| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARDIOVASCULAR |
1 Department of Bioengineering, University of Washington, Seattle, WA, USA
Ca2+-dependent activation of striated muscle involves cooperative interactions of cross-bridges and thin filament regulatory proteins. We investigated how interactions between individual structural regulatory units (RUs; 1 tropomyosin, 1 troponin, 7 actins) influence the level and rate of demembranated (skinned) cardiac muscle force development by exchanging native cardiac troponin (cTn) with different ratio mixtures of wild-type (WT) cTn and cTn containing WT cardiac troponin T/I + cardiac troponin C (cTnC) D65A (a site II inactive cTnC mutant). Maximal Ca2+-activated force (Fmax) increased in less than a linear manner with WT cTn. This contrasts with results we obtained previously in skeletal fibres (using sTnC D28A, D65A) where Fmax increased in a greater than linear manner with WT sTnC, and suggests that Ca2+ binding to each functional Tn activates < 7 actins of a structural regulatory unit in cardiac muscle and > 7 actins in skeletal muscle. The Ca2+ sensitivity of force and rate of force redevelopment (ktr) was leftward shifted by 0.1–0.2 –log [Ca2+] (pCa) units as WT cTn content was increased, but the slope of the force–pCa relation and maximal ktr were unaffected by loss of near-neighbour RU interactions. Cross-bridge inhibition (with butanedione monoxime) or augmentation (with 2 deoxy-ATP) had no greater effect in cardiac muscle with disruption of near-neighbour RU interactions, in contrast to skeletal muscle fibres where the effect was enhanced. The rate of Ca2+ dissociation was found to be > 2-fold faster from whole cardiac Tn compared with skeletal Tn. Together the data suggest that in cardiac (as opposed to skeletal) muscle, Ca2+ binding to individual Tn complexes is insufficient to completely activate their corresponding RUs, making thin filament activation level more dependent on concomitant Ca2+ binding at neighbouring Tn sites and/or crossbridge feedback effects on Ca2+ binding affinity.
(Received 24 January 2007;
accepted after revision 18 February 2007;
first published online 22 February 2007)
Corresponding author M. Regnier: Department of Bioengineering, University of Washington, Seattle, WA, USA, 98195. Email: mregnier{at}u.washington.edu
Related Article
J. Physiol. 2007 580: 358.
This article has been cited by other articles:
|
|
 |
|
  K. L. Kreutziger, N. Piroddi, B. Scellini, C. Tesi, C. Poggesi, and M. Regnier Thin filament Ca2+ binding properties and regulatory unit interactions alter kinetics of tension development and relaxation in rabbit skeletal muscle J. Physiol., August 1, 2008; 586(15): 3683 - 3700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Shiels and E. White The Frank-Starling mechanism in vertebrate cardiac myocytes J. Exp. Biol., July 1, 2008; 211(13): 2005 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Davis and S. B. Tikunova Ca2+ exchange with troponin C and cardiac muscle dynamics Cardiovasc Res, March 1, 2008; 77(4): 619 - 626. [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. E. Gillis, C. R. Marshall, and G. F. Tibbits Functional and evolutionary relationships of troponin C Physiol Genomics, December 19, 2007; 32(1): 16 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Norman, J. A. Rall, S. B. Tikunova, and J. P. Davis Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2580 - H2587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Kreutziger, T. E. Gillis, J. P. Davis, S. B. Tikunova, and M. Regnier Influence of enhanced troponin C Ca2+-binding affinity on cooperative thin filament activation in rabbit skeletal muscle J. Physiol., August 15, 2007; 583(1): 337 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. D. Gao and A. M. Murphy Local control in thin filament activation of cardiac muscle J. Physiol., April 15, 2007; 580(2): 358 - 358. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
