Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C

Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C
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DOI:
10.1023/b:mcbi.0000041849.60591.45
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发表时间:
2004-08-01
影响因子:
4.3
通讯作者:
Maughan, DW
Maughan, DW
中科院分区:
生物学3区
文献类型:
--
作者:
Palmer, BM;McConnell, BK;Maughan, DW

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在野生型(WT+/+)和纯合截短心脏MyBP-C(MyBP-C-t/t)雄性小鼠的皮肤乳头肌中检查心脏肌球蛋白结合蛋白-C(MyBP-C)对心肌硬度的作用。在MyBP-C-t/t心肌中通过凝胶电泳或Western印迹未检测到MyBP-C。强直桥依赖性肌丝刚度,即,MyBP-Ct/t心肌的僵硬度减去松弛刚度(281 +/- 44 kN/m(2))是WT+/+(633 +/- 141 kN/m(2))的44%。通过X射线衍射测定的MyBP-C-t/t中粗丝之间的中心间距(45.0 +/- 1.2 nm)与WT+/+中的中心间距(43.2 +/- 0.9 nm)无显著差异。如通过电子显微镜测定的,与WT+/+(44.5%)相比,MyBP-Ct/t(39.9%)中由肌原纤维组成的横截面积的分数减少了10%。这些数据表明,去皮MyBP-C-t/t心肌的刚性桥依赖性刚度降低56%可能不仅仅是由于每横截面积粗丝数量减少10%,还必须是由于缺乏MyBP-C的刚性桥连接粗丝刚度降低约50%。
The role of cardiac myosin binding protein-C (MyBP-C) on myocardial stiffness was examined in skinned papillary muscles of wild-type (WT+/+) and homozygous truncated cardiac MyBP-C (MyBP-C-t/t) male mice. No MyBP-C was detected by gel electrophoresis or by Western blots in the MyBP-C-t/t myocardium. Rigor-bridge dependent myofilament stiffness, i.e., rigor minus relaxed stiffness, in the MyBP-Ct/t myocardium (281 +/- 44 kN/m(2)) was 44% that in WT+/+ (633 +/- 141 kN/m(2)). The center-to-center spacing between thick filaments as determined by X-ray diffraction in MyBP-C-t/t (45.0 +/- 1.2 nm) was not significantly different from that in WT+/+ (43.2 +/- 0.9 nm). The fraction of cross-sectional area comprised of myofibrils, as determined by electron microscopy, was reduced in the MyBP-Ct/t (39.9%) by 10% compared to WT+/+ (44.5%). These data suggest that the 56% reduction in rigor-bridge dependent stiffness of the skinned MyBP-C-t/t myocardium could not be due solely to a 10% reduction in the number of thick filaments per cross-sectional area and must also be due to approximately 50% reduction in the stiffness of the rigor-bridge attached thick filaments lacking MyBP-C.