Single fiber analyses of type IIA myosin heavy chain distribution in hyper- and hypothyroid soleus

1993 ◽  
Vol 265 (3) ◽  
pp. C842-C850 ◽  
Author(s):  
V. J. Caiozzo ◽  
S. Swoap ◽  
M. Tao ◽  
D. Menzel ◽  
K. M. Baldwin
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Relative Proportion ◽  
Relative Number ◽  
Single Fiber ◽  
Type I ◽  
Shortening Velocity ◽  
Type I Fibers ◽  
Laser Cytometer

The objectives of this study were to 1) examine the effect of hypo- and hyperthyroidism (triiodothyronine treatment) on the distribution of type IIA myosin heavy chain (MHC) in the soleus at the single fiber level and 2) correlate changes in the single fiber distribution of type IIA MHC with the maximal shortening velocity of whole skeletal muscle. The presence of the type IIA MHC in single fibers was determined using a monoclonal antibody reactive to the type IIA MHC and quantified with a Meridian ACAS 570 interactive laser cytometer. The findings of this study demonstrate that 1) hyperthyroidism significantly increases the relative number of muscle fibers that express type IIA MHC, 2) not all type I fibers are capable of expressing fast type IIA MHC under hyperthyroid conditions, and 3) there is a high correlation between maximal shortening velocity and the relative number of type IIA fibers. This latter observation suggests that the maximal shortening velocity of whole skeletal muscle may not be solely determined by its fastest fiber(s) but rather by the relative proportion of fibers expressing fast type IIA MHC.

Working Capacity and Expression of Myosin Heavy Chain Isoforms in Skeletal Muscle of Chronic Alcoholic Men without Liver Disease after I Day and 4 Weeks of Alcohol Abstinence

1994 ◽  
Vol 86 (4) ◽  
pp. 433-440 ◽  
Author(s):  
L. Sestoft ◽  
P. Iversen ◽  
I. Nordgaard ◽  
S. Amris ◽  
T. Joen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Relative Proportion ◽  
Myosin Heavy Chain Isoforms ◽  
Type I ◽  
Working Capacity ◽  
Control Subjects ◽  
Alcohol Abstinence ◽  
Chain Type

1. The aim of this study was to examine the effect of chronic alcohol ingestion on working capacity and on the expression of myosin heavy chain isoforms in fibre types of human skeletal muscle. 2. Six alcoholic men having drunk more than 240 g of alcohol/day for more than 10 years underwent a test for working capacity and a muscle biopsy on the first day of alcohol abstinence (test 1) and again after 4 weeks of abstinence (test 2). The biopsies were analysed using histochemical, immunochemical and gel-electrophoretic techniques, and the results were compared with those from eight age-matched nonalcoholic control subjects. 3. The area of type IIB muscle fibres was decreased by 33% in the alcoholic patients compared with normal control subjects at both test 1 and test 2. The area of type IIA fibres was lower (13%) in alcoholic patients at test 1 than in the control group, and increased to the normal level at test 2. 4. The relative proportion of fibres expressing only myosin heavy chain type IIB isoforms was one-third of normal in the alcoholic patients at both tests 1 and 2. The relative proportion of fibres expressing only myosin heavy chain type IIA isoforms was the same in alcoholic patients at test 1 and in normal control subjects, but increased by 25% between test 1 and 2 in the alcoholic group. 5. The relative proportion of fibres showing co-expression of myosin heavy chain type IIA/IIB isoforms was about two-thirds of normal in alcoholic patients at both test 1 and test 2, whereas fibres with co-expression of myosin heavy chain type I/IIA were not seen in the control group, but were found in the alcoholic group, where they doubled from test 1 to test 2. 6. Thus, chronic heavy alcohol consumption modulates the expression of myosin heavy chain isoforms-in human skeletal muscle by decreasing the expression of myosin heavy chain type IIB and increasing the expression of myosin heavy chain type I. After 4 weeks of alcohol abstinence a shift in the expression of myosin heavy chain type I towards myosin heavy chain type IIA is evident, indicating that the effect of alcohol on myosin heavy chain expression is a reversible process. However, to obtain complete recovery with a normal level of myosin heavy chain type IIB expression, more than 4 weeks of abstinence is necessary. 7. Working capacity was low and unchanged by 4 weeks of alcohol abstinence. The low proportion of type IIB (fast twitch glycolytic) fibres at both test 1 and 2 coincided with a low lactate production during maximal exercise. The increased proportion of type I (slow twitch oxidative) fibres at test 1 coincided with an preferential lipid oxidation during the working period.

Force-velocity and force-power properties of single muscle fibers from elite master runners and sedentary men

1996 ◽  
Vol 271 (2) ◽  
pp. C676-C683 ◽  
Author(s):  
J. J. Widrick ◽  
S. W. Trappe ◽  
D. L. Costill ◽  
R. H. Fitts
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Power Output ◽  
Peak Power ◽  
Isometric Force ◽  
Peak Force ◽  
Peak Power Output ◽  
Type I ◽  
Shortening Velocity ◽  
Force Velocity

Gastrocnemius muscle fiber bundles were obtained by needle biopsy from five middle-aged sedentary men (SED group) and six age-matched endurance-trained master runners (RUN group). A single chemically permeabilized fiber segment was mounted between a force transducer and a position motor, subjected to a series of isotonic contractions at maximal Ca2+ activation (15 degrees C), and subsequently run on a 5% polyacrylamide gel to determine myosin heavy chain composition. The Hill equation was fit to the data obtained for each individual fiber (r2 > or = 0.98). For the SED group, fiber force-velocity parameters varied (P < 0.05) with fiber myosin heavy chain expression as follows: peak force, no differences: peak tension (force/fiber cross-sectional area), type IIx > type IIa > type I; maximal shortening velocity (Vmax, defined as y-intercept of force-velocity relationship), type IIx = type IIa > type I; a/Pzero (where a is a constant with dimensions of force and Pzero is peak isometric force), type IIx > type IIa > type I. Consequently, type IIx fibers produced twice as much peak power as type IIa fibers, whereas type IIa fibers produced about five times more peak power than type I fibers. RUN type I and IIa fibers were smaller in diameter and produced less peak force than SED type I and IIa fibers. The absolute peak power output of RUN type I and IIa fibers was 13 and 27% less, respectively, than peak power of similarly typed SED fibers. However, type I and IIa Vmax and a/Pzero were not different between the SED and RUN groups, and RUN type I and IIa power deficits disappeared after power was normalized for differences in fiber diameter. Thus the reduced absolute peak power output of the type I and IIa fibers from the master runners was a result of the smaller diameter of these fibers and a corresponding reduction in their peak isometric force production. This impairment in absolute peak power production at the single fiber level may be in part responsible for the reduced in vivo power output previously observed for endurance-trained athletes.

scholarly journals Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle

2009 ◽  
Vol 297 (4) ◽  
pp. R1037-R1048 ◽  
Author(s):  
Clay E. Pandorf ◽  
Weihua H. Jiang ◽  
Anqi X. Qin ◽  
Paul W. Bodell ◽  
Kenneth M. Baldwin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Fiber Type ◽  
Hindlimb Suspension ◽  
Chain Gene ◽  
Type I ◽  
Thyroid State

The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T3)] to suppress nearly all expression of type I MHC mRNA in the soleus muscle. HS + T3 was then withdrawn, and rats resumed normal ambulation and thyroid state, during which vehicle or CsA (30 mg·kg−1·day−1) was administered for 7 or 14 days. The findings demonstrate that, despite significant inhibition of Cn, pre-mRNA, mRNA, and protein abundance of type I MHC increased markedly during reloading relative to HS + T3 ( P < 0.05). Type I MHC expression was, however, attenuated by CsA compared with vehicle treatment. In addition, type IIa and IIx MHC pre-mRNA, mRNA, and relative protein levels were increased in Cn-treated compared with vehicle-treated rats. These findings indicate that Cn has a modulatory role in MHC transcription, rather than a role as a primary regulator of slow MHC gene expression.

scholarly journals Functional and structural adaptations of skeletal muscle to microgravity

2001 ◽  
Vol 204 (18) ◽  
pp. 3201-3208 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Peak Force ◽  
Type I ◽  
Type Ii ◽  
Shortening Velocity ◽  
Slow Type ◽  
Fiber Atrophy ◽  
Type I Fibers ◽  
Type Ii Fibers

SUMMARY Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20–48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm−2), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V0) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V0, peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established.

Polyadenylated RNA, actin mRNA, and myosin heavy chain mRNA in young and old human skeletal muscle

1996 ◽  
Vol 270 (2) ◽  
pp. E224-E229 ◽  
Author(s):  
S. Welle ◽  
K. Bhatt ◽  
C. Thornton
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Skeletal Muscle ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Type I ◽  
Polyadenylated Rna ◽  
Actin Mrna

The myofibrillar protein synthesis rate in old human skeletal muscle is slower than that in young adult muscle. To examine whether this difference in protein synthesis rate is explained by reduced availability of the mRNAs that encode the most abundant myofibrillar proteins, we determined relative hybridization signals from probes for actin mRNA, myosin heavy chain mRNA, and total polyadenylated RNA in vastus lateralis muscle biopsies taken from young (22- to 31-yr-old) and old (61- to 74-yr-old) human subjects. The mean fractional rate of myofibrillar synthesis was 38% slower in the older muscles, as determined by incorporation of a stable isotope tracer. Total actin and myosin heavy chain mRNAs, and polyadenylated RNA, were determined using slot-blot assays. Isoform-specific determinations of alpha-actin mRNA, type I myosin heavy chain mRNA, and type IIa myosin heavy chain mRNA were done with ribonuclease protection assays. Hybridization signals were expressed relative to tissue DNA content. There was no difference between age groups in total polyadenylated RNA or in any of the specific mRNAs. We conclude that the slower myofibrillar synthesis rate in older muscle is not caused by reduced mRNA availability.

Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?

2003 ◽  
Vol 285 (3) ◽  
pp. R570-R580 ◽  
Author(s):  
Vincent J. Caiozzo ◽  
Michael J. Baker ◽  
Karen Huang ◽  
Harvey Chou ◽  
Ya Zhen Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Muscle Fibers ◽  
Myosin Heavy Chain Isoforms ◽  
Single Fiber ◽  
Myosin Heavy Chain Isoform ◽  
Skeletal Muscle Fibers ◽  
Velocity Relationship ◽  
Force Velocity

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers ( n≈ 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I↔IIA↔IIX↔IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.

Myosin heavy chain isoforms of human muscle after short-term spaceflight

1995 ◽  
Vol 78 (5) ◽  
pp. 1740-1744 ◽  
Author(s):  
M. Y. Zhou ◽  
H. Klitgaard ◽  
B. Saltin ◽  
R. R. Roy ◽  
V. R. Edgerton ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Space Shuttle ◽  
Vastus Lateralis ◽  
Muscle Fibers ◽  
Rapid Change ◽  
Myosin Heavy Chain Isoforms ◽  
Single Fiber ◽  
Type I ◽  
Type Ii

The influence of microgravity on the myosin phenotype of skeletal muscle fibers in the vastus lateralis of eight crew members was studied before and after 5-day (n = 3) and 11-day (n = 5) spaceflights (space shuttle flights: STS-32, -33 and -34). Single-fiber electrophoresis analyses showed that the proportion of fibers expressing only slow (type I) myosin heavy chain (MHC) in the vastus lateralis was significantly lower after than before 11 days of spaceflight. Although the family of type II MHC isoforms was elevated post- compared with preflight, the distribution among the isoforms of type II MHC was not statistically different. Based on monoclonal and polyclonal antibodies specific for three adult MHC isoforms and single-fiber electrophoresis, approximately 3% of the fibers analyzed coexpressed all three adult MHC isoforms. The results from immunohistochemical staining with two different sets of antibodies indicate a reduction in the percentage of fibers expressing type I MHC as a result of spaceflight. The mean difference, however, was significant only when the fibers were categorized simply as type I or II. These changes appeared to be highly individualized among the astronauts. These results suggest that a rapid change in MHC isoform expression can occur in some muscle fibers after a relatively brief exposure to spaceflight.

Invited Review: Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

2001 ◽  
Vol 90 (1) ◽  
pp. 345-357 ◽  
Author(s):  
Kenneth M. Baldwin ◽  
Fadia Haddad
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Motor Proteins ◽  
Weight Bearing ◽  
Activity Level ◽  
Type I ◽  
Mechanical Stimuli ◽  
Energy Deprivation

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T3, 3,5,3′-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T3/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the β-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T3 or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T3 and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.

Effect of hypothyroidism on myosin heavy chain expression in rat pharyngeal dilator muscles

1992 ◽  
Vol 73 (1) ◽  
pp. 179-187 ◽  
Author(s):  
B. J. Petrof ◽  
A. M. Kelly ◽  
N. A. Rubinstein ◽  
A. I. Pack
Keyword(s):  
Thyroid Hormone ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Hormone Deficiency ◽  
Type I ◽  
Type Ii ◽  
Airway Patency ◽  
Obstructive Sleep ◽  
Type I Fibers ◽  
Fast Twitch

Although the association between hypothyroidism and obstructive sleep apnea is well established, the effect of thyroid hormone deficiency on contractile proteins in pharyngeal dilator muscles responsible for maintaining upper airway patency is unknown. In the present study, the effects of hypothyroidism on myosin heavy chain (MHC) expression were examined in the sternohyoid, geniohyoid, and genioglossus muscles of adult rats (n = 20). The relative proportions of MHC isoforms present were determined using MHC-specific monoclonal antibodies and oligonucleotide probes. All control muscles showed a paucity of type I MHC fibers, with greater than 90% of fibers containing fast-twitch type II MHCs. In the genioglossus muscle, a population of non-IIa non-IIb fast-twitch type II fibers (putatively identified as type IIx MHC fibers) were detected. Hypothyroidism induced significant changes in MHC expression in all muscles studied. In the sternohyoid, type I fibers increased from 6.2 to 16.9%, whereas type IIa fibers increased from 25.9 to 30.7%. Type I fibers in the geniohyoid increased from 1.2 to 12.8%, whereas type IIa fibers increased from 34.1 to 42.7%. The genioglossus showed the smallest relative increase in type I expression but the greatest induction of type IIa MHC. None of the muscles examined demonstrated reinduction of embryonic or neonatal MHC in response to thyroid hormone deficiency. In summary, hypothyroidism alters the MHC profile of pharyngeal dilators in a muscle-specific manner. These changes may play a role in the pathogenesis of obstructive apnea in hypothyroid patients.

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