Influence of Severe Hypoglycemia on Brain Extracellular Calcium and Potassium Activities, Energy, and Phospholipid Metabolism

Abstract

In the cerebral cortices of rats, during insulin-induced hypoglycemia, changes in the concentrations of labile phosphate compounds [ATP, ADP, AMP and phosphocreatine (PCr)] and glycolytic metabolites (lactate, pyruvate and glucose) as well as phospholipids and free fatty acids (FFA) were studied in relation to extracellular K and Ca activities. Changes in extracellular Ca and K activities occurred at approximately the onset of isoelectricity. The extracellular Ca activity dropped from 1.17 .+-. 0.14 mM to 0.18 .+-. 0.28 .mu.M and the K activity rose from 3.4 .+-. 0.94 mM to 48 .+-. 12 mM (means .+-. SD). Minutes prior to this ionic change the levels of ATP, PCr and phospholipids were unchanged while the levels of FFA remained unchanged or slightly elevated. Following the 1st ionic change the steady-state levels of ATP decreased by 40%, from 2.42 to 1.56 .mu.mol/g. PCr levels decreased by 75%, from 4.58 to 1.26 .mu.mol/g. Simultaneously, the levels of FFA increased from 338 to 642 nmol/g, arachidonic acid displaying the largest relative increase, 33 to 130 nmol/g. The first ionic change was followed by a short period of normalization of ionic concentrations followed by a sustained ionic change. This was accompanied by a small additional decrease in ATP (to 1.26 .mu.mol/g). The FFA levels increased to 704 nmol/g. There was a highly significant negative correlation between the levels of FFA and the energy charge of the tissue. The formation of FFA was accompanied by a decrease in the phospholipid pool. The largest relative decrease was observed in the inositol phosphoglycerides, followed by serine and ethanolamine phosphoglycerides. After 10 min of isoelectricity the levels of phospholipids had decreased by 5.12 .mu.mol/g while the levels of FFA had increased by 0.46 .mu.mol/g, indicating oxidative metabolism or washout of the released FFA. The attenuation of the rapid initial changes in the levels of the energy metabolites and FFA as well as the correlation between the energy charge and the levels of FFA suggests that a new steady state is established following the 1st ionic change. The importance of these reactions for the development of hypoglycemic neuronal damage is discussed.