title: Decreased redox-sensitive erythrocyte cation channel activity in aquaporin 9-deficient mice.
abstract: Survival of the malaria pathogen Plasmodium falciparum in host erythrocytes requires the opening of new permeability pathways (NPPs) in the host cell membrane, accomplishing entry of nutrients, exit of metabolic waste products such as lactate and movement of inorganic ions such as Cl⁻, Na⁺ and Ca²⁺. The molecular identity of NPPs has remained largely elusive but presumably involves several channels, which partially can be activated by oxidative stress in uninfected erythrocytes. One NPP candidate is aquaporin 9 (AQP9), a glycerol-permeable water channel expressed in erythrocytes. Gene-targeted mice lacking functional AQP9 (aqp⁻/⁻) survive infection with the malaria pathogen Plasmodium berghei better than their wild-type littermates (aqp9⁺/⁺). In the present study whole-cell patch-clamp recordings were performed to explore whether ion channel activity is different in erythrocytes from aqp⁻/⁻ and aqp9⁺/⁺ mice. As a result, the cation conductance (K⁺ > Na⁺ > Ca²⁺ ≫ NMDG⁺) was significantly lower in erythrocytes from aqp⁻/⁻ than in erythrocytes from aqp9⁺/⁺ mice. Oxidative stress by exposure for 15-30 min to 1 mM H₂O₂ or 1 mM tert-butyl-hydroperoxide enhanced the cation conductance and increased cytosolic Ca²⁺ concentration, effects significantly less pronounced in erythrocytes from aqp⁻/⁻ than in erythrocytes from aqp9⁺/⁺ mice. In conclusion, lack of AQP9 decreases the cation conductance of erythrocytes, an effect that possibly participates in the altered susceptibility of AQP9-deficient mice to infection with P. berghei.
authors: Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors: Yuliya V
authors: YV
authors: Kucherenko
authors: Stephan M
authors: SM
authors: Huber
authors: Søren
authors: S
authors: Nielsen
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004553:Electric Conductivity; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017136:Ion Transport; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: C491638:Aqp9 protein, mouse; D020346:Aquaporins; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D002118:Calcium