Control of aerobic glycolysis in the brain in vitro.
Protoveratrine-(5 microM) stimulated aerobic glycolysis of incubated rat brain cortex slices that accompanies the enhanced neuronal influx of Na+ is blocked by tetrodotoxin (3 microM) and the local anesthetics, cocaine (0.1 mM) and lidocaine (0.5 mM). On the other hand, high [K+]-stimulated aerobic glycolysis that accompanies the acetylcholine-sensitive enhanced glial uptakes of Na+ and water is unaffected by acetylcholine (2 mM). Experiments done under a variety of metabolic conditions show that there exists a better correlation between diminished ATP content of the tissue and enhanced aerobic glycolysis than between tissue ATP and the ATP-dependent synthesis of glutamine. Whereas malonate (2 mM) and amino oxyacetate (5 mM) suppress ATP content and O2 uptake, stimulate lactate formation, but have little effect on glutamine levels, fluoroacetate (3 mM) suppresses glutamine synthesis in glia, presumably by suppressing the operation of the citric acid cycle, with little effect on ATP content, O2 uptake, and lactate formation. Exogenous citrate (5 mM), which may be transported and metabolized in glia but not in neurons, inhibits lactate formation by cell free acetone-dried powder extracts of brain cortex but not by brain cortex slices. These results suggest that the neuron is the major site of stimulated aerobic glycolysis in the brain, and that under our experimental conditions glycolysis in glia is under lesser stringent metabolic control than that in the neuron. Stimulation of aerobic glycolysis by protoveratrine occurs due to diminution of the energy charge of the neuron as a result of stimulation of the sodium pump following tetrodotoxin-sensitive influx of Na+; stimulation by high [K+], NH4+, or Ca2+ deprivation occurs partly by direct stimulation of key enzymes of glycolysis and partly by a fall in the tissue ATP concentration.
D000109:Acetylcholine / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002951:Citrates / Q000502:physiology; D005260:Female; D005973:Glutamine / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects*; D011188:Potassium / Q000502:physiology; D011526:Protoveratrines / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D002951:Citrates; D011526:Protoveratrines; D005973:Glutamine; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; D012964:Sodium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium