Activation of Myocardial Contraction by the N-Terminal Domains of Myosin Binding Protein-C
| Author(s) | Todd J. Herron, Elena Rostkova, Gudrun Kunst, Rajiv Chaturvedi, Mathias Gautel, and Jonathan C. Kentish |
| Journal | Circ. Res., 98 |
Method Extract | |
| ... ...recovery trace. SL in the relaxed myocytes was computed online by Fast-Fourier analysis of the video image of the myocyte (IonOptix, Milton, Mass). Transfection of MyBP-C Fragments Cardiac MyBP-C fragments containing domains C0, C0-C1, C1-C2, C0-C2... ... | |
Abstract | |
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Abstract sarcomeres. Its C terminus binds tightly to myosin, whereas the N terminus contains binding sites for myosin S2 and possibly for the thin filament. To study the role of the N-terminal domains of cardiac MyBP-C (cMyBP-C), we added human N-terminal peptide fragments to human and rodent skinned ventricular myocytes. At concentrations —Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in striated muscleoptimal concentration (80 tension redevelopment ( different N-terminal peptides suggested that this activating effect of C0C2 resulted from binding by the pro/ala-rich C0-C1 linker region, rather than the terminal C0 domain. At a lower concentration (1 strongly sensitized cardiac myofibrils to Ca 2.3 (mouse myocytes) or abolished (human myocytes) in 1 regulatory pathway by which the thick filament can influence the activation of the thin filament, separately from its regulation by Ca relationship in cardiac muscle. 10 mol/L, the N-terminal C0C2 peptide activated force production in the absence of calcium (pCa 9). Force at themol/L) of C0C2 was 60% of that in maximal Ca2 (pCa 4.5), but the rate constant ofktr) matched or exceeded (by up to 80%) that produced by Ca2 alone. Experiments usingmol/L), exogenous C0C22 at a sarcomere length (SL) of 1.9 m but had no significant effect at SLm. This differential effect caused the normal SL dependence of myofibrillar Ca2 sensitivity to be reduced by 80%mol/L C0C2. These results suggest that cMyBP-C provides a2. Furthermore, the N-terminal region of cMyBP-C can influence the SL-tension (Frank–Starling)(Circ Res. 2006;98:1290-1298.) | |
| Keywords | sarcomere length, permeabilized myocytes, skinned myocytes |