The Ionic mechanism and propagation of action potentials.
The action potential is the result of a large, sudden increase in sodium permeability of the membrane. The resulting rush of sodium ions into the membrane and accumulation of positive charge on its inner surface drives the potential towards Ena. This is followed by repolarisation, whereby there is a large increase in the membranes permeability to potassium ions, hence the membrane returns to Ek. Explanation of the (ionic) mechanisms underlying generation of the action potential leads directly to understanding impulse propagation.
The main feature underlying the ion currents associated with the action potential is that both the sodium and potassium conductances are voltage dependent. Depolarisation increases the membrane’s conductance to sodium ions and, after a delay, potassium. Hence it becomes more likely for sodium ion channels to open with depolarisation. Following a small depolarisation, the number of sodium ion channels open increases and sodium enters the membrane down its electrochemical gradient. This produces further depolarisation, opening more sodium ion channels, with more rapid sodium entry. This effect of sodium conductance is regenerative and known as positive feedback. At the peak of the action potential there is an overshoot during which the membrane potential becomes positive on the inside. This is because sodium entry across the membrane continues beyond zero membrane potential until sodium equilibrium potential is reached
Conversely, the voltage dependence of potassium conductance is self-limiting and involves negative feedback. Depolarisation increases the number of potassium ion channels open and there is an efflux of potassium down its electrochemical gradient. Rather than causing more sodium channels to open, as is the case with sodium, the efflux leads to repolarisation and return of potassium conductance to its resting level. The depolarisation inactivates sodium channels; however, it is not the case that sodium channels simply close. The experimentally observed falling phase in the action potential occurs much more quickly. The return to normal is rapid due to the opening of voltage-activated potassium channels, so the increase in potassium permeability can last for several milliseconds so that in many cells, the membrane is actually hyperpolarised beyond its normal resting potential.
For an action potential to fire, an external stimulus must depolarise the membrane above threshold so stimulate a sufficient number of sodium ion channels. External stimuli can come in the form of an electrode, synaptic event or propagation of a depolarising wave along the cell membrane. The number of sodium channels activated by the stimulus is determined by the voltage dependence of the activation process. Opposing factors are current losses from the passive spread of current through intracellular and extracellular fluid and the hyperpolarising effect from potassium (and chlorine) channels. So the threshold level is the level of depolarisation at which the depolarising effect of open sodium channels can overcome these opposing factors.
Two changes develop during an action potential that make it impossible for the nerve fibre to produce a second action potential immediately: during the fall phase, inactivation of all the sodium ion channels and because activation of potassium channels is large, and only slowly returns to resting level. These two factors result in absolute refractory period. This is followed by relative refractory period, during which the threshold gradually returns to normal so sodium channels recover from inactivation.
A technique called voltage clamp allows one to measure ionic flux directly. The voltage clamp apparatus allows the manipulation of the membrane potential of a cell while measuring the membrane current. Effectively, the membrane potential is ‘clamped’ while the current flowing across the membrane is measured....
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