Recent reports have suggested that the HIV-1 Tat regulatory protein directly activates glutamate receptors in human and rat neurons. To determine if Tat acts directly on the NMDA-subtype of glutamate receptors, we expressed the NMDA NR1A and NR2A subunits in Xenopus oocytes. Oocytes were voltage-clamped at -60 mV in a bath solution containing no added Mg2+ and 100 uM glycine. The application of Tat (100 nM; with glycine) activated inward current responses with an amplitude of 800 +/-300 nA (n=11). Bath application of the competitive NMDA receptor antagonist APV (100 uM) blocked the Tat response completely (3 cells). The activation of the NMDA receptor channels by Tat was dependent on glycine; in the absence of added glycine, the application of Tat did not produce any response (n=3). In summary, we have shown that the HIV-1 Tat regulatory protein directly activates recombinant NMDA receptor channels, and suggest that the activation of these receptors in vivo by Tat could contribute to the neurotoxic effects associated with HIV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES090093-03
Application #
6838614
Study Section
(LST)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code