Different oxidants and PKC isozymes mediate the opposite effect of inhibition of Qi and Qo site of mitochondrial complex III on calcium currents in rat cortical neurons

The inhibition of the complex III of the mitochondrial respiratory chain under hypoxia-ischemia has been observed. However, the downstream events of this inhibition remain to be studied. In this paper, we used the Qi site inhibitor antimycin A and the Qo site inhibitor myxothiazol to inhibit the Qi site and the Qo site of the complex III and studied the effect and mechanism of the inhibition of these sites on voltage-gated Ca2+ currents (ICa) in rat prefrontal neurons with whole cell patch-clamp method in slices. The results showed that antimycin A inhibited ICa, but myxothiazol increased it. Further mechanism study showed that antimycin A inhibited ICa via the H2O2-hydroxyl radicals/cPKC (mainly PKCβI) pathway, whereas myxothiazol increased ICa via the superoxide anion/nPKC (mainly the PKCδ) pathway.