Functionally Abnormal Na+-K+ Pump in Erythrocytes of a Morbidly Obese Patient

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Abstract
The Na+-K+ pump in the erythrocytes of a mordibly obese patient shows a unique constellation of functional abnormalities. The number of pump units, measured by [3H]ouabain binding to intact cells, as well as the enzymatic activity of the (Na+-K+)-dependent ATPase in erythrocyte membranes were found to be markedly increased compared with control cells (18-fold and 14-fold, respectively). There was a concomitant fivefold increase in the rate of pump-mediated uptake of 86Rubidium (a K analogue); this was balanced by an increased rate of 86Rb efflux. In striking contrast to normal cells, however, a major portion of this efflux (80%) was inhibited by ouabain, and thus appeared to be mediated by the Na+-K+ pump. Erythrocytes from this patient had elevated levels of intracellular K+ and reduced levels of intracellular Na+. This finding, taken together with the ouabain inhibition of K+ efflux and the absence of associated abnormalities, argues against the possibility that the increased number of Na+-K+ pump units was a compensation for a primary increase in the permeability of the erythrocyte membrane to monovalent cations, as is seen in a variety of erythrocyte disorders. Further evidence for a primary abnormality of the enzyme was our observation that the cardiac glycoside ouabain bound to these cells with reduced affinity and had a right shifted dose response for pump inhibition. The markedly increased number of Na+-K+ pump units in these cells did not appear to extend to mononuclear leukocytes. In conclusion, the erythrocytes from this patient have a very large number of functionally abnormal Na+-K+ ATPase units. A unique abnormality of the erythrocyte Na+-K+ ATPase of these cells is the most likely explanation for these findings.