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Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number13281
Pages (from-to)1-9
JournalNature Communications
Early online date31 Oct 2016
Accepted/In press19 Sep 2016
E-pub ahead of print31 Oct 2016
Published31 Oct 2016


King's Authors


Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.

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