Open and closed states of the plasmodial surface anion channel.
BACKGROUND
The malaria parasite, Plasmodium falciparum, causes most of its clinical sequelae through its intracellular growth and multiplication in human red blood cells (RBCs). During this intracellular cycle, the parasite markedly alters the membrane transport properties of the host RBC through the induction of an unusual ion channel known as the plasmodial surface anion channel (PSAC). In addition to its unusual selectivity and pharmacology, PSAC exhibits atypical voltage-dependent gating; single-channel recordings reveal fast-flickering behavior interspersed with periods of inactivity. Detailed study of its gating properties have been complicated by the technical difficulty of obtaining single PSAC recordings, its small conductance, and various sources of error important for fast-flickering channels.


METHODS
Here, we developed an automated algorithm to analyze large amounts of single-channel data with particular emphasis on these sources of error. This algorithm was evaluated with high-quality single-channel and multichannel recordings obtained in the presence and absence of furosemide, a well-known PSAC antagonist.


CONCLUSIONS
Our analysis reveals that the adequate description of PSAC gating requires only one exponentially decaying open state, but at least three closed channel states. This model was further supported by single-channel recordings in the presence of furosemide, which inhibits PSAC with moderate affinity through an allosteric mechanism.
Desai
Sanjay A
SA
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. sdesai@niaid.nih.gov
D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D004910:Erythrocyte Membrane / Q000737:chemistry* / Q000469:parasitology / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000502:physiology
D007473:Ion Channels; C505335:surface anion channel protein, Plasmodium falciparum