RECOVERY OF MITOCHONDRIAL AND PLASMA-MEMBRANE FUNCTION FOLLOWING HYPOGLYCEMIC COMA - COUPLING OF ATP SYNTHESIS, K+ TRANSPORT, AND CHANGES IN EXTRACELLULAR AND INTRACELLULAR PH

The primary objective of the present study was to evaluate the recover y of plasma and mitochondrial membrane functions after 30 min of hypog lycemic coma and to establish whether a lingering accumulation of free fatty acids (FFAs) delays the recovery. A secondary objective was to study whether production of metabolic acids following glucose infusion leads to a fall in intracellular pH (pH(i)). Phosphocreatine, creatin e, ATP, ADP, and AMP, as well as glycogen, glucose, lactate, pyruvate, and FFAs of rat brain cortex and caudoputamen were measured, and ''fr ee'' ADP was calculated from the creatine kinase equilibrium. Extracel lular pH (pH(e)) and K+ concentration (K+ e) were measured with ion-se nsitive microelectrodes, and pH(i) was derived by the CO2 method. Gluc ose injection was followed by resumption of oxidative phosphorylation within approximately 2 min and by an equally rapid restoration of norm al K+ e levels. These functions recovered although tissue FFAs remaine d elevated for at least 7-8 min. Tissue lactate content increased only moderately and production of metabolic acids did not lead to intracel lular acidosis. After 15 min of recovery, pH(i) was moderately increas ed, although pH(e) fell toward 7.0. It is speculated that the dissocia tion between intra- and extracellular pH is compatible with an up-regu lation of an Na+/H+ antiporter, e.g., by phosphorylation.