Ca2+-dependent release of endogenous GABA from rat cortical slices from different pools by different stimulation conditions.
The previously reported inhibitory effect of (-)-baclofen on the electrically evoked release of endogenous GABA from rat brain slices indicated the possibility of existence of GABAB autoreceptors. In this study, we have tested an alternative explanation, i.e. the possibility that (-)-baclofen reduced an excitatory glutamatergic input to GABAergic neurons by inhibiting glutamate release, by investigating the interaction of 1 mmol/l L-glutamate with the inhibitory effect of 10 mumol/l (-)-baclofen. L-Glutamate did not affect the electrically evoked release of GABA on its own and did not abolish the effect of (-)-baclofen, suggesting that the latter was not secondary to a reduction of glutamate release. On the other hand, it greatly increased the basal release of GABA and more than doubled the GABA content of the slices at the end of the perfusion, indicating a marked enhancement of GABA synthesis. This additional GABA, apparently formed from exogenous L-glutamate, was not releasable by electrical stimulation at 0.5 or 24 Hz, but at least in part by stimulation with 30 mmol/l K+. The previously reported increase of GABA release at 12 Hz as compared to 4 Hz was studied in more detail. GABA released by electrical stimulation at 8-48 Hz was Ca2+-dependent and tetrodotoxin-sensitive. No evidence was obtained for a decrease of the amount of GABA released per impulse with increasing frequency in this range.(ABSTRACT TRUNCATED AT 250 WORDS)
Waldmeier
P C
PC
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Wicki
P
P
Feldtrauer
J J
JJ
Baumann
P A
PA
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D011963:Receptors, GABA-A; D009118:Muscimol; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D011188:Potassium; D002118:Calcium