The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers

Sampath K Gollapudi; Clare E Gallon; Murali Chandra

doi:10.1016/j.jmb.2013.01.028

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The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers

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The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers

Sampath K Gollapudi, Clare E Gallon and Murali Chandra

Journal of molecular biology, Vol.425(9), pp.1565-1581

05/13/2013

DOI: https://doi.org/10.1016/j.jmb.2013.01.028

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https://hdl.handle.net/2376/110854

PMCID: PMC3633627

PMID: 23357173

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Abstract

thin filament activation

cardiac troponin T

regulatory proteins

contractile dynamics

allosteric interaction

The cardiac muscle comprises dynamically interacting components that use allosteric/cooperative mechanisms to yield unique heart-specific properties. An essential protein in this allosteric/cooperative mechanism is cardiac muscle troponin T (cTnT), the central region (CR) and the T2 region of which differ significantly from those of fast skeletal muscle troponin T (fsTnT). To understand the biological significance of such sequence heterogeneity, we replaced the T1 or T2 domain of rat cTnT (RcT1 or RcT2) with its counterpart from rat fsTnT (RfsT1or RfsT2) to generate RfsT1-RcT2 and RcT1-RfsT2 recombinant proteins. In addition to contractile function measurements, dynamic features of RfsT1-RcT2- and RcT1-RfsT2-reconstituted rat cardiac muscle fibers were captured by fitting the recruitment–distortion model to the force response of small-amplitude (0.5%) muscle length changes. RfsT1-RcT2 fibers showed a 40% decrease in tension and a 44% decrease in ATPase activity, but RcT1-RfsT2 fibers were unaffected. The magnitude of length-mediated increase in crossbridge (XB) recruitment (E0) decreased by ~33% and the speed of XB recruitment (b) increased by ~100% in RfsT1-RcT2 fibers. Our data suggest the following: (1) the CR of cTnT modulates XB recruitment dynamics; (2) the N-terminal end region of cTnT has a synergistic effect on the ability of the CR to modulate XB recruitment dynamics; (3) the T2 region is important for tuning the Ca2+ regulation of cardiac thin filaments. The combined effects of CR–tropomyosin interactions and the modulating effect of the N-terminal end of cTnT on CR–tropomyosin interactions may lead to the emergence of a unique property that tunes contractile dynamics to heart rates. [Display omitted] ► The biological significance of sequence heterogeneity in cTnT is unknown. ► Myofilament cooperativity is modulated by the CR of cTnT. ► The CR of cTnT modulates the speed of XB recruitment dynamics. ► The N-terminus of cTnT affects the ability of the CR to interact with tropomyosin. ► A unique heart-specific feature emerges from the synergistic effect of N-terminus on CR.

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Title: The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers
Creators: Sampath K Gollapudi - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164-6520, USA
Clare E Gallon - University of Exeter Medical School, St Luke's Campus, Exeter EX1 2LU, UK
Murali Chandra - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164-6520, USA
Publication Details: Journal of molecular biology, Vol.425(9), pp.1565-1581
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier Ltd
Identifiers: 99900547025901842
Language: English
Resource Type: Journal article