A model of electrical activity and cytosolic calcium dynamics in vascular endothelial cells in response to fluid shear stress

A mathematical model is proposed to describe the intracellular Ca ²⁺ (Ca _i) transient and electrical activity of vascular endothelial cells (VEC) elicited by fluid shear stress (τ). The intracellular Ca ²⁺ store of the model VEC is comprised of a Ca _i-sensitive (sc) and an inositol (1,4,5)-trisphosphate (IP ₃)-sensitive compartment (dc). The dc [Ca ²⁺] is refilled by the sc whose [Ca ²⁺] is the same as extracellular [Ca ²⁺]. IP ₃ produced by the τ-deformed mechanoreceptors discharges the dc Ca ²⁺ into the cytosol. The increase of cytosolic[Ca ²⁺] induces Ca ²⁺ release (CICR) from the sc. The raised Ca _i activates a Ca _i-activated K ⁺ current (I _{K, Ca}) and inhibits IP ₃ production. The cell membrane potential is determined by I _{K, Ca}, voltage-dependent Na ⁺ and K ⁺ currents. Steady τ>0.1 dyne/cm² elicits a Ca _i varies sigmoidally with Log ₁₀(τ) with a maximal peak Ca _i of 150 nM at τ=4 dynes/cm². Step increases of τ fail to elicit a Ca ²⁺ response in cells previously stimulated by a lower shear. The Ca ²⁺ response gradually decreases with repetitive τ stimuli. Pulsatile shear elicits two to three times higher Ca _i and hyperpolarizes the cell more than steady shear of the same magnitude. The simulated Ca ²⁺ responses to τ are quantitatively and qualitatively similar to those observed in cultured VEC. The model provides a possible explanation of why the vasodilating stimulus is greater for pulsatile flow than for nonpulsatile flow.