Strain-specific variations in cation content and transport in mouse erythrocytes

Abstract

Studies of ion transport pathophysiology in hematological disorders and tests of possible new therapeutic agents for these disorders have been carried out in various mouse models because of close functional similarities between mouse and human red cells. We have explored strain-specific differences in erythrocyte membrane physiology in 10 inbred mouse strains by determining erythrocyte contents of Na(+), K(+), and Mg(2+), and erythrocyte transport of ions via the ouabain-sensitive Na-K pump, the amiloride-sensitive Na-H exchanger (NHE1), the volume and chloride-dependent K-Cl cotransporter (KCC), and the charybdotoxin-sensitive Gardos channel (KCNN4). Our data reveal substantial strain-specific and sex-specific differences in both ion content and trans-membrane ion transport in mouse erythrocytes. These differences demonstrate the feasibility of identifying specific quantitative trait loci for erythroid ion transport and content in genetically standardized inbred mouse strains.

Keywords: KCC; KCNN4; NHE1; Na-K pump; membrane transport.

Fig. 1.

Erythrocyte Na⁺, K⁺, and Mg²⁺ contents in 10 inbred strains of mice. Each panel shows the results for a single ion for all tested strains, with strain designations shown across the x-axis, and measurement of interest shown on the y-axis. Values (± SE) are shown with open circles (○) for females and filled circles (●) for males. Values are displayed in numerical order based on the mean value for males of each strain. A: erythrocyte cell Na⁺ (mmol/Kg Hb); B: erythrocyte cell K⁺ (mmol/Kg Hb); C: erythrocyte cell Mg²⁺ (mmol/Kg Hb).

Fig. 2.

Significant differences among strains for erythrocyte Na⁺, K⁺, and Mg²⁺ contents. Data were analyzed with Tukey's HSD test for males and females combined. (*P < 0.05).

Fig. 3.

Erythrocyte cation transport activities in 10 inbred strains of mice. Each panel shows the results for a single transport pathway for all tested strains, with strain designations shown across the x-axis, and measurement of interest shown on the y-axis. Values (± SE) are shown with open circles (○) for females and filled circles (●) for males. Values are displayed in numerical order based on the mean value for males of each strain. A: erythrocyte Na-K pump (mmol/10¹³ cells × h); B: erythrocyte Na-H exchange (mmol/10¹³ cells × h); C: erythrocyte K-Cl cotransport (mmol/10¹³ cells × h); D: erythrocyte Gardos channel (mmol/l cells × min).

Fig. 4.

Significant differences among strains for transport activities of the Na-K pump, Na-H exchange, K-Cl cotransport, and Gardos channel. Data were analyzed with Tukey's honestly significant difference test for males and females combined (*P < 0.05).