Abstract

The objective of this project is to apply the techniques of the in vitro motility assay to investigate regulation of cardiac muscle contraction. Using the in vitro motility assay, one can test in a simplified system with well defined proteins whether Ca2+ regulates crossbridge (XBr) kinetics as suggested by some skinned and intact muscle studies and test which specific proteins are responsible for the observed differences in regulation between cardiac and skeletal muscle. It will also be possible to test aspects of regulation which might depend on the specific arrangement of filaments in the sarcomere and test whether XBr's can activate the thin filament, producing superactivation. Although the in vitro motility assay has been used for some time now to investigate the properties of molecular motors, this is the first direct application to the study of regulation in the actin-myosin system under more physiological conditions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL052558-04
Application #
6242391
Study Section
Project Start
1997-09-01
Project End
1998-08-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Moreno-Gonzalez, Alicia; Gillis, Todd E; Rivera, Anthony J et al. (2007) Thin-filament regulation of force redevelopment kinetics in rabbit skeletal muscle fibres. J Physiol 579:313-26
Kohler, Jan; Chen, Ying; Brenner, Bernhard et al. (2003) Familial hypertrophic cardiomyopathy mutations in troponin I (K183D, G203S, K206Q) enhance filament sliding. Physiol Genomics 14:117-28
Liang, Bo; Chen, Ying; Wang, Chien-Kao et al. (2003) Ca2+ regulation of rabbit skeletal muscle thin filament sliding: role of cross-bridge number. Biophys J 85:1775-86
Regnier, Michael; Rivera, Anthony J; Wang, Chien-Kao et al. (2002) Thin filament near-neighbour regulatory unit interactions affect rabbit skeletal muscle steady-state force-Ca(2+) relations. J Physiol 540:485-97
Martyn, D A; Chase, P B; Regnier, M et al. (2002) A simple model with myofilament compliance predicts activation-dependent crossbridge kinetics in skinned skeletal fibers. Biophys J 83:3425-34
LaMadrid, M A; Chase, P B; Gordon, A M (2002) Motility assays of calcium regulation of actin filaments. Results Probl Cell Differ 36:133-48
Martyn, D A; Regnier, M; Xu, D et al. (2001) Ca2+ - and cross-bridge-dependent changes in N- and C-terminal structure of troponin C in rat cardiac muscle. Biophys J 80:360-70
Mariano, A C; Alexandre, G M; Silva, L C et al. (2001) Dimethyl sulphoxide enhances the effects of P(i) in myofibrils and inhibits the activity of rabbit skeletal muscle contractile proteins. Biochem J 358:627-36
Chase, P B; Chen, Y; Kulin, K L et al. (2000) Viscosity and solute dependence of F-actin translocation by rabbit skeletal heavy meromyosin. Am J Physiol Cell Physiol 278:C1088-98
Regnier, M; Rivera, A J; Chen, Y et al. (2000) 2-deoxy-ATP enhances contractility of rat cardiac muscle. Circ Res 86:1211-7

Showing the most recent 10 out of 25 publications