title: Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle.
abstract: The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca2+-regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca2+-ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC.NEW & NOTEWORTHYCalpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca2+-regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca2+-ATPase, undergo calpain-dependent proteolysis.
authors.affiliation: Faculty of Health and Welfare Science, Okayama Prefectural University, Okayama, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kanzaki
authors.affiliation: Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Watanabe
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Kuratani
authors.affiliation: School of Health Sciences, Sapporo Medical University, Hokkaido, Japan; and.
authors.forename: Takashi
authors.identifier: http://orcid.org/0000-0003-1797-3880
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Faculty of Education, Miyazaki University, Miyazaki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan; wada@hiroshima-u.ac.jp.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Wada
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D059748:Proteolysis; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D008565:Membrane Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C412507:junctophilin; D002154:Calpain; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: calcium-dependent protease; excitation-contraction coupling; muscle damage; proteolysis; triad