Role of intracellular Ca2+ and pH in positive inotropic response of cardiomyocytes to diacylglycerol.
Role of intracellular Ca2+ and pH in positive inotropic response of cardiomyocytes to diacylglycerol.
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细胞内 Ca2 和 pH 在心肌细胞对二酰基甘油的正性肌力反应中的作用。
DOI：
10.1152/ajpheart.1998.275.4.h1473
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Walker,JW
中科院分区：
文献类型：
--
作者：
Pi,Y;Walker,JW
二酰甘油被认为是介导心肌对α肾上腺素能激动剂血管紧张素II和内皮素的正性变力反应。本文研究了二酰甘油在成年大鼠心肌细胞中的作用机制，方法是从笼状化合物细胞内释放二辛酰甘油(DiC8)，同时用荧光指示剂监测钙瞬变和pH。DiC8使抽动幅度增加三到四倍，收缩时相钙瞬变增加两倍。其他参数不受diC8的持续影响，包括钙循环动力学、肌浆网钙含量或肌丝对钙的敏感性。DiC8对细胞内pH和Na+/H+逆向转运蛋白活性无明显影响。与这一发现一致的是，Na+/H+交换抑制剂N-乙基异丙基阿米洛利对diC8的正性变力反应没有影响。DiC8能显著增强心肌收缩时的钙离子浓度，提示兴奋-收缩偶联过程可能是二酰甘油-蛋白激酶C信号转导的重要且可能的首选靶点。
Diacylglycerol has been hypothesized to mediate the positive inotropic response of myocardium to the α-adrenergic agonists angiotensin II and endothelin. The mechanism of action of diacylglycerol was examined here in adult rat ventricular myocytes by releasing dioctanoylglycerol (diC8) intracellularly from a caged compound while monitoring Ca2+transients and pH with fluorescent indicators. DiC8caused a three- to fourfold increase in twitch amplitude and a twofold increase in the systolic Ca2+transient. No other parameter was consistently influenced by diC8, including the kinetics of Ca2+cycling, the Ca2+content of the sarcoplasmic reticulum, or the myofilament Ca2+sensitivity. DiC8also had no detectable effect on intracellular pH or Na+/H+antiport activity. Consistent with this finding, the Na+/H+exchange inhibitorN-ethylisopropyl amiloride was without effect on the positive inotropic response to diC8. The marked enhancement of systolic Ca2+by diC8suggests that the process of excitation-contraction coupling is an important and possibly preferred target of diacylglycerol-protein kinase C signaling in myocardium.