Palmitoyl carnitine increases intracellular calcium in adult rat cardiomyocytes

Earlier studies have demonstrated that palmitoyl carnitine (PC), a long cha in acyl carnitine, accumulates in the ischemic myocardium. Although perfusi on of hearts with PC is known to induce contractile dysfunction which resem bles ischemic contracture, the mechanisms underlying this derangement are n ot clear. In this study, we examined the effect of exogenous PC on the intr acellular concentration of calcium ([Ca2+](i)) in freshly isolated cardiomy ocytes from adult rat hearts. The results showed that PC elevated [Ca2+](i) in a dose-dependent (5-20 mu M) manner; 15 mu M PC evoked a marked and rev ersible increase in [Ca2+](i) without having any significant action on cell viability The PC (15 mu M)-induced increase in [Ca2+](i) was slightly depr essed but delayed in the absence of extracellular Ca2+. Pre-incubation of c ardiomyocytes with sarcolemmal (SL) L-type Ca2+-channel blockers, verapamil or diltiazem, and inhibitors of SL Na+-Ca2+ exchanger such as Ni2+ or amil oride, depressed the PC-evoked increase in [Ca2+](i) significantly. Ouabain , a Na+-K+ ATPase inhibitor, and low concentrations of extracellular Na+ en hanced the PC-induced increase in [Ca2+](i). Depletion of the sarcoplasmic reticulum (SR) Ca2+ stores by low micromolar concentrations of ryanodine (a SR Ca2+-release channel activator) or by thapsigargin (a SR Ca2+-pump ATPa se inhibitor) depressed the PC-mediated increase in [Ca2+](i). Combined blo ckade of the L-type Ca2+ channel, Na+-Ca2+ exchanger and the SR Ca2+-pump h ad an additive inhibitory effect on the PC response. These observations sug gest that the PC-induced increase in [Ca2+], is dependent on both Ca2+-infl ux from the extracellular space and Ca2+-release from the SR stores. Thus, the accumulation of PC in the myocardium may be partly responsible For the occurrence of intracellular Ca2+ overload in ischemic heart. (C) 1999 Acade mic Press.