Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 575K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Stelzer, J. E. Articles by Moss, R. L. Search for Related Content PubMed PubMed Citation Articles by Stelzer, J. E. Articles by Moss, R. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Social Bookmarking                      What's this?

¹ Department of Physiology, University of Wisconsin Medical School, Madison, WI 53706
² Department of Clinical Neurophysiology, University of Uppsala, Uppsala, Sweden

Correspondence to Richard L. Moss: rlmoss{at}physiology.wisc.edu

Recent evidence suggests that ventricular ejection is partly powered by a delayed development of force, i.e., stretch activation, in regions of the ventricular wall due to stretch resulting from torsional twist of the ventricle around the apex-to-base axis. Given the potential importance of stretch activation in cardiac function, we characterized the stretch activation response and its Ca²⁺ dependence in murine skinned myocardium at 22°C in solutions of varying Ca²⁺ concentrations. Stretch activation was induced by suddenly imposing a stretch of 0.5–2.5% of initial length to the isometrically contracting muscle and then holding the muscle at the new length. The force response to stretch was multiphasic: force initially increased in proportion to the amount of stretch, reached a peak, and then declined to a minimum before redeveloping to a new steady level. This last phase of the response is the delayed force characteristic of myocardial stretch activation and is presumably due to increased attachment of cross-bridges as a consequence of stretch. The amplitude and rate of stretch activation varied with Ca²⁺ concentration and more specifically with the level of isometric force prior to the stretch. Since myocardial force is regulated both by Ca²⁺ binding to troponin-C and cross-bridge binding to thin filaments, we explored the role of cross-bridge binding in the stretch activation response using NEM-S1, a strong-binding, non-force–generating derivative of myosin subfragment 1. NEM-S1 treatment at submaximal Ca²⁺-activated isometric forces significantly accelerated the rate of the stretch activation response and reduced its amplitude. These data show that the rate and amplitude of myocardial stretch activation vary with the level of activation and that stretch activation involves cooperative binding of cross-bridges to the thin filament. Such a mechanism would contribute to increased systolic ejection in response to increased delivery of activator Ca²⁺ during excitation–contraction coupling.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. E. Stelzer, H. S. Norman, P. P. Chen, J. R. Patel, and R. L. Moss Transmural variation in myosin heavy chain isoform expression modulates the timing of myocardial force generation in porcine left ventricle J. Physiol., November 1, 2008; 586(21): 5203 - 5214. [Abstract] [Full Text] [PDF]

				K. B. Campbell, A. M. Simpson, S. G. Campbell, H. L. Granzier, and B. K. Slinker Dynamic left ventricular elastance: a model for integrating cardiac muscle contraction into ventricular pressure-volume relationships J Appl Physiol, April 1, 2008; 104(4): 958 - 975. [Abstract] [Full Text] [PDF]

				T. Nagayama, E. Takimoto, S. Sadayappan, J. O. Mudd, J.G. Seidman, J. Robbins, and D. A. Kass Control of In Vivo Contraction/Relaxation Kinetics by Myosin Binding Protein C: Protein Kinase A Phosphorylation-Dependent and -Independent Regulation Circulation, November 20, 2007; 116(21): 2399 - 2408. [Abstract] [Full Text] [PDF]

				M. Chandra, M. L. Tschirgi, S. J. Ford, B. K. Slinker, and K. B. Campbell Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1595 - R1607. [Abstract] [Full Text] [PDF]

				K. S. McDonald Regulation of cardiac muscle contraction: how paramount are the sarcomeres? Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R961 - R962. [Full Text] [PDF]

				J. E. Stelzer, J. R. Patel, J. W. Walker, and R. L. Moss Differential Roles of Cardiac Myosin-Binding Protein C and Cardiac Troponin I in the Myofibrillar Force Responses to Protein Kinase A Phosphorylation Circ. Res., August 31, 2007; 101(5): 503 - 511. [Abstract] [Full Text] [PDF]

				D. A. Martyn, L. Smith, K. L. Kreutziger, S. Xu, L. C. Yu, and M. Regnier The Effects of Force Inhibition by Sodium Vanadate on Cross-Bridge Binding, Force Redevelopment, and Ca2+ Activation in Cardiac Muscle Biophys. J., June 15, 2007; 92(12): 4379 - 4390. [Abstract] [Full Text] [PDF]

				J. E. Stelzer, S. L. Brickson, M. R. Locher, and R. L. Moss Role of myosin heavy chain composition in the stretch activation response of rat myocardium J. Physiol., February 15, 2007; 579(1): 161 - 173. [Abstract] [Full Text] [PDF]

				P. P. Sengupta, J. Korinek, M. Belohlavek, J. Narula, M. A. Vannan, A. Jahangir, and B. K. Khandheria Left Ventricular Structure and Function: Basic Science for Cardiac Imaging J. Am. Coll. Cardiol., November 21, 2006; 48(10): 1988 - 2001. [Abstract] [Full Text] [PDF]

				H. L. Granzier and K. B. Campbell New Insights in the Role of Cardiac Myosin Binding Protein C As a Regulator of Cardiac Contractility Circ. Res., October 13, 2006; 99(8): 795 - 797. [Full Text] [PDF]

				J. E. Stelzer, J. R. Patel, and R. L. Moss Protein Kinase A-Mediated Acceleration of the Stretch Activation Response in Murine Skinned Myocardium Is Eliminated by Ablation of cMyBP-C Circ. Res., October 13, 2006; 99(8): 884 - 890. [Abstract] [Full Text] [PDF]

				J. E. Stelzer and R. L. Moss Contributions of Stretch Activation to Length-dependent Contraction in Murine Myocardium J. Gen. Physiol., October 1, 2006; 128(4): 461 - 471. [Abstract] [Full Text] [PDF]

				J. E. Stelzer, J. R. Patel, and R. L. Moss Acceleration of Stretch Activation in Murine Myocardium due to Phosphorylation of Myosin Regulatory Light Chain J. Gen. Physiol., August 28, 2006; 128(3): 261 - 272. [Abstract] [Full Text] [PDF]

				R. L. Moss and D. P. Fitzsimons Myosin Light Chain 2 Into the Mainstream of Cardiac Development and Contractility Circ. Res., August 4, 2006; 99(3): 225 - 227. [Full Text] [PDF]

				J. E. Stelzer, S. B. Dunning, and R. L. Moss Ablation of Cardiac Myosin-Binding Protein-C Accelerates Stretch Activation in Murine Skinned Myocardium Circ. Res., May 12, 2006; 98(9): 1212 - 1218. [Abstract] [Full Text] [PDF]

				Highlights From The Literature Physiology, April 1, 2006; 21(2): 83 - 85. [Full Text] [PDF]

				K. B. Campbell and M. Chandra Functions of Stretch Activation in Heart Muscle J. Gen. Physiol., January 30, 2006; 127(2): 89 - 94. [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents