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Permselectivity and pH-dependence of Plasmodium falciparum-induced anion currents in human erythrocytes

  • Ion Channels, Transporters
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Abstract

Intraerythrocytic survival of the malaria pathogen Plasmodium falciparum requires delivery of nutrients and disposal of waste products across the host erythrocyte membrane. Recent patch-clamp experiments have demonstrated inwardly and outwardly rectifying anion conductances in infected but not in control erythrocytes. A ClC-2-generated fraction of the inwardly rectifying current is activated by cell swelling and presumably subserves host cell volume regulation. In contrast, the outwardly rectifying current is insensitive to cell volume but allows the passage of lactate and is involved in the transport of nutrients. The present study was performed to characterize the permselectivity and pH sensitivity of the anion conductances using whole-cell recording. The outwardly rectifying and the inwardly rectifying currents exhibited permselectivities of Cl−≥Br−≈I−>SCN− and SCN−>I−>Br−>Cl−, respectively, as evident from the reversal potentials recorded under biionic conditions. While the inwardly rectifying current was not affected significantly by alterations of pH between 6.0 and 8.4, the outward rectifier was inhibited strongly by alkalinization to pH≥7.8. Fluxes of 14C-lactate and parasite growth were decreased markedly by the increase of bath pH, an effect that may at least in part be due to inhibition of the outward rectifier and subsequently impaired transport across the erythrocyte membrane.

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References

  • Alkhalil A, Cohn JV, Wagner MA, Cabrera JS, Rajapandi T, Desai SA (2004) Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes. Blood 104:4279–4286

    Article  CAS  PubMed  Google Scholar 

  • Barry PH, Lynch JW (1991) Liquid junction potentials and small cell effects in patch-clamp analysis. J Membr Biol 121:101–117

    CAS  PubMed  Google Scholar 

  • Baumeister S, Endermann T, Charpian S, Nyalwidhe J, Duranton C, Huber S, Kirk K, Lang F, Lingelbach K (2003) A biotin derivative blocks parasite induced novel permeation pathways in Plasmodium falciparum-infected erythrocytes. Mol Biochem Parasitol 132:35–45

    Article  CAS  PubMed  Google Scholar 

  • Breuer WV, Kutner S, Sylphen J, Ginsburg H, Cabantchik ZI (1987) Covalent modification of the permeability pathways induced in the human erythrocyte membrane by the malarial parasite Plasmodium falciparum. J Cell Physiol 133:55–63

    Article  CAS  PubMed  Google Scholar 

  • Cohn JV, Alkhalil A, Wagner MA, Rajapandi T, Desai SA (2003) Extracellular lysines on the plasmodial surface anion channel involved in Na+ exclusion. Mol Biochem Parasitol 132:27–34

    Article  CAS  PubMed  Google Scholar 

  • Cranmer SL, Conant AR, Gutteridge WE, Halestrap AP (1995) Characterization of the enhanced transport of L- and D-lactate into human red blood cells infected with Plasmodium falciparum suggests the presence of a novel saturable lactate proton cotransporter. J Biol Chem 270:15045–15052

    Google Scholar 

  • Desai SA, Bezrukov SM, Zimmerberg J (2000) A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406:1001–1005

    Article  CAS  PubMed  Google Scholar 

  • Duranton C, Huber S, Tanneur V, Lang K, Brand V, Sandu C, Lang F (2003) Electrophysiological properties of the Plasmodium Falciparum-induced cation conductance of human erythrocytes. Cell Physiol Biochem 13:189–198

    Article  CAS  PubMed  Google Scholar 

  • Duranton C, Huber SM, Tanneur V, Brand VB, Akkaya C, Shumilina EV, Sandu CD, Lang F (2004) Organic osmolyte permeabilities of the malaria-induced anion conductances in human erythrocytes. J Gen Physiol 123:417–426

    Article  CAS  PubMed  Google Scholar 

  • Egee S, Lapaix F, Decherf G, Staines HM, Ellory JC, Doerig C, Thomas SLY (2002) A stretch-activated anion channel is up-regulated by the malaria parasite Plasmodium falciparum. J Physiol (Lond) 542:795–801

    Article  Google Scholar 

  • El Tahir A, Malhotra P, Chauhan VS (2003) Uptake of proteins and degradation of human serum albumin by Plasmodium falciparum-infected human erythrocytes. Malar J 2:11

    Article  PubMed  Google Scholar 

  • Ginsburg H, Kirk K (1998) Membrane transport in the malaria-infected erythrocyte. In: Sherman IW (ed) Malaria: parasite biology, pathogenesis and protection. ACM Press, Washington

    Google Scholar 

  • Ginsburg H, Stein WD (2004) 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 197:113–134

    Article  CAS  PubMed  Google Scholar 

  • Ginsburg H, Krugliak M, Eidelman O, Cabantchik ZI (1983) New permeability pathways induced in membranes of Plasmodium falciparum infected erythrocytes. Mol Biochem Parasitol 8:177–190

    Article  CAS  PubMed  Google Scholar 

  • Ginsburg H, Kutner S, Krugliak M, Cabantchik ZI (1985) Characterization of permeation pathways appearing in the host membrane of Plasmodium falciparum infected red blood cells. Mol Biochem Parasitol 14:313–322

    Article  CAS  PubMed  Google Scholar 

  • Grunder S, Thiemann A, Pusch M, Jentsch TJ (1992) Regions involved in the opening of CIC-2 chloride channel by voltage and cell volume. Nature 360:759–762

    Article  CAS  PubMed  Google Scholar 

  • Huber SM, Uhlemann AC, Gamper NL, Duranton C, Kremsner PG, Lang F (2002) Plasmodium falciparum activates endogenous Cl− channels of human erythrocytes by membrane oxidation. EMBO J 21:22–30

    Article  CAS  PubMed  Google Scholar 

  • Huber SM, Duranton C, Henke G, Van De Sand C, Heussler V, Shumilina E, Sandu CD, Tanneur V, Brand V, Kasinathan RS, Lang KS, Kremsner PG, Hubner CA, Rust MB, Dedek K, Jentsch TJ, Lang F (2004) Plasmodium induces swelling-activated ClC-2 anion channels in the host erythrocyte. J Biol Chem 279:41444–41452

    Google Scholar 

  • Jensen JB, Trager W (1978) Plasmodium falciparum in culture: establishment of additional strains. Am J Trop Med Hyg 27:743–746

    CAS  PubMed  Google Scholar 

  • Kanaani J, Ginsburg H (1991) Transport of lactate in Plasmodium falciparum-infected human erythrocytes. J Cell Physiol 149:469–476

    Article  CAS  PubMed  Google Scholar 

  • Kirk K (2000) Malaria channelling nutrients. Nature 406:949–951

    Article  CAS  PubMed  Google Scholar 

  • Kirk K (2001) Membrane transport in the malaria-infected erythrocyte. Physiol Rev 81:495–537

    CAS  PubMed  Google Scholar 

  • Kirk K, Horner HA (1995) Novel anion dependence of induced cation transport in malaria-infected erythrocytes. J Biol Chem 270:24270–24275

    Google Scholar 

  • Kirk K, Horner HA, Elford BC, Ellory JC, Newbold CI (1994) Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel. J Biol Chem 269:3339–3347

    Google Scholar 

  • Kutner S, Baruch D, Ginsburg H, Cabantchik ZI (1982) Alterations in membrane permeability of malaria-infected human erythrocytes are related to the growth stage of the parasite. Biochim Biophys Acta 687:113–117

    CAS  PubMed  Google Scholar 

  • Lew VL, Macdonald L, Ginsburg H, Krugliak M, Tiffert T (2004) Excess haemoglobin digestion by malaria parasites: a strategy to prevent premature host cell lysis. Blood Cells Mol Dis 32:353–359

    Article  CAS  PubMed  Google Scholar 

  • Sherman IW (1983) Metabolism and surface transport of parasitized erythrocytes in malaria. Ciba Found Symp 94:206–221

    CAS  PubMed  Google Scholar 

  • Staalsoe T, Giha HA, Dodoo D, Theander TG, Hviid L (1999) Detection of antibodies to variant antigens on Plasmodium falciparum-infected erythrocytes by flow cytometry. Cytometry 35:329–336

    Article  CAS  PubMed  Google Scholar 

  • Staines HM, Rae C, Kirk K (2000) Increased permeability of the malaria-infected erythrocyte to organic cations. Biochim Biophys Acta 1463:88–98

    CAS  PubMed  Google Scholar 

  • Staines HM, Ellory JC, Kirk K (2001) Perturbation of the pump-leak balance for Na+ and K+ in malaria-infected erythrocytes. Am J Physiol 280:C1576–C1587

    CAS  Google Scholar 

  • Staines HM, Powell T, Ellory JC, Egee S, Lapaix F, Decherf G, Thomas SL, Duranton C, Lang F, Huber SM (2003) Modulation of whole-cell currents in Plasmodium falciparum-infected human red blood cells by holding potential and serum. J Physiol (Lond) 552:177–183

    Article  CAS  Google Scholar 

  • Thiemann A, Grunder S, Pusch M, Jentsch TJ (1992) A chloride channel widely expressed in epithelial and non-epithelial cells. Nature 356:57–60

    Article  CAS  PubMed  Google Scholar 

  • Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. Science 193:673–675

    CAS  PubMed  Google Scholar 

  • Verloo P, Kocken CH, Van der Wel A, Tilly BC, Hogema BM, Sinaasappel M, Thomas AW, De Jonge HR (2004) Plasmodium falciparum-activated chloride channels are defective in erythrocytes from cystic fibrosis patients. J Biol Chem 279:10316–10322

    Google Scholar 

Download references

Acknowledgements

This study was supported by the “Schwerpunktprogramm Life inside cells” of the Deutsche Forschungsgemeinschaft (DFG, La 315/11-1 and 11-2), by the “Forschungsschwerpunktprogramm des Landes Baden-Württemberg Dynamik und Modulation zellulärer Infektionsprozesse”. C.D. was supported by a grant from the Alexander von Humboldt foundation and C.S. by a Marie Curie fellowship. The authors have no conflicting financial interests.

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Authors and Affiliations

  1. Department of Physiology I, Eberhard-Karls-University Tübingen, Gmelinstrasse 5, 72076, Tubingen

    Christophe Duranton, Valerie Tanneur, Verena Brand, Ciprian D. Sandu, Canan Akkaya, Stephan M. Huber & Florian Lang

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  1. Christophe Duranton
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  2. Valerie Tanneur
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  3. Verena Brand
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  4. Ciprian D. Sandu
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  5. Canan Akkaya
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  6. Stephan M. Huber
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  7. Florian Lang
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Correspondence to Christophe Duranton.

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Duranton, C., Tanneur, V., Brand, V. et al. Permselectivity and pH-dependence of Plasmodium falciparum-induced anion currents in human erythrocytes. Pflugers Arch - Eur J Physiol 450, 335–344 (2005). https://doi.org/10.1007/s00424-005-1415-5

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  • DOI: https://doi.org/10.1007/s00424-005-1415-5

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