Rationale: Hypokalemia occurs in up to 20% of hospitalized patients, and is associated with increased incidence of ventricular and atrial fibrillation. It is unclear whether these differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia on cardiomyocytes. Objective: To investigate pro-arrhythmic mechanisms of hypokalemia in ventricular and atrial myocytes. Methods and Results: Experiments were performed in isolated rat myocytes exposed to simulated hypokalemia conditions (reduction of extracellular [K+] from 5.0 to 2.7 mM) and supported by mathematical modeling studies. Ventricular cells subjected to hypokalemia exhibited Ca2+ overload, and increased generation of both spontaneous Ca2+ waves and delayed afterdepolarizations (DADs). However, similar Ca2+-dependent spontaneous activity during hypokalemia was only observed in a minority of atrial cells that were observed to contain t-tubules. This effect was attributed to close functional pairing of the Na+-K+ ATPase and Na+-Ca2+ exchanger proteins within these structures, as reduction in Na+ pump activity locally inhibited Ca2+ extrusion. Ventricular myocytes and tubulated atrial myocytes additionally exhibited early afterdepolarizations (EADs) during hypokalemia, associated with Ca2+ overload. However, EADs also occurred in untubulated atrial cells, despite Ca2+ quiescence. These phase-3 EADs were rather linked to reactivation of non-equilibrium Na+ current, as they were rapidly blocked by tetrodotoxin. Na+ current-driven EADs in untubulated atrial cells were enabled by membrane hyperpolarization during hypokalemia and short action potential configurations. Brief action potentials were in turn maintained by ultra-rapid K+ current (IKur); a current which was found to be absent in tubulated atrial myocytes and ventricular myocytes. Conclusions: Distinct mechanisms underlie hypokalemia-induced arrhythmia in the ventricle and atrium, but also vary between atrial myocytes depending on subcellular structure and electrophysiology.

中文翻译：

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低钾血症通过心房和心室肌细胞的不同机制促进心律失常。

理由：低钾血症发生在高达 20% 的住院患者中，并且与心室和心房颤动的发病率增加有关。目前尚不清楚这些不同类型的心律失常是否是由低钾血症对心肌细胞的直接或不同影响所致。目的：探讨心室和心房肌细胞低钾血症的促心律失常机制。方法和结果：实验在暴露于模拟低钾血症条件（细胞外 [K+] 从 5.0 至 2.7 mM）下的分离的大鼠肌细胞中进行，并得到数学模型研究的支持。遭受低钾血症的心室细胞表现出 Ca2+ 超载，并增加了自发 Ca2+ 波和延迟后去极化 (DADs) 的产生。然而，仅在少数观察到含有 t 小管的心房细胞中观察到低钾血症期间类似的 Ca2+ 依赖性自发活动。这种效应归因于这些结构内 Na+-K+ ATPase 和 Na+-Ca2+ 交换蛋白的密切功能配对，因为 Na+ 泵活性的降低会局部抑制 Ca2+ 的排出。心室肌细胞和管状心房肌细胞在低钾血症期间还表现出早期后去极化 (EAD)，这与 Ca2+ 超载有关。然而，EADs 也发生在无管心房细胞中，尽管 Ca2+ 处于静止状态。这些阶段 3 EAD 与非平衡 Na+ 电流的重新激活相当相关，因为它们被河豚毒素迅速阻断。无管心房细胞中 Na+ 电流驱动的 EAD 是通过低钾血症和短动作电位配置期间的膜超极化来实现的。短暂的动作电位又由超快速 K+ 电流 (IKur) 维持；一种在管状心房肌细胞和心室肌细胞中不存在的电流。结论：不同的机制是低钾血症引起的心室和心房心律失常的基础，但心房肌细胞之间也存在差异，这取决于亚细胞结构和电生理学。