Overexpression of the HCN2 channel increases the arrhythmogenicity induced by hypokalemia

Kensuke Oshita, Yuko Kozasa, Yasuaki Nakagawa, Yoshihiro Kuwabara, Koichiro Kuwahara, Taku Nakagawa, Noriyuki Nakashima, Teruyuki Hiraki, Makoto Takano

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Hypokalemia, an abnormally low level of potassium (K+), is a electrolyte imbalance that commonly occurs in heart failure patients. Hypokalemia is well known to induce lethal ventricular arrhythmia. However, the effects of hypokalemia in failing hearts that have undergone electrophysiological remodeling, i.e., the reactivation of fetal-type ion channels, remain unexplored. We have examined the effect of hypokalemia in the myocytes of transgenic mice overexpressing the hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channel in the heart (HCN2-Tg mice). Perfusion with a mild hypokalemic solution containing 3 mM K+ induced ectopic ventricular automaticity in 55.0% of HCN2-Tg mouse myocytes. In the remaining HCN2-Tg mouse myocytes, the resting membrane potential (RMP) was more depolarized than that of wild-type myocytes subjected to the same treatment and could also be hyperpolarized by an HCN channel blocker. We conclude that in hypokalemia in our mice model, the HCN2 channel was constitutively activated at the hyperpolarized RMP, thereby destabilizing the electrophysiological activity of ventricular myocytes.

Original languageEnglish
Pages (from-to)653-660
Number of pages8
JournalJournal of Physiological Sciences
Volume69
Issue number4
DOIs
Publication statusPublished - Jul 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology

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