| First Author | Mamidi R | Year | 2014 |
| Journal | Front Physiol | Volume | 5 |
| Pages | 461 | PubMed ID | 25520665 |
| Mgi Jnum | J:310509 | Mgi Id | MGI:6759936 |
| Doi | 10.3389/fphys.2014.00461 | Citation | Mamidi R, et al. (2014) Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation. Front Physiol 5:461 |
| abstractText | 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 mum or 2.1 mum. 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 mum vs. 5.71 +/- 0.40 s(-1) at 2.1 mum, 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 mum vs. 8.90 +/- 0.37 s(-1) at 2.1 mum). 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. |
