Metabolic inhibition and electrical properties of type-1-like cortical astrocytes

Type-1-like cortical mouse astrocytes were studied in homogeneous cultures. Membrane input resistance and membrane potential were measured during drug-induced inhibition of glycolysis (sodium fluoride), mitochondrial respiration (antimycin-a) and Na+/K+ pump activity (ouabain). It was found that the electrical properties of the astrocytes recovered after a 60 min period with inhibited glycolysis or mitochondrial respiration, exhibiting only small reversible depolarizations. A 60 min period of high K(+)-induced depolarization, of cell swelling or of Na+/K+ pump inhibition does not lead to irreversible changes. Total block of energy metabolism, however, causes (1) a large depolarization, which is mainly mediated by external calcium, and (2) a 10-fold increase in input resistance, suggestive of an uncoupling of gap junctions. After an exposure period ranging between 45 and 60 min these conditions lead to irreversible damage. This damage appears to be independent of extracellular calcium and the degree of depolarization and to be specifically mediated by events occurring after the 60-min period of inhibited cell metabolism, that is during the recovery period.