Received for publication September 11, 2006.
Revised February 6, 2007.
Accepted for publication February 7, 2007.

Solute-inhibitor interactions in the plasmodial surface anion channel reveal complexities in the transport process

Abstract

Human red blood cells infected with the malaria parasite, P. 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. Here, we explored the effects of known PSAC antagonists on transport of different solutes. Unexpectedly, 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 non-specific PSAC antagonists. It could also be abolished by adding sorbitol or alanine, permeant solutes that do not exhibit residual uptake. 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 PSAC's unique selectivity properties.

Key words: Chloride, Amino Acid, Sugars, Antiprotozoal drugs