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, gp 120, 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 μM). The sustained oscillatory responses were also blocked completely and reversibly by the N-methyl-d-aspartate (NMDA) receptor antagonist CGS19755 (10 μM) and the Na⁺ channel blocker tetrodotoxin (1 μM). 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.