ORCID Profile
0000-0002-1278-3773
Current Organisations
Osaka University of Health and Sport Sciences
,
National Cerebral and Cardiovascular Center
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Publications
Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle
Publisher: American Physiological Society
Date: 02-2017
DOI: 10.1152/JAPPLPHYSIOL.00270.2016
Abstract: The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca 2+ -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 Ca 2+ -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 & NOTEWORTHY Calpain-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 Ca 2+ -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 Ca 2+ -ATPase, undergo calpain-dependent proteolysis.
Electrical Stimulation Prevents Preferential Skeletal Muscle Myosin Loss in Steroid-Denervation Rats
Publisher: Frontiers Media SA
Date: 10-08-2018
Contribution of impaired myofibril and ryanodine receptor function to prolonged low-frequency force depression after in situ stimulation in rat skeletal muscle
Publisher: Springer Science and Business Media LLC
Date: 20-02-2015
DOI: 10.1007/S10974-015-9409-1
Abstract: The aim of this study was to examine whether prolonged low-frequency force depression (PLFFD) that occurs in situ is the result of decreased myofibrillar Ca(2+) sensitivity and/or reduced sarcoplasmic reticulum (SR) Ca(2+) release. Intact rat gastrocnemius muscles were electrically stimulated via the sciatic nerve until force was reduced to ~50% of the initial and dissected 30 min following the cessation of stimulation. Skinned fibre and whole muscle analyses were performed in the superficial region composed exclusively of type IIB fibres. Fatiguing stimulation significantly reduced the ratio of force at low frequency to that at high frequency to 65% in skinned fibres (1 vs. 50 Hz) and 73% in whole muscles (20 vs. 100 Hz). In order to evaluate changes in myofibrillar Ca(2+) sensitivity and ryanodine receptor caffeine sensitivity, skinned fibres were activated in Ca(2+)- and caffeine-containing solutions, respectively. Skinned fibres from fatigued muscles displayed decreased caffeine sensitivity together with increased myofibrillar Ca(2+) sensitivity. Treatment with 2,2'-dithiodipyridine and reduced glutathione induced a smaller increase in myofibrillar Ca(2+)sensitivity in fatigued than in rested fibres. In fatigued muscles, S-glutathionylation of troponin I was increased and submaximal SR Ca(2+) release, induced by 4-chloro-m-cresol, was decreased. These findings suggest that in the early stage of PLFFD that occurs in fast-twitch muscles of exercising animals and humans, S-glutathionylation of troponin I may attenuate PLFFD by increasing myofibrillar Ca(2+) sensitivity and that under such a circumstance, PLFFD may be ascribable to failure of SR Ca(2+) release.
Effects of reduced muscle glycogen on excitation–contraction coupling in rat fast-twitch muscle: a glycogen removal study
Publisher: Springer Science and Business Media LLC
Date: 24-06-2019
DOI: 10.1007/S10974-019-09524-Y
Abstract: The aim of this study was to investigate the effects of an enzymatic removal of glycogen on excitation-contraction coupling in mechanically skinned fibres of rat fast-twitch muscles, with a focus on the changes in the function of Na
Eccentric muscle contraction potentiates titin stiffness-related contractile properties in rat fast-twitch muscles
Publisher: American Physiological Society
Date: 09-2022
DOI: 10.1152/JAPPLPHYSIOL.00327.2022
Abstract: It remains unclear whether eccentric contraction of skeletal muscle affects titin stiffness-related contractile properties. Here, we provide evidence that an acute bout of eccentric contraction can potentiate titin-based passive force, maximum active force at long sarcomere lengths, and length-dependent activation. This potentiation may resist muscle fatigue in the muscles of the exercising body.
Predominant cause of faster force recovery in females than males after intense eccentric contractions in mouse fast‐twitch muscle
Publisher: Wiley
Date: 26-08-2021
DOI: 10.1113/JP281927
Abstract: We investigated the mechanisms underlying faster force recovery from eccentric contractions (ECCs) in female than in male mice, focusing on mitochondrial responses. At 3 days after repeated ECCs (REC3), female mice showed faster recovery from ECC‐induced force depression than male mice. At REC3, the mitochondria in females displayed superior responses to those in males: (i) mitochondrial Ca 2+ uniporter content of muscles at REC3 was higher than that of rested muscles in females, and (ii) mitochondrial volume density in females was higher than that in males at REC3. Ovariectomized (OVX) female mice showed lower mitochondrial responses at REC3, similar to those observed in male mice, but oestrogen replacement nullified such lower responses in OVX. We concluded that: (i) superior mitochondrial responses after ECCs, at least in part, cause faster force recovery from ECCs in females than in males, and (ii) oestrogen contributes to such superior responses in the mitochondria in females. The purpose of this study was to investigate the mechanisms underlying sex differences in force recovery after eccentric contractions (ECCs). The left limbs of female and male mice were exposed to repeated ECCs (five sets of 50 contractions) elicited in vivo in the plantar flexor muscles. Isometric torques were measured before, immediately and at 3 days after ECCs (REC3), and gastrocnemius muscles obtained at REC3 were used for biochemical and morphological analyses. At REC3, a greater torque depression at 40 Hz was observed in males than females. Additionally, the following differences were observed at REC3: (i) in males but not females, triad structure was distorted, (ii) mitochondrial Ca 2+ uniporter (MCU) content was increased in females but not in males, and (iii) mitochondrial volume density at REC3 was lower in males than in females. To examine the contribution of oestrogen to torque recovery, female mice were assigned to sham‐operated (Sham), ovariectomized (OVX) and OVX treated with 17β‐oestradiol (OVX + E2) groups. At REC3, (i) greater torque depression at 40 Hz was observed in the OVX group than in the Sham and OVX + E2 groups, (ii) MCU content was increased in the Sham and OVX + E2 groups but not the OVX group, and (iii) mitochondrial volume density at REC3 was lower in the OVX group than the Sham and OVX + E2 groups. These results suggest that faster force recovery in females than in males is, at least partly, ascribable to superior mitochondrial responses, and oestrogen supplementation, in part, enhances such responses.
Sex differences in mitochondrial Ca2+ handling in mouse fast-twitch skeletal muscle in vivo
Publisher: American Physiological Society
Date: 02-2020
DOI: 10.1152/JAPPLPHYSIOL.00230.2019
Abstract: We investigated sex differences in mitochondrial Ca 2+ handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyto ) were measured in vivo using tibialis anterior muscles from male and female mice. The muscles were exposed to increasing concentrations of cyclopiazonic acid [CPA sarcoplasmic reticulum (SR) Ca 2+ -ATPase inhibitor] (from 10 to 30 to 50 μM at 10 min intervals). Thirty minutes after treatment, [Ca 2+ ] cyto was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca 2+ ] cyto in male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca 2+ uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca 2+ ] cyto increase. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared with males (mitochondria number: 13.1 ± 1.0 in males vs. 19.9 ± 2.3 in females mitochondrial volume: 0.034 ± 0.004 μm 3 /μm 3 fiber volume in males vs. 0.066 ± 0.008 μm 3 /μm 3 fiber volume in females, both P 0.05). There were no sex differences in the content of SR Ca 2+ -ATPase, mitochondrial Ca 2+ uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that 1) mitochondrial Ca 2+ uptake ability is greater in female than male myocytes, and 2) this superior Ca 2+ uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content but not to the expression of mitochondrial proteins related to mitochondrial Ca 2+ uptake. NEW & NOTEWORTHY This investigation presents evidence that female versus male fast-twitch muscle exhibits a greater mitochondrial calcium ion uptake capability that is partly conferred by the higher intermyofibrillar mitochondrial volume density.
Predominant cause of prolonged low-frequency force depression changes during recovery after in situ fatiguing stimulation of rat fast-twitch muscle
Publisher: American Physiological Society
Date: 11-2016
DOI: 10.1152/AJPREGU.00046.2016
Abstract: To investigate time-dependent changes in sarcoplasmic reticulum (SR) Ca 2+ release and myofibrillar (my-) Ca 2+ sensitivity during recovery from prolonged low-frequency force depression (PLFFD), rat gastrocnemius muscles were electrically stimulated in situ. After 0 h (R0), 0.5 h (R0.5), 2 h (R2), 6 h (R6), or 12 h of recovery, the superficial gastrocnemius muscles were excised and used for biochemical and skinned fiber analyses. At R0, R0.5, R2, and R6, the ratio of force at 1 Hz to that at 50 Hz was decreased in the skinned fibers. The ratio of depolarization-induced force to the maximum Ca 2+ -activated force (depol/Ca 2+ force ratio) was utilized as an indicator of SR Ca 2+ release. At R0, both the depol/Ca 2+ force ratio and my-Ca 2+ sensitivity were decreased. At R0.5 and R2, my-Ca 2+ sensitivity was recovered, while the depol/Ca 2+ force ratio remained depressed. At R6, my-Ca 2+ sensitivity was decreased again, whereas the depol/Ca 2+ force ratio was nearly restored. Western blot analyses demonstrated that decreased my-Ca 2+ sensitivity at R6 and reduced depol/Ca 2+ force ratio at R0, R0.5, and R2 were accompanied by depressions in S-glutathionylated troponin I and increases in dephosphorylated ryanodine receptor 1, respectively. These results indicate that, in the early stage of recovery, reduced SR Ca 2+ release plays a primary role in the etiology of PLFFD, whereas decreased my-Ca 2+ sensitivity is involved in the late stage, and suggest that S-glutathionylation of troponin I and dephosphorylation of ryanodine receptor 1 contribute, at least partly, to fatiguing contraction-induced alterations in my-Ca 2+ sensitivity and SR Ca 2+ release, respectively.
Effects of high-intensity interval exercise on muscle fatigue and SR function in rats: a comparison with moderate-intensity continuous exercise
Publisher: American Physiological Society
Date: 08-2020
DOI: 10.1152/JAPPLPHYSIOL.00223.2020
Abstract: Over the past decade, high-intensity interval exercise (HIIE) training has received attention as a more efficient training to improve endurance capacity. It is unclear, however, whether the extent of acute exercise-related muscle fatigue differs between HIIE and moderate-intensity continuous exercise, traditional endurance training. Here we provide evidence that restoration of force production takes a longer time after HIIE, which is ascribable to long-lasting depressions in Ca 2+ release of the sarcoplasmic reticulum.
Fatigue‐induced change in T‐system excitability and its major cause in rat fast‐twitch skeletal muscle in vivo
Publisher: Wiley
Date: 14-09-2020
DOI: 10.1113/JP279574
l
-arginine ingestion inhibits eccentric contraction-induced proteolysis and force deficit via S
-nitrosylation of calpain
Publisher: Wiley
Date: 2018
DOI: 10.14814/PHY2.13582
Effects of clenbuterol administration on mitochondrial morphology and its regulatory proteins in rat skeletal muscle
Publisher: Wiley
Date: 10-2019
DOI: 10.14814/PHY2.14266
Skeletal muscle fibre swelling contributes to force depression in rats and humans: a mechanically-skinned fibre study
Publisher: Springer Science and Business Media LLC
Date: 07-06-2019
DOI: 10.1007/S10974-019-09521-1
Abstract: This study investigated the effects of fibre swelling on force production in rat and human skinned muscle fibres, using osmotic compression to reverse the fibre swelling. In mechanically-skinned fibres, the sarcolemma is removed but normal excitation-contraction coupling remains functional. Force responses in mechanically-skinned fibres were examined with and without osmotic compression by polyvinylpyrrolidone 40 kDa (PVP-40) or Dextran 500 kDa (dextran). Fibre diameter increased to 116 ± 2% (mean ± SEM) when rat skinned type II fibres were immersed in the standard intracellular solution, but remained close to the in situ size when 3% (mass/volume) PVP-40 or 4% Dextran were present. Myofibrillar Ca
Intrinsic contractile dysfunction due to impaired sarcoplasmic reticulum Ca2+ release in compensatory hypertrophied muscle fibers following synergist ablation
Publisher: American Physiological Society
Date: 09-2023
DOI: 10.1152/AJPCELL.00127.2023
Abstract: Synergist ablation (SA) has widely been used to understand the mechanisms behind skeletal muscle hypertrophy. However, compensatory hypertrophied muscles display intrinsic contractile dysfunction, i.e., a hallmark of overuse. Here, we demonstrate that SA-induced compensatory hypertrophy is accompanied by muscle weakness due to impaired sarcoplasmic reticulum Ca 2+ release. This dysfunction may be caused by the degradation of triad proteins due to the reciprocal lification of reactive oxygen species and Ca 2+ signaling at the junctional space microdomain.
Thermal pretreatment facilitates recovery from prolonged low-frequency force depression in rat fast-twitch muscle
Publisher: Wiley
Date: 09-2018
DOI: 10.14814/PHY2.13853
Glutathione depression alters cellular mechanisms of skeletal muscle fatigue in early stage of recovery and prolongs force depression in late stage of recovery
Publisher: American Physiological Society
Date: 08-2023
DOI: 10.1152/AJPREGU.00097.2022
Abstract: The effects of reduced glutathione (GSH) on skeletal muscle fatigue were investigated. GSH was depressed by buthionine sulfoximine (BSO) (100 mg/kg body wt/day) treatment for 5 days, which decreased GSH content to ∼10%. Male Wistar rats were assigned to the control ( N = 18) and BSO groups ( N = 17). Twelve hours after BSO treatment, the plantar flexor muscles were subjected to fatiguing stimulation (FS). Eight control and seven BSO rats were rested for 0.5 h (early stage of recovery), and the remaining were rested for 6 h (late stage of recovery). Forces were measured before FS and after rest, and physiological functions were estimated using mechanically skinned fibers. The force at 40 Hz decreased to a similar extent in both groups in the early stage of recovery and was restored in the control but not in the BSO group in the late stage of recovery. In the early stage of recovery, sarcoplasmic reticulum (SR) Ca 2+ release was decreased in the control greater than in the BSO group, whereas myofibrillar Ca 2+ sensitivity was increased in the control but not in the BSO group. In the late stage of recovery, SR Ca 2+ release decreased and SR Ca 2+ leakage increased in the BSO group but not in the control group. These results indicate that GSH depression alters the cellular mechanism of muscle fatigue in the early stage and delays force recovery in the late stage of recovery, due at least in part, to the prolonged Ca 2+ leakage from the SR.
Effects of S-glutathionylation on the passive force–length relationship in skeletal muscle fibres of rats and humans
Publisher: Springer Science and Business Media LLC
Date: 02-11-2019
DOI: 10.1007/S10974-019-09563-5
Abstract: This study investigated the effect of S-glutathionylation on passive force in skeletal muscle fibres, to determine whether activity-related redox reactions could modulate the passive force properties of muscle. Mechanically-skinned fibres were freshly obtained from human and rat muscle, setting sarcomere length (SL) by laser diffraction. Larger stretches were required to produce passive force in human fibres compared to rat fibres, but there were no fibre-type differences in either species. When fibres were exposed to glutathione disulfide (GSSG 20 mM, 15 min) whilst stretched (at a SL where passive force reached ~ 20% of maximal Ca
Treatment with EUK-134 improves sarcoplasmic reticulum Ca2+release but not myofibrillar Ca2+sensitivity after fatiguing contraction of rat fast-twitch muscle
Publisher: American Physiological Society
Date: 05-2019
DOI: 10.1152/AJPREGU.00387.2018
Abstract: Skeletal muscles undergoing vigorous activity can enter a state of prolonged low-frequency force depression (PLFFD). This study was conducted to examine whether antioxidant treatment is capable of accelerating the recovery from PLFFD, with a focus on the function of the sarcoplasmic reticulum (SR) and myofibril. One hour before fatiguing stimulation (FS) was administered, rats received an intraperitoneal injection of Eukarion (EUK-134), which mimics the activities of superoxide dismutase and catalase. Intact muscles of the hindlimbs were electrically stimulated via the sciatic nerve until the force was reduced to ~50% of the initial force (FS). Thirty minutes after cessation of FS, the superficial regions of gastrocnemius muscles were dissected and used for biochemical and skinned-fiber analyses. Whole muscle analyses revealed that antioxidant alleviated the FS-induced decrease in the reduced glutathione content. Skinned-fiber analyses showed that the antioxidant did not affect the FS-induced decrease in the ratio of force at 1 Hz to that at 50 Hz. However, the antioxidant partially inhibited the FS-mediated decrease in the ratio of depolarization-induced force to the maximum Ca 2+ -activated force. Furthermore, the antioxidant completely suppressed the FS-induced increase in myofibrillar Ca 2+ sensitivity. These results suggest that antioxidant treatment is ineffective in facilitating the restoration of PLFFD, probably due to its negative effect on myofibrillar Ca 2+ sensitivity, which supersedes its positive effect on SR Ca 2+ release.
Effects of vigorous isometric muscle contraction on titin stiffness-related contractile properties in rat fast-twitch muscles
Publisher: American Physiological Society
Date: 12-2021
DOI: 10.1152/AJPREGU.00189.2021
Abstract: This study was conducted to examine the effects of an acute bout of vigorous isometric contractions on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ until the force was reduced to ∼50% of the initial force. Immediately after cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses. The stimulation resulted in a decrease in the titin-based passive force. The amounts of fragmented titin were unchanged by the stimulation. Protein kinase Cα-treatment increased the passive force in stimulated fibers to resting levels. The stimulation had no effect on the maximum Ca 2+ -activated force (max Ca 2+ force) at a sarcomere length (SL) of 2.4 μm and decreased myofibrillar (my)-Ca 2+ sensitivity at 2.6-μm SL. Stretching the SL to 3.0 μm led to the augmentation of the max Ca 2+ force and my-Ca 2+ sensitivity in both rested and stimulated fibers. For the max Ca 2+ force, the extent of the increase was smaller in stimulated than in rested fibers, whereas for my-Ca 2+ sensitivity, it was higher in stimulated than in rested fibers. These results suggest that vigorous isometric contractions decrease the titin-based passive force, possibly because of a reduction in phosphorylation by protein kinase Cα, and that the decreased titin stiffness may contribute, at least in part, to muscle fatigue.
Related Organisations
Japan Society For The Promotion Of Science
Location: No location found
Related Funding Activities
No related grants have been discovered for Daiki Watanabe.