Impact of inhibition of Qo site of mitochondrial complex III with myxothiazol on persistent sodium currents via superoxide and protein kinase C in rat hippocampal CA1 cells.
Inhibition of Qo site of mitochondrial complex III under hypoxia has received attention, but its downstream pathways remain unclear. We used Qo site inhibitor myxothiazol to mimic the inhibition of the Qo site of complex III and studied the effects of the inhibition of this site on persistent and transient sodium currents and neuron excitability in rat hippocampal CA1 cells. The results showed myxothiazol apparently increased persistent sodium currents but with a weak effect on transient sodium currents; the effect of myxothiazol on persistent sodium currents was blocked by protein kinase C inhibitor and superoxide scavengers, but not by hydrogen peroxide scavenger and hydroxyl radical formation inhibitor; myxothiazol could increase the activity of protein kinase C and neuron excitability. These results suggest that the inhibition of Qo site of mitochondrial complex III increases persistent sodium currents via superoxide production and protein kinase C activation.
Lai
Bin
B
State Key Laboratory of Medical Neurobiology, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China.
Zhang
Li
L
Dong
Lian-Yan
LY
Zhu
Yan-Hua
YH
Sun
Feng-Yan
FY
Zheng
Ping
P
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D053119:Benzophenanthridines; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D017665:Hydroxyl Radical / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
D000470:Alkaloids; D000935:Antifungal Agents; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007546:Isoquinolines; D008665:Metalloporphyrins; D008689:Methacrylates; C110658:N-(2-mercaptoproprionyl)-glycine; D010617:Phenanthridines; D013438:Sulfhydryl Compounds; D013449:Sulfonamides; D013844:Thiazoles; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013481:Superoxides; D017665:Hydroxyl Radical; C030517:myxothiazol; D012964:Sodium; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005998:Glycine