Impact of titin isoform on length dependent activation and cross-bridge cycling kinetics in rat skeletal muscle Journal Article

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Authors: Mateja, R. D.; Greaser, M. L.; de Tombe, P. P.
Article Title: Impact of titin isoform on length dependent activation and cross-bridge cycling kinetics in rat skeletal muscle
Abstract: The magnitude of length dependent activation in striated muscle has been shown to vary with titin isoform. Recently, a rat that harbors a homozygous autosomal mutation (HM) causing preferential expression of a longer, giant titin isoform was discovered (Greaser et al. 2005). Here, we investigated the impact of titin isoform on myofilament force development and cross-bridge cycling kinetics as function of sarcomere length (SL) in tibialis anterior skeletal muscle isolated from wild type (WT) and HM. Skeletal muscle bundles from HM rats exhibited reductions in passive tension, maximal force development, myofilament calcium sensitivity, maximal ATP consumption, and tension cost at both short and long sarcomere length (SL=2.8mum and SL=3.2mum, respectively). Moreover, the SL-dependent changes in these parameters were attenuated in HM muscles. Additionally, myofilament Ca(2+) activation-relaxation properties were assessed in single isolated myofibrils. Both the rate of tension generation upon Ca(2+) activation (kACT) as well as the rate of tension redevelopment following a length perturbation (kTR) were reduced in HM myofibrils compared to WT, while relaxation kinetics were not affected. We conclude that presence of a long isoform of titin in the striated muscle sarcomere is associated with reduced myofilament force development and cross-bridge cycling kinetics, and a blunting of myofilament length dependent activation. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.
Journal Title: Biochimica et biophysica acta
Volume: 1833
Issue: 4
ISSN: 0006-3002; 0006-3002
Publisher: Elsevier Inc  
Journal Place: Netherlands
Date Published: 2013
Start Page: 804
End Page: 811
Language: eng
DOI/URL:

10.1016/j.bbamcr.2012.08.011

10.1016/j.bbamcr.2012.08.011
Notes: ID: 13175; CI: Copyright (c) 2012; GR: HL075494/HL/NHLBI NIH HHS/United States; GR: HL07692/HL/NHLBI NIH HHS/United States; GR: HL62426/HL/NHLBI NIH HHS/United States; GR: P01 HL062426/HL/NHLBI NIH HHS/United States; GR: R01 HL075494/HL/NHLBI NIH HHS/United States; GR: R01 HL077196/HL/NHLBI NIH HHS/United States; GR: T32 HL007692/HL/NHLBI NIH HHS/United States; JID: 0217513; NIHMS402838; OID: NLM: NIHMS402838 [Available on 04/01/14]; OID: NLM: PMC3518735 [Available on 04/01/14]; PMCR: 2014/04/01 00:00; 2012/07/04 [received]; 2012/08/09 [revised]; 2012/08/10 [accepted]; 2012/08/23 [aheadofprint]; ppublish