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J. Cell Biol.,
Volume 140, Number 2, January 26, 1998 335-345
* Zentrum für Infektionsforschung, 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 CQR 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.
Institut für Physiologie der Universität Würzburg, D-97070 Würzburg, Germany
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