MULTIPLE POSTSYNAPTIC ACTIONS OF GABA VIA GABAB RECEPTORS ON CA1 PYRAMIDAL CELLS OF RAT HIPPOCAMPAL SLICES. PHAM, Tri M. and Jean-Claude LACAILLE. Centre de recherche en sciences neurologiques, D[acute]epartement de physiologie, Universit[acute]e de Montr[acute]eal, Montr[acute]eal, Qu[acute]ebec, Canada H3C 3J7.
APStracts 3:0017N, 1996.
1. The effects of GABA on non-GABA A receptors were investigated with intracellular recordings in CA1 pyramidal cells of rat hippocampal slices in the presence of antagonists of GABA A receptors (50[mu]M bicuculline [BIC] and 50[mu]M picrotoxin [PIC]), N-methyl-D-aspartate (NMDA) and non-NMDA receptors (100[mu]M 2-amino-5-phosphonopentanoic acid [AP-5] and 40[mu]M 6-cyano-7- nitroquinoxaline-2,3-dione [CNQX], respectively), and of a blocker of GABA uptake (1mM nipecotic acid [NIP]). The effects of GABA were compared with those of the selective GABA B agonist (-)baclofen (CGP-11973A, (-)BAC). 2. In the presence of these antagonists, micropressure application of GABA into stratum radiatum evoked hyperpolarizations with relatively fast peak latency (2 sec) and decay (12 sec). (-)BAC, in the absence of antagonists, hyperpolarized cells but with a slower time course (peak latency 8 sec, decay 78 sec). The mean equilibrium potential (E rev ) of responses to GABA (-94mV; n=11) and (-)BAC (-87mV; n=8) were similar, suggesting that both responses were mediated by K + conductances. 3. Bath applications of 1mM Ba 2+ partly antagonized GABA responses in a reversible manner. The mean amplitude of the Ba 2+ -resistant GABA response was 46% of control (n=16, p<0.05). In contrast, (-)BAC responses were completely abolished by Ba 2+ (n=15), and the effect was reversible. Thus both GABA and (-)BAC activate a common Ba 2+ -sensitive conductance, but GABA may also activate another Ba 2+ -resistant conductance. 4. The Ba 2+ -resistant GABA response had a similar time course to control GABA responses, but its E rev was more depolarized (-79 mV, n=8, p<0.05). 5. During recordings with electrodes containing KCl to reverse the Cl - gradient, although GABA responses were smaller in amplitude, their time course and E rev (-91 mV; n=10) were similar to those recorded with K-acetate electrodes. Thus, Cl - conductances may not be involved in these non-GABA A responses elicited by GABA. 6. During recordings with electrodes containing CsCl to block outward K + currents, hyperpolarizing GABA responses were not observed (n=8). In these conditions, GABA elicited depolarizing responses with a faster time course (peak latency 1 sec, decay 5 sec) than the hyperpolarizing responses recorded with electrodes containing KCl. Hence, GABA may produce hyperpolarizations by activating K + conductances, but it may also produce an additional depolarizing response via other Cs + -insensitive conductances. 7. During recordings with electrodes containing LiCl to interfere with G-protein activation, hyperpolarizing GABA responses were blocked and depolarizing responses were unmasked (n=5). These depolarizing responses were generally similar to those recorded with electrodes containing CsCl. GABA responses were also reduced during recordings with electrodes containing the irreversible G- protein activator guanosine-5'-O-(3-thiotriphosphate) (GTP[delta]S). Thus, hyperpolarizing GABA responses may involve G-protein activation, but the depolarizing responses may not. 8. Bath application of the selective GABA B antagonist CGP-35348 (1mM) did not significantly reduce hyperpolarizing GABA responses (18% reduction in amplitude, n=6, p>0.05), but completely suppressed (-)BAC responses (n=2). The more potent and selective GABA B antagonist CGP- 55845A (5[mu]M) abolished all GABA responses (n=7). Thus, all non-GABA A responses elicited by GABA may be mediated by GABA B receptors. 9. In conclusion, GABA, in the presence of GABA A antagonists, may produce in CA1 pyramidal cells two distinct postsynaptic responses mediated via GABA B receptors and G-protein activation: 1) GABA ( and (-)BAC) may activate a Ba 2+ -sensitive K + conductance, and 2) GABA ( but not (-)BAC) may also generate a Ba 2+ -insensitive K + conductance. GABA may also generate other ionic changes, via GABA B receptors, resulting in depolarization of pyramidal cells.

Received 1 March 1995; accepted in final form 10 January 1995.
APS Manuscript Number J136-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96