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

Corrons, Joan‐Lluís Vives; Besson, I

doi:10.1007/s002770100342

Cited by 10 publications

(9 citation statements)

References 22 publications

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“…Hereditary forms of hemolytic anemia can affect the RBC membrane (i.e., HS, elliptocytosis, and pyropoikilocytosis) ( Gallagher, 2004a ; Perrotta et al, 2008 ; Da Costa et al, 2013 ), its metabolism (i.e., enzymopathies) ( Zanella and Bianchi, 2000 ; van Wijk and van Solinge, 2005 ; Koralkova et al, 2014 ), cell hemoglobin (i.e., sickle cell anemia, unstable hemoglobin variants) ( Higgs et al, 2012 ; Ware et al, 2017 ), or cellular hydration (i.e., HS, hereditary xerocytosis or Gardos Channelopathy) ( Vives Corrons and Besson, 2001 ; Albuisson et al, 2013 ; Andolfo et al, 2013 , 2015 ; Beneteau et al, 2014 ; Faucherre et al, 2014 ; Glogowska et al, 2015 ; Fermo et al, 2017a ). While the primary genetic causes of these disorders are often well determined, less is known about the factors triggering the actual hemolysis.…”

Section: Rbc Deformability In Hereditary Hemolytic Anemiamentioning

confidence: 99%

“…Although reduced RBC deformability in HS mainly results from cytoskeletal disturbances ( Perrotta et al, 2008 ), spherocytes experience dehydration and increased leakage of K + ( De Franceschi et al, 1997 ; Gallagher, 2017 ). To compensate for this increased K + leakage, spherocytes are also found to have increased activity of the Na-K pump and the NKCC1 (also known as the Na-K-2Cl cotransporter, coded by gene SLC12A2) ( Vives Corrons and Besson, 2001 ). RBCs of transgenic mice deficient for ankyrin or spectrin show increased activity of the Na-K pump, but normal activities of the NKCC1 and K + -Cl - cotransporters ( Peters et al, 1999 ).…”

Section: Determinants Of Rbc Deformabilitymentioning

confidence: 99%

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Squeezing for Life – Properties of Red Blood Cell Deformability

et al. 2018

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Deformability is an essential feature of blood cells (RBCs) that enables them to travel through even the smallest capillaries of the human body. Deformability is a function of (i) structural elements of cytoskeletal proteins, (ii) processes controlling intracellular ion and water handling and (iii) membrane surface-to-volume ratio. All these factors may be altered in various forms of hereditary hemolytic anemia, such as sickle cell disease, thalassemia, hereditary spherocytosis and hereditary xerocytosis. Although mutations are known as the primary causes of these congenital anemias, little is known about the resulting secondary processes that affect RBC deformability (such as secondary changes in RBC hydration, membrane protein phosphorylation, and RBC vesiculation). These secondary processes could, however, play an important role in the premature removal of the aberrant RBCs by the spleen. Altered RBC deformability could contribute to disease pathophysiology in various disorders of the RBC. Here we review the current knowledge on RBC deformability in different forms of hereditary hemolytic anemia and describe secondary mechanisms involved in RBC deformability.

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Section: Rbc Deformability In Hereditary Hemolytic Anemiamentioning

confidence: 99%

Section: Determinants Of Rbc Deformabilitymentioning

confidence: 99%

Squeezing for Life – Properties of Red Blood Cell Deformability

et al. 2018

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“…Several studies have shown that defects in either band 3, ankyrin, or spectrin account for a large number of HS cases (24,29). Spherocytes are also characterized by a lower cellular K and increased Na content with dehydration (32). It has been suggested that these cation alterations are related to increased Na flux pathways such as Na pump, Na-K-2Cl cotransport (NKCC), and Na/Li exchanger.…”

mentioning

confidence: 99%

Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes

Rivera¹,

Franceschi²,

Peters³

et al. 2006

American Journal of Physiology-Cell Physiology

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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/1013cell × h in control mice), with an abnormal dependence on osmolality (EC50= 417 ± 42 in 4.1−/−vs. 460 ± 35 mosmol/kgH2O in control mice), suggestive of an upregulated functional state. While the affinity for internal protons was not altered (K0.5= 489.7 ± 0.7 vs. 537.0 ± 0.56 nM in control mice), the Vmaxof the H-induced Na/H exchange activity was markedly elevated in 4.1−/−erythrocytes ( Vmax91.47 ± 7.2 compared with 46.52 ± 5.4 mmol/1013cell × 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.

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“…Earlier studies could not delineate an association of membrane protein defects in HS red cells with the altered cation permeability (19,20). A subset of spherocytosis with low temperature leak (also having a band 3 deficiency) was found to have a series of mutations in the intramembrane domain of band 3 protein.…”

Section: Rare Red Cell Disorders Associated With Cation Permeability mentioning

confidence: 93%

Hereditary red cell membrane disorders and laboratory diagnostic testing

King

Zanella

2013

Int J Lab Hematology

109

101

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Summary This overview describes two groups of nonimmune hereditary hemolytic anemias caused by defects in membrane proteins located in distinct layers of the red cell membrane. Hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) represent disorders of the red cell cytoskeleton. Hereditary stomatocytoses represents disorders of cation permeability in the red cell membrane. The current laboratory screening tests for HS are the osmotic fragility test, acid glycerol lysis time test (AGLT), cryohemolysis test, and eosin‐5′‐maleimide (EMA)‐binding test. For atypical HS, SDS‐polyacrylamide gel electrophoresis of erythrocyte membrane proteins is carried out to confirm the diagnosis. The diagnosis of HE/HPP is based on abnormal red cell morphology and the detection of protein 4.1R deficiency or spectrin variants using gel electrophoresis. None of screening tests can detect all HS cases. Some testing centers (a survey of 25 laboratories) use a combination of tests (e.g., AGLT and EMA). No specific screening test for hereditary stomatocytoses is available. The preliminary diagnosis is based on presenting a compensated hemolytic anemia, macrocytosis, and a temperature or time dependent pseudohyperkalemia in some patients. Both the EMA‐binding test and the osmotic fragility test may help in differential diagnosis of HS and hereditary stomatocytosis.

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

Cited by 10 publications

References 22 publications

Squeezing for Life – Properties of Red Blood Cell Deformability

Squeezing for Life – Properties of Red Blood Cell Deformability

Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes

Hereditary red cell membrane disorders and laboratory diagnostic testing

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