Yu L, Netticadan T, Xu Y J, Panagia V, Dhalla N S
Laboratory of Membrane Biology, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
J Pharmacol Exp Ther. 1998 Jul;286(1):1-8.
Previous reports have demonstrated that lysophosphatidylcholine (LPC) increases the intracellular concentration of calcium ([Ca++]i) in the heart; however, the mechanisms responsible for this increase are not clear. We examined the effect of exogenous LPC on [Ca++]i in freshly isolated cardiomyocytes from adult rats. Our results showed that LPC elevated the [Ca++]i in a dose-dependent (2.5-10 microM) manner. The LPC (10 microM)-induced increase in [Ca++]i was augmented upon increasing the concentration of extracellular Ca++ and was abolished by the removal of Ca++ from the medium. Preincubation of cardiomyocytes with sarcolemmal L-type Ca++ channel blocker, verapamil, did not affect the LPC-evoked increase in [Ca++]i significantly. On the other hand, ouabain, a Na(+)-K+ ATPase inhibitor, and low concentrations of extracellular Na+ enhanced the LPC response. The LPC-induced increase in [Ca++]i was attenuated significantly by the inhibitors of Na(+)-Ca++ exchanger such as Ni++ and amiloride. Depletion of the sarcoplasmic reticulum (SR) Ca++ stores by low micromolar concentrations of ryanodine (a SR Ca(++)-release channel activator) or by thapsigargin (a SR Ca(++)-pump ATPase inhibitor) depressed the LPC-mediated increase in [Ca++]i. Combined blockade of Na(+)-Ca++ exchanger and inhibition of SR Ca(++)-pump or ryanodine receptor had an additive effect on the LPC response. These observations suggest that the increase in [Ca++]i induced by LPC depends on both Ca(++)-influx from the extracellular space and Ca(++)-release from the SR stores. Furthermore, Na(+)-Ca++ exchange plays a critical role in the LPC-mediated entry of Ca++ into cardiomyocytes.
先前的报告表明，溶血磷脂酰胆碱（LPC）可增加心脏细胞内的钙浓度（[Ca++]i）；然而，导致这种增加的机制尚不清楚。我们研究了外源性LPC对成年大鼠新鲜分离的心肌细胞中[Ca++]i的影响。我们的结果表明，LPC以剂量依赖性（2.5 - 10 microM）的方式升高[Ca++]i。LPC（10 microM）诱导的[Ca++]i增加在增加细胞外Ca++浓度时增强，并在从培养基中去除Ca++后被消除。用肌膜L型Ca++通道阻滞剂维拉帕米预孵育心肌细胞，对LPC诱发的[Ca++]i增加没有显著影响。另一方面，钠钾ATP酶抑制剂哇巴因和低浓度的细胞外Na+增强了LPC反应。Na+-Ca++交换体抑制剂如Ni++和阿米洛利可显著减弱LPC诱导的[Ca++]i增加。低微摩尔浓度的ryanodine（一种肌浆网Ca++释放通道激活剂）或毒胡萝卜素（一种肌浆网Ca++泵ATP酶抑制剂）耗尽肌浆网（SR）Ca++储存，可抑制LPC介导的[Ca++]i增加。联合阻断Na+-Ca++交换体并抑制SR Ca++泵或ryanodine受体对LPC反应有相加作用。这些观察结果表明，LPC诱导的[Ca++]i增加既依赖于细胞外空间的Ca++内流，也依赖于SR储存的Ca++释放。此外，Na+-Ca++交换在LPC介导的Ca++进入心肌细胞过程中起关键作用。
