The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length.
The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES .
A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus) having a kinase domain. The amino- terminal is involved in a Z line binding, and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the M line.
A powerful flexor of the thigh at the hip joint (psoas major) and a weak flexor of the trunk and lumbar spinal column (psoas minor). Psoas is derived from the Greek "psoa", the plural meaning "muscles of the loin". It is a common site of infection manifesting as abscess (PSOAS ABSCESS). The psoas muscles and their fibers are also used frequently in experiments in muscle physiology.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
Contractile tissue that produces movement in animals.
A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.
One of two types of muscle in the body, characterized by the array of bands observed under microscope. Striated muscles can be divided into two subtypes: the CARDIAC MUSCLE and the SKELETAL MUSCLE.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.
An actin capping protein that binds to the pointed-end of ACTIN. It functions in the presence of TROPOMYOSIN to inhibit microfilament elongation.
A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.
Muscle contraction with negligible change in the force of contraction but shortening of the distance between the origin and insertion.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Developmental events leading to the formation of adult muscular system, which includes differentiation of the various types of muscle cell precursors, migration of myoblasts, activation of myogenesis and development of muscle anchorage.
Muscular contractions characterized by increase in tension without change in length.
A species of the family Ranidae occurring in a wide variety of habitats from within the Arctic Circle to South Africa, Australia, etc.
Resistance and recovery from distortion of shape.
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
The properties, processes, and behavior of biological systems under the action of mechanical forces.
An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent.
Contractile activity of the MYOCARDIUM.
A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by TROPONIN.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.
The hollow, muscular organ that maintains the circulation of the blood.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae.
The performance of dissections, injections, surgery, etc., by the use of micromanipulators (attachments to a microscope) that manipulate tiny instruments.
Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The larger subunits of MYOSINS. The heavy chains have a molecular weight of about 230 kDa and each heavy chain is usually associated with a dissimilar pair of MYOSIN LIGHT CHAINS. The heavy chains possess actin-binding and ATPase activity.
The use of wings or wing-like appendages to remain aloft and move through the air.
A large class of structurally-related proteins that contain one or more LIM zinc finger domains. Many of the proteins in this class are involved in intracellular signaling processes and mediate their effects via LIM domain protein-protein interactions. The name LIM is derived from the first three proteins in which the motif was found: LIN-11, Isl1 and Mec-3.
The restriction of the MOVEMENT of whole or part of the body by physical means (RESTRAINT, PHYSICAL) or chemically by ANALGESIA, or the use of TRANQUILIZING AGENTS or NEUROMUSCULAR NONDEPOLARIZING AGENTS. It includes experimental protocols used to evaluate the physiologic effects of immobility.
Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.
Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Sharp instruments used for puncturing or suturing.
The use of instrumentation and techniques for visualizing material and details that cannot be seen by the unaided eye. It is usually done by enlarging images, transmitted by light or electron beams, with optical or magnetic lenses that magnify the entire image field. With scanning microscopy, images are generated by collecting output from the specimen in a point-by-point fashion, on a magnified scale, as it is scanned by a narrow beam of light or electrons, a laser, a conductive probe, or a topographical probe.
Bundles of actin filaments (ACTIN CYTOSKELETON) and myosin-II that span across the cell attaching to the cell membrane at FOCAL ADHESIONS and to the network of INTERMEDIATE FILAMENTS that surrounds the nucleus.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Skeletal muscle structures that function as the MECHANORECEPTORS responsible for the stretch or myotactic reflex (REFLEX, STRETCH). They are composed of a bundle of encapsulated SKELETAL MUSCLE FIBERS, i.e., the intrafusal fibers (nuclear bag 1 fibers, nuclear bag 2 fibers, and nuclear chain fibers) innervated by SENSORY NEURONS.
A form of interference microscopy in which variations of the refracting index in the object are converted into variations of intensity in the image. This is achieved by the action of a phase plate.
The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
Elements of limited time intervals, contributing to particular results or situations.
The physical characteristics and processes of biological systems.
Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
An optical source that emits photons in a coherent beam. Light Amplification by Stimulated Emission of Radiation (LASER) is brought about using devices that transform light of varying frequencies into a single intense, nearly nondivergent beam of monochromatic radiation. Lasers operate in the infrared, visible, ultraviolet, or X-ray regions of the spectrum.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
That phase of a muscle twitch during which a muscle returns to a resting position.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Refers to animals in the period of time just after birth.
A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.

Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease. (1/1432)

Pulmonary hyperinflation impairs the function of the diaphragm in patients with chronic obstructive pulmonary disease (COPD). However, it has been recently demonstrated that the muscle can counterbalance this deleterious effect, remodelling its structure (i.e. changing the proportion of different types of fibres). The aim of this study was to investigate whether the functional impairment present in COPD patients can be associated with structural subcellular changes of the diaphragm. Twenty individuals (60+/-9 yrs, 11 COPD patients and 9 subjects with normal spirometry) undergoing thoracotomy were included. Nutritional status and respiratory function were evaluated prior to surgery. Then, small samples of the costal diaphragm were obtained and processed for electron microscopy analysis. COPD patients showed a mean forced expiratory volume in one second (FEV1) of 60+/-9% predicted, a higher concentration of mitochondria (n(mit)) in their diaphragm than controls (0.62+/-0.16 versus 0.46+/-0.16 mitochondrial transections (mt) x microm(-2), p<0.05). On the other hand, subjects with air trapping (residual volume (RV)/total lung capacity (TLC) >37%) disclosed not only a higher n(mit) (0.63+/-0.17 versus 0.43+/-0.07 mt x microm(-2), p<0.05) but shorter sarcomeres (L(sar)) than subjects without this functional abnormality (2.08+/-0.16 to 2.27+/-0.15 microm, p<0.05). Glycogen stores were similar in COPD and controls. The severity of airways obstruction (i.e. FEV1) was associated with n(mit) (r=-0.555, p=0.01), while the amount of air trapping (i.e. RV/TLC) was found to correlate with both n(mit) (r=0.631, p=0.005) and L(sar) (r=-0.526, p<0.05). Finally, maximal inspiratory pressure (PI,max) inversely correlated with n(mit) (r=-0.547, p=0.01). In conclusion, impairment in lung function occurring in patients with chronic obstructive pulmonary disease is associated with subcellular changes in their diaphragm, namely a shortening in the length of sarcomeres and an increase in the concentration of mitochondria. These changes form a part of muscle remodelling, probably contributing to a better functional muscle behaviour.  (+info)

Morphology and mechanics of tongue movement in the African pig-nosed frog Hemisus marmoratum: a muscular hydrostatic model. (2/1432)

The goal of this study was to investigate morphological adaptations associated with hydrostatic elongation of the tongue during feeding in the African pig-nosed frog Hemisus marmoratum. Whereas previous studies had suggested that the tongue of H. marmoratum elongates hydraulically, the anatomical observations reported here favour a muscular hydrostatic mechanism of tongue elongation. H. marmoratum possesses a previously undescribed compartment of the m. genioglossus (m. genioglossus dorsoventralis), which is intrinsic to the tongue and whose muscle fibres are oriented perpendicular to the long axis of the tongue. On the basis of the arrangement and orientation of muscle fibres in the m. genioglossus and m. hyoglossus, we propose a muscular hydrostatic model of tongue movement in which contraction of the m. genioglossus dorsoventralis, together with unfolding of the intrinsic musculature of the tongue, results in a doubling in tongue length. Electron micrographs of sarcomeres from resting and elongated tongues show that no special adaptations of the sarcomeres are necessary to accommodate the observed doubling in tongue length during feeding. Rather, the sarcomeres of the m. genioglossus longitudinalis are strikingly similar to those of anuran limb muscles. The ability to elongate the tongue hydrostatically, conferred by the presence of the m. genioglossus dorsoventralis, is associated with the appearance of several novel aspects of feeding behaviour in H. marmoratum. These include the ability to protract the tongue slowly, thereby increasing capture success, and the ability to aim the tongue in azimuth and elevation relative to the head. Compared with other frogs, the muscular hydrostatic system of H. marmoratum allows more precise, localized and diverse tongue movements. This may explain why the m. genioglossus of H. marmoratum is composed of a larger number of motor units than that of other frogs.  (+info)

Dynamic distribution and formation of a para-sarcomeric banding pattern of prosomes during myogenic differentiation of satellite cells in vitro. (3/1432)

Myogenesis proceeds by fusion of proliferating myoblasts into myotubes under the control of various transcription factors. In adult skeletal muscle, myogenic stem cells are represented by the satellite cells which can be cultured and differentiate in vitro. This system was used to investigate the subcellular distribution of a particular type of prosomes at different steps of the myogenic process. Prosomes constitute the MCP core of the 26S proteasomes but were first observed as subcomplexes of the untranslated mRNPs; recently, their RNase activity was discovered. A monoclonal antibody raised against the p27K subunit showed that the p27K subunit-specific prosomes move transiently into the nucleus prior to the onset of myoblast fusion into myotubes; this represents possibly one of the first signs of myoblast switching into the differentiation pathway. Prior to fusion, the prosomes containing the p27K subunit return to the cytoplasm, where they align with the gradually formed lengthwise-running desmin-type intermediate filaments and the microfilaments, co-localizing finally with the actin bundles. The prosomes progressively form discontinuous punctate structures which eventually develop a pseudo-sarcomeric banding pattern. In myotubes just formed in vitro, the formation of this pattern seems to preceed that produced by the muscle-specific sarcomeric (alpha)-actin. Interestingly, this pattern of prosomes of myotubes in terminal in vitro differentiation was very similar to that of prosomes observed in vivo in foetal and adult muscle. These observations are discussed in relation to molecular myogenesis and prosome/proteasome function.  (+info)

Correlation between myofilament response to Ca2+ and altered dynamics of contraction and relaxation in transgenic cardiac cells that express beta-tropomyosin. (4/1432)

We compared the dynamics of the contraction and relaxation of single myocytes isolated from nontransgenic (NTG) mouse hearts and from transgenic (TG-beta-Tm) mouse hearts that overexpress the skeletal isoform of tropomyosin (Tm). Compared with NTG controls, TG-beta-Tm myocytes showed significantly reduced maximal rates of contraction and relaxation with no change in the extent of shortening. This result indicated that the depression in contraction dynamics determined in TG-beta-Tm isolated hearts is intrinsic to the cells. To further investigate the effect of Tm isoform switching on myofilament activity and regulation, we measured myofilament force and ATPase rate as functions of pCa (-log of [Ca2+]). Compared with controls, force generated by myofilaments from TG-beta-Tm hearts and myofibrillar ATPase activity were both more sensitive to Ca2+. However, the shift in pCa50 (half-maximally activating pCa) caused by changing sarcomere length from 1.8 to 2.4 microm was not significantly different between NTG and TG-beta-Tm fiber preparations. To test directly whether isoform switching affected the economy of contraction, force versus ATPase rate relationships were measured in detergent-extracted fiber bundles. In both NTG and TG-beta-Tm preparations, force and ATPase rate were linear and identically correlated, which indicated that crossbridge turnover was unaffected by Tm isoform switching. However, detergent extracted fibers from TG-beta-Tm demonstrated significantly less maximum tension and ATPase activity than NTG controls. Our results provide the first evidence that the Tm isoform population modulates the dynamics of contraction and relaxation of single myocytes by a mechanism that does not alter the rate-limiting step of crossbridge detachment. Our results also indicate that differences in sarcomere-length dependence of activation between cardiac and skeletal muscle are not likely due to differences in the isoform population of Tm.  (+info)

Myofibrillogenesis in the developing chicken heart: assembly of Z-disk, M-line and the thick filaments. (5/1432)

Myofibrillogenesis in situ was investigated by confocal microscopy of immunofluorescently labelled whole mount preparations of early embryonic chicken heart rudiments. The time-course of incorporation of several components into myofibrils was compared in triple-stained specimens, taken around the time when beating starts. All sarcomeric proteins investigated so far were already expressed before the first contractions and myofibril assembly happened within a few hours. No typical stress fibre-like structures or premyofibrils, structures observed in cultured cardiomyocytes, could be detected during myofibrillogenesis in the heart. Sarcomeric proteins like (&agr;)-actinin, titin and actin were found in a defined localisation pattern even in cardiomyocytes that did not yet contain myofibrils, making up dense body-like structures. As soon as the heart started to beat, all myofibrillar proteins were already located at their exact position in the sarcomere. The maturation of the sarcomeres was characterised by a short delay in the establishment of the pattern for M-line epitopes of titin with respect to Z-disk epitopes and the incorporation of the M-line component myomesin, which preceded that of myosin binding protein-C. Thus dense body-like structures, made up of titin, (&agr;)-actinin and actin filaments serve as the first organised complexes also during myofibrillogenesis in situ and titin functions as a ruler for sarcomere assembly as soon as its C termini have become localised. We suggest that assembly of thin and thick filament occurs independently during myofibrillogenesis in situ and that myomesin might be important for integrating thick filaments with the M-line end of titin.  (+info)

Different domains of the M-band protein myomesin are involved in myosin binding and M-band targeting. (6/1432)

Myomesin is a 185-kDa protein located in the M-band of striated muscle where it interacts with myosin and titin, possibly connecting thick filaments with the third filament system. By using expression of epitope-tagged myomesin fragments in cultured cardiomyocytes and biochemical binding assays, we could demonstrate that the M-band targeting activity and the myosin-binding site are located in different domains of the molecule. An N-terminal immunoglobulin-like domain is sufficient for targeting to the M-band, but solid-phase overlay assays between individual N-terminal domains and the thick filament protein myosin revealed that the unique head domain contains the myosin-binding site. When expressed in cardiomyocytes, the head domains of rat and chicken myomesin showed species-specific differences in their incorporation pattern. The head domain of rat myomesin localized to a central area within the A-band, whereas the head domain of chicken myomesin was diffusely distributed in the cytoplasm. We therefore conclude that the head domain of myomesin binds to myosin but that this affinity is not sufficient for the restriction of the domain to the M-band in vivo. Instead, the neighboring immunoglobulin-like domain is essential for the precise incorporation of myomesin into the M-band, possibly because of interaction with a yet unknown protein of the sarcomere.  (+info)

Effect of rate of distraction on loss of range of joint movement, muscle stiffness, and intramuscular connective tissue content during surgical limb-lengthening: a study in the rabbit. (7/1432)

Surgical lengthening of limbs often results in loss of range of joint movement and this has been shown to be associated with an increase in passive tension and an increase in collagen content of the muscles. In this study, we have investigated the length/tension properties and the connective tissue component of muscle distracted at three different rates in order to determine whether low rates of distraction would enable the connective tissue component, as well as the contractile component (number of serial sarcomeres), to adapt more completely to the increased functional length of the muscle and thus lead to improved range of joint movement. It was found that loss of range of movement varied with rate of distraction. At the low rate, there was no change in the passive tension or collagen content compared to muscles from sham-operated animals, and range of movement was significantly greater than at the other rates. At the medium rate, although the muscles showed good adaptation in terms of serial sarcomere number, passive tension and collagen content was increased and range of movement reduced, indicating that changes in the connective tissue component are important factors in loss of joint movement. In the case of muscle distracted at a high rate, failure of the muscle fibres to add on sufficient sarcomeres, combined with changes in the connective tissue, resulted in almost total loss of joint movement.  (+info)

Cross bridge-dependent activation of contraction in cardiac myofibrils at low pH. (8/1432)

Striated muscle contracts in the absence of calcium at low concentrations of MgATP ([MgATP]), and this has been termed rigor activation because rigor cross bridges attach and activate adjacent actin sites. This process is well characterized in skeletal muscle but not in cardiac muscle. Rigor cross bridges are also thought to increase calcium binding to troponin C and play a synergistic role in activation. We tested the hypothesis that cross bridge-dependent activation results in an increase in contractile activity at normal and low pH values. Myofibrillar ATPase activity was measured as a function of pCa and [MgATP] at pH 7.0, and the data showed that, at pCa values of >/=5.5, there was a biphasic relationship between activity and [MgATP]. Peak activity occurred at 10-50 microM MgATP, and [MgATP] for peak activity was lower with increased pCa. The ATPase activity of rat cardiac myofibrils as a function of [MgATP] at a pCa of 9.0 was measured at several pH levels (pH 5.4-7.0). The ATPase activity as a function of [MgATP] was biphasic with a maximum at 8-10 microM MgATP. Lower pH did not result in a substantial decrease in myofibrillar ATPase activity even at pH 5.4. The extent of shortening, as measured by Z-line spacing, was greatest at 8 microM MgATP and less at both lower and higher [MgATP], and this response was observed at all pH levels. These studies suggest that the peak ATPase activity associated with low [MgATP] was coupled to sarcomere shortening. These results support the hypothesis that cross bridge-dependent activation of contraction may be responsible for contracture in the ischemic heart.  (+info)

The serial sarcomere number of skeletal muscle changes in response to chronic length perturbation. The role of the intermediate filament desmin in regulating these changes was investigated by comparing the architectural adaptations of the tibialis anterior, extensor digitorum longus (EDL) and soleus from wild-type mice with those of homozygous desmin knockout mice after hindlimb immobilization. After 28 days, serial sarcomere number increased significantly in the lengthened wild-type tibialis anterior (by approximately 9 %) and EDL (by approximately 17 %). Surprisingly, muscles from desmin knockout mice also experienced significant serial remodeling, with the serial sarcomere number of the tibialis anterior increasing by approximately 10 % and that of the EDL by approximately 27 %. A consistent result was observed in the shortened soleus: a significant decrease in sarcomere number was observed in the muscles from both wild-type (approximately 26 %) and knockout (approximately 12 %) mice. Thus, ...
The purpose of the present study was to describe sarcomere dynamics in thin trabeculae that were dissected from the right ventricle of kittens. The muscles were mounted in an experimental chamber and perfused with a modified Krebs-Henseleit solution (25 degrees C). Sarcomere length (SL) was measured by laser diffraction techniques; force, by a silicon strain gauge; and velocity of sarcomere shortening, by the isovelocity release technique. Contractile activation was varied by changing the calcium concentration in the bathing medium ([Ca2+]o). Slack SL was 1.85 +/- 0.04 microns. When length of the muscle was held constant, the sarcomeres in the central region of the muscle shortened during the twitch by up to 21%. Both peak sarcomere isometric twitch force and unloaded velocity of sarcomere shortening (Vo) were a sigmoidal function of [Ca2+]o. Maximum Vo was 9.8 +/- 0.2 microns/sec; maximum sarcomere isometric twitch force was 108 +/- 13.8 mN/mm2. The shape of the force-SL relation was a ...
Cardiac myosin binding protein C phosphorylation affects cross-bridge cycles elementary steps in a site-specific manner.: Based on our recent finding that card
The examination of the expression profiles of other major sarcomere proteins revealed no significant preferential changes in any protein tested, other than titin (Fig. 3 C). When OD was normalized with that of MHC or actin, depending on the molecular weight, only titin was found to be significantly reduced (Fig. 3 C, bar graphs on the right). Therefore, proteins are reduced disproportionately in long-term disuse, with the effect on titin largest among the major sarcomere proteins.. In skeletal muscle, at least half of total protein is thick and thin filament based, and this fraction is lost at a faster rate than other muscle proteins in disuse (Jackman and Kandarian, 2004). The increase in the intensity of some bands in disused muscle (Fig. 3 B, arrows) indicates that the expression of nonsarcomere (or minor/unknown sarcomere) proteins may increase relative to that of the major sarcomere proteins tested in the present study.. It has been reported that gene expression is reduced for nebulin in ...
Mutungi, GM and Ranatunga, KW (2000) Sarcomere length changes during end-held (isometric) contractions in intact mammalian (rat) fast and slow muscle fibres. Journal of Muscle Research and Cell Motility, 21 (6). pp. 565-575. Full text not available from this repository ...
Heritable cardiomyopathy (HCM) is the leading cause of sudden cardiac arrest (SCA) in young people, affecting 1 in 500 individuals. HCM is chiefly caused by mutations in myofibrillar proteins of the cardiac sarcomere, and cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3) is one of the most commonly affected. cMyBP-C, an accessory protein that binds tightly to myosin, has an important role in thick filament regulation. Mice with genetic ablation of MYBPC3 exhibit cardiac hypertrophy, reduced ejection fraction, and increased relaxation times in vivo. Experiments with explanted hearts from these mice exhibit greater susceptibility to arrhythmias compared to WT, suggesting derangement of Ca2+ handling. The molecular mechanisms underlying the progression of HCM are poorly understood, and are difficult to tease apart in constitutive knock out models due to potential compensatory changes that can mask important aspects of the disease phenotype. We used a tamoxifen-induced conditional MYBPC3 ...
Background: Reversible lysine-acetylation of proteins is regulated by histone acetyl transferases and deacetylases (HDACs). Previous studies from this laboratory have shown that a class-II HDAC, HDAC4 is associated with cardiac sarcomeres, and that HDAC-inhibitors enhance the contractile activity of myofilaments. Since, HDAC4 has little or no deacetylase activity of its own, this study was undertaken to examine the presence of other HDACs on cardiac sarcomeres.. Methods and Results: We prepared skinned papillary muscle fibers of the mouse heart and subjected them to western analysis. Results showed that a class-I HDAC, HDAC3 was localized to cardiac sarcomeres. By immuno-histochemical and electron microscopic analyses we found that HDAC3 was localized to the A-band of cardiac sarcomeres. We therefore examined the reversible acetylation of the A-band protein, myosin heavy chains (MHCs). MHC isoforms were prepared from control and PTU-treated mice, and examined for acetylation by western analysis ...
Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this ...
Myomegalin has been characterized as a protein with the properties of a scaffold or structural protein that is expressed at high levels in skeletal and cardiac tissue, suggesting an important function in muscle, and which interacts with a cAMP-specific phosphodiesterase [13]. However, the precise function and interactions of this protein, and its five isoforms, have been largely unknown. We here describe how the smallest MMGL isoform, isoform 4, binds to known and predicted PKA targets in the cardiac myocyte, including some sarcomeric proteins, viz. cMyBPC, cTNI, ENO1, ENO3, CARP and COMMD4 (Tables 1 and 2). Moreover, we show that MMGL isoform 4 interacts with two regulatory subunits of PKA (Figure 3). Together these results describe MMGL isoform 4 as a novel sarcomeric AKAP, which, like mAKAP [14], is involved in assembling a PKA/PDE cAMP signalling module.. In addition to interacting with both types of regulatory subunits, viz. RI and RII, which qualifies MMGL isoform 4 as a dual-specific AKAP ...
臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。. To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of NTU Repository with Academic Hub to form NTU Scholars.. ...
Introduction. The Structure of Skeletal Muscle Skeletal muscles are all muscles that are attached to the skeleton such as the biceps and the hamstring. Within each muscle cell (also known as a muscle fibre) are structures called myofibrils as shown in the picture below: (Ref. The picture above was found at www.google.com) Myofibrils are made up of tiny units called sarcomeres. Sarcomeres are the smallest structures in a muscle that can contract; they are long filament-like structures, arranged in series - end to end - that run lengthways in the myofibril. Within the sarcomeres are two types of protein filaments that are actin and myosin - running lengthways, parallel to each other. The myosin filaments have cross-bridges across to the actin filaments, which during contraction allow them to bond with the actin filaments. The source of energy for this bonding is the molecule adenosine triphosphate (ATP). During the bonding, energy is released by the breaking down of ATP into adenosine ...
The cellular basis of the length-dependent increases in contractile force in the beating heart has remained unclear. Our aim was to investigate whether length-dependent mediated increases in contractile force are correlated with myosin head proximity to actin filaments, and presumably the number of cross-bridges activated during a contraction. We therefore employed x-ray diffraction analyses of beat-to-beat contractions in spontaneously beating rat hearts under open-chest conditions simultaneous with recordings of left ventricle (LV) pressure-volume. Regional x-ray diffraction patterns were recorded from the anterior LV free wall under steady-state contractions and during acute volume loading (intravenous lactate Ringers infusion at 60 ml/h, |5 min duration) to determine the change in intensity ratio ( I 1,0/ I 1,1) and myosin interfilament spacing ( d 1,0). We found no significant change in end-diastolic (ED) intensity ratio, indicating that the proportion of myosin heads in proximity to actin was
Dilated cardiomyopathy (DCM) is a myocardial disease with a high mortality rate. Approximately 40 genes have been found to be associated with DCM to date. Non-familial DCM can also be caused by gene mutations, suggesting that genetic factors were involved in the pathogenesis of DCM; therefore genetic testing is beneficial for the early diagnosis of DCM, which can facilitate the implementation of preventive measures by and within patients families. Here, we investigated the underlying genetic mutations involved in the cause of patients with DCM.
The structure and function of the sarcomere of striated muscle is well studied but the steps of sarcomere assembly and maintenance remain under-characterized. With the aid of chaperones and factors of the protein quality control system, muscle proteins can be folded and assembled into the contractile apparatus of the sarcomere. When sarcomere assembly is incomplete or the sarcomere becomes damaged, suites of chaperones and maintenance factors respond to repair the sarcomere. Here we show evidence of the importance of the M-line proteins, specifically myomesin, in the monitoring of sarcomere assembly and integrity in previously characterized zebrafish muscle mutants. We show that myomesin is one of the last proteins to be incorporated into the assembling sarcomere, and that in skeletal muscle, its incorporation requires connections with both titin and myosin. In diseased zebrafish sarcomeres, myomesin1a shows an early increase of gene expression, hours before chaperones respond to damaged muscle. ...
A theoretical framework for predicting the macroscopic behavior of a muscle myofibril based on the collective behavior of sarcomeres is presented. The analysis is accomplished by rigorously transforming the nonlinear dynamics of an assemblage of sarcomeres into a partial differential equation for the probability distribution function of sarcomere lengths in the presence of stochastic temporal fluctuations and biological variability. This enables the study of biologically relevant specimens with reasonable computational effort. The model is validated by a comparison to quantitative experimental results. Further, it reproduces experimental observations that cannot be explained by standard single sarcomere models, and provides new insights into muscle function and muscle damage during cyclic loading. We show that the accumulation of overstretched sarcomeres, which is related to muscle damage, depends on a delicate interplay between the dynamics of a large number of sarcomeres and the load ...
Ultrastructural measurements were carried out on the mouse biceps brachii and soleus muscles fixed at different states of contraction and stretch. At a sarcomere length of 2.7-2.9 µm the more peripheral actin filaments ran slightly obliquely from the Z-disk to the A-band. This is due to a mismatch between the rhombic actin lattice at the Z-disk and the hexagonal lattice at the M-line. For a perfect transformation of a rhombic lattice into a hexagonal lattice the ratio of the lattice spacings has to be 1:1.51. However, at this sarcomere length the ratio is about 1:2.0 (Z:M). During contraction the angle of the peripheral actin filaments remains approximately the same because the expansion of the M lattice is compensated for, partly by an increase in the Z-lattice spacing and partly by the bowing of the peripheral myosin filaments. When the sarcomeres are stretched beyond 3.0 µm the myosin filaments straighten out and the Z:M ratio decreases. The ratio of 1:1.51 is almost attained when there is ...
The effect of MgADP on the sarcomere length (SL) dependence of tension generation was investigated using skinned rat ventricular trabeculae. Increasing SL from 1.9 to 2.3 microm decreased the muscle width by approximately 11% and shifted the midpoint of the pCa-tension relationship (pCa(50)) leftward by about 0.2 pCa units. MgADP (0.1, 1, and 5 mmol/L) augmented maximal and submaximal Ca(2+)-activated tension and concomitantly diminished the SL-dependent shift of pCa(50) in a concentration-dependent manner. In contrast, pimobendan, a Ca(2+) sensitizer, which promotes Ca(2+) binding to troponin C (TnC), exhibited no effect on the SL-dependent shift of pCa(50), suggesting that TnC does not participate in the modulation of SL-dependent tension generation by MgADP. At a SL of 1. 9 microm, osmotic compression, produced by 5% wt/vol dextran (molecular weight approximately 464 000), reduced the muscle width by approximately 13% and shifted pCa(50) leftward to a similar degree as that observed when increasing
The |i|Journal of Biomedical Optics|/i| (JBO) publishes peer-reviewed papers on the use of novel optical systems and techniques for improved health care and biomedical research.
TY - JOUR. T1 - Differential contribution of cardiac sarcomeric proteins in the myofibrillar force response to stretch. AU - Ait Mou, Younss. AU - Le Guennec, Jean Yves. AU - Mosca, Emilio. AU - De Tombe, Pieter P.. AU - Cazorla, Olivier. PY - 2008/10. Y1 - 2008/10. N2 - The present study examined the contribution of myofilament contractile proteins to regional function in guinea pig myocardium. We investigated the effect of stretch on myofilament contractile proteins, Ca2+ sensitivity, and cross-bridge cycling kinetics (K tr) of force in single skinned cardiomyocytes isolated from the sub-endocardial (ENDO) or sub-epicardial (EPI) layer. As observed in other species, ENDO cells were stiffer, and Ca2+ sensitivity of force at long sarcomere length was higher compared with EPI cells. Maximal K tr was unchanged by stretch, but was higher in EPI cells possibly due to a higher α-MHC content. Submaximal Ca2+-activated K tr increased only in ENDO cells with stretch. Stretch of skinned ENDO muscle ...
A skeletal muscle that is stretched while contracting will produce more force at steady state than if it is stretched passively and then stimulated to contract. This phenomenon is known as residual fo
Each muscle fiber is made up of a collection of smaller fibers called Myofibrils. Muscle hypertrophy is due to an increase in the number of myofibrils within each fiber. Each myofibril extends the full length of the fiber, and is made up of a longitudinal arrangement of units called sarcomeres. The sarcomere is the structure responsible for the actual contraction. Each sarcomere consists of thick (myosin) and thin (actin) protein filaments that lie adjacent to one another horizontally, but are slightly separated longitudinally. Contraction occurs when the thick filaments attach to the thin filaments (crossbridge) and pull the thin filaments toward the center of the thick filament. The number of sarcomeres in series along a myofibril depends on the length and architecture of the specific muscle. The sartorius, which is the longest muscle in the body, has more than 100,000 sarcomeres in series, while a shorter muscle, such as the soleus, has closer to 10,000 sarcomeres in series. ...
contractile fiber, myofibril, protein-containing complex, striated muscle thin filament, Z disc, actin filament binding, cardiac muscle thin filament assembly, muscle fiber development, regulation of actin filament length, sarcomere organization
In this study, we aimed to further dissect the molecular components required for the coordinated organization of Z-line components into regular, hexagonal lattices. We took the approach of searching for protein interactions that anchor the COOH-terminal region of nebulin within the sarcomere. This allowed us to identify the specific binding of the nebulin modules M160-M183, from the peripheral (I-band side) region of the Z-line (Millevoi et al. 1998), with the intermediate filament protein, desmin. Studies are currently under investigation to determine whether desmin and nebulin indeed participate in a coordinated cytoskeletal network that could provide lateral linkages in the Z-line perimyofibrillar space, allowing for efficient force transmission and mechanochemical signaling.. This study has also led to the identification of a novel nebulin-binding protein, myopalladin, which we named based on its striking homology with the recently described ubiquitously expressed protein, palladin (Parast ...
The Frank-Starling law of the heart (also known as Starling's law and the Frank-Starling mechanism) represents the relationship between stroke volume and end diastolic volume . The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles , before contraction (the end diastolic volume), when all other factors remain constant. As a larger volume of blood flows into the ventricle, the blood stretches the cardiac muscle fibers, leading to an increase in the force of contraction. The Frank-Starling mechanism allows the cardiac output to be synchronized with the venous return, arterial blood supply and humoral length, without depending upon external regulation to make alterations. The physiological importance of the mechanism lies mainly in maintaining left and right ventricular output equality. Physiology The Frank-Starling mechanism occurs as the result of the length-tension relationship observed in skeletal muscles . As a muscle
Munich, Germany - Skeletal muscles are built from small contractile units, the sarcomeres. Many of these sarcomeres are connected in a well-ordered series to form myofibrils that span from one muscle end to the other. Contractions of these sarcomeres result in contraction of the entire muscle. Scientists at the Max Planck Institute (MPI) of Biochemistry…
We discovered a unique pattern of optical reflectance from fresh prerigor skeletal muscles, which can not be described using existing theories. A numerical fitting function was developed to quantify the equi-intensity contours of acquired reflectance images. Using this model, we studied the changes of reflectance profile during stretching and rigor process. We found that the prominent anisotropic features diminished after rigor completion. These results suggested that muscle sarcomere structures played important roles in modulating light propagation in whole muscle. When incorporating the sarcomere diffraction in a Monte Carlo model, we showed that the resulting reflectance profiles quantitatively resembled the experimental observation.. ©2007 Optical Society of America. Full Article , PDF Article ...
Sarcomeres are extremely highly ordered macromolecular assemblies where structural organization is intimately linked to their functionality as contractile units. Although the structural basis of actin and Myosin interaction is revealed at a quasiatomic resolution, much less is known about the molecular organization of the I-band and H-zone. We report the development of a powerful nanoscopic approach, combined with a structure-averaging algorithm, that allowed us to determine the position of 27 sarcomeric proteins in Drosophila melanogaster flight muscles with a quasimolecular, ∼5- to 10-nm localization precision. With this protein localization atlas and template-based protein structure modeling, we have assembled refined I-band and H-zone models with unparalleled scope and resolution. In addition, we found that actin regulatory proteins of the H-zone are organized into two distinct layers, suggesting that the major place of thin filament assembly is an M-line-centered narrow domain where short ...
The heart - a muscle working without exhaustion and breaks. Our organism, however, has its own ways of dealing with that. One of them is the so-called Frank-Starling mechanism.
Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. in cardiogenesis. Introduction Despite recent advances in pharmacologic and surgical therapies, chronic heart failure (CHF) is still a leading cause of death worldwide (1). Currently, heart transplant is thought to be the most effective therapy for end-stage CHF. However, this approach obviously cannot be used for all of the numerous affected patients and is not suitable for patients with a mild disease state. Therefore, there is increasing demand for new therapeutic targets for CHF. Cardiomyocytes, the most basic cellular unit of the myocardium, express several sarcomeric proteins, including myosin and actin; abnormalities in these sarcomeric proteins are major causes of idiopathic cardiomyopathies and lead to CHF (2C4). Type II myosin is the major constituent of sarcomeres. In the neck region of this protein, there are binding sites for a pair of myosin light chains, which ...
The smallest contractile unit of muscle fiber is the sarcomere. Sarcomeres are stacked throughout muscle tissue. These units are so small that some muscle cells contain thousands of...
Figure 2. Facing page. Differentiation of neonatal cardiomyocyte grafts. Host myocardium is shown only in day-3 panels (B, F, J, and N). Each time point shows serial sections from same heart. Bar=35 μm. Hematoxylin and eosin staining: A, At day 1, graft cardiomyocytes appeared small, round, and undifferentiated. Graft area was mostly surrounded by necrotic host myocardium and interstitial hemorrhage. B, At day 3, progressive wound healing was observed and graft cardiomyocytes began to elongate. C, At day 6, all necrotic host myocardium was removed. Graft cardiomyocytes began to enlarge and had early sarcomere formation (see also Figure 3⇓). Inset in C, Potential proliferation of graft neonatal cardiomyocytes was studied by double-staining for PCNA (blue) and α-cardiac myosin heavy chain (brown). PCNA-positive graft neonatal cardiomyocytes were observed from 3 days to 2 weeks, with peak frequency of 2% double-positive cells occurring at 6 days (as shown). Bar=10 μm. D, By 8 weeks, graft ...
A higher magnification of a field that suggests a non-satellite (resident) progenitor cell. No satellite cells are seen. The sarcomeres are formed. Z: Z lines;
Myosin Binding Protein-C (MyBP-C) comprises a family of accessory proteins that includes the cardiac, slow skeletal, and fast skeletal isoforms. The three isoforms share structural and sequence homology, and localize at the C-zone of the sarcomeric A-band where they interact with thick and thin filaments to regulate the cycling of actomyosin crossbridges. The cardiac isoform, encoded by MYBPC3, has been extensively studied over the last several decades due to its high mutational rate in congenital hypertrophic and dilated cardiomyopathy. It is only recently, however, that the MYBPC1 gene encoding the slow skeletal isoform (sMyBP-C) has gained attention. Accordingly, during the last five years it has been shown that MYBPC1 undergoes extensive exon shuffling resulting in the generation of multiple slow variants, which are co-expressed in different combinations and amounts in both slow and fast skeletal muscles. The sMyBP-C variants are subjected to PKA- and PKC-mediated phosphorylation in constitutive and
Hypertrophic cardiomyopathies are due to primary defects in sarcomerci function by mutations of genes coding for sarcomeric proteins composing the cardiac sarcomere ...
Relaxed sarcomeres contain myosin heads that have released their pull on the thin filaments. This allows them to return back to their relaxed state and cau
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Bundles of filaments and motors are central to contractility in cells. The classic example is striated muscle, where actomyosin contractility is mediated by highly organized sarcomeres which act as fundamental contractile units. However, many contractile bundles in vivo and in vitro lack sarcomeric organization. Here we propose a model for how contractility can arise in bundles without sarcomeric organization and validate its predictions with experiments on a reconstituted system. In the model, internal stresses in frustrated arrangements of motors with diverse velocities cause filaments to buckle, leading to overall shortening. We describe the onset of buckling in the presence of stochastic motor head detachment and predict that buckling-induced contraction occurs in an intermediate range of motor densities. We then calculate the size of the contractile units associated with this process. Consistent with these results, our reconstituted actomyosin bundles show contraction at relatively high ...
Although mutations in cMyBP‐C are one of the most frequent causes of hypertrophic cardiomyopathy on a per gene basis with ,150 individual mutations being documented, the majority of these mutations (≈60%) result not in a full‐length, mutated protein, but in a truncated peptide and these mutated alleles exhibit autosomal dominance.29, 30 We have shown that a truncated form of cMyBP‐C is produced from endogenous, normal cMyBP‐C as a result of ischemia-reperfusion injury and/or general cardiovascular stress and is generated from Ca2+ activated μ‐calpain activity.2 This fragment is stable, can be expressed inducibly in cardiomyocytes and causes cardiac disease, fibrosis, and eventually heart failure and death.4 This model displays pathology that is often seen in human cardiac fibrosis and myocardial disease: the hearts develop hypertrophy and show extensive interstitial fibrosis and perivascular fibrosis while maintaining systolic function. Thus, in terms of a fibrotic response, the ...
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Glycerol-extracted rabbit psoas muscle fibers were examined by electron microscopy both before and after ATP-induced isotonic shortening. Ultrastructural changes were correlated with the initial sarcomere length and the degree of shortening. The ultrastructural appearance of the resting fiber at rest length was identical with that described by H. E. Huxley and Hanson. At sarcomere lengths greater than 3.7 to 3.8 µ, the A and I filaments were detached and separated by a gap. The presence of gap filaments was confirmed, and evidence is presented which indicates that these filaments form connections between the ends of the A and I filaments. Shortening from initial sarcomere lengths at which the filaments overlapped took place through sliding of the filaments. If shortening was initiated from sarcomere lengths at which there was a gap, a narrowing of the I band was brought about by a curling of the I filaments at the boundary between the A and I bands. No evidence could be found that the I ...
The thin and thick filaments of muscle sarcomeres are interconnected by the giant protein titin, which is a scaffolding filament, signaling platform, and provider of passive tension and elasticity in myocytes. This review summarizes recent insight into the mechanisms behind how titin gene mutations cause hereditary cardiomyopathy and how titin protein is mechanically active in skeletal and cardiac myocytes. A main theme is the evolving role of titin as a modulator of contraction. Topics include strain-sensing via titin in the sarcomeric A-band as the basis for length-dependent activation, titin elastic recoil and refolding of titin domains as an energy source, and Ca2+-dependent stiffening of titin stretched during eccentric muscle contractions ...
Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The ...
Hypertrophic cardiomyopathy (HCM), an inherited disease of the heart muscle, is among the most common Mendelian cardiac diseases, occurring in 1 in 500 people (1). Advances in genetics have facilitated identification of a subpopulation of patients with pathogenic variants in cardiac sarcomere genes. The earliest family mapped by positional cloning had a disease-causing mutation at position 403 of the β-myosin heavy chain (MHC) protein (2). A knock-in mouse model of this variant recapitulated aspects of human disease (3); many other sarcomere genes have been implicated subsequently (4). In clinics today, coding regions of numerous cardiac sarcomere genes are routinely sequenced, and, excluding those patients with discrete upper septal thickening, clearly pathogenic variants are identified in 30% to 50% of patients (5), thus marking a subset of sarcomeric HCM.. Current therapy for HCM is primarily palliative. Beta-blockers, nondihydropyridine calcium channel blockers, and the class Ia ...
Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM ...
The Frank-Starling mechanism occurs as the result of the length-tension relationship observed in striated muscle, including for example skeletal muscles, arthropod muscle[4] and cardiac (heart) muscle.[5][6][7] As a muscle fiber is stretched, active tension is created by altering the overlap of thick and thin filaments. The greatest isometric active tension is developed when a muscle is at its optimal length. In most relaxed skeletal muscle fibers, passive elastic properties maintain the muscle fibers length near optimal, as determined usually by the fixed distance between the attachment points of tendons to the bones (or the exoskeleton of arthropods) at either end of the muscle. In contrast, the relaxed sarcomere length of cardiac muscle cells, in a resting ventricle, is lower than the optimal length for contraction.[1] There is no bone to fix sarcomere length in the heart (of any animal) so sarcomere length is very variable and depends directly upon blood filling and thereby expanding the ...
The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle ...
The efficient functioning of striated muscle is dependent upon the precise interactions and alignment of complex cytoskeletal networks. For example, sarcomeres, the basic contractile units of myofibrils, are comprised of uniformly arranged filament systems and regulatory proteins. The actin-containing thin filaments are anchored in the Z-lines and extend toward the middle of the sarcomere, the M-line, where they interact with the myosin-containing thick filaments to drive contraction. A third filament system is composed of single molecules of titin, the largest known vertebrate protein (∼3.7 MDa). Titin filaments span half sarcomeres, with their N-termini overlapping in the Z-lines and their C-termini overlapping in the M-lines, thus forming a continuous filament system among adjacent myofibrils (Obermann et al., 1996; Gregorio et al., 1998; Mues et al., 1998). Based on the assembly properties, molecular layout and modular structure of titin, it is proposed to act as a template for ...
Wang et al (Nat Med. 2014 May 11. doi: 10.1038/nm.3545.) just published a fascinating set of experiences in which they created a model of a Barth Syndrome cardiac dysfunction by using heart on chip technology. This technology involves using Barth patient derived induced pluripotent stem cell derived cardiomyocytes seeded on micropatterned fibronectin rectangles in order to recapitulate cardiac tissue structure. From these experiments, the authors were able to derive information about sarcomere organization, contractile dysfunction among other relevant parameters. This model, and the success of these experiments, holds great promise in the development of therapies for cardiomyopathy, as well as creating a system in which phenotype/genotype correlations of specific gene mutations can be better understood.. Hilary Vernon, MD PhD. ...
We found that the lengths of all sarcomeres spontaneously oscillated in an isolated skeletal myofibril, when both ends were fixed, submillimolar to millimolar concentrations of ATP, ADP and inorganic...
Muscles are how we, and almost all animals, move. As animals cannot get energy from the sun, movement is crucial for finding food, as well as for reproducing: without muscles, we cannot survive.. Muscles are complex tissues. Muscle cells are packed full of tiny cylinders of specialized contractile proteins. These cylinders, called sarcomeres, are arranged end to end into myofibrils. Muscle cells, or myofibers, contain many myofibrils. Inside a single muscle, there are multiple hierarchical levels of bundling: myofibrils are bundled into myofibers, then multiple myofibers are bundled into fascicles and then several fascicles are bundled together to form whole muscles. At each hierarchical level, each bundle is covered with a layer of connective tissue that supports the fibers inside it by supplying energy and oxygen via blood vessels and control via nerves.. Muscle contraction occurs at the level of the individual sarcomeres. Although each tiny cylinder only contracts by a minuscule amount, once ...
Human induced pluripotent stem cells (iPSCs) represent a powerful human model to study cardiac disease in vitro, notably channelopathies and sarcomeric cardiomyopathies. Different protocols for cardiac differentiation of iPSCs have been proposed either based on embroid body formation (3D) or, more recently, on monolayer culture (2D). We performed a direct comparison of the characteristics of the derived cardiomyocytes (iPSC-CMs) on day 27 ± 2 of differentiation between 3D and 2D differentiation protocols with two different Wnt-inhibitors were compared: IWR1 (inhibitor of Wnt response) or IWP2 (inhibitor of Wnt production). We firstly found that the level of Troponin T (TNNT2) expression measured by FACS was significantly higher for both 2D protocols as compared to the 3D protocol. In the three methods, iPSC-CM show sarcomeric structures. However, iPSC-CM generated in 2D protocols constantly displayed larger sarcomere lengths as compared to the 3D protocol. In addition, mRNA and protein analyses reveal
wp-content/uploads/2018/08/johns_hopkins_medicine_logo-300-x-156-300x156.jpg 0 0 admin /wp-content/uploads/2018/08/johns_hopkins_medicine_logo-300-x-156-300x156.jpg admin2014-08-08 15:04:382018-08-11 11:48:32Phosphorylation of protein kinase C sites Ser42/44 decreases Ca(2+)-sensitivity and blunts enhanced length-dependent activation in response to protein kinase A in human cardiomyocytes ...
Titin also known as connectin is a large filamentous protein that greatly contributes to passive myocardial stiffness. to passive myocardial stiffness in all tissue types but most in MLV least in BLA and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a viscous break that is on during diastole and off during systole. RAF265 Rabbit polyclonal to AIM1L. 1 Introduction Passive tension development in the sarcomere plays a critical role in diastolic function. The giant protein titin/connectin spans the half-sarcomere from Z-disk to M-line [1] and is responsible for the development of passive tension within the sarcomere [2]. Titin-based passive tension constitutes a large fraction of the myocardial passive tension; the other main contributor is the extracellular ...
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are two common cardiomyopathies with an estimated prevalence of 1:250 and 1:200 in adults (McKenna et al., 2017; Prondzynski et al., 2018). The prognoses of cardiomyopathies are poor, and the annual mortalities for DCM and HCM are 1.55% and 2.5%, respectively (Pelliccia et al., 2017; Vischer et al., 2009). During the past few decades, genetic screening has identified a list of autosomal inherited mutations as potential drivers or susceptible factors for cardiomyopathy, and approximately 40-50% of all cases can be attributed to genetic mutations (Zou et al., 2013; Paldino et al., 2018). Among these, genes coding sarcomere proteins are frequently found to be dysfunctional in both DCM and HCM, and it is estimated that around 30-40% DCM-associated mutations and 60% HCM-associated mutations occur in sarcomere genes (McNally et al., 2013; Hershberger et al., 2013; Veselka et al., 2017). Besides, mutations in a single sarcomere gene ...
Maintenance of muscle structure and function depends on the precise organization of contractile proteins into sarcomeres and coupling of the contractile apparatus to the sarcoplasmic reticulum (SR), which serves as the reservoir for calcium required for contraction. Several members of the Kelch superfamily of proteins, which modulate protein stability as substrate-specific adaptors for ubiquitination, have been implicated in sarcomere formation. The Kelch protein Klhl31 is expressed in a muscle-specific manner under control of the transcription factor MEF2. To explore its functions in vivo, we created a mouse model of Klhl31 loss of function using the CRISPR-Cas9 system. Mice lacking Klhl31 exhibited stunted postnatal skeletal muscle growth, centronuclear myopathy, central cores, Z-disc streaming, and SR dilation. We used proteomics to identify several candidate Klhl31 substrates, including Filamin-C (FlnC). In the Klhl31-knockout mice, FlnC protein levels were highly upregulated with no change ...
A growing body of evidence suggests that myosin heads are dynamically recruited to the thin filaments via mechanisms that displace myosin from the thick filament backbone and toward actin. The earliest evidence of such a process was the inference from x-ray diffraction patterns that there is a transfer of molecular mass from thick to thin filaments during the activation of muscle contraction (Haselgrove and Huxley, 1973). Although such a phenomenon could, in part, be a simple manifestation of myosin head binding to actin, the transfer of mass is observed even at long sarcomere lengths at which there is little overlap of thick and thin filaments and therefore little binding of myosin heads to actin. This apparent activation of head displacement is a puzzling but potentially important aspect of muscle contraction because movement of myosin heads closer to actin would presumably increase the probability of binding to actin and increase the rate and amplitude of force development. Recent work ...
STUDY RATIONALE:. Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by histopathologic findings of cardiac myocyte disarray and fibrosis, and clinical manifestations of unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and an increased risk for sudden death. It is a common disorder affecting approximately 1 in 1000 individuals in the general population. Dominantly-acting mutations in contractile proteins-genes encoding the elements of the sarcomere apparatus-- have been shown to be the genetic etiology of HCM. Contemporary management strategies for HCM focus on identification of individuals at high risk for sudden death and management of symptoms. There is no current therapy available which address disease prevention or phenotypic attenuation.. Dysregulation of intracellular calcium handling is a fundamental and early manifestation of sarcomere mutations. Animal models of HCM demonstrated abnormal Ca2+ cycling prior to the development of myocyte disarray ...
Monte S. Willis, MD, PhD - $50,000 Familial hypertrophic cardiomyopathies (FHC) are the most common underlying cause of sudden death in children and young adults, which result from mutations primarily in proteins responsible for heart contraction. It has been identified that the cardiac specific protein MuRF1 (Muscle Ring Finger-1), mediates the degradation of one of these proteins, the cardiac Myosin Binding Protein-C (cMyBP-c). Since cMyBP-c is the most commonly mutated protein in patients with FHC, and cMyBP-c is degraded very rapidly by heart cells in these patients, this study proposes that MuRF1 may be a key regulator of this degradation as a mechanism to clear damaged proteins. Moreover, it has been identified that MURF1 regulates the turnover of proteins that transport energy (ATP) throughout the cell, and that MuRF1 inhibits increases in muscle size (cardiomyocyte hypertrophy). Therefore, the assumption is that MuRF1 is a unifying mechanism for the major underlying defects in FHC. The ...
MAYWOOD, Ill. - A new blood test can detect heart attacks hours faster than the current gold-standard blood test, according to a study led by Loyola University Chicago Stritch School of Medicine researchers.. The new test measures a protein that is released to the bloodstream by dying heart muscle. The protein is called cardiac myosin binding protein-C (cMyBP-C). The study found that cMyBP-C is released to the blood within just 15 minutes of cardiac damage, and rises to significant levels in three hours.. This is a potential ultra-early biomarker that could confirm whether a patient has had a heart attack, leading to faster and more effective treatment, said Sakthivel Sadayappan, PhD, senior author of the study, published Dec. 13, 2013 in the American Journal of Physiology - Heart and Circulatory Physiology.. Between 60 and 70 percent of all patients who complain of chest pain do not have heart attacks. Many of these patients are admitted to the hospital, at considerable time and expense, ...
Alpha-connectin/titin-1 exists as an elastic filament that links a thick filament with the Z-disk, keeping thick filaments centered within the sarcomere during force generation. We have shown that the connectin filament has an affinity for calcium ions and its binding site(s) is restricted to the be …
When you compress these hyperactive segments, it creates an overload on the receptor as the nervous system slams the neuromuscular connection with more stimulus to try to shake off the compressive element and avoid the pain and trauma. If theres too much compression it can cause the muscle to contract harder, but enough compression to cause some overload can help stimulate and then fatigue the receptor, which helps to release the muscle or sarcomeres affected so theres less tension. From the sliding filament theory, this helps to expand the length of the sarcomere, allowing more range of motion to occur.. This is a similar mechanism to PNF style stretching, where a muscle is stretched into a near end range position, then contracted in a held position for a time (usually 10-20 seconds), and then tension is reduced which then produces new range of motion.. [embedplusvideo height=367″ width=600″ editlink=http://bit.ly/1ydSCAH standard=http://www.youtube.com/v/BJl5uPhWM6U?fs=1″ ...
Biology 42 - Human Biology (Spring 2007) Muscles [ Students and professors, please read. ] Assignment Questions. A. What is a sarcomere and what are the sequence of events that lead to contraction? The sarcomere extends between two Z lines and is composed of thin filaments of actin (I band) and thick filaments of myosin (H…
myomesin: protein from M-band of skeletal muscle; RefSeq NM_003970 (human); NM_008664 (mouse); XM_240481 (Myom2, rat), XM_237523 (Myom1, rat)
Telethonin兔多克隆抗体(ab121868)可与人样本反应并经WB, IHC实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
Kolmerer, B.; Witt, C. C.; Freiburg, A.; Millevoi, S.; Stier, G.; Sorimachi, H.; Pelin, K.; Carrier, L.; Schwartz, K.; Labeit, D. et al.; Gregorio, C. C.; Linke, W. A.; Labeit, S.: The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system. Reviews of Physiology, Biochemistry and Pharmacology 138, pp. 19 - 55 (1999 ...
Hello, Is there any way to modify the spacing within cells in Excel (2010)? I have never found any settings to affect this within the normal Excel controls. However, I am wondering if it can be...
Each sarcomere is delimited by two very dark colored bands called Z-discs or Z-lines (from the German zwischen meaning between ... The names of the various sub-regions of the sarcomere are based on their relatively lighter or darker appearance when viewed ... When a muscle contracts, the actin is pulled along myosin toward the center of the sarcomere until the actin and myosin ... These subunits are called sarcomeres. The muscle cell is nearly filled with myofibrils running parallel to each other on the ...
They run through the core of each thick filament and anchor it to the Z-line, the end point of a sarcomere. Titin also ... These subunits are called sarcomeres. The contractile nature of this protein complex is based on the structure of the thick and ... The muscle fiber relaxes and the entire sarcomere lengthens. The muscle fiber is now prepared for the next contraction. The ... Muscle contraction consists of the simultaneous shortening of multiple sarcomeres. What follows is a summary of muscle fiber ...
Made of repeating segments called Sarcomeres. Opercularisation the formation of the cerebral opercula during the intrauterine ...
Kreis, Thomas E.; Birchmeier, Walter (November 1980). "Stress fiber sarcomeres of fibroblasts are contractile". Cell. 22 (2): ... fibers in the ventral regions of non-motile cells show a periodic polarity that is similar to the organization of the sarcomere ...
The sarcomere does not contain organelles or a nucleus. Sarcomeres are marked by Z lines which show the beginning and the end ... Assuming that the length of biceps is 20 cm and the length of sarcomere is 2 micrometer, there are 100,000 sarcomeres along the ... The myofibrils of smooth muscle cells are not arranged into sarcomeres. The sarcomeres are composed of thin and thick filaments ... This causes the filaments to start sliding and the sarcomeres to become shorter. This requires a large amount of ATP, as it is ...
CS1 maint: Uses authors parameter (link) Scott AB (1994). "Change of eye muscle sarcomeres according to eye position". Journal ... so that a paralyzed muscle tends to get stretched-out by its antagonist and grows longer by addition of serial sarcomeres (the ... contractile units of skeletal muscles), while the antagonist tends to grow shorter by deletion of sarcomeres, thereby ...
... appears to be necessary for the proper incorporation of myosin filaments into sarcomeres and in the assembly of A- ... Titin, obscurin, obscurin-like-1 and myomesin form a ternary complex at sarcomeric M-bands that is critical for sarcomere ... Obscurin is expressed in cardiac and skeletal muscle, and plays a role in the organization of myofibrils during sarcomere ... Borisov AB, Martynova MG, Russell MW (Apr 2008). "Early incorporation of obscurin into nascent sarcomeres: implication for ...
In normal muscle cells, the various parts of the muscle fibers that make up the sarcomere are distributed evenly in a pattern ... Of the genes that have been linked to nemaline myopathy, most are also involved in encoding proteins in the sarcomeres in the ... At the microscopic level, muscle cells have structures called sarcomeres. Diseases in the nemaline myopathy group come about ... "Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in ...
In addition to sarcomeres, PKCε also targets cardiac mitochondria. Proteomic analysis of PKCε signaling complexes in mice ... PKCε translocates to cardiac muscle sarcomeres and modulates contractility of the myocardium. PKCε binds RACK2 at Z-lines with ... A role for focal adhesion kinase at costameres in strain-sensing and modulation of sarcomere length has been linked to ... PKCε translocation to sarcomeres and phosphorylation of cTnI and cMyBPC is involved in the κ-opioid- and α-adrenergic-dependent ...
At the sarcomere, AARP binds titin at I-bands, which is potentiated by homo-dimerization and can alter the protein kinase A/ ... AARP localizes to both nuclei and sarcomeres in muscle cells. ARPP may play a role in the differentiation of myocytes, as ARPP ... with longer resting sarcomere length, decreased fiber stiffness, expression of a longer titin isoform, greater degree of torque ... a link between the sarcomere and the nucleus in skeletal muscle". J. Mol. Biol. 339 (2): 313-25. doi:10.1016/j.jmb.2004.03.071 ...
HCM is described as a disease of the sarcomere, because mutations in the contractile proteins of the sarcomere have been ... The calcium sensitivity of the sarcomere, that is, the calcium concentration at which muscle contraction occurs, is directly ... Hwang PM, Sykes BD (Apr 2015). "Targeting the sarcomere to correct muscle function". Nature Reviews. Drug Discovery. 14: 313-28 ...
Desmin IFs are structural components of the sarcomeres in muscle cells. GFAP (glial fibrillary acidic protein) is found in ...
Nicol RL, Frey N, Pearson G, Cobb M, Richardson J, Olson EN (Jun 2001). "Activated MEK5 induces serial assembly of sarcomeres ...
Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE (Jan 2002). "Sarcomere protein gene mutations in ... Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE (Jan 2002). "Sarcomere protein gene mutations in ... This enables proper assembly of myofibrils and thus, more organized sarcomeres. It should be noted, however, that all of the ... This process converts chemical to mechanical energy, and propels shortening of the sarcomeres in order to generate ...
Gupta MP, Samant SA, Smith SH, Shroff SG (Apr 2008). "HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating ... Luther PK (2009). "The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling". Journal of Muscle Research and ... "Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy". Human Molecular Genetics. 17 (18): 2753-65. doi: ... different Z-line components and acts as a scaffold protein promoting the assembly of macromolecular complexes along sarcomeres ...
The sarcomeres become misaligned and result in the disorganization of muscle fibers. This mutation also results in muscle cell ...
Sarcomeres are added in parallel, as for example occurs in hypertrophic cardiomyopathy. In the heart, concentric hypertrophy is ...
2012) Lateral communication between stress fiber sarcomeres facilitates a local remodeling response. Biophys J. 103(10):2082-92 ... 2012) Lateral communication between stress fiber sarcomeres facilitates a local remodeling response. Biophys J. 103(10):2082-92 ...
The regular organisation of myofibrils into sarcomeres gives cardiac muscle cells a striped or striated appearance when looked ... These are organised into sarcomeres, the fundamental contractile units of muscle cells. ...
Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle ... at Z-lines towards the center of the sarcomere. Polymerization of globular actin (G-actin) leads to a structural filament (F- ... "Mutations in sarcomere protein genes in left ventricular noncompaction". Circulation. 117 (22): 2893-901. doi:10.1161/ ...
However the actions of elastic proteins such as titin are hypothesised to maintain uniform tension across the sarcomere and ... The power stroke moves the actin filament inwards, thereby shortening the sarcomere. Myosin then releases ADP but still remains ... Gordon AM, Huxley AF, Julian FJ (1966). "The variation in isometric tension with sarcomere length in vertebrate muscle fibres ... Physiologically, this contraction is not uniform across the sarcomere; the central position of the thick filaments becomes ...
Affected mice have disrupted z-band and sarcomere morphology. In this experimental model ryanodine and IP3 receptors have ... Hammarlund, M; Davis WS; Jorgensen EM (2000). "Mutations in β-Spectrin Disrupt Axon Outgrowth and Sarcomere Structure". Journal ...
... see Myofibril or Sarcomere Geometrisches Mittel, or Geometric mean. ...
Fiber length is the product of both the number of sarcomeres in series in the fiber and their individual lengths. As a fiber ... The force produced by a given muscle is proportional to the cross-sectional area, or the number of parallel sarcomeres present ... Because of this structure, fewer sarcomeres can be found in series, resulting in a shorter fiber length. This further allows ... Velocity is affected in the reverse manner - because sarcomeres shorten at a certain percentage per second under a certain ...
NM-IIB may play a role in formation of mature sarcomeres in myofibrils. It appears that NM-IIB plays an essential role in ...
This increase in pumping ability is the result of the addition of sarcomeres in series, which enables the heart to contract ... The concentric growth, on the other hand, induces parallel deposition of the sarcomeres. The growth of cardiomyocyte is in the ... This is explained by the Frank Starling mechanism, which describes the sarcomere's ability to contract with greater force as ... Concentric hypertrophy is characterized by an addition of sarcomeres (the contractile units of cardiac cells) in parallel. The ...
Within the sarcomere, actin and myosin fibers overlap in a contractile motion towards each other. Myosin filaments have club- ... The myosin heads move in a coordinated style; they swivel toward the center of the sarcomere, detach and then reattach to the ... When the muscle no longer needs to contract, the calcium ions are pumped from the sarcomere and back into storage in the ... Calcium ions are required for each cycle of the sarcomere. Calcium is released from the sarcoplasmic reticulum into the ...
It is located in the Z band of the muscle sarcomere. This protein helps to stabilize the actin filaments protecting it from ...
"Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy". The New England Journal of Medicine. 343 (23): 1688 ... a disease of the sarcomere". Cell. 77 (5): 701-12. doi:10.1016/0092-8674(94)90054-x. PMID 8205619. Lin D, Bobkova A, Homsher E ... "Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes". Heart. 94 (11): ...
Luther PK (2009). "The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling". Journal of Muscle Research and ... primary function of alpha-actinin 2 is to crosslink filamentous actin molecules and titin molecules from adjoining sarcomeres ...
Relaxed sarcomeres contain myosin heads that have released their pull on the thin filaments. This allows them to return back to ... Home / Science / Human Anatomy / Muscles / What Is the Difference Between Relaxed and Contracted Sarcomere? ... Relaxed sarcomeres contain myosin heads that have released their pull on the thin filaments. This allows them to return back to ... What Is the Difference Between Relaxed and Contracted Sarcomere? By Staff WriterLast Updated Mar 26, 2020 4:33:43 AM ET ...
Sarcomeres are the fundamental structural and contractile units in striated muscle and sarcomere length is an important ... Monitoring sarcomere structure changes in whole muscle using diffuse light reflectance. JinJun Xia; Amanda Weaver; David E. ... Sarcomere length of each sample was determined using a modified protocol to that described elsewhere.15 The results (Fig. 3c) ... To manipulate muscle sarcomere length, the psoas major muscles were used because of their appropriate anatomical locations. ...
Sarcomere length (SL) was measured by laser diffraction techniques; force, by a silicon strain gauge; and velocity of sarcomere ... Both peak sarcomere isometric twitch force and unloaded velocity of sarcomere shortening (Vo) were a sigmoidal function of [ ... Sarcomere dynamics in cat cardiac trabeculae.. P P de Tombe, H E ter Keurs ... When length of the muscle was held constant, the sarcomeres in the central region of the muscle shortened during the twitch by ...
The serial sarcomere number of skeletal muscle changes in response to chronic length perturbation. The role of the intermediate ... We speculate that desmin may play a role in regulating the optimal arrangement of sarcomeres within the muscle or in sensing ... Thus, although desmin is not essential for sarcomerogenesis or sarcomere subtraction in mouse hindlimb muscles, the results do ... Sarcomere number regulation maintained after immobilization in desmin-null mouse skeletal muscle ...
We show that the accumulation of overstretched sarcomeres, which is related to muscle damage, depends on a delicate interplay ... A coarse-grained model of the myofibril: Overall dynamics and the evolution of sarcomere non-uniformities ... The analysis is accomplished by rigorously transforming the nonlinear dynamics of an assemblage of sarcomeres into a partial ... Further, we show that biological variability rather than stochastic fluctuations are the main source for sarcomere non- ...
Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching ... Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching ... As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, ... As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, ...
Significance of sarcomere gene mutation in patients with dilated cardiomyopathy. * Y.D. Li ...
Sarcomere length changes during end-held (isometric) contractions in intact mammalian (rat) fast and slow muscle fibres. ... Mutungi, GM and Ranatunga, KW (2000) Sarcomere length changes during end-held (isometric) contractions in intact mammalian (rat ...
Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the. Marked sarcomere disorganization ... Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the ... Type II myosin is the major constituent of sarcomeres. In the neck region of this protein, there are binding sites for a pair ... it performs buy Inolitazone dihydrochloride specific roles in cardiogenesis by contributing to the formation of sarcomeres and ...
Actin molecules are bound to the Z line, which forms the borders of the sarcomere. Other bands appear when the sarcomere is ... The myofibrils of smooth muscle cells are not arranged into sarcomeres. The sarcomeres are what give skeletal and cardiac ... Length of the actin and myosin filaments (taken together as sarcomere length) affects force and velocity - longer sarcomeres ... A sarcomere is defined as the segment between two neighbouring Z-lines (or Z-discs, or Z bodies). In electron micrographs of ...
This page provides links to MyoSim models that have been published in the literature. Each sub-page provides MyoSim instruction files for each published figure. You can use these to reproduce the published simulations on your own computer ...
sarcomere (plural sarcomeres) *The contractile unit of the myofibril of a striated muscle. *2006, Brian R. MacIntosh, Phillip F ... Specific proteins are responsible for the bands and zones within each sarcomere.. ... Retrieved from "https://en.wiktionary.org/w/index.php?title=sarcomere&oldid=51977429" ...
An individual sarcomere is about 2.5 to 3.0 microns long. A myofibril is formed of a sequence of sarcomeres. A single muscle ... This composite structural and functional unit is known as a sarcomere. The chemical interactions of the thick and thin ... cell from a latissimus dorsi will have about 100,000 sarcomeres oriented in sequence (2). Skeletal muscle fibers are made up of ...
We found that the lengths of all sarcomeres spontaneously oscillated in an isolated skeletal myofibril, when both ends were ... Iwazumi, T. &Pollack, G. H. (1981) The effect of sarcomere non-uniformity on the sarcomere lengthtension relationship of ... of the average sarcomere length. The propagation of the sarcomere oscillation along the long axis of the myofibril was observed ... Stephenson, D. G. &Williams, D. A. (1982) Effects of sarcomere length on the force-pCa relation in fast- and slow-twitch ...
K. Wang, "Sarcomere-associated cytoskeletal lattices in striated muscle. Review and hypothesis," Cell and Muscle Motility, vol ... E. Ehler and M. Gautel, "The sarcomere and sarcomerogenesis," Advances in Experimental Medicine and Biology, vol. 642, pp. 1-14 ... A. Houmeida, A. Baron, J. Keen et al., "Evidence for the oligomeric state of elastic titin in muscle sarcomeres," Journal of ... S. Y. Boateng and P. H. Goldspink, "Assembly and maintenance of the sarcomere night and day," Cardiovascular Research, vol. 77 ...
Polarization gating enables sarcomere length measurements by laser diffraction in fibrotic muscle.. Young KW1, Dayanidhi S2, ... Sarcomere length (. , to 15 measurements per muscle) measured by laser diffraction (LD), PGLD, and bright field microscopy (BF ... PGLD enables sarcomere length measurements in highly scattering muscle tissue. No significant differences were found between ... Sarcomere length measured by polarization-gated laser diffraction (PGLD). Polarizing filters extract diffraction signal from ...
... Fuyu Kobirumaki-Shimozawa,1 Kotaro Oyama,1,2 ... 4. Sarcomere Length Measurement in the Whole Heart. Several groups have reported the results of SL measurement in the heart at ... 2. Sarcomere Length Dependence of Ca2+ Activation: Underling Mechanism for Frank-Starlings Law of the Heart. It is well ... Indeed, although it is generally thought that all sarcomeres within a cardiomyocyte uniformly respond to a change in [Ca2+]i to ...
Sarcomeres are the basic contractile units of striated muscle. Our knowledge about sarcomere dynamics has primarily come from ... Mean sarcomere length from a and b. d, Average sarcomere length taken from multiple images in each of three human subjects with ... f, Map of sarcomere length variations within d and e. Scale bars are 10 µm in a-c, and 25 µm in d-f ... d, Average sarcomere velocities derived from c. Shaded regions in c and d represent the mean ± s.e.m. of the five traces. ...
If patients could recognise themselves, or anyone else could recognise a patient from your description, please obtain the patients written consent to publication and send them to the editorial office before submitting your response [Patient consent forms] ...
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Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N. Engl. J. Med. 343:1688-1696. View this article ... there was no effect on the expression of other sarcomere proteins involved in sarcomere organization such as troponin T, desmin ... Epinephrine treatment induced sarcomere assembly through MLC2v phosphorylation. Original magnification, ×1,000 (A-C and E-G). ( ... the knockdown of cardiac-MLCK produced significant effects on sarcomere reassembly. si-cMK inhibited sarcomere reassembly after ...
Connecting Sarcomere Protein Mutations to Pathogenesis in Myopathies View all 34 Articles ... 2002). Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 105, 446-451. doi: 10.1161/ ... Contribution of Post-translational Phosphorylation to Sarcomere-Linked Cardiomyopathy Phenotypes. Margaret V. Westfall* ... Månsson, A. (2014). Hypothesis and theory: mechanical instabilities and non-uniformities in hereditary sarcomere myopathies. ...
Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant ... Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins ... HCM can be caused by mutations in components of the sarcomere (the hearts contractile unit), most notably myosin. ... These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere ...
Abstract 17543: DMPK E Disrupts Sarcomere Structure by Inhibition of SRF Transcriptional Activity. Ies Elzenaar, Amin ... Background: Heart failure is associated with elongation of cardiomyocytes and loss of sarcomeres. Although the transcription ... Abstract 17543: DMPK E Disrupts Sarcomere Structure by Inhibition of SRF Transcriptional Activity ... Abstract 17543: DMPK E Disrupts Sarcomere Structure by Inhibition of SRF Transcriptional Activity ...
Sarcomere length and first-order diffraction line width were measured by laser diffraction during elongation of activated frog ... Sarcomere strain and heterogeneity correlate with injury to frog skeletal muscle fiber bundles J Appl Physiol (1985). 2004 Nov; ... Sarcomere length and first-order diffraction line width were measured by laser diffraction during elongation of activated frog ... These data demonstrate a direct association and, perhaps, a causal relationship between sarcomere strain and fiber bundle ...
Sarcomeres, the smallest contractile units of striated muscle, are conventionally perceived as the most regular macromolecular ... However, recent studies have revealed complex multiple locations for several sarcomere proteins within the sarcomere and other ... From A to Z and back? Multicompartment proteins in the sarcomere Trends Cell Biol. 2006 Jan;16(1):11-8. doi: 10.1016/j.tcb. ... Sarcomeres, the smallest contractile units of striated muscle, are conventionally perceived as the most regular macromolecular ...
The sarcomere, the basic contractile unit of striated muscle cells, is widely accepted as being constructed of two sets of ... The elastic structure of sarcomere connecting structure of M lines and elastic skeleton of sarcomere, Jikeikai Med. J.28:153- ... The sarcomere, the basic contractile unit of striated muscle cells, is widely accepted as being constructed of two sets of ... Wang K. (1985) Sarcomere-Associated Cytoskeletal Lattices in Striated Muscle. In: Shay J.W. (eds) Cell and Muscle Motility. ...
Furthermore, stretch and sarcomere heterogeneity may modulate the susceptibility threshold for delayed afterdepolarizations and ... In a one-dimensional compartmental analysis, we bidirectionally coupled 50 sarcomere models in series to model calcium ... Arrhythmogenic Current Generation by Myofilament-Triggered Ca2+ Release and Sarcomere Heterogeneity. Timmermann, Viviane; ... diffusion and stress transfer between adjacent sarcomeres. These considerations enabled the model to capture 1) the effects of ...
Abstract 20063: Mitral Valve Alterations in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular ... Abstract 20063: Mitral Valve Alterations in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular ... Abstract 20063: Mitral Valve Alterations in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular ... Abstract 20063: Mitral Valve Alterations in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular ...
Also, sarcomere elongations with muscle lengthening were non-uniform across the muscle, with the highest sarcomere stretches ... It is then assumed implicitly that the sarcomere length measured at this single spot represents the sarcomere lengths at other ... It is then assumed implicitly that the sarcomere length measured at this single spot represents the sarcomere lengths at other ... Sarcomere lengths for a given muscle are typically measured at a single spot, often in the mid-belly of the muscle, and at a ...
However, iPSC-CM generated in 2D protocols constantly displayed larger sarcomere lengths as compared to the 3D protocol. In ... Differential Sarcomere and Electrophysiological Maturation of Human iPSC-Derived Cardiac Myocytes in Monolayer vs. Aggregation- ... "Differential Sarcomere and Electrophysiological Maturation of Human iPSC-Derived Cardiac Myocytes in Monolayer vs. Aggregation- ... However, iPSC-CM generated in 2D protocols constantly displayed larger sarcomere lengths as compared to the 3D protocol. In ...
At E9, assembled sarcomeres were detected in the knockout, and no structural alteration compared with wild-type sarcomeres was ... The loss of sarcomere structure precludes the analysis of E10.5 and 11.0 sarcomeres in knockout animals. **, P , 0.01. (C) ... To distinguish a role in sarcomere assembly from a role in stabilizing preexisting sarcomeres and to address potential ... Ultrastructural analysis of cardiac sarcomere maturation. (A) Sarcomeres assemble in both wild-type (WT) and knockout animals ( ...
... Sarah B. Scruggs,a ... Upon activation by various cellular stimuli, one target of PKCε translocation is to cardiac sarcomeres where PKCε plays a role ... It is noteworthy to mention that PKCε acting at cardiac sarcomeres has also been shown to have cardioprotective effects during ... Evidence has shown that PKCε translocation to sarcomeres and phosphorylation of cTnI and cMyBPC is involved in the κ-opioid- ...
Effects of Sarcomere Length and Ca^,2+, Binding on SH Reactivity of Myofilament Bound Troponin C in Porcine Skinned Cardiac ...
The myosin-interacting protein SMYD1 is essential for sarcomere organization Message Subject (Your Name) has sent you a message ... The myosin-interacting protein SMYD1 is essential for sarcomere organization. Steffen Just, Benjamin Meder, Ina M. Berger, ... The myosin-interacting protein SMYD1 is essential for sarcomere organization. Steffen Just, Benjamin Meder, Ina M. Berger, ... The myosin-interacting protein SMYD1 is essential for sarcomere organization. Steffen Just, Benjamin Meder, Ina M. Berger, ...
  • A theoretical framework for predicting the macroscopic behavior of a muscle myofibril based on the collective behavior of sarcomeres is presented. (caltech.edu)
  • Following myofibril assembly, many short sarcomeres are added to each myofibril. (uzh.ch)
  • How can the regular architecture of a many hundred sarcomeres long myofibril be built along a defined axis during muscle development? (mindzilla.com)
  • This strategy of tension release also led to a major defect in sarcomere and myofibril formation. (mindzilla.com)
  • Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. (uzh.ch)
  • The striated appearance of myofibrils makes laser diffraction 3 an ideal method to study sarcomere dynamics in single muscle fibers. (spiedigitallibrary.org)
  • Many of these sarcomeres are connected in a well-ordered series to form myofibrils that span from one muscle end to the other. (mindzilla.com)
  • As human muscles also contain myofibrils that are built by periodically arrayed sarcomeres, it is likely that a similar tension-based assembly model may also apply during human muscle development, so the scientists think. (mindzilla.com)
  • Contractions of these sarcomeres result in contraction of the entire muscle. (mindzilla.com)
  • The serial sarcomere number of skeletal muscle changes in response to chronic length perturbation. (biologists.org)
  • Hypertrophic cardiomyopathies are due to primary defects in sarcomerci function by mutations of genes coding for sarcomeric proteins composing the cardiac sarcomere. (humpath.com)
  • Relaxed sarcomeres contain myosin heads that have released their pull on the thin filaments. (reference.com)
  • Groups of thick and thin filaments that alternately overlap and move apart are called sarcomeres. (reference.com)
  • The analysis is accomplished by rigorously transforming the nonlinear dynamics of an assemblage of sarcomeres into a partial differential equation for the probability distribution function of sarcomere lengths in the presence of stochastic temporal fluctuations and biological variability. (caltech.edu)
  • We conducted a series of experiments to demonstrate that optical scattering properties measured in whole muscle are related to changes in sarcomere structure. (spiedigitallibrary.org)
  • Sarcomeres are the fundamental structural and contractile units in striated muscle and sarcomere length is an important predictor of muscle function. (spiedigitallibrary.org)
  • 1 Many muscle diseases ultimately are reflected in changes in sarcomere organization. (spiedigitallibrary.org)
  • Sarcomeres are aligned precisely in muscle fibers and are readily observed using light microscopy as alternating light and dark bands called the I-band and A-band. (spiedigitallibrary.org)
  • Therefore, it is not clear whether sarcomere changes can still be monitored in whole muscle. (spiedigitallibrary.org)
  • Because the periodic sarcomere structures can significantly alter light propagation directions in muscle, we hypothesize that changes in sarcomere structure can be monitored in whole muscle by measuring the scattering coefficient. (spiedigitallibrary.org)
  • Although whole muscle scattering coefficients have been measured before, 4 the effects of sarcomere structure changes have not been studied. (spiedigitallibrary.org)
  • To manipulate muscle sarcomere length, the psoas major muscles were used because of their appropriate anatomical locations. (spiedigitallibrary.org)
  • We speculate that desmin may play a role in regulating the optimal arrangement of sarcomeres within the muscle or in sensing the magnitude of the immobilization effect itself. (biologists.org)
  • Further, it reproduces experimental observations that cannot be explained by standard single sarcomere models, and provides new insights into muscle function and muscle damage during cyclic loading. (caltech.edu)
  • We show that the accumulation of overstretched sarcomeres, which is related to muscle damage, depends on a delicate interplay between the dynamics of a large number of sarcomeres and the load characteristics, such as its magnitude and frequency. (caltech.edu)
  • Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control - a concept that may also apply to vertebrate muscle or heart development. (uzh.ch)
  • Sarcomere length changes during end-held (isometric) contractions in intact mammalian (rat) fast and slow muscle fibres. (uea.ac.uk)
  • This tension buildup occurs before sarcomeres are formed and reaches through the entire muscle-tendon-skeleton system. (mindzilla.com)
  • This tension axis equips the muscle with positional information along which the sarcomeres must form. (mindzilla.com)
  • As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. (uzh.ch)
  • Thus, although desmin is not essential for sarcomerogenesis or sarcomere subtraction in mouse hindlimb muscles, the results do suggest subtle differences in the nature of sarcomere number adaptation. (biologists.org)
  • Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. (uzh.ch)
  • As observed in other species, ENDO cells were stiffer, and Ca 2+ sensitivity of force at long sarcomere length was higher compared with EPI cells. (elsevier.com)
  • Normal biomechanical and physiological functions of striated muscles are facilitated by the repeating sarcomere units. (spiedigitallibrary.org)
  • However, few studies, if any, have been conducted to investigate the possibility of using optical detection to examine sarcomere structure changes in whole muscles. (spiedigitallibrary.org)
  • In this paper, we study the reduced scattering coefficients derived from spatially resolved reflectance measurements 5 on pre- and postrigor whole muscles and investigate their relationships with sarcomere structure. (spiedigitallibrary.org)
  • A consistent result was observed in the shortened soleus: a significant decrease in sarcomere number was observed in the muscles from both wild-type (approximately 26 %) and knockout (approximately 12 %) mice. (biologists.org)
  • Munich, Germany - Skeletal muscles are built from small contractile units, the sarcomeres. (mindzilla.com)
  • The giant protein titin (connectin) extends from the Z-line of the sarcomere, where it binds to the thick filament (myosin) system, to the M-band, where it is thought to interact with the thick filaments. (wikipedia.org)
  • The interaction between actin and myosin filaments in the A-band of the sarcomere is responsible for the muscle contraction (sliding filament model). (wikipedia.org)
  • Relaxed sarcomeres contain myosin heads that have released their pull on the thin filaments. (reference.com)
  • HCM can be caused by mutations in components of the sarcomere (the heart's contractile unit), most notably myosin. (sciencemag.org)
  • Under a light microscope, muscle fibers have alternating black and white bands due to the contractile filaments myosin (anisotropic band, A-band) and actin (isotropic band, I-band) that make up sarcomeres. (frontiersin.org)
  • Reflecting the most recent advances in electron microscopic ultrastructure, the model unequivocally demonstrates that individual myofilaments neither change shape nor shorten, rather the proteins actin and myosin slide past one another, resulting in the shortening of the sarcomere itself. (shopanatomical.com)
  • Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. (uzh.ch)
  • A middle region of each sarcomere called the H-zone only contains myosin. (wikibooks.org)
  • It localizes to the thick filament of the sarcomere where it functions to regulate myosin-based contractility. (allencell.org)
  • Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy. (ox.ac.uk)
  • Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. (ox.ac.uk)
  • To determine the relationships between myosin conformations, sarcomere function, and cell biology we assessed contractility, relaxation, and cardiomyocyte morphology and metabolism, with and without an allosteric modulator of myosin ATPase activity. (ox.ac.uk)
  • The action of myosin attachment and actin movement results in sarcomere shortening. (wikipedia.org)
  • The myofibrils are composed of actin and myosin filaments, repeated in units called sarcomeres , which are the basic functional units of the muscle fiber. (wikipedia.org)
  • The principal cytoplasmic proteins are myosin and actin (also known as "thick" and "thin" filaments, respectively) which are arranged in a repeating unit called a sarcomere . (wikipedia.org)
  • Using electron microscopy, we have already been able to visualize some muscle building blocks in atomic detail, such as the protein complex of actin and myosin as the central element of the sarcomere. (mpg.de)
  • 2) The myosin heads then swivel, the Working Stroke , pulling the Z-lines closer together and shortening the sarcomeres. (unm.edu)
  • Type II myosin is the major constituent of sarcomeres. (biodiversityhotspot.org)
  • Among the several paralogs of the myosin regulatory light chain in vertebrates (5), myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v) is expressed in the myocardium, where it performs buy Inolitazone dihydrochloride specific roles in cardiogenesis by contributing to the formation of sarcomeres and in increasing the Ca2+ sensitivity of muscle tension at submaximal Ca2+ concentrations (6, 7). (biodiversityhotspot.org)
  • There were no differences in clinical and echocardiographic features between those children with sarcomere protein gene mutations and those without or between patients with 2 mutations and those with 1 or no mutations. (qxmd.com)
  • Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. (qxmd.com)
  • Clinical evaluations demonstrated familial disease in 6 of 11 probands with sarcomere gene mutations. (cdc.gov)
  • population the full spectrum of biophysical morphologic and practical changes associated with sarcomere gene mutations can be described prior to the analysis of overt HCM. (researchdataservice.com)
  • This review focusses on how sarcomeric gene mutations directly compromise sarcomere function in NM. (iospress.com)
  • Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives. (qxmd.com)
  • Sarcomere variants were the primary genetic basis of hypertrophic cardiomyopathy (HCM) and were recently detected in arrhythmogenic cardiomyopathy (ACM). (usda.gov)
  • Prediction of sarcomere mutations in subclinical hypertrophic cardiomyopathy. (cdc.gov)
  • Sarcomere protein mutations in hypertrophic cardiomyopathy induce subtle cardiac structural changes before the development of left ventricular hypertrophy (LVH). (cdc.gov)
  • We speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiomyopathy may be associated with left ventricular noncompaction. (cdc.gov)
  • Background: Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. (ox.ac.uk)
  • Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes. (researchdataservice.com)
  • Recent structural, biochemical, and immu-nocytochemical studies, however, have clearly indicated that the sarcomere has additional filamentous constituents besides thick and thin filament assemblies. (springer.com)
  • In Tβ4 null mice, immunofluorescence-based sarcomere analyses revealed shortened thin filament, sarcomere and titin spring length in cardiomyocytes, associated with precocious up-regulation of the short titin isoforms during the postnatal splicing transition. (ox.ac.uk)
  • The thin filament is a major constituent of the sarcomere, the smallest contractile unit in muscle. (iospress.com)
  • Further, it reproduces experimental observations that cannot be explained by standard single sarcomere models, and provides new insights into muscle function and muscle damage during cyclic loading. (caltech.edu)
  • The conditional knockout approach enabled the generation of adult animals to study titin's function in the mature heart and skeletal muscle, but expression kinetics of the Cre recombinase transgene preclude the analysis of titin's role in sarcomere assembly during early embryonic development. (rupress.org)
  • To distinguish a role in sarcomere assembly from a role in stabilizing preexisting sarcomeres and to address potential nonmuscle functions, we have converted our conditional M-line titin knockout into a complete knockout using germline recombination. (rupress.org)
  • We sought to determine whether Thymosin β4 (Tβ4), a peptide that regulates the availability of actin monomers for polymerization in non-muscle cells, plays a role in sarcomere assembly during cardiac morphogenesis and influences adult cardiac function. (ox.ac.uk)
  • Moreover, our system enables accurate measurement of sarcomere length in the isolated heart. (hindawi.com)
  • Within the H-zone is a thin M-line (from the German "Mittelscheibe", the disc in the middle of the sarcomere) formed of cross-connecting elements of the cytoskeleton. (wikipedia.org)
  • The names of the various sub-regions of the sarcomere are based on their relatively lighter or darker appearance when viewed through the light microscope. (wikipedia.org)
  • In this study, we use a titin M line-deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase. (rupress.org)
  • the peak-to-peak amplitude of oscillation reached as much as 30% of the average sarcomere length. (springer.com)
  • average sarcomere length, 2.2-2.6 μm) of which the optical thickness was appropriately chosen. (elsevier.com)
  • Sarcomeres are aligned precisely in muscle fibers and are readily observed using light microscopy as alternating light and dark bands called the I-band and A-band. (spiedigitallibrary.org)
  • Sarcomere mutations in cardiomyopathy, noncompaction, and the developing heart. (cdc.gov)
  • A muscle fiber from a biceps muscle may contain 100,000 sarcomeres. (wikipedia.org)
  • A single muscle cell from a latissimus dorsi will have about 100,000 sarcomeres oriented in sequence (2). (crossfit.com)
  • This composite structural and functional unit is known as a sarcomere. (crossfit.com)
  • Their smallest repeating functional unit is the sarcomere. (mpg.de)
  • Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control - a concept that may also apply to vertebrate muscle or heart development. (uzh.ch)
  • It appears that, at least in the case of the skeletal muscle sarcomere, temporal control of protein synthesis may be an important part of eucaryotic molecular morphogenesis. (caltech.edu)
  • Furthermore, stretch and sarcomere heterogeneity may modulate the susceptibility threshold for delayed afterdepolarizations and the aftercontraction wave propagation velocity. (uio.no)
  • Many sarcomeric genes have been implicated in congenital cardiomyopathies, such that understanding developmental sarcomere transitions will inform the aetiology and treatment. (ox.ac.uk)
  • Unlike in the adult knockout sarcomere, kinase-deficient titin does not integrate into the A band and, thus, fails to form a continuous filament system. (rupress.org)
  • Sarcomere variants were detected in NEBL, MYH7, MYH6 and TNNI3, with low prevalence in controls and predicted pathogenic in silico. (usda.gov)
  • Sarcomere variants in arrhythmogenic cardiomyopathy: Pathogenic factor or bystander? (usda.gov)
  • Our aim is to seek potential pathogenic variants of sarcomere genes in our ACM cohort and describe their characteristics.We performed targeted sequencing of 14 sarcomere genes in 84 patients with ACM and set strict criteria to identify potential pathogenic variants. (usda.gov)
  • Therefore, a more detailed knowledge of sarcomere assembly is crucial to better understand the pathogenic mechanisms within myopathies. (monash.edu)
  • Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts. (dropbox.com)
  • Clinical screening was performed on all available family members of the patients carrying sarcomere variants and specific variants were tested in screened family members by Sanger sequencing.We identified 6 sarcomere variants in 6 (7%) patients, which were all definite ACM. (usda.gov)
  • Patients with sarcomere variants all experienced major arrhythmic cardiac event (MACE) with the average age of the first documented MACE being 41.2 ± 11.0 years. (usda.gov)
  • Pedigrees analysis showed none of the sarcomere variants carriers among the family members were affected, indicating very low penetrance.We detected some sarcomere variants in our ACM cohort. (usda.gov)
  • Although those patients with sarcomere variants had severe arrhythmic burden, family co-segregation analysis didn't strongly support a primary role in the pathogenesis of ACM. (usda.gov)
  • Actin molecules are bound to the Z line, which forms the borders of the sarcomere. (wikipedia.org)
  • Within the muscle sarcomere, each tropomyosin molecule spans approximately __________ globular (G) actin molecules. (physiologyweb.com)
  • This power pack performs the actual muscle work: When the sarcomeres shorten, the muscle contracts. (mpg.de)
  • 1 Many muscle diseases ultimately are reflected in changes in sarcomere organization. (spiedigitallibrary.org)
  • Methods and Results-We used clinically available genetic testing on 3 cases referred for evaluation of left ventricular dysfunction and noncompaction of the left ventricle and found that all 3 individuals carried sarcomere mutations. (northwestern.edu)
  • Mutations in sarcomere protein genes in left ventricular noncompaction. (cdc.gov)
  • We conclude that left ventricular noncompaction is within the diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects. (cdc.gov)
  • Both peak sarcomere isometric twitch force and unloaded velocity of sarcomere shortening (Vo) were a sigmoidal function of [Ca2+]o. (ahajournals.org)
  • Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. (rupress.org)
  • Dewey M, Colflesh D, Brink P, Fan S-F, Gaylinn B, Gural N (1982) Structural, functional, and chemical changes in the contractile apparatus of Limulus striated muscle as a function of sarcomere shortening and tension development. (springer.com)
  • Full loss of myo18b function results in a complete lack of sarcomeric structure, revealing a highly surprising and essential role for myo18b in sarcomere assembly. (monash.edu)
  • Our ultimate goal is to elucidate the three-dimensional structure of the sarcomere as a whole and gain insights into its formation, maintenance and function," explains Stefan Raunser , coordinator of the joint project. (mpg.de)
  • To reconcile these apparent inconsistencies concerning contractile function in HCM it has been proposed that HCM sarcomere mutations may lead to improved energy cost of force production through inefficient or excessive ATP utilization (observe also "Improved energy cost of tension generation" section) and that this ultimately results in an energy deficiency that contributes to the pathogenesis of the disease (Ashrafian et al. (researchdataservice.com)
  • Sarcomeres are the basic contractile units of striated muscle. (nih.gov)