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 22.214.171.124), 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.
|ジャーナル||Proceedings of the National Academy of Sciences of the United States of America|
|出版ステータス||Published - 1995 5月 9|
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