Increased Cation Permeability in Mutant Mouse Red Blood Cells With Defective Membrane Skeletons

Cellular cation homeostasis in mouse erythrocytes with defective membrane skeletons was examined in three mouse mutants, hemolytic anemia (sphha/sphha), spherocytosis (sph/sph), and normoblastosis (nb/nb), and compared with reticulocytes produced by repetitive bleeding of congenic normal mice. To as...

Full description

Saved in:

Bibliographic Details
Published in:	Blood Vol. 86; no. 11; pp. 4307 - 4314
Main Authors:	Joiner, Clinton H., Franco, Robert S., Jiang, Maorong, Franco, Mark S., Barker, Jane E., Lux, Samuel E.
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 01-12-1995 The Americain Society of Hematology
Subjects:	Anemia, Hemolytic - blood Anemia, Hemolytic - genetics Anemias. Hemoglobinopathies Animals Biological and medical sciences Biological Transport, Active Cytoskeleton - drug effects Diseases of red blood cells Erythroblastosis, Fetal - blood Erythroblastosis, Fetal - genetics Erythrocyte Membrane - metabolism Hematologic and hematopoietic diseases Homeostasis Humans Infant, Newborn Medical sciences Mice Mice, Mutant Strains Permeability Potassium - blood Reticulocytes - metabolism Sodium - blood Sodium-Potassium-Exchanging ATPase - blood Sodium-Potassium-Exchanging ATPase - genetics Spherocytosis, Hereditary - blood Spherocytosis, Hereditary - genetics Vertebrata Erythrocytic membrane disease Hemolytic anemia Mammalia Mouse Membrane transport Animal Rodentia Red blood cell Hemopathy Cations Mutation
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Cellular cation homeostasis in mouse erythrocytes with defective membrane skeletons was examined in three mouse mutants, hemolytic anemia (sphha/sphha), spherocytosis (sph/sph), and normoblastosis (nb/nb), and compared with reticulocytes produced by repetitive bleeding of congenic normal mice. To assess reticulocyte maturity, nucleic acid and transferrin receptor contents were measured by fluorescence flow cytometry; mutant cells were somewhat more mature than normal reticulocytes by these criteria. Red blood cell (RBC) sodium contents (Na+c) in homozygous sphha/sphha, sph/sph, and nb/nb animals were 30.1 ± 0.9, 28.9 ± 0.3, and 26.9 ± 1.5 mmol/L cell, respectively, whereas cellular potassium (K+c) was 102 ± 2.6, 101 ± 7.8, and 97.4 ± 3.0. Na+c and K+c in normal reticulocyte preparations were 11.3 ± 0.7 and 123 ± 10, respectively. Net Na+ and K+ fluxes in the presence of ouabain were markedly increased in mutant RBCs. Sodium uptake was 14.8 ± 1.6, 15.4 ± 3.3, and 14.7 ± 3.1 mmol/L cell/h in sphha/sphha, sph/sph, and nb/nb mutants, respectively, whereas K+ loss was 17.0 ± 4.0, 15.0 ± 3.8, and 14.1 ± 2.6. Normal mouse reticulocytes gained Na+ at a rate of 3.9 ± 1.0 mmol/L cell/h and lost K+ at 6.0 ± 2.1, rates indistinguishable from those in mature mouse RBCs. Potassium loss from sphha/sphha and nb/nb cells was not dependent on the presence of a Na+ gradient, and net cation movements were insensitive to bumetanide (sphha/sphha and nb/nb RBCs) and to chloride replacement with sulfamate (nb/nb cells). We conclude that mutant mouse RBCs with dysfunctional membrane skeletons have increased passive permeability to monovalent cations. These findings support a role of the membrane skeleton in the maintenance of the membrane permeability barrier and suggest that the abnormal permeability associated with human hereditary spherocytosis and elliptocytosis may be a consequence of the membrane skeleton defects reported in these disorders.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood.V86.11.4307.bloodjournal86114307