Glycolysis and brain function: [K+]o stimulation of protein synthesis and K+ uptake require glycolysis.

Glucose is essentially the sole energy substrate in the normally functioning brain. There are, however, situations in which other substrates can partially substitute for glucose and maintain an apparently normal brain function. However, in no case has it been possible to completely substitute other substrates for glucose and maintain normal brain function. Studies on insulin-induced hypoglycemia suggest that this glucose dependence does not result from its involvement in ATP generation. Two explantation that have been offered are that toxic catabolites arise if nonglucose substrates are oxidized or that glycolysis is necessary to maintain neurotransmitter metabolism. We consider a third basis for the glucose requirement: our past studies have shown that hippocampal slice protein synthesis is activated by small increases in extracellular [K+] ([K+]o), and that this results from activation of K+ uptake into brain cells. We find that this process specifically requires aerobic glycolysis. The basis for the requirement appears to be that [K+]o activation of the Na+-K+ pump is specifically dependent on glycolytically generated energy. Thus, it is possible that glucose is required to maintain normal K+ clearance from the extracellular space during neural activity. This could partially account for the dependence of brain function on glycolysis.