Encyclopedia of Malaria

Living Edition
| Editors: Peter G. Kremsner, Sanjeev Krishna

Permeabilization of Host Cell Membrane

  • Stéphane Egée
  • Guillaume Bouyer
  • Serge L. Y. Thomas
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-8757-9_38-1



By replicating within red blood cells, malaria parasites are largely hidden from immune recognition, but parasites enter an unusual closed environment where some nutrients are limited and where accumulation of hazardous metabolic end products can rapidly become deleterious. Therefore, to survive within erythrocytes, parasites circumvent the relative low permeability of the host plasma membrane by altering the permeability of the host plasma membrane either by upregulating existing carriers or by creating new permeation pathways (NPPs). Recent electrophysiological studies of Plasmodium-infected erythrocytes have demonstrated that these changes reflect transmembrane transports through ion channels or pores in the infected erythrocyte.


The intraerythrocytic stage of malaria parasite’s life cycle allows Plasmodiumgenus to escape host immune system threatening and recognition. However, by...


Membrane Current Infected Erythrocyte Host Cell Membrane Trophozoite Stage Flux Experiment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.



The labex GR-Ex, reference ANR-11-LABX-0051 is funded by the program “Investissements d’avenir” of the French National Research Agency, reference ANR-11-IDEX-0005-02.


  1. Baumeister S, Winterberg M, Duranton C, Huber SM, Lang F, Kirk K, Lingelbach K. Evidence for the involvement of Plasmodium falciparum proteins in the formation of new permeability pathways in the erythrocyte membrane. Mol Microbiol. 2006;60(2):493–504.CrossRefPubMedGoogle Scholar
  2. Bernhardt I, Ellory JC. Red cell membrane transport in Health and disease. Berlin/Heidelberg: Springer; 2003.CrossRefGoogle Scholar
  3. Bouyer G, Egee S, Thomas SL. Three types of spontaneously active anionic channels in malaria-infected human red blood cells. Blood Cells Mol Dis. 2006;36(2):248–54.CrossRefPubMedGoogle Scholar
  4. Bouyer G, Egee S, Thomas SL. Toward a unifying model of malaria-induced channel activity. Proc Natl Acad Sci U S A. 2007;104(26):11044–9.PubMedCentralCrossRefPubMedGoogle Scholar
  5. Bouyer G, Thomas SLY, Egee S. Protein kinase-regulated inwardly rectifying anion and organic osmolyte channels in malaria-infected erythrocytes. Open Biol J. 2011;4:10–7.CrossRefGoogle Scholar
  6. Bouyer G, Thomas S, Egée S (2012) Patch-clamp analysis of membrane transport in erythrocytes, In: Kaneez FS, editor. Patch clamp technique, ISBN: 978-953-51-0406-3, InTech, Available from: http://www.intechopen.com/books/patch-clamp-technique/patch-clamp-analysis-of-membrane-transport-in-erythrocytes
  7. Cobbold SA, Martin RE, Kirk K. Methionine transport in the malaria parasite Plasmodium falciparum. Int J Parasitol. 2011;41(1):125–35.CrossRefPubMedGoogle Scholar
  8. Cohn JV, Alkhalil A, Wagner MA, Rajapandi T, Desai SA. Extracellular lysines on the plasmodial surface anion channel involved in Na + exclusion. Mol Biochem Parasitol. 2003;132(1):27–34.CrossRefPubMedGoogle Scholar
  9. Desai SA. Why do malaria parasites increase host erythrocyte permeability? Trends Parasitol. 2014;30(3):151–9.PubMedCentralCrossRefPubMedGoogle Scholar
  10. Desai SA, McCleskey EW, Schlesinger PH, Krogstad DJ. A novel pathway for Ca++ entry into Plasmodium falciparum-infected blood cells. Am J Trop Med Hyg. 1996;54(5):464–70.PubMedGoogle Scholar
  11. Desai SA, Bezrukov SM, Zimmerberg J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature. 2000;406(6799):1001–5.CrossRefPubMedGoogle Scholar
  12. Duranton C, Huber S, Tanneur V, Lang K, Brand V, Sandu C, Lang F. Electrophysiological properties of the Plasmodium falciparum-induced cation conductance of human erythrocytes. Cell Physiol Biochem. 2003;13(4):189–98.CrossRefPubMedGoogle Scholar
  13. Egee S, Lapaix F, Decherf G, Staines HM, Ellory JC, Doerig C, Thomas SL. A stretch-activated anion channel is up-regulated by the malaria parasite Plasmodium falciparum. J Physiol. 2002;542(Pt 3):795–801.PubMedCentralCrossRefPubMedGoogle Scholar
  14. Ekland EH, Akabas MH, Fidock DA. Taking charge: feeding malaria via anion channels. Cell. 2011;145(5):645–7.CrossRefPubMedGoogle Scholar
  15. Esposito A, Tiffert T, Mauritz JM, Schlachter S, Bannister LH, Kaminski CF, Lew VL. FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells. PLoS One. 2008;3(11):e3780.PubMedCentralCrossRefPubMedGoogle Scholar
  16. Fishbein WN, Davis JI, Foellmer JW, Casey MR. Clinical assay of the human erythrocyte lactate transporter. II. Analysis and display of normal human data. Biochem Med Metab Biol. 1988;39(3):351–9.CrossRefPubMedGoogle Scholar
  17. Ginsburg H, Stein WD. The new permeability pathways induced by the malaria parasite in the membrane of the infected erythrocyte: comparison of results using different experimental techniques. J Membr Biol. 2004;197(2):113–34.CrossRefPubMedGoogle Scholar
  18. Ginsburg H, Stein WD. How many functional transport pathways does Plasmodium falciparum induce in the membrane of its host erythrocyte? Trends Parasitol. 2005;21(3):118–21.CrossRefPubMedGoogle Scholar
  19. Ginsburg H, Krugliak M, Eidelman O, Cabantchik ZI. New permeability pathways induced in membranes of Plasmodium falciparum infected erythrocytes. Mol Biochem Parasitol. 1983;8(2):177–90.CrossRefPubMedGoogle Scholar
  20. Glogowska E, Dyrda A, Cueff A, Bouyer G, Egee S, Bennekou P, Thomas SL. Anion conductance of the human red cell is carried by a maxi-anion channel. Blood Cells Mol Dis. 2010;44(4):243–51.CrossRefPubMedGoogle Scholar
  21. Halestrap AP. Monocarboxylate and other organic anion transport. In: Bernhardt I, Ellory JC, editors. Red cell membrane transport in health and disease. Berlin/Heidelberg: Springer; 2003.Google Scholar
  22. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981;391(2):85–100.CrossRefPubMedGoogle Scholar
  23. Hoffman JF, Joiner W, Nehrke K, Potapova O, Foye K, Wickrema A. The hSK4 (KCNN4) isoform is the Ca2 + -activated K+ channel (Gardos channel) in human red blood cells. Proc Natl Acad Sci U S A. 2003;100(12):7366–71.PubMedCentralCrossRefPubMedGoogle Scholar
  24. Huber SM, Uhlemann AC, Gamper NL, Duranton C, Kremsner PG, Lang F. Plasmodium falciparum activates endogenous Cl(−) channels of human erythrocytes by membrane oxidation. Embo J. 2002;21(1–2):22–30.PubMedCentralCrossRefPubMedGoogle Scholar
  25. Huber SM, Duranton C, Lang F. Patch-clamp analysis of the “new permeability pathways” in malaria-infected erythrocytes. Int Rev Cytol. 2005;246:59–134.CrossRefPubMedGoogle Scholar
  26. Kaestner L, Christophersen P, Bernhardt I, Bennekou P. The non-selective voltage-activated cation channel in the human red blood cell membrane: reconciliation between two conflicting reports and further characterisation. Bioelectrochemistry. 2000;52(2):117–25.CrossRefPubMedGoogle Scholar
  27. Kanaani J, Ginsburg H. Transport of lactate in Plasmodium falciparum-infected human erythrocytes. J Cell Physiol. 1991;149(3):469–76.CrossRefPubMedGoogle Scholar
  28. Kirk K. Membrane transport in the malaria-infected erythrocyte. Physiol Rev. 2001;81(2):495–537.PubMedGoogle Scholar
  29. Krugliak M, Ginsburg H. The evolution of the new permeability pathways in Plasmodium falciparum–infected erythrocytes–a kinetic analysis. Exp Parasitol. 2006;114(4):253–8.CrossRefPubMedGoogle Scholar
  30. Krugliak M, Zhang J, Ginsburg H. Intraerythrocytic Plasmodium falciparum utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins. Mol Biochem Parasitol. 2002;119(2):249–56.CrossRefPubMedGoogle Scholar
  31. Lew VL, Tiffert T, Ginsburg H. Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells. Blood. 2003;101(10):4189–94.CrossRefPubMedGoogle Scholar
  32. Lew VL, Macdonald L, Ginsburg H, Krugliak M, Tiffert T. Excess haemoglobin digestion by malaria parasites: a strategy to prevent premature host cell lysis. Blood Cells Mol Dis. 2004;32(3):353–9.CrossRefPubMedGoogle Scholar
  33. Martin RE, Kirk K. Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Blood. 2007;109(5):2217–24.CrossRefPubMedGoogle Scholar
  34. Martin RE, Henry RI, Abbey JL, Clements JD, Kirk K. The ‘permeome’ of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum. Genome Biol. 2005;6(3):R26.PubMedCentralCrossRefPubMedGoogle Scholar
  35. Martin RE, Ginsburg H, Kirk K. Membrane transport proteins of the malaria parasite. Mol Microbiol. 2009;74(3):519–28.CrossRefPubMedGoogle Scholar
  36. Mauritz JM, Esposito A, Ginsburg H, Kaminski CF, Tiffert T, Lew VL. The homeostasis of Plasmodium falciparum-infected red blood cells. PLoS Comput Biol. 2009;5(4):e1000339.PubMedCentralCrossRefPubMedGoogle Scholar
  37. Nguitragool W, Bokhari AA, Pillai AD, Rayavara K, Sharma P, Turpin B, Aravind L, Desai SA. Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells. Cell. 2011;145(5):665–77.PubMedCentralCrossRefPubMedGoogle Scholar
  38. Nguitragool W, Rayavara K, Desai SA. Proteolysis at a specific extracellular residue implicates integral membrane CLAG3 in malaria parasite nutrient channels. PLoS One. 2014;9(4):e93759.PubMedCentralCrossRefPubMedGoogle Scholar
  39. Saliba KJ, Kirk K. Nutrient acquisition by intracellular apicomplexan parasites: staying in for dinner. Int J Parasitol. 2001;31(12):1321–30.CrossRefPubMedGoogle Scholar
  40. Saliba KJ, Martin RE, Broer A, Henry RI, McCarthy CS, Downie MJ, Allen RJ, Mullin KA, McFadden GI, Broer S, et al. Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite. Nature. 2006;443(7111):582–5.PubMedGoogle Scholar
  41. Staines HM, Ellory JC, Kirk K. Perturbation of the pump-leak balance for Na(+) and K(+) in malaria- infected erythrocytes. Am J Physiol Cell Physiol. 2001;280(6):C1576–87.PubMedGoogle Scholar
  42. Staines HM, Powell T, Ellory JC, Egee S, Lapaix F, Decherf G, Thomas SL, Duranton C, Lang F, Huber SM. Modulation of whole-cell currents in Plasmodium falciparum-infected human red blood cells by holding potential and serum. J Physiol. 2003;552(Pt 1):177–83.PubMedCentralCrossRefPubMedGoogle Scholar
  43. Staines HM, Ashmore S, Felgate H, Moore J, Powell T, Ellory JC. Solute transport via the new permeability pathways in Plasmodium falciparum-infected human red blood cells is not consistent with a simple single-channel model. Blood. 2006;108(9):3187–94.PubMedCentralCrossRefPubMedGoogle Scholar
  44. Staines HM, Alkhalil A, Allen RJ, De Jonge HR, Derbyshire E, Egee S, Ginsburg H, Hill DA, Huber SM, Kirk K, et al. Electrophysiological studies of malaria parasite-infected erythrocytes: current status. Int J Parasitol. 2007;37(5):475–82.PubMedCentralCrossRefPubMedGoogle Scholar
  45. Vander Jagt DL, Hunsaker LA, Campos NM, Baack BR. D-lactate production in erythrocytes infected with Plasmodium falciparum. Mol Biochem Parasitol. 1990;42(2):277–84.CrossRefPubMedGoogle Scholar
  46. Zarchin S, Krugliak M, Ginsburg H. Digestion of the host erythrocyte by malaria parasites is the primary target for quinoline-containing antimalarials. Biochem Pharmacol. 1986;35(14):2435–42.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Stéphane Egée
    • 1
    • 2
    • 3
  • Guillaume Bouyer
    • 1
    • 2
    • 3
  • Serge L. Y. Thomas
    • 1
    • 2
    • 3
  1. 1.Integrative Biology of Marine Models, Comparative Physiology of Erythrocytes, Station Biologique de RoscoffSorbonne Universités, UPMC Univ. Paris 06, UMR 8227RoscoffFrance
  2. 2.Integrative Biology of Marine Models, Comparative Physiology of Erythrocytes, Station Biologique de RoscoffCNRS, UMR 8227RoscoffFrance
  3. 3.Laboratory of Excellence GR-ExParisFrance