The red blood cell: a model for ouabain receptor regulation in the heart?

The assumption that the red blood cell can be used as a model for ouabain receptor regulation in heart muscle has been tested using isolated tissues from humans, guinea pigs, and chickens. The following results were obtained: The affinity of the ouabain receptor was similar in both human erythrocytes and right atrial appendage, but the density of binding sites was much lower on the erythrocytes. There was no correlation between the binding capacity in both tissues. Ouabain receptor occupation was closely correlated with inhibition of Na+/K+-transport in human erythrocytes and chick heart nonmuscle cells in culture. In contrast, in chick heart muscle cells, an occupation of 40% of the receptors decreased the Na+/K+-transport rate by only 10%. In hypokalemia, the ouabain binding capacity was increased in human and guinea pig erythrocytes but not in guinea pig heart muscle. Such increases were seen in chick heart nonmuscle cells in moderate hypokalemia but in heart muscle cells only after severe hypokalemia. Incubation of chick heart muscle cells in toxic but not in "therapeutic" ouabain concentrations increased the number of ouabain receptors. Increases in receptor number attenuated the positive inotropic and toxic actions of ouabain. These variations between ouabain receptor regulation in red blood cells and heart muscle of several species may be attributable to the lack of a "sodium pump reserve" in erythrocytes and heart nonmuscle cells. Such variations indicate that the human erythrocyte is not a suitable model for the ouabain receptor in the human heart.