Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current If

Anna Moroni, Luisa Gorza, Monica Beltrame, Biagio Gravante, Thomas Vaccari, Marco E. Bianchi, Claudia Altomare, Renato Longhi, Catherine Heurteaux, Maurizio Vitadello, Antonio Malgaroli, Dario DiFrancesco

Research output: Contribution to journalArticle

Abstract

The pacemaker current If of the sinoatrial node (SAN) is a major determinant of cardiac diastolic depolarization and plays a key role in controlling heart rate and its modulation by neurotransmitters. Substantial expression of two different mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit SAN, suggesting that the native channels may be formed by different isoforms. Here we report the cloning and heterologous expression of HCN1 from rabbit SAN and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid protein that, in human embryonic kidney 293 cells, displayed electrophysiological properties similar to those of I f, suggesting that HCN1 can form a pacemaker channel. The presence of HCN1 in the SAN myocytes but not in nearby heart regions, and the electrophysiological properties of the channels formed by it, suggest that HCN1 plays a central and specific role in the formation of SAN pacemaker currents.

Original languageEnglish
Pages (from-to)29233-29241
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number31
DOIs
Publication statusPublished - Aug 3 2001

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Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Pacemakers
Sinoatrial Node
Muscle Cells
Cloning
Depolarization
Rabbits
Neurotransmitter Agents
Protein Isoforms
Modulation
Organism Cloning
Amino Acids
Messenger RNA
Heart Rate
Kidney
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current If. / Moroni, Anna; Gorza, Luisa; Beltrame, Monica; Gravante, Biagio; Vaccari, Thomas; Bianchi, Marco E.; Altomare, Claudia; Longhi, Renato; Heurteaux, Catherine; Vitadello, Maurizio; Malgaroli, Antonio; DiFrancesco, Dario.

In: Journal of Biological Chemistry, Vol. 276, No. 31, 03.08.2001, p. 29233-29241.

Research output: Contribution to journalArticle

Moroni, A, Gorza, L, Beltrame, M, Gravante, B, Vaccari, T, Bianchi, ME, Altomare, C, Longhi, R, Heurteaux, C, Vitadello, M, Malgaroli, A & DiFrancesco, D 2001, 'Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current If', Journal of Biological Chemistry, vol. 276, no. 31, pp. 29233-29241. https://doi.org/10.1074/jbc.M100830200
Moroni, Anna ; Gorza, Luisa ; Beltrame, Monica ; Gravante, Biagio ; Vaccari, Thomas ; Bianchi, Marco E. ; Altomare, Claudia ; Longhi, Renato ; Heurteaux, Catherine ; Vitadello, Maurizio ; Malgaroli, Antonio ; DiFrancesco, Dario. / Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current If. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 31. pp. 29233-29241.
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