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 (86)Rb(+), (43)K(+), and (22)Na(+) 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.
Staines
H M
HM
University Laboratory of Physiology, Oxford OX1 3PT, United Kingdom.
Ellory
J C
JC
Kirk
K
K
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003600:Cytosol / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology* / Q000469:parasitology*; D006801:Humans; D008288:Malaria / Q000378:metabolism*; D008954:Models, Biological; D010963:Plasmodium falciparum; D011188:Potassium / Q000378:metabolism; D011197:Potassium Radioisotopes / Q000493:pharmacokinetics; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D011197:Potassium Radioisotopes; D012414:Rubidium Radioisotopes; D012979:Sodium Radioisotopes; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium