1932

Abstract

Some hours after invading the erythrocytes of its human host, the malaria parasite induces an increase in the permeability of the erythrocyte membrane to monovalent ions. The resulting net influx of Na+ and net efflux of K+, down their respective concentration gradients, converts the erythrocyte cytosol from an initially high-K+, low-Na+ solution to a high-Na+, low-K+ solution. The intraerythrocytic parasite itself exerts tight control over its internal Na+, K+, Cl, and Ca2+ concentrations and its intracellular pH through the combined actions of a range of membrane transport proteins. The molecular mechanisms underpinning ion regulation in the parasite are receiving increasing attention, not least because PfATP4, a P-type ATPase postulated to be involved in Na+ regulation, has emerged as a potential antimalarial drug target, susceptible to inhibition by a wide range of chemically unrelated compounds.

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2015-10-15
2024-04-19
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Literature Cited

  1. Allen RJ, Kirk K. 1.  2004. The membrane potential of the intraerythrocytic malaria parasite Plasmodium falciparum. J. Biol. Chem. 279:11264–72 [Google Scholar]
  2. Alleva LM, Kirk K. 2.  2001. Calcium regulation in the intraerythrocytic malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 117:121–28 [Google Scholar]
  3. Alves E, Bartlett PJ, Garcia CR, Thomas AP. 3.  2011. Melatonin and IP3-induced Ca2+ release from intracellular stores in the malaria parasite Plasmodium falciparum within infected red blood cells. J. Biol. Chem. 286:5905–12 [Google Scholar]
  4. Atamna H, Ginsburg H. 4.  1997. The malaria parasite supplies glutathione to its host cell—investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum. Eur. J. Biochem. 250:670–79 [Google Scholar]
  5. Bennett TN, Kosar AD, Ursos LM, Dzekunov S, Singh Sidhu AB. 5.  et al. 2004. Drug resistance-associated PfCRT mutations confer decreased Plasmodium falciparum digestive vacuolar pH. Mol. Biochem. Parasitol. 133:99–114 [Google Scholar]
  6. Bennett TN, Patel J, Ferdig MT, Roepe PD. 6.  2007. Plasmodium falciparum Na+/H+ exchanger activity and quinine resistance. Mol. Biochem. Parasitol. 153:48–58 [Google Scholar]
  7. Biagini GA, Bray PG, Spiller DG, White MR, Ward SA. 7.  2003. The digestive food vacuole of the malaria parasite is a dynamic intracellular Ca2+ store. J. Biol. Chem. 278:27910–15 [Google Scholar]
  8. Bokhari AA, Mita-Mendoza NK, Fuller A, Pillai AD, Desai SA. 8.  2014. High guanidinium permeability reveals dehydration-dependent ion selectivity in the plasmodial surface anion channel. Biomed. Res. Int. 2014:741024 [Google Scholar]
  9. Bosia A, Ghigo D, Turrini F, Nissani E, Pescarmona GP, Ginsburg H. 9.  1993. Kinetic characterization of Na+/H+ antiport of Plasmodium falciparum membrane. J. Cell Physiol. 154:527–34 [Google Scholar]
  10. Bouyer G, Cueff A, Egee S, Kmiecik J, Maksimova Y. 10.  et al. 2011. Erythrocyte peripheral type benzodiazepine receptor/voltage-dependent anion channels are upregulated by Plasmodium falciparum. Blood 118:2305–12 [Google Scholar]
  11. Brochet M, Collins MO, Smith TK, Thompson E, Sebastian S. 11.  et al. 2014. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca2+ signals at key decision points in the life cycle of malaria parasites. PLOS Biol. 12:e1001806 [Google Scholar]
  12. Bullen HE, Charnaud SC, Kalanon M, Riglar DT, Dekiwadia C. 12.  et al. 2012. Biosynthesis, localization, and macromolecular arrangement of the Plasmodium falciparum translocon of exported proteins (PTEX). J. Biol. Chem. 287:7871–84 [Google Scholar]
  13. Carey AF, Singer M, Bargieri D, Thiberge S, Frischknecht F. 13.  et al. 2014. Calcium dynamics of Plasmodium berghei sporozoite motility. Cell. Microbiol. 16:768–83 [Google Scholar]
  14. Cheemadan S, Ramadoss R, Bozdech Z. 14.  2014. Role of calcium signaling in the transcriptional regulation of the apicoplast genome of Plasmodium falciparum. Biomed. Res. Int. 2014:869401 [Google Scholar]
  15. Cohn JV, Alkhalil A, Wagner MA, Rajapandi T, Desai SA. 15.  2003. Extracellular lysines on the plasmodial surface anion channel involved in Na+ exclusion. Mol. Biochem. Parasitol. 132:27–34 [Google Scholar]
  16. Desai SA. 16.  2012. Ion and nutrient uptake by malaria parasite-infected erythrocytes. Cell. Microbiol. 14:1003–9 [Google Scholar]
  17. Desai SA. 17.  2014. Why do malaria parasites increase host erythrocyte permeability?. Trends Parasitol. 30:151–59 [Google Scholar]
  18. Desai SA, Bezrukov SM, Zimmerberg J. 18.  2000. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406:1001–5 [Google Scholar]
  19. Desai SA, Krogstad DJ, McCleskey EW. 19.  1993. A nutrient-permeable channel on the intraerythrocytic malaria parasite. Nature 362:643–46 [Google Scholar]
  20. Desai SA, McCleskey EW, Schlesinger PH, Krogstad DJ. 20.  1996. A novel pathway for Ca2+ entry into Plasmodium falciparum-infected blood cells. Am. J. Trop. Med. Hyg. 54:464–70 [Google Scholar]
  21. Desai SA, Rosenberg RL. 21.  1997. Pore size of the malaria parasite's nutrient channel. PNAS 94:2045–9 [Google Scholar]
  22. Duranton C, Huber S, Tanneur V, Lang K, Brand V. 22.  et al. 2003. Electrophysiological properties of the Plasmodium falciparum-induced cation conductance of human erythrocytes. Cell. Physiol. Biochem. 13:189–98 [Google Scholar]
  23. Eckstein-Ludwig U, Webb RJ, Van Goethem ID, East JM, Lee AG. 23.  et al. 2003. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424:957–61 [Google Scholar]
  24. Egee S, Lapaix F, Decherf G, Staines HM, Ellory JC. 24.  et al. 2002. A stretch-activated anion channel is up-regulated by the malaria parasite Plasmodium falciparum. J. Physiol. 542:795–801 [Google Scholar]
  25. Elford BC, Haynes JD, Chulay JD, Wilson RJ. 25.  1985. Selective stage-specific changes in the permeability to small hydrophilic solutes of human erythrocytes infected with Plasmodium falciparum. Mol. Biochem. Parasitol. 16:43–60 [Google Scholar]
  26. Ellekvist P, Maciel J, Mlambo G, Ricke CH, Colding H. 26.  et al. 2008. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption. PNAS 105:6398–402 [Google Scholar]
  27. Ellekvist P, Ricke CH, Litman T, Salanti A, Colding H. 27.  et al. 2004. Molecular cloning of a K+ channel from the malaria parasite Plasmodium falciparum. Biochem. Biophys. Res. Commun. 318:477–84 [Google Scholar]
  28. Elliott JL, Saliba KJ, Kirk K. 28.  2001. Transport of lactate and pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum. Biochem. J. 355:733–39 [Google Scholar]
  29. Flannery EL, McNamara CW, Kim SW, Kato TS, Li F. 29.  et al. 2015. Mutations in the P-type cation-transporter ATPase 4, PfATP4, mediate resistance to both aminopyrazole and spiroindolone antimalarials. ACS Chem. Biol. 10:413–20 [Google Scholar]
  30. Furuyama W, Enomoto M, Mossaad E, Kawai S, Mikoshiba K, Kawazu S. 30.  2014. An interplay between 2 signaling pathways: melatonin-cAMP and IP3-Ca2+ signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum. Biochem. Biophys. Res. Commun. 446:125–31 [Google Scholar]
  31. Gao X, Gunalan K, Yap SS, Preiser PR. 31.  2013. Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum. Nat. Commun. 4:2862 [Google Scholar]
  32. Garay RP, Garrahan PJ. 32.  1973. The interaction of sodium and potassium with the sodium pump in red cells. J. Physiol. 231:297–325 [Google Scholar]
  33. Gati WP, Stoyke AF, Gero AM, Paterson AR. 33.  1987. Nucleoside permeation in mouse erythrocytes infected with Plasmodium yoelii. Biochem. Biophys. Res. Commun. 145:1134–41 [Google Scholar]
  34. Gazarini ML, Garcia CR. 34.  2004. The malaria parasite mitochondrion senses cytosolic Ca2+ fluctuations. Biochem. Biophys. Res. Commun. 321:138–44 [Google Scholar]
  35. Gazarini ML, Thomas AP, Pozzan T, Garcia CR. 35.  2003. Calcium signaling in a low calcium environment: how the intracellular malaria parasite solves the problem. J. Cell Biol. 161:103–10 [Google Scholar]
  36. Ginsburg H, Handeli S, Friedman S, Gorodetsky R, Krugliak M. 36.  1986. Effects of red blood cell potassium and hypertonicity on the growth of Plasmodium falciparum in culture. Z. Parasitenkd. 72:185–99 [Google Scholar]
  37. Ginsburg H, Krugliak M, Eidelman O, Cabantchik ZI. 37.  1983. New permeability pathways induced in membranes of Plasmodium falciparum infected erythrocytes. Mol. Biochem. Parasitol. 8:177–90 [Google Scholar]
  38. Ginsburg H, Kutner S, Krugliak M, Cabantchik ZI. 38.  1985. Characterization of permeation pathways appearing in the host membrane of Plasmodium falciparum infected red blood cells. Mol. Biochem. Parasitol. 14:313–22 [Google Scholar]
  39. Glushakova S, Lizunov V, Blank PS, Melikov K, Humphrey G, Zimmerberg J. 39.  2013. Cytoplasmic free Ca2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes. Malar. J. 12:41 [Google Scholar]
  40. Gold DA, Kaplan AD, Lis A, Bett GC, Rosowski EE. 40.  et al. 2015. The toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole. Cell Host Microbe 17:642–52 [Google Scholar]
  41. Gunn RB, Frohlich O, King PA, Shoemaker DG. 41.  1989. Anion transport. Red Blood Cell Membranes: Structure, Function, Clinical Implications P Agre, JC Parker 563–96 New York: CRC [Google Scholar]
  42. Guttery DS, Pittman JK, Frenal K, Poulin B, McFarlane LR. 42.  et al. 2013. The Plasmodium berghei Ca2+/H+ exchanger, PbCAX, is essential for tolerance to environmental Ca2+ during sexual development. PLOS Pathog. 9:e1003191 [Google Scholar]
  43. Hayashi M, Yamada H, Mitamura T, Horii T, Yamamoto A, Moriyama Y. 43.  2000. Vacuolar H+-ATPase localized in plasma membranes of malaria parasite cells, Plasmodium falciparum, is involved in regional acidification of parasitized erythrocytes. J. Biol. Chem. 275:34353–58 [Google Scholar]
  44. Hayward R, Saliba KJ, Kirk K. 44.  2006. The pH of the digestive vacuole of Plasmodium falciparum is not associated with chloroquine resistance. J. Cell Sci. 119:1016–25 [Google Scholar]
  45. Henry RI, Cobbold SA, Allen RJ, Khan A, Hayward R. 45.  et al. 2010. An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum. J. Biol. Chem. 285:18615–26 [Google Scholar]
  46. Homewood CA, Neame KD. 46.  1974. Malaria and the permeability of the host erythrocyte. Nature 252:718–19 [Google Scholar]
  47. Huber SM, Duranton C, Lang F. 47.  2005. Patch-clamp analysis of the “new permeability pathways” in malaria-infected erythrocytes. Int. Rev. Cytol. 246:59–134 [Google Scholar]
  48. Huber SM, Uhlemann AC, Gamper NL, Duranton C, Kremsner PG, Lang F. 48.  2002. Plasmodium falciparum activates endogenous Cl channels of human erythrocytes by membrane oxidation. EMBO J. 21:22–30 [Google Scholar]
  49. Iverson C, Christiansen S, Flanagin A, Fontanarosa PB, Glass RM. 49.  et al. 2007. AMA Manual of Style: A Guide for Authors and Editors New York: Oxf. Univ. Press, 10th ed..
  50. Jimenez-Diaz MB, Ebert D, Salinas Y, Pradhan A, Lehane AM. 50.  et al. 2014. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. PNAS 111:E5455–62 [Google Scholar]
  51. Kirk K, Ashworth KJ, Elford BC, Pinches RA, Ellory JC. 51.  1991. Characteristics of 86Rb+ transport in human erythrocytes infected with Plasmodium falciparum. Biochim. Biophys. Acta 1061:305–8 [Google Scholar]
  52. Kirk K, Elford BC, Ellory JC. 52.  1992. The increased K+ leak of malaria-infected erythrocytes is not via a Ca2+-activated K+ channel. Biochim. Biophys. Acta 1135:8–12 [Google Scholar]
  53. Kirk K, Horner HA. 53.  1995. Novel anion dependence of induced cation transport in malaria-infected erythrocytes. J. Biol. Chem. 270:24270–75 [Google Scholar]
  54. Kirk K, Horner HA, Elford BC, Ellory JC, Newbold CI. 54.  1994. Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel. J. Biol. Chem. 269:3339–47 [Google Scholar]
  55. Kirk K, Lehane AM. 55.  2014. Membrane transport in the malaria parasite and its host erythrocyte. Biochem. J. 457:1–18 [Google Scholar]
  56. Kirk K, Wong HY, Elford BC, Newbold CI, Ellory JC. 56.  1991. Enhanced choline and Rb+ transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Biochem. J. 278:Part 2521–25 [Google Scholar]
  57. Klonis N, Tan O, Jackson K, Goldberg D, Klemba M, Tilley L. 57.  2007. Evaluation of pH during cytostomal endocytosis and vacuolar catabolism of haemoglobin in Plasmodium falciparum. Biochem. J. 407:343–54 [Google Scholar]
  58. Kramer R, Ginsburg H. 58.  1991. Calcium transport and compartment analysis of free and exchangeable calcium in Plasmodium falciparum-infected red blood cells. J. Protozool. 38:594–601 [Google Scholar]
  59. Krishna S, Woodrow C, Webb R, Penny J, Takeyasu K. 59.  et al. 2001. Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms. J. Biol. Chem. 276:10782–87 [Google Scholar]
  60. Kuhn Y, Rohrbach P, Lanzer M. 60.  2007. Quantitative pH measurements in Plasmodium falciparum-infected erythrocytes using pHluorin. Cell. Microbiol. 9:1004–13 [Google Scholar]
  61. Lee P, Ye Z, Van Dyke K, Kirk RG. 61.  1988. X-ray microanalysis of Plasmodium falciparum and infected red blood cells: effects of qinghaosu and chloroquine on potassium, sodium, and phosphorus composition. Am. J. Trop. Med. Hyg. 39:157–65 [Google Scholar]
  62. Lehane AM, Hayward R, Saliba KJ, Kirk K. 62.  2008. A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites. J. Cell Sci. 121:1624–32 [Google Scholar]
  63. Lehane AM, Kirk K. 63.  2008. Chloroquine resistance-conferring mutations in pfcrt give rise to a chloroquine-associated H+ leak from the malaria parasite's digestive vacuole. Antimicrob. Agents Chemother. 52:4374–80 [Google Scholar]
  64. Lehane AM, Ridgway MC, Baker E, Kirk K. 64.  2014. Diverse chemotypes disrupt ion homeostasis in the malaria parasite. Mol. Microbiol. 94:327–39 [Google Scholar]
  65. Levano-Garcia J, Dluzewski AR, Markus RP, Garcia CR. 65.  2010. Purinergic signalling is involved in the malaria parasite Plasmodium falciparum invasion to red blood cells. Purinergic Signal 6:365–72 [Google Scholar]
  66. Lew VL, Bookchin RM. 66.  1986. Volume, pH, and ion-content regulation in human red cells: analysis of transient behavior with an integrated model. J. Membr. Biol. 92:57–74 [Google Scholar]
  67. Lew VL, Macdonald L, Ginsburg H, Krugliak M, Tiffert T. 67.  2004. Excess haemoglobin digestion by malaria parasites: a strategy to prevent premature host cell lysis. Blood Cells Mol. Dis. 32:353–59 [Google Scholar]
  68. Lew VL, Tiffert T, Ginsburg H. 68.  2003. Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells. Blood 101:4189–94 [Google Scholar]
  69. Lew VL, Tsien RY, Miner C, Bookchin RM. 69.  1982. Physiological [Ca2+]i level and pump-leak turnover in intact red cells measured using an incorporated Ca chelator. Nature 298:478–81 [Google Scholar]
  70. Marchetti RV, Lehane AM, Shafik SH, Winterberg M, Martin RE, Kirk K. 70.  2015. A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum. Nat. Commun. 6:6721 [Google Scholar]
  71. Martin RE, Henry RI, Abbey JL, Clements JD, Kirk K. 71.  2005. The ‘permeome’ of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum. Genome Biol. 6:R26 [Google Scholar]
  72. Martin RE, Kirk K. 72.  2004. The malaria parasite's chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily. Mol. Biol. Evol. 21:1938–49 [Google Scholar]
  73. Mauritz JM, Esposito A, Ginsburg H, Kaminski CF, Tiffert T, Lew VL. 73.  2009. The homeostasis of Plasmodium falciparum-infected red blood cells. PLOS Comput. Biol. 5:e1000339 [Google Scholar]
  74. Mauritz JM, Seear R, Esposito A, Kaminski CF, Skepper JN. 74.  et al. 2011. X-ray microanalysis investigation of the changes in Na, K, and hemoglobin concentration in Plasmodium falciparum-infected red blood cells. Biophys. J. 100:1438–45 [Google Scholar]
  75. Nguitragool W, Bokhari AA, Pillai AD, Rayavara K, Sharma P. 75.  et al. 2011. Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells. Cell 145:665–77 [Google Scholar]
  76. Niggli V, Sigel E. 76.  2008. Anticipating antiport in P-type ATPases. Trends Biochem. Sci. 33:156–60 [Google Scholar]
  77. Nkrumah LJ, Riegelhaupt PM, Moura P, Johnson DJ, Patel J. 77.  et al. 2009. Probing the multifactorial basis of Plasmodium falciparum quinine resistance: evidence for a strain-specific contribution of the sodium-proton exchanger PfNHE. Mol. Biochem. Parasitol. 165:122–31 [Google Scholar]
  78. Nyalwidhe J, Baumeister S, Hibbs AR, Tawill S, Papakrivos J. 78.  et al. 2002. A nonpermeant biotin derivative gains access to the parasitophorous vacuole in Plasmodium falciparum-infected erythrocytes permeabilized with streptolysin O. J. Biol. Chem. 277:40005–11 [Google Scholar]
  79. Overman RR. 79.  1948. Reversible cellular permeability alterations in disease; in vivo studies on sodium, potassium and chloride concentrations in erythrocytes of the malarious monkey. Am. J. Physiol. 152:113–21 [Google Scholar]
  80. Pillai AD, Addo R, Sharma P, Nguitragool W, Srinivasan P, Desai SA. 80.  2013. Malaria parasites tolerate a broad range of ionic environments and do not require host cation remodelling. Mol. Microbiol. 88:20–34 [Google Scholar]
  81. Prole DL, Marrion NV. 81.  2012. Identification of putative potassium channel homologues in pathogenic protozoa. PLOS ONE 7:e32264 [Google Scholar]
  82. Pulcini S, Staines HM, Pittman JK, Slavic K, Doerig C. 82.  et al. 2013. Expression in yeast links field polymorphisms in PfATP6 to in vitro artemisinin resistance and identifies new inhibitor classes. J. Infect. Dis. 208:468–78 [Google Scholar]
  83. Rodriguez-Navarro A, Benito B. 83.  2010. Sodium or potassium efflux ATPase: a fungal, bryophyte, and protozoal ATPase. Biochim. Biophys. Acta 1798:1841–53 [Google Scholar]
  84. Rohrbach P, Friedrich O, Hentschel J, Plattner H, Fink RH, Lanzer M. 84.  2005. Quantitative calcium measurements in subcellular compartments of Plasmodium falciparum-infected erythrocytes. J. Biol. Chem. 280:27960–69 [Google Scholar]
  85. Rotmann A, Sanchez C, Guiguemde A, Rohrbach P, Dave A. 85.  et al. 2010. PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum. Mol. Microbiol. 76:1591–606 [Google Scholar]
  86. Rottmann M, McNamara C, Yeung BK, Lee MC, Zou B. 86.  et al. 2010. Spiroindolones, a potent compound class for the treatment of malaria. Science 329:1175–80 [Google Scholar]
  87. Ruiz FA, Luo S, Moreno SN, Docampo R. 87.  2004. Polyphosphate content and fine structure of acidocalcisomes of Plasmodium falciparum. Microsc. Microanal. 10:563–67 [Google Scholar]
  88. Salcedo-Sora JE, Ward SA, Biagini GA. 88.  2012. A yeast expression system for functional and pharmacological studies of the malaria parasite Ca2+/H+ antiporter. Malar. J. 11:254 [Google Scholar]
  89. Saliba KJ, Allen RJ, Zissis S, Bray PG, Ward SA, Kirk K. 89.  2003. Acidification of the malaria parasite's digestive vacuole by a H+-ATPase and a H+-pyrophosphatase. J. Biol. Chem. 278:5605–12 [Google Scholar]
  90. Saliba KJ, Kirk K. 90.  1999. pH regulation in the intracellular malaria parasite, Plasmodium falciparum: H+ extrusion via a V-type H+-ATPase. J. Biol. Chem. 274:33213–19 [Google Scholar]
  91. Saliba KJ, Kirk K. 91.  2001. H+-coupled pantothenate transport in the intracellular malaria parasite. J. Biol. Chem. 276:18115–21 [Google Scholar]
  92. Saliba KJ, Martin RE, Broer A, Henry RI, McCarthy CS. 92.  et al. 2006. Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite. Nature 443:582–85 [Google Scholar]
  93. Spillman NJ, Allen RJ, Kirk K. 93.  2008. Acid extrusion from the intraerythrocytic malaria parasite is not via a Na+/H+ exchanger. Mol. Biochem. Parasitol. 162:96–99 [Google Scholar]
  94. Spillman NJ, Allen RJW, Kirk K. 94.  2013. Na+ extrusion imposes an acid load on the intraerythrocytic malaria parasite. Mol. Biochem. Parasitol. 189:1–4 [Google Scholar]
  95. Spillman NJ, Allen RJ, McNamara CW, Yeung BK, Winzeler EA. 95.  et al. 2013. Na+ regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host Microbe 13:227–37 [Google Scholar]
  96. Staines HM, Alkhalil A, Allen RJ, De Jonge HR, Derbyshire E. 96.  et al. 2007. Electrophysiological studies of malaria parasite-infected erythrocytes: current status. Int. J. Parasitol. 37:475–82 [Google Scholar]
  97. Staines HM, Chang W, Ellory JC, Tiffert T, Kirk K, Lew VL. 97.  1999. Passive Ca2+ transport and Ca2+-dependent K+ transport in Plasmodium falciparum-infected red cells. J. Membr. Biol. 172:13–24 [Google Scholar]
  98. Staines HM, Ellory JC, Kirk K. 98.  2001. Perturbation of the pump-leak balance for Na+ and K+ in malaria-infected erythrocytes. Am. J. Physiol. Cell. Physiol. 280:C1576–87 [Google Scholar]
  99. Staines HM, Rae C, Kirk K. 99.  2000. Increased permeability of the malaria-infected erythrocyte to organic cations. Biochim. Biophys. Acta 1463:88–98 [Google Scholar]
  100. Thomas SL, Bouyer G, Cueff A, Egee S, Glogowska E, Ollivaux C. 100.  2011. Ion channels in human red blood cell membrane: actors or relics?. Blood Cells Mol. Dis. 46:261–65 [Google Scholar]
  101. Tran CV, Saier MH Jr. 101.  2004. The principal chloroquine resistance protein of Plasmodium falciparum is a member of the drug/metabolite transporter superfamily. Microbiology 150:1–3 [Google Scholar]
  102. Vaidya AB, Morrisey JM, Zhang Z, Das S, Daly TM. 102.  et al. 2014. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum. Nat. Commun. 5:5521 [Google Scholar]
  103. van Schalkwyk DA, Saliba KJ, Biagini GA, Bray PG, Kirk K. 103.  2013. Loss of pH control in Plasmodium falciparum parasites subjected to oxidative stress. PLOS ONE 8:e58933 [Google Scholar]
  104. Varotti FP, Beraldo FH, Gazarini ML, Garcia CR. 104.  2003. Plasmodium falciparum malaria parasites display a THG-sensitive Ca2+ pool. Cell Calcium 33:137–44 [Google Scholar]
  105. Waller KL, McBride SM, Kim K, McDonald TV. 105.  2008. Characterization of two putative potassium channels in Plasmodium falciparum. Malar. J. 7:19 [Google Scholar]
  106. Wu B, Rambow J, Bock S, Holm-Bertelsen J, Wiechert M. 106.  et al. 2015. Identity of a Plasmodium lactate/H+ symporter structurally unrelated to human transporters. Nat. Commun. 6:6284 [Google Scholar]
  107. Wunsch S, Sanchez CP, Gekle M, Grosse-Wortmann L, Wiesner J, Lanzer M. 107.  1998. Differential stimulation of the Na+/H+ exchanger determines chloroquine uptake in Plasmodium falciparum. J. Biol. Chem. 140:335–45 [Google Scholar]
  108. Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F. 108.  et al. 2015. A basis for rapid clearance of circulating ring-stage malaria parasites by the spiroindolone KAE609. J. Infect. Dis. In press. doi: 10.1093/infdis/jiv358
  109. Zipprer EM, Neggers M, Kushwaha A, Rayavara K, Desai SA. 109.  2014. A kinetic fluorescence assay reveals unusual features of Ca++ uptake in Plasmodium falciparum-infected erythrocytes. Malar. J. 13:184 [Google Scholar]
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