PC12 and HEL cell communication in a reconstituted synapse analyzed with mathematical modeling

A synapse simulating model comprising of the nerve growth factor (NGF)-differentiated PC12 cells releasing neurotransmitter (NT) and sensor 92.1.7.human erythroleukemia (HEL) cells has been used for simulating the connection between neurons and target cells. A Ca(2+) elevation was observed in both cell types when the PC12 cells were challenged with nicotine. The response patterns of individual cell were subsequently analyzed mathematically. The Ca(2+) signals of the PC12 cells were described by an equation representing a simple bi-exponential function. The NT-noradrenaline discharged by the PC12 cells in response to nicotine caused heterogeneous secondary Ca(2+) elevations in the HEL cells after a certain delay. Model fitting of this response disclosed slow "hidden" oscillations and heterogeneous secondary Ca(2+) signals could be grouped on the basis of the oscillation frequency. As determined in control experiments with noradrenaline (NA), the value of oscillation frequency also revealed a good correlation with the NT concentration.