The influence of different InsP3 receptor isoforms on Ca2+ signaling in tracheal smooth muscle cells

In airway myocytes, like in many cells, Ca2+ signaling is controlled by inositol 1,4,5-trisphosphate (InsP3) via InsP3 receptors (InsP3R) located in the sarco–endoplasmic reticulum. Three types of InsP3R 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 InsP3R on the time course of cytosolic Ca2+ 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 InsP3 production, signal spikes, several spikes with declining maxima, and sustained oscillations appear. Our model reproduces the time courses of cytosolic Ca2+ 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 InsP3R, it offers an explanation to the experimental observation of qualitatively different responses of cells within a presumably homogeneous tissue.