The pacemaker "funny" current (If) 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 If 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 If relative to other proposed pacemaker mechanisms such as SR Ca2+ transients confirm that the If-mediated rate control is a key process in pacemaker generation and autonomic control.

Pacemaker channels / M. Baruscotti, D. DiFrancesco. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 1015:(2004), pp. 111-121. [10.1196/annals.1302.009]

Pacemaker channels

M. Baruscotti
Primo
;
D. DiFrancesco
Ultimo
2004

Abstract

The pacemaker "funny" current (If) 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 If 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 If relative to other proposed pacemaker mechanisms such as SR Ca2+ transients confirm that the If-mediated rate control is a key process in pacemaker generation and autonomic control.
Autonomic rate modulation; Cardiac rate; HCN channels; If current; Pacemaker current
Settore BIO/09 - Fisiologia
2004
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/12758
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