Mechanism of Inhibition of Phosphorylation in Brain Mitochondria by Electrical Impulses

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Abstract
Oxidative esterification of orthophosphate by mitochondria isolated from nervous tissue can be almost completely inhibited by electrical currents which do not affect dehydrogenases or the cytochrome enzymes. A twofold increase in oxidation occurs at the same time, presumably as a result of increased availability of orthophosphate and adenylate phosphate acceptors. Evidence is presented to show that the oxidative phosphorylation coupled to reduced DPN, and not that dependent upon coenzyme A, is sensitive to electrical "stimulation". A 60% inhibition of phosphorylation is obtained with pyruvate, malate, or DPN-H2 as substrates, while with alpha-ketoglutarate the inhibition is less than 40%; the difference being attributable to the insensitive CoA-linked phosphorylation in the last case. The turnover of the adenylates and pyridine micleotides within the mitochondria was followed during oxidative phosphorylation by means of P32. Equilibrium between the intramitochondrial "orthophosphate" (released after protein denaturation) and the adenylate and pyridine systems is reached in a few minutes. Electrical stimulation delays this equilibrium time and inhibits the turnover rate of all fractions. Dinitrophenol diminishes the P turnover only 50-60% in concns. which produce complete inhibition of phosphorylation. Since electric currents by contrast inhibit turnover rates almost as much as net P esterification, the 2 agents act by different mechanisms. It would appear that dinitrophenol largely inhibits mitochondrial phosphatases, while electrical stimulation primarily blocks P coupling mechanisms.