Goldhaber JI, Deutsch N, Alexander LD, Weiss JN
Departments of Medicine, University of California Los Angeles School of Medicine, Los Angeles, California, USA
J Cardiovasc Pharmacol Ther. 1998 Jan;3(1):37-42. doi: 10.1177/107424849800300105.
Lysophospholipids such as lysophosphatidylcholine (LPC) have many direct electrophysiological effects on cardiac muscle and have been implicated as a cause of lethal ventricular arrhythmias during acute myocardial ischemia. Because extracellular K(+) accumulation is also a key arrhythmogenic factor during acute ischemia, we examined the effects of LPC on cellular K(+) balance, including its interaction with adenosine triphosphate-sensitive K(+) (K(ATP)) channels. METHODS AND RESULTS: Isolated rabbit interventricular septa paced at 75 beats/min were loaded with (42)K(+) to measure unidirectional K(+) efflux rate (in (42)K(+) washout experiments) or tissue K(+) content ((42)K(+) uptake experiments) and action potential duration (APD) during exposure to 20 µM LPC for 30 minutes. LPC caused tissue K(+) content to decrease by 15 +/- 2% (n = 4) at a steady rate over 30 minutes, associated with gradual APD shortening and a delayed increase in unidirectional K(+) efflux rate. Pretreatment with 12 µM cromakalim to selectively activate K(ATP) channels shortened APD by 44 +/- 66% and had no effect on net tissue K(+) content during control aerobic perfusion. However, cromakalim increased net K(+) loss during exposure to LPC to 22 +/- 4%, a 47% increase. CONCLUSIONS: LPC induced net K(+) loss in heart, which was potentiated by the K(ATP) channel agonist cromakalim. This ATP finding suggests that if LPC accumulates to similar levels during myocardial ischemia and hypoxia, it may be an important mechanism in net K(+) loss.
溶血磷脂如溶血磷脂酰胆碱（LPC）对心肌有许多直接电生理作用，并被认为是急性心肌缺血期间致死性室性心律失常的一个原因。由于细胞外钾（K⁺）蓄积也是急性缺血期间的一个关键致心律失常因素，我们研究了LPC对细胞钾平衡的影响，包括其与三磷酸腺苷敏感性钾（KATP）通道的相互作用。
以75次/分钟的频率起搏的离体兔室间隔用⁴²K⁺负载，以测量单向钾外流速率（在⁴²K⁺洗脱实验中）或组织钾含量（⁴²K⁺摄取实验）以及在暴露于20μM LPC 30分钟期间的动作电位时程（APD）。LPC使组织钾含量在30分钟内以稳定速率下降15±2%（n = 4），这与APD逐渐缩短和单向钾外流速率延迟增加相关。用12μM克罗卡林预处理以选择性激活KATP通道，在对照有氧灌注期间使APD缩短44±6%，且对组织净钾含量无影响。然而，克罗卡林在暴露于LPC期间使净钾丢失增加至22±4%，增加了47%。
LPC诱导心脏净钾丢失，这被KATP通道激动剂克罗卡林增强。这一发现提示，如果LPC在心肌缺血和缺氧期间蓄积至相似水平，它可能是净钾丢失的一个重要机制。
