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 [Ca
2+]
c but did not alter the 4-AP-mediated depolarization. The effect of CoQ10 on evoked glutamate release was abolished by blocking the Ca
v2.2 (N-type) and Ca
v2.1 (P/Q-type) Ca
2+ 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 Ca
2+ entry and ERK/synapsin I signaling pathway.
Keywords:
qsSearchArea=searchText">CoQ10; qsSearchArea=searchText">glutamate release; qsSearchArea=searchText">cerebrocortical nerve terminals; qsSearchArea=searchText">ERK; qsSearchArea=searchText">voltage-dependent Ca2+ channels