scholarly journals Skeletal muscle fiber atrophy: altered thin filament density changes slow fiber force and shortening velocity

2005 ◽  
Vol 288 (2) ◽  
pp. C360-C365 ◽  
Author(s):  
D. A. Riley ◽  
J. L. W. Bain ◽  
J. G. Romatowski ◽  
R. H. Fitts

Single skinned fibers from soleus and adductor longus (AL) muscles of weight-bearing control rats and rats after 14-day hindlimb suspension unloading (HSU) were studied physiologically and ultrastructurally to investigate how slow fibers increase shortening velocity ( V0) without fast myosin. We hypothesized that unloading and shortening of soleus during HSU reduces densities of thin filaments, generating wider myofilament separations that increase V0 and decrease specific tension (kN/m2). During HSU, plantarflexion shortened soleus working length 23%. AL length was unchanged. Both muscles atrophied as shown by reductions in fiber cross-sectional area. For AL, the 60% atrophy accounted fully for the 58% decrease in absolute tension (mN). In the soleus, the 67% decline in absolute tension resulted from 58% atrophy plus a 17% reduction in specific tension. Soleus fibers exhibited a 25% reduction in thin filaments, whereas there was no change in AL thin filament density. Loss of thin filaments is consistent with reduced cross bridge formation, explaining the fall in specific tension. V0 increased 27% in soleus but was unchanged in AL. The V0 of control and HSU fibers was inversely correlated ( R = −0.83) with thin filament density and directly correlated ( R = 0.78) with thick-to-thin filament spacing distance in a nonlinear fashion. These data indicate that reduction in thin filament density contributes to an increased V0 in slow fibers. Osmotically compacting myofilaments with 5% dextran returned density, spacing, and specific tension and slowed V0 to near-control levels and provided evidence for myofilament spacing modulating tension and V0.

2002 ◽  
Vol 92 (2) ◽  
pp. 817-825 ◽  
Author(s):  
Danny A. Riley ◽  
James L. W. Bain ◽  
Joyce L. Thompson ◽  
Robert H. Fitts ◽  
Jeffrey J. Widrick ◽  
...  

Slow type I fibers in soleus and fast white (IIa/IIx, IIx), fast red (IIa), and slow red (I) fibers in gastrocnemius were examined electron microscopically and physiologically from pre- and postflight biopsies of four astronauts from the 17-day, Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission. At 2.5-μm sarcomere length, thick filament density is ∼1,012 filaments/μm2 in all fiber types and unchanged by spaceflight. In preflight aldehyde-fixed biopsies, gastrocnemius fibers possess higher percentages (∼23%) of short thin filaments than soleus (9%). In type I fibers, spaceflight increases short, thin filament content from 9 to 24% in soleus and from 26 to 31% in gastrocnemius. Thick and thin filament spacing is wider at short sarcomere lengths. The Z-band lattice is also expanded, except for soleus type I fibers with presumably stiffer Z bands. Thin filament packing density correlates directly with specific tension for gastrocnemius fibers but not soleus. Thin filament density is inversely related to shortening velocity in all fibers. Thin filament structural variation contributes to the functional diversity of normal and spaceflight-unloaded muscles.


2003 ◽  
Vol 95 (6) ◽  
pp. 2425-2433 ◽  
Author(s):  
Julian E. Stelzer ◽  
Jeffrey J. Widrick

Cross-sectional area (CSA), peak Ca2+-activated force (Po), fiber specific force (Po/CSA), and unloaded shortening velocity ( Vo) were measured in slow-twitch [containing type I myosin heavy chain (MHC)] and fast-twitch (containing type II MHC) chemically skinned soleus muscle fiber segments obtained from three strains of weight-bearing and 7-day hindlimb-suspended (HS) mice. HS reduced soleus slow MHC content (from ∼50 to ∼33%) in CBA/J and ICR strains without affecting slow MHC content in C57BL/6 mice (∼20% of total MHC). Two-way ANOVA revealed HS-induced reductions in CSA, Po, and Po/CSA of slow and fast fibers from all strains. Fiber Vo was elevated post-HS, but not consistently across strains. No MHC × HS treatment interactions were observed for any variable for C57BL/6 and CBA/J mice, and the two significant interactions found for the ICR strain (CSA, Po) appeared related to inherent pre-HS differences in slow vs. fast fiber CSA. In the mouse HS models studied here, fiber atrophy and contractile dysfunction were partially dependent on animal strain and generally independent of fiber MHC isoform content.


1997 ◽  
Vol 82 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Jeffrey J. Widrick ◽  
Robert H. Fitts

Widrick, Jeffrey J., and Robert H. Fitts. Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise. J. Appl. Physiol. 82(1): 189–195, 1997.—This study examined the effectiveness of resistance exercise as a countermeasure to non-weight-bearing-induced alterations in the absolute peak force, normalized peak force (force/fiber cross-sectional area), peak stiffness, and maximal shortening velocity ( V o) of single permeabilized type I soleus muscle fibers. Adult rats were subjected to one of the following treatments: normal weight bearing (WB), non-weight bearing (NWB), or NWB with exercise treatments (NWB+Ex). The hindlimbs of the NWB and NWB+Ex rats were suspended for 14 days via tail harnesses. Four times each day, the NWB+Ex rats were removed from suspension and performed 10 climbs (∼15 cm each) up a steep grid with a 500-g mass (∼1.5 times body mass) attached to their tail harness. NWB was associated with significant reductions in type I fiber diameter, absolute force, normalized force, and stiffness. Exercise treatments during NWB attenuated the decline in fiber diameter and absolute force by almost 60% while maintaining normalized force and stiffness at WB levels. Type I fiber V oincreased by 33% with NWB and remained at this elevated level despite the exercise treatments. We conclude that in comparison to intermittent weight bearing only (J. J. Widrick, J. J. Bangart, M. Karhanek, and R. H. Fitts. J. Appl. Physiol. 80: 981–987, 1996), resistance exercise was more effective in attenuating alterations in type I soleus fiber absolute force, normalized force, and stiffness but was less effective in restoring type I fiber V oto WB levels.


1996 ◽  
Vol 80 (3) ◽  
pp. 981-987 ◽  
Author(s):  
J. J. Widrick ◽  
J. J. Bangart ◽  
M. Karhanek ◽  
R. H. Fitts

This study examined the effectiveness of intermittent weight bearing (IWB) as a countermeasure to non-weight-bearing (NWB)-induced alterations in soleus type I fiber force (in mN), tension (Po; force per fiber cross-sectional area in kN/m-2), and maximal unloaded shortening velocity (Vo, in fiber lengths/s). Adult rats were assigned to one of the following groups: normal weight bearing (WB), 14 days of hindlimb NWB (NWB group), and 14 days of hindlimb NWB with IWB treatments (IWB group). The IWB treatment consisted of four 10-min periods of standing WB each day. Single, chemically permeabilized soleus fiber segments were mounted between a force transducer and position motor and were studied at maximal Ca2+ activation, after which type I fiber myosin heavy-chain composition was confirmed by sodium dodecyl sufate-polyacrylamide gel electrophoresis. NWB resulted in a loss in relative soleus mass (-45%), with type I fibers displaying reductions in diameter (-28%) and peak isometric force (-55%) and an increase in Vo (+33%). In addition, NWB induced a 16% reduction in type I fiber Po, a 41% reduction in type I fiber peak elastic modulus [Eo, defined as (delta force/delta length) x (fiber length/fiber cross-sectional area] and a significant increase in the Po/Eo ratio. In contrast to NWB, IWB reduced the loss of relative soleus mass (by 22%) and attenuated alterations in type I fiber diameter (by 36%), peak force (by 29%), and Vo (by 48%) but had no significant effect on Po, Eo, or Po/Eo. These results indicate that a modest restoration of WB activity during 14 days of NWB is sufficient to attenuate type I fiber atrophy and to partially restore type I peak isometric force and Vo to WB levels. However, the NWB-induced reductions in Po and Eo, which we hypothesize to be due to a decline in the number and stiffness of cross bridges, respectively, are considerably less responsive to this countermeasure treatment.


1998 ◽  
Vol 85 (5) ◽  
pp. 1949-1956 ◽  
Author(s):  
J. J. Widrick ◽  
K. M. Norenberg ◽  
J. G. Romatowski ◽  
C. A. Blaser ◽  
M. Karhanek ◽  
...  

Soleus muscle fibers from the rat display a reduction in peak power and Ca2+ sensitivity after hindlimb suspension. To examine human responses to non-weight bearing, we obtained soleus biopsies from eight adult men before and immediately after 17 days of bed rest (BR). Single chemically skinned fibers were mounted between a force transducer and a servo-controlled position motor and activated with maximal (isotonic properties) and/or submaximal (Ca2+ sensitivity) levels of free Ca2+. Gel electrophoresis indicated that all pre- and post-BR fibers expressed type I myosin heavy chain. Post-BR fibers obtained from one subject displayed increases in peak power and Ca2+ sensitivity. In contrast, post-BR fibers obtained from the seven remaining subjects showed an average 11% reduction in peak power ( P < 0.05), with each individual displaying a 7–27% reduction in this variable. Post-BR fibers from these subjects were smaller in diameter and produced 21% less force at the shortening velocity associated with peak power. However, the shortening velocity at peak power output was elevated 13% in the post-BR fibers, which partially compensated for their lower force. Post-BR fibers from these same seven subjects also displayed a reduced sensitivity to free Ca2+( P < 0.05). These results indicate that the reduced functional capacity of human lower limb extensor muscles after BR may be in part caused by alterations in the cross-bridge mechanisms of contraction.


2014 ◽  
Vol 206 (4) ◽  
pp. 559-572 ◽  
Author(s):  
Isabelle Fernandes ◽  
Frieder Schöck

Mutations in nebulin, a giant muscle protein with 185 actin-binding nebulin repeats, are the major cause of nemaline myopathy in humans. Nebulin sets actin thin filament length in sarcomeres, potentially by stabilizing thin filaments in the I-band, where nebulin and thin filaments coalign. However, the precise role of nebulin in setting thin filament length and its other functions in regulating power output are unknown. Here, we show that Lasp, the only member of the nebulin family in Drosophila melanogaster, acts at two distinct sites in the sarcomere and controls thin filament length with just two nebulin repeats. We found that Lasp localizes to the Z-disc edges to control I-band architecture and also localizes at the A-band, where it interacts with both actin and myosin to set proper filament spacing. Furthermore, introducing a single amino acid change into the two nebulin repeats of Lasp demonstrated different roles for each domain and established Lasp as a suitable system for studying nebulin repeat function.


1987 ◽  
Vol 62 (6) ◽  
pp. 2180-2186 ◽  
Author(s):  
R. W. Tsika ◽  
R. E. Herrick ◽  
K. M. Baldwin

The purpose of this study was to investigate the role of chronic weight-bearing activity as the primary inducer of compensatory muscle growth and changes in myosin isoform expression in rodent fast-twitch plantaris muscle. Thus, female rats were subjected to the independent and simultaneous exposure of functional overload (induced via synergist removal) and hindlimb unweighting (suspension) for 6 wk. Groups (n = 7/group) consisted of normal-control (NC); overload (OV); normal-suspension (N-SUS); and overload-suspension (OV-SUS). Body weight of both suspension groups was significantly less than both the NC and OV groups (P less than 0.001). Compared with the NC group, normalized plantaris weight (mg/g body wt) of both the OV and OV-SUS groups was greater, whereas that of the N-SUS was lower (P less than 0.001). However, normalized plantaris weight was greater in OV compared with OV-SUS by 35% (P less than 0.001). Myofibril protein content (mg/g) and Ca2+-regulated myofibril adenosinetriphosphatase (ATPase) specific activity were similar for all groups except that ATPase was lower in the OV group compared with the other groups (P less than 0.05). Native myosin isoform analysis revealed a significant increase in the expression of slow and intermediate myosin and the repression of fast myosin 1 (Fm1) in OV compared with NC. This shift in expression was not as pronounced in the OV-SUS group. Interestingly, only traces of slow myosin were observed in the N-SUS group compared with the other groups. These results suggest that weight bearing is an essential component of the overload model for inducing significant increases in both muscle mass and slow myosin isoform expression. Second, lack of weight bearing, while not markedly affecting fast myosins, appears to repress the expression of slow myosin.


1988 ◽  
Vol 65 (3) ◽  
pp. 1231-1237 ◽  
Author(s):  
E. O. Hauschka ◽  
R. R. Roy ◽  
V. R. Edgerton

The morphological and histochemical properties of the rat soleus were studied after 1 wk of hindlimb suspension, one model that removes the weight-bearing function of the hindlimbs. To examine the effectiveness of weight support activity in maintaining soleus mass, fiber size, and succinate dehydrogenase (SDH) activity, the hindlimbs of adult male Sprague-Dawley rats were suspended (HS) and half of these rats were walked on a treadmill for 40 min/day (10 min every 6 h) at 5 m/min and a 19 degree grade (HS-WS). Significant reductions in soleus mass and fiber size were found after 1 wk of HS. Weight support activity decreased the atrophic response by approximately 50%. In the alkaline myofibrillar adenosine triphosphatase (ATPase) dark-staining fibers, SDH activity was higher in the HS than control rats, whereas it was similar to control in the HS-WS rats. Total SDH activity (SDH activity X cross-sectional area) in fibers staining lightly for ATPase in HS and HS-WS rats was lower than in control rats, whereas in the darkly stained ATPase fibers it was similar among the three groups. No changes were observed in fiber type percentages after 1 wk of HS or HS-WS. The results suggest that short-duration, daily weight support activity can ameliorate, but not prevent, soleus atrophy induced by HS. Furthermore, fiber cross-sectional area is more responsive to periodic weight support in dark than light ATPase fibers. These results also demonstrate that muscle fiber atrophy need not be associated with a loss in SDH activity.


1992 ◽  
Vol 73 (2) ◽  
pp. S58-S65 ◽  
Author(s):  
B. Jiang ◽  
Y. Ohira ◽  
R. R. Roy ◽  
Q. Nguyen ◽  
E. I. Ilyina-Kakueva ◽  
...  

The adaptation of single fibers in medial gastrocnemius (MG), a fast-twitch extensor, and tibialis anterior (TA), a fast-twitch flexor, was studied after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Cross-sectional area (CSA) and succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar adenosinetriphosphatase (ATPase) activities were determined in fibers identified in frozen serial cross sections. Fibers were categorized as light, dark, or intermediate on the basis of myosin ATPase staining and alkaline preincubation and immunohistochemically as reacting with slow, fast, or both slow and fast myosin heavy chain monoclonal antibodies. Because there was a close relationship between these two means of categorizing fibers, all fibers were categorized on the basis of the immunohistochemical reaction. The percentage of slow- and fast-twitch fibers of the MG and TA were unchanged in either group. Mean fiber size of all fibers, irrespective of type, was unaffected in either muscle after flight or suspension. The fibers that expressed both fast and slow myosin heavy chains were smaller than control in the MG of both experimental groups. Compared with control, the SDH and total SDH activities in the MG were significantly less in suspended rats, with the fast-twitch fibers showing the largest difference. The ATPase activity in the MG was higher in flight than in control or suspended rats. There were no significant effects of flight on fibers of the TA. In contrast, the TA in suspended rats had higher GPD activities than either control or flight rats.(ABSTRACT TRUNCATED AT 250 WORDS)


1986 ◽  
Vol 250 (3) ◽  
pp. C474-C479 ◽  
Author(s):  
S. S. Segal ◽  
T. P. White ◽  
J. A. Faulkner

Skeletal muscle grafts have a deficit in tension development compared with control muscles, even after accounting for reduced mass and total muscle cross-sectional area. Our purpose was to determine relationships among the architecture, tissue composition, and contractile properties of rat soleus muscle grafts. Data were compared with control soleus muscles obtained from littermates. Female Wistar rats were anesthetized with pentobarbital sodium for grafting of soleus muscles with nerve implant and for dissection of muscles 56 days after grafting. Compared with control values, the maximum specific tension (N/cm2) of grafts was 76%, the interstitial (inulin) space was 135%, and the connective tissue protein concentration was 177%. For grafts, total muscle length and fiber length were 91 and 123% of control values, respectively. The extrapolated shortening velocity at zero load (fiber lengths/s) for grafts was not different from the control value. The deficit in specific tension of grafts is explained by a greater concentration of noncontractile tissue components. Changes in muscle architecture and composition following grafting had little affect on contraction dynamics.


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