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 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.
Lo
T M
TM
Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455.
Fallert
C J
CJ
Piser
T M
TM
Thayer
S A
SA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009568:Nitrendipine / Q000494:pharmacology; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D010875:Pipecolic Acids; D013779:Tetrodotoxin; C053672:selfotel; D016202:N-Methylaspartate; D009568:Nitrendipine; D002118:Calcium