A 3-phase model for sickle cell hydration changes.

Young sickle cells are initially dehydrated in phase 1 by the combined action of 3 well-described pathways. During phase 2, which is deoxygenation-dependent, K⁺ is further depleted and Na⁺ is increased. Finally, a combination of severe K⁺ depletion (and therefore little or no outwardly directed K⁺ gradient) and activation of a novel 1 mM bumetanide–sensitive pathway (allowing rapid Na⁺ entry) results in rehydration of the cells.