Gating movements and ion permeation in HCN4 pacemaker channels.

ABSTRACT: The HCN1-4 channel family is responsible for the hyperpolarization-activated cation current I_f/I_h that controls automaticity in cardiac and neuronal pacemaker cells. We present cryoelectron microscopy (cryo-EM) structures of HCN4 in the presence or absence of bound cAMP, displaying the pore domain in closed and open conformations. Analysis of cAMP-bound and -unbound structures sheds light on how ligand-induced transitions in the channel cytosolic portion mediate the effect of cAMP on channel gating and highlights the regulatory role of a Mg²⁺ coordination site formed between the C-linker and the S4-S5 linker. Comparison of open/closed pore states shows that the cytosolic gate opens through concerted movements of the S5 and S6 transmembrane helices. Furtherm

SUBMITTER: Saponaro A 

PROVIDER: S-EPMC8294335 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature