title: Inhibitory effect of taurine on veratridine-evoked D-[3H]aspartate release from murine corticostriatal slices: involvement of chloride channels and mitochondria.
abstract: We have previously shown that the inhibitory neuromodulator taurine attenuates the release of preloaded D-[3H]aspartate from murine corticostriatal slices evoked by ischemic conditions or by application of the sodium channel agonist veratridine. The release of D-[3H]aspartate (a non-metabolized analog of glutamate) was used as an index of glutamate release. The aim of the present study was to reveal the molecular mechanisms responsible for this inhibitory effect of taurine. It was shown that 10 mM taurine suppresses D-[3H]aspartate release evoked by 0.1 mM veratridine, but does not affect the high-K+ -(50 mM) or ouabain- (0.1 mM) evoked release. Taurine had no effect in Ca2+ -free medium when the synaptic exocytosis of D-[3H]aspartate was inhibited. Nor did it suppress the release from slices preloaded with the competitive glutamate uptake blocker DL-threo-beta-hydroxyaspartate (THBA), which inhibits D-[3H]aspartate release mediated by the reverse action of glutamate transporters. Omission of Cl- from the incubation medium reduced the effect of taurine, signifying the involvement of a Cl- channel. The glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline did not block the taurine effect, although picrotoxin, a less specific blocker of agonist-gated chloride channels, completely prevented the effect of taurine on veratridine-induced D-[3H]aspartate release. The respiratory chain blocker rotenone or mitochondrial protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in combination with the mitochondrial ATPase inhibitor oligomycin, which inhibits the mitochondrial Ca2+ uniporter, also reduced the effect of taurine. The results obtained in the present study show that taurine acts specifically on the release of preloaded D-[3H]aspartate evoked by veratridine, but not on that evoked by other depolarizing agents, and affects the release mediated both by synaptic exocytosis and the reverse action of glutamate transporter. Taurine may attenuate D-[3H]aspartate release by regulation of mitochondrial Ca2+ sequestration and by activation of a chloride channel, but not that governed by GABA(A) or strychnine-sensitive glycine receptors.
authors.affiliation: University of Tampere, Medical School, Brain Research Center, Tampere, Finland. Svetlana.Molchanova@uta.fi
authors.forename: Svetlana M
authors.initials: SM
authors.lastname: Molchanova
authors.forename: Simo S
authors.initials: SS
authors.lastname: Oja
authors.forename: Pirjo
authors.initials: P
authors.lastname: Saransaari
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D062687:Sodium Channel Agonists; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013654:Taurine / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
chemical_list: D027322:Amino Acid Transport System X-AG; D018118:Chloride Channels; D062687:Sodium Channel Agonists; D013654:Taurine; D001224:Aspartic Acid; D014701:Veratridine; D002118:Calcium