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 underlying this perturbation were investigated using a combination of ⁸⁶Rb⁺,⁴³K⁺, and ²²Na⁺ flux measurements and a semiquantitative hemolysis technique. From >15 h postinvasion, there appeared in the infected erythrocyte membrane new permeation pathways (NPP) that caused a significant increase in the basal ion permeability of the erythrocyte membrane and that were inhibited by furosemide (0.1 mM). The NPP showed the selectivity sequence Cs⁺ > 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 increased 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 postinvasion). Incorporation of the measured ion transport rates into a mathematical model of the human erythrocyte indicates that the induction of the NPP, together with the impairment of the Na⁺/K⁺ pump, accounts for the altered Na⁺ and K⁺ levels in the host cell cytosol, as well as predicting an initial decrease, followed by a lytic increase in the volume of the host erythrocyte.