Perturbation of the pump-leak balance for Na+ and K+ in malaria-infected erythrocytes

In human erythrocytes infected with the mature form of the malaria parasite Plasmodium falciparum, the cytosolic concentration of Na+ is increased and that of K+ is decreased. In this study, the membrane transport changes und erlying this perturbation were investigated using a combination of Rb-86(+) , K-43(+), and Na-22(+) flux measurements and a semiquantitative hemolysis technique. From >15 h postinvasion, there appeared in the infected erythroc yte membrane new permeation pathways (NPP) that caused a significant increa se in the basal ion permeability of the erythrocyte membrane and that were inhibited by furosemide (0.1 mM). The NPP showed the selectivity sequence C s+ > Rb+ > K+ > Na+, with the K+-to-Na+ permeability ratio estimated as 2.3 . From 18 to 36 h postinvasion, the activity of the erythrocyte Na+/K+ pump increased in response to increased cytosolic Na+ (a consequence of the inc reased leakage of Na+ via the NPP) but underwent a progressive decrease in the latter 12 h of the parasite's occupancy of the erythrocyte (36-48 h pos tinvasion). Incorporation of the measured ion transport rates into a mathem atical model of the human erythrocyte indicates that the induction of the N PP, together with the impairment of the Na+/K+ pump, accounts for the alter ed Na+ and K+ levels in the host cell cytosol, as well as predicting an ini tial decrease, followed by a lytic increase in the volume of the host eryth rocyte.