Deoxygenation-induced cation fluxes in sickle cells. III. Cation selectivity and response to pH and membrane potential.

Deoxygenation of sickle cells increases membrane permeability to Na, K, and Ca and contributes to cellular cation depletion. This study examines the physiological nature of the pathway that mediates deoxygenation-induced movements of monovalent cations. Deoxygenation-induced Rb influx was a linear function of external Rb concentration, with no evidence of saturation. Activation of the deoxygenation-induced pathway was fostered by alkaline pH (7.5), whereas ion movements via the activated pathway were optimal between pH 6.9 and 7.0 in cells incubated in media in which NO3 replaced Cl to eliminate KCl cotransport. The deoxygenation-induced pathway exhibited no selectivity among the alkali metal cations Li, Na, K, Rb, or Cs, but the monovalent organic cations tetramethylammonium, tetraethylammonium, and N-methylglucamine were excluded. Sickle cells incubated in low-Cl media (external Cl, 40 mM) to depolarize the membrane exhibited increased deoxygenation-induced K efflux and reduced Na influx. Cells treated with valinomycin to hyperpolarize the membrane showed increased deoxygenation-induced Na influx. These characteristics of the deoxygenation-induced transport pathway, linear concentration dependence, lack of cation selectivity, and response to membrane potential, argue against a carrier-mediated mechanism in favor of a diffusional process. The exclusion of small organic cations, however, suggests that factors other than ion size influence deoxygenation-induced permeability.