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: 288/3/C633    most recent 00269.2004v1 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 (18) Citing Articles via Google Scholar Google Scholar Articles by Meeks, M. K. Articles by Rembold, C. M. Search for Related Content PubMed PubMed Citation Articles by Meeks, M. K. Articles by Rembold, C. M.

VASCULAR BIOLOGY

Heat shock protein 20-mediated force suppression in forskolin-relaxed swine carotid artery

Cardiovascular Division, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia

Submitted 7 June 2004 ; accepted in final form 21 October 2004

Increases in cyclic nucleotide levels induce smooth muscle relaxation by deactivation [reductions in myosin regulatory light chain (MRLC) phosphorylation (e.g., by reduced [Ca²⁺])] or force suppression (reduction in force without reduction in MRLC phosphorylation). Ser¹⁶-heat shock protein 20 (HSP20) phosphorylation is the proposed mediator of force suppression. We evaluated three potential hypotheses whereby Ser¹⁶-HSP20 phosphorylation could regulate smooth muscle force: 1) a threshold level of HSP20 phosphorylation could inactivate a thin filament as a whole, 2) phosphorylation of a single HSP20 could fully inactivate a small region of a thin filament, or 3) HSP20 phosphorylation could weakly inhibit myosin binding at either the thin- or thick-filament level. We tested these hypotheses by analyzing the dependence of force on Ser¹⁶-HSP20 phosphorylation in swine carotid media. First, we determined that swine HSP20 has a second phosphorylation site at Ser¹⁵⁷. Ser¹⁵⁷-HSP20 phosphorylation values were high and did not change during contractile activation or forskolin-induced relaxation. Forskolin significantly increased Ser¹⁶-HSP20 phosphorylation. The relationship between Ser¹⁶-HSP20 phosphorylation and force remained linear and was shifted downward in partially activated muscles relaxed with forskolin. Neither forskolin nor nitroglycerin induced actin depolymerization as detected using the F/G-actin ratio method in smooth muscle homogenates. These results suggest that force suppression does not occur in accordance with the first hypothesis (inactivation of a thin filament as a whole). Our data are more consistent with the second and third hypotheses that force suppression is mediated by full or partial inhibition of local myosin binding at the thin- or thick-filament level.

cAMP; cGMP; nitric oxide; vascular smooth muscle

This article has been cited by other articles:

				S. Chen, R. Wang, Q.-F. Li, and D. D. Tang Abl knockout differentially affects p130 Crk-associated substrate, vinculin, and paxillin in blood vessels of mice Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H533 - H539. [Abstract] [Full Text] [PDF]

				D. D. Tang p130 Crk-Associated Substrate (CAS) in Vascular Smooth Muscle Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2009; 14(2): 89 - 98. [Abstract] [PDF]

				D. D. Tang and Y. Anfinogenova Physiologic Properties and Regulation of the Actin Cytoskeleton in Vascular Smooth Muscle Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 130 - 140. [Abstract] [PDF]

				D. D. Tang Intermediate filaments in smooth muscle Am J Physiol Cell Physiol, April 1, 2008; 294(4): C869 - C878. [Abstract] [Full Text] [PDF]

				C. M. Rembold, A. D. Tejani, M. L. Ripley, and S. Han Paxillin phosphorylation, actin polymerization, noise temperature, and the sustained phase of swine carotid artery contraction Am J Physiol Cell Physiol, September 1, 2007; 293(3): C993 - C1002. [Abstract] [Full Text] [PDF]

				C. M. Rembold Force suppression and the crossbridge cycle in swine carotid artery Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1003 - C1009. [Abstract] [Full Text] [PDF]

				Y. Anfinogenova, R. Wang, Q.-f. Li, A. M. Spinelli, and D. D. Tang Abl Silencing Inhibits CAS-Mediated Process and Constriction in Resistance Arteries Circ. Res., August 17, 2007; 101(4): 420 - 428. [Abstract] [Full Text] [PDF]

				R. J. Sandoval, E. R. Injeti, J. M. Williams, W. T. Georthoffer, and W. J. Pearce Myogenic contractility is more dependent on myofilament calcium sensitization in term fetal than adult ovine cerebral arteries Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H548 - H556. [Abstract] [Full Text] [PDF]