Effect of hindlimb suspension on the functional properties of slow and fast soleus fibers from three strains of mice

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.

1992 ◽  
Vol 73 (2) ◽  
pp. S51-S57 ◽  
Author(s):  
Y. Ohira ◽  
B. Jiang ◽  
R. R. Roy ◽  
V. Oganov ◽  
E. Ilyina-Kakueva ◽  
...  

Morphological and enzymatic responses in fibers expressing fast, slow, or both types of myosin heavy chain (MHC) were studied in rats after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Although the percentage of slow-twitch fibers was unchanged, a higher percentage of fibers that expressed both slow and fast MHC was observed in flight and suspended rats than in synchronous ground-based controls. The soleus was 25 and 34% smaller than control after 14 days of flight and suspension, with the reduction in fiber cross-sectional area (CSA) being greater in slow- than in fast-twitch fibers in both experimental groups. The activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) were not significantly affected by flight or suspension. The total SDH activity (i.e., SDH activity x CSA) decreased significantly in the slow-twitch fibers of the flight and the fast-twitch fibers of the suspended rats, in large part due to fiber atrophy. A shift in MHC expression in 14 and 9% of the fibers in flight and suspended rats occurred without a change in myosin adenosinetriphosphatase activity. The SDH and GPD activities of the fibers that expressed both slow and fast MHC were slightly higher than the slow-twitch fibers and slightly lower than the fast-twitch fibers. These data indicate that events were initiated within 14 days of spaceflight or suspension that began to reconfigure the protein profiles of 9–14% of the slow-twitch fibers from typical slow-twitch toward those of fast-twitch fibers, while all fibers were dramatically losing total protein.(ABSTRACT TRUNCATED AT 250 WORDS)


2001 ◽  
Vol 90 (6) ◽  
pp. 2203-2211 ◽  
Author(s):  
J. J. Widrick ◽  
J. G. Romatowski ◽  
K. M. Norenberg ◽  
S. T. Knuth ◽  
J. L. W. Bain ◽  
...  

The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (Po) was observed for the type I fibers (0.68 ± 0.02 vs. 0.64 ± 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and Po where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [ V o, in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 ± 0.03 vs. 0.76 ± 0.02 FL/s) and IIa fibers (2.33 ± 0.25 vs. 3.10 ± 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of Po. These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of Po but increased V o after a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in Po were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A. Riley, M. Karhanek, S. W. Trappe, T. A. Trappe, D. L. Costill, and R. H. Fitts. J Physiol (Lond) 516: 915–930, 1999].


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.


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.


1984 ◽  
Vol 56 (6) ◽  
pp. 1594-1601 ◽  
Author(s):  
R. R. Roy ◽  
R. D. Sacks ◽  
K. M. Baldwin ◽  
M. Short ◽  
V. R. Edgerton

Interrelationships of selected mechanical and biochemical properties of hindlimb extensor muscles following low thoracic cord transection were studied. Kittens were spinalized (Sp) at 2 wk and maintained for 6–12 mo. Some Sp animals were exercised (Sp-E) on a treadmill 25–30 min/day, 5 days/wk. In situ contractile properties of the slow-twitch soleus (SOL) and fast-twitch medical gastrocnemius (MG) muscles of normal (N), Sp, and Sp-E cats were determined. Exercise did not affect most parameters; thus Sp and Sp-E groups are considered collectively. The cross-sectional areas (CSA) of the SOL and MG decreased by 43 and 32%, respectively. Specific tension (tension/CSA) was maintained in the SOL but decreased (P less than 0.05) in the MG. Contraction time (CT) and half-relaxation time were significantly shorter in the SOL but unchanged in the MG. Maximum shortening velocity (Vmax) and myosin ATPase (mumol X mg-1 X min-1) increased (P less than 0.05) in the SOL of both groups and the MG of Sp. Frequency-tension responses of both muscles shifted toward that resembling a “faster” muscle. These results substantiate the existence of relatively independent regulatory mechanisms for Vmax and CT and show that myosin ATPase levels are more closely related to Vmax than CT. Although the changes in the SOL were consistent with the hypothesis that slow fibers are converted to fast, the elevated Vmax and myosin ATPase of the MG suggest that significant changes also occur within a “fast” fiber-type category.


2000 ◽  
Vol 88 (3) ◽  
pp. 904-916 ◽  
Author(s):  
G. R. Adams ◽  
F. Haddad ◽  
S. A. McCue ◽  
P. W. Bodell ◽  
M. Zeng ◽  
...  

Both slow-twitch and fast-twitch muscles are undifferentiated after birth as to their contractile protein phenotype. Thus we examined the separate and combined effects of spaceflight (SF) and thyroid deficiency (TD) on myosin heavy chain (MHC) gene expression (protein and mRNA) in muscles of neonatal rats (7 and 14 days of age at launch) exposed to SF for 16 days. Spaceflight markedly reduced expression of the slow, type I MHC gene by ∼55%, whereas it augmented expression of the fast IIx and IIb MHCs in antigravity skeletal muscles. In fast muscles, SF caused subtle increases in the fast IIb MHC relative to the other adult MHCs. In contrast, TD prevented the normal expression of the fast MHC phenotype, particularly the IIb MHC, whereas TD maintained expression of the embryonic/neonatal MHC isoforms; this response occurred independently of gravity. Collectively, these results suggest that normal expression of the type I MHC gene requires signals associated with weight-bearing activity, whereas normal expression of the IIb MHC requires an intact thyroid state acting independently of the weight-bearing activities typically encountered during neonatal development of laboratory rodents. Finally, MHC expression in developing muscles is chiefly regulated by pretranslational processes based on the tight relationship between the MHC protein and mRNA data.


2000 ◽  
Vol 278 (4) ◽  
pp. C709-C717 ◽  
Author(s):  
Vincent J. Caiozzo ◽  
Fadia Haddad ◽  
Mike Baker ◽  
Sam McCue ◽  
Kenneth M. Baldwin

In a previous study, it was shown that a combined treatment of hyperthyroidism and hindlimb suspension effectively converted the slow-twitch soleus muscle to a fast-twitch muscle. The objective of this study was to test the hypothesis that hypothyroidism [absence of triiodothyronine (−T3)] and mechanical overload (OV) would convert the plantaris (Plan) muscle from a fast- to a slow-twitch muscle. Single-fiber analyses demonstrated that the normal rodent Plan muscle was composed of ∼13 different fiber types as defined by myosin heavy chain (MHC) isoform content. The largest proportion of fibers (∼35%) coexpressed the fast type IIX and IIB MHC isoforms (i.e., type IIX/IIB fibers). In this context, the combined intervention of −T3 and OV produced a significant reduction in the relative proportion of the fast type IIB MHC isoform and a concomitant increase in the slow type I MHC isoform. These transitions were manifested by a large decrease in the proportion of type IIX/IIB fibers and a large increase in fibers coexpressing all four MHC protein isoforms. The mechanical consequences of these transitions, however, were modest, producing a 15% decrease in maximal shortening velocity. The findings of this study demonstrate that −T3+ OV does produce a partial shift toward a slower phenotype; however, the high degree of polymorphism found in the Plan muscle represents a unique design that appears to minimize the functional consequences of these significant MHC transitions.


1989 ◽  
Vol 67 (2) ◽  
pp. 636-642 ◽  
Author(s):  
R. N. Michel ◽  
A. E. Olha ◽  
P. F. Gardiner

The present study was designed to determine the contribution of weight bearing to the adaptations of the plantaris (PL) to synergist removal. PL from female rats were exposed to 28 days of a simultaneous condition of synergist ablation and hindlimb suspension. At 28 days, contractile responses and morphological measures were obtained and compared with muscles that either had synergists intact or were weight bearing or a combination of both. Synergist ablation prolonged PL maximum isometric twitch tension (Pt), time to peak tension (12%), and one-half relaxation time (12%); increased Pt (26%), maximum isometric tetanic tension (Po, 44%), fatigue resistance (FI, 42%), and fast fiber cross-sectional area (FT CSA, 20%); and decreased Pt/Po (13%) over nonablation counterparts. Suspension decreased PL Pt (26%), Po (26%), rest length (16%), FT CSA (31%), and slow-twitch fiber (ST) number (24%) but increased FI (75%) over weight-bearing counterparts. PL from weight-bearing animals were heavier than from suspended animals, and the extent of this response was greatest after synergist removal. Whole muscle and ST CSA and ST area contribution were greater only in weight-bearing synergist ablation muscles. Daily weight bearing (4 h) in synergist ablation hindlimb suspension groups caused PL weights and ST expressions to be halfway between 24-h suspension and 24-h weight-bearing groups. Our results suggest that weight bearing is not essential to the induction of several adaptations associated with synergist ablation but is required to cause the large muscle mass and ST expression characteristic of this model.


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