Deactivation retards recovery from inactivation in Shaker K+ channels

In Na+ channels, recovery from inactivation begins with a delay, followed by an exponential course, and hyperpolarization shortens the delay as well as hastens the entire exponential phase. These findings have been taken to indicate that Na+ channels must deactivate to recover from inactivation, and deactivation facilitates the unbinding of the inactivating particle. In contrast, it is demonstrated in this study that recovery from inactivation in Shaker K+ channels begins with no delay on repolarization. Moreover, hyperpolarization hastens only the initial phase (fast component) of recovery yet retards the later phases of recovery by increasing the proportion of slow components. The time course of slow inward "tail" K+ currents, which presumably result from the open state(s) traversed by the recovering inactivated channel, always matches the fast, but not the slow, components of recovery, suggesting that the fast and the slow components primarily correspond to recovery via the open state (unblocking of the inactivating particle before channel deactivation) and via the closed state (deactivation before unblocking), respectively. Besides, changing external K+ concentration effectively alters the absolute value of the initial recovery speed, but not its voltage dependence. It seems that Shaker K+ channel deactivation hinders, rather than facilitates, the unbinding of the inactivating particle and therefore retards recovery from inactivation, whereas external K+ may enhance unbinding of the inactivating particle by binding to a site located near the external entrance of the pore.