Excitable Tissues

Excitable Tissues
In the body there are two excitable tissues: Nerve & Muscle.
The term excitability refers to an ability of a tissue to receive
stimuli & respond to them.
These stimuli can be electrical, chemical, mechanical, or
thermal.
Excitable tissues respond to various stimuli by rapidly
changing their resting membrane potentials & generating
electrochemical impulses (action potentials, APs).
Nerve & muscle cells are capable of producing electrical
signals when exited. Once started, APs are propagated
throughout an excitable cell.
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 The Physiology of Nerve
The function of a neuron is to communicate or relay information to
another cell by way of an electrical impulse.
A network of billions of nerve cells (neurons) linked together in a
highly organized fashion to form rapid control center of the body.
The functions of nervous system (NS) include:
Integrating center for homeostasis, movement, and almost all
other body functions.

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Nervous System vs. Endocrine System
Similarities:
They both monitor stimuli & react so as to maintain the
homeostasis.
Differences:
The NS is a rapid, fast-acting system whose effects do
not always persevere.
The endocrine system acts slower (via blood-borne
chemical signals called hormones and its actions are
usually much longer lasting.

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 Nerve tissue
Two principal cell types that make the nervous system are
called neurons & neuroglia cells.
Neurons Neuroglia cells
Are functional units of the NS Supporting cells
(functional, signal conducting cells) 20x outnumber
Neurons are specialized for neurons
- generation & transmission of impulses
can multiply after
- sensory function
maturation
- generation of thought
- storage of memory
potential causes of
glioma (brain tumour)
- integrates idea
- coordinates muscular activities
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 The Neuroglia
are non excitable cells found in
association with neurons.
provide supporting functions to NS.
are 6 types of supporting cells. They
include:
1. Microglia phgocytosis
2. Astrocytes provide nourishment
3. Oligodendrocytes coat axons
4. Ependymal cells secrete CSF
5. Schwann cells form myelin sheaths
6. Satellite cells unknown function

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 The Neurons
Are functional & structural units of the nervous system.
A typical neuron has the following 3 distinct functional parts:
cell body, dendrites (extend outward from the cell body) & axon.

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Neurons: Functional structures
Neurons are specialized to conduct information from one part
of the body to another.
There are many & different types of neurons but most have
certain structural & functional characteristics in common:
An input region (dendrites/cell body).
A conducting component (axon).
A secretory (output) region (axon terminal).

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 Functional structures, contd
Nerve cell body
An enlarged part of nerve cell containing nucleus, abundant
cytoplasm & cell organelles.
Its sometimes also called soma.
Clusters of soma in CNS are known as nuclei.
Clusters of somata in PNS are known as ganglia.
Receives information from dendrites & sends messages out
through the axon.
Biosynthetic center of the neuron.
The primary site for maintaining the life of the nerve cell
which support the dendrites & axon.
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 Functional structures, contd
Dendrite
An incoming nerve cell process that can act as a receptor or
connect to a separate specialized receptors.
Conducts stimulus information to the nerve cell body.
Produces voltage changes in the response to various stimuli &
assists in nerve impulse formation.
Axon Hillock
The junction site b/n the nerve cell body & the axon.
Processes voltage changes or generator potentials (GPs) from
the cell body & dendrites, and assists in the formation of a
transmittable nerve impulse.
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 Functional structures, contd
Axon
Originates from a special region of cell body called axon hillock.
Very small in diameter, but can be very long (e.g. the length of a
leg, up to 1.5 m).
Transmit AP from soma toward the end of axon terminals where
they cause NT release.
If an axon is cut, the distal portion degenerates due a disruption of
the cytoplasm extending from the cell body.
Each nerve cell has only one axon. It can be either myellinated or
unmyellinated.

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 Functional structures, contd
Axon Terminals
Are bulbous distal endings of many branches that extend from the
end of an axon.
These bulb-like structures can also be called synaptic knobs,
buttons or even end feet.
Serves as a secretory component that releases NTs in response to
AP.
Node of Ranvier
Is a space or gap (myelin free zone). Located b/n the myelin sheaths
formed by cells such as Schwann cell.
The exposed cell membrane located in the node can facilitate the
formation & transmission of nerve impulses.
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 Functional structures, contd
Schwann cell
A specialized cell that supports & maintains the fibers (axons and
dendrites) of nerve cells in the PNS.
Assists in the repair & regeneration of nerve fibers.
Wraps around a section of a nerve fiber & creates a protective
myelin sheath, containing myelin material.
Myelin sheath
A whitish, fatty myelin material acts as an excellent insulator &
protector of the nerve cell fiber.
It envelops the axon except at its ending & at nodes of Ranvier.
Axons of many neurons are myelinated; while some neurons are
unmyelinated.
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 Functional Classification of the Neurons
Based on their functions there are 3 classes of neurons:
A. Sensory (Afferent) neurons
conduct impulses from the periphery to the center/CNS.
B. Motor neurons (Efferent)
conduct impulses from the CNS to the periphery.
C. Interneurons/Association/Integrative/ neurons
conduct nerve impulses from sensory area to motor area
(b/n sensory & motor neurons).
exclusively found in the CNS.

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 Classification of Ion Channels
I. Leak channels
II. Gated channels
Na+ channels Ca+ channels
are three major types are three major types
1. Na+-leak channels 1. Voltage-gated Ca2+ channels
2. Voltage-gated Na+ channels with subtypes
3. Ligand-gated (chemical-gated) 2. Ligand-gated Ca2+ channels
Na+ channels 3. G-protein-gated Ca2+ channels
K+ channels
are four major classes:
1. K+-leak channels
2. Voltage-gated K+ channels
3. Ligand-gated K+ channels
4. G-protein-gated K+ channels 15
 Action Potential (AP)
Action potential: a short lasting event in which the electrical
membrane potential of a rapidly rises & falls that occur in the
excitable cells.
Useful for cell-to-cell communication.
Neurons communicate with one another by means of nerve
action potential (nerve impulse).

NB: All cells have slightly excess of positive charges outside &
negative charges inside of the membrane. Most of the membrane
potential is due to the passive diffusion of Na+& K+ ions down
their concentration gradients.

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 Nerve Action Potentials
Nerve signals are transmitted by the action potentials,
which are rapid changes in the membrane potential
that spread rapidly along nerve fiber membrane.

Each AP begins with a sudden change from a normal

negative resting membrane potential (RMP) to a
positive potential & then ends with an almost equally
rapid change back to a negative potential.

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Nerve Action Potentials contd
At rest, voltage sensitive Na+ & K+ gates in the plasma
membrane of a nerve cell are nearly closed & Na+/K+ pump
moves 3Na+ ions to the ECF & 2K+ ions to the ICF.
This combination of activity contributes to the formation of a
resting membrane potential (RMP) of -90 millivolts (mV).

A negative state of ICF (-90 mV) compared to a positive ECF

is due to unequal flow of ions across the cell membrane.

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 Resting membrane potential (RMP)
All cells have a voltage difference across their plasma
membrane. This is called membrane potential (VM).
VM at rest is called RMP. At rest, there are electro-positivity
out & electro-negativity inside cell membrane of a neuron.
The RMP of a typical neuron is -90 mV.

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What are the causes of the RMP?
1. An outward diffusion of K+ through K+ leak channels.
There is very high conc. of Na+ in ECF while there is very high
conc. of K+ in ICF. As a result, the K+ is constantly leaking out
of the cell.
2. The Na+-K+ ATPase is constantly pumps 3Na+ ions outward &
2K+ ions inward for every ATP used. Thus, more positive charge
is leaving than entering.
3. There are negatively charged non-diffusible proteins within the
ICF that cannot travel through the membrane.

What this adds up to is the fact that the inside of the cell is negative
with respect to the outside. The interior has less positive charge
than the exterior.

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 Generation of a Nerve Impulse (AP)
At rest, the ICF of axon has a voltage about -90 mV (RMP).
When the membrane of the axon is properly stimulated, the
Na+ ions begin to leak into the ICF. This causes the voltage to
change to a less negative state.
When the ICF voltage reaches a threshold of about -60 mV,
the Na+ gates open.
As Na+ gates open, the Na+ ions flow through Na+ channels
increases, and this quickly changes the voltage from a resting
level of -90 mV to +35 mV.
This rapid shift from a negative to a positive state is called
DEPOLATIZATION. At +35 mV, the Na+ gates close.
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Generation of a Nerve Impulse, contd
When the Na+ gates close at +35 mV, the depolarization process
stops.
The +35 mV condition causes the K+ gates to open & allows K+
ions to flow from the ICF to ECF.
The rapid flow of K+ reverses the membrane potential from +35
mV to about -90 mV. This is called REPOLARIZATION.

If the axon is myelinated due to a Schwann cell, nerve impulse

forms only in the Nodes of Ranvier & skips over the insulating
myelin sheath from node to node.

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Generation of a Nerve Impulse, contd
At the conclusion of each repolarization event, the
Na+/K+ pump move Na+ & K+ ions back to their main
storage areas & reset the membrane.

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Generation of a Nerve Impulse, contd
When the nerve impulse reaches the axon terminal, a set of
events will be triggered which will release a certain amount
of neurotransmitter (NT), e.g. acetylcholine (Ach).
The NT then accumulates in a synapse & generates a
postsynaptic voltage potential in the next cell of a nerve
pathway sequence.
If the postsynaptic potential is positive, then it is called an
Excitatory Postsynaptic Potential (EPSP).
If the postsynaptic potential is negative, then it is called an
Inhibitory Postsynaptic Potential (IPSP).
EPSPs stimulate further nerve impulses, whereas, IPSPs
inhibit nerve impulses.
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 The Stages of AP
A. Resting stage
Is the RMP before the AP begins.
Polarized stage with -90 mV negative membrane.
B. Depolarization stage
Initiated b/c of the rapid inflow of Na+ ions to the inside, creating
positivity inside as membrane permeability to Na+ ions.
C. Repolarization stage
Initiated when Na+ channels
begin to close & K+ channels
open more than normal after
few seconds time, so that K+
ions will diffuse rapidly to
the exterior & regains the
negativity.
Figure. Action potential. When a stimulus depolarizes the
membrane to a threshold, an AP is generated.
 Summary of Action Potential
An immediate change of the RMP into depolarization that is
followed by reestablishment of the RMP (repolarization) is called
action potential or nerve impulse.
If RMP changes from -90 mV to threshold level (-60 mV) voltage
gated Na+ channels open, and Na+ influx depolarization. Na+
channels become inactivated soon.
Opening of voltage gated K+ channels K+ efflux repolarization.

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 All-or-None Principle
Once an AP has been elicited at any point on the membrane of a
normal fiber, the depolarization process travels over the entire
membrane if conditions are right, or it does not travel at all if
conditions are not right. This is called the all-or-none principle,
and it applies to all normal excitable tissues.
As long as a stimulus is strong enough to cause depolarization to
threshold, voltage-gated Na & K channels open, & an AP occurs.
A much stronger stimulus cannot cause a larger AP b/c the size of an
AP is always the same.
A weak stimulus that fails to cause a threshold-level depolarization
does not elicit an AP.
For a brief time after an AP begins, a muscle ber or neuron cannot
generate another AP. This time is called the refractory period.
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 Refractory Period
During the time interval b/n the opening of Na+ activation
gate & the opening of Na+ inactivation gate, a Na+ channel
cannot be stimulated. This is called the refractory period.
There are two forms of refractory period:
A. Absolute Refractory Period /ARP/
Another AP can not be generated regardless of the strength
of the stimulus.
ARP begins at the start of the upward stroke & extends into
the downward stroke.
B. Relative Refractory Period /RRP/
The RRP begins when the ARP ends.
New AP can occur in an excitable fiber if the stimulus is
sufficient/strong enough.
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 Conduction of Action Potential
If an AP is generated at the axon hillock, it will travel all the way
down to the synaptic knob.
The manner in which it travels depends on whether the neuron is
myelinated or unmyelinated.
Propagation of AP
1. Sweeping/Continuous conduction of AP
Occur in unmyelinated neurons.
In this situation, wave of de- and re-polarization simply travels
from one patch of the membrane to the next adjacent patch.

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2. Jumping/Saltatory conduction of AP
Occur in myelinated neurons.
Recall that the myelin sheath is not
completed. There exist myelin free
regions along the axon, the nodes of
Ranvier.
Velocity is faster
Economizes ATP

Rates of AP conduction depends upon:

1. Level of myelination
- Faster in myelinated than in unmyelinated
2. Size of nerve fiber
- Faster in large sized than in smaller ones
3. Age: - Slower in babies & in elderly
- Maximum b/n the age 5-15 years
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 Synaptic Transmission
Synapse is a junction b/n two cells in which one must be a
neuron.
It is the site of transmission from one neuron to the next.
There are two modes of synaptic transmission:
(1) Chemical synapses
(2) Electrical synapses
Almost all the synapses used for signal transmission in the
CNS of humans are chemical synapses.
One neuron will transmit impulse to another neuron or to a
muscle or a gland cell by releasing chemicals called
neurotransmitters.

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Synaptic Transmission, contd
Advantages of chemical synapses
1) Slower signal transmission, which can be either excitatory or
inhibitory.
2) The signal can be modified as it passes from one neuron to next.
Advantages of electrical synapses
1) Faster signal transmission & only excitatory.
2) Can synchronize the activity of postsynaptic neurons.

There are 3 types of chemical synapses:

1. Neuroneuronal junction (presynaptic & postsynaptic neurons)
2. Neuromuscular junction
3. Neuroglandualr junction

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Synaptic Transmission, contd
Components of Synapses:
1. Presynaptic terminal contains
neurotransmitter (NT).
2. Synaptic cleft contains ECF &
enzymes.
3. Postsynaptic neuron contains
receptor for the action of NT.

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 Mechanism of Chemical Synaptic Transmission
An AP reaches presynaptic axon
terminal of presynaptic cell & causes
V-gated Ca2+ channels to open.
Ca2+ rushes in, binds to the regulatory
proteins & initiates NT release by the
exocytosis.
NT diffuses across synaptic cleft &
then bind to the specific receptors on
postsynaptic membrane & initiate
postsynaptic potentials.
NT-receptor interaction results in
either EPSP/IPSP.
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Mechanism of Synaptic Transmission, contd

When the NT-R combination triggers the opening of

ligand-gated Na + channels, this leads to membrane
depolarization, EPSP.
E.g. Ach on Nicotinic receptors
When the NT-R combination triggers the opening of
ligand-gated K+ or Cl- channels, this leads to membrane
hyperpolarization, IPSP.
E.g. GABA on GABAb receptors

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 Neurotransmitter Removal
Why do we want to remove Ach
from the NMJ?
How was Ach removed from
the NMJ?
Transmitter action is rapidly
terminated.
One of 3 processes can remove
NT from the synaptic cleft:
Diffusion or
Enzymatic degradation
(Ach), and/or
Reuptake of NT into the
nerve ending or other cell. 36
 Types of Nerve Fibers

1. Group A (, , , )
Have large diameters & thick myelin sheaths.
Axons of somatic sensory neurons & motor neurons serving
the skin, skeletal muscles, and joints.
How does this influence their AP conduction?
2. Group B
Type B are lightly myelinated & have intermediate diameter.
Belong to the autonomic preganglionic neurons.
3. Group C
Type C are unmyelinated & have the smallest diameter.
ANS fibers serving visceral organs, visceral sensory fibers, &
small somatic sensory fibers are Type B & Type C fibers.

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Properties of synaptic transmission
1. Unidirectional conduction
2. Fatigue - in the response of postsynaptic neurons after
repeated stimulation by the presynaptic neurons.
3. Synaptic potentiation (facilitation): the persistence of out
put signals after the stoppage of the input signal.

Synapse is a target for the action of several groups of drugs:

Caffeine, theophylline: synaptic transmission.
Hypnotics, anesthetics, tranquilizers: synaptic transmission.

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