Interplay between VSD, pore, and membrane lipids in electromechanical coupling in HCN channels.

ABSTRACT: Hyperpolarized-activated and cyclic nucleotide-gated (HCN) channels are the only members of the voltage-gated ion channel superfamily in mammals that open upon hyperpolarization, conferring them pacemaker properties that are instrumental for rhythmic firing of cardiac and neuronal cells. Activation of their voltage-sensor domains (VSD) upon hyperpolarization occurs through a downward movement of the S4 helix bearing the gating charges, which triggers a break in the alpha-helical hydrogen bonding pattern at the level of a conserved Serine residue. Previous structural and molecular simulation studies had however failed to capture pore opening that should be triggered by VSD activation, presumably because of a low VSD/pore electromechanical coupling efficiency and the limited timescales acces

SUBMITTER: Elbahnsi A 

PROVIDER: S-EPMC10317503 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature