Repolarization

In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of K+ ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K+ channel pore. In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of K+ ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K+ channel pore. Repolarization typically results from the movement of positively charged K+ ions out of the cell. The repolarization phase of an action potential initially results in hyperpolarization, attainment of a membrane potential, termed the afterhyperpolarization, that is more negative than the resting potential. Repolarization usually takes several milliseconds. Repolarization is a stage of an action potential in which the cell experiences a decrease of voltage due to the efflux of potassium (K+) ions along its electrochemical gradient.  This phase occurs after the cell reaches its highest voltage from depolarization. After repolarization, the cell hyperpolarizes as it reaches resting membrane potential (-70mV). In afterhyperpolarization, the cell sits at more negative potential than rest (about -80mV) due to the slow inactivation of voltage gated K+ delayed rectifier channels, which are the primary K+ channels associated with repolarization. At these low voltages, all of the voltage gated K+ channels close, and the cell returns to resting potential. A cell which is experiencing repolarization is said to be in its absolute refractory period.  Other voltage gated K+ channels which contribute to repolarization include A-type channels and Ca2+-activated K+ channels. Blockages in repolarization can arise due to modifications of the voltage-gated K+ channels. This is demonstrated with selectively blocking voltage gated K+ channels with the antagonist tetraethylammonium (TEA). By blocking the channel, repolarization is effectively stopped. Dendrotoxins are another example of a selective pharmacological blocker for voltage gated K+ channels. The lack of repolarization means that neuron stays at a high voltage, which slows sodium channel deinactivation to a point where there is not enough inwards Na+ current to depolarize and sustain firing. The structure of the voltage gated K+ channel is that of six transmembrane helices along the lipid bilayer. The selectivity of this channel to voltage is mediated by four of these transmembrane domains (S1-S4) - the voltage sensing domain. The other two domains (S5, S6) form the pore by which ions traverse. Activation and deactivation of the voltage gated K+ channel is triggered by conformational changes in the voltage sensing domain. Specifically, the S4 domain moves such that it activates and deactivates the pore. During activation, there is outward S4 motion, causing tighter VSD-pore linkage. Deactivation is characterized by inward S4 motion. The switch from depolarization into repolarization is dependent on the kinetic mechanisms of both voltage gated K+ and Na+ channels. Although both voltage gated Na+ and K+ channels activate at roughly the same voltage (-50 mV), Na+ channels have faster kinetics and activate/deinactivate much more quickly. Repolarization occurs as the influx of Na+ decreases (channels deinactivate) and the efflux of K+ ions increases as its channels open. Another type of K+ channel that helps to mediate repolarization in the human atria is the SK channel, which are K+ channels which are activated by increases in Ca2+ concentration. Specifically, these channels are activated when Ca2+ binds to calmodulin (CaM) because the N-lobe of CaM interacts with the channel’s S4/S5 linker to induce conformational change.