Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1833, Issue 4, Pages 804-811Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2012.08.011
Keywords
Titin; Myofilament length dependent activation; Sarcomere length; Actin-myosin interaction
Categories
Funding
- NIH [HL62426, HL07692, HL075494, HL77196]
Ask authors/readers for more resources
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=2.8 mu m and SL = 3.2 mu m, respectively). Moreover, the SL-dependent changes in these parameters were attenuated in HM muscles. Additionally, myofilament Ca2+ activation-relaxation properties were assessed in single isolated myofibrils. Both the rate of tension generation upon Ca2+ activation (k(ACT)) as well as the rate of tension redevelopment following a length perturbation (k(TR)) 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. (C) 2012 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available