A MATHEMATICAL-MODEL OF CYTOSOLIC CALCIUM DYNAMICS IN HUMAN UMBILICALVEIN ENDOTHELIAL-CELLS

Important among the responses of endothelial cells are cytosolic free calcium transients. These transients are mediated by several factors, including blood-borne agonists, extracellular calcium, and fluid-impos ed shear forces. The transients are characterized by a rapid rise foll owed by a plateau phase. Abase mathematical model is presented that re asonably reproduces the measured calcium transient in cultured human u mbilical vein endothelial cells responding to thrombin. Kinetic equati ons for receptor activation and calcium mobilization comprise the mode l. A graded response of intracellular free calcium to increasing conce ntrations of agonist is predicted. Also predicted is the elevation of the peak value and the plateau level by steady nonspecific leak of cal cium across the plasma membrane. The influences of capacitative calciu m entry, calcium-induced calcium release, and buffering by cytosolic p roteins are investigated parametrically. The model predicts significan t depletion of cellular calcium in response to agonist stimulation.