Pharmacological characterization of pre- and postsynaptic GABAB receptors in the deep nuclei of rat cerebellar slices.
Whole-cell current-and voltage-clamp recordings were made from deep nuclear neurons in cerebellar slices from seven- to nine-day-old rats. Baclofen, a GABAB agonist, produced a slow postsynaptic hyperpolarization associated with a decrease in input resistance. The hyperpolarization was G-protein-dependent, blocked by intracellular Cs+ and antagonized by CGP 35348, a GABAB antagonist. In dialysed neurons recorded with Cs+ -containing pipettes, baclofen suppressed deep nuclear neuronal inhibitory postsynaptic potentials and inhibitory postsynaptic currents evoked by electrical stimulations of the Purkinje cell axons. This effect was blocked by CGP 35348, indicating that the suppressions were mediated by presynaptic GABAB receptors. The inability of CGP 35348 or uptake inhibitors (nipecotic acid and NO-711) to alter the decay of inhibitory postsynaptic currents evoked by maximal stimulation suggested that GABAB receptors are not activated by the stimulation of the GABAergic input. Paired-pulse depression of inhibitory postsynaptic currents was not blocked by CGP 35348. Moreover, neither uptake inhibitors nor CGP 35348 produced any significant changes to the whole-cell current produced by a tetanic stimulation of Purkinje cell axons, suggesting that GABAB autoreceptors were also not activated by endogenous GABA release. Our findings indicate that while pre- and postsynaptic GABAB receptors are present in the deep nuclei of the rat cerebellum, they are not activated by electrical stimulation of the Purkinje cell axons.
Morishita
W
W
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Sastry
B R
BR
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D019204:GTP-Binding Proteins; D001418:Baclofen