Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes.
Blood-Proteins, Bumetanide, Erythrocyte-Volume, Erythrocytes, Hydrogen, Hydrogen-Ion-Concentration, Hypertonic-Solutions, Ion-Transport, Isotonic-Solutions, Mice-Inbred-C57BL, Mice-Knockout, Na(+)-K(+)-Exchanging-ATPase, Okadaic-Acid, Osmolar-Concentration, Ouabain, Phthalic-Acids, Protein-Kinase-Inhibitors, Sodium, Sodium-Hydrogen-Antiporter, Sodium-Potassium-Chloride-Symporters, Symporters
Am J Physiol Cell Physiol 2006 Nov; 291(5):C880-6.
Moderate hemolytic anemia, abnormal erythrocyte morphology (spherocytosis), and decreased membrane stability are observed in mice with complete deficiency of all erythroid protein 4.1 protein isoforms (4.1(-/-); Shi TS et al. J Clin Invest 103: 331, 1999). We have examined the effects of erythroid protein 4.1 (4.1R) deficiency on erythrocyte cation transport and volume regulation. 4.1(-/-) mice exhibited erythrocyte dehydration that was associated with reduced cellular K and increased Na content. Increased Na permeability was observed in these mice, mostly mediated by Na/H exchange with normal Na-K pump and Na-K-2Cl cotransport activities. The Na/H exchange of 4.1(-/-) erythrocytes was markedly activated by exposure to hypertonic conditions (18.2 +/- 3.2 in 4.1(-/-) vs. 9.8 +/- 1.3 mmol/10(13) cell x h in control mice), with an abnormal dependence on osmolality (EC(50) = 417 +/- 42 in 4.1(-/-) vs. 460 +/- 35 mosmol/kgH(2)O in control mice), suggestive of an upregulated functional state. While the affinity for internal protons was not altered (K(0.5) = 489.7 +/- 0.7 vs. 537.0 +/- 0.56 nM in control mice), the V(max) of the H-induced Na/H exchange activity was markedly elevated in 4.1(-/-) erythrocytes (V(max) 91.47 +/- 7.2 compared with 46.52 +/- 5.4 mmol/10(13) cell x h in control mice). Na/H exchange activation by okadaic acid was absent in 4.1(-/-) erythrocytes. Altogether, these results suggest that erythroid protein 4.1 plays a major role in volume regulation and physiologically downregulates Na/H exchange in mouse erythrocytes. Upregulation of the Na/H exchange is an important contributor to the elevated cell Na content of 4.1(-/-) erythrocytes.
Rivera, A; De, Franceschi L.; Peters, L L.; Gascard, P; Mohandas, N; and Brugnara, C, "Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes." (2006). Faculty Research 2000 - 2009. 1401.