Pacemaker Channels

MIRKO BARUSCOTTI,

MIRKO BARUSCOTTI

Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, Italy

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DARIO DIFRANCESCO,

Corresponding Author

DARIO DIFRANCESCO

Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, Italy

INFM-Milan University Unit, 20133 Milan, Italy

Address for correspondence: Prof. Dario DiFrancesco, Ph.D., Dept. of Biomolecular Sciences and Biotechnology, Lab. of Molecular Physiology and Neurobiology, via Celoria 26, 20133 Milano, Italy. Voice: 39-02-5031-4931; fax: 39-02-5031-4932. [email protected]Search for more papers by this author

MIRKO BARUSCOTTI,

MIRKO BARUSCOTTI

Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, Italy

Search for more papers by this author

DARIO DIFRANCESCO,

Corresponding Author

DARIO DIFRANCESCO

Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, Italy

INFM-Milan University Unit, 20133 Milan, Italy

First published: 08 July 2009

https://doi.org/10.1196/annals.1302.009

Citations: 58

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Abstract

Abstract: The pacemaker “funny” current (I_f) has been the object of detailed investigations since its original description in sinoatrial node myocytes in the late 1970s; its role in underlying generation of spontaneous activity and autonomic modulation of cardiac rate has been amply demonstrated. In the late 1990s four isoforms of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular components of native pacemaker channels, were cloned, and structure-function relation studies provided a molecular interpretation of several features of the native channels. Its role in pacemaking makes I_f a natural target of heart rate modulating agents; several heart rate reducing molecules are known today that exert their action by specific inhibition of f-channels. Experiments aimed at determining the role of I_f relative to other proposed pacemaker mechanisms such as SR Ca²⁺ transients confirm that the I_f-mediated rate control is a key process in pacemaker generation and autonomic control.

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Volume1015, Issue1

Cardiac Engineering: From Genes and Cells to Structure and Function

May 2004

Pages 111-121

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