Recovery of Mitochondrial and Plasma Membrane Function following Hypoglycemic Coma: Coupling of ATP Synthesis, K+Transport, and Changes in Extra- and Intracellular pH

Abstract

The primary objective of the present study was to evaluate the recovery of plasma and mitochondrial membrane functions after 30 min of hypoglycemic 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 (pHi). Phosphocreatine, creatine, ATP, ADP, and AMP, as well as glycogen, glucose, lactate, pyruvate, and FFAs of rat brain cortex and caudoputamen were measured, and "free" ADP was calculated from the creatine kinase equilibrium. Extracellular pH (pHe) and K+ concentration (K+e) were measured with ion-sensitive microelectrodes, and pHi was derived by the CO2 method. Glucose injection was followed by resumption of oxidative phosphorylation within approximately 2 min and by an equally rapid restoration of normal K+e levels. These functions recovered although tissue FFAs remained elevated for at least 7-8 min. Tissue lactate content increased only moderately and production of metabolic acids did not lead to intracellular acidosis. After 15 min of recovery, pHi was moderately increased, although pHe fell toward 7.0. It is speculated that the dissociation between intra- and extra-cellular pH is compatible with an up-regulation of an Na+/H+ antiporter, e.g., by phosphorylation.