Structures of the Human HCN1 Hyperpolarization-Activated Channel.

ABSTRACT: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the control of rhythmic activity in cardiac and neuronal pacemaker cells. In HCN, the polarity of voltage dependence is uniquely reversed. Intracellular cyclic adenosine monophosphate (cAMP) levels tune the voltage response, enabling sympathetic nerve stimulation to increase the heart rate. We present cryo-electron microscopy structures of the human HCN channel in the absence and presence of cAMP at 3.5 Å resolution. HCN channels contain a K⁺ channel selectivity filter-forming sequence from which the amino acids create a unique structure that explains Na⁺ and K⁺ permeability. The voltage sensor adopts a depolarized conformation, and the pore is closed. An S4 helix of unprecedented l

SUBMITTER: Lee CH 

PROVIDER: S-EPMC5496774 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature