title: Activation of presynaptic GABAB receptors inhibits evoked IPSCs in rat magnocellular neurons in vitro.
abstract: 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 gamma-aminobutyric acid-B (GABAB) 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 microM) without apparent effect on the holding current (Vh = -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 microM), a GABAB receptor antagonist. In testing for involvement of synaptically activated presynaptic GABAB receptors, we only recorded paired-pulse facilitation at most ISIs tested (50-500 ms), suggesting that the classical GABAB 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 GABAB 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 GABAB 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.
authors.affiliation: Neuroscience Research Group, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Mouginot
authors.forename: S B
authors.initials: SB
authors.lastname: Kombian
authors.forename: Q J
authors.initials: QJ
authors.lastname: Pittman
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D018756:GABA Antagonists; D009557:Nipecotic Acids; D009943:Organophosphorus Compounds; D010091:Oximes; D018080:Receptors, GABA-B; D010566:Virulence Factors, Bordetella; C078793:NNC 711; C066430:CGP 35348; D037342:Pertussis Toxin; D001418:Baclofen