Intracellular pH as a regulatory signal in astrocyte metabolism

An intracellular alkalinization is observed in mammalian astrocytes in response to repetitive neuronal activity in vivo. The alkalinizing effect of potassium released from electrically active neurons predominates over many other influences on the intracellular pH of astrocytes, including acid loads induced by glutamate and ammonium. There is evidence that this pH signal, elicited by neuronal activity, may facilitate glucose utilization and glutamine formation in astrocytes. This short review surveys the mechanisms of the intracellular pH changes induced in astrocytes by extracellular potassium, glutamate, and ammonium. It then focuses upon the regulatory effects of these pH changes on glucose utilization, as estimated primarily by rates of deoxyglucose phosphorylation, and on the uptake and metabolism of glutamate. Many studies in this field exploit the advantages of astrocyte cell culture. However, the conditions of cell culture can diminish expression of the intracellular alkalinization induced by potassium and thus lead to underestimation of the metabolic significance of this pH signal.