Clusterization of Inositol Trisphosphate Receptors Determines the Shape of the Calcium Oscillation Peak in Platelet Cytosol
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Platelets, which are anucleate blood cells, should have the capacity to respond to an external stimulus within 1 second. This capacity is maintained by calcium signaling, the process of intracellular signal transmission mediated by an increase of the calcium ion concentration in the cytosol due to calcium release from the endoplasmic reticulum through the inositol trisphosphate receptor channel (IP3R). The increase of the calcium concentration in the platelet cytosol is not monotonous, but rather has an oscillatory character, similar to the processes in many other cell types. The regularities that underlie the development of these oscillations were subjected to theoretical and experimental analysis in the present study. Total internal reflection microscopy of platelets immobilized on fibrinogen and loaded with the Fura-2 calcium-sensitive fluorescent label was used to monitor the dynamics of calcium concentration. The mathematical model of the IP3R–ATPase pair from  modified to take the platelet parameters into account was used to describe the process of oscillation development. The results of the study demonstrated a characteristic peak shape for calcium oscillations in the platelet: theoretical description of the peak shape essentially required the introduction of corrections that had the physical meaning of cooperative IP3R activation.
Keywords:blood platelets intracellular signaling thrombin inositol trisphosphate calcium signaling mathematical modeling fluorescence microscopy.
The authors are grateful to the Corresponding RAS Member F.I. Ataullakhanov (CTP PCP RAS) for support and discussion of the data and to V.V. Mustyatsa (Rogachev NMRC PHOI) for technical support.
The work was supported by grant 17-74-20045 of the Russian Science Foundation.
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