HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/C1367    most recent 00243.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Lieu, D. K. Articles by Barakat, A. I. Search for Related Content PubMed PubMed Citation Articles by Lieu, D. K. Articles by Barakat, A. I.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Differential membrane potential and ion current responses to different types of shear stress in vascular endothelial cells

¹Department of Mechanical and Aeronautical Engineering and ²Section of Neurobiology, Physiology and Behavior, University of California, Davis, California 95616

Submitted 11 June 2003 ; accepted in final form 30 January 2004

Vascular endothelial cells (ECs) distinguish among and respond differently to different types of fluid mechanical shear stress. Elucidating the mechanisms governing this differential responsiveness is the key to understanding why early atherosclerotic lesions localize preferentially in arterial regions exposed to low and/or oscillatory flow. An early and very rapid endothelial response to flow is the activation of flow-sensitive K⁺ and Cl^– channels that respectively hyperpolarize and depolarize the cell membrane and regulate several important endothelial responses to flow. We have used whole cell current- and voltage-clamp techniques to demonstrate that flow-sensitive hyperpolarizing and depolarizing currents respond differently to different types of shear stress in cultured bovine aortic ECs. A steady shear stress level of 10 dyn/cm² activated both currents leading to rapid membrane hyperpolarization that was subsequently reversed to depolarization. In contrast, a steady shear stress of 1 dyn/cm² only activated the hyperpolarizing current. A purely oscillatory shear stress of 0 ± 10 dyn/cm² with an oscillation frequency of either 1 or 0.2 Hz activated the hyperpolarizing current but only minimally the depolarizing current, whereas a 5-Hz oscillation activated neither current. These results demonstrate for the first time that flow-activated ion currents exhibit different sensitivities to shear stress magnitude and oscillation frequency. We propose that flow-sensitive ion channels constitute components of an integrated mechanosensing system that, through the aggregate effect of ion channel activation on cell membrane potential, enables ECs to distinguish among different types of flow.

ion channels; atherosclerosis; mechanotransduction

This article has been cited by other articles:

				Y. Fang, E. R. Mohler III, E. Hsieh, H. Osman, S. M. Hashemi, P. F. Davies, G. H. Rothblat, R. L. Wilensky, and I. Levitan Hypercholesterolemia Suppresses Inwardly Rectifying K+ Channels in Aortic Endothelium In Vitro and In Vivo Circ. Res., April 28, 2006; 98(8): 1064 - 1071. [Abstract] [Full Text] [PDF]

				Y. Fang, G. Schram, V. G. Romanenko, C. Shi, L. Conti, C. A. Vandenberg, P. F. Davies, S. Nattel, and I. Levitan Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2 Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1134 - C1144. [Abstract] [Full Text] [PDF]

				A. Gojova and A. I. Barakat Vascular endothelial wound closure under shear stress: role of membrane fluidity and flow-sensitive ion channels J Appl Physiol, June 1, 2005; 98(6): 2355 - 2362. [Abstract] [Full Text] [PDF]

				A. Makino, M. Glogauer, G. M. Bokoch, S. Chien, and G. W. Schmid-Schonbein Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases Am J Physiol Cell Physiol, April 1, 2005; 288(4): C863 - C871. [Abstract] [Full Text] [PDF]