A minimal generic model of bacteria-induced intracellular Ca2+ oscillations in epithelial cells.
The toxin alpha-hemolysin expressed by uropathogenic Escherichia coli bacteria was recently shown as the first pathophysiologically relevant protein to induce oscillations of the intracellular Ca(2+) concentration in target cells. Here, we propose a generic three-variable kinetic model describing the Ca(2+) oscillations induced in single rat renal epithelial cells by this toxin. Specifically, we take into account the interplay between 1), the cytosolic Ca(2+) concentration; 2), IP(3)-sensitive Ca(2+) channels located in the membrane separating the cytosol and endoplasmic reticulum; and 3), toxin-related activation of production of IP(3) by phospholipase C. With these ingredients, the predicted response of cells exposed to the toxin is in good agreement with the results of experiments.
Oxhamre
Camilla
C
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Richter-Dahlfors
Agneta
A
Zhdanov
Vladimir P
VP
Kasemo
Bengt
B
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D001703:Biophysics / Q000379:methods; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D020013:Calcium Signaling; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D009991:Oscillometry; D051381:Rats; D013997:Time Factors; D010738:Type C Phospholipases / Q000737:chemistry
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium