HCN channels sense temperature and determine heart rate responses to heat.

ABSTRACT: Heart rate increases with heat, [1-3] constituting a fundamental physiological relationship in vertebrates. Each normal heartbeat is initiated by an action potential generated in a sinoatrial nodal pacemaker cell. Pacemaker cells are enriched with hyperpolarization activated cyclic nucleotide-gated ion channels (HCN) that deliver cell membrane depolarizing inward current that triggers action potentials. HCN channel current increases due to cAMP binding, a mechanism coupling adrenergic tone to physiological 'fight or flight' heart rate acceleration. However, the mechanism(s) for heart rate response to thermal energy is unknown. We used thermodynamical and homology computational modeling, site-directed mutagenesis and mouse models to identify a concise motif on the S4-S5 linker of the cardia

SUBMITTER: Wu Y 

PROVIDER: S-EPMC10491304 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature