Abstract
The endothelial lining of blood vessels is subjected to a wide range of haemodynamically-generated shear-stress forces throughout the vascular system1. In vivo and in vitro, endothelial cells change their morphology2,3 and biochemistry4 in response to shear stress in a force- and time-dependent way, or when a critical threshold is exceeded5'6. The initial stimulus–response coupling mechanisms have not been identified, however. Recently, Lansman et al.7 described stretch-activated ion channels in endothelial cells and suggested that they could be involved in the response to mechanical forces generated by blood flow. The channels were relatively non-selective and were opened by membrane stretching induced by suction. Here we report whole-cell patch-clamp recordings of single arterial endothelial cells exposed to controlled levels of laminar shear stress in capillary flow tubes. A K+ selective, shear-stress-activated ionic current (designated IK.s) was identified which is unlike previously described stretch-activated currents. IK.s varies in magnitude and duration as a function of shear stress (half-maximal effect at 0.70 dyn cm−2), desensitizes slowly and recovers rapidly and fully on cessation of flow. IK.s activity represents the earliest and fastest stimulus–response coupling of haemodynamic forces to endothelial cells yet found. We suggest that localized flow-activated hyperpolarization of endothelium involving IK.s may participate in the regulation of vascular tone.
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References
Fry, D. L. Circulation Res. 22, 165–197 (1968).
Flaherty, J. T. et al. Circulation Res. 30, 23–32 (1972).
Dewey, C. F. Jr, Bussolari, S. R., Gimbrone, M. A. Jr & Davies, P. F. J. biomech. Engng 103, 177–185 (1981).
Davies, P. F., Dewey, C. F. Jr, Bussolari, S. R., Gordon, E. J. & Gimbrone, M. A. Jr J. clin. Invest. 73, 1121–1129 (1984).
Frangos, J. A., Eskin, S. G., McIntire, L. V. & Ives, C. L. Science 227, 1477–1479 (1985).
Davies, P. F., Remuzzi, A., Gordon, E. J., Dewey, C. F. Jr & Gimbrone, M. A. Jr Proc. natn. Acad. Sci. U.S.A. 83, 2114–2117 (1986).
Lansman, J. B., Hallam, T. J. & Rink, T. J. Nature 325, 811–813 (1987).
Dewey, C. F. Jr Adv. exp. Med. Biol. 115, 55–103 (1979).
Hille, B. Ionic Channels in Excitable Membranes 111–114 (Sinauer, Sunderland, Mass., 1984).
Olesen, S.-P., Davies, P. F. & Clapham, D. E. Circulation Res. (in the press).
Parnavelas, J. G., Kelly, W. & Burnstock, G. Nature 316, 724–725 (1985).
Arfors, K.-E. & Bergquist, D. Thromb. Res. 4, 447–461 (1974).
Holtz, J., Forstermann, U., Pohl, U., Giesler, M. & Bassenge, E. J. Cardiovasc. Pharmac. 6, 1161–1169 (1984).
Rhodin, J. A. G. J. Ultrastruct. Res. 18, 181–223 (1967).
Davies, P. F. Lab. Invest. 55, 5–24 (1986).
Segal, S. S. & Duling, B. R. Circulation Res. 61, II20–II25 (1987).
Mekata, F. J. Physiol., Lond. 371, 257–265 (1986).
Furchgott, R. F. & Zawadzki, J. V. Nature 288, 373–376 (1980).
Vanhoutte, P. M., Rubanyi, G. M., Miller, V. M. & Houston, D. S. A Rev. Physiol. 48, 307–320 (1986).
Peach, M. J., Singer, M. A. & Loeb, A. L. Biochem. Pharmac. 34, 1867–1874 (1985).
Caro, C. G., Fitzgerald, J. M. & Schroter, R. C. Proc. R. Soc. B 177, 109–159 (1971).
Ku, D. N., Giddens, D. P., Zarins, C. K. & Glagov, S. Arteriosclerosis 5, 293–301 (1985).
Sachs, F. in Ionic Channels in Cells and Model Systems (ed. Latorre, R.) 181–193 (Plenum, New York, 1986).
Schwartz, S. M. In Vitro 14, 966–980 (1978).
Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflugers Arch. ges. Physiol. 391, 85–100 (1981).
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Olesen, SP., Claphamt, D. & Davies, P. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331, 168–170 (1988). https://doi.org/10.1038/331168a0
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DOI: https://doi.org/10.1038/331168a0
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