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A more recent version of this article appeared on July 27, 2001
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M100830200v1
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Papers In Press, published online ahead of print April 27, 2001
J. Biol. Chem, 10.1074/jbc.M100830200
Submitted on January 29, 2001
Revised on April 27, 2001
Accepted on April 27, 2001

HCN1 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, and Dario DiFrancesco

Dept. of General Physiology and Biochemistry, Università degli Studi di Milano, Milano, Mi 20133

Corresponding Author: anna.moroni{at}unimi.it

The pacemaker current If of the sino-atrial 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 (rbHCN1), and its specific localization in pacemaker myocytes. rbHCN1 is an 822 aa protein which, in HEK 293 cells, displayed electrophysiological properties similar to those of If, 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.


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