期刊
BIOPHYSICAL JOURNAL
卷 90, 期 11, 页码 4119-4127出版社
CELL PRESS
DOI: 10.1529/biophysj.105.078147
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- NHLBI NIH HHS [R37 HL082900, P01 HL 47053, P01 HL047053, R01 HL 82900] Funding Source: Medline
- NIAMS NIH HHS [AR 02110] Funding Source: Medline
Myosin-binding protein-C (MyBP-C) is a thick filament-associated protein that binds tightly to myosin. Given that cMyBP-C may act to modulate cooperative activation of the thin. lament by constraining the availability of myosin cross-bridges for binding to actin, we investigated the role of MyBP-C in the regulation of cardiac muscle contraction. We assessed the Ca2+ sensitivity of force (pCa(50)) and the activation dependence of the rate of force redevelopment (k(tr)) in skinned myocardium isolated from wild-type (WT) and cMyBP-C null (cMyBP-C-/-) mice. Mechanical measurements were performed at 22 degrees C in the absence and presence of a strong-binding, nonforce-generating analog of myosin subfragment-1 (NEM-S1). In the absence of NEM-S1, maximal force and k(tr) and the pCa(50) of isometric force did not differ between WT and cMyBP-C-/- myocardium; however, ablation of cMyBP-C-accelerated k(tr) at each submaximal force. Treatment of WT and cMyBP-C-/- myocardium with 3 mu M NEM-S1 elicited similar increases in pCa(50), but the effects of NEM-S1 to increase k(tr) at submaximal forces and thereby markedly reduce the activation dependence of ktr occurred to a greater degree in cMyBP-C-/- myocardium. Together, these results support the idea that cMyBP-C normally acts to constrain the interaction between myosin and actin, which in turn limits steady- state force development and the kinetics of cross- bridge interaction.
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