TY - JOUR
T1 - Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease
AU - Boyett, Mark
AU - Yanni Gerges, Joseph
AU - Tellez, James O
AU - Bucchi, Annalisa
AU - Mesirca, Pietro
AU - Cai, Xue
AU - Logantha, Sunil Jit R.J.
AU - Wilson, Claire
AU - Anderson, Cali
AU - Ariyaratnam, Jonathan
AU - Stuart, Luke
AU - Nakao, Shu
AU - Allah, Eman Abd
AU - Jones, Sandra A.
AU - Lancaster, Matthew
AU - Stephenson, Robert S
AU - Chandler, Natalie
AU - Smith, Matthew
AU - Bussey, Carol
AU - Monfredi, Oliver
AU - Morris, Gwilym
AU - Billeter, Rudi
AU - Mangoni, Matteo E.
AU - Zhang, Henggui
AU - Hart, George
AU - D'Souza, Alicia
N1 - Funding Information:
Many people have been involved in the work on the sinus and AV nodes in the laboratory of M.R.B. at the Universities of Leeds and Manchester since the 1980's and, on the occasion of M.R.B.'s retirement, M.R.B. would like to thank them. A special thank you is owed to Itsuo Kodama and Haruo Honjo from the University of Nagoya who introduced M.R.B. to nodal tissue, and Halina Dobrzynski who pioneered many of the strategies and techniques used and who led many of the studies reviewed here. The work was generously supported by a series of five five-year programme grants (final programme grant, PG/15/16/31330) as well as project grants, scholarships and fellowships from the British Heart Foundation to M.R.B. This work is currently supported by a British Heart Foundation Intermediate Fellowship to A.D. (FS/19/1/34035), a British Heart Foundation Ph.D. Studentship to C.A., and a Fondation Leducq grant to M.E.M., M.R.B. and others (TNE FANTASY 19CV03).
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/11/2
Y1 - 2021/11/2
N2 - The funny current, I
f, was first recorded in the heart 40 or more years ago by Dario DiFrancesco and others. Since then, we have learnt that I
f 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 I
f 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 I
f 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.
AB - The funny current, I
f, was first recorded in the heart 40 or more years ago by Dario DiFrancesco and others. Since then, we have learnt that I
f 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 I
f 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 I
f 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.
KW - Ageing
KW - Athletic training
KW - Cardiac arrhythmias
KW - Cardiac conduction system
KW - Circadian rhythm
KW - Heart failure
U2 - 10.1016/j.pbiomolbio.2021.06.008
DO - 10.1016/j.pbiomolbio.2021.06.008
M3 - Review article
SN - 0079-6107
VL - 166
SP - 61
EP - 85
JO - Progress in biophysics and molecular biology
JF - Progress in biophysics and molecular biology
ER -
