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

• 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
• DOI: 10.1016/0006-8993(92)91125-X
• ISSN: 0006-8993

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.