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) 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 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 Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Qiu, W.-P. Articles by Kass, D. A. Search for Related Content PubMed PubMed Citation Articles by Qiu, W.-P. Articles by Kass, D. A.

Differential effects of pulsatile versus steady flow on coronary endothelial membrane potential

Division of Cardiology, Department of Medicine and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21287

Submitted 16 December 2002 ; accepted in final form 11 March 2003

Steady shear stress stimulates transient hyperpolarization coupled to calcium-sensitive potassium (K_Ca) channels and sustained depolarization linked to chloride-selective channels. Physiological flow is pulsatile not static, and whereas in vivo data suggest phasic shear stress may preferentially activate K_Ca channels, its differential effects on both currents remain largely unknown. To determine this interaction, coronary endothelial cells were cultured in glass capillary flow tubes, loaded with the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol, and exposed to constant or pulsatile shear stress. The latter was generated by a custom servoperfusion system employing physiological pressure and flow waveforms. Steady shear induced a sustained depolarization inhibited by the Cl^- channel blocker DIDS. Even after exposure to steady flow, subsequent transition to pulsatile shear stress further stimulated DIDS-sensitive depolarization. DIDS pretreatment "unmasked" a pulsatile flow-induced hyperpolarization of which magnitude was further enhanced by nifedipine, which augments epoxygenase synthesis. Pulse-shear hyperpolarization was fully blocked by K_Ca channel inhibition (charybdotoxin + apamin), although these agents had no influence on membrane potential altered by steady flow. Thus K_Ca-dependent hyperpolarization is preferentially stimulated by pulsatile over steady flow, whereas both can stimulate Cl^--dependent depolarization. This supports studies showing greater potency of pulsatile flow for triggering K_Ca-dependent vasorelaxation.

calcium-sensitive potassium channels; steady shear stress; vasorelaxation; endothelium-derived hyperpolarizing factor

This article has been cited by other articles:

				O. C. Colgan, G. Ferguson, N. T. Collins, R. P. Murphy, G. Meade, P. A. Cahill, and P. M. Cummins Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stress Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3190 - H3197. [Abstract] [Full Text] [PDF]

				P.-h. G. Chao, A. C. West, and C. T. Hung Chondrocyte intracellular calcium, cytoskeletal organization, and gene expression responses to dynamic osmotic loading Am J Physiol Cell Physiol, October 1, 2006; 291(4): C718 - C725. [Abstract] [Full Text] [PDF]

				D. K. Lieu, P. A. Pappone, and A. I. Barakat Differential membrane potential and ion current responses to different types of shear stress in vascular endothelial cells Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1367 - C1375. [Abstract] [Full Text] [PDF]