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.

Abstract Inhibition of Q o site of mitochondrial complex III under hypoxia has received attention, but its downstream pathways remain unclear. We used Q o site inhibitor myxothiazol to mimic the inhibition of the Q o 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 Q o site of mitochondrial complex III increases persistent sodium currents via superoxide production and protein kinase C activation.