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.
SUMMARY AND CONCLUSIONS
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
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