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

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; Sandra Jones; 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

doi:10.1016/j.pbiomolbio.2021.06.008

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

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, Sandra Jones, Matthew Lancaster, Robert Stephenson, Natalie Chandler, Matthew Smith, Carol Bussey, Oliver MonfrediGwilym Morris, Rudi Billeter, Matteo E Mangoni, Henggui Zhang, George Hart, Alicia D'Souza

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	61-85
Journal	Progress in Biophysics and Molecular Biology
Volume	166
Early online date	28 Jun 2021
DOIs	https://doi.org/10.1016/j.pbiomolbio.2021.06.008
Publication status	E-pub ahead of print - 28 Jun 2021

Bibliographical note

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).

Keywords

Cardiac conduction system
Cardiac arrhythmias
Athletic training
Circadian rhythm
Ageing
Heart failure
Ageing,Heart failure

ASJC Scopus subject areas

Molecular Biology
Biophysics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://eprints.whiterose.ac.uk/177084/Licence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

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Boyett, M. R., Yanni, J., Tellez, J., Bucchi, A., Mesirca, P., Cai, X., Logantha, S. J. R. J., Wilson, C., Anderson, C., Ariyaratnam, J., Stuart, L., Nakao, S., Abd Allah, E., Jones, S., Lancaster, M., Stephenson, R., Chandler, N., Smith, M., Bussey, C., ... D'Souza, A. (2021). Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease. Progress in Biophysics and Molecular Biology, 166, 61-85. Advance online publication. https://doi.org/10.1016/j.pbiomolbio.2021.06.008

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title = "Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease",

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.",

keywords = "Cardiac conduction system, Cardiac arrhythmias, Athletic training, Circadian rhythm, Ageing, Heart failure, Ageing,Heart failure",

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

note = "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).",

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Boyett, MR, Yanni, J, Tellez, J, Bucchi, A, Mesirca, P, Cai, X, Logantha, SJRJ, Wilson, C, Anderson, C, Ariyaratnam, J, Stuart, L, Nakao, S, Abd Allah, E, Jones, S, Lancaster, M, Stephenson, R, Chandler, N, Smith, M, Bussey, C, Monfredi, O, Morris, G, Billeter, R, Mangoni, ME, Zhang, H, Hart, G & D'Souza, A 2021, 'Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease', Progress in Biophysics and Molecular Biology, vol. 166, pp. 61-85. https://doi.org/10.1016/j.pbiomolbio.2021.06.008

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T1 - Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease

AU - Boyett, Mark R

AU - Yanni, Joseph

AU - Tellez, James

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 - Abd Allah, Eman

AU - Jones, Sandra

AU - Lancaster, Matthew

AU - Stephenson, Robert

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).

PY - 2021/6/28

Y1 - 2021/6/28

N2 - 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.

AB - 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.

KW - Cardiac conduction system

KW - Cardiac arrhythmias

KW - Athletic training

KW - Circadian rhythm

KW - Ageing

KW - Heart failure

KW - Ageing,Heart failure

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SN - 0079-6107

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JO - Progress in Biophysics and Molecular Biology

JF - Progress in Biophysics and Molecular Biology

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Cite this