Journal article
Cardiomyopathy-Related Mutations in Cardiac Troponin C, L29Q and G159D, Have Divergent Effects on Rat Cardiac Myofiber Contractile Dynamics
Biochemistry research international, Vol.2012, pp.1-11
2012
Handle:
https://hdl.handle.net/2376/112620
PMCID: PMC3447348
PMID: 23008774
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 bothCa2+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 (cTnCWT),cTnCL29Q, andcTnCG159Dmutants.cTnCL29Qfibers demonstrated a significant decrease inCa2+sensitivity, butcTnCG159Dfibers did not. Both mutants had no effect onCa2+-activated maximal tension. The rate of XB recruitment dynamics increased incTnCL29Q(26%) andcTnCG159D(25%) fibers. The rate of XB distortion dynamics increased incTnCG159Dfibers (15%). Thus, thecTnCL29Qmutant modulates the equilibrium between the non-cycling and cycling pool of XB by affecting theon/offkinetics of the regulatory units (Tropomyosin-Troponin); whereas, thecTnCG159Dmutant increases XB cycling rate. Different effects on contractile dynamics may offer clue regarding howcTnCL29QandcTnCG159Dcause divergent effects on cardiac phenotypes.
Metrics
5 Record Views
Details
- Title
- Cardiomyopathy-Related Mutations in Cardiac Troponin C, L29Q and G159D, Have Divergent Effects on Rat Cardiac Myofiber Contractile Dynamics
- Creators
- Sampath K Gollapudi - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology (VCAPP), Washington State University, Pullman, WA 99164-6520, USAMurali Chandra - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology (VCAPP), Washington State University, Pullman, WA 99164-6520, USA
- Publication Details
- Biochemistry research international, Vol.2012, pp.1-11
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Identifiers
- 99900548274601842
- Language
- English
- Resource Type
- Journal article