Ion Regulation in the Malaria Parasite

Some hours after invading the erythrocytes of its human host, the malaria parasite Plasmodium falciparum induces an increase in the permeability of the erythrocyte membrane to monovalent ions. The resulting net influx of Na⁺ and net efflux of K⁺, down their respective concentration gradients, converts the erythrocyte cytosol from an initially high-K⁺, low-Na⁺ solution to a high-Na⁺, low-K⁺ solution. The intraerythrocytic parasite itself exerts tight control over its internal Na⁺, K⁺, Cl^-, and Ca²⁺ concentrations and its intracellular pH through the combined actions of a range of membrane transport proteins. The molecular mechanisms underpinning ion regulation in the parasite are receiving increasing attention, not least because PfATP4, a P-type ATPase postulated to be involved in Na⁺ regulation, has emerged as a potential antimalarial drug target, susceptible to inhibition by a wide range of chemically unrelated compounds.