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 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.
Wu
Pei-Ying
PY
State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai, China.
Lai
Bin
B
Dong
Yi
Y
Wang
Ze-Min
ZM
Li
Zi-Cheng
ZC
Zheng
Ping
P
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D020134:Catalytic Domain / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D008689:Methacrylates / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055366:Synaptic Potentials / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology
D015220:Calcium Channels; D007527:Isoenzymes; D008689:Methacrylates; D016877:Oxidants; D013844:Thiazoles; D000968:Antimycin A; C030517:myxothiazol; D011493:Protein Kinase C; D014450:Electron Transport Complex III