Brain cellular and mitochondrial respiration in media of altered pH

This study was designed to investigate the effects of altered pH on cellular aerobic energy metabolism in the immature and adult rat cerebral cortex. Cerebral cortical slice respiration was measured polarographically in acid and alkaline media. In separate experiments, the extracellular pH was changed by altering the HCO3- concentration or the intracellular pH and extracellular pH were changed by altering the CO2. Respiratory rates and oxidative phosphorylation in adult rat cerebral mitochondria also were measured in media with an altered pH. Increased intracellular pH inhibited respiratory rates in cortical slices from immature rats more than in tissue from adults. Decreasing the pH to 6.7 produced no changes in respiration in mature cortical slices and moderate inhibition of immature tissue respiration. In cerebral mitochondria, altered pH caused inhibition of State 3 respiration, respiratory control ratios, and ADP/O ratios. These changes were greater and occurred with smaller pH changes in the alkaline compared to the acid direction. From the results of these studies, we conclude that brain cellular respiration is not affected by moderate decreases in intracellular pH. With increased pH, there is inhibition of cellular and mitochondrial respiration, which may be the mechanism for the rise in lactic acid previously observed to result from hypocarbia in vivo.