Significance of Erythrocyte Sodium Flux in the Pathophysiology and Genetic Expression of Hereditary Spherocytosis

Zipursky, Alvin; Israels, L. G.

doi:10.1203/00006450-197111000-00005

Cited by 6 publications

(2 citation statements)

References 5 publications

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“…Several studies have shown that the erythrocyte "permeability" to sodium and potassium is increased in HS and that the increased sodium permeability is associated with increased activity of the Na-K ATPase. [7][8][9][10][11][12] It has been postulated that the associated increase in adenosine triphosphate (ATP) consumption leads to ATP depletion during erythrostasis, followed by increased calcium entry, activation of the Gardos channel, and dehydration. 8,13 A more recent study found no changes in the transport activity of Na-K-2Cl cotransport and Na/Li exchange in human HS erythrocytes, whereas sodium potassium pump activity was increased and potassium chloride cotransport activity was decreased.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Franceschi

Rivera

Fleming

et al. 2005

Blood

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It has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 +/- 1.06 vs 6.08 +/- 0.09 mM cell x minute; P < .04) and a decrease in Km (1.01 +/- 0.06 vs 1.47 +/- 1.02 microM; P < .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments.

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Section: Introductionmentioning

confidence: 99%

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Franceschi

Rivera

Fleming

et al. 2005

Blood

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“…Hereditary spherocytosis (HS) is a common inherited RBC membrane defect associated with haemolytic anaemia and heterogeneous inheritance and clinical presentation [13,14,15]. One distinguishing characteristic of HS is the presence of circulating dense and dehydrated spherocytes that are intrinsically leaky to sodium [15,16,17,18,19]. Up to now, increased membrane passive permeability to cations has been reported for the spherocytic (sph) RBCs in several animals [20] and only a few cases of HS have been examined for defects in the various components of the ouabain-resistant pathways [20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

Red cell membrane Na+ transport systems in hereditary spherocytosis: relevance to understanding the increased Na+ permeability

Corrons

Besson

2001

Ann Hematol

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Red blood cells (RBCs) in hereditary spherocytosis (HS) show high sodium (Na+) and potassium (K+) movement across the membrane, resulting in dehydration. In general, these abnormal cation fluxes have been interpreted as "increased leaks" due to passive or electrodiffusional permeability of the RBC membrane. A study to elucidate the contribution of concomitant ouabain-resistant pathways (Na-K-2Cl cotransport and Na-Li countertransport) to abnormal Na+ permeability present in RBCs of subjects with HS has been undertaken. Accordingly, erythrocyte Na+ and K+ content and transmembrane cation movements via the Na-K pump, Na-K-2Cl cotransport, Na-Li countertransport, and Na+ passive diffusion, were measured in 25 non-splenectomized patients with HS and compared with the results obtained from the study of 11 patients with congenital non-spherocytic haemolytic anaemia (CNSHA) due to hereditary elliptocytosis (7 cases) and RBC enzyme defects (4 cases) and of 30 normal controls. Compared to the controls, patients with HS exhibited a highly significant (P<0.001) increase in all the Na+ transmembrane movements via passive diffusion (411+/-243 vs 105+/-40), Na-K pump (2615+/-970 vs 1874+/-359), Na-K-2Cl cotransport (males: 371+/-138 vs 190+/-42; females: 401+/-134 vs 104+/-44) and Na-Li countertransport (207+/-131 vs 98+/-41). This was associated with increased Na+ and decreased K+ content, resulting in a reduction of total cation (Na+ + K+) RBC concentration. Furthermore, significant correlations were also found between the patients' RBC cationic content and the mean corpuscular haemoglobin concentration (MCHC) (r=0.51, P<0.05) and between the Na+ passive leak and the haematocrit value (r=-0.44, P<0.05). In the patients with CNSHA, a less significant (P<0.01) increase of active (Na-K pump) and passive (leak) transmembrane permeability to Na+ was associated with normal transmembrane movements via Na-K-2Cl cotransport and Na-Li countertransport. The present study demonstrates that in HS, RBCs are characterized by a variable, but always significant increase of all the membrane transport systems leading to the extrusion of Na+, and that these abnormalities, regardless of their relation to membrane structural defects, may probably be valuable for the differential diagnosis between HS and other congenital defects of RBCs.

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Hemolytic Anemias: Failure of the Red Cell Membrane

Shohet

Ness

1976

Medical Clinics of North America

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Significance of Erythrocyte Sodium Flux in the Pathophysiology and Genetic Expression of Hereditary Spherocytosis

Cited by 6 publications

References 5 publications

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis

Red cell membrane Na+ transport systems in hereditary spherocytosis: relevance to understanding the increased Na+ permeability

Hemolytic Anemias: Failure of the Red Cell Membrane

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