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| Subject Categories: Membranes & Transport | Molecular Biology of Disease |
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| The EMBO Journal
(2007) 26, 4423–4432, doi:10.1038/sj.emboj.7601868 Published online 4 October 2007 |
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| HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice |
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| Stefan Herrmann1, 3, Juliane Stieber1, 3, Georg Stöckl2, Franz Hofmann2 and Andreas Ludwig1 |
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1 Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany 2 Institut für Pharmakologie und Toxikologie, Technische Universität München, München, Germany 3 These authors contributed equally to this work To whom correspondence should be addressed Juliane Stieber, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Tel.: +49 9131 85 26936; Fax: +49 9131 85 22774; E-mail: Stieber@pharmakologie.uni-erlangen.de Andreas Ludwig, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Tel.: +49 9131 85 22220; Fax: +49 9131 85 22774; E-mail: ludwig@pharmakologie.uni-erlangen.de Received 30 March 2007; Accepted 5 September 2007; Published online 4 October 2007. |
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| Abstract |
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| 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 If 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 If 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. |
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| Keywords: arrhythmia, HCN4, hyperpolarization-activated channels, pacemaking, sinoatrial node |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSOscillations in cellular reactions Nature News and Views (21 Jun 1979) Presynaptic facilitation by hyperpolarization-activated pacemaker channels Nature Neuroscience News and Views (01 Feb 2000) RESEARCHHCN4 provides a ?depolarization reserve? and is not required for heart rate acceleration in mice The EMBO Journal Article The EMBO Journal Article (20 Feb 2008) |
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