This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 99/8/884    most recent 01.RES.0000245191.34690.66v1 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire 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. Related Collections Contractile function Animal models of human disease Genetically altered mice Heart failure - basic studies Related Article

(Circulation Research. 2006;99:884.)
© 2006 American Heart Association, Inc.

Integrative Physiology

Protein Kinase A–Mediated Acceleration of the Stretch Activation Response in Murine Skinned Myocardium Is Eliminated by Ablation of cMyBP-C

Julian E. Stelzer, Jitandrakumar R. Patel, Richard L. Moss

From the Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison.

Correspondence to Julian E. Stelzer, Department of Physiology, University of Wisconsin Medical School, 1300 University Ave, Madison, WI 53706. E-mail stelzer{at}physiology.wisc.edu

ß-Adrenergic agonists induce protein kinase A (PKA) phosphorylation of the cardiac myofilament proteins myosin binding protein C (cMyBP-C) and troponin I (cTnI), resulting in enhanced systolic function, but the relative contributions of cMyBP-C and cTnI to augmented contractility are not known. To investigate possible roles of cMyBP-C in this response, we examined the effects of PKA treatment on the rate of force redevelopment and the stretch activation response in skinned ventricular myocardium from both wild-type (WT) and cMyBP-C null (cMyBP-C^–/–) myocardium. In WT myocardium, PKA treatment accelerated the rate of force redevelopment and the stretch activation response, resulting in a shorter time to the peak of delayed force development when the muscle was stretched to a new isometric length. Ablation of cMyBP-C accelerated the rate of force redevelopment and stretch activation response to a degree similar to that observed in PKA treatment of WT myocardium; however, PKA treatment had no effect on the rate of force development and the stretch activation response in null myocardium. These results indicate that ablation of cMyBP-C and PKA treatment of WT myocardium have similar effects on cross-bridge cycling kinetics and suggest that PKA phosphorylation of cMyBP-C accelerates the rate of force generation and thereby contributes to the accelerated twitch kinetics observed in living myocardium during ß-adrenergic stimulation.

Key Words: cross-bridge kinetics • ß-adrenergic agonists • positive inotropy • contractile protein function

Related Article:

New Insights in the Role of Cardiac Myosin Binding Protein C As a Regulator of Cardiac Contractility

Henk L. Granzier and Kenneth B. Campbell
Circ. Res. 2006 99: 795-797. [Full Text] [PDF]

This article has been cited by other articles:

				B. A. Colson, T. Bekyarova, M. R. Locher, D. P. Fitzsimons, T. C. Irving, and R. L. Moss Protein Kinase A-Mediated Phosphorylation of cMyBP-C Increases Proximity of Myosin Heads to Actin in Resting Myocardium Circ. Res., August 1, 2008; 103(3): 244 - 251. [Abstract] [Full Text] [PDF]

				Y. Lecarpentier, N. Vignier, P. Oliviero, A. Guellich, L. Carrier, and C. Coirault Cardiac Myosin-Binding Protein C Modulates the Tuning of the Molecular Motor in the Heart Biophys. J., July 15, 2008; 95(2): 720 - 728. [Abstract] [Full Text] [PDF]

				Y.-H. Yeh, R. Wakili, X.-Y. Qi, D. Chartier, P. Boknik, S. Kaab, U. Ravens, P. Coutu, D. Dobrev, and S. Nattel Calcium-Handling Abnormalities Underlying Atrial Arrhythmogenesis and Contractile Dysfunction in Dogs With Congestive Heart Failure Circ Arrhythmia Electrophysiol, June 1, 2008; 1(2): 93 - 102. [Abstract] [Full Text] [PDF]

				L. M. Hanft, F. S. Korte, and K. S. McDonald Cardiac function and modulation of sarcomeric function by length Cardiovasc Res, March 1, 2008; 77(4): 627 - 636. [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]

				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]

				A. C. Hinken and R. J. Solaro A Dominant Role of Cardiac Molecular Motors in the Intrinsic Regulation of Ventricular Ejection and Relaxation Physiology, April 1, 2007; 22(2): 73 - 80. [Abstract] [Full Text] [PDF]

				S. Brickson, D. P. Fitzsimons, L. Pereira, T. Hacker, H. Valdivia, and R. L. Moss In vivo left ventricular functional capacity is compromised in cMyBP-C null mice Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1747 - H1754. [Abstract] [Full Text] [PDF]

				A. Neulen, N. Blaudeck, S. Zittrich, D. Metzler, G. Pfitzer, and R. Stehle Mn2+-dependent protein phosphatase 1 enhances protein kinase A-induced Ca2+ desensitisation in skinned murine myocardium Cardiovasc Res, April 1, 2007; 74(1): 124 - 132. [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]