title: Coenzyme Q10 inhibits the release of glutamate in rat cerebrocortical nerve terminals by suppression of voltage-dependent calcium influx and mitogen-activated protein kinase signaling pathway.
abstract: This study investigates the effects and possible mechanism of coenzyme Q10 (CoQ10) on endogenous glutamate release in the cerebral cortex nerve terminals of rats. CoQ10 inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). CoQ10 reduced the depolarization-induced increase in cytosolic [Ca2+]c but did not alter the 4-AP-mediated depolarization. The effect of CoQ10 on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels and mitogen-activated protein kinase kinase (MEK). In addition, CoQ10 decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK. Moreover, the inhibition of glutamate release by CoQ10 was strongly attenuated in mice without synapsin I. These results suggest that CoQ10 inhibits glutamate release from cortical synaptosomes in rats through the suppression of the presynaptic voltage-dependent Ca2+ entry and ERK/synapsin I signaling pathway.
authors.affiliation: School of Medicine, Fu Jen Catholic University, and Department of Anesthesiology, Far-EAstern Memorial Hospital, No. 510 Zhongzheng Road, Xinzhuang District, New Taipei City, Taiwan 24205.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.forename: Shu-Kuei
authors.initials: SK
authors.lastname: Huang
authors.forename: Su-Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015761:4-Aminopyridine; D002118:Calcium; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D002998:Clonazepam; D003620:Dantrolene; D018698:Glutamic Acid; D018942:Macrolides; D048052:Mitogen-Activated Protein Kinase 3; D026902:Potassium Channel Blockers; D016704:Synapsins; D013841:Thiazepines; D014451:Ubiquinone; C079032:CGP 37157; C040929:bafilomycin A1; C024989:coenzyme Q10