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Deletion of the titin N2B region accelerates myofibrillar force development but does not alter relaxation kinetics

Item Type:Article
Title:Deletion of the titin N2B region accelerates myofibrillar force development but does not alter relaxation kinetics
Creators Name:Elhamine, F. and Radke, M. and Pfitzer, G. and Granzier, H. and Gotthardt, M. and Stehle, R.
Abstract:Cardiac titin is the main determinant of sarcomere stiffness during diastolic relaxation. To explore whether titin stiffness affects the kinetics of cardiac myofibrillar contraction and relaxation, we used subcellular myofibrils from left ventricles of homozygous (KO) and heterozygous (HET) N2B-KO mice which express truncated cardiac titins lacking the unique elastic N2B region. Compared to myofibrils from wildtype (WT) mice, myofibrils from KO and HET mice exhibit increased passive myofibrillar stiffness. To determine the kinetics of Ca(2+)-induced force development (rate constant kACT), myofibrils from KO, HET and WT mice were stretched to the same sarcomere length (2.3 µm) and rapidly Ca(2+) activated. Additionally, mechanically-induced force redevelopment kinetics (rate constant kTR) was determined by slackening and re-stretching myofibrils during Ca(2+) activation. Myofibrils from KO mice exhibited significant higher kACT, kTR and maximum Ca(2+) activated tension than myofibrils from WT. In contrast, the kinetic parameters of biphasic force relaxation induced by rapidly reducing [Ca(2+)] were not significantly different among the three genotypes. These results indicate that increased titin stiffness promotes myocardial contraction by accelerating the formation of force-generating cross-bridges without decelerating relaxation.
Keywords:Cross-Bbridge Kinetics, Muscle Relaxation, Passive Tension, Titin Genotype Effects, Diastolic Dysfunction, Animals, Mice
Source:Journal of Cell Science
ISSN:0021-9533
Publisher:Company of Biologists
Volume:127
Number:Pt 17
Page Range:3666-3674
Date:1 September 2014
Official Publication:https://doi.org/10.1242/jcs.141796
PubMed:View item in PubMed

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