INHIBITORY CHOLINERGIC CONTROL OF ENDOGENOUS GABA RELEASE FROM ELECTRICALLY STIMULATED CORTICAL SLICES AND K-DEPOLARIZED SYNAPTOSOMES()

In the present study we characterize the optimal experimental conditio ns under which to investigate the cholinergic regulation of endogenous electrically evoked gamma-aminobutyric acid (GABA) release from guine a pig cortical slices. Superfusion with the neuronal GABA reuptake inh ibitor, SKF89976A (10 mu M) caused cortical GABA release to be linearl y correlated with the frequency of electrical stimulation (5, 10, 20 H z). Electrically evoked GABA release (10 Hz) was tetrodotoxin-sensitiv e and Ca2+-dependent and was under GABA(B) autoreceptor control. Under these experimental conditions, acetylcholine (0.1-10 mu M) and physos tigmine (30 mu M) decreased the electrically evoked GABA release while the M-2 receptor antagonist AFDX-116 (0.01-0.1 mu M) counteracted the se effects. Similar results were also observed in a cortical synaptoso mal preparation stimulated with K+ (10 mM). These findings demonstrate an inhibitory cholinergic regulation of electrically evoked GABA rele ase via M-2 receptors located on cortical GABAergic terminals. (C) 199 7 Elsevier Science Ltd. All rights reserved.