HIV-1 envelope protein evokes intracellular calcium oscillations in rat hippocampal neurons

Treatment of single rat hippocampal neurons with 200 pM recombinant HIV-1 envelope glycoprotein, gp120, resulted in large increases in the intracellular free calcium concentration ([Ca2+]i) as measured with indo-1-based microfluorimetry. Three patterns of [Ca2+]i increases were observed: in one patt...

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Bibliographic Details
Published in:	Brain research Vol. 594; no. 2; p. 189
Main Authors:	Lo, T M, Fallert, C J, Piser, T M, Thayer, S A
Format:	Journal Article
Language:	English
Published:	Netherlands 30-10-1992
Subjects:	Action Potentials - drug effects Animals Calcium - metabolism Cells, Cultured Hippocampus - cytology Hippocampus - drug effects Hippocampus - metabolism HIV Envelope Protein gp120 - pharmacology N-Methylaspartate - antagonists & inhibitors Neurons - drug effects Neurons - metabolism Nitrendipine - pharmacology Pipecolic Acids - pharmacology Rats Tetrodotoxin - pharmacology
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Summary:	Treatment of single rat hippocampal neurons with 200 pM recombinant HIV-1 envelope glycoprotein, gp120, resulted in large increases in the intracellular free calcium concentration ([Ca2+]i) as measured with indo-1-based microfluorimetry. Three patterns of [Ca2+]i increases were observed: in one pattern the [Ca2+]i rose rapidly and transiently as a single peak, in a second pattern gp120 induced [Ca2+]i oscillations that subsided when the protein was removed, and in a third pattern the oscillations continued long after washout of gp120. Both single peak and oscillatory [Ca2+]i increases were completely blocked by the Ca2+ channel blocker nitrendipine (1 microM). The sustained oscillatory responses were also blocked completely and reversibly by the N-methyl-D-aspartate (NMDA) receptor antagonist CGS19755 (10 microM) and the Na+ channel blocker tetrodotoxin (1 microM). Complete block by antagonists of Ca2+, Na+, and NMDA-gated ion channels suggests that at least two cells are required to maintain the [Ca2+]i oscillations. We hypothesize that gp120 acts as an excitotoxin by increasing synaptic activity in the network of neurons established in primary culture.
ISSN:	0006-8993
DOI:	10.1016/0006-8993(92)91125-X