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An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum.

Henry, Roselani I, Cobbold, Simon A., Allen, Richard J. W., Khan, Asif, Hayward, Rhys, Lehane, Adele M., Bray, Patrick, Howitt, Susan M., Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, Saliba, Kevin J. and Kirk, Kiaran (2010) 'An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum.'. The Journal of Biological Chemistry, Vol 285, Issue 24, pp. 18615-18626.

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Abstract

The intraerythrocytic malaria parasite exerts tight control over its ionic composition. In this study, a combination of fluorescent ion indicators and (36)Cl(-) flux measurements was used to investigate the transport of Cl(-) and the Cl(-)-dependent transport of "H(+)-equivalents" in mature (trophozoite stage) parasites, isolated from their host erythrocytes. Removal of extracellular Cl(-), resulting in an outward [Cl(-)] gradient, gave rise to a cytosolic alkalinization (i.e. a net efflux of H(+)-equivalents). This was reversed on restoration of extracellular Cl(-). The flux of H(+)-equivalents was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and, when measured in ATP-depleted parasites, showed a pronounced dependence on the pH of the parasite cytosol; the flux was low at cytosolic pH values < 7.2 but increased steeply with cytosolic pH at values > 7.2. (36)Cl(-) influx measurements revealed the presence of a Cl(-) uptake mechanism with characteristics similar to those of the Cl(-)-dependent H(+)-equivalent flux. The intracellular concentration of Cl(-) in the parasite was estimated to be approximately 48 mm in situ. The data are consistent with the intraerythrocytic parasite having in its plasma membrane a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive transporter that, under physiological conditions, imports Cl(-) together with H(+)-equivalents, resulting in an intracellular Cl(-) concentration well above that which would occur if Cl(-) ions were distributed passively in accordance with the parasite's large, inwardly negative membrane potential.

Item Type: Article
Uncontrolled Keywords: Anion Transport; Chloride Transport; Parasitology; Plasma Membrane; Proton Transport; Malaria; Plasmodium falciparum; pH
Subjects: QU Biochemistry > Cells and Genetics > QU 375 Cell physiology
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1074/jbc.M110.120980
Depositing User: Mary Creegan
Date Deposited: 07 Sep 2010 10:48
Last Modified: 06 Feb 2018 13:00
URI: https://archive.lstmed.ac.uk/id/eprint/1031

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