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Mamidi R, Gresham KS, Stelzer JE. Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation. Front Physiol. 2014;5:461doi: 10.3389/fphys.2014.00461.
Mamidi, R., Gresham, K. S., & Stelzer, J. E. (2014). Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation. Frontiers in physiology, 5461. https://doi.org/10.3389/fphys.2014.00461
Mamidi, Ranganath, et al. "Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation." Frontiers in physiology vol. 5 (2014): 461. doi: https://doi.org/10.3389/fphys.2014.00461
Mamidi R, Gresham KS, Stelzer JE. Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation. Front Physiol. 2014 Dec 02;5:461. doi: 10.3389/fphys.2014.00461. eCollection 2014. PMID: 25520665; PMCID: PMC4251301.
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Front Physiol. 2014 Dec 02;5:461. doi: 10.3389/fphys.2014.00461. eCollection 2014.

Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation.

Frontiers in physiology

Ranganath Mamidi, Kenneth S Gresham, Julian E Stelzer

Affiliations

  1. Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University Cleveland, OH, USA.

PMID: 25520665 PMCID: PMC4251301 DOI: 10.3389/fphys.2014.00461

Abstract

Enhanced cardiac contractile function with increased sarcomere length (SL) is, in part, mediated by a decrease in the radial distance between myosin heads and actin. The radial disposition of myosin heads relative to actin is modulated by cardiac myosin binding protein-C (cMyBP-C), suggesting that cMyBP-C contributes to the length-dependent activation (LDA) in the myocardium. However, the precise roles of cMyBP-C in modulating cardiac LDA are unclear. To determine the impact of cMyBP-C on LDA, we measured isometric force, myofilament Ca(2+)-sensitivity (pCa50) and length-dependent changes in kinetic parameters of cross-bridge (XB) relaxation (k rel), and recruitment (k df) due to rapid stretch, as well as the rate of force redevelopment (k tr) in response to a large slack-restretch maneuver in skinned ventricular multicellular preparations isolated from the hearts of wild-type (WT) and cMyBP-C knockout (KO) mice, at SL's 1.9 μm or 2.1 μm. Our results show that maximal force was not significantly different between KO and WT preparations but length-dependent increase in pCa50 was attenuated in the KO preparations. pCa50 was not significantly different between WT and KO preparations at long SL (5.82 ± 0.02 in WT vs. 5.87 ± 0.02 in KO), whereas pCa50 was significantly different between WT and KO preparations at short SL (5.71 ± 0.02 in WT vs. 5.80 ± 0.01 in KO; p < 0.05). The k tr, measured at half-maximal Ca(2+)-activation, was significantly accelerated at short SL in WT preparations (8.74 ± 0.56 s(-1) at 1.9 μm vs. 5.71 ± 0.40 s(-1) at 2.1 μm, p < 0.05). Furthermore, k rel and k df were accelerated by 32% and 50%, respectively at short SL in WT preparations. In contrast, k tr was not altered by changes in SL in KO preparations (8.03 ± 0.54 s(-1) at 1.9 μm vs. 8.90 ± 0.37 s(-1) at 2.1 μm). Similarly, KO preparations did not exhibit length-dependent changes in k rel and k df. Collectively, our data implicate cMyBP-C as an important regulator of LDA via its impact on dynamic XB behavior due to changes in SL.

Keywords: cMyBP-C; cross-bridge kinetics; length-dependent activation; myofilament function; sarcomere length

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