Differential stimulation of the Na+/H+ exchanger determines chloroquine uptake in Plasmodium falciparum

Stefan Wünsch, Cecilia P. Sanchez, Michael Gekle, Lars Große-Wortmann, Jochen Wiesner, Michael Lanzer

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Here we describe the identification and characterization of a physiological marker that is associated with the chloroquine-resistant (CQR) phenotype in the human malarial parasite Plasmodium falciparum. Single cell in vivo pH measurements revealed that CQR parasites consistently have an elevated cytoplasmic pH compared to that of chloroquine-sensitive (CQS) parasites because of a constitutively activated Na+/H+ exchanger (NHE). Together, biochemical and physiological data suggest that chloroquine activates the plasmodial NHE of CQS parasites, resulting in a transitory phase of rapid sodium/hydrogen ion exchange during which chloroquine is taken up by this protein. The constitutively stimulated NHE of COR parasites are capable of little or no further activation by chloroquine. We propose that the inability of chloroquine to stimulate its own uptake through the constitutively activated NHE of resistant parasites constitutes a minimal and necessary event in the generation of the chloroquine-resistant phenotype.

Original languageEnglish (US)
Pages (from-to)335-345
Number of pages11
JournalJournal of Cell Biology
Volume140
Issue number2
DOIs
StatePublished - Jan 26 1998
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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