Skeletal muscle contractility and myosin function decline following ovariectomy in mature female ... more Skeletal muscle contractility and myosin function decline following ovariectomy in mature female mice. In the present study we tested the hypothesis that estradiol replacement can reverse those declines. Four-month-old female C57BL/6 mice ( n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated immediately with placebo or 17β-estradiol (OVX + E2) while other mice were treated 30 days postsurgery. Thirty or sixty days postsurgery, soleus muscles were assessed in vitro for contractile function and susceptibility to eccentric contraction-induced injury. Myosin structural dynamics was analyzed in extensor digitorum longus (EDL) muscles by electron paramagnetic resonance spectroscopy. Maximal isometric tetanic force was affected by estradiol status ( P < 0.001) being ∼10% less in soleus muscles from OVX compared with sham-operated mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX + E2 mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin...
We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps... more We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps muscle strength, cross-sectional area, and neural activation. Women (age 20.0 +/- 0.5 yr) randomly assigned to Con training (CTG; n = 16), Ecc training (ETG; n = 19), and control (CG; n = 19) groups were tested before and after 10 wk of unilateral Con or Ecc knee-extension training. Average torque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8% for CTG, 6.8 and 36.2% for ETG, and 4.7 and -1.7% for CG, respectively. Increases by CTG and ETG were greater than for CG (P &lt; 0.05). For CTG, the increase was greater when measured with Con than with Ecc testing. For ETG, the increase was greater when measured with Ecc than with Con testing. The increase by ETG with Ecc testing was greater than the increase by CTG with Con testing. Corresponding changes in the integrated voltage from an electromyogram measured during strength testing were 21.7 and 20.0% for CTG, 7.1 and 16.7% for ETG, and -8.0 and -9.1% for CG. Quadriceps cross-sectional area measured by magnetic resonance imaging (sum of 7 slices) increased more in ETG (6.6%) than in CTG (5.0%) (P &lt; 0.05). We conclude that Ecc is more effective than Con isokinetic training for developing strength in Ecc isokinetic muscle actions and that Con is more effective than Ecc isokinetic training for developing strength in Con isokinetic muscle actions. Gains in strength consequent to Con and Ecc training are highly dependent on the muscle action used for training and testing. Muscle hypertrophy and neural adaptations contribute to strength increases consequent to both Con and Ecc training.
The objectives of this research were to determine the contribution of excitation-contraction (E-C... more The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in Po (approximately 51%) compared with caffeine-induced force (approximately 11-21%), we estimate that E-C coupling failure can explain 57-75% of the Po decrement from 0 to 5 days postinjury. Comparable reductions in Po and K+-induced force (51%), and minor reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol-induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease in Po during the first several days after injury primarily stems from a failure in the E-C coupling process.
Our aim was to study how mouse skeletal muscle membranes are altered by eccentric and isometric c... more Our aim was to study how mouse skeletal muscle membranes are altered by eccentric and isometric contractions. A fluorescent dialkyl carbocyanine dye (DiOC18(3)) was used to label muscle membranes, and the membranes accessible to the dye were observed by confocal laser scanning microscopy. Experiments were done on normal mouse soleus muscles and soleus muscles injured by 20 eccentric or 20 isometric contractions. Longitudinal optical sections of control muscle fibers revealed DiOC18(3) staining of the plasmalemma and regularly spaced transverse bands corresponding in location to the T-tubular system. Transverse optical sections showed an extensive reticular network with the DiOC18(3) staining. Injured muscle fibers showed distinctively different staining patterns in both longitudinal and transverse optical sections. Longitudinal optical sections of the injured fibers revealed staining in a longitudinally-oriented pattern. No correlations were found between the abnormal DiOC18(3) staining and the reductions in maximal isometric tetanic force or release of lactate dehydrogenase (P≥0.32). Additionally, no difference in the extent of abnormal staining was found between muscles performing eccentric contractions and those performing the less damaging isometric contractions. However, many fibers in muscles injured by eccentric contractions showed swollen regions with marked loss of membrane integrity and an elevated free cytosolic calcium concentration as observed in Fluo-3 images. In conclusion, a loss of cell membrane integrity results from contractile activity, enabling DiOC18(3) staining of internal membranes. The resulting staining pattern is striking and fibers with damaged cell membranes are easily distinguished from uninjured ones.
Journal of Muscle Research and Cell Motility, 1998
The primary purpose of this study was to determine the relationship between myosin heavy chain (M... more The primary purpose of this study was to determine the relationship between myosin heavy chain (MHC) and actin contents and maximum isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles following eccentric contraction-induced injury. Po and protein contents were measured in injured (n=80) and contralateral control (n = 80) EDL muscles at the following time points after in vivo injury: sham, 0, 0.25, 1, 3, 5, 14, and 28 days. Po was reduced by 37 ± 2.3% to 49 ± 3.8% (p ≤ 0.05), while MHC and actin contents were unaltered from 0 to 3 days after injury. Whereas Po partially recovered between 3 and 5 days (from −49 ± 3.8% to −35 ± 3.6%), MHC and actin contents in the injured muscles declined by 19 ± 4.9% and 20 ± 5.3%, respectively, by 5 days compared with control muscles. Decrements in Po were similar to the reductions in MHC and actin contents at 14 (∼24%) and 28 (∼11%) days. Evaluation of myofibrillar and soluble protein fractions indicated significant reductions in the content of major proteins at 5 and 14 days. Immunoblots of heat shock protein 72 revealed elevations starting at 0.25 days, peaking during 1–3 days, and declining after 5days. These findings indicate that decreased contractile protein content is not related to the initial decrease in Po. However, decreased MHC and actin contents could account for 58% of the Po reduction at 5 days, and for nearly all the decrements in Po from 14 to 28 days.
Skeletal muscle contractility and myosin function decline following ovariectomy in mature female ... more Skeletal muscle contractility and myosin function decline following ovariectomy in mature female mice. In the present study we tested the hypothesis that estradiol replacement can reverse those declines. Four-month-old female C57BL/6 mice ( n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated immediately with placebo or 17β-estradiol (OVX + E2) while other mice were treated 30 days postsurgery. Thirty or sixty days postsurgery, soleus muscles were assessed in vitro for contractile function and susceptibility to eccentric contraction-induced injury. Myosin structural dynamics was analyzed in extensor digitorum longus (EDL) muscles by electron paramagnetic resonance spectroscopy. Maximal isometric tetanic force was affected by estradiol status ( P < 0.001) being ∼10% less in soleus muscles from OVX compared with sham-operated mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX + E2 mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin...
We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps... more We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps muscle strength, cross-sectional area, and neural activation. Women (age 20.0 +/- 0.5 yr) randomly assigned to Con training (CTG; n = 16), Ecc training (ETG; n = 19), and control (CG; n = 19) groups were tested before and after 10 wk of unilateral Con or Ecc knee-extension training. Average torque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8% for CTG, 6.8 and 36.2% for ETG, and 4.7 and -1.7% for CG, respectively. Increases by CTG and ETG were greater than for CG (P &lt; 0.05). For CTG, the increase was greater when measured with Con than with Ecc testing. For ETG, the increase was greater when measured with Ecc than with Con testing. The increase by ETG with Ecc testing was greater than the increase by CTG with Con testing. Corresponding changes in the integrated voltage from an electromyogram measured during strength testing were 21.7 and 20.0% for CTG, 7.1 and 16.7% for ETG, and -8.0 and -9.1% for CG. Quadriceps cross-sectional area measured by magnetic resonance imaging (sum of 7 slices) increased more in ETG (6.6%) than in CTG (5.0%) (P &lt; 0.05). We conclude that Ecc is more effective than Con isokinetic training for developing strength in Ecc isokinetic muscle actions and that Con is more effective than Ecc isokinetic training for developing strength in Con isokinetic muscle actions. Gains in strength consequent to Con and Ecc training are highly dependent on the muscle action used for training and testing. Muscle hypertrophy and neural adaptations contribute to strength increases consequent to both Con and Ecc training.
The objectives of this research were to determine the contribution of excitation-contraction (E-C... more The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in Po (approximately 51%) compared with caffeine-induced force (approximately 11-21%), we estimate that E-C coupling failure can explain 57-75% of the Po decrement from 0 to 5 days postinjury. Comparable reductions in Po and K+-induced force (51%), and minor reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol-induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease in Po during the first several days after injury primarily stems from a failure in the E-C coupling process.
Our aim was to study how mouse skeletal muscle membranes are altered by eccentric and isometric c... more Our aim was to study how mouse skeletal muscle membranes are altered by eccentric and isometric contractions. A fluorescent dialkyl carbocyanine dye (DiOC18(3)) was used to label muscle membranes, and the membranes accessible to the dye were observed by confocal laser scanning microscopy. Experiments were done on normal mouse soleus muscles and soleus muscles injured by 20 eccentric or 20 isometric contractions. Longitudinal optical sections of control muscle fibers revealed DiOC18(3) staining of the plasmalemma and regularly spaced transverse bands corresponding in location to the T-tubular system. Transverse optical sections showed an extensive reticular network with the DiOC18(3) staining. Injured muscle fibers showed distinctively different staining patterns in both longitudinal and transverse optical sections. Longitudinal optical sections of the injured fibers revealed staining in a longitudinally-oriented pattern. No correlations were found between the abnormal DiOC18(3) staining and the reductions in maximal isometric tetanic force or release of lactate dehydrogenase (P≥0.32). Additionally, no difference in the extent of abnormal staining was found between muscles performing eccentric contractions and those performing the less damaging isometric contractions. However, many fibers in muscles injured by eccentric contractions showed swollen regions with marked loss of membrane integrity and an elevated free cytosolic calcium concentration as observed in Fluo-3 images. In conclusion, a loss of cell membrane integrity results from contractile activity, enabling DiOC18(3) staining of internal membranes. The resulting staining pattern is striking and fibers with damaged cell membranes are easily distinguished from uninjured ones.
Journal of Muscle Research and Cell Motility, 1998
The primary purpose of this study was to determine the relationship between myosin heavy chain (M... more The primary purpose of this study was to determine the relationship between myosin heavy chain (MHC) and actin contents and maximum isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles following eccentric contraction-induced injury. Po and protein contents were measured in injured (n=80) and contralateral control (n = 80) EDL muscles at the following time points after in vivo injury: sham, 0, 0.25, 1, 3, 5, 14, and 28 days. Po was reduced by 37 ± 2.3% to 49 ± 3.8% (p ≤ 0.05), while MHC and actin contents were unaltered from 0 to 3 days after injury. Whereas Po partially recovered between 3 and 5 days (from −49 ± 3.8% to −35 ± 3.6%), MHC and actin contents in the injured muscles declined by 19 ± 4.9% and 20 ± 5.3%, respectively, by 5 days compared with control muscles. Decrements in Po were similar to the reductions in MHC and actin contents at 14 (∼24%) and 28 (∼11%) days. Evaluation of myofibrillar and soluble protein fractions indicated significant reductions in the content of major proteins at 5 and 14 days. Immunoblots of heat shock protein 72 revealed elevations starting at 0.25 days, peaking during 1–3 days, and declining after 5days. These findings indicate that decreased contractile protein content is not related to the initial decrease in Po. However, decreased MHC and actin contents could account for 58% of the Po reduction at 5 days, and for nearly all the decrements in Po from 14 to 28 days.
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