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 (FFAs) were studied in relation to extracellular potassium and calcium activities. Changes in extracellular calcium and potassium activities occurred at approximately the onset of isoelectricity . The extracellular calcium activity dropped from 1.17 +/- 0.14 mM to 0.18 +/- 0.28 mM and the potassium 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 FFAs remained unchanged or slightly elevated. Following the first ionic change the steady-state levels of ATP decreased by 40%, from 2.42 to 1.56 mumol/g. PCr levels decreased by 75%, from 4.58 to 1.26 mumol/g. Simultaneously, the levels of FFAs 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 mumol/g). The FFA levels increased to 704 nmol/g. There was a highly significant negative correlation between the levels of FFAs and the energy charge of the tissue. The formation of FFAs 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.(ABSTRACT TRUNCATED AT 250 WORDS)