TY - JOUR
T1 - Differential stimulation of the Na+/H+ exchanger determines chloroquine uptake in Plasmodium falciparum
AU - Wünsch, Stefan
AU - Sanchez, Cecilia P.
AU - Gekle, Michael
AU - Große-Wortmann, Lars
AU - Wiesner, Jochen
AU - Lanzer, Michael
PY - 1998/1/26
Y1 - 1998/1/26
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.140.2.335
DO - 10.1083/jcb.140.2.335
M3 - Article
C2 - 9442109
AN - SCOPUS:0039701257
SN - 0021-9525
VL - 140
SP - 335
EP - 345
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -