Keeping red blood cells hydrated in sickle cell disease

In a study appearing online on May 17 in advance of publication in the June print issue of the Journal of Clinical Investigation, Thomas Jentsch and colleagues from Universitдt Hamburg investigated the role of K-Cl cotransport activity in red blood cell volume. The authors generated mice lacking the K-Cl cotransporters Kcc1 and Kcc3. As red blood cell K-Cl cotransport activity was unchanged in mice lacking Kcc1, decreased in mice lacking Kcc3, and almost completely lost in mice lacking both Kcc1 and Kcc3, the authors concluded that K-Cl cotransport in red blood cells is largely mediated by Kcc3. The authors went on to show that disruption of both K-Cl cotransporters in a mouse model of sickle cell disease was able to partially rescue the cells from dehydration. However, the proportion of the densest red blood cells remained unaffected. This result, if extrapolated to human sickle disease, predicts that inhibitors of K-Cl cotransport, if used alone, would not be maximally effective in reversing the red cell dehydration that causes sickling.-Journal of Clinical Investigation