title: A model of electrical activity and cytosolic calcium dynamics in vascular endothelial cells in response to fluid shear stress.
abstract: A mathematical model is proposed to describe the intracellular Ca2+ (Cai) transient and electrical activity of vascular endothelial cells (VEC) elicited by fluid shear stress (tau). The intracellular Ca2+ store of the model VEC is comprised of a Cai-sensitive (sc) and an inositol (1,4,5)-trisphosphate (IP3)-sensitive compartment (dc). The dc [Ca2+] is refilled by the sc whose [Ca2+] is the same as extracellular [Ca2+]. IP3 produced by the tau-deformed mechanoreceptors discharges the dc Ca2+ into the cytosol. The increase of cytosolic [Ca2+] induces Ca2+ release (CICR) from the sc. The raised Cai activates a Cai-activated K+ current (IK,Ca) and inhibits IP3 production. The cell membrane potential is determined by IK,Ca, voltage-dependent Na+ and K+ currents. Steady tau > 0.1 dyne/cm2 elicits a Cai transient which reaches peak value at 19-54 sec. The peak Cai varies sigmoidally with Log10(tau) with a maximal peak Cai of 150 nM at tau = 4 dynes/cm2. Step increases of tau fail to elicit a Ca2+ response in cells previously stimulated by a lower shear. The Ca2+ response gradually decreases with repetitive tau stimuli. Pulsatile shear elicits two to three times higher Cai and hyperpolarizes the cell more than steady shear of the same magnitude. The simulated Ca2+ responses to tau 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.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: A Y
authors.initials: AY
authors.lastname: Wong
authors.forename: G A
authors.initials: GA
authors.lastname: Klassen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology; D018056:Hemorheology; D006801:Humans; D008465:Mechanoreceptors / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D011673:Pulsatile Flow / Q000502:physiology; D013314:Stress, Mechanical; D014664:Vasodilation / Q000502:physiology*
chemical_list: D002118:Calcium