Lysophosphoglycerides are amphiphilic phospholipids that accumulate in ischemic myocardium and elicit electrophysiological alterations in normoxic Purkinje fibers and ventricular muscle that are analogous to alterations characteristic of ischemic tissue in vivo and that are compatible with altered sarcolemmal permeability to divalent cations. To assess directly the potential influence of lysophosphoglycerides on calcium transport, we characterized changes in the accumulation of 45Ca2+ by cultured cardiac myocytes exposed to selected concentrations of lysophosphatidyl choline (LPC). Perfusion for 10 min with 80 microM LPC augmented the amount of 45Ca2+ in myocytes compared with that in control cells (5.1 +/- 0.7 vs. 2.8 +/- 0.26 nmols Ca2+/mg protein, respectively; P less than 0.005) but did not alter total cell calcium content measured by atomic absorption spectrometry (11.6 +/- 1.0 nmols/mg protein), suggesting equivalent augmentation of bidirectional Ca2+ flux by LPC. In contrast, perfusion for 15 min with 100 microM LPC not only augmented 45Ca2+ accumulation but also increased total cellular Ca2+ content, as the quantity of 45Ca2+ accumulated reached 16.9 +/- 1.4 nmols/mg protein, a value substantially exceeding the normal total Ca2+ content (P less than 0.0025 compared with control cells). In contrast to results observed after only a 5-min exposure to 100 microM LPC, Ca2+ accumulation induced by 15 min of perfusion was not precluded by verapamil (10(-8)M), could not be reversed by perfusion without LPC, and was associated with complete cessation of beating, markedly altered morphology, and substantial depletion of cellular creatine kinase activity. Thus LPC may not only contribute to malignant ventricular dysrhythmias but also may potentiate ischemic injury by facilitating calcium ingress.