EXTRACELLULAR PH IN THE RAT-BRAIN DURING HYPOGLYCEMIC COMA AND RECOVERY

It has previously been shown that hypoglycemic coma is accompanied by marked energy failure and by loss of cellular ionic homeostasis. The general proposal is that shortage of carbohydrate substrate prevents lactic acid formation and thereby acidosis during hypoglycemic coma. The objective of the present study was to explore whether rapid downhill ion fluxes, known to occur during coma, are accompanied by changes in extra- and/or intracellular pH (pH(e) and/or pH(i)), and how these relate to the de- and repolarization of cellular membranes. Cortical pH(e) was recorded by microelectrodes in insulin-injected rats subjected to 30 min of hypoglycemic coma, with cellular membrane depolarization. Some rats were allowed up to 180 min of recovery after glucose infusion and membrane repolarization. Arterial blood gases and physiological parameters were monitored to maintain normotension, normoxia, normocapnia, and normal plasma pH. Following depolarization during hypoglycemia, a prompt, rapidly reversible alkaline pH(e) shift of about 0.1 units was observed in 37/43 rats. Immediately thereafter, all rats showed an acid pH shift of about 0.2 units. This shift developed during the first minute, and pH(e) remained at that level until repolarization was induced. Following repolarization, there was an additional, rapid, further lowering of pH(e) by about 0.05 units, followed by a more prolonged decrease in pH(e) that was maximal at 90 min of recovery (ΔpH(e) of approximately -0.4 units). The pH(e) then slowly normalized but was still decreased (-0.18 pH units after 180 min when the experiment was terminated. The calculated pH(i) showed no major alterations during hypoglycemic coma or after membrane repolarization following glucose administration. The results demonstrate that hypoglycemic coma is accompanied by a decrease in pH(e) of almost the same magnitude as observed in status epilepticus, and that a lingering extracellular acidosis is observed during recovery from hypoglycemia. It is proposed that, at least in part, the initial extracellular alkaline/acid shift is caused by H+ influx or HCO3- outflux (alkaline shift) followed by H+ efflux or HCO3- influx (acid shift) through conductance channels that are opened during depolarization. The alkaline shift appears before the depolarization has occurred and the acid shift after the depolarization, when mainly the chemical gradient provides the driving force. It is speculated that Na+/H+ exchange contributes to the further extracellular acidification seen during repolarization.