Mechanisms of Frank-Starling law of the heart and stretch activation in striated muscles may have a common molecular origin
Mechanisms of Frank-Starling law of the heart and stretch activation in striated muscles may have a common molecular origin
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DOI：
10.1007/s10974-020-09595-2
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发表时间：
2021-02-11
影响因子：
2.7
通讯作者：
Jin, Jian-Ping
中科院分区：
文献类型：
--
作者：
Kawai, Masataka;Jin, Jian-Ping
当舒张末容量增加时，脊椎动物的心肌会产生越来越大的收缩压力，这一特性被称为“弗兰克-斯塔林定律”，或“长度依赖激活(LDA)”。在这一机制中，随着肌节长度(SL)的增加，产生更大的力，而粗丝和细丝之间的重叠减少，表明单位长度的重叠产生的力增加。为了在分子水平上解释这种现象，我们检验了几个假说：随着肌肉长度的增加，(1)晶格间距减小，(2)钙敏感性增加，(3)肌球蛋白头的重排促进肌球蛋白的相互作用，(4)在超松弛状态下SL的增加激活了交叉桥(CBS)，(5)较长SL的串联刚度增加促进了更大的基本力/CB来解释LDA，以及(6)在昆虫肌肉中观察到的拉伸激活(SA)和在脊椎动物肌肉中观察到的LDA可能具有类似的机制。SA也被称为延迟张力或振荡功，普遍存在于昆虫的飞行肌肉以及脊椎动物的骨骼肌和心肌中。在松弛的肌肉中观察到的肌节僵硬可能对LDA的机制有重要贡献。在脊椎动物横纹肌中，肌节僵硬主要是由肌球蛋白引起的，肌球蛋白是一种从Z线到M线的单一丝状蛋白，与肌球蛋白粗丝紧密相关。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，肌动蛋白发挥着类似的作用，可能解释了LDA，并可能构成Frank-Starling反应的分子机制。
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.