PubMed 17914461

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: HCN3 , HCN4

Title: HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice.

Authors: Stefan Herrmann, Juliane Stieber, Georg Stöckl, Franz Hofmann, Andreas Ludwig

Journal, date & volume: EMBO J., 2007 Oct 31 , 26, 4423-32

PubMed link:

Cardiac pacemaking involves a variety of ion channels, but their relative importance is controversial and remains to be determined. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, which underlie the I(f) current of sinoatrial cells, are thought to be key players in cardiac automaticity. In addition, the increase in heart rate following beta-adrenergic stimulation has been attributed to the cAMP-mediated enhancement of HCN channel activity. We have now studied mice in which the predominant sinoatrial HCN channel isoform HCN4 was deleted in a temporally controlled manner. Here, we show that deletion of HCN4 in adult mice eliminates most of sinoatrial I(f) and results in a cardiac arrhythmia characterized by recurrent sinus pauses. However, the mutants show no impairment in heart rate acceleration during sympathetic stimulation. Our results reveal that unexpectedly the channel does not play a role for the increase of the heart rate; however, HCN4 is necessary for maintaining a stable cardiac rhythm, especially during the transition from stimulated to basal cardiac states.