cyclic AMP Regulation and Its Command in the Pacemaker Channel HCN4

Frontiers in Physiology

Gerhard Thiel¹  Andrea Saponaro²  Alessandro Porro²  Anna Moroni² 

[1] Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany;Department of Biosciences, University of Milan, Milan, Italy;

关键词: cyclic AMP;    hyperpolarization-activated cyclic nucleotide-gated (HCN) channels;    regulation;    structure;    “funny” current;    heart rate;   

DOI  :  10.3389/fphys.2020.00771

来源: DOAJ

【 摘 要 】

Direct regulation of the pacemaker “funny” current (If) by cyclic AMP (cAMP) underlies heart rate modulation by the autonomic nervous system. At the molecular level, cAMP activates hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that drive If in sinoatrial node (SAN) myocytes. Even though HCN channel genes were identified more than 20 years ago, the understanding of how cAMP regulates their gating is still fragmented. Here we summarize present understanding on how the cAMP signal is transmitted from the cytosolic to the transmembrane (TM) domain in HCN4. We further discuss how detailed structural knowledge prompted the development of pharmacological/genetic tools for the control of cAMP regulation in these channels.

【 授权许可】

Unknown