1.

Cell Homeostasis Body Fluid Compartments

1.1 Cell Membrane (structure, functions , action potential )

Human Body structure

HUMAN BODY system organ tissue Cell

Coordination of Systems and Organs

Claude Bernard (1813-1878)

La fixit du milieu intrieur est la condition de la vie libre.

The fixity of the internal environment is the condition for free life.

Homeostasis
Walter Cannon (1929)

HOMEOSTASIS

Cannon W.B., 1939

-all mechanisms through which bodily equilibrium is maintained ( body fluid composition, temperature, blood pressure, blood glucose level)

INTERNAL MILIEU

Claude Bernard
-,, all around ,, cells - offers nutritives substances - realises elimination of metabolites

The cell : morpho functional unit of human body.

Cell Membrane
- separates / unites two compartments with different composition - intracellular space (compartment , environment) - extracellular space ( compartment )

extracelular Na+ K
+

intracelular 15 mM/L 120 mM/L 20 mM/L 30 g/dL 290

142 mM/L 4.4 mM/L 102 mM/L 7 g/dL 5.5 mM/L 291

ClProteins Glucose Osmolarity

Cell membrane

Functions of the cell membrane :

Transport

Intercellular comunications

Enzymatic activity

Intercellular recognition

Sending informations

Attachment to cytoskeleton

Hystory :
Overton (1895): if a substance is more lipo-soluble , it has a better permeability through the membrane - conclusions regarding the lipid profile of the cell membrane . Davson and Danielli (1935) they introduce the concept of a protein structure for the cell membrane . Singer & Nicholson (1972)- they offer the model of ,,fluid mosaic,,phospholipids and cholesterol form a a fluid lipid bilayer where proteins can move free. In conclusion cell membrane is a dynamic structure with specific characteristics in order to accomplish various functions.

The cell membrane is a lipid bilayer semipermeable structure allowing the passage only for some molecules . - no H2O, ions, hidrophyle molecules. - yes - gas, hidrophobe substances . Membrane proteines allow transport for H2O, ions and hidrophyle molecules .

CELL MEMBRANE

lipids proteins glucides

MEMBRANE LIPIDS:

-phospho-lipids -cholesterol - contain fat acids - C chain, (carboxil group terminal) - particular characteristics: - hidrophyle part ( C chain) - hidrophobe part ( carboxil group )

-phospholipids

- lipid bilayer - hidrophobe head (inside ) - hidrophyle head (outside)

MEMBRANE PROTEINS

A. INTEGRAL PROTEINS - connected with hidrophobe layer of the membrane . 1.transmembrane proteins: cross lipidic bilayer - channels: - pomps: - pores -receptors:

2.proteins expressed only on one face of the membrane

B. PERIPHERAL MEMBRANE PROTEINS - connected with hidrophyle part of the lipidic layer or with integral proteins - cytoskeleton - role in membrane rigidity - glicocalix -role n intercellular atachment

MEMBRANE PROTEINS

A. INTEGRAL PROTEINS - c on n ecte d w ith h id rop ho be la y er

of th e m em bra ne .

1. tra nsm em bra ne p rote ins: c ross lipidic b ila ye r - channels: allows the passage only for substances with small molecule with
electric charge - gates acctive or innactive - selectivity

- pomps: - pores -receptors: 2. prot eins ex pr esse d o nly o n o n e fa c e of t he m em b ra n e

MEMBRANE PROTEINS

A. INTEGRAL PROTEINS - c on n ecte d w ith h id rop ho be la y er of t he

m em bra ne .

1. tra nsm em bra ne p rote ins: c ross lipidic

bila ye r - channels: - pomps: - pores - channels without gates , allways open. - ex. aquaporines ( allow the passage for water renal colector tube)

-receptors: 2. prot eins ex pr esse d o nly o n o n e fa c e of

the m e m b ra n e

MEMBRANE PROTEINS

A. INTEGRAL PROTEINS - co nnected with hidropho be layer o f the m em brane .

1. transm em brane pro teins: cross lipidic bilayer - channels: - pomps: allow ions transfer against concentration gradient or voltage gradient. - pores: - receptors:

2. pro teins expressed o nly o n o ne face o f the m em brane

MEMBRANE PROTEINS

A. INTEGRAL PROTEINS - c on n ecte d w ith h id rop ho be la y er of t he m em bra n e .

1. tra nsm em bra ne p rote ins: c ross lipidic b ila ye r - channels: - pomps: - pores -receptors:

2. prot eins ex pr esse d o nly o n o n e fa c e of t he m em b ra n e

Membrane Receptors
are protein molecules that react with ligands inducing special reactions
inside the cells. The most important receptors are classified as adrenergic and cholinergic

1. Adrenergic receptors are of 2 types ALPHA and BETA .They react to sympathetic neurotransmitter - norepinephrine .

 The actions of norepinephrine depend on the type of receptors

activated :

Alpha 1 receptors - contraction of smooth muscles in vessels and

bronchioles Alpha 2 receptors - contraction of smooth muscles of digestive sphincters. Beta 1 receptors - excitatory effects on heart . Beta 2 receptors - relaxation of smooth muscle in bronchioles and muscular vessels.

2. Cholinergic receptors are of 2 types nicotinic and muscarinic. They react especially to acetylcholine Nicotinic receptors are stimulated by acetylcholine and nicotine. They are found in all ganglionic synapses and neuromuscular junctions where are blocked by curara. .Muscarinic receptors are stimulated by acetylcholine and muscarine. They are found at target organs when acetylcholine is released by postganglionic neurons (parasympathetic). They are blocked by atropine.

Enzimes
Proteins that play important roles in protein synthesis inside the cells - adenylate cyclase - guanilate cyclase - phospholipase C - protein kinases A, C

 Second M essengers - substances inside the cells that mediate the

action of ligands acting on the cells

cAMP cGMP IP3 Diacyl-glicerol

PERIPHERAL PROTEINS CYTOSKELETON-CYTOSKELETON-

The skeleton maintains the shape of the cells ( during cell divisions), realises some selective movements or activities of intercellular transport ( vesicles )

C YTOSKELETON CYTOSKELETON

Transport of substances across the cell membrane

- Using as a criterium the dimensions of transported molecules: - microtransfer system - macrotransfer system

1. Microtransfer system
PASSIVE TRANSPORT - transport according the concentration gradients of substances - without energy consumer

ACTIVE TRANSPORT -against gradients - with energy consumer

Transport of substances across the cell membrane

1. PASSIVE TRANSPORT
1 .1.DIFFUSION :

-3 types : - simple diffusion . - diffusion facilitated by carrier protein - diffusion using channel proteins 1.2. OSMOSIS

1. PASSIVE TRANSPORT

1.1.1 .Simple Diffusion

- without energy consumer - takes place until all concentrations are equal. -substance flow depends of : - concentrations difference ( D ) -membrane permeability ( P ) Fick low : - surface ( S)

Flow D x P x S

- liposoluble substances cross the membrane dissolving in lipidic bilayer (O2, CO2) - Hidrosoluble substances cross membranes using membrane proteins ( channels )

Simple Diffusion

1.1.2. Diffusion facilitated by carrier protein

- Selectivity - Specificity - Saturation - takes place according gradients . - with superior speed and debit than concentrations difference - uses a carrier protein - without energy consumer - stops when concentrations become equal. - limitated by a maximum capacity of transport imitat induced by the saturation of the transporter ( ex. glucose ) - low transport capacity in comparation with ions channels (102-103 molecules/sec)

1.1.3.Diffusion using channel A = poarta activare (deschis de depolarizare) proteins

- for particles with electric charge. - takes place according gradients . - with superior speed and debit than concentrations difference without energy consumer - stops when concentrations become equal.

B = poarta inactivare (nchis de depolarizare )

Ions channels : - High selectivity for only one ion - With permeability modulation of the channel ( ex.- membrane potential )

Na channel

1.2. OSMOSIS
-Mechanism of passive transport -Allows passage of water from a compartment with lower concentrations in a compartment with higher concentration Osmotic pressure - a force used to stop the movement of water through a membrane which separate a solution from pure water.

Transport of substances across the cell membrane

2. ACTIVE TRANSPORT

- against gradients
- with energy consumer

2. 1. PRIMARY ACTIVE TRANSPORT 2.2. SECONDARY ACTIVE TRANSPORT

2. ACTIVE TRANSPORT 2. 1. PRIMARY ACTIVE TRANSPORT

- uses a system directed coupled with an energy reactions . - ionic pumps - energy source = ATP ( synthesized by mithocondrion ) - ATP -- ADP + P (ATP-ase) - ATP-ase Na/K or Na pump - in almost cell membranes. ( role in maintenance of high concentration of K inside the cell - maintenance of membrane potential ) - inhibited by medicines - digitala, ouabaina

Ca2+

Ca ATP-ase 4 Muscle cell . 4 Endoplasmic reticulum .

H+

H+ ATP- ase 4 renal tubular cells acidification of urine .

2.2. SECONDARY ACTIVE TRANSPORT

4 the primary active transport generate chemical gradients or electrical gradients which represent ,,forces used to transfer of other substances using a common transporter. 4 simport co-transport ( glucose ) 4 antiport contra- transport ( Na-K )

INT

Transport of substances across the cell membrane - macrotransfer system4 CYTOSIS - Transport of big particles across cell membrane - 5-400 nm. - Specific for macromolecules: - proteins - lipoproteins - polizaharides
Endocytosis vesicles are incorporated in cells by invagination , using ATP. phagocytosis for solid particles - pinocytosis for liquid particles Exocytosis vesicles are eliminated from the membrane . Trancytosis - macromolecules cross cell membrane .

MEMBRANE POTENTIAL
- Because of the selective permeability of cell membrane, there is a differentiated repartition of ions inside and outside of the cell. - Inside predominate potassium ions,while outside predominate sodium ions, the interior of the cell being more negative as compared with the exterior. The difference of electrical charges creates a membrane potential of -70 mV at rest (resting potential). Potassium ions have a tendency to leak out by facilitated diffusion through channel proteins. Most of sodium channels are gated and remained closedv keeping the concentration outside high. The difference is maintained by the active transport of ions across the membrane by the sodium-potassium pump .

 When the cell receives a

signal, like a voltage variation,the permeability of the membrane changes because voltage gated sodium channels open and sodium flows inward. The inside of the cell briefly becomes more positive than outside. The abrupt modification of the polarity, with a depolarising and a repolarising phase, constitutes the action potential. When the depolarization is ended the sodium channels close and potassium channels open. Finally, the sodium potassium pump becomes operational and restores the resting potential .

Action Potential

 The resting and action potentials can be measured using intracellular

microelectrodes, made of thin glass tubes with a sharp tip, filled with potassium chloride. The microelectrodes can be introduced in the cell without the destruction of the membrane and the difference of electrical potential is recorded on oscilloscope.