Document Detail


Deoxygenation permeabilizes sickle cell anaemia red cells to magnesium and reverses its gradient in the dense cells.
MedLine Citation:
PMID:  2213597     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Our findings of a low total magnesium content in the dense fraction (over 1.118 g ml-1) of sickle cell anaemia (SS) red cells seemed inconsistent with the low Mg2+ permeability and outward Mg2+ gradient seen in normal red cells, and prompted studies of the Mg2+ permeability and equilibria in the SS cells. 2. Deoxygenation and sickling induced Mg2+ permeabilization in SS cells, supporting non-specificity of the sickling-induced cation permeabilization, previously described for Na+, K+ and Ca2+. The extent of Mg2+ permeabilization was comparable in SS cells with normal or high density. 3. Compared with normal-density SS cells and normal red cells, the dense SS cells showed a much larger increase in the fraction of ionized magnesium ([Mg2+]i) on deoxygenation, resulting in [Mg2+]i levels sufficient to reverse the normal inward direction of the transmembrane Mg2+ gradient. 4. The molar ratio of 2,3-diphosphoglycerate (2,3-DPG) to haemoglobin was markedly reduced in the dense SS cells. Since 2,3-DPG and ATP are the main cytoplasmic Mg2+ buffers, their further reduction upon binding to deoxyhaemoglobin accounts for the high [Mg2+]i in the deoxygenated dense SS cells; the resulting outward electrochemical Mg2+ gradient, together with sickling-induced Mg2+ permeabilization, could explain the decreased total magnesium content of these cells. 5. The above findings suggested that the documented low sodium pump fluxes in dense SS cells may result from an increased Mg2+:ATP ratio, which is known to inhibit Na(+)-K+ exchange fluxes through the sodium pump. If so, deoxygenation, by increasing the Mg2+:ATP ratio, should inhibit the pump further, whereas increasing ATP should relieve the inhibition. Experiments designed to test this possibility showed that in these dense SS cells, the ouabain-sensitive K(86Rb) influx was low in oxygenated cells, was reduced further by deoxygenation, but was substantially increased after treatment with inosine, pyruvate and phosphate to increase their organic phosphate pool. These results were thus consistent with such a mechanism for Na+ pump inhibition in the dense SS cells.
Authors:
O E Ortiz; V L Lew; R M Bookchin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of physiology     Volume:  427     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-11-21     Completed Date:  1990-11-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  211-26     Citation Subset:  IM    
Affiliation:
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
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MeSH Terms
Descriptor/Qualifier:
2,3-Diphosphoglycerate
Anemia, Sickle Cell / blood*
Biological Transport, Active
Cell Membrane Permeability
Diphosphoglyceric Acids / blood
Erythrocytes, Abnormal / metabolism*
Humans
Magnesium / blood*
Oxygen / blood*
Grant Support
ID/Acronym/Agency:
HL21016/HL/NHLBI NIH HHS; HL28018/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Diphosphoglyceric Acids; 138-81-8/2,3-Diphosphoglycerate; 7439-95-4/Magnesium; 7782-44-7/Oxygen
Comments/Corrections

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