| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Institut National de la Santé et de la Recherche Médicale U451-LOA-Ensta-Ecole Polytechnique, 91761 Palaiseau Cedex; and Services 2 d'ORL and 3 d'Explorations Fonctionnelles Cardiovasculaires et Respiratoires, Centre Hospitalier et Universitaire de Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control (n = 12) and mdx (n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice (P < 0.001). The total number of cross bridges per square millimeter (×109), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge (r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC (P < 0.001) than control mice and a reduction in type IIX MHC (P < 0.001) and slow myosin isoforms (P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.
mdx mice; cross bridge; muscle efficiency; skeletal muscle
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THE MDX mouse is a widely used animal model of human Duchenne muscular dystrophy, since a point mutation in the dystrophin gene results in lack of dystrophin (11). In skeletal muscle, this cytoskeletal protein forms a mechanical link between the submembranous network of cytoskeletal actin, a complex of membrane-bound glycoproteins and the extracellular matrix (32). Disruption of this linkage is presumed to cause sarcolemmal instability, stress-induced rupture of the sarcolemma, and/or excessive Ca2+ influx through altered ion channels (8, 32). This results in a progressive replacement of contractile muscle fibers by fat or connective tissue that is generally thought to account for severe muscle atrophy and weakness (24). Recent studies, however, have shown that the decrease in diaphragm strength in mdx mice is more pronounced than that predicted by the fibrosis area (18, 22). This suggests that, in addition to a reduction in contractile tissue, qualitative alterations of the contractile apparatus may also contribute to diaphragm weakness. However, the extent to which diaphragm mechanical changes in mdx mice reflect alterations in the molecular mechanics of myosin remains to be determined.
In striated muscles, cross bridges represent the molecular motors of force generation. According to the most widely accepted theory of contraction (12), cross bridges act as independent force generators. Therefore, muscle force depends on the elementary force produced per cross bridge and the total number of cross bridges formed (12, 13). The aim of our study was to determine the number, kinetics, and single force of cross bridges in diaphragm from mdx mice. Huxley's equations (12) were used to calculate the single force of cross bridges, total number of cross bridges, rate constant for attachment and detachment, peak mechanical efficiency, and total duration of the cross-bridge cycle (5, 16, 17) in control and mdx mouse diaphragm. We also studied the myosin isoform composition in control and mdx diaphragm. We tested two hypotheses: 1) that changes in diaphragm tension in dystrophic mice were related to modifications in the total number of cross bridges and/or in the amount of force generated per cross bridge and 2) that changes in the kinetics of the cross-bridge cycle were associated with changes in myosin isoform expression.
Glossary
| Lo | Optimal initial muscle length |
| s | Resting sarcomere length at Lo |
| Po | Maximum isometric tension |
| Vmax | Maximum shortening velocity |
| x | Instantaneous movement of the myosin head relative to actin (0  x h)
|
| h | Step size of the cross bridge |
| l | Distance between two actin sites |
| f1 | Maximum value of the rate constant for cross-bridge attachment at x = 0 |
| g1 | Maximum value of the rate constant for cross-bridge detachment at x = 0 |
| g2 | Maximum value of the rate constant for cross-bridge detachment at
x  h
|
| m | Cross-bridge number per mm2 (× 109) at Po |
 |
Elementary force per cross bridge |
| Effmax | Peak mechanical efficiency |
| MHC | Myosin heavy chain |
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Experimental Protocol
Experiments were conducted on 6-mo-old male mdx mice (n = 12) and age-matched control mice (C57BL/10ScSn, n = 12) obtained from Jackson Laboratory (Bar Harbor, ME). Care of the animals conformed to the Helsinki Convention. After anesthesia with pentobarbital sodium (40 mg/kg body wt ip), the animals were subjected first to a laparotomy and then to a thoracotomy. A strip of the ventral part of the costal diaphragm was carefully dissected out from the muscle in situ. The insertions on the central tendon and ribs were kept intact. The diaphragm strip was rapidly mounted in a tissue chamber containing Krebs-Henseleit solution (in mM): 118 NaCl, 24 NaHCO3, 4.7 KCl, 1.2 MgSO4 · 7 H2O, 1.1 KH2PO4, 2.5 CaCl2 · 6 H2O, and 4.5 glucose. The solution was bubbled with 95% O2-5% CO2 and maintained at 26°C and pH 7.4. The costal end of the muscle strip was held in a stationary clip at the bottom of the chamber; the central tendon end was maintained with a second clip, attached to an electromagnetic force-transducer device. After a 15-min equilibration period the muscle was supramaximally stimulated via two platinum electrodes arranged longitudinally on either side of the muscle. A force-frequency curve was determined by stimulating muscle strips at 25, 33, 50, 75, 100, and 200 Hz (train duration 300 ms, 10/min). Maximum isometric tension (Po) was generally achieved at a stimulation frequency of 100 Hz. Experiments were carried out at Lo, i.e., the initial resting length corresponding to the apex of the initial length-active tension curve. At the end of the experiment, the cross-sectional area (in mm2) was calculated from the ratio of muscle weight to muscle length at Lo, with the assumption of a muscle density of 1. The electromagnetic lever system has been described elsewhere (5, 16, 17). Lo was 6.8 ± 0.4 and 7.1 ± 0.3 mm in control and mdx diaphragm muscle strips, respectively (not significant).Mechanical Parameters
Force-velocity relationship.
The peak velocity (V) of 10 afterloaded contractions was plotted against the isotonic load level
normalized per cross-sectional area (P), obtained by successive load
increments from zero load up to the isometric tension.
Po, i.e., peak force normalized
per cross-sectional area, was measured from the fully isometric
contraction (in mN/mm2). Maximum
unloaded shortening velocity
(Vmax, in
Lo/s) was
measured from the contraction abruptly clamped to zero load just after stimulus. The experimental P-V
relationship was fitted according to Hill's equation (10): (P + a)(V + b) = (cPmax + a)b, where 
a and b
are the asymptotes of the hyperbola, as determined by multilinear
regression and the least-squares method, and
cPmax is the calculated Po at
V = 0. The curvature G of the P-V relationship is
equal to cPmax/a.
Cross-bridge number and kinetics.
Huxley's equations were used to calculate the rate of total energy
release (E, in
mW/mm2), the isotonic tension
(PHux, in
mN/mm2), and the rate of
mechanical energy
(WM, in
mW/mm2) as a function of
V (12).
E is given as
|
(1) |
h (12);
e is the free energy required to split
one ATP molecule (6, 12, 13), l is the distance between two actin sites, and 
= (f1 + g1)h/2 = b (12). For reasons of equation
dimensions, was multiplied by s/2
compared with the initial hypothesis (12). Consequently, calculations of f1,
g1, and
g2 were divided
by s/2 compared with those previously detailed (5, 16, 17) and are given by the following
equations
|
(2) |
|
(3) |
|
(4) |
|
(5) |
1) is
E0/(ems/2)
(12)
|
(6) |
|
(7) |
, in pN) is = PHux max/(ms/2)
|
(8) |
Values of Huxley's equation constants.
Stroke sizes ranging from 5 to 11 nm have been determined by using
optical tweezers (7, 19). These values correspond to the
three-dimensional structure of the myosin head (23) and support a
one-to-one coupling for ATP energy transduction, which is inherent to
Huxley's theory (6, 12, 13). In our study we chose a stroke size value
(h) of 11 nm;
l = 36 nm (30). The free energy
required to split one ATP molecule per contraction site
(e) is 5.1 × 10 20 J. Because
w is
0.75e (12),
w = 3.8 × 1020 J.
Myosin Electrophoresis
Preparations of crude myosin were obtained from the ventral part of the costal diaphragm, as previously described (5). Electrophoresis was performed in a Bio-Rad Mini-Protean II Dual Slab Cell electrophoresis system for 32 h at 4°C and 70 V (constant voltage). Long-duration electrophoresis was performed to discriminate between developmental (i.e., embryonic and neonatal) and adult heavy chains (1, 14). Control electrophoresis showing developmental myosin heavy chains (MHCs) from newborn mouse (1 day postnatal) skeletal muscles was also performed. MHCs were separated in dissociating conditions with 0.75 mM SDS-PAGE minigel electrophoresis (20). The stacking gel was composed of 4% acrylamide (2.67% bisacrylamide), 70 mM Tris (pH 6.8), 30% glycerol, 4 mM EDTA, and 0.1% SDS. The composition of the separating gel was 8% acrylamide (1% bisacrylamide), 0.2 M Tris, pH 8.8, 0.1 M glycine, and 0.4% SDS. Separate upper and lower running buffers were used. The upper running buffer consisted of 0.1 M Tris (base), 150 mM glycine, 11.5 mM 2-mercaptoethanol, and 0.1% SDS. The lower running buffer consisted of 50 mM Tris (base), 75 mM glycine, and 0.05% SDS. Both buffers were prepared shortly before use and cooled at 4°C. Gels were stained with 0.2% Coomassie blue, 50% ethanol, and 10% acetic acid and destained with 5% ethanol and 5% acetic acid. The different MHC isoforms were quantified by one-dimensional densitometry (model GS-690, Bio-Rad, Hercules, CA) with Macintosh software for Bio-Rad's image analysis system. The amount of each isoform was determined by the area of each peak. Data are expressed as percentages of the area of each peak divided by the sum of the areas of all peaks. It is widely considered that these methods provide reliable, reproducible data (1, 14). It has been suggested that an MHC band is detectable when present in ~1% of the sample (3). Identification of the specific myosin isoform bands was based on previous studies (1, 14, 20).Statistical Analysis
Values are means ± SE. After ANOVA, comparisons between groups were performed using Student's unpaired t-test. All comparisons were two-tailed, and P < 0.05 was considered statistically significant.| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Contractile Performance of the Diaphragm
Mechanical parameters of the diaphragm are presented in Fig. 1. Po was markedly depressed in mdx mice compared with age-matched controls (50% difference between mdx and control, P < 0.001). In addition, there was an ~30% reduction in Vmax in the mdx mice (P < 0.001).
|
Diaphragm Cross-Bridge Mechanics
The mdx mouse diaphragm exhibited an ~48% reduction in the total number of cross bridges per square millimeter compared with controls (P < 0.001; Fig. 2). Moreover, was
significantly lower in mdx than in
control mice (5% difference between
mdx and control, P < 0.001; Fig. 2).
Cross-bridge kinetics in control and
mdx mice are presented in Fig.
3. The total duration of the cross bridge cycle (tc) was
significantly shorter in mdx than in
control mice (P < 0.05; Fig. 3).
There was no difference in
f1 between groups (Fig. 3). In mdx mice,
g2 was
significantly lower than in control mice
(P < 0.001; Fig. 3). Conversely,
g1 was
significantly higher in mdx than in
control mice (P < 0.05; Fig. 3). The
G curvature of the force-velocity hyperbola was
significantly lower in mdx than in
control mice (9.5 ± 0.7 vs. 6.4 ± 0.3, P < 0.001). Moreover, Effmax and the relative tension at
which Effmax occurred were significantly lower in mdx than in
control mice (P < 0.001 and P < 0.05, respectively; Fig.
4).
|
|
|
Relationships Between Parameters
In the overall population, Po was linked to the total number of cross bridges and. Indeed, there was a strong
linear relationship between Po and
the total number of cross bridges per square millimeter (P < 0.001; Fig.
5A): the
greater the number of cross bridges, the higher was
Po. There was also a linear
relationship between Po and (P < 0.001; Fig.
5B). However, when separate
correlations for mdx and control mice
were performed, there was no longer any correlation between
Po and .
|
Myosin Isoform Composition
The electrophoretic separation of the different MHC isoforms present in normal and mdx mouse diaphragm is shown in Fig. 6. The mdx diaphragm contained a greater amount of type IIA MHC than controls (60 ± 1 vs. 37 ± 1%, P < 0.001), whereas the proportion of type IIX MHC was significantly lower (36 ± 2 vs. 55 ± 2, P < 0.001). In addition, there was a lower proportion of slow myosin isoforms in mdx than in control mice (3 ± 1 vs. 5 ± 1%, P < 0.01). Type IIB myosin isoforms, which represented 3 ± 1% of MHC in control diaphragm, represented only 1 ± 1% of MHC in mdx mouse diaphragm (P < 0.01). None of the adult diaphragm muscles demonstrated reinduction of developmental MHC isoforms (Fig. 6). In the overall population, there was a negative correlation between the proportion of type IIA MHC and both Vmax and Po (r =0.83 and
r = 0.82, respectively), whereas the proportion of type IIX MHC was positively correlated to
Vmax and
Po
(r = 0.87 and
r = 0.73, respectively). However, when
separate correlations for mdx and
control mice were performed, there was no correlation between the
proportion of type IIA or IIX MHC isoforms and either
Vmax or
Po.
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
We demonstrated that, in mdx mice, diaphragm dystrophy was associated with functional and quantitative changes in myosin molecular motors. Reduced diaphragm strength was associated with a decrease in the number of cross bridges generating contractile force and also in the elementary force generated per actomyosin interaction. In mdx mouse diaphragm, there were changes in the cross-bridge kinetics and a reduction in peak mechanical efficiency. Molecular myosin dysfunction was associated with changes in myosin isoform pattern, mainly characterized by a shift from the type IIX to the type IIA MHC isoform.
Relevance of the Experimental Model
In our study, cross-bridge kinetics and were calculated from
mechanical data in isolated diaphragm muscle by using Huxley's classic
equations (5, 12, 16, 17). In muscle strips, series compliance and
muscle fiber heterogeneity may affect mechanical properties and
cross-bridge cycling kinetics. Given that impaired muscle compliance
has been reported in mdx diaphragm
(24), we cannot totally exclude the possibility that the small
difference in the calculated unitary force per cross bridge may be due
entirely to the differences in the passive properties of the tissue. It is important to note that experiments designed to apply the principles of Huxley's theory were performed on isolated frog sartorius muscles, and not on isolated fibers (12). The equations can therefore be applied
to multicellular preparations such as diaphragm muscle strips. The
question arises as to whether Huxley's model can be applied to muscles
with heterogeneous MHC isoform composition. In his paper
(12), Huxley demonstrates that his equations accurately fit the
force-velocity characteristics shown by Hill in frog sartorius muscle
(10). The model thus accurately fits the mechanical properties of a
muscle that is composed of different MHCs. In heterogeneous muscle the
force-velocity characteristics are thought to reflect the relative
contribution of each fiber type (30). Likewise, according to Huxley's
equations (12), cross-bridge characteristics are thought to reflect the
average value of the myosin molecular motors.
In normal skeletal muscle, novel methodologies such as optical tweezers (7, 19, 21) and glass needle techniques (31) have enabled direct measurement of cross-bridge unitary force. In these studies the single force produced by a unitary myosin head was found to vary from 1 to 9 pN. The cross-bridge single force reported in our study was of the same order of magnitude as that previously measured in skeletal muscle myosins (7, 19, 31).
Force and Number of Cross Bridges
According to the theory of muscle contraction (12, 13), Po is related to m ×. Our results showed that
diaphragm from mdx mice exhibited an
~50% reduction in m, a finding in
agreement with the decrease in viable contractile tissue reported in
mdx diaphragm (18, 22, 24). Moreover,
we found that the elementary force produced per myosin head was lower
in diaphragm from mdx mice than from
controls (Fig. 2). Although moderate (~5%), the difference in force
produced per cross-bridge interaction between control and
mdx mouse diaphragm was highly
significant. Moreover, linear relationships between muscle tension and
either or m suggested that
decreases in m and accounted for
the impaired respiratory muscle function in the dystrophic mouse (Fig.
5). This result is in good agreement with the proposal that
"viable" fibers from mdx mouse
diaphragm have an impaired capacity to produce force (18, 22).
Theoretically, reduced elementary force produced per myosin head may result from molecular modifications of the myosin head structure and/or from functional alterations in the actomyosin interaction (26). It has been suggested that different myosin isoforms differ substantially in their force-generating capacities (4, 9, 22). In 3-mo-old mdx mouse diaphragm, a transitory expression of embryonic myosin isoforms has been found, which might contribute to the weaker force observed (22). However, in 6-mo-old mdx mouse diaphragm, developmental MHC isoforms were not observed (Fig. 6), as previously reported in older mdx mouse diaphragm (22). Alternatively, one can hypothesize that changes in the relative proportion of adult myosin isoforms observed in mdx mouse diaphragm may help explain changes in cross-bridge force. Compared with controls, 6-mo-old mdx diaphragm exhibited an increase in type IIA MHC and a corresponding decrease in type IIX MHC, with small changes in the fast-to-slow MHC ratio. In skeletal muscle the amount of force generated by slow myosin isoform has been reported to be higher than that produced by fast myosin isoforms (4). Conversely, no significant difference in isometric tension has been found among fast fiber types (4). Therefore, it is unlikely that changes in the relative proportion of myosin isoforms would account for the reduced force per cross bridge in the mdx mouse, even if a substantial number of fibers expressed varying amounts of type IIA + type IIX myosins in mdx diaphragm.
Cross-Bridge Kinetics and Reduced Muscle Efficiency
In our study, Effmax was lower in mdx than in control diaphragm, and the percentage of total tension at peak efficiency was shifted toward lower levels of load (Fig. 4). Similar findings have been reported in rabbit diaphragm during congestive heart failure (16). These two abnormalities may place the mdx mouse diaphragm in disadvantageous energetic conditions, particularly during a breathing effort. Moreover, tc was significantly shorter in mdx than in control mouse diaphragm (Fig. 3). If it is assumed that one molecule of ATP is hydrolyzed per cross-bridge cycle (6, 12, 13), then the overall cycle of ATP splitting takes place more rapidly in mdx than in control mouse diaphragm. Accordingly, the rate of myosin ATPase activity per cross bridge (i.e., the reciprocal of tc) was expected to be higher in mdx mouse diaphragm, consistent with the decreased Effmax (16, 30). Reduced efficiency of skeletal muscles and a shorter time cycle have generally been explained by a reduced percentage of slow-twitch type I fibers and an increased percentage of fast-twitch type II fibers (30). In mdx mice, there was a slight but significant decrease in the proportion of slow myosin isoforms (3% compared with 5% in controls). However, it is unlikely that this 2% decrease was an important factor in explaining the reduction in Effmax and tc. Moreover, because of the lower actomyosin ATPase activity of the type IIA MHC isoform (25), the shift from the type IIX to the type IIA MHC isoform in mdx mice would be expected to prolong tc, thereby increasing Effmax. It is therefore unlikely that changes in the relative proportion of myosin isoforms in the mdx mouse would account for the reduction in Effmax and tc.Our results showed that Vmax was significantly lower in mdx than in control mouse diaphragm. Vmax is thought to be governed by the rate constant of cross-bridge dissociation at the end of the working stroke (g2) (12). In accordance with this theory, we found a significantly lower g2; i.e., the time for cross-bridge dissociation was higher in mdx than in control mice. Several studies have identified a correlation between Vmax and either maximum actin-activated myosin ATPase activity (2) or the myosin isoform composition (3, 27). With the diversity of fast-twitch fiber subtypes taken into account, other studies have also found a correlation between Vmax and the relative expression of fast myosin isoforms (3, 15). However, no significant differences in shortening velocity between type IIA and type IIX fibers have been reported (3). It is thus unlikely that the higher proportion of type IIA MHC and the lower proportion of type IIX MHC can explain the reduced Vmax in mdx mouse diaphragm. Different hypotheses have been proposed to explain changes in velocity of movement in skeletal muscle fibers. It has been suggested that myosin light chain isoforms have a role in determining Vmax (3, 27). Thus we cannot exclude the possibility that changes occurred in myosin light chain isoform composition and that these changes contributed to the reduction in shortening velocity in mdx mouse diaphragm. Alternatively, it has been proposed that distinct molecular mechanisms regulate actin-activated ATPase activity and the velocity of filament movement (26, 29), so that changes in actin-activated ATP hydrolysis can occur without significant alteration in the velocity of filament movement. Such mechanisms may play a role in dissociating changes in shortening velocity and actin-activated ATP hydrolysis.
Our study has certain limitations, which need to be discussed. When all
cross bridges generating contractile force were taken into account, we
found that the elementary peak force generated per myosin interaction
was lower in mdx than in control mice. Given the nonhomogeneity in mdx mouse
diaphragm, it is possible that some cross bridges were mildly affected
and thus generated normal or subnormal force per cross-bridge
interaction, whereas others were more severely affected and thus
generated very low force per cross-bridge interaction. Because the
calculated reflected a mean value based on all the cross bridges,
it is possible that this mean value was higher than the elementary
force produced by the more severely affected cross bridges. Absence of
dystrophin is the primary defect in Duchenne muscular dystrophy and
diaphragm from mdx mice (11, 32).
Although the precise mechanism whereby lack of dystrophin causes muscle
degeneration is unknown, it is widely thought that the absence of
dystrophin directly or indirectly results in sarcolemma instability,
increased intracellular free Ca2+,
enhanced net degradation of muscle proteins, and cell necrosis (28).
Our results indicated that myosin motor dysfunction also occurred in
mdx mouse diaphragm and may, at least
in part, account for diaphragm weakness. However, the nature and train
of events that lead to myosin motor dysfunction remain to be elucidated.
In conclusion, in mdx mouse diaphragm, the decline in the total number of cross bridges was associated with a reduction in the elementary force produced per actomyosin interaction. Changes in MHC isoforms may help explain some, but not all, of the modifications in the kinetics of myosin molecular motors. Further studies are needed to determine whether functional and/or structural abnormalities are involved in molecular motor dysfunction in diaphragm from mdx mice.
| |
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: C. Coirault, INSERM 451-LOA-Ecole Polytechnique, Batterie de l'Yvette, 91761 Palaiseau Cedex, France (E-mail: coirault{at}enstay.ensta.fr).
Received 30 November 1998; accepted in final form 5 August 1999.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Agbulut, O.,
Z. Li,
V. Mouly,
and
G. S. Butler-Browne.
Analysis of skeletal and cardiac muscle from desmin knock-out and normal mice by high resolution separation of myosin heavy-chain isoforms.
Biol. Cell
88:
131-135,
1996[Medline].
2.
Bárány, M.
ATPase activity of myosin correlated with speed of muscle shortening.
J. Gen. Physiol.
50:
197-218,
1967
3.
Bottinelli, R.,
R. Betto,
S. Schiaffino,
and
C. Reggiani.
Unloaded shortening velocity and myosin heavy chain and alkali light chain isoform composition in rat skeletal muscle fibres.
J. Physiol. (Lond.)
478:
341-349,
1994
4.
Bottinelli, R.,
S. Schiaffino,
and
C. Reggiani.
Force-velocity relations and myosin heavy chain isoform compositions of skinned fibres from rat skeletal muscle.
J. Physiol. (Lond.)
437:
655-672,
1991
5.
Coirault, C.,
F. Lambert,
T. Joseph,
F.-X. Blanc,
D. Chemla,
and
Y. Lecarpentier.
Developmental changes in crossbridge properties and myosin isoforms in hamster diaphragm.
Am. J. Respir. Crit. Care Med.
156:
959-967,
1997
6.
Eisenberg, E.,
T. L. Hill,
and
Y. D. Chen.
Cross-bridge model of muscle contraction. Quantitative analysis.
Biophys. J.
29:
195-227,
1980[Medline].
7.
Finer, J. T.,
R. M. Simmons,
and
J. A. Spudich.
Single myosin molecule mechanics: piconewton forces and nanometre steps.
Nature
368:
113-119,
1994[Medline].
8.
Fong, P.,
P. R. Turner,
W. F. Denetclaw,
and
R. A. Steinhardt.
Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin.
Science
150:
673-676,
1990.
9.
Harris, D. E.,
S. S. Work,
R. K. Wright,
N. R. Alpert,
and
D. M. Warshaw.
Smooth, cardiac and skeletal muscle myosin force and motion generation assessed by cross-bridge mechanical interactions in vitro.
J. Muscle Res. Cell Motil.
15:
11-19,
1994[Medline].
10.
Hill, A. V.
The heat of shortening and the dynamic constants of muscle.
Proc. R. Soc. Lond. Biol. Sci.
126:
136-195,
1938
11.
Hoffman, E. P.,
A. P. Monaco,
C. C. Feener,
and
L. M. Kunkel.
Conservation of the Duchenne muscular dystrophy gene in mice and humans.
Science
238:
347-350,
1987
12.
Huxley, A. F.
Muscle structure and theories of contraction.
Prog. Biophys. Biophys. Chem.
7:
255-318,
1957[Medline].
13.
Huxley, A. F.,
and
R. M. Simmons.
Proposed mechanism of force generation in striated muscle.
Nature
233:
533-538,
1971[Medline].
14.
Janmot, C.,
and
A. d'Albis.
Electrophoretic separation of developmental and adult rabbit skeletal muscle myosin heavy chain isoforms: example of application to muscle denervation study.
FEBS Lett.
353:
13-15,
1994[Medline].
15.
Larsson, L.,
and
R. L. Moss.
Maximum velocity of shortening in relation to myosin isoform composition in single fibres from human skeletal muscles.
J. Physiol. (Lond.)
472:
595-614,
1993
16.
Lecarpentier, Y.,
D. Chemla,
F.-X. Blanc,
J.-C. Pourny,
T. Joseph,
B. Riou,
and
C. Coirault.
Mechanics, energetics, and crossbridge kinetics of rabbit diaphragm during congestive heart failure.
FASEB J.
12:
981-989,
1998
17.
Lecarpentier, Y.,
C. Coirault,
G. Lerebours,
P. Desché,
E. Scalbert,
F. Lambert,
and
D. Chemla.
Effects of angiotensin-converting enzyme inhibition on crossbridge properties of diaphragm in cardiomyopathic hamsters of the dilated Bio 53-58 strain.
Am. J. Respir. Crit. Care Med.
155:
630-636,
1997[Abstract].
18.
Lynch, G. S.,
J. A. Rafael,
R. T. Hinkle,
N. M. Cole,
J. S. Chamberlain,
and
J. A. Faulkner.
Contractile properties of diaphragm muscle segments from old mdx and old transgenic mdx mice.
Am. J. Physiol.
272 (Cell Physiol. 41):
C2063-C2068,
1997
19.
Molloy, J. E.,
J. E. Burns,
J. Kendrick-Jones,
R. T. Tregear,
and
D. C. S. White.
Movement and force produced by a single myosin head.
Nature
378:
209-212,
1995[Medline].
20.
Mortola, J. P.,
and
L. Naso.
Electrophoretic analysis of contractile proteins of the diaphragm in chronically hypoxic rats.
Am. J. Physiol.
269 (Lung Cell. Mol. Physiol. 13):
L371-L376,
1995
21.
Nishizaka, T.,
H. Miyata,
H. Yoshikawa,
S. Ishiwata,
and
K. Kinosita.
Unbinding force of a single motor molecule measured using optical tweezers.
Nature
377:
251-254,
1995[Medline].
22.
Petrof, B. J.,
H. H. Stedman,
J. B. Shrager,
J. Eby,
H. L. Sweeney,
and
A. M. Kelly.
Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm.
Am. J. Physiol.
265 (Cell Physiol. 34):
C834-C841,
1993
23.
Rayment, I.,
W. R. Rypniewski,
K. Schmidt-Bäse,
R. Smith,
D. R. Tomchick,
M. M. Benning,
D. A. Winkelmann,
G. Wesenberg,
and
H. M. Holden.
Three-dimensional structure of myosin subfragment-1: a molecular motor.
Science
261:
50-58,
1993
24.
Shrager, J. B.,
H. H. Stedman,
H. L. Sweeney,
B. Petrof,
and
A. M. Kelly.
The mdx mouse and mdx diaphragm. Implications for the pathogenesis of Duchenne muscular dystrophy.
In: Neuromuscular Development and Disease, edited by A. M. Kelly,
and H. M. Blau. New York: Raven, 1992, p. 317-328.
25.
Sieck, G. C.,
W. Z. Zhan,
Y. S. Prakash,
M. J. Daood,
and
J. F. Watchko.
SDH activity and ATPase activities of different fiber types in rat diaphragm muscle.
J. Appl. Physiol.
79:
1629-1639,
1995
26.
Spudich, J. A.
How molecular motors work.
Nature
372:
515-518,
1994[Medline].
27.
Sweeney, H. L.,
M. J. Kushmerick,
K. Mabuchi,
F. A. Sreter,
and
J. Gergely.
Myosin alkali light chain and heavy chain variations correlate with altered shortening velocity of isolated skeletal muscle fibers.
J. Biol. Chem.
263:
9034-9039,
1988
28.
Turner, P. R.,
T. Westwood,
C. M. Regen,
and
R. A. Steinhardt.
Increased protein degradation results from elevated free calcium levels found in muscle from mdx mice.
Nature
335:
735-738,
1988[Medline].
29.
Uyeda, T. Q. P.,
K. M. Ruppel,
and
J. A. Spudich.
Enzymatic activities correlate with chimaeric substitutions at the actin-binding face of myosin.
Nature
368:
567-569,
1994[Medline].
30.
Woledge, R. C.,
N. A. Curtin,
and
E. Homsher.
Energetic aspects of muscle contraction.
Monogr. Physiol. Soc.
41:
27-117,
1985.
31.
Yanagida, T.,
T. Harada,
and
A. Ishijima.
Nano-manipulation of actomyosin molecular motors in vitro: a new working principle.
Trends Biol. Sci.
18:
319-324,
1993.
32.
Zubryzcka-Gaarn, E. E.,
D. E. Bulman,
G. Karpati,
A. H. Burghes,
B. Belfall,
H. J. Klamut,
J. Talbot,
R. S. Hodges,
P. N. Ray,
and
R. G. Worton.
The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle.
Nature
333:
466-469,
1988[Medline].
This article has been cited by other articles:
|
|
 |
|
  G. D'Antona, L. Brocca, O. Pansarasa, C. Rinaldi, R. Tupler, and R. Bottinelli Structural and functional alterations of muscle fibres in the novel mouse model of facioscapulohumeral muscular dystrophy J. Physiol., November 1, 2007; 584(3): 997 - 1009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Consolino, F. Duclos, J. Lee, R. A. Williamson, K. P. Campbell, and S. V. Brooks Muscles of mice deficient in {alpha}-sarcoglycan maintain large masses and near control force values throughout the life span Physiol Genomics, July 14, 2005; 22(2): 244 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Laws and A. Hoey Progression of kyphosis in mdx mice J Appl Physiol, November 1, 2004; 97(5): 1970 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Coirault, B. Pignol, R. N. Cooper, G. Butler-Browne, P.-E. Chabrier, and Y. Lecarpentier Severe muscle dysfunction precedes collagen tissue proliferation in mdx mouse diaphragm J Appl Physiol, May 1, 2003; 94(5): 1744 - 1750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Grange, T. G. Gainer, K. M. Marschner, R. J. Talmadge, and J. T. Stull Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stress Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1090 - C1101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hosaka, T. Yokota, Y. Miyagoe-Suzuki, K. Yuasa, M. Imamura, R. Matsuda, T. Ikemoto, S. Kameya, and S.'i. Takeda {alpha}1-Syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration J. Cell Biol., September 16, 2002; 158(6): 1097 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Watchko, T. L. O'Day, and E. P. Hoffman Functional characteristics of dystrophic skeletal muscle: insights from animal models J Appl Physiol, August 1, 2002; 93(2): 407 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Blake, A. Weir, S. E. Newey, and K. E. Davies Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle Physiol Rev, April 1, 2002; 82(2): 291 - 329. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
P < 0.001 compared with
controls.
