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

Boyett, Mark R.; Yanni, Joseph; Tellez, James; Bucchi, Annalisa; Mesirca, Pietro; Cai, Xue; Logantha, Sunil Jit R.J.; Wilson, Claire; Anderson, Cali; Ariyaratnam, Jonathan; Stuart, Luke; Nakao, Shu; Abd Allah, Eman; Jones, Sandra; Lancaster, Matthew; Stephenson, Robert; Chandler, Natalie; Smith, Matthew; Bussey, Carol; Monfredi, Oliver; Morris, Gwilym; Billeter, Rudi; Mangoni, Matteo E.; Zhang, Henggui; Hart, George; D'Souza, Alicia

Abstract

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 physiological 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.

Citation

Boyett, M. R., Yanni, J., Tellez, J., Bucchi, A., Mesirca, P., Cai, X., …D'Souza, A. (in press). Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease. Progress in Biophysics and Molecular Biology, https://doi.org/10.1016/j.pbiomolbio.2021.06.008

• Journal Article Type: Article
• Acceptance Date: Jun 14, 2021
• Online Publication Date: Jun 28, 2021
• Deposit Date: Jul 14, 2021
• Publicly Available Date: Jun 29, 2022
• Journal: Progress in Biophysics and Molecular Biology
• Print ISSN: 0079-6107
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.pbiomolbio.2021.06.008
• Keywords: Cardiac conduction system; Cardiac arrhythmias; Athletic training; Circadian rhythm; Ageing; Heart failure
• Public URL: https://hull-repository.worktribe.com/output/3804126