Increase of Na-K-ATPase activity, glutamate, and aspartate uptake in dog erythrocytes associated with hereditary high accumulation of GSH, glutamate, glutamine, and aspartate.

We have found convincing evidence for the presence of Na-K-ATPase and high potassium (K) and low sodium (Na) concentrations in the erythrocytes of some dogs associated with hereditary high concentrations of erythrocyte glutathione and some amino acids, glutamate, glutamine, and aspartate. The Na-K-ATPase activity of the erythrocyte membranes of the dogs was about 3 times that of human erythrocyte membranes, whereas the enzyme activity was not detected in control dogs with a normal level of blood glutathione. The Michaelis constant of the enzyme for ATP (Km ATP) was 6.6 X 10(-3)M in the dogs' erythrocytes and 5.0 X 10(-4)M in the human erythrocytes. The concentration of K in the erythrocytes in the dogs examined was about 11 times that of the controls, whereas the erythrocyte Na concentration in the dogs was about one-third that of the controls. The concentrations of K and Na in the plasma of the dogs were equal to those of the controls. Furthermore, L-3H-glutamate and L-3H-aspartate uptake by those cells with high activity of Na-K-ATPase greatly increased, while L-3H-glutamine uptake was unchanged. It appeared that Na+ and K+ gradients created by Na-K-ATPase across the cell membrane might stimulate glutamate and aspartate uptake by the cells, thus causing the high accumulation of such amino acids in the cells.