Mathematical modeling of neuronal response to neuropeptides: Angiotensin II signaling via G-protein coupled receptor

We have developed a mathematical model of the AT1 mediated pathways including activation of PLC, PKC, IPS, and channel mediated variation of the cytosolic Ca2+ level after Angiotensin II stimulation. Different Ca2+ responses and the respective time courses of activated PKC and Ca2+ dependent proteins, e.g. CaMKII are described in the model. The obtained simulation results are in good agreement with the measurement data found in literature. For example, the model describes the state-dependent exposure to Angll: increase in Ca2+ at low baseline Ca2+ levels as well as the decrease in Ca2+ at high (chronic activated) baseline. Additionally, simulation studies revealed that variations in the Na-Ca-exchanger transport characteristics could account for the observed cell-to-cell variability. Additional pathways were included in the model, e.g. MAPK, thus enabling the description of relevant transcription factor patterns. Also a Hodgkin-Huxley model approach is used to investigate the function of cell signaling in altering the firing behavior of NTS neurons in response to various baroreceptor stimuli.