Energetics and glucose metabolism in hippocampal slices during depolarization: 31P and 13C NMR studies

Alterations in the energy state and glucose metabolism of hippocampal slices exposed to high extracellular K+ ([K+]o) were monitored using 31P and 13C NMR spectroscopy. Slices were perfused (37 degrees C) continuously within the NMR spectrometer and tissue viability and metabolic activity were maintained for at least 18 h. 31P spectra showed that upon exposure to 40 mM [K+]o, there was a rapid compromise in tissue energetics where, by 15 min of exposure, the ratio of phosphocreatine and of nucleoside triphosphates to inorganic phosphate (extra- and intracellular) decreased 30-50% relative to pre-exposure values. This was accompanied by a pH decrease of approximately 0.3 units in both the intra and extracellular environments. A lower but stable energy state was reached at approximately 15 min of exposure and full recovery was observed by 30 min following the removal of high [K+]o. Utilizing 13C NMR in the presence of [1-13C]glucose, an immediate and dramatic acceleration in tissue glycolysis was observed when slices were exposed to 40 mM [K+]o: the rates of both [1-13C]glucose consumption and [3-13C] acetate synthesis increased by approximately 20 fold. By 60 min following the removal of high-[K+]o, pre-exposure rates of tissue glycolysis were restored. The results indicated that the rapid and dramatic induction of energy production via glycolysis probably accounts for the ability of hippocampal slices to maintain viability and recuperate from brief but intense depolarizing conditions which are reminiscent of seizure states in vivo.