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Biochemistry Research International
Volume 2012 (2012), Article ID 824068, 11 pages
http://dx.doi.org/10.1155/2012/824068
Research Article

Cardiomyopathy-Related Mutations in Cardiac Troponin C, L29Q and G159D, Have Divergent Effects on Rat Cardiac Myofiber Contractile Dynamics

Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology (VCAPP), Washington State University, Pullman, WA 99164-6520, USA

Received 14 May 2012; Revised 6 July 2012; Accepted 8 August 2012

Academic Editor: Danuta Szczesna-Cordary

Copyright © 2012 Sampath K. Gollapudi and Murali Chandra. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Previous studies of cardiomyopathy-related mutations in cardiac troponin C (cTnC)—L29Q and G159D—have shown diverse findings. The link between such mutant effects and their divergent impact on cardiac phenotypes has remained elusive due to lack of studies on contractile dynamics. We hypothesized that a cTnC mutant-induced change in the thin filament will affect global myofilament mechanodynamics because of the interactions of thin filament kinetics with both C a 2 + binding and crossbridge (XB) cycling kinetics. We measured pCa-tension relationship and contractile dynamics in detergent-skinned rat cardiac papillary muscle fibers reconstituted with the recombinant wild-type rat cTnC ( c T n C W T ), c T n C L 2 9 Q , and c T n C G 1 5 9 D mutants. c T n C L 2 9 Q fibers demonstrated a significant decrease in C a 2 + sensitivity, but c T n C G 1 5 9 D fibers did not. Both mutants had no effect on C a 2 + -activated maximal tension. The rate of XB recruitment dynamics increased in c T n C L 2 9 Q (26%) and c T n C G 1 5 9 D (25%) fibers. The rate of XB distortion dynamics increased in c T n C G 1 5 9 D fibers (15%). Thus, the c T n C L 2 9 Q mutant modulates the equilibrium between the non-cycling and cycling pool of XB by affecting the on/off kinetics of the regulatory units (Tropomyosin-Troponin); whereas, the c T n C G 1 5 9 D mutant increases XB cycling rate. Different effects on contractile dynamics may offer clue regarding how c T n C L 2 9 Q and c T n C G 1 5 9 D cause divergent effects on cardiac phenotypes.