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 approximately 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 microM, 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.
Peng
L
L
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
Juurlink
B H
BH
Hertz
L
L
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D003847:Deoxyglucose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010042:Ouabain; D003847:Deoxyglucose; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium