ALTERATIONS IN THE GAMMA-AMINOBUTYRIC ACID-GATED CHLORIDE CHANNEL FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN THE GERBIL

The role of inhibitory neurotransmission in selective neuronal degeneration after transient forebrain ischemia was studied by binding of t-[S-35]butylbicyclophosphorothionate ([S-35]TBPS) to the gamma-aminobutyric acid (GABA)-gated chloride channel and measurement of GABA(A) receptor function in Mongolian gerbil brain. [S-35]TBPS binding to the hippocampus, striatum, and cortex quantified by autoradiography and muscimol-stimulated Cl-36- uptake in synaptoneurosomes of the same regions were examined 1, 4, and 29 days after a 5-min bilateral carotid occlusion. [S-35]TBPS binding was decreased in the pyramidal cell dendritic layers, stratum oriens, and stratum lacunosum-moleculare of the CA 1 hippocampus, 4 and 29 days after occlusion, and in the stratum radiatum 29 days after occlusion. [S-35]TBPS binding sites in the lateral striatum decreased 47% 4 days after occlusion. At the same time, there was a corresponding decrease in muscimol-stimulated Cl-36- uptake in the striatal synaptoneurosomes. Muscimol-stimulated Cl-36- uptake in the hippocampus decreased slightly 4 days after occlusion and more so after 29 days, although these decreases were not significant. No changes were observed in somatosensory cortex at any time point. These data suggest that a portion of GABA(A) receptors in areas sensitive to ischemic insult are associated with degenerating neurons, whereas other GABA(A) receptors are spared.