title: Modeling of TRPV₄-C₁ -mediated calcium signaling in vascular endothelial cells induced by fluid shear stress and ATP.
abstract: 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 [Formula: see text] through various calcium channels on the plasma membrane. In this paper, a novel dynamic model has been proposed for transient receptor potential vanilloid 4 [Formula: see text]-mediated intracellular calcium dynamics in VECs induced by fluid shear stress and ATP. Our model includes [Formula: see text] signaling pathways through P2Y receptors and [Formula: see text] channels (indirect mechanism) and captures the roles of the [Formula: see text] compound channels in VEC [Formula: see text] signaling in response to fluid shear stress (direct mechanism). In particular, it takes into account that the [Formula: see text] compound channels are regulated by intracellular [Formula: see text] and [Formula: see text] 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 [Formula: see text] response to shear stress.
authors.affiliation: Department of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, No. 2, Linggong Rd., Dalian, 116023, China.
authors.forename: Long-Fei
authors.initials: LF
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiang
authors.forename: Kai-Rong
authors.initials: KR
authors.lastname: Qin
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008955:Models, Cardiovascular; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000378:metabolism; D033081:Shear Strength / Q000502:physiology; D013314:Stress, Mechanical; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D058848:Receptors, Purinergic P2X4; D058470:Receptors, Purinergic P2Y; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium