TY - JOUR
T1 - Overexpression of the HCN2 channel increases the arrhythmogenicity induced by hypokalemia
AU - Oshita, Kensuke
AU - Kozasa, Yuko
AU - Nakagawa, Yasuaki
AU - Kuwabara, Yoshihiro
AU - Kuwahara, Koichiro
AU - Nakagawa, Taku
AU - Nakashima, Noriyuki
AU - Hiraki, Teruyuki
AU - Takano, Makoto
N1 - Funding Information:
Acknowledgements This work was supported by JSPS KAKENHI Grant number 16H05124. The authors thank Ms. Akemi Sakamoto and Ms. Hideko Yoshitake. for the secretary work.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s12576-019-00684-7
DO - 10.1007/s12576-019-00684-7
M3 - Article
C2 - 31087220
AN - SCOPUS:85065676192
SN - 1880-6546
VL - 69
SP - 653
EP - 660
JO - Journal of Physiological Sciences
JF - Journal of Physiological Sciences
IS - 4
ER -