Microsecond Simulations Indicate 3_10 Helix Transition Facilitates Translation of the S4 Segment of Kv1.2 and Suggest a Hydrophobic Gating Barrier

Abstract

The stabilization and motion of the arginine-containing S4 segment have been of considerable interest for studies of voltage-regulated potassium channels, with several competing models for the gating. Here, we present results from atomistic simulations on microsecond scale both of integral Kv1.2/2.1 channels as well as voltage sensors. The results support a model where the crystal structure reflects the open-inactivated state, but starts a transition towards a normal open state with increasing 3_10 helix structure upon hyperpolarization (but not when depolarized).