Sodium Channel Activation and Inactivation.

Results from more recent experiments have shown that the mechanism that controls the sodium ion current lies in the voltage sensitive sodium channel protein. A propagating action potential gives rise to positive charge moving inside of the axon, which causes a decrease in the transmembrane potential. This change in transmembrane potential results in a conformation change in the sodium ion channel. The four S4 segment alpha helices translocate, which leads to an opening of the channel pore. Sodium ions flow down the concentration gradient and the voltage gradient, causing the potential inside of the axon to become more positive. Thereafter, a second mechanism comes to play. The linker loop between the S4 & S5 domains alters its conformation to move into the channel and block further sodium ion flow. The blocking effect of the linker is often likened to that of ball, on a chain, moving in to block ion movement through the channel. It is this second phenomenon that results in inactivation state of the channel.

An extracellular electrical stimulus can alter the transmembrane potential in a way that is similar to the way a propagating action potential alters the transmembrane potential. The process of normal action potential propagation involves sequentially gating open sodium ion channels in a timed, proximal to distal, fashion. When the upstream sodium ion channels open the potential inside the nerve membrane becomes more positive. This increase in potential causes the transmembrane potential downstream, distally, to rise and to cause those ion channels to go from a resting state to an active state. This process gives rise to a propagated action potential. When an extracellular current is applied, as when electrically activating a nerve, the potential in the vicinity of the axon decreases, giving rise to a decrease in the transmembrane potential at the site containing the voltage gated sodium ion channels. This change in voltage results in opening of the channels in the resting state and initiates the same sequence of events that occur when a propagating action potential invades the axon membrane.