Abstract
The human immunodeficiency virus type 1 (HIV-1) regulatory protein Tat is neurotoxic and may be involved in the neuropathogenesis of HIV-1 dementia, in part via N-methyl-D-aspartate (NMDA) receptor activation. Here, in acutely isolated rat hippocampal neurons, Tat evoked inward currents reversing near 0 mV, with a negative slope conductance region characteristic of NMDA receptor activation. Although the NMDA receptor antagonist ketamine blocked Tat's actions, competitive glutamate- and glycine-binding site antagonists were ineffective (AP-5 and 5,7-dichlorokynurenate, respectively). Evidence for Tat acting at a distinct modulatory site on the NR1 subunit of NMDA receptors was provided by findings that 1 μM Zn2+ abolished Tat-evoked responses in all neurons tested. Thus, Tat appears to excite neurons via direct activation of the NMDA receptor at an allosteric Zn2+-sensitive site.
Original language | English (US) |
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Pages (from-to) | 399-403 |
Number of pages | 5 |
Journal | Journal of neurovirology |
Volume | 9 |
Issue number | 3 |
DOIs | |
State | Published - Jun 2003 |
Externally published | Yes |
Keywords
- AIDS
- Excitatory amino acid receptors
- HIV-1
- NMDA
- Zinc
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Virology