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Structural of Biological Membranes
Basis of selective permeability:
Membrane allowing the passage of only some selected small molecules e.g. ions and metabolites. It is then impermeable to large molecules (proteins and nucleic acids).
- Active transport by protein pumps e.g. Na/K ATPase – Facilitated diffusion through ion channels with different principles of gating.
- Functional types >
Glycocalyx = formed from glycoproteins on the surface of cell membranes.
- Structural types >
- Peripherally associated: Adhering strongly to the either the cytoplasmic surface (when they’re on the inside) or the extracellular surface (when they’re on the outside) of the cell membrane. They are not attached in any way to the membrane by covalent bonds.
Integral: Associated with and are through the lipid bilayer itself.
A. Transmembrane proteins: Crossing through the membrane one or more times.
B. Proteins embedded in the phospholipid bilayer without crossing it through to the other side.
C. Lipid-anchored proteins that are not embedded in the bilayer. They are covalently bound to either a lipid (e.g. a glycosyl phospholipid such as glycosylphosphatidylinositol) or a fatty acid.
Basic concept of resting membrane voltage maintenance:
The Na/K ATPase pump constantly moves 3 Na+ outside of the cell and 2 K+ inside. This way, a high concentration of K ions in the ICF and a high concentration of Na ions in ECF is also maintained.
Resting Membrane Voltage: A condition of Membrane Excitability
Diffusion potential: The magnitude of voltage generated by the movement of a certain ion by diffusion down its concentration gradient through the membrane.
Equilibrium potential: The diffusion potential of a certain ion when it is at equilibrium. Equilibrium is achieved when e.g: Diffusion of K across the membrane down its concentration gradient to the outside, the inside eventually becomes so negatively-charged in comparison to the outside that the K ions are trapped by ionic attraction forces inside the inner compartment of the membrane. The halting of the K ion movement makes the system become in equilibrium, with the transmembrane voltage set at the calculated value of 92.4 mV. Said transmembrane voltage value is therefore technically the potential generated by the separation of Cl anions (in) from the K cations (now out) on either side.
- Equilibrium potential calculation: The Nernst Equation
Ex= – RT/zxF . ln(conc. of Xi/conc. of Xo);
R= molar gas constant ; T= Absolute temperature ; zx= Valency of the ion X ; F= The Faraday Constant.
Goldmann Hodgkin-Katz Voltage Equation: For Vm calculation taking into account the permeability of specific ions.
Vrev: The reverse potential i.e. -85 mV, being the voltage at which the net current is 0 and is so called since it is the voltage at which the current would reverse direction.
Vrev = RT/F . ln( (Pk.conc.of Ko + PNa.conc.of No + PCl.conc.of Cli)/(Pk.conc.of Ki + PNa.conc.of Nai + PCl.conc.of Clo)).
Equilibrium Potential (Ex)/mV
- Total resting membrane potential = -85 mV.
Conductivity: A low conductivity for Na ions is maintained through the closing of Na channels at rest, while a high one for K is present due to the presence of open K channels. There is a continuous back-and-forth ‘leakage’ of K ions through the membrane, which leads to no significant change in RMP. The high resting membrane K conductivity is what the RMP depends on.
Na and K Currents
Ix = gx . (E – Ex); I = Single channel current – g = Specific voltage and time-dependent conductance – E = Membrane voltage.
During depolarization and transpolarization: A high g of Na. During repolarization or hyperpolarization: A high E-EK as the electrical gradient for K ions is high in the outward direction [the E (Vm) is still in the positives as there is an aftermath of depolarization].
Action Potential: A propagation of an electrical signal which is induced by the increase in the current of sodium moving into the cell
Characteristics of the action potential: All-or-nothing response – propagation without decrement along the cell membrane’s length – the succession of a refractory period in which it is impossible to elicit the same change in membrane potential at the same magnitude.
Dependence of the magnitude of the synaptic i.e. action potential: On the concentration of acetylcholine transmitted to the post-synaptic membrane.
Local currents: The mode of propagation of the action potential along the length of the membrane from the small patch of membrane whose Na channels opened and which consequently depolarized.
Sequence of Events during the Action Potential
Opening of Na channels: Done through the binding of an excitatory neurotransmitter to the channel; it opens as a conformational change is induced in it.
Positive feedback: The opening of the first ligand-gated-Na channel elicits the opening of neighboring voltage-gated Na channels, eventually leading to an influx of Na ions into the cell down both their electrical and chemical gradients.
- The increase in positive charges in the ICF lead to the efflux of some potassium ions through the membrane, being repelled by the sodium ions. This efflux occurs at the point of transpolarization, when the peak membrane potential of +50mV is reached, and the overlap between influx and efflux of Na and K ions only lasts until shortly after transpolarization.
- As the movement of Na ions into the cell halts, the outward movement of K continues on in order to make the inner compartment of the membrane more and more negative. This results in the repolarization of the membrane back to its RMP of -85 mV, and a possible further hyperpolarization to more highly negative values.
- The sodium channels are closed at this point, and are in an inactivated state during the refractory period.
- Absolute refractory period: Spans from the point of eliciting the action potential by exceeding the threshold one until the near-completion of repolarization. It is characterized by the impossibility of any triggering of a new action potential, irrespective of the magnitude or duration of the stimulus.
- Relative refractory period: Spans from a ¾ completion point of repolarization (the downward slope). It is characterized by the need of a stimulus higher than that which would be enough for the typical threshold potential level, or one of longer duration.
Speed of electrical signal propagation dependence:
On: Local currents’ intensity, value of resistance of the myelin sheath, and the resistance of the neurolemma itself.
Definition: Small increases of Vm to the positive side, at an extent proportional to the subthreshold depolarizing stimulus applied, or small decreases of Vm to the negative side, at an extent proportional to the hyperpolarizing stimulus.
Main difference to action potentials: Their decrement as they propagate along the cell membrane.
Differences in Action Potential Duration in Different Muscle Tissues
Notes by: Lina El Rifaei