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Publication : Decreased redox-sensitive erythrocyte cation channel activity in aquaporin 9-deficient mice.

First Author  Kucherenko YV Year  2012
Journal  J Membr Biol Volume  245
Issue  12 Pages  797-805
PubMed ID  22836670 Mgi Jnum  J:323085
Mgi Id  MGI:6877305 Doi  10.1007/s00232-012-9482-y
Citation  Kucherenko YV, et al. (2012) Decreased redox-sensitive erythrocyte cation channel activity in aquaporin 9-deficient mice. J Membr Biol 245(12):797-805
abstractText  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 Ca(2)(+). 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(+) > Ca(2)(+) >> 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 H(2)O(2) or 1 mM tert-butyl-hydroperoxide enhanced the cation conductance and increased cytosolic Ca(2)(+) 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.
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