Inhibition of Q i site of mitochondrial complex III with antimycin A decreases persistent and transient sodium currents via reactive oxygen species and protein kinase C in rat hippocampal CA1 cells

Abstract

Hypoxia-induced inhibition of Q i site of mitochondrial complex III under hypoxia has received attention, but its downstream pathways remain unclear. In this paper, we used Q i site inhibitor antimycin A to mimic the inhibition of the Q i site of mitochondrial complex III and studied the effects of the inhibition of this site on persistent sodium currents, transient sodium currents, and neuronal excitability in rat hippocampal CA1 cells with whole cell patch-clamp methods. The results showed that antimycin A decreased the amplitude of both persistent and transient sodium currents; antioxidant 2-mercaptopropionylglycine or 1,10 phenanthroline abolished the effect of antimycin A; the complex III Q o site inhibitor stigmatellin, the protein kinase C inhibitor chelerythrine, but not the protein kinase A inhibitor H89, canceled the effect of antimycin A; antimycin A decreased the amplitude of both persistent and transient sodium currents only at more depolarized membrane potentials and the decrease percentage of both persistent and transient sodium currents after antimycin A at potentials above −50 mV increased with the change in potentials toward more depolarized direction; exogenous application of H 2O 2 inhibited the amplitude of both persistent and transient sodium currents; the amount of current required to trigger spikes was increased and the number of spikes produced by varying levels of currents was decreased by antimycin A. These results suggest that the inhibition of Q i site of mitochondrial complex III decreases both persistent and transient sodium currents via reactive oxygen species and protein kinase C in rat hippocampal CA1 cells.