Modeling of -mediated calcium signaling in vascular endothelial cells induced by fluid shear stress and ATP

摘要

The calcium signaling plays a vital role in flow-dependent vascular endothelial cell (VEC) physiology. Variations in fluid shear stress and ATP concentration in blood vessels can activate dynamic responses of cytosolic-free through various calcium channels on the plasma membrane. In this paper, a novel dynamic model has been proposed for transient receptor potential vanilloid 4 -mediated intracellular calcium dynamics in VECs induced by fluid shear stress and ATP. Our model includes signaling pathways through P2Y receptors and channels (indirect mechanism) and captures the roles of the compound channels in VEC signaling in response to fluid shear stress (direct mechanism). In particular, it takes into account that the compound channels are regulated by intracellular and concentrations. The simulation studies have demonstrated that the dynamic responses of calcium concentration produced by the proposed model correlate well with the existing experimental observations. We also conclude from the simulation studies that endogenously released ATP may play an insignificant role in the process of intracellular response to shear stress.