The plasmodial surface anion channel is functionally conserved in divergent malaria parasites.
The plasmodial surface anion channel (PSAC), a novel ion channel induced on human erythrocytes infected with Plasmodium falciparum, mediates increased permeability to nutrients and presumably supports intracellular parasite growth. Isotope flux studies indicate that other malaria parasites also increase the permeability of their host erythrocytes, but the precise mechanisms are unknown. Channels similar to PSAC or alternative mechanisms, such as the upregulation of endogenous host transporters, might fulfill parasite nutrient demands. Here we evaluated these possibilities with rhesus monkey erythrocytes infected with Plasmodium knowlesi, a parasite phylogenetically distant from P. falciparum. Tracer flux and osmotic fragility studies revealed dramatically increased permeabilities paralleling changes seen after P. falciparum infection. Patch-clamp of P. knowlesi-infected rhesus erythrocytes revealed an anion channel with striking similarities to PSAC: its conductance, voltage-dependent gating, pharmacology, selectivity, and copy number per infected cell were nearly identical. Our findings implicate a family of unusual anion channels highly conserved on erythrocytes infected with various malaria parasites. Together with PSAC's exposed location on the host cell surface and its central role in transport changes after infection, this conservation supports development of antimalarial drugs against the PSAC family.
Lisk
Godfrey
G
The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Desai
Sanjay A
SA
D000818:Animals; D000838:Anions / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000187:drug effects; D004594:Electrophysiology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008253:Macaca mulatta; D008288:Malaria / Q000378:metabolism; D016778:Malaria, Falciparum / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009996:Osmotic Fragility; D018408:Patch-Clamp Techniques; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D016790:Plasmodium knowlesi / Q000235:genetics / Q000502:physiology*; D014316:Tritium / Q000378:metabolism
D000838:Anions; D007473:Ion Channels; D014316:Tritium