Palmitoyl carnitine increases intracellular calcium in adult rat cardiomyocytes.
Earlier studies have demonstrated that palmitoyl carnitine (PC), a long chain acyl carnitine, accumulates in the ischemic myocardium. Although perfusion of hearts with PC is known to induce contractile dysfunction which resembles ischemic contracture, the mechanisms underlying this derangement are not clear. In this study, we examined the effect of exogenous PC on the intracellular concentration of calcium ([Ca(2+)](i)) in freshly isolated cardiomyocytes from adult rat hearts. The results showed that PC elevated [Ca(2+)](i)in a dose-dependent (5-20 microm) manner; 15 microm PC evoked a marked and reversible increase in [Ca(2+)](i)without having any significant action on cell viability. The PC (15 microm)-induced increase in [Ca(2+)](i)was slightly depressed but delayed in the absence of extracellular Ca(2+). Pre-incubation of cardiomyocytes with sarcolemmal (SL) l -type Ca(2+)-channel blockers, verapamil or diltiazem, and inhibitors of SL Na(+)-Ca(2+)exchanger such as Ni(2+)or amiloride, depressed the PC-evoked increase in [Ca(2+)](i)significantly. Ouabain, a Na(+)-K(+)ATPase inhibitor, and low concentrations of extracellular Na(+)enhanced the PC-induced increase in [Ca(2+)](i). Depletion of the sarcoplasmic reticulum (SR) Ca(2+)stores by low micromolar concentrations of ryanodine (a SR Ca(2+)-release channel activator) or by thapsigargin (a SR Ca(2+)-pump ATPase inhibitor) depressed the PC-mediated increase in [Ca(2+)](i). Combined blockade of the l -type Ca(2+)channel, Na(+)-Ca(2+)exchanger and the SR Ca(2+)-pump had an additive inhibitory effect on the PC response. These observations suggest that the PC-induced increase in [Ca(2+)](i)is dependent on both Ca(2+)-influx from the extracellular space and Ca(2+)-release from the SR stores. Thus, the accumulation of PC in the myocardium may be partly responsible for the occurrence of intracellular Ca(2+)overload in ischemic heart.
Laboratory of Membrane Biology, Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
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Netticadan
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Yu
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Dhalla
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Panagia
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010172:Palmitoylcarnitine / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012433:Ryanodine; D010172:Palmitoylcarnitine; D010042:Ouabain; D019284:Thapsigargin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium