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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.
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: | 17 Jul 2020 10:57 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/1031 |
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