Cerebral Extracellular Calcium Activity in Severe Hypoglycemia: Relation to Extracellular Potassium and Energy State

The changes in extracellular Ca 2+ (Ca e ) and K + (K e ) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N 2 O anaesthesia), there was an increase in K e which, at ∼13 m M, was associated with a fall in Ca e . K e peaked at 48 ± 12 m M, and Ca e at 0.18 ± 0.28 m M. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Ca e recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity, but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.