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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


Mark R. Boyett

Joseph Yanni

James Tellez

Annalisa Bucchi

Pietro Mesirca

Xue Cai

Sunil Jit R.J. Logantha

Claire Wilson

Cali Anderson

Jonathan Ariyaratnam

Luke Stuart

Shu Nakao

Eman Abd Allah

Matthew Lancaster

Robert Stephenson

Natalie Chandler

Matthew Smith

Carol Bussey

Oliver Monfredi

Gwilym Morris

Rudi Billeter

Matteo E. Mangoni

Henggui Zhang

George Hart

Alicia D'Souza


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.


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,

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
Keywords Cardiac conduction system; Cardiac arrhythmias; Athletic training; Circadian rhythm; Ageing; Heart failure
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