Na+ extrusion imposes an acid load on the intraerythrocytic malaria parasite

The intraerythrocytic malaria parasite has, on its plasma membrane, a H(+)-extruding V-type H(+)-ATPase that plays a central role in maintaining the resting cytosolic pH at around 7.3. Previous studies have demonstrated the presence in the parasite of an unknown acidification mechanism that is revealed on inhibition of the V-type H(+)-ATPase. Here we show that this acidification is dependent on the presence of extracellular Na(+), and is associated with the activity of a plasma membrane Na(+)-ATPase that is inhibited by the novel antimalarial spiroindolone NITD246 and is postulated to export Na(+) ions in counter-transport with H(+) ions. The proposed import of H(+) by the Na(+)-extruding Na(+)-ATPase necessitates "abundant H(+) pumping" by the V-type H(+)-ATPase (Ginsburg H. Abundant proton pumping in Plasmodium falciparum, but why? Trends in Parasitology 2002;18:483-6) and has significant implications for the energy budget of the parasite.