
Conference publicationsAbstractsXXIX conferenceStochastic integration of minimal model of platelet activationCenter for Theoretical Problems of PhysicoChemical Pharmacology RAS, 119991, Moscow, ul. Kosygin, d. 4 Moscow State University. M.V. Lomonosov Moscow State University, Department of Physics, 119991, Moscow, Leninsky Gory, 1 1 pp. (accepted)Calcium ions play a key role in platelet activation, affecting intracellular mechanisms that directly or indirectly stop bleeding. It is known that when activated by various types of activators, platelets exhibit stochastic oscillations of calcium concentration, while the fundamental laws underlying them are not entirely clear. A minimal mathematical model is proposed that describes the experimentally observed sequences of stochastic ragged peaks of calcium concentration in platelets. The aim of this work is to identify the fundamental mechanisms that describe the dynamics of calcium concentration in platelets. The following tasks were performed: a system of differential equations was constructed that describe the shape of the peak of calcium concentration observed in the experiment; an algorithm was developed to identify fundamental patterns in the experimental sequences of calcium peaks; a stochastic model was developed that reproduces these patterns. To describe the ragged shape of the calcium concentration peak, the de YoungKeizer model was modified, in which the kinetic constants were changed according to the platelet proteome. It was assumed that in order to open the inositol triphosphate receptor, all of its four subunits should be open, and the buffering of calcium ions by proteins in the cytosol was also taken into account. This allowed us to describe the characteristic peak shape with a rapid rise and a slow decline. We found that in cells immobilized on antibodies, in cells activated by ADP and collagen, the mean interspike intervals were linearly dependent on corresponding standard deviations, which suggests that the process of occurrence of peaks in human platelets is Poisson process. At the same time, we shown the unity of the mechanisms of oscillations development under the conditions described above and also we theoretically predicted the minimum interspike interval of 1.6 ± 0.4 s. Finally, by using a modified Gillespie algorithm with Tauleaping, we performed a stochastic integration of the minimal model, which allowed us to reproduce the experimental patterns described above while maintaining the description of the ragged calcium peak shape.
