Universität zu Köln

Elhamine, Fatiha, Radke, Michael H., Pfitzer, Gabriele, Granzier, Henk, Gotthardt, Michael ORCID: 0000-0003-1788-3172 and Stehle, Robert (2014). Deletion of the titin N2B region accelerates myofibrillar force development but does not alter relaxation kinetics. J. Cell Sci., 127 (17). S. 3666 - 3675. CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9137

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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 the left ventricles of homozygous and heterozygous N2B-knockout mice which express truncated cardiac titins lacking the unique elastic N2B region. Compared with myofibrils from wild-type mice, myofibrils from knockout and heterozygous mice exhibit increased passive myofibrillar stiffness. To determine the kinetics of Ca2+-induced force development (rate constant k(ACT)), myofibrils from knockout, heterozygous and wildtype mice were stretched to the same sarcomere length (2.3 mu m) and rapidly activated with Ca2+. Additionally, mechanically induced force-redevelopment kinetics (rate constant k(TR)) were determined by slackening and re-stretching myofibrils during Ca2+-mediated activation. Myofibrils from knockout mice exhibited significantly higher k(ACT), k(TR) and maximum Ca2+-activated tension than myofibrils from wild-type mice. By contrast, the kinetic parameters of biphasic force relaxation induced by rapidly reducing [Ca2+] 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Elhamine, Fatiha UNSPECIFIED UNSPECIFIED UNSPECIFIED Radke, Michael H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Granzier, Henk UNSPECIFIED UNSPECIFIED UNSPECIFIED Gotthardt, Michael UNSPECIFIED orcid.org/0000-0003-1788-3172 UNSPECIFIED Stehle, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-430164
DOI:	10.1242/jcs.141796
Journal or Publication Title:	J. Cell Sci.
Volume:	127
Number:	17
Page Range:	S. 3666 - 3675
Date:	2014
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9137
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LENGTH-DEPENDENT ACTIVATION; FRANK-STARLING MECHANISM; CALCIUM SENSITIVITY; SARCOMERE-LENGTH; CARDIAC-MUSCLE; TROPONIN-I; MYOCARDIUM; LATTICE; TENSION; MURINE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43016