Sequeira Vasco, van der Velden Jolanda
Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, O|2 building, 11W-53, De Boelelaan 1118, 1081 HV, Amsterdam, the Netherlands.
ICIN- Netherlands Heart Institute, Utrecht, The Netherlands.
Biophys Rev. 2017 Jun;9(3):259-267. doi: 10.1007/s12551-017-0272-8. Epub 2017 Jun 21.
The Frank-Starling Law dictates that the heart is able to match ejection to the dynamic changes occurring during cardiac filling, hence efficiently regulating isovolumetric contraction and shortening. In the last four decades, efforts have been made to identify a common fundamental basis for the Frank-Starling heart that can explain the direct relationship between muscle lengthening and its increased sensitization to Ca. The term 'myofilament length-dependent activation' describes the length-dependent properties of the myofilaments, but what is(are) the underlying molecular mechanism(s) is a matter of ongoing debate. Length-dependent activation increases formation of thick-filament strongly-bound cross-bridges on actin and imposes structural-mechanical alterations on the thin-filament with greater than normal bound Ca. Stretch-induced effects, rather than changes in filament spacing, appear to be primarily involved in the regulation of length-dependent activation. Here, evidence is provided to support the notion that stretch-mediated effects induced by titin govern alterations of thick-filament force-producing cross-bridges and thin-filament Ca-cooperative responses.
弗兰克 - 斯塔林定律表明，心脏能够使射血与心脏充盈期间发生的动态变化相匹配，从而有效地调节等容收缩和缩短。在过去的四十年里，人们一直在努力寻找弗兰克 - 斯塔林心脏的共同基本基础，以解释肌肉拉长与其对钙敏感性增加之间的直接关系。“肌丝长度依赖性激活”一词描述了肌丝的长度依赖性特性，但潜在的分子机制是什么仍存在争议。长度依赖性激活增加了肌动蛋白上粗肌丝强结合横桥的形成，并对结合钙高于正常水平的细肌丝施加结构 - 力学改变。拉伸诱导的效应，而非细丝间距的变化，似乎主要参与长度依赖性激活的调节。在此，提供证据支持这样一种观点，即肌联蛋白诱导的拉伸介导效应控制着粗肌丝产生力的横桥的改变以及细肌丝钙协同反应。
