Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes |
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Authors: | Alper Seth L Vandorpe David H Peters Luanne L Brugnara Carlo |
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Institution: | aMolecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA, USA;bRenal Unit, Beth Israel Deaconess Medical Center, Boston, MA, USA;cDepartment of Laboratory Medicine, The Children's Hospital, Boston, MA, USA;dDepartment of Medicine, Harvard Medical School, Boston, MA, USA;eDepartment of Pathology, Harvard Medical School, Boston, MA, USA;fThe Jackson Laboratory, Bar Harbor, ME, USA |
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Abstract: | The resting membrane potential of the human erythrocyte is largely determined by a constitutive Cl− conductance 100-fold greater than the resting cation conductance. The 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)-sensitive electroneutral Cl− transport mediated by the human erythroid Cl−/HCO3− exchanger, AE1 (SLC4A1, band 3) is > 10,000-fold greater than can be accounted for by the Cl− conductance of the red cell. The molecular identities of conductive anion pathways across the red cell membrane remain poorly defined. We have examined red cell Cl− conductance in the Ae1−/− mouse as a genetic test of the hypothesis that Ae1 mediates DIDS-sensitive Cl− conductance in mouse red cells. We report here that wildtype mouse red cell membrane potential resembles that of human red cells in the predominance of its Cl− conductance. We show with four technical approaches that the DIDS-sensitive component of erythroid Cl− conductance is reduced or absent from Ae1−/− red cells. These results are consistent with the hypothesis that the Ae1 anion exchanger polypeptide can operate infrequently in a conductive mode. However, the fragile red cell membrane of the Ae1−/− mouse red cell exhibits reduced abundance or loss of multiple polypeptides. Thus, loss of one or more distinct, DIDS-sensitive anion channel polypeptide(s) from the Ae1−/− red cell membrane cannot be ruled out as an explanation for the reduced DIDS-sensitive anion conductance. |
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Keywords: | Cl− /HCO3− exchange Patch clamp Isotopic flux Light scattering Ionophore |
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