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+ concentration and induces degeneration of human and animal neurons in culture. Using 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 dramatic and persistent increase in [Ca2+]i which is prevented by drugs that either deplete (caffeine, carbachol, thapsigargin) or block (dantrolene) Ca2+ release from intracellular stores. In contrast, N-methyl-d-aspartate (NMDA) receptors or voltage-dependent calcium channels do not participate in these effects, as: (i) the increase in [Ca2+]i was not affected by NMDA receptor antagonists or calcium channel blockers; and (ii) and GP120 did not generate any current in whole-cell recording. Dantrolene, a ryanodine stores inhibitor, also prevented neuronal death induced by GP120. Our results show that the GP120-induced rise in [Ca2+]i originates from intracellular calcium stores, and suggest that intracellular stores of calcium may play a determinant role in the pathological actions of GP120.
Medina
I
I
INSERM, Unit 29, Hôpital de Port-Royal, Paris, France.
Ghose
S
S
Ben-Ari
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D003620:Dantrolene / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014741:Video Recording
D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D015699:HIV Envelope Protein gp120; D003620:Dantrolene; D002118:Calcium; D016257:Fura-2