The Journal of Neurophysiology Vol. 79 No. 3 March 1998, pp. 1508-1517
Copyright ©1998 The American Physiological Society

Activation of Presynaptic GABA_B 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, Calgary, Alberta, T2N 4N1, Canada

Mouginot, Didier, Samuel B. Kombian, and Quentin J. Pittman. Activation of presynaptic GABA_B receptors inhibits evoked IPSCs in rat magnocellular neurons in vitro. J. Neurophysiol. 79: 1508-1517, 1998. 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 -aminobutyric acid-B (GABA_B) 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-dependent manner (EC₅₀: 0.68 µM) without apparent effect on the holding current (V_h = 80 mV) or input resistance and altered neither the kinetic properties, nor the reversal potential of IPSCs. Concomittant to IPSC depression, baclofen enhanced the paired-pulse ratio for two consecutive IPSCs [interstimulus interval (ISI): 50 ms], an effect consistent with a presynaptic locus of action. Both actions of baclofen were abolished by CGP35348 (500 µM), a GABA_B receptor antagonist. In testing for involvement of synaptically activated presynaptic GABA_B receptors, we only recorded paired-pulse facilitation at most ISIs tested (50-500 ms), suggesting that the classical GABA_B 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_B receptors. The nonselective K⁺ channel blocker Ba²⁺ abolished baclofen's effect and pertussis toxin (PTX) pretreatment (200-500 ng/ml for 18-24 h) was ineffective in blocking the baclofen-induced inhibition, making an involvement of PTX-sensitive G protein unlikely. The present results show that presynaptic GABA_B 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.

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