Model of the calcium response of thrombocytus on activation
Center for Theoretical Problems of Physico-Chemical Pharmacology RAS, 119991, Moscow, ul. Kosygin, d. 4
1Moscow State University. M.V. Lomonosov Moscow State University, Department of Physics, 119991, Moscow, Leninsky Gory, 1
Calcium ions are the main secondary messengers during platelet activation, an irreversible process that ensures the formation of blood clots to prevent bleeding. From experimental data it is known that, depending on the concentration and type of activator, platelets can form various calcium responses: a stable low level, oscillations with the number of peaks increasing with increasing activator concentration, and a consistently high level. A model is proposed that qualitatively and quantitatively describes the dynamics of the concentration of calcium in platelets without loss of predictive power.
The purpose of the study is to identify mechanisms that describe the dynamics of the concentration of calcium in platelets. The following tasks were performed: a system of differential equations was constructed that describes the dynamics of calcium concentration in the platelets of healthy donors; the behavior of the model was investigated by changing the parameters responsible for the metabolic functions of the cell; The role of diffusion in the distribution of calcium in the platelet cytoplasm was studied by analyzing the reaction-diffusion system obtained by adding a diffusion term to the equation of the rate of change in calcium concentration.
The Keizer-de-Young model was modified for oscillations in calcium concentration caused by an increase in the concentration of inositol-3-phosphate, a secondary messenger that conducts a signal from the cell membrane to the EPR. This model cannot describe the shape of the calcium peak and the average number of peaks per unit time that are characteristic of platelets. The cooperativity of the inositol triphosphate receptors together with the inclusion of cytosolic calcium buffers made it possible to describe the experimental data. The model predicts the shape of peaks with a rapid rise, a slow decline and an average frequency of 0.4 Hz.
Platelets are not the same in size, age, and ATP concentration. A decrease in the volume and value of the parameter associated with the concentration of ATP leads to an increase in the frequency of oscillations and the average concentration of calcium. Adding a diffusion term to the equation for the dynamics of calcium concentration made it possible to describe the experimental data: calcium waves propagate at a speed of up to 5 μm / s.
Thus, the formation of a calcium response in a platelet is controlled by the method of releasing calcium ions from intracellular storages, while the peak shape and frequency of oscillations in the concentration of calcium are determined by the buffering of calcium in the cytosol.