© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Up-regulation of endothelial stretch-activated cation channels by fluid shear stress
aDepartment of Nephrology, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany
bDepartment of Gynecology, MC Benjamin Franklin, Freie Universität, Berlin, Germany
* Corresponding author. Tel.: +49-30-8445-2389; fax: +49-30-8445-4141 hoy{at}zedat.fu-berlin.de
Objective: Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca2+ influx through SAC could induce an intracellular Ca2+ signal stimulating Ca2+-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested whether laminar shear stress (LSS) regulates SAC function. Methods: Electrophysiological properties of SAC were investigated in human umbilical vein endothelial cells (HUVEC) subjected to defined levels of LSS in a flow-cone apparatus. Results: In HUVEC, we identified a Ca2+ permeable SAC that was activated by membrane stretch. Single-channel current densities of SAC in cell-attached patches were significantly increased in HUVEC exposed to an LSS of 5 dyn/cm2 for 4 h (1.15±0.17 SAC/patch) compared to HUVEC kept in stationary culture (0.46±0.07 SAC/patch). Exposure of HUVEC to a higher LSS of 15 dyn/cm2 for 4 h induced similar up-regulation of SAC (1.27±0.21 SAC/patch). After 24 h exposure to LSS of 15 dyn/cm2, single-channel current densities of SAC remained up-regulated (1.07±0.18 SAC/patch) compared to controls. In addition, stretch-sensitivity of SAC (channel activity NPo at –30 mmHg) significantly increased after 2 h of exposure to LSS of 5 and 15 dyn/cm2 and remained up-regulated after 24 h. Inhibition of protein kinases and tyrosine kinases by H7 and genistein, respectively, prevented LSS-induced alteration of SAC function. Conclusion: Single-channel current density and mechanosensitivity of SAC in HUVEC is up-regulated by LSS. Up-regulation of SAC function leads to enhanced mechanosensitive Ca2+ influx, and represents a novel adaptive mechanism of the endothelium in the presence of altered hemodynamic forces.
KEYWORDS Endothelial function; Hemodynamics; Hypertension; Ion channels; Mechanotransduction
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
E. Metaxa, H. Meng, S. R. Kaluvala, M. P. Szymanski, R. A. Paluch, and J. Kolega Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H736 - H742. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. R. Uhrenholt, J. Schjerning, P. M. Vanhoutte, B. L. Jensen, and O. Skott Intercellular calcium signaling and nitric oxide feedback during constriction of rabbit renal afferent arterioles Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1124 - F1131. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. D'Arcangelo, V. Ambrosino, M. Giannuzzo, C. Gaetano, and M. C. Capogrossi Axl receptor activation mediates laminar shear stress anti-apoptotic effects in human endothelial cells Cardiovasc Res, September 1, 2006; 71(4): 754 - 763. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Yao and C. J. Garland Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels Circ. Res., October 28, 2005; 97(9): 853 - 863. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. W. Blackstone and D. M. Bridge Model Systems for Environmental Signaling Integr. Comp. Biol., August 1, 2005; 45(4): 605 - 614. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Grgic, I. Eichler, P. Heinau, H. Si, S. Brakemeier, J. Hoyer, and R. Kohler Selective Blockade of the Intermediate-Conductance Ca2+-Activated K+ Channel Suppresses Proliferation of Microvascular and Macrovascular Endothelial Cells and Angiogenesis In Vivo Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 704 - 709. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Zhang and T. L. Pallone Response of descending vasa recta to luminal pressure Am J Physiol Renal Physiol, September 1, 2004; 287(3): F535 - F542. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sultan, M. Gosling, S. Abu-Hayyeh, N. Carey, and J. T. Powell Flow-dependent increase of ICAM-1 on saphenous vein endothelium is sensitive to apamin Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H22 - H28. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sukharev and D. P. Corey Mechanosensitive Channels: Multiplicity of Families and Gating Paradigms Sci. Signal., February 10, 2004; 2004(219): re4 - re4. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Brakemeier, A. Kersten, I. Eichler, I. Grgic, A. Zakrzewicz, H. Hopp, R. Kohler, and J. Hoyer Shear stress-induced up-regulation of the intermediate-conductance Ca2+-activated K+ channel in human endothelium Cardiovasc Res, December 1, 2003; 60(3): 488 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Wojciak-Stothard and A. J. Ridley Shear stress-induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases J. Cell Biol., April 28, 2003; 161(2): 429 - 439. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Ashida, H. Takechi, T. Kita, and H. Arai Vortex-mediated Mechanical Stress Induces Integrin-dependent Cell Adhesion Mediated by Inositol 1,4,5-Trisphosphate-sensitive Ca2+ Release in THP-1 Cells J. Biol. Chem., March 7, 2003; 278(11): 9327 - 9331. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Del Prete, S. P. Baker, and P. Grigg Stretch Responses of Cutaneous RA Afferent Neurons in Mouse Hairy Skin J Neurophysiol, March 1, 2003; 89(3): 1649 - 1659. [Abstract] [Full Text] [PDF] |
||||









