Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia.
Effects of increasing extracellular K+ or intracellular 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 microM), 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 microM tetrodotoxin, which blocks Na+ channels. The carboxylic sodium ionophore, monensin (10 microM), more than doubled [14C]dGlc phosphorylation; this effect was only partially blocked by ouabain and unaffected by tetrodotoxin. L-Glutamate (500 microM) 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.
Takahashi
S
S
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892-4030, USA.
Driscoll
B F
BF
Law
M J
MJ
Sokoloff
L
L
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005865:Gestational Age; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D007700:Kinetics; D008985:Monensin / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology
D002250:Carbon Radioisotopes; D018698:Glutamic Acid; D013779:Tetrodotoxin; D010042:Ouabain; D003994:Bucladesine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D014701:Veratridine; D015763:2-Amino-5-phosphonovalerate; D008985:Monensin; D003847:Deoxyglucose; D012964:Sodium; D005947:Glucose; D011188:Potassium