Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease

The funny current, If, was first recorded in the heart 40 or more years ago by Dario DiFrancesco and others. Since then, we have learnt that If plays an important role in pacemaking in the sinus node, the innate pacemaker of the heart, and more recently evidence has accumulated to show that If may play an important role in action potential conduction through the atrioventricular (AV) node. Evidence has also accumulated to show that regulation of the transcription and translation of the underlying Hcn genes plays an important role in the regulation of sinus node pacemaking and AV node conduction under normal physiological conditions-in athletes, during the circadian rhythm, in pregnancy, and during postnatal development-as well as pathological states -ageing, heart failure, pulmonary hypertension, diabetes and atrial fibrillation. There may be yet more pathological conditions involving changes in the expression of the Hcn genes. Here, we review the role of If and the underlying HCN channels in physi-ological and pathological changes of the sinus and AV nodes and we begin to explore the signalling pathways (microRNAs, transcription factors, GIRK4, the autonomic nervous system and inflammation) involved in this regulation. This review is dedicated to Dario DiFrancesco on his retirement. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

This review summarizes the discovery of the funny current If in the heart several decades ago, as well as its important role in the sinus node and atrioventricular node. Studies have shown that the transcription and translation of Hcn genes play a crucial role in pacemaking in the sinus node and conduction in the atrioventricular node under normal physiological conditions and pathological states.