Voltage-dependent sodium channels

The Voltage-dependent sodium channels (Na_vs) are big glycoproteins which span the full thickness of the plasma membrane of most excitable cells. The Nine distinct Navα subunits have been specified, in which most are expressed in neurons. In the resting potential they are closed. If their area of membrane is depolarized by only some milli volts then they remain closed as shown in figure. Though, if the membrane is depolarized to the threshold voltage or beyond, Navs alter shape therefore the channels open, permitting Na+ ions to flow down their electrochemical gradient into the neuron.

The Channel opening, activation as sown in figure is an extremely fast event (~10 µs). During the action potential in a neuron a given sodium channel will stay open for about 0.5–1 ms. At this time about 6000 Na+ ions will flow throughout the channel. The combined effect of sodium influx via a few hundred Navs will generate the upstroke of the spike which is the depolarizing phase of the action potential. Some of the voltage-dependent sodium channels only require to be driven beyond threshold initially to trigger an action potential as the localized influx of Na+ causes a depolarization that drives the other channels to open, driving a positive feedback explosive that rise in Na+ permeability.

Figure: Behavior of a voltage-dependent sodium channel (a) at rest if it is in the closed state and (b) during the spike of an action potential, if it is activated.

At the top of the spike the self-regenerative rise in the sodium permeability is halted for three causes which are as shown below:

- All of the available Navs in the active area of membrane have opened.

- The ionic driving force for sodium gets less as the membrane depolarizes towards the sodium equilibrium potential.

- The voltage-dependent sodium channels flip into the inactivated state. During this state the channel does not allow the flow of any ions (Note that this is not similar as the closed state since the inactivated state cannot be made to open).Additionally to curtailing the spike, it is this inactivation of Navs which is responsible for the absolute refractory period. The inactivation wears off subsequent to a few milliseconds as the channel relaxes into the closed state, from that it can be reactivated by consequent depolarization.