GABA-A RECEPTOR FUNCTION IN THE EARLY PERIOD AFTER TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT

The purpose of this study was to evaluate the function of the GABA(A) receptor following transient forebrain ischaemia. The GABA-stimulated chloride (Cl-36-) uptake into synaptoneurosomes was determined as an i ndicator of GABA(A) receptor function. Synaptoneurosomes were isolated from control rats and rats in which the forebrain was made ischaemic by way of the two-vessel occlusion model. Animals subjected to ischaem ia were killed at the end of the ischaemic insult and at 30 min or 2 o r 5 h of recirculation. The results showed a reduction at 75% in GABA- mediated Cl-36- uptake in synaptoneurosomes isolated from animals shor tly (<0.5 h) after the ischaemic episode (P < 0.01). After longer reci rculation periods the GABA-mediated Cl-36- uptake reached preischaemic control levels. To investigate whether alterations in Cl-36- uptake w ere related to the synaptoneurosomal metabolic status, the synaptoneur osomal ATP content was measured. The time course of the ATP recovery c orrelated with the recovery of the GABA-mediated Cl-36- uptake (r = 0. 7, P < 0.001). To investigate the importance of ATP in GABA-mediated C l-36- uptake more directly, synaptoneurosomes isolated from control ra ts were exposed to chemically induced ATP depletion with rotenone, an inhibitor of oxidative phosphorylation. This resulted in similar reduc tions in both ATP level and GABA-stimulated Cl-36- uptake as observed after in vivo ischaemia. These findings indicate that GABA(A) receptor function is transiently impaired in the early postischaemic period in a way which is closely related to alterations in cellular energy meta bolism. The relevance of these findings to the development of ischaemi c cell death is discussed.