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.
Muscle Fibers, Skeletal
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.
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.
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.
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.
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.
Myosin Heavy Chains
LIM Domain Proteins
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.
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.
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.
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.
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.
Fluorescent Antibody Technique
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.
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)
Sarcomere number regulation maintained after immobilization in desmin-null mouse skeletal muscle | Journal of Experimental...
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, ...
Sarcomere dynamics in cat cardiac trabeculae. | Circulation Research
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...
Cardiac myosin binding protein C phosphorylation affects cross-bridge cycles elementary steps in a site-specific manner.: Based on our recent finding that card
Disuse-induced Preferential Loss of the Giant Protein Titin Depresses Muscle Performance via Abnormal Sarcomeric Organization |...
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 ...
Sarcomere length changes during end-held (isometric) contractions in intact mammalian (rat) fast and slow muscle fibres. - UEA...
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 ...
Abstract P078: Dysregulated Calcium Handling in a Conditional Cardiac Myosin Binding Protein C Knockout Model of Hypertrophic...
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 ...
Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C | BMC...
Cardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA). Efficient phosphorylation requires that PKA be anchored close to its targets by A-kinase anchoring proteins (AKAPs). Cardiac Myosin Binding Protein-C (cMyBPC) and cardiac troponin I (cTNI) are hypertrophic cardiomyopathy (HCM)-causing sarcomeric proteins which regulate contractility in response to PKA phosphorylation. During a yeast 2-hybrid (Y2H) library screen using a trisphosphorylation mimic of the C1-C2 region of cMyBPC, we identified isoform 4 of myomegalin (MMGL) as an interactor of this N-terminal cMyBPC region. As MMGL has previously been shown to interact with phosphodiesterase 4D, we speculated that it may be a PKA-anchoring protein (AKAP). To investigate this possibility, we assessed the ability of MMGL isoform 4 to interact with PKA regulatory subunits R1A and R2A using Y2H-based direct protein-protein interaction assays. Additionally, to further
Abstract 20476: Cardiac Myosin Heavy Chain Isoforms Are Acetylated at Lysine Residues, Resulting in Enhanced Enzymatic and...
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 ...
A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle -...
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 is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C | BMC Cell...
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 . 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 , 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 ...
Cardiac myosin binding protein C and MAP-kinase activating death domain-containing gene polymorphisms and diastolic heart...
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.. ...
The Structure of Skeletal Muscle. - A-Level Physical Education (Sport & Coaching) - Marked by Teachers.com
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 ...
NAVER Academic | Effects of Sustained Length-Dependent Activation on In Situ Cross-Bridge Dynamics in Rat Hearts
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
Significance of sarcomere gene mutation in patients with dilated cardiomyopathy | GMR | Genetics and Molecular Research | The...
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.
ZFIN Publication: Prill et al., 2019
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 coarse-grained model of the myofibril: Overall dynamics and the evolution of sarcomere non-uniformities - CaltechAUTHORS
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 ...
Changes in Striated Muscle Fibres During Contraction and Growth with Particular Reference to Myofibril Splitting | Journal of...
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 ...
Effects of MgADP on length dependence of tension generation in skinned rat cardiac muscle. - Semantic Scholar
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
Monitoring sarcomere structure changes in whole muscle using diffuse light reflectance
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.
Differential contribution of cardiac sarcomeric proteins in the myofibrillar force response to stretch<...
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 ...
Mechanisms of residual force enhancement in skeletal muscle: insights from experiments and mathematical models | SpringerLink
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
Print content: Muscle Architecture | FitClick
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. ...
Neb - Nebulin - Mus musculus (Mouse) - Neb gene & protein
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
Myopalladin, a Novel 145-Kilodalton Sarcomeric Protein with Multiple Roles in Z-Disc and I-Band Protein Assemblies | JCB
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 ...
Frank-Starling law of the heart
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
Scientists Discover Important Mechanism for Muscle Building
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…
OSA | Imaging 2D optical diffuse reflectance in skeletal muscle
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 ...
Experimentally Increasing Titin Compliance in a Novel Mouse Model Attenuates the Frank-Starling Mechanism But Has a Beneficial...
TY - JOUR. T1 - Experimentally Increasing Titin Compliance in a Novel Mouse Model Attenuates the Frank-Starling Mechanism But Has a Beneficial Effect on Diastole. AU - Methawasin, M.. AU - Hutchinson, K.R.. AU - Lee, E.J.. AU - Smith, J.E.. AU - Saripalli, C.. AU - Hidalgo, C.G.. AU - Ottenheijm, C.A.C.. AU - Granzier, H.. PY - 2014. Y1 - 2014. U2 - 10.1161/CIRCULATIONAHA.113.005610. DO - 10.1161/CIRCULATIONAHA.113.005610. M3 - Article. C2 - 24599837. VL - 129. SP - 1924. EP - 1936. JO - Circulation. JF - Circulation. SN - 0009-7322. IS - 19. ER - ...
Search Results | RUP
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 ...
Frank-Starling Mechanism | The Lecturio Online Medical Library
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 | Beneficial Effects of RAF...
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 ...
What is the smallest contractile unit of a muscle fiber? | Reference.com
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...
Survival, Integration, and Differentiation of Cardiomyocyte Grafts | Circulation
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-s | Open-i
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;
UNC45B is a molecular chaperone that mediates the folding of thick-filament myosin during sarcomere formation; however, UNC45B may also mediate specific functions of non-muscle myosins (NMMs) ...
Frontiers | MYBPC1, an Emerging Myopathic Gene: What We Know and What We Need to Learn | Physiology
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
Group of diseases - Humpath.com - Human pathology
Hypertrophic cardiomyopathies are due to primary defects in sarcomerci function by mutations of genes coding for sarcomeric proteins composing the cardiac sarcomere ...
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 their relaxed state and cau
sarcomere - oi
C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation<...
TY - JOUR. T1 - C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation. AU - Harris, Samantha P.. AU - Belknap, Betty. AU - Van Sciver, Robert E.. AU - White, Howard D.. AU - Galkin, Vitold E.. PY - 2016/2/9. Y1 - 2016/2/9. N2 - Mutations in genes encoding myosin, the molecular motor that powers cardiac muscle contraction, and its accessory protein, cardiac myosin binding protein C (cMyBP-C), are the two most common causes of hypertrophic cardiomyopathy (HCM). Recent studies established that the N-terminal domains (NTDs) of cMyBP-C (e.g., C0, C1, M, and C2) can bind to and activate or inhibit the thin filament (TF). However, the molecular mechanism(s) by which NTDs modulate interaction of myosin with the TF remains unknown and the contribution of each individual NTD to TF activation/inhibition is unclear. Here we used an integrated structure-function approach using cryoelectron microscopy, biochemical kinetics, and force measurements to ...
Welcome to CDC stacks | Contractile Units in Disordered Actomyosin Bundles Arise from F-Actin Buckling - 33757 | CDC Public...
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 ...
Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles | Journal of Experimental Biology...
The active isometric force produced by muscles varies with muscle length in accordance with the force-length relationship. Compared with isometric contractions at the same final length, force increases after active lengthening (force enhancement) and decreases after active shortening (force depression). In addition to cross-bridges, titin has been suggested to contribute to force enhancement and depression. Although titin is too compliant in passive muscles to contribute to active tension at short sarcomere lengths on the ascending limb and plateau of the force-length relationship, recent evidence suggests that activation increases titin stiffness. To test the hypothesis that titin plays a role in force enhancement and depression, we investigated isovelocity stretching and shortening in active and passive wild-type and mdm (muscular dystrophy with myositis) soleus muscles. Skeletal muscles from mdm mice have a small deletion in the N2A region of titin and show no increase in titin stiffness ...
Sarcomere | Cell and Developmental Biology | SUNY Upstate Medical University
Diagram of a sarcomere bounded by the Z-bands. The left side (peach color) of the sarcomere represents a half sarcomere found in vertebrate skeletal myofibrils. Note that the nebulin molecules are part of and extend the entrie length of the thin filaments. The right side (pink color) of the sarcomere reflects a half sarcomere in cardiac muscle cells. The smaller nebulin isoform, nebulette, begins within the Z-band and extends only a short distance along the thin filament. Titin is shown with its NH2 termini from adjacent sarcomeres overlapping in the Z-band. Groups of three titin filaments are shown aligned together in the half sarcomere and overlapping in the Z-band. Groups of three titin filaments are shown alighned together in the half sarcomere and overlapping in the M-band with groups of three from the other half sarcomere. The scale of the drawing does not allow the ratio of six titins per half-thick filament or the two nebulin isoforms per actin thin filament to be illustrated. The ...
MMI‐0100 Inhibits Cardiac Fibrosis in a Mouse Model Overexpressing Cardiac Myosin Binding Protein C | Journal of the American...
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 ...
CARDIAC MYOSIN BINDING PROTEIN C MUTATIONS IN FAMILIES WITH HYPERTROPHIC CARDIOMYOPATHY: DISEASE EXPRESSION IN RELATION TO AGE,...
UCL Discovery is UCLs open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.
Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency. -...
RATIONALE: Most sarcomere gene mutations that cause hypertrophic cardiomyopathy are missense alleles that encode dominant negative proteins. The potential exceptions are mutations in the MYBPC3 gene (encoding cardiac myosin-binding protein-C [MyBP-C]), which frequently encode truncated proteins. OBJECTIVE: We sought to determine whether there was evidence of haploinsufficiency in hypertrophic cardiomyopathy caused by MYBPC3 mutations by comparing left ventricular muscle from patients undergoing surgical myectomy with samples from donor hearts. METHODS AND RESULTS: MyBP-C protein and mRNA levels were quantitated using immunoblotting and RT-PCR. Nine of 37 myectomy samples had mutations in MYBPC3: 2 missense alleles (Glu258Lys, Arg502Trp) and 7 premature terminations. No specific truncated MyBP-C peptides were detected in whole muscle homogenates of hypertrophic cardiomyopathy tissue. However, the overall level of MyBP-C in myofibrils was significantly reduced (P|0.0005) in tissue containing either a
CONTRACTILITY AND ULTRASTRUCTURE IN GLYCEROL-EXTRACTED MUSCLE FIBERS | JCB
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 ...
Most recent papers with the keyword Cardiac Contractility Modulation | Read by QxMD
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 ...
Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for...
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 ...
Novel mutations in the sarcomeric protein myopalladin in patients with dilated cardiomyopathy - MDC Repository
Recently, missense mutations in titin-associated proteins have been linked to the pathogenesis of dilated cardiomyopathy (DCM). The objective of this study was to search for novel disease-associated mutations in the two human titin-binding proteins myopalladin and its amino-terminal-interacting partner cardiac ankyrin-repeat protein (CARP). In a cohort of 255 cases with familial and sporadic DCM, we analyzed the coding regions and all corresponding intron flanks located in the MYPN and CARP-encoding ANKRD1 gene. Two heterozygous missense mutations were detected in the MYPN gene (p.R955W and p.P961L), but neither of these mutations was found in 300 healthy controls. Both mutations were located in the alpha-actinin-binding region of myopalladin. Endomyocardial biopsies from the p.R955W carrier showed normal subcellular localization of myopalladin and alpha-actinin in cardiac myocytes, while their regular sarcomeric staining pattern was significantly disrupted in the p.P961L carrier, indicating ...
Hypertrophic Cardiomyopathy | JACC: Journal of the American College of Cardiology
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 ...
CIENCIASMEDICASNEWS: Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy. - PubMed - NCBI
Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that can be found in both children and adults and is associated with many causative mutations. In children who are not the index case of HCM in their families, current recommendations call only for targeted genetic testing for familial mutations. However, clinical experience suggests that de novo mutations are possible, as are mutations inherited from apparently an unaffected parent. A chart review was conducted of all patients who received HCM genetic testing at Johns Hopkins from 2004 to 2013. In total, 239 patient charts were analyzed for personal and familial genetic findings. Eighty-one patients with sarcomere gene mutations were identified, of which 66 had a clinical diagnosis of HCM. Importantly, eight patients had ,1 pathogenic or likely pathogenic mutation, including six patients who were diagnosed with HCM as children (18 or younger). In this analysis, when a sarcomere mutation is identified in a family, the ...
A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice | Science
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 ...
Frank-Starling law - Wikipedia
The Frank-Starling mechanism occurs as the result of the length-tension relationship observed in striated muscle, including for example skeletal muscles, arthropod muscle and cardiac (heart) muscle. 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. 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 molecular composition of the sarcomeric M-band correlates with muscle fiber type
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 ...
Muscle-specific RING finger-2 (MURF-2) is important for microtubule, intermediate filament and sarcomeric M-line maintenance in...
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 ...
A new model of the cardiomyopathy seen in Barth syndrome
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. ...
Spontaneous oscillatory contraction of sarcomeres in skeletal myofibrils | SpringerLink
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...
Proteins transmit force : Vertebrata - AskNature
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 ...
IJMS | Free Full-Text | Differential Sarcomere and Electrophysiological Maturation of Human iPSC-Derived Cardiac Myocytes in...
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
Phosphorylation of protein kinase C sites Ser42/44 decreases Ca(2+)-sensitivity and blunts enhanced length-dependent activation...
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 ...
Heat Shock Protein 70 | BACE1 Inhibitors for the Treatment of Alzheimers Disease
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  and is responsible for the development of passive tension within the sarcomere . Titin-based passive tension constitutes a large fraction of the myocardial passive tension; the other main contributor is the extracellular ...
Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function in tnnt2 mutant zebrafish |...
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 ...
JCI - Deficiency in Kelch protein Klhl31 causes congenital myopathy in mice
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 ...
Regulation of contraction in mammalian striated muscles-the plot thick-ens | JGP
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 ...
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Friedrich, O, Weber, C, Both, M, von Wegner, F, Chamberlain, J S, Garbe, C S and Fink, R H A (2008). Sarcomere Structure and Motor-Protein Function in an Animal Model of Duchenne Muscular Dystrophy (mdx mouse). 87th Annual Meeting of the German Physiological Society ...
Publications | Page 8 | Heidelberg Collaboratory for Image Processing (HCI)
Friedrich, O, Weber, C, Both, M, von Wegner, F, Chamberlain, J S, Garbe, C S and Fink, R H A (2008). Sarcomere Structure and Motor-Protein Function in an Animal Model of Duchenne Muscular Dystrophy (mdx mouse). 87th Annual Meeting of the German Physiological Society ...
Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem - Tabular View - ClinicalTrials.gov
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 ...
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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 ...
Stritch researcher: New blood test could detect heart attacks more quickly | Stritch School of Medicine
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, ...
Calcium binding to an elastic portion of connectin/titin filaments
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 …
Foam Rolling Isnt Stretching, But Its Still Important - DeanSomerset.com
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″ ...
SMART: Pfam domain PPAK
PPAK is a repeated protein motif found in the PEVK (Pro-Glu-Val-Lys) domain of the titin protein and in a number of other proteins. Titin ( EC 18.104.22.168 ) is a giant elastic protein found in striated muscle that is a key component in the assembly and functioning of sarcomeres [ (PUBMED:15507486) ]. PPAK motifs (PPAK refers to the four amino acids found at the beginning of the motif) occur 60 times in human soleus titin [ (PUBMED:11276084) ]. PPAK motifs occur in groups of 2-12 that are separated by regions rich in glutamic acid (approximately 45%) and termed polyE segments. The charge fluctuation between the PPAK and polyE regions suggests ionic interactions between these segments and their involvement in the elastic function of titin. ...
Muscles | Ichthus77
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 Summary Report | CureHunter
myomesin: protein from M-band of skeletal muscle; RefSeq NM_003970 (human); NM_008664 (mouse); XM_240481 (Myom2, rat), XM_237523 (Myom1, rat)
Publications | Max Planck Institute for Medical Research
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 ...
Modify the spacing within cells in Excel
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...
a. To determine: The term that describes "stores and releases calcium." | bartleby
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Essential Mineral Elements in Plant Nutrition
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Endurance Training for Pain & Rehab
In a trigger point, the sarcomeres are over-contracted … which means that the sarcomeres up and down the line are, to some ... For a much more detailed explanation of how this all works, see Micro Muscles and the Dance of the Sarcomeres. ... The smallest functional unit of muscle physiology is the sarcomere, which is like a microscopic muscle: a bundle of overlapping ... A muscle is basically several million sarcomeres working in together.3. ...
How can we identify the best way to train each muscle? | by Chris Beardsley | Medium
4. Working sarcomere lengths. What it is: Working sarcomere lengths describe the lengths of the sarcomeres inside the fibers of ... The working sarcomere lengths describe the lengths of the sarcomeres inside a muscle over its joint angle range of motion. It ... Working sarcomere lengths - muscles that contain sarcomeres that can be stretched substantially will be more easily damaged ... Depending on the number of sarcomeres in the muscle fibers of a muscle (and on other factors), the length of any sarcomere ...
Load dependency in force-length relations in isolated single cardiomyocytes<...
The new method allowed stretching cells to 2.2μm or more in end-diastolic sarcomere length. ESFLR virtually behaves in a load ... The new method allowed stretching cells to 2.2μm or more in end-diastolic sarcomere length. ESFLR virtually behaves in a load ... The new method allowed stretching cells to 2.2μm or more in end-diastolic sarcomere length. ESFLR virtually behaves in a load ... The new method allowed stretching cells to 2.2μm or more in end-diastolic sarcomere length. ESFLR virtually behaves in a load ...
Optimal range for parvalbumin as relaxing agent in adult cardiac myocytes: Gene transfer and mathematical modeling -...
The muscle fibers within muscle cells are divided into myofibrils, which are further divided into , the contractile units...
Radiotherapy for malignant conditions: Strahlentherapie Pasing
Deletion of the titin N2B region accelerates myofibrillar force development but does not alter relaxation kinetics<...
Cardiac titin is the main determinant of sarcomere stiffness during diastolic relaxation. To explore whether titin stiffness ... abstract = "Cardiac titin is the main determinant of sarcomere stiffness during diastolic relaxation. To explore whether titin ... N2 - Cardiac titin is the main determinant of sarcomere stiffness during diastolic relaxation. To explore whether titin ... AB - Cardiac titin is the main determinant of sarcomere stiffness during diastolic relaxation. To explore whether titin ...
frigidaire washer parts diagram
bioRxiv Channel Allen Institute for Cell Science
Is the Tongue the Strongest Muscle in Your Body?
John K-J Li - Dynamics of the Vascular System, page 92 read online
Molecular muscle machines bulk up | Research | Chemistry World
Is stretching overrated? - Yoga Spy
Stretching doesnt cause the muscle to build more sarcomeres. Im not sure if you mean more sarcomeres in parallel ( ie ... The only thing that will increase the sarcomeres is resistance training, where the load stresses the muscle cell to hypertrophy ... Continued stretching causes the muscle to build more sarcomeres, the contractile units that comprise a muscle. ...
Trigger Points and Continuing Misdiagnosis - Know Thyself Advisor
The sarcomeres are the small sections of each fibre. From one section to another defines the length of a sarcomere. In the ... In each fibre we have microscopic units called sarcomeres. Just to make a small movement in a muscle millions of sarcomeres ... Trigger point therapy sessions address this issue by equalising sarcomere length.. Normally sarcomeres are like little pumps ( ... It is a primary location for trigger points because this is where sarcomeres tend to remain contracted. However its not quite ...
Search Results | Journal of General Physiology | Rockefeller University Press
Research topic on muscle mechanics in Frontiers in Physiology | Biomedical Engineering
2) Methods to quantify sarcomere length changes and viewpoints on sarcomere length heterogeneity/homogeneity along muscle ... 4) Approaches to link different scales of neuro-musculo-skeletal mechanics from sarcomere level to whole body level 5) Clinical ... One particular challenge is to quantify length changes of sarcomeres. However, this is not only a methodological challenge, but ... Resulting prospects range from homogeneous sarcomere lengths or amplitude-wise varying but the same direction of length changes ...
Quick Answer: Can Vitamin D Deficiency Cause Tongue Problems? - case journals
In the heart, Na/K-ATPase regulates intracellular Na+ and Ca2?+ (via NCX), | Selectivity on-target of bromodomain chemical...
If you look on the internet, youll find some bold claims about what massage will do. Removing toxins, halting delayed onset muscle soreness (DOMS), increasing range of movement by lengthening muscles, and realigning scar tissue to name but a few. So can it really do those things? Probably not. If you think about it, how can touching the skin remove toxins? How did they get in you in the first place? If youve been partying a bit too hard of late and youre feeling a bit rough because of it, the
Süter Gıda | Essay Report: Contraction and Comfort of Cardiac Fibers
The actin filament is drawn with the myosin go on the way to the center of the sarcomere producing contraction from the cardiac ... The sarcomere which is the contractile device with the myocardial microscopic cells include myosin, troponin, tropomysin and ... actin filaments. Shortening with the sarcomeres leads to contraction on the cardiac fibers. Intercalated discs have adjoining ... by intercalated discs towards the contractile cardiomyocytes caused by pacemaker tissue which journeys between sarcomeres ...
MyosinMyofibrilFilamentsStriated muscleLengthsProteinsCardiomyocytesMyofibrilsHypertrophicSingle sarcomereSerial sarcomereMusclesRole in sarcomere assemblyDiffractionMeasurement of sarcomere lengthRegions of the sarcomereAverage sarcomere lengthDynamicsLoss of sarcomeresAssembly of sarcomeresFormation of sarcomeresFibersGenesMutations in cardiomyopathyNormal sarcomereAdjacent sarcomeresCardiac muscleGeneMuscle fiberPhosphorylationHeterogeneityMorphogenesisKnockoutMYH7VariantsIsometric tensionSliding FilameMoleculesFunctional unitShortenTropomyosinContractilityOrganizationShortensLeft ventricular
- 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 (based on the 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)
- 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)
- A myofibril is formed of a sequence of sarcomeres. (crossfit.com)
- 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 phosphate (P i ) were present, and Ca 2+ was removed. (springer.com)
- The propagation of the sarcomere oscillation along the long axis of the myofibril was observed occasionally in single myofibrils and frequently in bundles of myofibrils. (springer.com)
- A theoretical framework for predicting the macroscopic behavior of a muscle myofibril based on the collective behavior of sarcomeres is presented. (caltech.edu)
- Representing complete sarcomere the smallest functional unit of myofibril of striated muscle with lines or disks at either end, and scaled to tens of thousands of times actual size, this first-ever working model graphically illustrates the sliding filament theory of skeletal muscle contraction. (shopanatomical.com)
- Following myofibril assembly, many short sarcomeres are added to each myofibril. (uzh.ch)
- Whereas the highly regular organization of the myofibril has been studied in detail, in vivo assembly of sarcomeres remains a poorly understood process. (monash.edu)
- The sarcomere is the smallest contractile unit in the myofibril. (unm.edu)
- These proteins are organized into thick and thin filaments called myofilaments, which repeat along the length of the myofibril in sections called sarcomeres. (wikipedia.org)
- Sarcomeres are composed of long, fibrous proteins as filaments that slide past each other when a muscle contracts or relaxes. (wikipedia.org)
- The relationship between the proteins and the regions of the sarcomere are as follows: Actin filaments, the thin filaments, are the major component of the I-band and extend into the A-band. (wikipedia.org)
- Narrowing and widening of an H-zone and an I-band were observed corresponding to the shortening and lengthening of a sarcomere, suggesting that thick and thin filaments slide past each other. (springer.com)
- Groups of thick and thin filaments that alternately overlap and move apart are called sarcomeres. (reference.com)
- Groups of three titin filaments are shown aligned together in the half sarcomere and overlapping in the Z-band. (upstate.edu)
- Groups of three titin filaments are shown alighned together in the half sarcomere and overlapping in the M-band with groups of three from the other half sarcomere. (upstate.edu)
- Thick and thin filaments, and titin are shown in this illustration (for simplicity, only two titin molecules per half thick filament are shown) (cf. [ 37 ] for electron microscopic images of titin molecules in the sarcomere). (hindawi.com)
- The sarcomere, the basic contractile unit of striated muscle cells, is widely accepted as being constructed of two sets of parallel and interdigitated protein filaments that are discontinuous and inextensible. (springer.com)
- The purpose of this chapter is to outline and develop key evidence that has led to the notion that the sarcomere contains two sets of distinct cytoskeletal filaments that are continuous and extensible. (springer.com)
- the other set is an extensive network of intermediate filaments enveloping each sarcomere and interlinking other cellular organelles (an exosarcomeric lattice). (springer.com)
- In hiPSC-derived cardiomyocytes, we observed mEGFP-tagged MLC-2a in a striated appearance along myofilaments, reflecting its localization to the thick filaments of sarcomeres, and absence from the Z-disk and I-band. (allencell.org)
- After stage 3 we might expect there to be some increase in the internal resistance to shortening since the actin filaments must now overlap, and after stage 4 the actin filaments from one half of the sarcomere might interfere with the cross-bridge formation in the other half of the sarcomere. (alpfmedical.info)
- These observations suggest a novel model of sarcomere assembly where Myo18b coordinates the integration of preformed thick and thin filaments into the sarcomere. (monash.edu)
- By using this system, we confirmed the ability of the unit cell (sarcomere) structure model to explain the intensity change of diffraction lines accompanying the dissociation from both ends of thick filaments in a high salt solution. (elsevier.com)
- Also, we found that myofibrils with a long sarcomere length shorten to a slack length accompanying the decrease in overlap between thick and thin filaments produced by the dissociation of thick filaments. (elsevier.com)
- The I bands appear lighter because these regions of the sarcomere mainly contain the thin actin filaments, whose smaller diameter allows the passage of light between them. (wikipedia.org)
- A sarcomere (Greek σάρξ sarx "flesh", μέρος meros "part") is the complicated unit of striated muscle tissue. (wikipedia.org)
- K. Wang, "Sarcomere-associated cytoskeletal lattices in striated muscle. (hindawi.com)
- Sarcomeres are the basic contractile units of striated muscle. (nih.gov)
- Sarcomeres are the fundamental structural and contractile units in striated muscle and sarcomere length is an important predictor of muscle function. (spiedigitallibrary.org)
- Sarcomeres, the smallest contractile units of striated muscle, are conventionally perceived as the most regular macromolecular assemblies in biology, with precisely assigned localizations for their constituent proteins. (nih.gov)
- 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)
- a , Mean (± s.e.m) sarcomere lengths versus ankle angle, measured in the lateral gastrocnemius of seven anaesthetized mice using a 1-mm-diameter microendoscope placed on the muscle. (nih.gov)
- Sarcomere lengths have been a crucial outcome measure for understanding and explaining basic muscle properties and muscle function. (frontiersin.org)
- Sarcomere lengths for a given muscle are typically measured at a single spot, often in the mid-belly of the muscle, and at a given muscle length. (frontiersin.org)
- It is then assumed implicitly that the sarcomere length measured at this single spot represents the sarcomere lengths at other locations within the muscle, and force-length, force-velocity, and power-velocity properties of muscles are often implied based on these single sarcomere length measurements. (frontiersin.org)
- The objective of this study was to measure sarcomere lengths at defined locations along and across an intact muscle, at different muscle lengths. (frontiersin.org)
- Using second harmonic generation (SHG) imaging technique, sarcomere patterns in passive mouse tibialis anterior (TA) were imaged in a non-contact manner at five selected locations ("proximal," "distal," "middle," "medial," and "lateral" TA sites) and at three different lengths encompassing the anatomical range of motion of the TA. (frontiersin.org)
- We showed that sarcomere lengths varied substantially within small regions of the muscle and also for different sites across the entire TA. (frontiersin.org)
- However, iPSC-CM generated in 2D protocols constantly displayed larger sarcomere lengths as compared to the 3D protocol. (mdpi.com)
- The variation of sarcomere length is compared to the variation in thick filament lengths in Limulus reported by Dewey et al. (springer.com)
- The contractile apparatus at various sarcomere lengths. (springer.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)
- See, for example, Figure 2, which shows that different muscles not only have different resting lay sarcomere lengths, but also different operating ranges. (movementsci.com)
- The heterogeneity of resting lay lengths is further evidenced by a cadaver study by Ward and colleagues 9 , who reported sarcomere lengths of every major lower extremity muscle (Table 1). (movementsci.com)
- Working sarcomere lengths - the working sarcomere lengths of a muscle over its physiological range of motion determine whether it can experience stretch-mediated hypertrophy . (medium.com)
- The susceptibility of a muscle to muscle damage after a workout is affected by: (1) prevailing fiber type, (2) the level of voluntary activation that can be attained, (3) the size of the muscle, and (4) the working sarcomere lengths of the muscle fibers. (medium.com)
- In order to test this idea it is necessary to measure the active increment of isometric tension at different known sarcomere lengths. (alpfmedical.info)
- The measurements have to be done on a single fibre and there are some technical difficulties because sarcomeres at the ends of a fibre may take up lengths different from those in the middle. (alpfmedical.info)
- A. F. Huxley and his colleagues overcame these difficulties by building an apparatus which used optical servomechanisms to maintain the sarcomere lengths in the middle of a fibre constant during a contraction. (alpfmedical.info)
- There is a 'plateau' of constant tension at sarcomere lengths between 2.05 and 2.2 fxm. (alpfmedical.info)
- Now let us see if the length-tension diagram shown in Fig. 10.9 can be related to these dimensions, starting at long sarcomere lengths and working through to short ones. (alpfmedical.info)
- Specific proteins are responsible for the bands and zones within each sarcomere . (wiktionary.org)
- It provides binding sites for numerous proteins and is thought to play an important role as sarcomeric ruler and as blueprint for the assembly of the sarcomere. (wikipedia.org)
- Several proteins important for the stability of the sarcomeric structure are found in the Z-line as well as in the M-band of the sarcomere. (wikipedia.org)
- Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. (sciencemag.org)
- However, recent studies have revealed complex multiple locations for several sarcomere proteins within the sarcomere and other cellular compartments such as the nucleus. (nih.gov)
- The comparison of disassembly in the developing and mature knockout sarcomere suggests diverse functions for titin's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titin-binding proteins. (rupress.org)
- Sarcomere assembly is a process orchestrated by the sequential expression of structural and signaling proteins, which ultimately leads to the formation of mature myofibrils. (rupress.org)
- In this study, we show that titin's M-line region is dispensable for initial sarcomere assembly, including the correct localization of M-band proteins, but that it is required to fortify the sarcomere structure and for lateral growth. (rupress.org)
- Monitoring the localization and embryonic expression of M-band proteins and proposed substrates of the titin kinase, we were able to attribute the sarcomere disassembly to titin's structural functions. (rupress.org)
- Background-Mutations in the genes encoding sarcomere proteins have been associated with both hypertrophic and dilated cardiomyopathy. (northwestern.edu)
- Structure of sarcomere and myofilament proteins. (comprehensivephysiology.com)
- Mutational analysis in a cohort of 63 unrelated adult probands with left ventricular noncompaction and no other congenital heart anomalies was performed by denaturing high-performance liquid chromatography analysis and direct DNA sequencing of 6 genes encoding sarcomere proteins. (cdc.gov)
- Yet it is not known how TnT mutation causes dysfunction of sarcomere microdomains and how these events contribute to misalignment of sarcomeric proteins in presence of DCM TnT-R173W. (ox.ac.uk)
- The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. (emory.edu)
- Recently, we developed a novel system in which the length of a particular, single sarcomere in cardiomyocytes can be measured at ~30 nm precision. (hindawi.com)
- Heart failure is associated with elongation of cardiomyocytes and loss of sarcomeres. (ahajournals.org)
- The sarcomere is the basic contractile unit for striated muscles such as cardiomyocytes. (mayo.edu)
- MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner. (elsevier.com)
- Troponin destabilization impairs sarcomere-cytoskeleton interactions in iPSC-derived cardiomyocytes from dilated cardiomyopathy patients. (ox.ac.uk)
- We previously reported that induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from patients with a dilated cardiomyopathy (DCM) mutation, troponin T (TnT)-R173W, display sarcomere protein misalignment and impaired contractility. (ox.ac.uk)
- Cardiac contraction originates at a subcellular - molecular, indeed - scale, within specific components of the cardiomyocytes (i.e. cardiac cells) called sarcomeres. (bioqic.de)
- 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)
- Myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as alternating dark and light bands. (wikipedia.org)
- The myofibrils of smooth muscle cells are not arranged into sarcomeres. (wikipedia.org)
- The left side (peach color) of the sarcomere represents a half sarcomere found in vertebrate skeletal myofibrils. (upstate.edu)
- The striated appearance of myofibrils makes laser diffraction 3 an ideal method to study sarcomere dynamics in single muscle fibers. (spiedigitallibrary.org)
- Myofibrils are constructed and lined up in a chain-like formation to create what are called sarcomeres. (wikibooks.org)
- During cardiomyocyte beating, the contraction of sarcomeres can be seen in the changes in spacing between striations, and some myofibrils buckle. (allencell.org)
- As the sarcomeres contract the myofibrils contract. (unm.edu)
- Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives. (qxmd.com)
- Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. (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)
- 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 serial sarcomere number of skeletal muscle changes in response to chronic length perturbation. (biologists.org)
- These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly. (elsevier.com)
- In immobilized muscles, sarcomere length measurement by traditional LD method was not possible. (nih.gov)
- Our knowledge about sarcomere dynamics has primarily come from in vitro studies of muscle fibres and analysis of optical diffraction patterns obtained from living muscles. (nih.gov)
- 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)
- To manipulate muscle sarcomere length, the psoas major muscles were used because of their appropriate anatomical locations. (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)
- 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)
- Sarcomeres are the basic force producing units of muscles. (frontiersin.org)
- In multiple classes, I was taught that muscles, and thus their sarcomeres, produce the most amount of force while at resting length. (movementsci.com)
- According to the sliding filament theory by Andrew Huxley and Ralph Niedergerke, muscles contract when Z-discs come closer together thus shortening the sarcomeres. (wikibooks.org)
- That is why we want to investigate and compare the composition and the structure of sarcomeres in young and aged muscles," Frank Schnorrer and Dirk Görlich refer to one of the goals of this large-scale project. (mpg.de)
Role in sarcomere assembly3
- 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)
- Polarization gating enables sarcomere length measurements by laser diffraction in fibrotic muscle. (nih.gov)
- Sarcomere length measured by polarization-gated laser diffraction (PGLD). (nih.gov)
- Sarcomere length and first-order diffraction line width were measured by laser diffraction during elongation of activated frog tibialis anterior muscle fiber bundles (i.e., eccentric contraction) at nominal fiber strains of 10, 25, or 35% (n = 18) for 10 successive contractions. (nih.gov)
- Diffraction pattern line width, a measure of sarcomere length heterogeneity, increased significantly with muscle activation and then continued to increase with successive stretches of the activated muscle. (nih.gov)
- The variation in sarcomere length along the fiber, as determined by the 0th to 1st diffraction order spacing, was dependent upon the fiber preparation. (springer.com)
- The diameters of diffraction rings represented the average sarcomere length. (elsevier.com)
Measurement of sarcomere length1
- Moreover, our system enables accurate measurement of sarcomere length in the isolated heart. (hindawi.com)
Regions of the sarcomere1
- 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)
Average sarcomere length2
- We propose that QDs are the ideal tool for the study of sarcomere dynamics during excitation-contraction coupling in healthy and diseased cardiac muscle. (hindawi.com)
- Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans. (nih.gov)
- High-speed data acquisition enabled observation of sarcomere contractile dynamics with millisecond-scale resolution. (nih.gov)
- These experiments point the way to in vivo imaging studies demonstrating how sarcomere performance varies with physical conditioning and physiological state, as well as imaging diagnostics revealing how neuromuscular diseases affect contractile dynamics. (nih.gov)
- Sarcomere dynamics in cat cardiac trabeculae. (ahajournals.org)
- The purpose of the present study was to describe sarcomere dynamics in thin trabeculae that were dissected from the right ventricle of kittens. (ahajournals.org)
- 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)
- ovr expression) and uptake (FATP1 overexpression) reveal gender-specific changes in cardiac lipid dynamics, affecting myocardial compliance and sarcomere activity. (grantome.com)
- Together, it pursues an innovative, interdisciplinary concept that combines quantitative proteomics and nanoantibody engineering (Görlich) with super-resolution light microscopy (Schnorrer, Gautel), electron cryo-tomography (Raunser), and biochemical as well as functional genetic analyses of sarcomere dynamics in Drosophila flies (Schnorrer), but also in zebrafish and mouse (Gautel). (mpg.de)
Loss of sarcomeres1
- It was found that periods of stretch as short as 1/2 h daily were sufficient not only to prevent loss of sarcomeres but actually to cause an increase in the number of sarcomeres in series. (painscience.com)
Assembly of sarcomeres1
- Consistent with the ability of MEK5 to induce serial assembly of sarcomeres in vitro, cardiac-specific expression of activated MEK5 in transgenic mice resulted in eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death. (elsevier.com)
Formation of sarcomeres1
- In addition, several studies have postulated that beta1 integrins have a role in the formation of sarcomeres. (biologists.org)
- Iwazumi, T. & Pollack, G. H. (1981) The effect of sarcomere non-uniformity on the sarcomere lengthtension relationship of skinned fibers. (springer.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)
- As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. (uzh.ch)
- Only when the sarcomeres of the muscle fibers of a muscle are stretched onto the descending limb of the length-tension relationship can mechanical tension be increased during full range of motion exercises. (medium.com)
- Familial disease caused by mutations in cardiac sarcomere protein genes, which accounts for most cases in adolescents and adults, is believed to be a very rare cause of HCM. (qxmd.com)
- This study shows that familial disease is common among infants and children with HCM and that, in most cases, disease is caused by mutations in cardiac sarcomere protein genes. (qxmd.com)
- Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. (qxmd.com)
- 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)
- Mutations in sarcomere protein genes in left ventricular noncompaction. (cdc.gov)
- Many sarcomeric genes have been implicated in congenital cardiomyopathies, such that understanding developmental sarcomere transitions will inform the aetiology and treatment. (ox.ac.uk)
Mutations in cardiomyopathy1
- Sarcomere mutations in cardiomyopathy, noncompaction, and the developing heart. (cdc.gov)
- Extrapolating to an in vitro cardiomyocyte model, the altered postnatal splicing was corrected with addition of synthetic Tβ4, whereby normal sarcomere length was restored. (ox.ac.uk)
- The sarcomeres give skeletal and cardiac muscle their striated appearance, which was first described by Van Leeuwenhoek. (wikipedia.org)
- The right side (pink color) of the sarcomere reflects a half sarcomere in cardiac muscle cells. (upstate.edu)
- Both skeletal muscle and cardiac muscle have sarcomeres. (histology-world.com)
- Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts. (dropbox.com)
- 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 evaluations demonstrated familial disease in 6 of 11 probands with sarcomere gene mutations. (cdc.gov)
- We conclude that left ventricular noncompaction is within the diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects. (cdc.gov)
- Loss of titin's M line leads to impaired stability of the muscle fiber with the disassembly of existing sarcomeres. (rupress.org)
- The muscle fiber relaxes and the entire sarcomere lengthens. (wikipedia.org)
- A muscle fiber is divided into functional units known as sarcomeres which are defined as the distance between 2 sets of Z - lines. (mhhe.com)
- 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)
- They also demonstrate that muscle injury is accompanied by a progressive increase in sarcomere length heterogeneity, yielding lower yield tension as injury progresses. (nih.gov)
- The results suggest that in conditions of calcium overload, the vulnerable window of stretch-release to trigger suprathreshold delayed afterdepolarizations can be affected by heterogeneity in sarcomere length. (uio.no)
- Furthermore, stretch and sarcomere heterogeneity may modulate the susceptibility threshold for delayed afterdepolarizations and the aftercontraction wave propagation velocity. (uio.no)
- 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)
- 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 in arrhythmogenic cardiomyopathy: Pathogenic factor or bystander? (usda.gov)
- 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)
- Cleworth DR, Edman KAP (1972) Changes in sarcomere length during isometric tension development in frog skeletal muscle. (springer.com)
- This two-filament sarcomere model provides a structural basis for the powerful sliding-filament theory of muscle contraction. (springer.com)
- This power pack performs the actual muscle work: When the sarcomeres shorten, the muscle contracts. (mpg.de)
- Using a human iPSC-CM model combined with CRISPR/Cas9-engineered isogenic controls, we uncovered that TnT-R173W destabilizes molecular interactions of troponin with tropomyosin, and limits binding of PKA to local sarcomere microdomains. (ox.ac.uk)
- Small molecule-based activation of AMPK can restore TnT microdomain interactions, and partially recovers sarcomere protein misalignment as well as impaired contractility in DCM TnT-R173W iPSC-CMs. (ox.ac.uk)
- 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)