Woodley S L, Ikenouchi H, Barry W H
Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132.
J Mol Cell Cardiol. 1991 Jun;23(6):671-80. doi: 10.1016/0022-2828(91)90977-t.
Lysophosphatidylcholine (LPC) accumulates in myocardial tissues during ischemia, and has toxic effects which may contribute to the arrhythmias and relaxation abnormalities that occur during acute ischemia. These effects of LPC may be mediated in part by calcium overload. To test this hypothesis, spontaneously contracting cultured embryonic chick ventricular myocytes were superfused with various concentrations of LPC (10, 50 and 100 microM) while effects on contractile motion (video motion detector) and changes in free intracellular calcium ion concentration ([Ca2+]i indo-1 fluorescence) were determined. At concentrations greater than or equal to 10 microM, a dose-related, time-dependent effect occurred after exposure to LPC, consisting of the development of contracture and marked elevation of [Ca2+]i. LPC also produced a dose-related, time-dependent inhibition of K+ uptake, indicating there was inhibition of the Na(+)-K+ ATPase Na+ pump. However, the LPC-induced increase in [Ca2+]i was not due to Na+ overload caused by inhibition of the Na(+)-K+ ATPase Na+ pump because superfusion with a zero-Na+ solution did not prevent an increase in [Ca2+]i after LPC exposure; and the increase in [Ca2+]i after exposure to LPC occurred too rapidly to be accounted for by Na+ pump inhibition. Removal of extracellular Ca2+ prevented the rise in [Ca2+]i, after exposure to LPC but treatment with verapamil failed to inhibit the increase in [Ca2+]i induced by LPC. We conclude that LPC produces contracture due to an increase [Ca2+]i. These effects are seen at concentrations of 10 microM and greater, are not due to altered Na(+)-K+ ATPase Na+ pump or calcium channel function, and are probably related to the detergent properties of this amphiphile. There effects may account in part for myocardial dysfunction during ischemia in intact tissue.
溶血磷脂酰胆碱（LPC）在心肌缺血时会在心肌组织中蓄积，具有毒性作用，可能导致急性缺血时出现的心律失常和舒张功能异常。LPC的这些作用可能部分由钙超载介导。为验证这一假说，用不同浓度的LPC（10、50和100微摩尔）对自发收缩的培养胚胎鸡心室肌细胞进行灌流，同时测定对收缩运动（视频运动探测器）的影响以及细胞内游离钙离子浓度（[Ca2+]i，indo-1荧光）的变化。当浓度大于或等于10微摩尔时，暴露于LPC后会出现剂量相关、时间依赖性效应，包括挛缩的发展和[Ca2+]i的显著升高。LPC还产生剂量相关、时间依赖性的钾摄取抑制，表明存在对钠钾ATP酶钠泵的抑制。然而，LPC诱导的[Ca2+]i升高并非由于钠钾ATP酶钠泵抑制导致的钠超载，因为用无钠溶液灌流并不能阻止LPC暴露后[Ca2+]i的升高；且暴露于LPC后[Ca2+]i的升高发生得太快，无法用钠泵抑制来解释。去除细胞外钙可防止LPC暴露后[Ca2+]i的升高，但用维拉帕米处理未能抑制LPC诱导的[Ca2+]i升高。我们得出结论，LPC因[Ca2+]i升高而产生挛缩。这些效应在10微摩尔及更高浓度时可见，并非由于钠钾ATP酶钠泵或钙通道功能改变，可能与这种两亲分子的去污剂特性有关。这些效应可能部分解释了完整组织缺血时的心肌功能障碍。
