Beyond pacemaking: HCN channels in sinoatrial node function

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are key proteins involved in the initiation and regulation of the heartbeat. Pacemaker cells within the sinoatrial node generate the electrical impulse that underlies the contraction of all atrial and ventricular cardiomyocytes. To generate a stable heart rhythm, it is necessary that the spontaneous activity of pacemaker cells is synchronized. Entrainment processes in the sinoatrial node create synchrony and also mediate heart rate regulation. In the past years it has become clear that the role of HCN channels goes beyond just pacemaking and that the channels play pivotal roles in these entrainment processes that coordinate and balance sinoatrial node network activity. Here, we review the role of HCN channels in the central pacemaker process and highlight new aspects of the contribution of HCN channels to stabilizing the electrical activity of the sinoatrial node network, especially during heart rate regulation by the autonomic nervous system. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

HCN channels are essential for heart rhythm initiation and regulation, synchronizing pacemaker cells for stable heart function. Entrainment processes in the sinoatrial node play a crucial role in coordinating heart activity and regulating heart rate.