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

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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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ASJC Scopus subject areas

  • Biochemistry

Cite this

Moroni, A., Gorza, L., Beltrame, M., Gravante, B., Vaccari, T., Bianchi, M. E., 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, 276(31), 29233-29241. https://doi.org/10.1074/jbc.M100830200