Intrinsic Opening of BK Channels Derives from Inherent Leakage in Hydrophobic Gating.

ABSTRACT: The big potassium (BK) channels remain open with a small limiting probability of P _o ~ 10^-7 at minimal Ca²⁺ and negative voltages < -100 mV. The molecular origin and functional significance of such "intrinsic opening" are not understood. Here we combine atomistic simulations and electrophysiological experiments to show that the intrinsic opening of BK channels is an inherent property of the vapor barrier, generated by hydrophobic dewetting of the BK inner pore in the deactivated state. The vapor barrier only gives rise to a finite free energy barrier, of ~ 8 kcal/mol, and cannot completely shut down K⁺ flow even when the voltage sensor domains are fully deactivated. This results in the leaking currents that can be measured at negative volt

SUBMITTER: Jia Z 

PROVIDER: S-EPMC11760684 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature