Interaction of Na+ and K+ transport with aerobic energy metabolism in slices of Morris hepatoma 3924A

Addition of increasing concentrations of glucose to slices of Morris hepatoma 3924A greatly stimulated aerobic lactate production and reduced respiration by 20%. Neither the adenine nucleotide content of the slices nor the calculated rate of adenosine 5' triphosphate synthesis was altered. Ouabain reduced the rate of O ₂ uptake (by 20 to 25%) and of aerobic lactate production (by 25 to 50%) without affecting adenine nucleotide contents. The reduction by ouabain of the calculated rate of adenosine 5' triphosphate synthesis was similar whether the slices were utilizing only endogenous substrate or exogenous glucose also. Raising the medium K ⁺ concentration (and correspondingly reducing Na ⁺) partially overcame the inhibition of ion transport by ouabain and partially restored the rates of respiration and aerobic lactate production toward control levels. Electron microscopic observations of mitochondria within the slices incubated under different conditions showed variations in configuration between 'orthodox', 'condensed' and degenerating forms. Slices preincubated at 1° showed mitochondria in the condensed form: they were restored to the orthodox configuration during incubation at 38° in oxygenated medium. Oligomycin and glucose enhanced the transition, but ouabain reduced the number of mitochondria undergoing the change. The results suggest that in hepatoma 3924A utilization of adenosine 5' triphosphate by ion transport exerts a simultaneous control of both respiration and aerobic glycolysis, which is presumably mediated by alterations in the availability of adenosine 5' diphosphate. The mitochondria undergo conformational transitions under conditions likely to affect local availability of adenosine 5' diphosphate within the cell compartments, but the transitions are not all readily interpretable by comparison with the effects of externally added adenosine diphosphate on isolated mitochondria.