pH Regulation in the Intracellular Malaria Parasite, Plasmodium falciparum

The mechanism by which the intra-erythrocytic form of the human malaria parasite, Plasmodium falciparum, extrudes H ions and thereby regulates its cytosolic pH (pHi), was investigated using saponin-permeabilized parasitized erythrocytes. The parasite was able both to maintain its resting pHi 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 ATPdependent. Amiloride and the related compound ethylisopropylamiloride caused a substantial reduction in the resting pHi of the parasite, whereas EMD 96785, a potent and allegedly selective inhibitor of Na/H exchange, had relatively little effect. The resting pHi of the parasite was also reduced by the sulfhydryl reagent N-ethylmaleimide, by the carboxyl group blocker N,N*-dicyclohexylcarbodiimide, and by bafilomycin A1, a potent inhibitor of V-type H-ATPases. Bafilomycin A1 blocked pHi 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.