The effects of magnesium on the mitochondrial function after cerebral ischemia

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It is well known that mitochondria play a role as a generator of ATP by increasing the proton gradient across the inner mitochondrial membrane and by coupling the proton gradient to phospholylation with ATP synthetase. Mitochondria are also key regulators of cytosolic calcium concentration by activating an inward flow via the uniporter in the inner mitochondrial membrane and by outward flow via the Ca^<2+>/Na^+ exchanger and an Na^+-independent mechanism in the inner mitochondrial membrane. Thus, maintenance of mitochondrial function coupled to mitochondrial membrane potential (Ψ_m) is crucial for cell survival. In the present study, changes in mitochondrial membrane potential were measured in vivo at the site of a DC electrode using a potentiometric dye, JC-1, and a rat model of focal ischemia. Two μl of dye (control group) or dye with oligomycin, an ATP synthetase inhibitor, (oligomycin group) was injected into the parieto-temporal cortex through the DC electrode. With the initiation of ischemia, a decrease in mitochondrial potential was observed within 20 seconds in the oligomycin group (earlier than the onset of DC deflection, p=0.02). In contrast, in the control group, mitochondrial potential was maintained at 91±5% of the pre-ischemia level for 118±38 seconds before showing full depolarization simultaneously with DC deflection. During the period of ischemia, the mitochondrial potential was higher in the control group (66±9%) than in the oligomycin group (46±8%, p=0.0002), whereas DC potential was lower in the control group (-18±3) than in the oligomycin group (-15±2mV, p=0.04). These observations suggest that mitochondria consume ATP during ischemia by reversing ATP synthetase activity, which compromises cellular membrane potential by consuming ATP.