GABAA receptor function in the early period after transient forebrain ischaemia in the rat.
The purpose of this study was to evaluate the function of the GABAA receptor following transient forebrain ischaemia. The GABA-stimulated chloride (36Cl-) uptake into synaptoneurosomes was determined as an indicator of GABAA 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 ischaemia were killed at the end of the ischaemic insult and at 30 min or 2 or 5 h of recirculation. The results showed a reduction of 75% in GABA-mediated 36Cl- uptake in synaptoneurosomes isolated from animals shortly (< 0.5 h) after the ischaemic episode (P < 0.01). After longer recirculation periods the GABA-mediated 36Cl- uptake reached preischaemic control levels. To investigate whether alterations in 36Cl- uptake were related to the synaptoneurosomal metabolic status, the synaptoneurosomal ATP content was measured. The time course of the ATP recovery correlated with the recovery of the GABA-mediated 36Cl- uptake (r = 0.7, P < 0.001). To investigate the importance of ATP in GABA-mediated 36Cl- uptake more directly, synaptoneurosomes isolated from control rats were exposed to chemically induced ATP depletion with rotenone, an inhibitor of oxidative phosphorylation. This resulted in similar reductions in both ATP level and GABA-stimulated 36Cl- uptake as observed after in vivo ischaemia. These findings indicate that GABAA receptor function is transiently impaired in the early postischaemic period in a way which is closely related to alterations in cellular energy metabolism. The relevance of these findings to the development of ischaemic cell death is discussed.
Verheul
H B
HB
Department of Neurosurgery, University Hospital, Utrecht, The Netherlands.
de Leeuw
F E
FE
Scholten
G
G
Tulleken
C A
CA
Lopes da Silva
F H
FH
Ghijsen
W E
WE
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D016548:Prosencephalon / Q000098:blood supply / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D015424:Reperfusion; D012402:Rotenone / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D018079:Receptors, GABA; D012402:Rotenone; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate