Organic osmolyte permeabilities of the malaria-induced anion conductances in human erythrocytes.

Abstract

Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces new permeability pathways (NPPs) in the host cell membrane. Isotopic flux measurements demonstrated that the NPP are permeable to a wide variety of molecules, thus allowing uptake of nutrients and release of waste products. Recent patch-clamp recordings demonstrated the infection-induced up-regulation of an inwardly and an outwardly rectifying Cl(-) conductance. The present experiments have been performed to explore the sensitivity to cell volume and the organic osmolyte permeability of the two conductances. It is shown that the outward rectifier has a high relative lactate permeability (P(lactate)/P(Cl) = 0.4). Sucrose inhibited the outward-rectifier and abolished the infection-induced hemolysis in isosmotic sorbitol solution but had no or little effect on the inward-rectifier. Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC(50)s in the range of 0.1 and 1 microM, respectively. In contrast, the IC(50)s of NPPB and furosemide for the inward-rectifying current were >10 microM. Osmotic cell-shrinkage inhibited the inwardly but not the outwardly rectifying conductance. In conclusion, the parasite-induced outwardly-rectifying anion conductance allows permeation of lactate and neutral carbohydrates, whereas the inward rectifier seems largely impermeable to organic solutes. All together, these data should help to resolve ongoing controversy regarding the number of unique channels that exist in P. falciparum-infected erythrocytes.

• Authors: Christophe Duranton, Stephan M Huber, Valerie Tanneur, Verena B Brand, Canan Akkaya, Ekaterina V Shumilina, Ciprian D Sandu, Florian Lang
• Journal: The Journal of general physiology (J Gen Physiol) Vol. 123 Issue 4 Pg. 417-26 (Apr 2004) ISSN: 0022-1295 [Print] United States
• PMID: 15051807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anions
• Hypertonic Solutions
• Hypotonic Solutions
• Isotonic Solutions
• Lactic Acid

Topics

• Animals
• Anions (metabolism)
• Erythrocytes (metabolism, parasitology)
• Humans
• Hypertonic Solutions (pharmacology)
• Hypotonic Solutions (pharmacology)
• Isotonic Solutions (pharmacology)
• Lactic Acid (metabolism)
• Malaria, Falciparum (metabolism)
• Patch-Clamp Techniques
• Plasmodium falciparum
• Water-Electrolyte Balance (physiology)