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Membrane potential, action potencial,

sensory receptors

STRUCTURE OF THE CELL MEMBRANE, BIOLOGICAL MEMBRANES

The fundamental functional unit of the living organisms is the cell which internal milieu

divided by the cell membrane from the external environment. The structure of the cell

membrane shows similarity in every cell type.

The elemental structure of the biological membranes consist of phospholipide bilayer

(5-10 nm) The two main component of the membrane are the lipids responsible for

fluidity and the proteins which determine the rigidity. There are non-covalent, strong

interaction between the components of the membrane. The fluidity of the membrane

depends on the ratio of saturated and unsaturated fatty acid side chains. There are

strong interaction between the phospholipide molecules consisting saturated fatty acid

whereas by reason of bending at the location of the double bond which can be found in

the unsaturated fatty acids the structure will be loosening. The membrane become

disordered, but the cholesterol - consisting of sterane frame - and the membrane

proteins make the membrane more rigid.

The phospholipide bilayer consist of a polar head group (hydrophil) which is

orientated to the water phase, whereas the apolar tail group (hydrophobe) is located

farther from the water phase. The strength of the interactions between the hydrophobe

fatty acid side chains of the membrane lipids are influenced by several agent. As the

temperature is increasing the strength of the hydrophobe interaction is increasing as

well. The more the number of the carbon atoms in the apolar region the stronger is the

interaction. Multiple (second-, triple) bondings also elevate the strength of the

interaction.

The components of the phospholipid bilayer

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The glycolipids which translocated on the surface of the membrane and together with

the glycoproteins are able to determine the specific antigens. The lipids which are

turning to the inner side of the membrane can interact with other membrane proteins

responsible for cell signaling between the extra-, and intracellular space.

Shematic structure of the biological membrane

The proteins are important components of the biological membranes. They can be found

on the exterior and interior surface as well as can be integrated in the membranes.

Integrated transmembrane proteins are responsible for sensing, binding and

transporting the molecules which are important for the cells. The biological membranes

are working as semipermeable membrane.

o proteins channels (provides transport for water and ions)

o transport molecules (Carrier proteins)

o peripheral proteins linked to other proteins

o linker proteins providing interaction between the extracellular matrix and

the actin cytoskeleton

Marker proteins: peripheral proteins on the external surface which are specific for

specimen or tissue.

Receptor proteins recognise specific patterns, e.g. bacterial cell surface antigens

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A „fluid mosaic” modell

Modell of the structure of the membranes by 1972 S.J. Singer és Garth L. Nicolson

Fluid – lateral movement of the components

Mosaic – the mosaic-like arrangements of the macromolecules

THE MAIN COMPONENTS OF THE INTRA-AND EXTRACELLULAR SPACE

Water Ions

o Kations (K+, Na+, Ca2+) o Anions (Cl-, H2PO4− és HPO42− ions)

Proteins o Mainly intracellular localization o Negatively charged polyvalent (having more than one valence)

macromolecules (pH! – isoelectric point)

RESTING MEMBRANE POTENTIAL

The electrical potential difference (voltage) across a cell's plasma membrane. (V).

Its value varies in different cell types (-100 mV > Uresting < -30 mV)

Forces controlling the movements of charged particles: electro-chemical potential

Chemical potential energy:

The chemical potential of a thermodynamic system is the amount of energy (Joule) by which the system would change if an additional particle were introduced (~ number of the particles!)

Concentration gradient → diffusion: moving the particles through the permeable membrane from a high concentration area to a low concentration area → diffusion potential.

Electric potential

Energy of the charged particle in electric field. An electric field creates a force that can move the charged particles (the work of the electric field) → moving charged particles = electric current.

Electro-chemical potential the combination (sum) of the chemical and the electric potential energy.

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BERNSTEIN’A POTASSIUM HYPOTHESIS (1902)

For creation of the resting membrane potential potassium could be responsible. Mobility of potassium is possible:

o The cell membrane is selectively permeable to potassium: o Ca2+ sensitive potassium channels o Inwardly rectifying potassium channels o Voltage-gated potassium channels o “Tandem pore domain potassium channel” – “leak channel”

1952: Hodgkin and Huxley suggested the leakage of current First description: Ketchum, KA; Joiner, WJ; Sellers, AJ; Kaczmarek, LK;

Goldstein, SA. (1995) A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature, 376 (6542): 690-5

The intracellular potassium concentration is high and the extracellular potassium concentration. is low.

NERNST EQUATION

Equilibrium potential: What membrane potential (E) can compensate (balance) the concentration gradient (X1 /X2).

The inward and outward flows of the ions are balanced, are in dynamic equilibrium.

Results does not match the experimental results: the ions are not independent of each other and are not a closed system.

𝐸=𝑅𝑇

𝑧𝐹ln

𝑐1

𝑐2

DONNAN POTENTIAL

Donnan equilibrium or Donnan distribution

Diffusion of ions with altering mobility (K+, Cl-) through a semipermeable membrane results in diffusion potential. If one of the charged particle (intracellular proteins) cannot diffuse through the membrane equilibrium concentration difference will be created between the two sides of the membrane

GOLDMAN-HODGKIN-KATZ EQUATION

To determine the potential across a cell's membrane taking into account all of the ions with different PERMEABILITIES through the membrane. The membrane potential is the result of a „compromise” between the various equilibrium potentials, each weighted by the membrane permeability and absolute concentration of the ions.

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Considering number N positive and number N negative ions:

.

•Em = membrane potential

•Pion = permeability concerning each ions

•[ion]out = extracellular concentration

•[ion]in = intracellular concentration

•R= universal gas constant

•T= absolute temperature

•F= Faraday constant

NA-K ATPASE

Developing the resting membrane potential the main roles have K+ and Na+ ions (different distribution and permeability). The concentration of Na+ is higher extracellularly, while the concentration of K+ is higher intracellularly. The Na-K pumps works against these concentration gradients using ATP (3 Na+ out; 2 K+ into).

Its work plays essential role establishing membrane potential.

TYPES OF SODIUM AND POTASSIUM CHANNELS

The ion channels composed of transmembrane transport proteins which can be divided into two groups.

Types of sodium channels

● Ligand-gated sodium channels

● Voltage-gated (sensitive, dependent) sodium channels

o contains a voltage sensor (Sensitive, dependent) to voltage changes in the membrane potential)

o activation gate (extracellular side)

o inactivation gate (intracellular side)

● Ca2+ sensitive (KCa)

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● Inwardly rectifying (KIR)

● “Tandem pore domain potassium channel” – “leaking channel” (K2p)

● Voltage-gated potassium channels (KV )

o Sensitive (dependent) to voltage changes in the membrane potential

Action potential

Action potential: a momentary reversal of membrane potential (- 65mV to + 40 mV) that will be followed by the restoration of the original membrane potential after a certain time period (1-400ms).

It is a result of ions moving through the membranes.

The local membrane potential changes upon stimulus. If the change reaches a threshold (threshold potential), then action potential occurs.

Action potentias happen in different phases (depolarisation and repolarisation).

Action potentials are „all or none” phenomena: any stimulation above the voltage

threshold results in the same action potential response. In any stimulation below the

voltage threshold will not result action potential response.

Phase of the action potential

Resting potential, condition of the voltage-gated Na channels (NaV):

o Aktivation gate is closed

o Inactivation gate is opened

Depolarization (increasing phase)

o Due to the stimulus over the threshold potential the voltage-gated Na

channels open

Activation gate is opened

Inactivation gate is closed

o Na+ influx occurs in the cell followed by positively charged extracellular milieu

Peak phase

o Na+ influx become slower

alteration of the membrane potential is getting closer to the value of

the equilibrium potential of Na+ (EmV_Na+ = +45,1 mV it can be

calculated by Nernst-equation)

part of the Na+ channels are inactivated

o K+ channels start to open

Repolarization (decreasing phase)

o Voltage-gated K+ channels totally open leading to great K+ out flow from the

cell

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o Condition of the voltage-gated Na+ channels:

Activation gate is opened

Inactivation gate is closed refracter periode

Undershoot (hyperpolarization)

o K+ influx become slower

alteration of the membrane potential is getting closer to the value of

the equilibrium potential of K+ (EmV_K+ = -101,2 mV it can be

calculated by the Nernst equation)

K+ channels totally close

o the slowly inactivating great number of K+ channels lead to hyperpolarization

Regeneration after action potential

o alteration of the absolute value of the intracellular ion concentration is low

during the action potential (0.0001% - 1% in thick and thin axons).

o Na-K ATPase set back the resting potential but not immediatly

Refracter periode

During the refracter periode emerging of a new action potential is partly inhibited

o Absolute refrakter periode – the occurance of a new action potential is totally

inhibited since the Na+ channels are inactive state

o Relative refrakter periode – the greater the depolarization than the threshold

potential can trigger the action potential

Source:

Biofizika előadás jegyzet

http://www.tankonyvtar.hu/hu/tartalom/tamop425/0019_1A_Elettani_alapismeretek/ch02.

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