Activation of presynaptic GABA receptors inhibits evoked IPSCs in rat
magnocellular neurons in vitro.
Didier Mouginot, Samuel B. Kombian and Quentin J. Pittman.
Neuroscience Research Group, University of Calgary, 3330 Hospital Drive,
NW, Calgary, Alberta, Canada, T2N 4N.
APStracts 4:0316N, 1997.
ABSTRACT
Whole cell recordings (nystatin-perforated patch) were carried out on
magnocellular neurons of the rat supraoptic nucleus (SON) to study the
modulation of inhibitory postsynaptic currents (IPSCs) by GABA receptors.
Field stimulation adjacent to the SON in the presence of kynurenic acid,
evoked monosynaptic GABAergic IPSCs. Baclofen reversibly reduced the amplitude
of the IPSCs in a dose-dependant manner (EC50:0.68 M) without apparent effect
on the holding current (V = -80 mV) or input resistance, and altered neither
the kinetic properties, nor the reversal potential of IPSCs. Concomittnat to
IPSC depression, baclofen enhanced the paired- pulse ratio for two consecutive
IPSCs (interstimulus interval (ISI): 50ms), an effect consistant with a
presynaptic locus of action. Both baclofen's action were abolished by CGP35348
(500 M), a GABA receptor antagonist. In testing for involvement of
synaptically-activated presynpatic GABA receptors, we only recorded paired-
pulse facilitation at most ISIs tested (50 to 500 ms), suggesting that the
classical GABA autoreceptors may not normally be activated in our conditions.
However, enhancement of local GABA concentration by perfusion of a GABA uptake
inhibitor (NO-711) revealed an action of endogenous GABA at these presynaptic
GABA receptors. The non-selective K+ channel blocker Ba2+ abolished baclofen's
effect while pertussis toxin (PTX) pretreatment (200-500 ng/ml for 8-24 hours)
was ineffective in blocking the baclofen-induced inhibition, making an
involvement of PTX-sensitive G protein unlikely. The present results show that
presynaptic GABA receptors that are coupled to PTX-insensitive G- proteins may
be activated by endogenous GABA under conditions of reduced GABA uptake, thus
regulating the inhibitory synaptic input to SON.
Received 27 June 1997; accepted in final form 8 October 1997.
APS Manuscript Number J545-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997