Increased permeability of the malaria-infected erythrocyte to organic cations

The human malaria parasite, Plasmodium falciparum?, induces in the plasma m embrane of its host red blood cell new permeation pathways (NPP) that allow the influx of a variety of low molecular weight solutes. In this study we have demonstrated that the NPP confer upon the parasitised erythrocyte a su bstantial permeability to a range of monovalent organic (quaternary ammoniu m) cations, the largest having an estimated minimum cross-sectional diamete r of 11-12 Angstrom. The rate of permeation of these cations showed a marke d dependence on the nature of the anion present, increasing with the lyotro picity of the anion. There was no clear relationship between the permeation rate and either the size or the hydrophobicity of these solutes. However, the data were consistent with the rate of permeation being influenced by a combination of these two factors, with the pathways showing a marked prefer ence for the relatively small and hydrophobic phenyltrimethylammonium ion o ver larger or less hydrophobic solutes. Large quaternary ammonium cations i nhibited flux via the NPP, as did long-chain n-alkanols. For both classes o f compound the inhibitory potency increased with the size and hydrophobicit y of the solute. This study extends the range of solutes known to permeate the NPP of malaria-infected erythrocytes as well as providing some insight into the factors governing the rate of permeation. (C) 2000 Elsevier Scienc e B.V. All rights reserved.