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

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 Ca²⁺ 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 H₂O₂-hydroxyl radicals/cPKC (mainly PKCβI) pathway, whereas myxothiazol increased I_Ca via the superoxide anion/nPKC (mainly the PKCδ) pathway.