Journal Article

Up-regulation of endothelial stretch-activated cation channels by fluid shear stress

Susanne Brakemeier, Ines Eichler, Hartmut Hopp, Ralf Köhler and Joachim Hoyer

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 53, issue 1, pages 209-218
Published in print January 2002 | ISSN: 0008-6363
Published online January 2002 | e-ISSN: 1755-3245 | DOI: https://dx.doi.org/10.1016/S0008-6363(01)00476-X
Up-regulation of endothelial stretch-activated cation channels by fluid shear stress

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Abstract

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

Journal Article.  4570 words.  Illustrated.

Subjects: Cardiovascular Medicine

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