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The conductance of red blood cells from sickle cell patients: ion selectivity and inhibitors
Author(s) -
Ma Y.L.,
Rees D. C.,
Gibson J. S.,
Ellory J. C.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.229609
Subject(s) - deoxygenation , chemistry , biophysics , conductance , dids , divalent , intracellular , biochemistry , membrane , biology , organic chemistry , combinatorics , catalysis , mathematics
Key points • The high cation permeability in red blood cells (RBCs) from patients with sickle cell disease (SCD) is central to pathogenesis and includes a deoxygenation‐induced pathway termed P sickle . • Here whole‐cell patch clamp configuration was used to record from RBCs of SCD patients and showed a conductance reversibly induced upon deoxygenation, permeable to univalent (Na + , K + , Rb + ) and divalent (Ca 2+ , Mg 2+ ) cations, and sensitive to tarantula spider toxin GsMTx‐4, Mn 2+ and o ‐vanillin. • Divalent cation permeability is particularly important as entry of Ca 2+ stimulates the Gardos channel whilst Mg 2+ loss will stimulate KCl cotransport. • In oxygenated RBCs, the conductance was pH sensitive, increasing as pH fell from 7.4 to 6, but unaffected when pH was raised from 7.4 to 8. • Results show a conductance that shares many features with the P sickle flux pathway, and indicating its possible identity as a stretch‐activated channel with activation requiring sickle cell haemoglobin (HbS) polymerisation.