The influence of different InsP(3) receptor isoforms on Ca(2+) signaling in tracheal smooth muscle cells.
In airway myocytes, like in many cells, Ca(2+) signaling is controlled by inositol 1,4,5-trisphosphate (InsP(3)) via InsP(3) receptors (InsP(3)R) located in the sarco-endoplasmic reticulum. Three types of InsP(3)R exist, labeled Types 1, 2, and 3, which differ in their gating kinetics. We analyze a possible impact of the different gating kinetics of Type 1 and Type 3 InsP(3)R on the time course of cytosolic Ca(2+) concentration in tracheal smooth muscle cells upon agonist stimulation. Previous experimental data in rat tracheal myocytes showed that upon gradually increased stimulation with acetylcholine (ACh), a contractile agonist that acts via InsP(3) production, signal spikes, several spikes with declining maxima, and sustained oscillations appear. Our model reproduces the time courses of cytosolic Ca(2+) measured in tracheal myocytes. Moreover, by postulating slight variations in the model parameters which determine the total number of receptors expressed and the ratio between Type 1 and Type 3 InsP(3)R, it offers an explanation to the experimental observation of qualitatively different responses of cells within a presumably homogeneous tissue.
Haberichter
Thomas
T
Theoretical Biophysics, Institute of Biology, Humboldt University Berlin, Invalidenstr. 43, 10115 Berlin, Germany. thomas@gnsbiotech.com
Roux
Etienne
E
Marhl
Marko
M
Mazat
Jean-Pierre
JP
D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D015220:Calcium Channels / Q000145:classification* / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D003198:Computer Simulation; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000145:classification / Q000378:metabolism / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014132:Trachea / Q000166:cytology / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D002118:Calcium