文章基本信息

标题：Proposed mechanism for the length dependence of the force developed in maximally activated muscles
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作者：Lorenzo Marcucci ; Takumi Washio ; Toshio Yanagida 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-13
DOI：10.1038/s41598-018-36706-4
出版社：Springer Nature
摘要：The molecular bases of the Frank-Starling law of the heart and of its cellular counterpart, the length dependent activation (LDA), are largely unknown. However, the recent discovery of the thick filament activation, a second pathway beside the well-known calcium mediated thin filament activation, is promising for elucidating these mechanisms. The thick filament activation is mediated by the tension acting on it through the mechano-sensing (MS) mechanism and can be related to the LDA via the titin passive tension. Here, we propose a mechanism to explain the higher maximum tension at longer sarcomere lengths generated by a maximally activated muscle and test it in-silico with a single fiber and a ventricle model. The active tension distribution along the thick filament generates a reservoir of inactive motors at its free-end that can be activated by passive tension on a beat-to-beat timescale. The proposed mechanism is able to quantitatively account for the observed increment in tension at the fiber level, however, the ventricle model suggests that this component of the LDA is not crucial in physiological conditions.