Mobilization of intracellular calcium stores participates in the rise of [Ca2+](i) and the toxic actions of the HIV coat protein GP120

The HIV envelope glycoprotein, GP120, increases intracellular Ca2+ concentr ation and induces degeneration of human and animal neurons in culture. Usin g patch-clamp recordings and Ca2+ imaging techniques, we have now examined the contribution of intracellular stores of calcium in the effects of GP120 . We report that in rat hippocampal neuronal cultures, GP120 induces a dram atic and persistent increase in [Ca2+](i) which is prevented by drugs that either deplete (caffeine, carbachol, thapsigargin) or block (dantrolene) Ca 2+ release from intracellular stores. In contrast, N-methyl-D-aspartate (NM DA) receptors or voltage-dependent calcium channels do not participate in t hese effects, as: (i) the increase in [Ca2+](i) was not affected by NMDA re ceptor antagonists or calcium channel blockers; and (ii) and GP120 did not generate any current in whole-cell recording. Dantrolene, a ryanodine store s inhibitor, also prevented neuronal death induced by GP120. Our results sh ow that the GP120-induced rise in [Ca2+](i) originates from intracellular c alcium stores, and suggest that intracellular stores of calcium may play a determinant role in the pathological actions of GP120.