S4 MUTATIONS ALTER THE SINGLE-CHANNEL GATING KINETICS OF SHAKER K+ CHANNELS

The S4 sequence comprises at least part of the voltage sensor in Shaker K+ channels. Two site-directed mutations in the Shaker S4 sequence, R368Q and R377K, which decrease the voltage dependence of the whole-cell current, alter voltage-dependent gating at the single-channel level. Compared with the wild-type channel, they increase the latency to first opening, destabilize the open state, and alter the equilibria of voltage-dependent transitions, so that some of the charge movement occurs after the first opening. Whether these changes reflect a new mechanism of activation is a key question. Although the mutations alter the kinetics of many steps in the gating process, we conclude that the mutant channels are likely to activate using the same fundamental mechanism as wild-type channels.