Pharmacological and developmental evidence that the potassium-induced stimulation of deoxyglucose uptake in astrocytes is a metabolic manifestation of increased Na+-K+-ATPase activity

There is disagreement in the literature whether or not deoxyglucose accumulation, a measure of glycolytic activity, is increased in astrocytes during exposure to elevated concentrations of the potassium ion (K+). In the present work we have confirmed our previous finding that deoxyglucose accumulation in primary cultures of well-differentiated mouse astrocytes shows a robust increase when the K+ concentration in the incubation medium is raised to or above 12 mM. This response is inhibited by ouabain (with a half-maximum effect at similar to 0.1 mM), indicating that it is a metabolic manifestation of the activity of an Na+-K+-ATPase, The stimulation at this high level of K+ indicates a remarkably low K+ affinity of the Na+-K-+-ATPase involved, enabling it to be activated by above-normal concentrations of K+, At a resting concentration of K+ (5.4 mM), at least one half of the deoxyglucose accumulation is also a reflection of Na'-K'-ATPase activity, as shown by its susceptibility to inhibition by ouabain, Ouabain has some effect even at a concentration of 0.1 mu M, indicating participation of not only the alpha(1) isoform which has a low affinity to ouabain, but also of the alpha(2) isoform, which has a high affinity. The stimulatory effect of elevated K+ is absent in immature astrocytes and only develops after prolonged time in culture. It could not be evoked in a seemingly similar culture of rat astrocytes, which has previously been shown to lack Na+-K+-ATPase activity as well as the alpha(2) isoform of the ATPase. This isoform has unequivocally been found to be expressed by astrocytes in situ.