Calcium-dependent gating of MthK, a prokaryotic potassium channel

Abstract

MthK is a calcium-gated, inwardly rectifying, prokaryotic potassium channel. Although little functional information is available for MthK, its high-resolution structure is used as a model for eukaryotic Ca 2+-dependent potassium channels. Here we characterize in detail the main gating characteristics of MthK at the single-channel level with special focus on the mechanism of Ca2+ activation. MthK has two distinct gating modes: slow gating affected mainly by Ca2+ and fast gating affected by voltage. Millimolar Ca2+ increases MthK open probability over 100-fold by mainly increasing the frequency of channel opening while leaving the opening durations unchanged. The Ca2+ dose-response curve displays an unusually high Hill coefficient (n = ∼8), suggesting strong coupling between Ca2+ binding and channel opening. Depolarization affects both the fast gate by dramatically reducing the fast flickers, and to a lesser extent, the slow gate, by increasing MthK open probability. We were able to capture the mechanistic features of MthK with a modified MWC model. © The Rockefeller University Press.