The effect of N,N'-p-phenylenedimaleimide (PMD) on deoxygenation-induced K loss in sickle erythrocytes

A variety of thiol reactive agents have been found to have antisickling properties thought to be due to the ability of these drugs to bind to hemoglobin, resulting in increased hemoglobin-oxygen affinity. Because thiol reactive agents also influence K movements in red cells and deoxygenation leads to K loss and Na gain in sickle erythrocytes, the authors investigated the possibility that deoxygenation-induced K loss could be influenced by thiol agents, independent of an effect on hemoglobin-oxygen affinity. Experiments were performed with the thiol crosslinking agent N,N'-p-phenylenedimaleimide (PMD). The authors found that PMD inhibited deoxygenation-induced K loss in sickle erythrocytes. This effect was not due to sickling inhibition as PMD-treated cells gained Na with deoxygenation, nor could the effect be explained by monofunctional PMD binding to membrane sulfhydryl groups, as a monofunctional analogue of PMD was not able to retard deoxygenation-induced K loss. These findings support a role for membrane sulfhydryl groups in deoxygenation-induced K movements in sickle red cells and suggest that this K loss may be prevented by crosslinking of certain membrane sulfhydryl groups.