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.

中文翻译：

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HCN2通道的过表达增加了由低血钾引起的心律失常。

低钾血症（钾（K +）含量异常低）是一种电解质失衡，通常发生在心力衰竭患者中。低钾血症众所周知会诱发致命性室性心律失常。然而，低钾血症在经历了电生理重塑（即胎儿型离子通道的重新激活）的衰竭心脏中的作用尚未得到探索。我们已经检查了低钾血症在过表达心脏中超极化激活的环状核苷酸敏感（HCN）通道的转基因小鼠（HCN2-Tg小鼠）的心肌细胞中的作用。在55.0％的HCN2-Tg小鼠心肌细胞中灌注含有3 mM K +的轻度低钾溶液诱导的异位心室自动性。在其余的HCN2-Tg小鼠心肌细胞中，静息膜电位（RMP）比经过相同处理的野生型肌细胞更去极化，并且也可以通过HCN通道阻滞剂超极化。我们得出结论，在我们的小鼠模型的低钾血症中，HCN2通道在超极化RMP上被组成性激活，从而破坏了心室肌细胞的电生理活性。