The conductance of red blood cells from sickle cell patients: ion selectivity and inhibitors

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.