Proposed mechanism for the length dependence of the force developed in maximally activated muscles View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-02-04

AUTHORS

Lorenzo Marcucci, Takumi Washio, Toshio Yanagida

ABSTRACT

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. More... »

PAGES

1317

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-36706-4

DOI

http://dx.doi.org/10.1038/s41598-018-36706-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111916571

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30718530


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