title: A comparison of the effect of calcium channel ligands and GABAB agonists and antagonists on transmitter release and somatic calcium channel currents in cultured neurons.
abstract: Glutamate release has been examined from cultured cerebellar granule neurons in the rat using the technique of prelabelling the releasable pool of glutamate with [3H]glutamine. Glutamate release was stimulated in control neurons by 2-min incubation with 50 mM K+, or in neurons continuously depolarized in Ca2(+)-free 50 mM K+ medium, by 2-min incubation with medium containing 5 mM Ca2+. The ability of the Ca2(+)-channel agonist (+)-202-791 to increase the stimulated release of [3H]glutamate was approximately doubled in the depolarized condition. The antagonist enantiomer (-)-202-791 produced a small inhibition of K(+)-stimulated release, whereas (-)-202-791 completely inhibited Ca2(+)-stimulated release from depolarized neurons at concentrations greater than 10 nM. (-)-Baclofen (100 microM) inhibited transmitter release similarly (25-30%) under the two conditions. Calcium-channel currents were recorded from cultured dorsal root ganglion neurons under control conditions at a holding potential of -80 mV, or in neurons depolarized to -30 mV. (-)-202-791 produced a greater effect at -30 than at -80 mV although even at -30 mV the inhibition was slow in onset and incomplete. (-)-Baclofen (100 microM) inhibited the amplitude of the calcium-channel current at both holding potentials by 30-50%, although it did not clearly slow activation of the current at the depolarized holding potential. The GABAB receptors associated with inhibition of glutamate release and of calcium-channel currents were both markedly blocked by phaclofen but not by 2-OH-saclofen. These findings suggest that the GABAB receptor associated with inhibitory modulation of transmitter release, and that associated with inhibition of calcium-channel currents show pharmacological similarities, and are able to exert their action even at levels of steady depolarization at which most N-type channels should be inactivated.
authors.affiliation: Department of Pharmacology, St George's Hospital Medical School, London, U.K.
authors.forename: E
authors.initials: E
authors.lastname: Huston
authors.forename: R H
authors.initials: RH
authors.lastname: Scott
authors.forename: A C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D004594:Electrophysiology; D018756:GABA Antagonists; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009539:Nicotinic Acids / Q000494:pharmacology*; D010069:Oxadiazoles; D013237:Stereoisomerism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D018756:GABA Antagonists; D005971:Glutamates; D018377:Neurotransmitter Agents; D009539:Nicotinic Acids; D010069:Oxadiazoles; D010566:Virulence Factors, Bordetella; C049834:PN 202-791; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen