Different oxidants and PKC isozymes mediate the opposite effect of inhibition of Q(i) and Q(o) site of mitochondrial complex III on calcium currents in rat cortical neurons

Abstract

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 Q(i) site inhibitor antimycin A and the Q(o) site inhibitor myxothiazol to inhibit the Q(i) site and the Q(o) site of the complex III and studied the effect and mechanism of the inhibition of these sites on voltage-gated Ca(2+) currents (I(Ca)) in rat prefrontal neurons with whole cell patch-clamp method in slices. The results showed that antimycin A inhibited I(Ca), but myxothiazol increased it. Further mechanism study showed that antimycin A inhibited I(Ca) via the H(2)O(2)-hydroxyl radicals/cPKC (mainly PKCbetaI) pathway, whereas myxothiazol increased I(Ca) via the superoxide anion/nPKC (mainly the PKCdelta) pathway.