A MINIMAL MODEL FOR CALCIUM SIGNAL GENERATED BY TYROSINE KINASE AND G-PROTEIN LINKED RECEPTORS - A STOCHASTIC COMPUTER-SIMULATION WITH CALSIM

A software was designed to simulate the calcium signal following hormo ne or growth factor stimulation in epithelial cells. The software writ ten in C runs on a PC under Windows environment. It is based on a Mark ov process where the dynamic of the system is characterised by phenome nological transition probabilities. Moreover a minimal model is propos ed to analyse the role of plasma channels and IP3 receptors, together with the opposite action of the CaATPase pumps, in the cytosolic and e ndoplasmic reticulum (ER) calcium signal control. The simulation is ap plied on the calcium response following stimulation by carbacol (prote in G coupled receptors) or epidermal growth factor (tyrosine kinase ty pe receptors) in A431 epithelial cells. The experimental calcium signa ls can be grouped in three classes; a spike and a return to the basal level (signal A), a spike and a decrease to a plateau level (signal B) or a slow increase to a plateau (signal C). Epidermal growth factor i nduces signal A and B while carbacol gives signal B and C. When a 'pse udo' steady state is reached oscillations occur. Computer simulations show that signal A can result from the activation of IP3 receptors whi le signal C would result from the activation of the plasma channels, s ignal B appears as the additive contribution of both channels, while o scillations are compatible with a calcium induced calcium release mech anism. Simulations suggest that the calcium dynamic in the ER is a mir ror of cytosolic calcium but that a simple way to produce similar calc ium elevation in these two compartments is to activate plasma channels . Implications of such a mechanism is discussed. (C) 1997 Elsevier Sci ence Ireland Ltd.