The Generation, Evolution And Physiological Responses Of Intracelluar Calcium Oscillations And Waves

Calcium is a ubiquitous second messenger. The calcium oscillations and waves of intracellular concentration regulate multiple cellular physiological processes. It triggers life at fertilization and controls the development and differentiation of cells.In this dissertation, by establishing a series of improved nonlinear dynamic models, the generation, evolution and physiological responses of intracellular calcium oscillations and waves were meticulously studied. Various numerical and analytical methods were applied to deal quantitatively with those models and to analyze extensively some characteristic of calcium oscillations and waves. After having compared with experimental data, the obtained results from models could be used to explain qualitatively the relevant experimental discoveries, especially those about the functions and effects of intracellular calcium signals. The creative points and main conclusions of this dissertation are as follows:1. An intracellular calcium oscillations model including mitochondrial calcium cycle is constructed. With this model, the experimental conclusion that the build-up of mitochondrial calcium initiates a program of cell death (apoptosis) is first verified. And is also first confirmed that mitochondrial calcium uptake can increase the frequency of cytosolic calcium oscillations, which was discovered in experiments. In addition, it is found that increasing mitochondrial calcium activity, the frequency of cytosolic calcium oscillation will be raised.2. An improved model of intracellular calcium oscillations is established with the consideration of the effects of buffers on cytoplasm calcium. With this model, two ways concerning the control of cytoplasm calcium oscillations are worked out. One is to regulate the dissociation constant of the calcium buffer, the other is to regulate the total concentration of the buffer.3. By considering the fact that protein phosphatase could be activated by calcium, a unified model concerning the protein phosphorylation-dephosphorylation cycle driven by cytosolic calcium oscillations is first set up. Calculations from the model are presented to show that the fraction of phosphorylated protein is directly proportional to the frequency of cytosolic calcium oscillations. Furthermore, when cytosolic calcium oscillations are turned into a steady state, at the same cytosolic concentration of calcium, the fraction of activated phosphorylated protein is remarkably decreased. The results obtained from the model are in agreement with those from previous theoretical and experimental ones now available.4. The analytical solutions concerning intracellular calcium spiral and target wave in the Xenopus laevis oocyte are obtained. In addition, it is claimed that unless the inactivation parameter of the IP3R is greater than 2.43s intracellular calcium periodic waves cannot be generated.5. The intracellular calcium wave model in frog sympathetic neurons is established. Then the analytical expressions of velocity and waveform of calcium solitary pulse wave are derived. The propagation velocity of solitary pulse wave obtainedby the model is 21.5 ms-1, in accordance with results of experiment.The work presented in this dissertation provides not only the way to regulate cytosolic calcium oscillations for experiment, but also theoretical basis for the control of protein phosphorylation-dephosphorylation cycle driven by calcium oscillations to achieve control of cell physiological responses.