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 th e heart; however, the mechanisms responsible for this increase are not clear. We examined the effect of exogenous LPC on [Ca++](i) in freshl y isolated cardiomyocytes from adult rats. Our results showed that LPC elevated the [Ca++](i) in a dose-dependent (2.5-10 mu M) manner. The IPC (10 mu M)-induced increase in [Ca++]i was augmented upon increasin g the concentration of extracellular Ca++ and was abolished by the rem oval of Ca++ from the medium. Preincubation of cardiomyocytes with sar colemmal L-type Ca++ channel blocker, verapamil, did not affect the LP C-evoked increase in [Ca++](i) significantly. On the other hand, ouaba in, 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 s uch 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 ryano dine receptor had an additive effect on the LPC response. These observ ations suggest that the increase in [Ca++](i) induced by LPC depends o n 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.