Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia

Effects of increasing extracellular K⁺ or iutracellular Na⁺ concentrations on glucose metabolism in cultures of rat astroglia and neurons were examined. Cells were incubated in bicarbonate buffer, pH 7.2, containing 2 mM glucose, tracer amounts of [¹⁴C]deoxyglucose ([¹⁴C]dGlc), and 5.4, 28, or 56 mM KCl for 10, 15, or 30 min, and then for 5 min in [¹⁴C]dGlc- free buffer to allow efflux of unmetabolized [¹⁴C]dGlc. Cells were then digested and assayed for labeled products, which were shown to consist of 96- 98% [¹⁴C]deoxyglucose 6-phosphate. Increased K⁺ concentrations significantly raised [¹⁴C]deoxyglucose 6-phosphate accumulation in both neuronal and mixed neuronal-astroglial cultures at 15 and 30 min but did not raise it in astroglial cultures. Veratridine (75 μM), which opens voltage- dependent Na⁺ channels, significantly raised rates of [¹⁴C]dGlc phosphorylation in astroglial cultures (+20%), and these elevations were blocked by either 1 mM ouabain, a specific inhibitor of Na⁺,K⁺-ATPase (EC 3.6.1.37), or 10 μM tetrodotoxin, which blocks Na⁺ channels. The carboxylic sodium ionophore, monensin (10 μM), more than doubled [¹⁴C]dGlc phosphorylation; this effect was only partially blocked by ouabain and unaffected by tetrodotoxin. L-Glutamate (500 μM) also stimulated [¹⁴C]dGlc phosphorylation in astroglia-not through N-methyl-D-aspartate or non-N- methyl-D-aspartate receptor mechanisms but via a Na⁺-dependent glutamate- uptake system. These results indicate that increased uptake of Na⁺ can stimulate energy metabolism in astroglial cells.