Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes

The resting membrane potential of the human erythrocyte is largely determined by a constitutive Cl- conductance similar to 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 greaterthan 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. (C) 2008 Elsevier Inc. All rights reserved.