| First Author | Herrmann S | Year | 2007 |
| Journal | EMBO J | Volume | 26 |
| Issue | 21 | Pages | 4423-32 |
| PubMed ID | 17914461 | Mgi Jnum | J:139560 |
| Mgi Id | MGI:3808780 | Doi | 10.1038/sj.emboj.7601868 |
| Citation | Herrmann S, et al. (2007) HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice. EMBO J 26(21):4423-32 |
| abstractText | 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. |
