Inhibitory effect of high oxygen pressure on potassium- induced activation of pyruvate dehydrogenase and glucose metabolism in rat brain slices.
The effects of high oxygen pressure on pyruvate dehydrogenase (pyruvate: lipoate oxidoreductase (decarboxylating and acceptor-acylating), EC 1.2.4.1) activity, tissue concentration of ATP, and CO2 production from glucose were studied in rat brain cortical slices. The increase in pyruvate dehydrogenase activity and the lowering of cellular ATP, occurring during potassium-induced depolarization at 1 atm of oxygen, were reversed by increasing the oxygen pressure to 5 atm. When brain slices were incubated at 1 atm oxygen with [U-14C]glucose, a high potassium medium approximately doubled the production of 14CO2. Oxygen at 5 atm abolished this potassium-dependent increase in 14CO2 production with no significant effect on glucose oxidation in normal Krebs-Ringer phosphate medium. Adding 4 atm helium to 1 atm oxygen did not interfere with the ability of potassium ions to activate pyruvate dehydrogenase, lower ATP, or increase glucose oxidation. The results show that toxic effects of hyperbaric oxygen, not manifest in "resting" tissue, may be revealed during stress such as potassium depolarization. The site of the toxic effects of oxygen is probably the cell membrane where excess oxygen appears to interfere with the action of the sodium pump, calcium transport or other processes stimulated by increased concentrations of extracellular potassium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism*; D006931:Hyperbaric Oxygenation; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption; D011188:Potassium / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats
D011768:Pyruvate Dehydrogenase Complex; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D005947:Glucose; D011188:Potassium