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Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes
Seth L Alper1, David H Vandorpe, Luanne L Peters
1Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. salper@bidmc.harvard.edu
Blood Cells, Molecules & Diseases
|March 11, 2008
Summary
The study investigated the role of the AE1 anion exchanger in red blood cell (RBC) chloride (Cl-) conductance. Results suggest AE1 may contribute to DIDS-sensitive Cl- conductance, but other channels might also be involved.
Area of Science:
- Physiology
- Molecular Biology
- Membrane Transport
Background:
- Erythrocyte membrane potential is dominated by chloride (Cl-) conductance.
- The molecular basis of conductive anion pathways in red blood cells (RBCs) is not fully understood.
- The AE1 anion exchanger (SLC4A1) mediates electroneutral Cl-/HCO3- transport in human RBCs.
Purpose of the Study:
- To genetically test if AE1 mediates 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive Cl- conductance in mouse RBCs.
- To investigate the contribution of AE1 to the overall Cl- conductance in mouse erythrocytes.
Main Methods:
- Electrophysiological measurements of membrane potential in wildtype and Ae1(-/-) mouse RBCs.
- Utilized four distinct technical approaches to assess DIDS-sensitive Cl- conductance.
- Analyzed protein expression in Ae1(-/-) mouse RBC membranes.
Main Results:
- Wildtype mouse RBCs exhibit a Cl--dominant membrane potential, similar to human RBCs.
- Ae1(-/-) mouse RBCs show a significant reduction or absence of DIDS-sensitive Cl- conductance.
- Ae1(-/-) mouse RBC membranes display reduced abundance or loss of multiple polypeptides.
Conclusions:
- The findings support the hypothesis that the AE1 polypeptide can function in a conductive mode.
- The reduced DIDS-sensitive anion conductance in Ae1(-/-) RBCs might also be due to the loss of other distinct anion channel polypeptides.
- Further research is needed to definitively identify all conductive anion pathways in mouse erythrocytes.
