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 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 (), , and mutants. fibers demonstrated a significant decrease in sensitivity, but fibers did not. Both mutants had no effect on -activated maximal tension. The rate of XB recruitment dynamics increased in (26%) and (25%) fibers. The rate of XB distortion dynamics increased in fibers (15%). Thus, the 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 mutant increases XB cycling rate. Different effects on contractile dynamics may offer clue regarding how and cause divergent effects on cardiac phenotypes.