FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury
Open accessAbstract
Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice.
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Disruptions to sarcomeric and sarcolemmal structures have been observed within days of the eccentric exercise bout.
“As the normal progression of damage and regeneration processes occur, disruptions to sarcomeric (contractile apparatus) and sarcolemmal (membrane) structures have been observed within days of the eccentric exercise bout (35, 55, 56).”
From Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice (2021) · cites this paper as [35]
Functional capacity is significantly impaired immediately and for several days after 150 eccentric contractions.
“Here in this study, as with many others (34, 35, 42–44), we reaffirm that functional capacity is significantly impaired immediately, and for several days after, 150 eccentric contractions.”
From Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice (2021) · cites this paper as [35]
Similar findings have been described previously wherein muscle function had recovered, but markers of muscle damage and regeneration, particularly centralized nuclei, are still visible weeks after eccentric contraction-induced muscle damage.
“This is not surprising as similar findings have been described previously wherein muscle function had recovered, but markers of muscle damage and regeneration, particularly centralized nuclei, are still visible weeks after eccentric contraction-induced muscle damage (35, 44).”
From Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice (2021) · cites this paper as [35]
The novel observation that 20E treatment fully recovers skeletal muscle function in just 7 days after eccentric damage is much earlier than other studies using similar eccentric damage protocols in mice.
“The novel observation that 20E treatment fully recovers skeletal muscle function in just 7 days after eccentric damage is much earlier than other studies using similar eccentric damage protocols in mice (34, 35, 42, 47).”
From Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice (2021) · cites this paper as [35]
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Self-citation
- Authors
- Corona, B. T., Rouviere, C., Hamilton, S. L., & Ingalls, C. P.
- Affiliations
- Georgia State University (US)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2008-08
- Volume
- 105
- Issue
- 2
- Pages
- 527-537
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- PMC
- PMC2519949
- OpenAlex
- W2045975937
- Cited by
- 22
- References
- 40
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2016: 3 · 2014: 4 · 2013: 1 · 2012: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Applied Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041802, AR-41802)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Surgery › Muscle and Compartmental Disorders
- Keywords
- FKBP12, excitation-contraction uncoupling, ryanodine receptor, sarcoplasmic reticulum, muscle strength deficits, muscle injury recovery, tibialis anterior, extensor digitorum longus, sex differences, skeletal muscle
- MeSH terms
- Central Nervous System Stimulants, Animals, Body Weight, Caffeine, Electric Stimulation, Female, Isometric Contraction, Male, Muscle Contraction, Organ Size, Sex Characteristics, Mice, Knockout, Muscle, Skeletal, Tacrolimus Binding Protein 1A, Mice, Muscle Strength
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