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Mechanisms of Frank-Starling law of the heart and stretch activation in striated muscles may have a common molecular origin
Journal of Muscle Research and Cell Motility ( IF 2.7 ) Pub Date : 2021-02-11 , DOI: 10.1007/s10974-020-09595-2
Masataka Kawai 1 , Jian-Ping Jin 2
Affiliation  

Vertebrate cardiac muscle generates progressively larger systolic force when the end diastolic chamber volume is increased, a property called the “Frank-Starling Law”, or “length dependent activation (LDA)”. In this mechanism a larger force develops when the sarcomere length (SL) increased, and the overlap between thick and thin filament decreases, indicating increased production of force per unit length of the overlap. To account for this phenomenon at the molecular level, we examined several hypotheses: as the muscle length is increased, (1) lattice spacing decreases, (2) Ca2+ sensitivity increases, (3) titin mediated rearrangement of myosin heads to facilitate actomyosin interaction, (4) increased SL activates cross-bridges (CBs) in the super relaxed state, (5) increased series stiffness at longer SL promotes larger elementary force/CB to account for LDA, and (6) stretch activation (SA) observed in insect muscles and LDA in vertebrate muscles may have similar mechanisms. SA is also known as delayed tension or oscillatory work, and universally observed among insect flight muscles, as well as in vertebrate skeletal and cardiac muscles. The sarcomere stiffness observed in relaxed muscles may significantly contributes to the mechanisms of LDA. In vertebrate striated muscles, the sarcomere stiffness is mainly caused by titin, a single filamentary protein spanning from Z-line to M-line and tightly associated with the myosin thick filament. In insect flight muscles, kettin connects Z-line and the thick filament to stabilize the sarcomere structure. In vertebrate cardiac muscles, titin plays a similar role, and may account for LDA and may constitute a molecular mechanism of Frank-Starling response.



中文翻译:

弗兰克-斯塔林心脏定律和横纹肌拉伸激活的机制可能具有共同的分子起源

当舒张末期容积增加时,脊椎动物心肌会产生逐渐增大的收缩力,这一特性称为“弗兰克-史达林定律”或“长度依赖性激活 (LDA)”。在这种机制中,当肌节长度 (SL) 增加时,会产生更大的力,并且粗细丝之间的重叠减少,表明每单位重叠长度产生的力增加。为了在分子水平上解释这种现象,我们检验了几个假设:随着肌肉长度的增加,(1)晶格间距减小,(2)Ca 2+敏感性增加,(3)肌动蛋白介导的肌球蛋白头重排以促进肌动球蛋白相互作用,(4)增加的SL在超松弛状态下激活交叉桥(CB),(5)更长的SL增加系列刚度促进更大的基本力/ CB考虑到 LDA,以及 (6) 在昆虫肌肉中观察到的拉伸激活 (SA) 和脊椎动物肌肉中的 LDA 可能具有相似的机制。SA 也称为延迟张力或振荡工作,在昆虫飞行肌肉以及脊椎动物骨骼肌和心肌中普遍观察到。在放松的肌肉中观察到的肌节僵硬可能对 LDA 的机制有重要影响。在脊椎动物横纹肌中,肌节僵硬主要由肌动蛋白引起,一种从 Z 线到 M 线的单一丝状蛋白,与肌球蛋白粗丝紧密结合。在昆虫飞行肌肉中,kettin 连接 Z 线和粗丝以稳定肌节结构。在脊椎动物的心肌中,titin 起着类似的作用,可能是 LDA 的原因,并可能构成 Frank-Starling 反应的分子机制。

更新日期:2021-02-11
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