pH regulation in the intracellular malaria parasite, Plasmodium falciparum. H(+) extrusion via a V-type H(+)-ATPase.
The mechanism by which the intra-erythrocytic form of the human malaria parasite, Plasmodium falciparum, extrudes H(+) ions and thereby regulates its cytosolic pH (pH(i)), was investigated using saponin-permeabilized parasitized erythrocytes. The parasite was able both to maintain its resting pH(i) and to recover from an imposed intracellular acidification in the absence of extracellular Na(+), thus ruling out the involvement of a Na(+)/H(+) exchanger in both processes. Both phenomena were ATP-dependent. Amiloride and the related compound ethylisopropylamiloride caused a substantial reduction in the resting pH(i) of the parasite, whereas EMD 96785, a potent and allegedly selective inhibitor of Na(+)/H(+) exchange, had relatively little effect. The resting pH(i) of the parasite was also reduced by the sulfhydryl reagent N-ethylmaleimide, by the carboxyl group blocker N,N'-dicyclohexylcarbodiimide, and by bafilomycin A(1), a potent inhibitor of V-type H(+)-ATPases. Bafilomycin A(1) blocked pH(i) recovery in parasites subjected to an intracellular acidification and reduced the rate of acidification of a weakly buffered solution by parasites under resting conditions. The data are consistent with the hypothesis that the malaria parasite, like other parasitic protozoa, has in its plasma membrane a V-type H(+)-ATPase, which serves as the major route for the efflux of H(+) ions.
Saliba
K J
KJ
Division of Biochemistry, Faculty of Science, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
Kirk
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010963:Plasmodium falciparum / Q000201:enzymology / Q000378:metabolism*; D017494:Proton Pumps / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012964:Sodium / Q000008:administration & dosage; D025262:Vacuolar Proton-Translocating ATPases
D003470:Culture Media; D004791:Enzyme Inhibitors; D017494:Proton Pumps; D006859:Hydrogen; D000255:Adenosine Triphosphate; D012964:Sodium; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases