title: Voltage sensing and activation gating of HCN pacemaker channels.
abstract: Activation of pacemaker channels underlie the spontaneous diastolic depolarization of sinoatrial node cells in the heart. Four similar genes encoding these hyperpolarization-activated, cyclic nucleotide-gated channels were recently cloned and subsequently named HCN1-4. Here we review the physiological role of HCN channels and recent findings regarding mechanisms of channel gating. Like all other voltage-gated channels, site-directed mutagenesis analysis indicates that the highly charged S4 transmembrane domain is the voltage sensor. However, unlike most other channels channel, opening occurs in response to membrane hyperpolarization rather than depolarization.
authors.affiliation: Department of Medicine, Division of Cardiology and Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: David R
authors.initials: DR
authors.lastname: Piper
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sanguinetti
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008958:Models, Molecular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins; D015221:Potassium Channels
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578665:HCN1 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels