PT  - JOURNAL ARTICLE
AU  - Godfrey Lisk
AU  - Seth Scott
AU  - Tsione Solomon
AU  - Ajay D. Pillai
AU  - Sanjay A. Desai
TI  - Solute-Inhibitor Interactions in the Plasmodial Surface Anion Channel Reveal Complexities in the Transport Process
AID  - 10.1124/mol.106.030734
DP  - 2007 May 01
TA  - Molecular Pharmacology
PG  - 1241--1250
VI  - 71
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/71/5/1241.short
4100  - http://molpharm.aspetjournals.org/content/71/5/1241.full
SO  - Mol Pharmacol2007 May 01; 71
AB  - Human red blood cells infected with the malaria parasite Plasmodium falciparum have markedly increased permeabilities to diverse organic and inorganic solutes. The plasmodial surface anion channel (PSAC), recently identified with electrophysiological methods, contributes to the uptake of many small solutes. In this study, we explored the effects of known PSAC antagonists on transport of different solutes. We were surprised to find that the transport of two solutes, phenyltrimethylammonium and isoleucine, was only partially inhibited by concentrations of three inhibitors that abolish sorbitol or alanine uptake. Residual uptake via endogenous transporters could not account for this finding because uninfected red blood cells (RBCs) do not have adequate permeability for these solutes. In infected RBCs, the residual uptake of these solutes could be abolished by higher concentrations of specific and nonspecific PSAC antagonists. Adding sorbitol or alanine, permeant solutes that do not exhibit residual uptake, could also abolish it. The residual uptake did not exhibit anomalous mole fraction behavior and had a steep activation energy. These observations exclude uptake via unrelated pathways and instead point to differences in how PSAC recognizes and transports various solutes. We propose a possible model that also may help explain the unique selectivity properties of PSAC. The American Society for Pharmacology and Experimental Therapeutics