar solution
o Ex. 1M of glucose in solution = 1 osmole
o Ex. 1M of NaCl = 2 osmoles becauses it ionizes in solution to Na+ and Cl-

Tonicity

Function of the concentration of non-permeating solutes (those unable to cross the cell
membrane) outside relative to inside of the cell

Osmosis relates to total solute concentration while tonicity relates to how a cell functions
in a concentration
Isotonic
o Equal concentrations of non-permeating solute outside and inside the cell
o No change in cell volume
Hypertonic
o Higher concentration of non-permeating solute outside than inside the cell
o the cell shrinks as water moves out
Hypotonic
o Lower concentration of non-permeating solute outside than inside the cell
o The cell swells as water moves in
When a cell containing non-permeating solute is placed in a solution of equal
concentration of permeating solute, the permeating solute will enter the cell, diffusing
down its concentration gradient but the non-permeating solute will not
o This will create the osmotic driving force for water diffusion into the cell creating
a hypotonic solution

Compartmentalized Membrane Transport

Is vesicular transport (in an intracellular compartment) needed to transport

macromolecules across the plasma membrane
Endocytosis
o Movement of molecules into the cell with the formation of endosomes
o Phagocytosis (cell eating)
Cell extends membrane around particle to create a phagosome
o Pinocytosis (cell drinking)
Plasma membrane indents to form endosome around solutes

Exocytosis
o Movement of molecules out of the cell to the ECF using secretory vesicles
Ex. neurotransmitter release at synapses

Epithelial Transport

Transport of materials across entire cell layers

The epithelial cells have 2 surfaces
o Apical membrane faces external environment (lumen)
o Basolateral membrane faces the internal environment (interstitial fluid)
Tight junctions
o Form a selective barrier that limits movement between cells
o Solutes cannot pass between the cells that are connected by tight junctions

Epithelial Ion Transport

Example: Epithelial transport of Na+ ions and glucose

Na+ and glucose enter the cell by a co-transporter across the apical membrane (secondary
transport), powered by the outward transport of Na+ across the basolateral membrane by
the Na+/K+ pump (primary active transport)
Buildup of intracellular glucose creates a driving force for its diffusion from the cell
through basolateral channels

Epithelial Water Transport

Movement of water across an epithelial cell layer occurs by osmosis and depends upon
the active transport of solutes to create an osmotic gradient

Here, the pumps concentrate the non-permeating solutes in the interstitial fluid which
creates a gradient that allows water to diffuse across the epithelial cells down the osmotic
gradient

Transcytosis

Movement of macromolecules across an epithelial cell layer by vesicular transport

It is a combination of endocytosis and exocytosis across a cell

Bio 2A03 Lecture 3

Intercellular Chemical Messengers

Perform cell to cell communication

Hormones
o Secreted by endocrine cells
o They reach target cells via blood
o They are slow acting because blood takes time to circulate
o Although they have a slow onset, they are longer lasting than neural signals
o Eg. Insulin, glucose
Neurotransmitters
o Secreted by nerve cells at synapse with target cell
o They are fast acting because the secretory cells are very close to target cells
o Eg. Acetylcholine, adrenaline
Autocrine/Paracrine agents
o Local homeostatic response
o Reach target cells by diffusion
o Autocrine when the secretory and target cells are the same cell
o Paracrine when the secretory and target cells are neighboring cells
o Eg. Nitric oxide

Signal Transduction Pathways

Detect intercellular messengers and convert them into an intracellular response

They have 4 features:
o Specificity
The signal molecule fits in its receptors while other molecules do not
o Amplification
1 receptor binding can lead to several million intracellular signals
o Desensitization/Adaptation
Feedback can shut off the receptor
o Integration
The intracellular signal can be the result of integration of multiple receptor
inputs (i.e. the overall response is a combination of individual responses
from different receptors)

Receptors

The number of receptors bound dictates the magnitude of the cells response. It is
controlled by:
o Messengers concentration
o Number of receptors present
o Receptors affinity for messenger
An increase in the number of receptors (R) increases the number bound by messenger
o Vmax increases but Km doesnt change

o
An increase in the affinity for messengers can increase the number of bound receptors at
the same messenger concentration
o Km decreases but Vmax remains the same

o
Intracellular Receptors

Bind to lipophilic messengers (ex. steroid hormones)

Act as transcription factors to alter gene transcription and the translation of a specific
protein
Receptors can be located in the cytosol or in the nucleus

Membrane-bound receptors

Bind to lipophobic messengers

3 main types include: channel linked, enzyme linked, and G-protein-linked receptors
Channel linked
o Channel acts as a receptor called ligand-gated channel
o Respond very quickly to messenger binding
o A change in the electrical properties of the ell can initiate the cellular response to
messenger binding
o Ex. messenger binding opens ion channel

o
Enzyme-linked
o Ligand-binding domain on extracellular surface and an enzyme active site on the
intracellular surface
o Messenger binding alters the activity of the intracellular enzyme domain of the
receptor
o Eg. Tyrosine kinase receptors phosphorylate proteins to induce cellular responses

o
G-protein-linked
o Messenger activates membrane proteins called G-proteins that begin a signaling
cascade
o Some G-protein-linked receptors regulate ion channels
These ion channels respond more slowly to messenger binding, due to the
time required for the -subunit to be activate and bind to the ion channel
In this case, the channel itself does not act as the receptor
o Other G-protein-linked receptors regulate enzymes that produce secondary
messengers (eg. Adenylyl cyclase to produce cAMP)
o G-proteins can be stimulatory (Gs) or inhibitory (Gi)

Messengers

Primary (first) Messenger: intercellular chemical messengers that reach the cell surface
o Ex. hormones
Secondary (second) messengers: intracellular messengers produced by the binding of the
first messengers
o They act as chemical relays from the plasma membrane to the biochemical
machinery inside the cell
o Ex. G-protein receptor regulating the phosphatidylunositol (PIP2) second
messenger system

o
Second Messenger Amplification

Second messenger systems can amplify the signal from the first messenger
Ex. G-protein receptor regulating cAMP production by adenylate cyclase

Bio 2A03 Lecture 4

Endocrine Glands

Secrete hormones directly into ECF

Opposite to exocrine glands because these secrete products to the outside
Endocrine system and nervous system have overlapping features:
o Endocrine glands are often under nervous control
o Some hormones are released from neurons (neurohormones) rather than endocrine
glands
o Many substances can act as hormones in the circulation or as neurotransmitters in
the brain
o The hypothalamus-pituitary complex is the neuro-endocrine interface

3 Classes of Hormones

Amines
o Derived from amino acids tyrosine and tryptophan
Protein and Polypeptide Hormones
Steroid Hormones
o Derived from cholesterol

Amines

Catecholamines
o All are derived from tyrosine
o Dopamine
Neurotransmitter and hypothalamic hormone that inhibits prolactin
secretion
o Norepinephrine and epinephrine
are neurotransmitter and adrenomedullary hormones
Serotonin

o Neurotransmitter and hormone derived from tryptophan that is involved in sleep,

suppressing stress responses, and mood
Thyroid hormones
o Thyroxine (T4) and triodo-thyronine (T3)
o Hormones derived from tyrosine that regulates metabolic rate and growth

Catecholamine synthesis

All chatecholamines are derived from tyrosine

Each successive enzymatic step converts tyrosine to a different catecholamine
The particular catecholamine secreted by an endocrine organ depends on the presence
and activity of appropriate enzymes
Ex. Tyrosine L-dopa dopamine norepinephrine epinephrine
o Tyrosine cannot just jump straight to norepinephrine. It needs to do it in
successive steps

o
Protein and Polypeptide hormones

Growth Hormone
o Hormone released by the anterior pituitary
Atrial natriuretic peptide

o Hormone released by the heart to regulate sodium reabsorption by the kidneys

They are synthesized by protelytic cleavage of a prehormone in the ER, and the resulting
prohormones are then further cleaved to hormones during packaging into vesicles by
Golgi apparatus
o Hormones and prohormones are released by Ca2+-initiated exocytosis

o
Steroid Hormones

all are derivatives of cholesterol

o the ring structure of cholesterol is preserved so all steroid hormones are lipophilic
(cant be stored in vesicles)
Are produced by:
o Gonads
o Placenta (sex hormones)
o Adrenal cortex
Mineralocorticoids (aldosterone)
Involved in ion balance
Glucocorticoids (cortisol)
Involved in glucose metabolism and stress response
sex hormones (testosterone and estrogen)

Hydrophilic Hormones

peptides, proteins and some amines

cannot diffuse across membranes so they are secreted by exocytosis and bind to
cell surface receptors
Hydrophobic Hormones

steroids and some amines

can diffuse through membranes and bind to intracellular receptors but require carrier
proteins for transport in the blood

Effects on Target Cells

Direct
o Activate or inhibit some function of the cell
Indirect
o Permissive effects
o Alter the sensitivity of the target cell to other hormones by up or downregulating
their receptors

Controls on Hormone Secretion

Hormone secretion is controlled by:

Neural controls
o Direct from the CNS (hypothalamic hormones) or via autonomic nervous system
Another hormone (trophic hormone)
o Release of one hormone affects release of other hormones
Changes in a homeostatically regulated variable
o Ex. changes in blood glucose level cause release of insulin and glucagon

Hypothalamus-Pituitary Complex

Located in the brain

Hypothalamus
o Is composed of neural tissue
o Axons from hypothalamus terminate in the posterior pituitary where they release
neurohormones into the blood
Posterior pituitary
o Is composed of neural tissue
o Also called neurohypophysis
Anterior Pituitary
o Is composed of epithelial tissue
o Also called adenohypophysis

o Neurosecretory cells in the hypothalamus release trophic hormones into

hypothalamus-pituitary portal system
o Trophic hormones stimulate release of different hormones from the anterior
pituitary
Posterior Pituitary Hormones

Octapeptides
o Peptides composed of 8 amino acid
o Synthesized in soma of giant neurons of the hypothalamus transported down
axons stored in synaptic vesicles in terminal knobs at blood vessels in
posterior pituitary released when action potentials reach axon terminals
Antidiuretic Hormone (ADH)
o Ex. Vasopressin
o Released from neurons from paraventricular nucleus of hypothalamus
o Released in response to:
low blood volume
low blood pressure
high ECF osmotic pressure (detected by hypothalamus osmoreceptors)
o promotes water retention at kidney and raises blood pressure by vasoconstricting
systemic arterioles
Oxytocin
o Released from neurons from supra-optic nucleus of hypothalamus
o Regulates reproductive functions such as
Uterine contractions
Milk ejection

Hypothalamic - Anterior Pituitary Hormones

There are 7 different hypothalamic tropic hormones

o When released, they are at very high local concentrations
o They are released like neurotransmitters by action potentials
o All are short polypeptides except dopamine
o Prolactin Releasing Hormone (PRH) stimulates prolactin release
o Prolactin Inhibiting Hormone (PIH) inhibits prolactin release
o Thyrotropin Releasing Hormone (TRH) stimulates TSH release
o Corticotropin Releasing Hormone (CRH) stimulates ACTH release
o Growth Hormone Releasing Hormone (GHRH) stimulates GH release
o Growth Hormone Inhibiting Hormone (GHIH) inhibits GH release
o Gonadotropin Releasing Hormone (GnRH) stimulates LH and FSH release
There are at least 6 anterior pituitary hormones that are released into general circulation
o Prolactin (PL)
General reproductive functions

Promotes breast development and milk production

Suppresses ovulation during breast-feeding
Thyroid Stimulating Hormone (TSH)
Thyroid growth
Stimulates T3 and T4 hormone release
Adrenocorticotrophic Hormone (ACTH)
Promotes glucocorticoid release from the adrenal cortex in response to
stress
Growth Hormone (GH)
Promotes IGF-1 release to promote growth
Alters protein synthesis
Alters carbohydrate and lipid metabolism throughout body
Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)
Stimulates sex hormone production
Promotes ovulation and development of reproductive tissue

Gigantism and Acromegaly

Pituitary Adenomas
o Abnormal growth of endocrine cells within the pituitary gland
o Tumor cells that increase secretion of hormones are functional adenomas
30% of functional adenomas secrete growth hormone

Negative Feedback Loops

Short loop
o Occurs when anterior pituitary tropic hormone inhibits the release of
hypothalamic tropic hormone
Long loop
o Occurs when the target hormone inhibits the release of a tropic hormone

Bio 2A03 Lecture 5

Adrenal Cortex

Mineralocorticoid hormones
o Regulate ion homeostasis
o Ex. aldoestrone
Glucocorticoid hormones
o Regulate the stress response and metabolic homeostasis
o Ex. cortisol
In response to stress, cortisol triggers energy metabolization
It stimulates production of gluconeogenesis, plasma glucose, lipolysis,
proteolysis

Adrenal Medulla

Contains chromaffin cells that secrete catecholamines when the sympathetic nervous
system is activated

Beta Blockers

Are antagonists that block the beta receptors to which first messengers bind
Ex. propanolol

Pancreas

Secretes glucagon and insulin which regulate glucose homeostasis

Glucagon
o Secreted by alpha cells
o Stimulates glucose release into the blood in response to a fall in blood glucose
concentration
Insulin
o Secreted by beta cells
o Promotes glucose uptake from the blood in response to a rise in blood glucose
concentration

Diabetes

Type 1 Diabetes
o Glucose production fails
o Caused by auto-immune destruction of beta cells
o Target cells are under-stimulated
Type 2 Diabetes
o Occurs when target cells cannot detect insulin (insulin resistance)
o Stimulation by insulin does not cause glucose uptake

Hormone Interactions

Antagonism
o Hormones with opposing effects
o Ex. insulin and glucose
o Results in fine tuned regulation
o Effects in the same direction can be additive or synergistic (equal to or greater
than the sum of individual effects)
Permissive
o Hormones are required to for another hormones to work
o Ex. thyroid hormones are needed to synthesize epinephrine receptors in some
cells

Thyroid Gland

Secretes T3 and T4 in response to TSH from the anterior pituitary

o Regulates metabolic rate
Secretes calcitonin
o Regulates blood calcium levels
Follicles in the thyroid gland contain thyroglobulin (the precursor to thyroid hormones)
When TSH is released into the blood from the pituitary, receptors on follicular cells are
stimulated and thyroid hormones are released
o They are permissive hormones

Parathyroid Gland

Secretes parathyroid hormone

o Regulates metabolic rate
o Secretes calcitonin

Pineal Gland

Located in the brain but is composed of epithelial tissue

Receives signals from the CNS
Secretes melatonin which is important for establishing circadian rhythms (sleep cycles)

Gonads

Secrete sex hormones

o Males androgens (testosterone and androstenedione)
o Females Estrogens (estradiol and progesterone)

Placenta

Secretes sex hormones in pregnant females

Secondary Endocrine Organs

Heart

Atrial Natriuretic Peptide

o Responds to heart stretch
o Regulates Na+ reabsorption by the kidneys

Liver

Kidney

Insulin-like Growth Factors (IGF)

o Released in response to growth hormone
o Stimulates growth

Eryhtropoietin
o Released in response to a change in kidneys demand for oxygen
o Causes RBC production

Bio 2A03 Lecture 6

Types of Cells in the Nervous System

Structure of a Typical Neuron

Dendrites
o Numerous small branches
o RECEIVE incoming information from other neurons via synapses
o Graded potentials occur here
Cell body (soma)
o Contains nucleus and most organelles
o Metabolic functions and synthesis of biomolecules occur here
Axon hillock
o Axons originate here
o Are trigger zones where action potentials are initiated as a result of summation of
graded potentials
Axon

o Thick process that rapidly conducts outgoing information coded as action

potentials
o RECEIVE information
Synapse
o Area where a presynaptic neuron makes a specialized contact and communicates
with post synaptic neuron
Terminal
o Presynaptic compartment that sends information to other neurons or effector cells

3 Structural Classes of Neurons

Bipolar
o One axon and a dendrite originating from a cell body in the middle
Pseudo-unipolar
o One peripheral axon and a central axon that look like they are continuous but
connect to a cell body in the middle
Multipolar
o Lots of dendrites projecting from the cell body

Signal always travels in one direction only

Axonal Transport

Axons range in length from 1mm to 1 m

Axons help transport substances produced in the cell body
Diffusion is too slow, so specialized mechanisms that involve vesicles (axonal transport)
are required
Anterograde transport

o From cell body to axon terminal

Retrograde transport
o From axon terminal to cell body

Organization of Nervous System

Afferent division
o Conducts information from external and internal sensors to the CNS for
integration
Efferent Division
o Conducts information from the CNS to effector organs

3 Functional Classes of Neurons

Afferent Neurons
o Pseudo-unipolar neurons with peripheral axon endings terminating in the
peripheral organ and central axon terminating in the CNS
o Sensory receptors
Sense external environment
Include somatosensory system (skin, muscles, joints) and special senses
(hearing, smell, taste)
o Visceral Receptors
Sense internal environment
Eg. Blood pressure (baroreceptors)
Efferent Neurons
o Multipolar neuron with cell body and dendrites in the CNS
o Enters PNS as it travels to the effector organ
o Efferent motor neurons innervate skeletal muscle

o Efferent neurons of the autonomic nervous system innervate many organs and
tissues in the body
Interneurons
o 99% of all neurons in the body
o All are in the CNS
o Perform all the functions of the CNS including
Processing sensory information from the afferent neurons
Sending command to effector neurons

Classes of Glial Cells (Glia)

Glial cells in CNS Oligodendrocytes

Glial cells in PNS Schwann cells
Form an insulating wrap of myelin around the axons of neurons
o Myelin consists of concentric layers of plasma membranes of either
Oligodendrocytes or Schwann cells
Substantially reduce the leakage of ions across the membrane
o Provides electrical insulation
Helps neurons transport action potentials more rapidly

1 Oligodendrocyte
Form several myelin sheaths
Myelinates sections of several axons

1 Schwann Cell
Forms one myelin sheath
Myelinates one section of an axon

Bio 2A03 Lecture 7

Membrane Potential

Resting membrane potential:

o membrane potential across the membrane when the cell is at rest (i.e. not sending
or receiving signals)
o For neurons, resting Vm ~ -70 mV
Membrane potential is the result of extremely small differences in the number of charged
particles across the membrane
o Differences only occur at the micro level (i.e. right next to the membrane)
o Principle of electrical neutrality
States that at a macro level, there are equal number of cations (+) and
anions (-) on either side of the plasma membrane
Neurons communicate by generating electrical signals in the form of changes in Vm

Factors that determine Vm

Concentration gradients of ions

o The Na+/K+ pump (ATPase) contributes indirectly to the membrane potentiall by
creating the Na+ and K+ concentration gradients
o Na+/K+-ATPase also contributes directly to the Vm because it is electrogenic
i.e. each pumping cycle removes 3 Na+ out and 2K+ in, a net removal of
positive charge from the cell
Permeability of ions (Pion)
o The tendency of an ion to move across the membrane is referred to as its
conductance
Conductance increases as the membrane becomes more permeable to that
ion
K+ has a higher conductance than Na+

Equilibrium Potential and Nernst Equation

At
and
log

room temp of 37
replacing ln with

Electrical Signaling

Occurs through changes in membrane potential via changes in PNa and PK

Hyperpolarization

o Getting more negative than the resting potential

o If PK increases, Vm will move towards -94 mV
Depolarization
o Getting less negative than the resting potential
o If PNa increases, Vm will move towards +60 mV
Repolarization
o When Vm returns to the resting Vm (-70 mV) after depolarization

2 Types of Electrical Signals

Graded Potentials
o Short distance
o Decremental signals (decrease over time) that initiate the firing of action
potentials
o Occur in dendrites and cell body
Action Potentials
o All or none events
o Transmit signals long distances along axons
o Can be initiated by strong graded potentials

Changes in Membrane Potential (Vm)

Occur in response to ion channel opening and closing

Electrical signals that occur in neurons are due to the action of ion channels called gated
channels
o They open/close in response to stimuli
o Affect movement of specific ions
o Ion movement causes electrical signal

The resting Vm is dictated by leak channels

o They are always open unlike gated channels

Types of Gated Channels

Ligand Gated
o Open when a ligand binds to them
Voltage Gated
o Open when membrane potential changes
Mechanically Gated
o Open via stretching

Graded Potentials

They are called graded because the size of

the graded potential depends on the size of the
stimulus
Graded potentials can cause hyperpolarization or depolarization depending on the type of
channels that open or close

Graded potentials occur when ion channels are opened or closed on the dendrites/cell
body causing ions to flow
o These currents/ions travel to adjacent sections of the membrane causing voltage
changes in these areas
As the graded potential spreads from the site of stimulation, the current spreads over
larger areas and some current leaks through background leak channels
o This is what causes the signal to decrement (decrease)
Summation
o The sum of all graded potentials
o Determines whether an action potential will occur
the sum of all graded potentials will generate an action potential if the
depolarization is above a critical level called the threshold when it spreads
to the axon

Action Potentials

are large changes in membrane potential that occur in axons

excitable membranes have the ability to generate action potential via large rapid
depolarizations that are used to send electrical signals long distances
strong depolarization makes Vm become positive
The process is underpinned by changes in PNa and PK as a result of voltage-gated Na+ and
K+ channels

Phase 1 Rapid Depolarization

o when graded potentials depolarize Vm to threshold, there is a rapid opening of
voltage-gated Na+ channels (PNa >> PK such that Na+ entry exceeds K+ exit)
o Vm approaches but does not reach ENa of +60 mV
Phase 2 Repolarization
o Before Vm reaches ENa, voltage gated Na+ channels inactivate and voltage-gated
K+ channels open (PK >> PNa such that K+ exit will now exceed Na+ entry

o Vm moves away from ENa and towards Ek to the resting Vm of -70 mV

Phase 3 After-hyperpolarization
o Voltage gated K+ channels are slow to close, so PK is still higher than what it is at
rest
o Hyperpolarization occurs as Vm continues to approach EK
o The hyperpolarization causes the voltage-gated K+ channels to close, after which
the membrane potential slowly returns to its resting value

Voltage-Gated Na+ Channels

Closed (resting stage) depolarization open (activated) inactivated

repolarization closed (resting stage)
The inactivated stage is caused by inactivation gate while the closed stage is caused by
the activation stage
o In contrast, voltage-gated K+ channels have only one gate that opens slowly in
response to depolarization
the rapid activation followed by the slow inactivation are both induced by the initial
depolarization

Refractory Period

the period of reduced excitability during and after an action potential

Absolute Refractory Period (1-2 ms)

o The action potential will not be affected by the second stimulus while Na+ entry
is occurring
o During repolarization, most voltage-gated Na+ channels are still activated and
cannot open
Relative refractory period (5-15 ms)
o Many voltage-gated K+ channels are still open and oppose depolarizing stimuli
o Most Na+ gates are no longer activated

Propagation of Action Potentials

When an AP is initiated at the axon hillock, the depolarization produces a current that
spreads to adjacent areas of the membrane
o This is because the positive charges at the region of depolarization are attracted to
the negative charges in neighboring regions
o The spreading current depolarizes adjacent regions
The neighboring region becomes depolarized enough to generate an AP
Positive current moves from one axon region to the next
o AP cannot move backward because the previous region is in the absolute
refractory state
The speed of AP conduction increases with axon diameter, because it decreases resistance
to current flow along the axon

Saltatory Conduction

APs are rather slow events involving diffusion of ions

APs can leap from one node to the next by salutatory conduction
o The APs jumps from one Node of Ranvier to another
o The speed increases because the Nodes are exposed to the ECF where voltagegated Na+ and K+ channels are concentrated
o Also the myelin makes it much harder for current to leak out through open ion
channels

Propagation of APs in Myelinated Axons

APs are generated the same way, though the depolarizing current flows rapidly over
longer distances because of the insulation provided by myelin
Nodes of ranvier are spaced such that there is enough current remaining to bring the next
Node to threshold

Myelination

Only vertebrates have myelinated axons

Advantages include:
o Much higher conduction velocity
o Saves space axons can be much thinner for a given conduction velocity
o Metabolically cheaper APs occur only at nodes, so voltage-gated channels and
ATPase are only needed at nodes

AP Stimulus Intensity

All action potentials are the same size

o So stimulus intensity is encoded by action potential frequency
o Stronger, longer-lasting graded potentials (i.e. stimuli) produce more action
potentials (i.e. increased frequency)

Bio 2A03 Lecture 8

Synapses

3 common synapses
o Axodendritic synapse between an axon and a dendrite
o Axosomatic synapse between an axon and a cell body
o Axoaxonic synapse between 2 axons
Synaptic cleft
o Space between a pre- and a post-synaptic terminals
2 types of synapses
o Electrical
o Chemical

Electrical Synapses

Can occur from neuron to neuron or neuron to glia

Occurs via gap junctions (cytoplasms of 2 neurons are connected)
o direct cytoplasmic connections between pre and post-synaptic cells that allow
electrical signals to be transmitted from one neuron to another
Advantages
o Allow for rapid communication between cells
o Synchronize activity of connected cells
Disadvantages
o Often bidirectional communication
o No capacity for modulation or amplification of the signal (i.e. signal in
presynaptic cell = signal in postsynaptic cell)

Chemical Synapses

Arrival of an action potential leads to neurotransmitter release into the synaptic cleft
Neurotransmitter binds to receptors on the post-synaptic membrane and causes a response
Can be neuron-neuron or neuron-effector cell (ex. muscle/gland)
Advantages
o Unidirectional
o Facilitate integration
Disadvantage
o Relatively slow

Chemical Synaptic Transmission

1) Action potential
2) Voltage-gated Calcium channels open
3) Ca2+ entry triggers vesicle docking and secretion (this is where most of the delay comes
from)
4) Neurotransmitter diffuses and binds to receptor

5) Response in cell
a. Often includes changes in permeability of K, Na, or Cl that induce a graded
potential
6) Degradation by enzymes at multiple locations
7) Reuptake into presynaptic terminal
a. the neurotransmitter is either degraded or recycled
8) diffusion out of the synaptic cleft
9) reuptake and metabolism by surrounding glial cells

the
All

Response is terminated by removal of transmitter from

cleft
of the above steps decrease receptor occupancy and
thus decrease postsynaptic response

Classes of Neurotransmitters

There are 6 different classes of neurotransmitters

o Many have dual roles as neurotransmitters and neurohormones
o Many can bind to both fast and slow-acting receptors
o Acetylcholine is the most abundant neurotransmitter in the PNS
o Amino acid neurotransmitters are the most abundant in the CNS
The 6 Classes include
o Choline derivative
o Biogenic amines
o Amino acids
o Purines
o Neuropeptides
o Unique Molecules

Signal Transduction at Chemical Synapses

Neurotransmitter crosses the synaptic cleft and binds to the postsynaptic receptor

The receptors include:

o Channel-linked (ionotropic) receptors
Neurotransmitter binding causes fast changes in Vm
The channel returns to its resting state as soon as neurotransmitter leaves
o G protein-coupled (metabotropic) receptors
Are slow acting
The typical response is a change in Vm of the postsynaptic neuron called a postsynaptic
potential (PSP)
o Excitatory PSP (EPSP) cause depolarizing graded potential
o Inhibitory PSP (IPSP) often cause hyperpolarizing graded potential

Ionotropic Receptors

Have a fast response

Neurotransmitter binding opens/closes a channel directly and ion flux causes a graded
potential
o The resulting depolarization is called a fast postsynaptic potential
o Many fast EPSPs result from opening ionotropic receptors selective for both Na+
and K+
Since the resting Vm is closer to EK than to ENa, there is a larger
electrochemical driving force (Vm Eion) on Na+ than on K+

Metabotropic Receptors: Direct Coupling

Neurotransmitter binds to receptor activates G protein opens/closes ion channels

Ex. Closing K+ channels results in K+ having less influence on Vm, so other leak
conductances (Na+) have a greater relative influence of Vm and the membrane
depolarizes

Metabotropic Receptors: 2nd Messengers

Neurotransmitter binds to receptor activates G protein activates/inhibits enzyme

(effector molecule) produces secondary messenger
The secondary messenger can then produce other cell responses or open/close ion
channels

Ionotropic Receptors and GABA

Gamma-aminobutyric acid (GABA) is released at inhibitory synapses in the CNS

GABAA receptors are channel-linked receptors allow Cl- to pass through once activated
by ligand binding
GABA binding to the GABA receptor causes hyperpolarization (i.e. IPSP) of the
postsynaptic membrane as Cl- enters
Reduces the probability than an action potential will fire in the postsynaptic cell
o i.e. it decreases activity of postsynaptic cell
Anti-anxiety drugs allosterically modulate GABAA receptors and allow more Cl- to pass
through the channel

Mechanisms that affect Neurotransmitter Release

AP frequency in the presynaptic neuron

o Suprathreshold stimuli (stimuli strong enough to cause an AP even if in the
refractory period) increase AP frequency
o As AP frequency increases, [Ca2+]inside in the axon terminal increases
o Higher levels of [Ca2+]inside result in more neurotransmitter release
Autoreceptors
o Promote or inhibit neurotransmitter release from the presynaptic terminal
o Are located on the presynaptic membrane

Presynaptic Facilitation or Inhibition

o Axoaxonic synapses (modulatory synapses) facilitate or inhibit neurotransmitter
release

Summation of PSPs

Summation is when multiple PSPs add together to form a stronger signal

It is necessary because a single EPSP is rarely of sufficient magnitude on its own to
induce an action potential

Bio 2A03 Lecture 9

Brain

Cerebellum
o Motor coordination and balance
Cerebral Cortex
o Perception
o Body movement
o Integrating center
o Complex thought processing
Brainstem
o Integrates information from cranial nerves
o Control center for autonomic functions
Thalamus
o Integrates sensory and motor information
o Sensory relay station to cortex
Hypothalamus
o Food intake
o Thermoregulation
o Neuroendocrine functions
o Circadian rhythms

Cerebrospinal Fluid (CSF)

Has a similar composition to plasma

Is distributed by ventricular network of cavities in brain and spinal cord
Total volume is ~150 mL
We produce 400-500 mL/day (recycled 3 times/day)

Functional Organization of the CNS

has an orderly arrangement of neurons

White matter
o Regions with shit tons of axons
o The lipid content of the myelin that cover the axons makes them appear white
Grey matter
o Regions of cell body, dendrites, and axon terminals clustered together
o Lack of myelin makes them appear grey
o This is where synaptic communication and integration occurs
Glial cells other than Oligodendrocytes are located in the CNS
Projection Fibres
o Connect cerebral cortex with lower levels of brain or spinal cord
Association Fibres
o Connect 2 areas of cerebral cortex on the same side of the brain
Commissural fibres
o Connect same cortical regions on 2 sides of the brain
o Transfer of information between the 2 hemisphere occurs through these
Corpus callosum
o Primary location of commissural fibres
o Connects the 2 hemispheres

Cerebral Cortex

The cerebral cortex is divided into 2 hemispheres which tend to control the opposite sides
of the body
o One hemisphere often dominates for particular functions
o For ex. left brain is dominant for hand movement which is why most people are
right-handed
Each lobe of the cortex is sub-divided into areas that are specialized for different
functions

Functional areas of the primary somatosensory cortex and primary motor cortex are
topographically organized
o Neighboring regions of the brain control neighboring regions of the body
The size of each area reflects the number of neural circuits devoted to each function

Brainstem

Composed of the medulla oblongata and pons

Controls many autonomic functions such as respiratory system, cardiovascular system
Most of the cranial nerves arise from the brainstem
o Glossopharyngeal (IX) are cranial nerves that motor control swallowing and
salivary glands; taste
o Vagus (X) are cranial nerves that motor control larynx and pharynx

Spinal Cord

A spinal nerve branches off either side of the spinal cord and exits the vertebral column
between most adjacent vertebrae
The spinal nerves are designated according to where they leave the spinal cord
o Cervical (8) around the neck area
o Thoracic (12) around the upper-middle area of the back
o Lumbar (5) around the lower area of the back
o Sacral (5) near the buttocks/gonads
o Coccygeal (1)
Each spinal nerve travels to adjacent regions of the body which can be mapped by
sensory regions on the skin (dermatomes)

Spinal Cord Gray Matter

Afferent axons enter gray matter of spinal cord via dorsal roots with cell bodies in dorsal
root ganglia (pseudo-unipolar neurons)
Efferent neurons have cell bodies in the grey matter and their axons leave the spinal cord
via ventral roots (multipolar neurons)
Dorsal and ventral roots merge at a short distance from the spinal cord to form the spinal
nerves

Spinal Cord White Matter

The white matter consists of ascending and descending tracts of axons that provide
communication between the brain and spinal cord, or between levels of spinal cord
All tracts are bilateral
Afferent or efferent neurons will usually synapse with interneurons in grey matter, which
project along tracts within white matter
Ascending and descending tracts generally cross to the opposite side of origin (the
contralateral side) although some exceptions exist where they remain on the same side
(ipsilateral)

Reflexes

Automatic patterned responses to stimuli that do not require conscious intervention are
called reflexes
Reflex arcs consist of five components
o Stimulus sensory receptor afferent neuron integration center efferent
neuron effector organ response

Stretch Reflex

The patellar tendon stretch reflex is the only monosynaptic reflex in the human body
The muscle spindle senses stretching which triggers action potentials in afferent neurons
Synapses with efferent neurons in spinal cord (integration centre)
o Excitatory connection with efferent neurons to the quadriceps
o Inhibitory connection with afferent neurons to the hamstrings

Contraction of the quadriceps muscle and relaxation of the hamstrings shortens the
quadriceps muscle

Withdrawal and Crossed-Extensor Reflex

This is the reflex you experience if you accidently step on a sharp object
The reflex arc for this reflex is:
o Stimulus sharp object
o Sensory receptor nociceptor
o Afferent neuron
o Integration centre spinal cord
o Efferent neuron
o Effector organ quadriceps and hamstrings
o Response OUCH!

Voluntary Movements

Movement is controlled by voluntary and involuntary pathways

The pyramidal tracts which project from the motor cortex, control the fine voluntary
movements of the extremities
Other tracts and brain regions control the core and neck muscles for voluntary movement,
posture, and balance

Sensory Receptors

Are classified based on the mode of stimulus they detect

o Photoreceptors light
o Chemoreceptors chemicals from taste, smell etc
o Thermoreceptors temperature
o Mechanoreceptors vibrations, sounds, touch
Baroreceptors detect blood pressure and regulate the heart and vasculature
Chemoreceptors sense O2, CO2, and pH of the blood and regulate breathing
Stretch receptors sense stomach distension after a meal
Sensory receptors can be specialized endings of afferent neurons or a separate cell that
synapses with an afferent neuron
Sensory unit
o Comprises a single afferent neuron and all of the receptors with which it is
associated
The receptor potential is the graded potential induced by a stimulus in a sensory receptor
o Sensory receptors tend to adapt over time
The strength of the signal gradually decreases over time
o Information about stimulus intensity is transmitted based on action potential
frequency

Sensory Systems

Afferent neuron transmits sensory information to the CNS

A single afferent neuron can diverge to several second-order interneurons
Second-order interneurons can receive and integrate signals from many different neurons
o This is called convergence
Many but not all interneurons transmit information to the thalamus, a major relay centre
for sensory input

Temperature Receptors

Temperature receptors in the skin are free nerve endings for which action potential firing
is sensitive to temperature
Thermoreceptors
o Sense skin temperature in the normal physiological range for skin from ~20 to
45C
o Temperature nociceptors detect tissue-damaging temperatures (>45C)
The 2 types of thermoreceptors are
o Warm receptors (~30-45C)
o Cold receptors (~20-35C)
Temperature sensitive transient receptor potential (TRP) ion channels underlie
temperature sensation

Temperature Receptors

Thermoreceptor afferents (receptors + afferent neurons) synapse with interneurons in the

spinal cord
The thermal signal is sent to the thalamus where it is relayed to other parts of the brain

Vision and Photoreceptors

Photoreceptors are light sensitive receptors

o Rods: detect dim light and do not distinguish colours
o Cones: detect bright light and underlie colour vision
3 types of cones which are best suited to detect red, blue, green
Light detection by rhodospin influences the activity of a G-protein, which regulates the
opening of ion channels
Light is sensed by a reduction in the action potential frequency of afferent neurons
Light stimuli reduce G-protein activation, close Na+ hcnnales, hyperpolarize the
receptor, and reduce the stimulation of bipolar cells
Photoreceptors synapse with bipolar interneurons in the eye, which synapse with neurons
in the optic nerve
o Light must travel several cell layers before reaching the photoreceptors
The optic nerve (cranial nerve II) transmits information to the thalamus, which is then
relayed to the visual cortex

Lecture 10
Autonomic Nervous System

Control areas are located in the brainstem and hypothalamus

Control areas receive afferent neural information from sensory afferents (Eg.
Chemoreceptors, baroreceptors) and higher brain centers (eg. Thalamus)
Sympathetic Nervous System (SNS)
o Active during periods of excitation or physical activity
o Has a large influence on the cardiovascular system (fight or flight response)
Parasympathetic Nervous System (PSNS)
o Active during periods of rest
o Stimulates digestive organ systems
o inhibits the cardiovascular system (rest and digest)
SNS and PSNS innervate many of the same organs, but usually have opposing effects

Anatomy of the ANS

Pre-Ganglionic Fibres
o Cell body in the brainstem or spinal cord
o Thinly myelinated axon projects to autonomic ganglia

Autonomic Ganglia
o Are located at the target organ in the PSNS
o Paravertebral (next to vertebral column) in the SNS
Post-Ganglionic Fibres
o Cell body in the autonomic ganglia
o Unmyelinated axon projects to visceral effector organs

Parasympathetic Nervous System (PSNS)

PSNS efferent signals are transmitted primarily in the vagus (cranial nerve X), as well as
other cranial nerves and the pelvic nerve
Pre-ganglionic neurons pass uninterrupted to the target organ
Post-ganglionic neurons are very short and innervate the target tissue
Final neurotransmitter is always acetylcholine (ACh)

PSNS Neurotransmitters and Receptors

ACh receptors
o Nicotinic receptors
Are ionotropic receptors expressed by all post-ganglionic neurons
Have high affinity for nicotine found in tobacco
o Muscarinic receptors
Are metabotropic receptors expressed at the effector organ
Have high affinity for muscarine found in toxic mushrooms
ACh action at synapses is short lived because it is rapidly broken down by
acetylcholinesterase
o ACh does not circulate in the blood because the blood contains high-activity nonspecific cholinesterases

Sympathetic Nervous System (SNS)

SNS efferent signals are transmitted via spinal nerves

Pre-ganglionic neurons exit the spinal cord and synapse with post-ganglionic neurons in
the SNS ganglia within the sympathetic chain

Post-ganglionic fibres leave the sympathetic chain (or collateral ganglion) to innervate
the target tissue
Final neurotransmitter is usually noradrenaline (norepinephrine)

SNS Neurotransmitters and Receptors

Acetylcholine (ACh) is released from pre-ganglionic neurons and act on nicotinic

receptors expressed by post-ganglionic neurons
Post-ganglionic sympathetic neurons release norepinephrine
o The chromaffin cells of the adrenal medule release 80% adrenaline, 20%
noradrenalin and small amounts of dopamine
Effector organs that respond to norepinephrine or epinephrine express adrenergic
receptors

Adrenergic Receptors

Are metabotropic receptors and bind both epinephrine and norepinephrine

2 classes of adrenergic receptors
o Alpha () adrenergic receptors
1 and 2 subclasses
o Beta () adrenergic receptors
1, 2, and 3 subclasses
Signal transduction mechanism for 1 (PIP2) differs from 2 and all the subclasses
o Check slide 10 of Lecture 11

Lecture 12
Types of Muscles

Skeletal Muscle

o Connected to at least 2 bones

o Some exceptions include some facial muscles, larynx, urethral sphincter
Smooth Muscle
o No striations
o Found in blood vessels, Gastrointestinal tract, uterus
Cardiac Muscle
o Show characteristics of both skeletal and smooth muscles

Skeletal Muscle Structure

The cells are called muscle fibres, due to their elongated shape, and are divided into
bundles (fasicicles) by additional connective tissue (perimysium and endomysium)
Tendons are continuous with the other layer of connective tissue (epimysium)

Muscle fibres are multinucleated cells

o each fibre is controlled by only 1 motor neuron
T tubules project inwards from the fibre surface
Myofibrils contain the contractile machinery
Sacroplasmic reticulum is distributed throughout cyoplasma
Mitochondria are situated in 2 locations
o Subsacrolemmal next to sacrolemma
o Intermyofibrillar interspersed with myofibrils

The Sacromere

Skeletal (and cardiac) muscle is striated due to the orderly arrangement of thick and thin
filaments in myofibrils
Z-lines Sacromeres are bordered by Z-lines, which anchor the thin filaments (actin)

M line Thick filaments (myosin) are joined at the M-line (M for myosin) and are
anchored by titin
A band a region of thick filaments (myosin)
H zone region between opposing ends of thin filaments
I band regions of thin filaments that do not overlap myosin

Thin Filaments

Backbone is composed of actin

G-actin (for globular protein) bind together to form F-actin (fibrous protein)
Tropomyosin partly covers the myosin cross-bridge binding site when the muscle is
relaxed
Troponin regulates the location of tropomyosin in response to Ca2+ during muscle
contraction

Thick Filaments

are made of myosin protein, composed of a head region with ATPase activity and actin
binding site (Crossbridge)
each myosin protein is a dimer of 2 inter-twined subunits
A thick filament is composed of hundreds of myosin proteins, with heads staggered along
the filament
The Sliding Filament Model
o Muscle shortening occurs as thick and thin filaments slide past each other

The Crossbridge Cycle

1) Myosin binds to actin
When myosin is in its energized state (when ADP and PI are bound), it has a high
affinity for actin
This step only occurs when Ca2+ is present
2) Power stroke
The binding of myosin to actin triggers the release of PI and later ADP from the
ATPase site of myosin
During the process, the myosin head pivots towards the middle of the sacromere
and pulls the thin filaments along with it
The conformational change shifts myosin into its low-energy state
3) Rigor
In its low energy form, myosin are tightly bound
This is the cause of rigor mortis the stiffening of the body after death, which
lasts until the myofibrils break down
4) Myosin and Actin unbind

The binding of ATP to myosins ATPase site triggers a conformational change in

the protein
The affinity of myosin for actin decreases, so the myosin detaches
5) Cocking of the myosin head
Soon after ATP binds, it is hydrolyzed to ADP and Pi
The energy released shifts myosin into its energized state
6) Energized myosin binds to actin and the cycle continues as long as Ca2+ is present
Ca2+ is essential for crossbridge attachment
The binding of Ca2+ to troponin causes a conformational change in the complex
Tropomyosin shifts from its tresting position, uncovering the myosin crossbridge
binding sites

Excitation-Contraction Coupling

1) ACh is released from the axon terminal of a motor neuron and binds to receptors in the
motor end plate
This binding elicits an end-plate potential, which triggers an action potential in
the muscle cells
2) Action potential propagates along the sarcolemma and down T tubules
Action potentials target charged amino acid residues on DHP receptors
Conformational change in DHP (dihydropyridine) opens the ryanodine receptor
channel it is associated with
3) The action potential triggers Ca2+ release from Sacroplasmic reticulum (SR)
Ca2+-induced Ca2+ release some of the Ca2+ binds to other SR Ca2+ channels
and causes them to open
4) Ca2+ binds to troponin, exposing myosin-binding sites
5) Crossbridge cycle begins (i.e. muscle fiber contracts)
6) Ca2+ is actively transported back into lumen of SR following the action potential
7) Tropomyosin blocks myosin-binding sites (i.e. muscle fiber relaxes)
Muscle Innervation

Muscle is innervated by myelinated motor neurons of the somatic nervous system which
leave the spoinal cord in spinal nerves via ventral roots
The synapse with muscle fibers is called the neuromuscular junction and the region on
the post-synaptic membrane of the muscle is called the motor endplate
Muscles have excitable membranes that strongly depolarize (end-plate potential) when
neurotransmitter binds, which stimulates an action potential

Excitation-Contraction Coupling

Acetylcholine is released at neuromuscular junctions where it binds nicotinic receptors on

the post-synaptic membrane
Nicotinic receptors are ionotropic cation channels that open and allow Na+ influx when
ACh binds
ACh binding causes a very large end-plate potential. Thus an action potential in the motor
neuron always generates an action potential in the muscle

Mechanics of Skeletal Muscle Contraction

A twitch is the mechanical response of an individual muscle fibre to a single action

potential in isolation
Latent period
o Events in the Excitation-Contraction coupling takes a few milliseconds to
stimulate contraction
Contraction Phase
o cytosolic [Ca2+] is rising

Relaxation Phase
o cytosolic [Ca2+] is decreasing (reuptake into SR)
A single twitch is reproducible in magnitude and shape

Fibre Diameter

The capacity of a muscle fibre to generate force/tension depends on its diameter

Larger diameter fibres can generate more force because they contain more sacromeres
(thick and thin filaments)
The number of thick and thin filaments per unit cross-sectional area is constant, so
changing area is the best way to increase strength

Fibre Length

the length of a muscle fibre, relative to resting length, also affects force generation
force generation by a sacromere is maximal at the length when all of the myosin crossbridges can bind to actin
force generation falls when the sacromere is so short that thin filaments start overlapping
force generation also falls when some or all of the cross-bridges cannot bind to actin

Motor Unit

groups of fibres innervated by a single motor neuron

o one neuron innervates many fibres

Muscle Fibre Recruitment

most muscle contraction is not to maximum effort (i.e. it is sub-maximal)

the CNS regulates the amount of force generated by regulating the number of motor units
that are recruited to contract
o more motor units = greater force
The Size Principle
o Motor units with fewer and small fibres are recruited before those with more and
large fibres
o This occurs because neurons from larger motor units have larger cell bodies
o Larger cells are harder to depolarize to threshold, and thus require more intense
stimulation from the CNS to generate an action potential
o This contributes to the precise control of muscular force

Skeletal Muscle Metabolism

Different energy source predominate after different durations of exercise

o Creatin phosphate (CrP) Anaerobic glycolysis Oxidative Phosphorylation

Skeletal Muscle Fibre Types

Muscle is composed of different fibre types, which differ in contraction speed and
metabolic phenotype
Oxidative fibres have a high mitochondrial abundance and primarily use aerobic
metabolism (oxidative phosphorylation)
Glycolytic fibres have fewer mitochondria and support contraction with anaerobic
metabolism (glycolysis)
3 main fibre types:
o Slow oxidative (Type I) slow contracting, high aerobic capacity
o Fast oxidative (Type IIa) fast contracting, high aerobic capacity
o Fast glycolytic (Type IIb) fast contracting, low aerobic capacity, high
glycolytic capacity
The differences in contraction velocity exist because each fibre type expresses different
myosin isoforms
Different muscles have different fibre type compositions
o Muscles with primarily type IIb fibres (extraocular muscle) contract much faster
than muscles with mostly type I fibres (soleus)
o Muscles with primarily type IIa fibres Gastrocnemius
Many muscles have a mixture of fibre types

Muscle Fibre Type Recruitment

In muscles with a mix of fibre types, the first fibres to be recruited are type I fibres then
type IIa fibres
o This is related to the size of their motor units
Type IIb are usually only recruited when large amounts of force are needed

In bird flight muscle, which do not contain type I fibres, type IIa fibres support steady
flight whereas type IIb fibres are only used for takeoff

Lecture 12
Muscle Spindles
Muscle spindles are composed of a small number of modified muscle fibres (intrafusal
fibres) that are innervated by sensory neurons
When the muscle lengthens, the intrafusal fibres are stretched, which induces action
potentials in the sensory neurons in proportion to the degree of stretch
Golgi Tendon Organ

Golgi tendon organs (GTO) are capsules of connective tissue intertwined with collagen
fibres in tendons
When the muscle stretches the tendons, the GTOs are activated, increasing the action
potential frequency in proportion to the tension in the tendon (and thus, the muscle)

Other Muscle Types

Skeletal and cardiac muscles are striated, but smooth muscles are not
Skeletal muscle is innervated by somatic (motor) neurons, but smooth and cardiac
muscles are innervated by autonomic neurons
o This means that the skeletal muscle is the only muscle that you can control
yourself
Smooth Muscle
All muscle types contain thick and thin filaments and generate force through the crossbridge cycle
Thick and thin filaments in smooth muscles are oriented at oblique angles and are not
arranged in sacromeres
Instead of toponin and tropomyosin, excitation-contraction in smooth muscle involves
Ca2+ binding to calmodulin, which activates myosin light chain kinase
Myosin light chain kinase phosphorylates and activates myosin ATPase
Large influx in Ca2+ is what causes the contraction in smooth muscles

Blood Reading Assignment (pg. 432-438)

Bruises (Contusions)

Are caused by damage to blood vessels which allows blood to escape into the tissues
The more blood that leaks into the tissues, the bigger the bruise
The closer the blood vessel damage is to the skin, the more colorful the bruise
Conversion of hemoglobin to bile is what changes the colours of the bruise

Plasma

Liquid portion of blood

Transports proteins, hormones, electrolytes, organic nutrients and waste products

Erythrocytes

Cellular components of the blood (RBC)

Transport oxygen and carbon dioxide

Leukocytes

White blood cells

Defend the body against pathogens

Platelets

Are cell fragments which are critical in the formation of blood clots to prevent loss of
blood

Hematocrit

Fractional contribution of the erythrocytes to the blood

Is determined by centrifuging a sample of blood in a tube and is represented as a
percentage
When centrifuged, the elements of the blood are separated based on density
o Because erythrocytes are denser than other elements of the blood, they are pulled
to the bottom of the tube
o Plasma, the least dense component, remains at the top
o Between these layers is the buffy coat (layer of leukocytes and platelets)
Our blood is mostly made of erythrocytes and plasma and very little leukocytes and
platelets

For men, the normal range of hematocrit is 42-52% while for women, it is 37-47%
Polycythemia
o Higher than normal concentration of erythrocytes in the blood

o This is a normal adaptive response in low-oxygen environments, such as high

altitudes
Plasma

Aqueous solution in which solutes are dissolved

o Solutes include proteins, small nutrients, metabolic waste products, fases, and
electrolytes
o Proteins are the most abundant solutes in plasma by weight but the smaller solutes
are present in higher concentrations
Plasma has a similar composition to interstitial fluid in terms of solutes because the
capillary walls that separate these two are highly permeable to small solutes
o Plasma and interstitial fluid differ significantly with respect to protein
concentrations
o This is due to low permeability to proteins
Plasma proteins are categorized into 3 main groups
o Albumins
Synthesized by the liver
Most abundant plasma proteins
Male a large contribution to the osmotic pressure of plasma, which affects
the movement of fluid across capillaries
o Globulins
Transport lipids, steroid hormones, and other substances in the blood
Play a critical role in the bloods ability to form clots
Important in defending the body against foreign substances
o Fibrinogen
Synthesized by the liver
Key substance in the formation of blood clots
Serum is plasma from which fibrinogen and other clotting proteins have been removed

Erythrocytes

Are most abundant cells in the blood

They lack nuclei, mitochondria, and other organelles such as ribosomes necessary for
manufacturing proteins
Their shape is a biconcave disk which is due to the presence of cytosolic protein called
spectrin
o Spectrin is a fibrous protein that forms a network linked to the plasma membrane
o The spectrin net is flexible, giving erythrocytes the ability to bend and flex as
necessary to move through capillaries
o In addition to the flexibility, the biconcave shape gives erythrocytes a large
surface area which makes them suitable for exchange

Oxygen and Carbon Dioxide Transport

Erythrocytes deliver oxygen from lungs to respiring cells

Erythrocytes deliver carbon dioxide from respiring cells to lungs
Erythrocytes have a high capacity for carrying these gases because their cytoplasm
contains two proteins:
o Hemoglobin
Binds and transports oxygen and carbon dioxide
o Carbonic Anhydrase
Transports carbon dioxide only

Hemoglobins Reversible Binding of Oxygen and Carbon Dioxide

Hemoglobin is composed of 4 polypeptide chains of 2 types (2 alpha and 2 beta chains)

each of which has an iron-containing structure known as a heme group
The iron in hemoglobin is present in the ferrous form (Fe2+) which imparts a red color to
the erythrocytes and hence to the blood
This iron is the site to which a molecule of oxygen binds
Each hemoglobin can bind to 4 oxygens because there are 4 heme groups in each
hemoglobin molecule
Carbon dioxide binds reversibly to amino acids within the polypeptide chains however
hemoglobin transports considerably less carbon dioxide than oxygen

Carbonic Anhydrase and the Carbon Dioxide-Bicarbonate Reaction

Carbonic anhydrase is an enzyme that catalyzes the reversible conversion of carbon

dioxide and water to carbonic acid
The pathway continues with the reversible dissociation of carbonic acid to yield a H ion
and a bicarbonate ion

Carbon dioxide can be converted to free H ions which affects the pH of the blood

Effects at High Altitude

When oxygen levels in the blood are low, more erythrocytes are produced
The larger number of erythrocytes transports more oxygen to the tissues that need them
This is why athletes train at higher altitudes where oxygen is less than sea level
Athletes also increase their number of erythrocytes by directly injecting blood cells into
their system or injecting erythropoietin, the chemical that stimulates erythrocyte synthesis
Increasing the concentration of erythrocytes increases resistance to blood flow

o The increasing resistance can increase friction between blood and the walls of the
blood vessels weakening the walls and making them more susceptible to
atherosclerosis
Life Cycle of Erythrocytes

Erythrocytes remain for only about 120 days

They cannot undergo cell division because they dont have nucleus or cell organelles
Erythropoiesis process by which the bone marrow produces erythrocytes

Erythrocyte Production

All blood cells develop from precursor cells called hematopoietic (blood forming) stem
cells located in the bone marrow
Erythrocytes and most leukocytes come to full maturity in the bone marrow
T lymphocytes migrate to the thymus gland before they develop to maturity
Hematopoietic Growth Factors (HGFs) are cytokines that are responsible for
development of specific blood cells
o Erythropoietin is HGF that stimulates erythrocyte production
o Colony-stimulating factors and interleukins are HGFs involved in leukocyte
production
Erythropoietin is released in response to low oxygen levels in the blood
Erythropoietin travels in the bloodstream to the bone marrow, where it triggers
differentiation of pluripotent cells to erythrocytes
o During differentiation, erythrocytes produce hemoglobin and lose their nuclei and
organelles
the last cell stage prior to development into the mature erythrocyte is the reticulocyte
which is a RBC with some ribosomes still present in the cytoplasm giving the cell a
weblike (or reticular) appearance
Under normal conditions, only erythrocytes are released into the blood stream
Iron is needed for hemoglobin synthesis
o Iron can be received from iron, folic acid, vitamin B12
o Some iron is stored in the liver and some is recycled from old erythrocytes

Anemia

Condition where the oxygen carrying capacity of the blood is reduced

Can happen due to a reduction in the amount of hemoglobin per cell or reduction in the
number of erythrocytes in the blood

Filtering and Destruction of Erythrocytes by the Spleen

Spleen is a lymphoid organ that stores blood cells and removes old erythrocytes from the
circulation
Some old erythrocytes are hemolyzed in the bloodstream but most are engulfed by
macrophages in the spleen and liver
When macrophages destroy erythrocytes, hemoglobin is catabolized
o After iron is removed, the resulting heme is converted to bilirubin (yellow)
o The bilirubin travels to the liver where it is catabolized further
o Most products of the catabolism are released into the small intestines and
ultimately excreted in the feces
o Jaundice is the result of increased bilirubin levels in the plasma due to excessive
erythrocyte hemolysis
Iron that was released by hemoglobin catabolism is recycled to form new hemoglobin
Iron is transported in blood bound to a protein called transferrin
o Transferrin picks up ion from the GI tract or from the spleen and transports the
iron to the red bone marrow for erythrocyte production, or to the liver where some
iron can be stored bound to the protein ferritin

Lecture 13
Need for Circulatory System

Diffusion times (t) are proportional to the distance (x)2 over which diffusion occurs
Diffusion is to slow to transport nutrients and gases in humans so circulatory system is
needed to do this job

Circulatory System

A fast convection system that rapidly circulates fluids between surfaces in contact with
the external milieu and cells deep inside organisms
Roles of a circulatory system include:
o Distribution system
Dissolved gases and molecules for nutrition, growth and repair
o Chemical signaling, heat dissipation etc.

General Layout of the Circulatory System

Propulsive Organ Arterial System Capillaries Venous System Propulsive

Organ
Propulsive Organ (heart)
o Creates the pressure driving blood flow
o Also has sensory and endocrine functions
Arterial System

o Distributes the blood

o Helps regulate blood pressure
Capillaries
o Location of gas and nutrient exchange
Venous System
o Returns blood to heart
o Acts as a blood volume reservoir

Mammalian Circulatory System

Is composed of 2 circuits
Pulmonary Circulation
o Goes to the lungs
o Picks up oxygen at the lungs
o Is a low pressure system (20 mmHg)
o Right ventricle lungs left atrium
Systemic Circulation
o Delivers oxygen to other organs and tissues
o High pressure system (100 mmHg)
o Left ventricle tissues right atrium
Both circuits have an arterial (blood travels away from the heart) and a venous system
(returns blood to heart)
Blood flow is equal in each circuit (5 L/min)
Blood flows in series from the pulmonary to the system circulation
o All blood flows through one, then the other
Blood in systemic circulation flows in parallel to each organ/tissue
o Blood leaving the left ventricle flows through the vascular bed of only one organ
before returning to the heart
The heart receive its own parallel circulation from the coronary artery

Blockage in Circumflex Coronary Artery

If there is a blockage in the coronary artery, the heart wont get enough oxygen
The inadequate blood flow to the cardiac tissue can cause heart attack

The Heart

Is composed of 3 layers:
o Epicardium outer connective tissue
o Myocardium cardiac muscle
o Endocardium endothelium that extends throughout the cardiovascular system
The left ventricle is much thicker than the right ventricle because the heart needs to work
harder when the pressure gets higher. In order to send the blood out, high pressure is
needed.

Papillary Muscles

Tend to pull the aortic valve to allow blood flow

These muscles contract when ventricles contract
These muscles do not cause the valve to open, they are causing the valve to not collapse
When ventricles contract, the papillary muscles contract closing the valve
Aortic valves are very rigid to resist collapsing into the ventricle

Cardiac Cycle

The series of events that occur during one full cycle of contraction and relaxation
Phases of the cycle are delineated by the opening and closing of the heart valves and are
characterized by changes in pressure and volume
Systole
o Period of ventricular contraction
Diastole
o Period of ventricular relaxation

Know Figures 13-18 and 13-19 (slide 11)

Cardiac Output

Cardiac output = stroke volume x heart rate

Cardiac output at rest is approximately 5 L/min
End-Diastolic Volume (EDV) peak volume
End-Systolic Volume (ESV) lowest volume
Stroke Volume
o Volume of blood ejected with each heart beat
o SV = EDV ESV
Systolic Pressure
o Peak aortic pressure caused by ventricular contraction
Diastolic Pressure
o Lowest aortic pressure
Mean Arterial Pressure
o MAP = (SP + 2DP)/3

Heart Sounds

Pulse

The heart sounds are the sounds of valves closing, not the sound of heart contracting or
blood moving

The pressure pulse created by the peak pressure during ventricular contraction is
propagated along the veins

Cardiac Muscle

There are 3 cell types:

o Contractile
Make up more than 99% of cardiac cells
All are electrically interconnected by gap junctions
Only innervated by neurons of the SNS
o Pacemaker
Make up less than 1% of the cardiac cells
Are cells specialized to create hearts rhythm
Are innervated by both PSNS and SNA neurons
o Conduction fibres
Cardiac muscle is excitable
o It can generate action potentials just like other forms of muscles

Contractile Fibres

Have properties of both skeletal muscle (striations, actin and myosin) and smooth
muscles (gap junctions)
Cardiac cells are interconnected in syncytium (single units all acting together) through
gap junctions
o Gap junctions are small diameter protein channels that link cytosols
They are located at the intercalated disks where fibres are held together
The heart contains 2 syncytia 1 atrial and 1 ventricular
Action potentials spread from cell to cell through gap junctions which increases the speed
of conduction through contractile cells

Action Potentials in Contractile Cells

The action potentials in cardiac contractile muscles last much longer than those in
neurons or skeletal muscle fibres
The main difference is that cardiac fibres have an extended depolarization phase due to
long lasting increase in permeability to Ca2+ and a transient reduction in K+ permeability

Resting membrane potential is low in contractile cells (-90 mV)

Phases of Action Potentials in Contractile Cells

1) Rapid depolarization
Sodium channels open
Sodium moves in
2) Small Repolarization
Sodium channels become inactivated
Sodium movement in decreases
3) Plateau
Potassium inward rectifier channels close
Potassium movement out decreases
Calcium L-type channels open
Calcium moves in
4) Repolarization
Potassium delayed rectifier channels open
Potassium moves out
Calcium L-type channels close
Calcium movement in decreases
5) Resting Potential
Potassium channels (both types) open
Potassium moves out
Sodium and Calcium channels remain closed
Little sodium or calcium moves in
Pacemaker Cells

Determine the rate at which the heart beats because they spontaneously generate action
potentials
They are located in 2 regions
o Sinoatrial node (SA)
o Atrioventricular node (AV)
o SA node has a higher intrinsic rate (70 impulses.min) than the AV node (50
impulses/min) which implies that the AV node can take over if SA fails or
transmission to AV is blocked

Slow depolarization is caused by Na+ leak channels

Conduction Fibres

Include intermodal pathway, bundle of His (atrioventricular bundle), and Purkinje fibres
Conduction action potentials are much faster than contractile cells (at 4 m/s) and are
responsible for rapidly spreading the impulse generated by pacemaker cells
Conduction fibres also connect the atrial syncytium with the ventricular syncytium at the
AV node

Sequence of Electrical Events that Triggers a Heartbeat

1) Action potential initiated in the SA node
Action potential spreads through atrial muscle faster in the intermodal pathway
and slower between fibres
2) Transmission is slowed by 0.1s at the AV node
Separates atrial from ventricular excitation
3) Action potential through the AV node to the bundle of His
Divides into left and right bundle branches
4) Action potential enters the network of Purkinje fibres and is transmitted through ventricle
from apex towards valves

1)

2)

3)

4)

Fast conduction through conducting fibres helps coordinate where and when contraction
happens

Electrocardiogram (ECG)

Spreading of the action potential throughout heart can be detected by ECG

Depolarization during an action potential makes the outside of the cell in that area
negative
An ECG signal is only observed when one region of heart has a different membrane
potential than another

The ECG is not the same as an action potential

Parts of the ECG

P wave
o Caused by atrial depolarization
QRS complex
o Wave of ventricular depolarization
o Potentials created as depolarization spreads
T wave
o Caused by ventricular depolarization

Excitation-Contraction Coupling in Cardiac Cells

When an action potential arrives at the cell, it triggers a muscle contraction

After the action potential is initiated, the mechanisms of cross-bridge cycling and
excitation-contraction coupling are similar in cardiac muscle and skeletal muscle

Autonomic Regulation of the Heart

Heart rate is affected by changes in rates of action potentials generated by the pacemaker
Pacemakers are innervated by the autonomic nervous system
o SNS and PSNS have opposite effects on heart rate
o SNS releases norepinephrine through cardiac nerve that acts on 1 adrenergic
receptors in SA node to increase heart rate
o PSNS releases acetylcholine through vagus nerve that acts on M2 muscarinic
receptors in SA node to decrease heart rate
o Vagal tone from the PSNS predominates at rest, which reduces heart rate below
the endogenous rate of the SA pacemaker (i.e. rate without any inputs)

SNS and PSNS affect heart rate by changing the rate of spontaneous depolarization
(dictated by background leak permeabilities), not by altering the shape or duration of
the action potential

o Stroke volume is affected by the SNS but not by the PSNS

SNS innervations of conduction fibres increases the speed of signal propagation
(increases the time available for cardiac filling during diastole)
SNS innervations of contractile fibres increases the force of contraction
o Activation of 1 adrenergic receptors in contractile fibres enhances various
components of Ca2+ cycling
o Intracellular [Ca2+] (and thus muscle force/tension) rises faster and greater,
and is then removed more quickly from the cytosol

Hormonal Regulation of the Heart

Epinephrine
o Affects heart rate and contractility in the same was norepinephrine from the ANS
Thyroid hormones; Insulin; Glucagon
o Each increase cardiac contractility, but their importance in short term regulation
of cardiac function is unclear

Regulation of the Heart by Cardiac Filling

Stroke Volume (SV) = EDV ESV

Ejection Fraction = SV/EDV x 100
At rest, half of the blood in the heart at EDV remains in the heart at ESV
Ejection fraction increases with exercise

Frank-Starling Law (Intrinsic Control)

Increased EDV stretches the cardiac fibres which increases force of contraction and thus
stroke volume
Its most important function is to coordinate output from the 2 sides of the heart
o What goes in must equal what goes out
Venous return the rate of blood flow into the atria
Venous return can be altered to regulate EDV and thus cardiac output

The ANS and the rate of venous return are the most important factor regulating cardiac
output

Regulation of Cardiac Output