Activation of mTORC1 signalling in rat skeletal muscle is independent of the EC-coupling sequence but dependent on tension per se in a dose-response relationship

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Aim: mTORC1 is regarded as an important key regulator of protein synthesis and hypertrophy following mechanical stimuli in skeletal muscle. However, as excitation and tension development is tightly coupled in most experimental models, very little and largely indirect evidence exist for such a mechanosensitive pathway. Here, we sought to examine whether activation of mTORC1 signalling is dependent on tension per se in rat skeletal muscle. Methods: To examine the mechanosensitivity of mTORC1, rat EDL muscles were exposed to either excitation-induced eccentric contractions (ECC), passive stretching (PAS) with identical peak tension (Tpeak) and Tension-Time-Integral (TTI), or ECC with addition of inhibitors of the myosin ATPases (IMA). To further explore the relationship between tension and mTORC1 signalling, rat EDL muscles were subjected to PAS of different magnitudes of Tpeak while standardizing TTI and vice versa. Results: PAS and ECC with equal Tpeak and TTI produced similar responses in mTORC1 signalling despite different modes of tension development. When active tension during ECC was nearly abolished by addition of IMA, mTORC1 signalling was reduced to a level comparable to non-stimulated controls. In addition, when muscles were exposed to PAS of varying levels of Tpeak with standardized TTI, activation of mTORC1 signalling displayed a positive relationship with peak tension. Conclusions: The current study directly links tension per se to activation of mTORC1 signalling, which is independent of an active EC-coupling sequence. Moreover, activation of mTORC1 signalling displays a positive dose-response relationship with peak tension.

OriginalsprogEngelsk
Artikelnummere13336
TidsskriftActa Physiologica
Vol/bind227
Nummer3
Antal sider12
ISSN1748-1708
DOI
StatusUdgivet - nov. 2019

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