Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle
Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle
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DOI：
10.1113/jphysiol.2003.049759
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发表时间：
2003-11-15
影响因子：
5.5
通讯作者：
Granzier, H
中科院分区：
文献类型：
--
作者：
Fukuda, N;Wu, YM;Granzier, H
我们已经探索了巨大的弹性蛋白肌联蛋白在心脏的Frank-Starling机制的作用，通过测量肌节长度（SL）依赖于不同肌联蛋白为基础的被动刚度特性的皮肤心肌激活。我们研究了牛左心室（BLV）的肌肉，它表达了高水平的刚性肌联蛋白亚型，和牛左心房（BLA）的肌肉，它表达了更顺应肌联蛋白亚型。被动张力也不同，在每种肌肉类型通过操纵激活前的拉伸前的历史。我们发现，SL依赖性的Ca 2+敏感性和最大Ca 2+激活张力的增加显着更明显时，肌联蛋白为基础的被动张力高。小角度X射线衍射实验表明，SL的依赖性减少的丝间晶格间距是更大的BLV比BLA和晶格间距耦合与钛基被动张力。这些结果支持的概念，肌联蛋白为基础的被动张力促进肌动球蛋白的相互作用，通过减少晶格间距。这项工作表明，肌联蛋白可能是一个因素参与的Frank-Starling机制的心脏，通过促进肌动球蛋白相互作用，响应拉伸。
We have explored the role of the giant elastic protein titin in the Frank-Starling mechanism of the heart by measuring the sarcomere length (SL) dependence of activation in skinned cardiac muscles with different titin-based passive stiffness characteristics. We studied muscle from the bovine left ventricle (BLV), which expresses a high level of a stiff titin isoform, and muscle from the bovine left atrium (BLA), which expresses more compliant titin isoforms. Passive tension was also varied in each muscle type by manipulating the pre-history of stretch prior to activation. We found that the SL-dependent increases in Ca2+ sensitivity and maximal Ca2+-activated tension were markedly more pronounced when titin-based passive tension was high. Small-angle X-ray diffraction experiments revealed that the SL dependence of reduction of interfilament lattice spacing is greater in BLV than in BLA and that the lattice spacing is coupled with titin-based passive tension. These results support the notion that titin-based passive tension promotes actomyosin interaction by reducing the lattice spacing. This work indicates that titin may be a factor involved in the Frank-Starling mechanism of the heart by promoting actomyosin interaction in response to stretch.