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SR Ca2+ leak in skeletal muscle fibers increases fatigue resistance

pattismith

Senior Member
Messages
3,931
SR Ca2+ leak in skeletal muscle fibers acts as an intracellular signal to increase fatigue resistance


Abstract

Effective practices to improve skeletal muscle fatigue resistance are crucial for athletes as well as patients with dysfunctional muscles. To this end, it is important to identify the cellular signaling pathway that triggers mitochondrial biogenesis and thereby increases oxidative capacity and fatigue resistance in skeletal muscle fibers. Here, we test the hypothesis that the stress induced in skeletal muscle fibers by endurance exercise causes a reduction in the association of FK506-binding protein 12 (FKBP12) with ryanodine receptor 1 (RYR1).
This will result in a mild Ca2+ leak from the sarcoplasmic reticulum (SR), which could trigger mitochondrial biogenesis and improved fatigue resistance. After giving mice access to an in-cage running wheel for three weeks, we observed decreased FKBP12 association to RYR1, increased baseline [Ca2+]i, and signaling associated with greater mitochondrial biogenesis in muscle, including PGC1α1. After six weeks of voluntary running, FKBP12 association is normalized, baseline [Ca2+]i returned to values below that of nonrunning controls, and signaling for increased mitochondrial biogenesis was no longer present.

The adaptations toward improved endurance exercise performance that were observed with training could be mimicked by pharmacological agents that destabilize RYR1 and thereby induce a modest Ca2+ leak.

We conclude that a mild RYR1 SR Ca2+ leak is a key trigger for the signaling pathway that increases muscle fatigue resistance.


  • Accepted: 16 November 2018
 

Violeta

Senior Member
Messages
2,895
I just found this study saying that NADPH affects the sarcoplasmic reticulum release of calcium. I'm not sure what to think of it, or how I could use the information.

https://www.ncbi.nlm.nih.gov/pubmed/14699012

Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome​


https://www.sciencedirect.com/science/article/abs/pii/S0960896603000427

Furthermore, in another study CFS/ME patients were reported to exhibit a reported a loss of Na+/K+ and Ca+, -ATPase pump regulation, as well as alterations in the ryanodine channels within the sarcoplasmic reticulum membrane. This was related to increased fluidity of the sarcoplasmic membrane due to ROS induced formation of lipid hydroperoxides, which the authors suggested to support the hypothesis that sarcolemma conduction system with some aspects of Ca+ transport was negatively influenced in CFS/ME.

Homeopathic calcium phosphate helps with one of my first symptoms of ME/CFS, muscles of the legs discomfort on going up stairs. (A homeopathic remedy can correct the body's use of a mineral.)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278904/#:~:text=We propose that inorganic phosphate,performance as originally suggested by

Role of phosphate and calcium stores in muscle fatigue​


We propose that inorganic phosphate (Pi), which increases substantially during fatigue, may enter the sarcoplasmic reticulum (SR), combine with Ca2+ and form an insoluble precipitate of calcium phosphate (CaPi), leading to reduced SR Ca2+ release and a consequent decline in muscle performance as originally suggested by Fryer et al. (1995). This mechanism provides a simple explanation for the failure of SR Ca2+ release in fatigue and may lend itself to therapeutic interventions in the future.

What would cause the increase of phosphate during fatigue?

Initial evidence came from the observation that increasing [Pi]myo causes reduced SR Ca2+ release in both skinned and intact fibres. In fatigued muscles the store of releasable Ca2+ in the SR declines mirroring the decline in SR Ca2+ release. In muscle fibres with inoperative creatine kinase the rise of [Pi]myo is absent during fatigue and the failure of SR Ca2+ release is delayed. These results can all be explained if inorganic phosphate can move from the myoplasm into the SR during fatigue and cause precipitation of CaPi within the SR. The relevance of this mechanism in different types of fatigue in humans is considered.

It looks as though this paragraph is saying that it has something to do with inoperative creatine kinase, but the part that follows seems contradictive to what is said in the above paragraph. I'll continue reading.
 
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