Inactivation of the Sodium Channel

Inactivation of the Sodium Channel

VOLUME 70, 1977 | CLAY M. ARMSTRONG and FRANCISCO BEZANILLA
The paper by Clay M. Armstrong and Francisco Bezanilla investigates the relationship between gating current (Ig) and sodium channel inactivation. They find that no component of Ig has the time course of inactivation, suggesting that little or no charge movement is associated with this process. However, inactivation affects Ig by immobilizing about two-thirds of the gating charge. This immobilization can be observed by measuring ON charge movement during a pulse and comparing it to OFF charge after the pulse. The OFF:ON ratio is near 1 for short pulses where no inactivation occurs, and drops to about one-third with a time course parallel to inactivation. Other correlations between inactivation and immobilization include their shared voltage dependence and the recovery of charge movement with the time course of recovery from inactivation. The authors interpret this as meaning that the immobilized charge returns slowly to the "off" position with the time course of recovery from inactivation, and the small current generated is lost in baseline noise. At -150 mV, recovery is very rapid, and the immobilized charge forms a distinct slow component of current as it returns to the off position. After inactivation is destroyed by pronase, there is no immobilization of charge. A model is presented where inactivation gains its voltage dependence by coupling to the activation gate. The paper also discusses the existence of multiple open states of sodium channels and the implications for gating current components.The paper by Clay M. Armstrong and Francisco Bezanilla investigates the relationship between gating current (Ig) and sodium channel inactivation. They find that no component of Ig has the time course of inactivation, suggesting that little or no charge movement is associated with this process. However, inactivation affects Ig by immobilizing about two-thirds of the gating charge. This immobilization can be observed by measuring ON charge movement during a pulse and comparing it to OFF charge after the pulse. The OFF:ON ratio is near 1 for short pulses where no inactivation occurs, and drops to about one-third with a time course parallel to inactivation. Other correlations between inactivation and immobilization include their shared voltage dependence and the recovery of charge movement with the time course of recovery from inactivation. The authors interpret this as meaning that the immobilized charge returns slowly to the "off" position with the time course of recovery from inactivation, and the small current generated is lost in baseline noise. At -150 mV, recovery is very rapid, and the immobilized charge forms a distinct slow component of current as it returns to the off position. After inactivation is destroyed by pronase, there is no immobilization of charge. A model is presented where inactivation gains its voltage dependence by coupling to the activation gate. The paper also discusses the existence of multiple open states of sodium channels and the implications for gating current components.
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