Intrinsic opening of BK channels derives from the leakage of hydrophobic gating

Abstract

Many ion channels contain sub-nanometer hydrophobic pores that have been suggested to undergo hydrophobic dewetting transitions to form vapor barriers and block ion permeation as a mechanism for channel gating. However, support for such a hydrophobic gating mechanism, which differs from the canonical gating mechanism based on physical blockage, has been indirect and mainly comes from computational, structural and mutagenesis analyses. The key difficulty is the lack of effective assays to functionally study the hydrophobic gate in the closed state, when dewetting has happened and the vapor barrier is formed.