Significance of two transmembrane ion gradients for human erythrocyte volume stabilization

Abstract

SummaryFunctional completeness of erythrocytes depends on high deformability of these cells, that allows them to pass through narrow tissue capillaries. The erythrocytes high deformability is provided due to maintenance of discoid shape with an optimal cell surface area to volume ratio. This ratio can be maintained due to cell volume stabilization at a given cell surface area. We studied role of Na/K-ATPase and transmembrane Na+ and K+ gradients in human erythrocyte volume stabilization at non-selective increase in cell membrane permeability to cations by using mathematical simulation. The simulation took into account a contribution of glycolytic metabolites and adenine nucleotides to cytoplasm osmotic pressure in the cells. It was shown that in the presence of Na/K-ATPase activated by intracellular sodium ions and two oppositely directed gradients of Na+ and K+ ions in the cell, the volume of the erythrocyte deviates from the optimal value by no more than 10% with a change in the non-selective permeability of the cell membrane to cations from 50 to 200% of the normal value. The transport Na/K-ATPase, which sets the ratio of transmembrane fluxes of sodium and potassium ions equal to 3:2, provides the best stabilization of the erythrocyte volume exactly at a non-selective increase in the permeability of the cell membrane, when the permeability for sodium and potassium ions increases equally. Such increase in erythrocyte membrane permeability is caused by oxidation of the membrane components and by mechanical stress during circulation. In the case of only one transmembrane ion gradient (Na+), the cell loses the ability to stabilize the volume when the cell membrane is damaged. In this case even small variations of cell membrane permeability cause dramatic changes in the cell volume. Our results reveal that the presence of two oppositely directed transmembrane ion gradients (Na+ and K+) and the transport Na/K-ATPase activated by intracellular sodium are fundamentally important conditions for the stabilization of cellular volume in human erythrocytes.