Mechanisms of lysophosphatidylcholine-induced increase in intracellular calcium in rat cardiomyocytes.

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.