I. Malaria, an infectious disease responsible for the estimated 300 million to 500 million clinical cases and 1.5 million to 2.7 million human deaths each year, is caused by a single-celled parasite that invades the red blood cells of its host. It was known that growth of the malaria parasite in human red blood cells (RBCs) was accompanied by an increased uptake of many solutes including anions, sugars, purines, amino acids, and organic cations. We have studied the permeability of infected RBCs using whole-cell and patch-clamp methods. Whole-cell experiments showed that while uninfected RBCs had ohmic conductances of less than 100 pS, trophozoide-infected cells exhibited voltage-dependent, non-saturating currents that were 150-fold larger. Patch-clamp measurements and noise spectral analysis revealed that an anion channel on the infected RBC surface, present in at about 1,000 copies per cell, is responsible for these currents. Its pharmacological properties and substrate selectivities match those seen with tracer studies, which suggests that this channel accounts for the increased uptake of small solutes in infected RBCs and plays a primary role in a sequential diffusive pathway for parasite nutrient acquisition. II. Sugar permeation through Escherichia coli maltoporin, a trimer protein that facilitates maltodextrin translocation across outer bacterial membranes, was investigated at the single channel level. For large sugars, such as maltohexaose, elementary events of individual sugar molecule penetration into the channel were readily observed. At small sugar concentrations an elementary event consists of maltoporin channel closure by one third of its initial conductance in sugar-free solution. Statistical analysis of such closures at higher sugar concentrations shows that all three pores of the maltoporin channel transport sugars independently. Interestingly, while channel conductance is only slightly asymmetric, asymmetry in dependence of the sugar binding constant on the voltage polarity is about 20 times higher. Combining our data with observations made with bacteriophage-l, we conclude that the sugar residence time is much more sensitive to (and is decreased by) voltages that are negative from the intra-cell side of the bacterial membrane.
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