Paradoxical absence of M lines and downregulation of creatine kinase in mouse extraocular muscle

2003 ◽  
Vol 95 (2) ◽  
pp. 692-699 ◽  
Author(s):  
Francisco H. Andrade ◽  
Anita P. Merriam ◽  
Wei Guo ◽  
Georgiana Cheng ◽  
Colleen A. McMullen ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Extraocular Muscle ◽  
Skeletal Muscles ◽  
Extraocular Muscles ◽  
Muscle Group ◽  
M Protein ◽  
Striated Muscles ◽  
Functional Requirements ◽  
Active Muscle ◽  
Leg Muscles

The M lines are structural landmarks in striated muscles, necessary for sarcomeric stability and as anchoring sites for the M isoform of creatine kinase (CK-M). These structures, especially prominent in fast skeletal muscles, are missing in rodent extraocular muscle, a particularly fast and active muscle group. In this study, we tested the hypotheses that 1) myomesin and M protein (cytoskeletal components of the M lines) and CK-M are downregulated in mouse extraocular muscle compared with the leg muscles, gastrocnemius and soleus; and 2) the expression of other cytosolic and mitochondrial CK isoforms is correspondingly increased. As expected, mouse extraocular muscles expressed lower levels of myomesin, M protein, and CK-M mRNA than the leg muscles. Immunocytochemically, myomesin and M protein were not detected in the banding pattern typically seen in other skeletal muscles. Surprisingly, message abundance for the other known CK isoforms was also lower in the extraocular muscles. Moreover, total CK activity was significantly decreased compared with that in the leg muscles. Based on these data, we reject our second hypothesis and propose that other energy-buffering systems may be more important in the extraocular muscles. The downregulation of major structural and metabolic elements and relative overexpression of two adenylate kinase isoforms suggest that the extraocular muscle group copes with its functional requirements by using strategies not seen in typical skeletal muscles.

scholarly journals E-box sites and a proximal regulatory region of the muscle creatine kinase gene differentially regulate expression in diverse skeletal muscles and cardiac muscle of transgenic mice.

1996 ◽  
Vol 16 (9) ◽  
pp. 5058-5068 ◽  
Author(s):  
M A Shield ◽  
H S Haugen ◽  
C H Clegg ◽  
S D Hauschka
Keyword(s):  
Creatine Kinase ◽  
Skeletal Muscles ◽  
Transgene Expression ◽  
Regulatory Region ◽  
Regulatory Sequences ◽  
Striated Muscles ◽  
Muscle Creatine Kinase ◽  
E Box ◽  
Muscle Creatine ◽  
E Boxes

Previous analysis of the muscle creatine kinase (MCK) gene indicated that control elements required for transcription in adult mouse muscle differed from those required in cell culture, suggesting that distinct modes of muscle gene regulation occur in vivo. To examine this further, we measured the activity of MCK transgenes containing E-box and promoter deletions in a variety of striated muscles. Simultaneous mutation of three E boxes in the 1,256-bp MCK 5' region, which abolished transcription in muscle cultures, had strikingly different effects in mice. The mutations abolished transgene expression in cardiac and tongue muscle and caused a reduction in expression in the soleus muscle (a muscle with many slow fibers) but did not affect expression in predominantly fast muscles: quadriceps, abdominals, and extensor digitorum longus. Other regulatory sequences with muscle-type-specific activities were found within the 358-bp 5'-flanking region. This proximal region conferred relatively strong expression in limb and abdominal skeletal muscles but was inactive in cardiac and tongue muscles. However, when the 206-bp 5' enhancer was ligated to the 358-bp region, high levels of tissue-specific expression were restored in all muscle types. These results indicate that E boxes and a proximal regulatory region are differentially required for maximal MCK transgene expression in different striated muscles. The overall results also imply that within skeletal muscles, the steady-state expression of the MCK gene and possibly other muscle genes depends on transcriptional mechanisms that differ between fast and slow fibers as well as between the anatomical and physiological attributes of each specific muscle.

PARTICIPATION OF SKELETAL MUSCLE AND KIDNEY DURING NONSHIVERING THERMOGENESIS IN COLD-ACCLIMATED RATS

1963 ◽  
Vol 41 (4) ◽  
pp. 953-964 ◽  
Author(s):  
L. Jansky ◽  
J. S. Hart
Keyword(s):  
Oxygen Consumption ◽  
Skeletal Muscles ◽  
Direct Evidence ◽  
Striated Muscles ◽  
Noradrenaline Infusion ◽  
Leg Muscles ◽  
Exposure To Cold ◽  
Sodium Barbital ◽  
Shivering Thermogenesis

The oxygen consumption of the partly isolated leg muscles and of the kidney was measured in situ in cold-acclimated rats before and during exposure to cold or during noradrenaline infusion. All rats had been anesthetized with sodium barbital and those exposed to cold had been fully curarized to prevent muscle activity. During cold exposure and noradrenaline infusion oxygen consumption of the rats was approximately doubled, and the oxygen consumption of leg muscles was approximately doubled without increase in blood flow. No increase in oxygen consumption was observed in the kidney during exposure to cold or noradrenaline infusion in spite of an increase of 75% in the oxygen consumption of the whole animal. Direct evidence for significant participation of striated muscles in non-shivering thermogenesis has thus been obtained. However, it appears unlikely that the maximal potential increase in oxygen consumption of cold-acclimated rats at very low temperatures could be attributed solely to the metabolic activity of skeletal muscles.

The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin

1998 ◽  
Vol 111 (13) ◽  
pp. 1801-1811 ◽  
Author(s):  
J.D. Porter ◽  
J.A. Rafael ◽  
R.J. Ragusa ◽  
J.K. Brueckner ◽  
J.I. Trickett ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Extraocular Muscle ◽  
Skeletal Muscles ◽  
Extraocular Muscles ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Fiber Types ◽  
Eye Muscle ◽  
Muscle Sparing

The extraocular muscles are one of few skeletal muscles that are structurally and functionally intact in Duchenne muscular dystrophy. Little is known about the mechanisms responsible for differential sparing or targeting of muscle groups in neuromuscular disease. One hypothesis is that constitutive or adaptive properties of the unique extraocular muscle phenotype may underlie their protection in dystrophinopathy. We assessed the status of extraocular muscles in the mdx mouse model of muscular dystrophy. Mice showed mild pathology in accessory extraocular muscles, but no signs of pathology were evident in the principal extraocular muscles at any age. By immunoblotting, the extraocular muscles of mdx mice exhibited increased levels of a dystrophin analog, dystrophin-related protein or utrophin. These data suggest, but do not provide mechanistic evidence, that utrophin mediates eye muscle protection. To examine a potential causal relationship, knockout mouse models were used to determine whether eye muscle sparing could be reversed. Mice lacking expression of utrophin alone, like the dystrophin-deficient mdx mouse, showed no pathological alterations in extraocular muscle. However, mice deficient in both utrophin and dystrophin exhibited severe changes in both the accessory and principal extraocular muscles, with the eye muscles affected more adversely than other skeletal muscles. Selected extraocular muscle fiber types still remained spared, suggesting the operation of an alternative mechanism for muscle sparing in these fiber types. We propose that an endogenous upregulation of utrophin is mechanistic in protecting extraocular muscle in dystrophinopathy. Moreover, data lend support to the hypothesis that interventions designed to increase utrophin levels may ameliorate the pathology in other skeletal muscles in Duchenne muscular dystrophy.

PARTICIPATION OF SKELETAL MUSCLE AND KIDNEY DURING NONSHIVERING THERMOGENESIS IN COLD-ACCLIMATED RATS

1963 ◽  
Vol 41 (1) ◽  
pp. 953-964 ◽  
Author(s):  
L. Jansky ◽  
J. S. Hart
Keyword(s):  
Oxygen Consumption ◽  
Skeletal Muscles ◽  
Direct Evidence ◽  
Striated Muscles ◽  
Noradrenaline Infusion ◽  
Leg Muscles ◽  
Exposure To Cold ◽  
Sodium Barbital ◽  
Shivering Thermogenesis

The oxygen consumption of the partly isolated leg muscles and of the kidney was measured in situ in cold-acclimated rats before and during exposure to cold or during noradrenaline infusion. All rats had been anesthetized with sodium barbital and those exposed to cold had been fully curarized to prevent muscle activity. During cold exposure and noradrenaline infusion oxygen consumption of the rats was approximately doubled, and the oxygen consumption of leg muscles was approximately doubled without increase in blood flow. No increase in oxygen consumption was observed in the kidney during exposure to cold or noradrenaline infusion in spite of an increase of 75% in the oxygen consumption of the whole animal. Direct evidence for significant participation of striated muscles in non-shivering thermogenesis has thus been obtained. However, it appears unlikely that the maximal potential increase in oxygen consumption of cold-acclimated rats at very low temperatures could be attributed solely to the metabolic activity of skeletal muscles.

Distribution of c-protein isoforms in sarcomeres of developing chick skeletal muscle

1988 ◽  
Vol 46 ◽  
pp. 226-227
Author(s):  
D. A. Fischman ◽  
J. E. Dennis ◽  
T. Obinata ◽  
H. Takano-Ohmuro
Keyword(s):  
Skeletal Muscles ◽  
Thick Filament ◽  
Protein Isoforms ◽  
Actin Binding ◽  
Striated Muscles ◽  
C Protein ◽  
Sarcomeric Protein ◽  
Thick Filaments ◽  
Cross Bridges ◽  
Bridge Bearing

C-protein is a 150 kDa protein found within the A bands of all vertebrate cross-striated muscles. By immunoelectron microscopy, it has been demonstrated that C-protein is distributed along a series of 7-9 transverse stripes in the medial, cross-bridge bearing zone of each A band. This zone is now termed the C-zone of the sarcomere. Interest in this protein has been sparked by its striking distribution in the sarcomere: the transverse repeat between C-protein stripes is 43 nm, almost exactly 3 times the 14.3 nm axial repeat of myosin cross-bridges along the thick filaments. The precise packing of C-protein in the thick filament is still unknown. It is the only sarcomeric protein which binds to both myosin and actin, and the actin-binding is Ca-sensitive. In cardiac and slow, but not fast, skeletal muscles C-protein is phosphorylated. Amino acid composition suggests a protein of little or no αhelical content. Variant forms (isoforms) of C-protein have been identified in cardiac, slow and embryonic muscles.

RESULTS OF POLARIZED LIGHT USE FOR STUDY OF STRESS-STRAIN STATE OF CORNEA IN PATHOLOGY OF EXTRAOCULAR MUSCLES

2020 ◽  
pp. 65-69
Author(s):  
Nataliia Mykhailivna Kovtun ◽  
Ihor Volodymyrovych Kaplin
Keyword(s):  
Interference Pattern ◽  
Optical Anisotropy ◽  
Extraocular Muscle ◽  
Strain State ◽  
Polarized Light ◽  
Attachment Site ◽  
Rectus Muscle ◽  
Extraocular Muscles ◽  
Asymmetric Distortion ◽  
Interference Picture

The parameters of interference patterns observed on the cornea in a polarized light in pathology of extraocular muscles were quantitatively evaluated. A study of the shape of 147 interference patterns observed on the cornea in a polarized light showed that the horizontal deviation of an eye in 56 % of cases was caused by the displacement of the attachment of the upper rectus muscle towards the inner rectus muscle. During illumination of the cornea of a live eye with polarized light, a specific interference pattern in the form of a rhombus formed by rainbow stripes (isochromes) is observed. It is established that such an interference pattern is the result of the influence of extraocular muscles on the cornea. The findings showed that the weakening of the force of one of muscles leads to asymmetric distortion of the shape of the interference rhombus, which is manifested with a reduced length of the corresponding section of the diagonal. On the contrary, as the force of the muscle increases, the corresponding section of the diagonal enhances. The displacement of the attachment site of direct extraocular muscle along the line of action is equivalent to a change in effort on its part, indicated appropriately by the shape of the interference rhombus. As the muscle moves away from the line of action, the angle of the interference rhombus is shifted away from the corresponding meridian. Key words: polarized light, optical anisotropy, cornea, extra−ocular muscles, interference picture.

Phylogenetic implications of the superfast myosin in extraocular muscles

2002 ◽  
Vol 205 (15) ◽  
pp. 2189-2201 ◽  
Author(s):  
Fred Schachat ◽  
Margaret M. Briggs
Keyword(s):  
Myosin Heavy Chain ◽  
Gene Cluster ◽  
Heavy Chain ◽  
Striated Muscle ◽  
Extraocular Muscles ◽  
Chromosome 17 ◽  
Striated Muscles ◽  
Chromosome 11 ◽  
Phylogenetic Implications ◽  
Myh Gene

SUMMARY Extraocular muscle exhibits higher-velocity and lower-tension contractions than other vertebrate striated muscles. These distinctive physiological properties are associated with the expression of a novel extraocular myosin heavy chain (MYH). Encoded by the MYH13 gene, the extraocular myosin heavy chain is a member of the fast/developmental MYH gene cluster on human chromosome 17 and the syntenic MYH cluster on mouse chromosome 11. Comparison of cDNA sequences reveals that MYH13 also encodes the atypical MYH identified in laryngeal muscles, which have similar fast contractile properties. Comparing the MYH13 sequence with the other members of the fast/developmental cluster, the slow/cardiac MYH genes and two orphan skeletal MYH genes in the human genome provides insights into the origins of specialization in striated muscle myosins. Specifically, these studies indicate (i) that the extraocular myosin is not derived from the adult fast skeletal muscle myosins, but was the first member of the fast/developmental MYH gene cluster to diverge and specialize, (ii) that the motor and rod domains of the MYH13 have evolved under different selective pressures and (iii) that the MYH13 gene has been largely insulated from genomic events that have shaped other members of the fast/developmental cluster. In addition, phylogenetic footprinting suggests that regulation of the extraocular MYH gene is not governed primarily by myogenic factors, but by a hierarchical network of regulatory factors that relate its expression to the development of extraocular muscles.

Extremity Swelling

2018 ◽  
pp. 136-139
Author(s):  
Jennifer Repanshek
Keyword(s):  
Creatine Kinase ◽  
Clinical Picture ◽  
Muscle Pain ◽  
Clinical Status ◽  
Clinical History ◽  
Muscle Group ◽  
Heat Illness ◽  
Single Muscle ◽  
Muscle Disorders ◽  
Intravenous Fluid Administration

The case illustrates the classic clinical features and emergent management of rhabdomyolysis. The pathophysiology results from the breakdown of muscle from intense exercise, drug or alcohol use, seizure activity, trauma, heat illness, or muscle disorders. The clinical history is of a severe muscle pain, sometimes focused on a single muscle group or extremity but often diffuse. Rhabdomyolysis should be suspected in a patient with vague complaints of muscle pain, and an elevation in creatine kinase is diagnostic in this clinical picture. Patients who have been diagnosed with rhabdomyolysis must also be carefully evaluated for compartment syndrome. The mainstay of treatment is aggressive intravenous fluid administration. Serial creatine kinase values as well as the patient’s evolving clinical status should guide further management.

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