Overexpression of the HCN2 channel increases the arrhythmogenicity induced by hypokalemia
Overexpression of the HCN2 channel increases the arrhythmogenicity induced by hypokalemia
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DOI：
10.1007/s12576-019-00684-7
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发表时间：
2019-07-01
影响因子：
2.3
通讯作者：
Takano, Makoto
中科院分区：
文献类型：
--
作者：
Oshita, Kensuke;Kozasa, Yuko;Takano, Makoto
低钾血症是一种异常低的钾(K+)水平，是一种电解质失衡，通常发生在心力衰竭患者中。众所周知，低钾血症可导致致死性室性心律失常。然而，低钾血症对经历电生理重塑的衰竭心脏的影响，即胎儿型离子通道的重新激活，仍未被探讨。我们研究了低血钾对在心脏过度表达超极化激活的环核苷酸敏感(HCN)通道的转基因小鼠(HCN2-TG小鼠)心肌细胞的影响。含3 mM K+的轻度低血钾液灌流可诱导55.0%的HCN2-TG小鼠心肌细胞异位自律性。在剩余的HCN2-TG小鼠心肌细胞中，静息膜电位(RMP)比同样处理的野生型心肌细胞更去极化，并且也可以被HCN通道阻滞剂超极化。我们的结论是，在我们的小鼠低钾血症模型中，HCN通道在超极化的RMP处被结构性地激活，从而破坏了心室肌细胞的电生理活动。
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.