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Abnormal permeability pathways in human red blood cells.

J C Ellory1, H C Robinson, J A Browning

  • 1Department of Physiology, Anatomy and Genetics, Sherrington Building, Parks Road, Oxford, OX1 3PT, UK.

Blood Cells, Molecules & Diseases
|April 17, 2007
PubMed
Summary

Abnormal red blood cell (RBC) permeability pathways were investigated in sickle cell disease (SCD) and hereditary stomatocytosis. Findings reveal novel conductance pathways contributing to RBC dehydration and hemolysis in SCD.

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Area of Science:

  • Physiology
  • Pathology
  • Biophysics

Background:

  • Abnormal red blood cell (RBC) permeability is implicated in various conditions.
  • Sickle cell disease (SCD) involves abnormal hemoglobin (HbS) leading to altered RBC function.
  • Understanding these pathways is crucial for disease management.

Purpose of the Study:

  • To investigate abnormal ion and non-electrolyte conductance pathways in human RBCs.
  • To characterize the P(sickle) conductance in deoxygenated sickle RBCs.
  • To explore the role of mutated band 3 in hereditary stomatocytosis.

Main Methods:

  • Whole-cell patch-clamp recordings on normal and sickle RBCs.
  • Radioisotopic assays to confirm non-electrolyte permeability.
  • Pharmacological inhibition studies using DIDS, Zn(2+), and Gd(3+).

Main Results:

  • Deoxygenated sickle RBCs exhibit a unique conductance (P(sickle)) permeable to Na+, K+, and Ca2+, and partially inhibited by DIDS and Zn(2+).
  • Gd(3+) significantly reduced conductance in both normal and sickle RBCs.
  • Deoxygenated sickle cells, but not normal RBCs, underwent hemolysis in isosmotic non-electrolyte solutions, inhibited by DIDS, suggesting P(sickle) permeability to non-electrolytes.
  • Mutated band 3 in hereditary stomatocytosis acts as a univalent cation conductance pathway.

Conclusions:

  • P(sickle) is a significant conductance pathway in deoxygenated sickle RBCs, contributing to cell dehydration and potentially hemolysis.
  • P(sickle) may also allow non-electrolyte passage under specific conditions.
  • Mutations in band 3 can create abnormal cation conductance pathways in RBCs, extending the understanding of RBC permeability disorders.