Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes.
Invasion by the human malaria parasite, Plasmodium falciparum, is associated with marked yet selective increases in red blood cell (RBC) membrane permeability. We previously identified an unusual voltage-dependent ion channel, the plasmodial surface anion channel (PSAC), which may account for these increases. Since then, controversy has arisen about whether there are additional parasite-induced anion channels on the RBC membrane and whether these channels are parasite-encoded proteins or the result of modifications of an endogenous host protein. Here, we used genetically divergent parasite isolates and quantitative transport measurements to examine these questions. Our studies indicate that PSAC alone can adequately account for the increased permeability of infected RBCs to key solutes. Two distinct parasite isolates, grown in RBCs from a single donor, exhibit channel activity with measurably different voltage-dependent gating, a finding difficult to reconcile with simple activation or modification of a host protein. Instead, this difference in channel gating can be conservatively explained by a small number of polymorphisms in a parasite gene that encodes PSAC. The absence of known eukaryotic ion channel homologues in the completed P falciparum genome suggests a novel channel gene, and substantiates PSAC as a target for antimalarial development.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Abdulnaser
A
Alkhalil
Jamieson V
JV
Cohn
Marissa A
MA
Wagner
Jennifer S
JS
Cabrera
Thavamani
T
Rajapandi
Sanjay A
SA
Desai
D000818:Animals; D004594:Electrophysiology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology* / Q000502:physiology; D005665:Furosemide; D006461:Hemolysis; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics*; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*
D007473:Ion Channels; D015800:Protozoan Proteins; C505335:surface anion channel protein, Plasmodium falciparum; D005665:Furosemide