THE ROLE OF INTRACELLULAR CALCIUM IN ANTIMONY-INDUCED TOXICITY IN CULTURED CARDIAC MYOCYTES

Trivalent antimony, delivered as potassium antimonyl tartrate (PAT), h as been previously shown to induce an oxidative stress and toxicity in cultured neonatal rat cardiac myocytes. The present study investigate s the effect of PAT on intracellular free calcium ([Ca2+](i)), which h as been implicated in the toxicity of agents inducing oxidative stress , and explores its role in PAT toxicity. Exposure to 50 or 200 mu M PA T led to progressive elevation in diastolic or resting [Ca2+](i) and e ventually a complete loss of [Ca2+](i) transients that occurred well b efore cell death as assessed by LDH release. Prior loading of myocytes with the intracellular calcium chelator BAPTA (10 to 40 mu M), protec ted against PAT toxicity in the presence and absence of extracellular calcium, and demonstrated a crucial role for [Ca2+](i) in PAT toxicity . Exposure to 200 mu M PAT in the absence of extracellular calcium sli ghtly elevated [Ca2+](i), but only to levels comparable to resting [Ca 2+](i) for cells in 1.8 mM extracellular calcium. This demonstrated th at although PAT toxicity was dependent on [Ca2+](i), a large increase above resting levels was not needed, and also that some calcium was mo bilized from intracellular stores. However, the caffeine-releasable po ol of sarcoplasmic reticulum calcium was increased, not depleted, by e xposure to 200 mu M PAT. These results demonstrate that PAT disrupts [ Ca2+](i) handling and support a role for a calcium-dependent event, bu t do not support the necessity of events in PAT-induced cell death tha t are mediated by a large elevation in [Ca2+](i). (C) 1997 Academic Pr ess.