Cited by 151Cardiac electrophysiology and arrhythmiasIon channel regulation and functionCardiac pacing and defibrillation studies

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The cardiac pacemaker current

Baruscotti, Mirko, Barbuti, Andrea, Bucchi, Annalisa·2010·Journal of Molecular and Cellular Cardiology

DOI 10.1016/j.yjmcc.2009.06.019

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Abstract

In mammals cardiac rate is determined by the duration of the diastolic depolarization of sinoatrial node (SAN) cells which is mainly determined by the pacemaker I(f) current. f-channels are encoded by four members of the hyperpolarization-activated cyclic nucleotide-gated gene (HCN1-4) family. HCN4 is the most abundant isoform in the SAN, and its relevance to pacemaking has been further supported by the discovery of four loss-of-function mutations in patients with mild or severe forms of cardiac rate disturbances. Due to its selective contribution to pacemaking, the I(f) current is also the pharmacological target of a selective heart rate-reducing agent (ivabradine) currently used in the clinical practice. Albeit to a minor extent, the I(f) current is also present in other spontaneously active myocytes of the cardiac conduction system (atrioventricular node and Purkinje fibres). In working atrial and ventricular myocytes f-channels are expressed at a very low level and do not play any physiological role; however in certain pathological conditions over-expression of HCN proteins may represent an arrhythmogenic mechanism. In this review some of the most recent findings on f/HCN channels contribution to pacemaking are described.

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2 retracted

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Authors: Baruscotti, M., Barbuti, A., & Bucchi, A.
Affiliations: University of Milan (IT)
Corresponding author: Baruscotti, Mirko
ORCID: Baruscotti, Mirko
Barbuti, Andrea
Bucchi, Annalisa
Venue: Journal of Molecular and Cellular Cardiology
Publisher: Elsevier BV
Published: 2010-01
Volume: 48
Issue: 1
Pages: 55-64
ISSN: 0022-2828 (ISSN-L)
DOI: 10.1016/j.yjmcc.2009.06.019
OpenAlex: W2040918451
Cited by: 149
References: 153
Citations by year: 2026: 3 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 1 · 2021: 12 · 2020: 8 · 2019: 4 · 2018: 9 · 2017: 8 · 2016: 8 · 2015: 6 · 2014: 20 · 2013: 14 · 2012: 11
FWCI: 1.86
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Molecular and Cellular Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: European Commission
Ministero dell'Università e della Ricerca
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
Keywords: HCN channels, HCN4, sinoatrial node, cardiac pacemaking, ivabradine, heart rate regulation, cardiac arrhythmias, atrioventricular node, Purkinje fibers
MeSH terms: Animals, Heart Rate, Humans, Models, Biological, Myocardium, Sinoatrial Node, Cyclic Nucleotide-Gated Cation Channels

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