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.
Yu
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Laboratory of Membrane Biology, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Netticadan
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Xu
Y J
YJ
Panagia
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V
Dhalla
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NS
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology
D008246:Lysophospholipids; D019831:Sodium-Calcium Exchanger; C025059:lysophosphatidylserine; D012433:Ryanodine; D019284:Thapsigargin; D000584:Amiloride; D002118:Calcium