L antigens of sheep red blood cell membranes and modulation of ion transport

Abstract

Sheep are polymorphic with respect to the intracellular Na+ and K+ concentrations of their erythrocytes. Erythrocytes of sheep of the high-K+ (HK) phenotype have high K+ and low Na+ concentrations; erythrocytes from sheep of the allelic low-K+ (LK) phenotype have abnormally low K+ and high Na+ concentrations. The difference is due to differences in rates of cation transport: higher Na+-K+ pump flux in HK cells and higher K+-Cl- cotransport in LK cells. The HK/LK polymorphism is associated with a polymorphism of red blood cell antigens: the L antigen is only on LK cells, and HK cells have only the M antigen. There are two classes of L antigen that assort together: Lp, which is associated with Na+-K+ pumps, and Ll, which is associated with K+-Cl- cotransporters. There are functional consequences of these associations: anti-Lp antibody stimulates the pump and anti-Ll antibody inhibits cotransport. The use of these antibodies has permitted delineation of the roles of the antigens in modulating the function of the transporters. In this review, we summarize the evidence that these antigens are entities distinct from the pump. The Lp antigen reacts reversibly with the Na+-K+ pump; the antigen inhibits the pump, mainly by promoting nonspecific inhibition by intracellular K+. The antigen also modulates pump differentiation in immature cells. In contrast, the Ll antigen stimulates K+-Cl- cotransport. The evidence suggests that the two polymorphisms are controlled by a single genetic locus and that all of the distinct properties of ion transporters in LK cells are attributable to interactions with L antigens.