Idiopathic dilated cardiomypathy (DCM) is characterized by the progressive depression of cardiac function and left ventricular dilation in the absence of coronary artery disease. There is evidence to suggest that humoral immunity plays an important role in the pathogenesis of DCM. In particular, the role of autoantibodies in the pathogenesis of DCM has been emphasized (1). Sera from patients with DCM show a variety of autoantibodies, including those against membrane proteins, mitochondrial proteins, heat-shock proteins, and myocyte structural sarcolemmal proteins. Because all these antibodies are not present in each patient with DCM, it is apparent that all these autoantibodies are not pathogenic in DCM. To date, only 2 autoantibodies have satisfied the criteria of cause-and-effect relationship for DCM, and both these antibodies display stimulatory activities. The first comes from a report that program death receptor-1 (PD-1) mice develop autoantibodies against cardiac troponin 1 (cTpn 1) and ...
sarcolemmal definition: Adjective (comparative more sarcolemmal, superlative most sarcolemmal) 1. Of or pertaining to a sarcolemma...
Contraction in a muscle cell is produced by an [[Action potential,action potential travelling]] along a motor neurone and arriving at a [[Synapse]]. The voltage gradient causes voltage-gated calcium [[Ion channels,ion channels]] in the [[Presynaptic,presynaptic neurone]] to open, triggering [[Vesicles,vesicles]] containing [[Neurotransmitter,neurotransmitters]], specifically acetylcholine, to travel towards the [[Sarcolemma,sarcolemma]]; fusing with the [[Plasma membrane,membrane and]] releasing acetylcholine into the [[Synaptic cleft,synaptic cleft]] ,ref,Bowness E, Braid K, Brazier J, Burrows C, Craig K, Gillham R, Towle J. (2009), A2-level Biology The Revision Guide Exam Board AQA, page 57-60, Newcastle-upon-Tyne: CGP books.,/ref,. They diffuse across the cleft where they bind to specific [[Receptor,receptors]] called [[Nicotinic cholinergic receptors,nicotinic cholinergic receptors]] on the [[Sarcolemma,sarcolemma]], where the [[Depolarisation,depolarisation]] travels ...
View Notes - AP1 from BIOL 239 at New Mexico. Total score: 1. 1.25/3 = 41.6667% Total score adjusted by 0.0 1) binds to receptors on the sarcolemma Maximum possible score: 3 Which of the following is
The present study provides new information regarding the GLUT4 translocation process by directly monitoring the dynamic trafficking of GLUT4 depots during early translocation, steady-state recycling, and re-internalization of GLUT4 in skeletal muscle in situ in a living animal on insulin injection. We have previously studied the early translocation phase (15), but the present study adds considerably to the former by monitoring at higher magnification and higher time resolution. A major new finding is that the majority of insulin-mediated GLUT4 translocation does not involve any high degree of movement of GLUT4 storage vesicles (,1 μm) over longer or even shorter distances, e.g., from the cell interior to the sarcolemma. Surprisingly, the storage vesicles, whether located in the perinuclear region, at the sarcolemma, or at the t-tubules, remain stationary and "melt" away as they are depleted locally without any significant movement away from their original position (Figs. 2 and 3). Another major ...
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Sarcolemmal ATP-sensitive potassium channels (KATP) act as metabolic sensors that facilitate adaptation of the left ventricle to changes in energy requirements. This study examined the mechanism by which KATP dysfunction impairs the left ventricular response to stress using transgenic mouse strains with cardiac-specific disruption of KATP activity (SUR1-tg mice) or Kir6.2 gene deficiency (Kir6.2 KO). Both SUR1-tg and Kir6.2 KO mice had normal left ventricular mass and function under unstressed conditions. Following chronic transverse aortic constriction, both SUR1-tg and Kir6.2 KO mice developed more severe left ventricular hypertrophy and dysfunction as compared with their corresponding WT controls. Both SUR1-tg and Kir6.2 KO mice had significantly decreased expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and a group of energy metabolism related genes at both protein and mRNA levels. Furthermore, disruption of KATP repressed expression and promoter activity of ...
Results: Intralipid infusion reduced whole body glucose infusion rate 26% in women and 38% in men (p,0.05) and insulin stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by intralipid. ...
Phospholipids are believed to play an important role in pathology and physiology of the myocardium. Because of the distinct physico-chemical properties of plasmalogens we studied the plasmalogen content and distribution in the sarcolemma of cultured rat myocytes. Treatment with phospholipase A2 degraded all glycerophospholipids in the outer monolayer. The hydrolysis ... read more products were analyzed for plasmalogen content. It is shown that the inner sarcolemmal leaflet is highly enriched in phosphatidylcholine and ethanolamine plasmalogen. This distribution of the plasmalogens might affect bilayer stability and thereby be involved in the destruction of the sarcolemma upon ischemia and reperfusion. show less ...
Two mechanisms of passive Ca2+ transport, Na+-Ca2+ exchange and Ca2+-Ca2+ exchange, were studied using highly-purified dog heart sarcolemmal vesicles. About 80% of the Ca2+ accumulated by Na+-Ca2+ exchange or Ca2+-Ca2+ exchange could be released as free Ca2+, while up to 20% was probably bound. Na+-Ca2+ exchange was simultaneous, coupled countertransport of Na+ and Ca2+. The movement of anions during Na+-Ca2+ exchange did not limit the initial rate of Na+-Ca2+ exchange. Na+-Ca2+ exchange was electrogenic, with a reversal potential of about -105 mV. The apparent flux ratio of Na+-Ca2+ exchange was 4 Na+:1 Ca2+. Coupled cation countertransport by the Na+-Ca2+ exchange mechanism required a monovalent cation gradient with the following sequence of ion activation: Na+ much greater than Li+ greater than Cs+ greater than K+ greater than Rb+. In contrast to Na+-Ca2+ exchange, Ca2+-Ca2+ exchange did not require a monovalent cation gradient, but required the presence of Ca2+ plus a monovalent cation on both sides
Previous findings support the idea that one function of the DGC is to provide mechanical reinforcement of the sarcolemma and to maintain membrane integrity during cycles of contraction and relaxation (Weller et al., 1990; Clarke et al., 1995; Petrof et al., 1993). To test the involvement of sarcolemmal damage in the pathogenesis of muscle fiber degeneration and necrosis, we injected animal models for muscular dystrophy with EBD. Intracellular accumulation of the dye in skeletal muscle fibers indicated loss of sarcolemmal integrity due to plasma membrane disruptions. As a further test of altered membrane permeability, we examined the intracellular deposition of serum proteins in skeletal muscle fibers in the murine models and in patients with DMD and CMD.. Our results demonstrated that focal plasma membrane defects have actually occurred in vivo and not, as argued, during biopsy (Bradley and Fulthorpe, 1978). The diffuse intracellular distribution of the tracer implied a break in the structural ...
We demonstrated that MG53 is crucial to the emergency membrane repair response in cardiomyocytes and protects the heart from stress-induced loss of cardiomyocytes. Disruption of the sarcolemmal membrane by mechanical, electric, chemical, or metabolic insults caused rapid and robust translocation of MG53 toward the injury sites. Ablation of MG53 prevented sarcolemmal resealing after infrared laser-induced membrane damage in intact heart, and exacerbated mitochondrial dysfunction and loss of cardiomyocytes during ischemia/reperfusion injury. Unexpectedly, the MG53-mediated cardiac membrane repair was mediated by a cholesterol-dependent mechanism: depletion of membrane cholesterol abolished, and its recovery restored injury-induced membrane translocation of MG53. The redox status of MG53 did not affect initiation of MG53 translocation, whereas MG53 oxidation conferred stability to the membrane repair patch.. ...
GRC is a Ca2+-permeable nonselective cation channel belonging to the TRP channel family, which translocates from the cell interior to the surface in response to growth factors (Kanzaki et al., 1999; Boels et al., 2001). GRC is normally expressed in adult striated muscles, with low expression in the sarcolemma except in cardiac intercalated discs (Fig. 1). In normal hamster myotubes, sarcolemmal GRC expression was transiently elevated only on the first day of cell fusion, whereas in BIO14.6 myotubes, this initial expression continued (Fig. 2; unpublished data). Intriguingly, in normal myotubes, cell stretch increased sarcolemmal GRC expression, which required entry of external Ca2+ (Fig. 2, b and c). This triggering Ca2+ could have entered via a low level of GRC initially present in the sarcolemma. However, little is known as to what initially triggers the surface translocation of GRC during the formation of myotubes. The situation was somewhat similar in the case of GRC-transfected CHO cells; an ...
Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the sarcolemma membrane. Mutations in alpha II-spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for Guillain-Barré syndrome and infantile congenital heart disease. Alternate splicing of alpha II-spectrin has been documented and results in multiple transcript variants; specifically, cardiomyocytes have four identified alpha II-spectrin splice variants. As opposed to alpha I-spectrin that is principally found in erythrocytes, alpha II-spectrin is expressed in most tissues. In cardiac tissue, alpha II-spectrin is found in myocytes at Z-discs, costameres, and the sarcolemma membrane, and in cardiac fibroblasts along the surface of the cytoskeletal network. Alpha ...
Calcium is essential for the maintenance of contraction in the heart, and it has been suggested that the glycoprotein matrix on the external surface of cardiac cells is a critical factor in the supply of activator calcium to the beating heart. Sialic acid residues are important calcium-binding sites in the matrix and treatment with neuraminidase, an enzyme which cleaves sialic acid from oligosaccharide chains, has been reported to abolish spontaneous contraction in cultured heart cells, without causing general breakdown in the plasma membrane. However, we report here that in intact, electrically stimulated guinea pig atrial preparations, neuraminidase treatment produces no significant changes in resting tension or force of contraction. It is also without effect on the response to calcium removal and replacement, and inotropic or toxic concentrations of cardiac glycosides. In these experiments, up to 79% of the total tissue sialic acid was removed, and electron microscopy studies showed that this
TY - JOUR. T1 - Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics. AU - Gumina, Richard J.. AU - Pucar, Darko. AU - Bast, Peter. AU - Hodgson, Denice M.. AU - Kurtz, Christopher E.. AU - Dzeja, Petras P.. AU - Miki, Takashi. AU - Seino, Susumu. AU - Terzic, Andre. PY - 2003/6/1. Y1 - 2003/6/1. N2 - Although ischemic preconditioning induces bioenergetic tolerance and thereby remodels energy metabolism that is crucial for postischemic recovery of the heart, the molecular components associated with preservation of cellular energy production, transfer, and utilization are not fully understood. Here myocardial bioenergetic dynamics were assessed by 18O-assisted 31P-NMR spectroscopy in control or preconditioned hearts from wild-type (WT) or Kir6.2-knockout (Kir6.2-KO) mice that lack metabolism-sensing sarcolemmal ATP-sensitive K+ (KATP) channels. In WT vs. Kir6.2-KO hearts, preconditioning induced a significantly higher total ATP turnover (232 ± 20 vs. ...
The Na+-Ca2+ exchanger (NCX) of cardiac sarcolemma, transports 3 Na+ for 1 Ca2+,1 is the main mechanism of Ca2+ extrusion from ventricular myocytes, and contributes to relaxation.2,3⇓ NCX exhibits a thermodynamically defined reversal potential (ENCX) analogous to those of ion channels (eg, ENa and ECa). Based on the transport stoichiometry, ENCX=3ENa−2ECa. Thus, when the membrane potential (Em) exceeds ENCX, Ca2+ entry (outward INCX) is favored. The exact role of Ca2+ influx via outward INCX during the cardiac action potential (AP) is controversial, but it can contribute to sarcoplasmic reticulum (SR) Ca2+ loading and Ca2+-induced Ca2+ release from the SR.2,4,5⇓⇓ More detailed information about how NCX varies during the AP is essential for understanding its physiological role in health and disease.. Because there is no selective INCX blocker, INCX is often recorded after other currents are blocked, sometimes accompanied by controls using nonselective INCX blockers (eg, Ni2+), to isolate ...
Monoclonal clone# G2 antibody for DYSTROPHIN/DMD detection. Host: Mouse.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Human. DYSTROPHIN/DMD information: Molecular Weight: 425828 MW; Subcellular Localization: Cell membrane, sarcolemma ;
ECM of skeletal muscle consists of a basement membrane (BM) surrounding each myofiber and interstitial connective tissue (endomysium) between the myofibers. The attachment of myofibers to the BM is mainly mediated by integrins and the dystrophin-glycoprotein complex (DGC; Mayer, 2003; Michele and Campbell, 2003). Integrins are expressed throughout the sarcolemma of myofibers but are highly enriched at two force-transducing and force-regulating structures, the myotendinous junctions (MTJs), which connect myofibers to tendons, and the costameres, which are focal adhesion-like structures that connect the sarcomeric z bands with the sarcolemma.. Integrins are a large family of α/β heterodimeric adhesion receptors (Bouvard et al., 2001; Hynes, 2002). Several β1 integrins were shown to play essential roles during myogenesis and muscle homeostasis (Mayer, 2003). Antibody perturbation studies and β1 integrin gene ablations in flies and mice demonstrated that β1 integrins regulate proliferation and ...
Standard electrophysiological techniques were used for potential recording and current injection under current-clamp conditions (Erxleben et al., 1995). For two-electrode voltage-clamp experiments, an Axoclamp 2B (Axon Instruments Inc., Foster City, CA) was used. These experiments were performed on fibers of the last abdominal segment which are compact (270-450 μm long with a diameter of 50-80 μm). Injection of current in the middle of the fibers and recording at several points over the length of the fiber showed that they are isopotential and thus suitable for two-electrode voltage-clamp. For isolation of Ca or Ba currents and suppression of K currents, a solution (TEA solution) consisting of 160 mM tetraethyl-ammonium, 2 mM 4-aminopyridine (4-AP), 320 mM NaCl, 8 mM KCl, 20 mM HEPES, pH 7.4, was used with either 10 mM CaCl2 or BaCl2. In addition, the recording and current electrodes were filled with 3 M CsCl to suppress K currents. Voltage-activated Ca or Ba currents were separated from ...
A theoretical ionic model of ventricular myocyte used by Bluhm et al. (8) to analyze changes in sarcolemmal ion fluxes following step changes in cardiac muscle length predicted that a sudden increase in muscle length might induce changes in sarcolemmal Na+ influx with a subsequent increase in intracellular Na+ concentration ([Na+]i) and a concomitant increase in systolic Ca2+ entry through the Na+/Ca2+ exchanger (NCX). However, the mechanism by which the increase in [Na+]i takes place was not proposed. Since NHE1 is an important Na+ entry pathway in cardiomyocytes and it is activated by ANG II, ET-1, and Ald, it seems a suitable candidate for the stretch-mediated increase in Na+ influx.. The first evidence suggesting myocardial stretch-mediated NHE1 activation emerged from experiments published in 1998 in which stretching cat papillary muscles maintained in bicarbonate-free medium (condition in which NHE1 is the only active pHi regulatory mechanism) produced an intracellular alkalinization that ...
Other iris/ciliary body signature genes have known roles in myosin phosphorylation (PPP1R12B), sarcolemmal calcium homeostasis (CASQ2), and ATP availability (CKMT2), all of which may contribute to ciliary body/trabecular meshwork contractility ...
Greiser and colleagues (10) also report that, consistent with previous studies, the remaining RyR2 clusters were hyperphosphorylated at the protein kinase A (PKA) phosphorylation site (Ser2808), which may compensate for the reduction in RyR2 protein expression and help sustain subsarcolemmal Ca2+ release despite reduced L-type Ca2+ currents (Figure 1B). However, RAP myocytes exhibited reduced RyR2 phosphorylation at the calmodulin-dependent protein kinase II (CaMKII) phosphorylation site (Ser2815) and no changes in CaMKII activity. This finding contrasts with previous studies that reported increased atrial CaMKII activity and CaMKII-dependent RyR2-Ser2815 phosphorylation in human AF (5). Moreover, other studies have shown that treatment with CaMKII inhibitors or selective disruption of the Ser2815 CaMKII phosphorylation site prevented AF in animal models through a reduction of SR Ca2+ leak (12). One explanation for this discrepancy could be the limited duration of pacing in the rabbit model used ...
Postnatal maturation of the rat heart is characterized by major changes in the mechanism of excitation-contraction (E-C) coupling. In the neonate, the t tubules and sarcoplasmic reticulum (SR) are not fully developed yet. Consequently, Ca(2+)-induced Ca(2+) release (CICR) does not play a central role in E-C coupling. In the neonate, most of the Ca(2+) that triggers contraction comes through the sarcolemma. In this work, we defined the contribution of the sarcolemmal Ca(2+) entry and the Ca(2+) released from the SR to the Ca(2+) transient during the first 3 wk of postnatal development. To this end, intracellular Ca(2+) transients were measured in whole hearts from neonate rats by using the pulsed local field fluorescence technique. To estimate the contribution of each Ca(2+) flux to the global intracellular Ca(2+) transient, different pharmacological agents were used. Ryanodine was applied to evaluate ryanodine receptor-mediated Ca(2+) release from the SR, nifedipine for dihydropyridine-sensitive L-type
Anastasi, G ; Amato, A ; Tarone, G ; Vita, G ; Monici, M.C ; Magaudda, L ; Brancaccio, M ; Sidoti, A ; Trimarchi, F ; Favaloro, A ; Cutroneo, ...
Bits of the sarcolemma fold inwards across the muscle fibre and stick into the sarcoplasm (a muscle cells cytoplasm). These folds are called transverse (T) tubules and they help to spread electrical impulses throughout the sarcoplasm so they reach all parts of the muscle fibre. ...
collagen trimer, extracellular exosome, extracellular matrix, extracellular space, extracellular vesicle, proteinaceous extracellular matrix, sarcolemma
Mutations in the genes coding for either dystrophin or dysferlin cause distinct forms of muscular dystrophy. Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. This link extends to the extracellular matrix by β-dystroglycans interaction with α-dystroglycan, which binds extracellular matrix proteins, including laminin α2, agrin and perlecan, that possess laminin globular domains. The absence of dystrophin disrupts this link, leading to compromised muscle sarcolemmal integrity. Dysferlin, on the other hand, plays an important role in the Ca2+-dependent membrane repair of damaged sarcolemma in skeletal muscle. Because dysferlin and dystrophin play different roles in maintaining muscle cell integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin deficiency would exacerbate the pathology in dysferlin-null mice and allow further characterization of the role of dysferlin in skeletal muscle. To test our hypothesis, we generated
TY - JOUR. T1 - Amylin and diabetic cardiomyopathy - amylin-induced sarcolemmal Ca2+ leak is independent of diabetic remodeling of myocardium. AU - Liu, Miao. AU - Hoskins, Amanda. AU - Verma, Nirmal. AU - Bers, Donald M. AU - Despa, Sanda. AU - Despa, Florin. PY - 2017. Y1 - 2017. N2 - Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca2+ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the hypothesis that ...
Myofiber growth and myofibril assembly at the myotendinous junction (MTJ) of stretch-hypertrophied rabbit skeletal muscle was studied by in situ hybridization, immunofluorescence, and electron microscopy. In situ hybridization identified higher levels of myosin heavy chain (MHC) mRNA at the MTJ of fibers stretched for 4 d. Electron microscopy at the MTJ of these lengthening fibers revealed a large cytoplasmic space devoid of myofibrils, but containing polysomes, sarcoplasmic reticulum and T-membranes, mitochondria, Golgi complexes, and nascent filament assemblies. Tallies from electron micrographs indicate that myofibril assembly in stretched fibers followed a set sequence of events. (a) In stretched fiber ends almost the entire sarcolemmal membrane was electron dense but only a portion had attached myofibrils. Vinculin, detected by immunofluorescence, was greatly increased at the MTJ membrane of stretched muscles. (b) Thin filaments were anchored to the sarcolemma at the electron dense sites. ...
Am J Physiol. 1997 Sep;273(3 Pt 2):H1544-54. Research Support, Non-U.S. Govt; Research Support, U.S. Govt, Non-P.H.S.; Research Support, U.S. Govt, P.H.S.
Ca2+ channel β-subunit interactions with pore-forming α-subunits are long-thought to be obligatory for channel trafficking to the cell surface and for tuning of basal biophysical properties in many tissues. Unexpectedly, we demonstrate that transgenic expression of mutant α1C subunits lacking capacity to bind CaVβ can traffic to the sarcolemma in adult cardiomyocytes in vivo and sustain normal excitation-contraction coupling. However, these β-less Ca2+ channels cannot be stimulated by β-adrenergic pathway agonists, and thus adrenergic augmentation of contractility is markedly impaired in isolated cardiomyocytes and in hearts. Similarly, viral-mediated expression of a β-subunit-sequestering peptide sharply curtailed β-adrenergic stimulation of WT Ca2+ channels, identifying an approach to specifically modulate β-adrenergic regulation of cardiac contractility. Our data demonstrate that β subunits are required for β-adrenergic regulation of CaV1.2 channels and positive inotropy in the ...
In this study, we have identified the syt1-2 mutant by its hypersensitivity to high NaCl. The reduced fitness of syt1-2 seedlings was observed under control growing conditions but was highly enhanced with respect to the wild type under high osmolarity. These growth defects were evaluated at the cellular level by confocal microscopy, leading to the observation that the syt1-2 mutant presented reduced plasma membrane integrity, which in turn causes a decrease in cell viability.. Based on current knowledge from the animal literature, there are two situations in which a defect in a single protein can result in an abnormally sensitive plasma membrane. It could be more susceptible to injury due to structural weakness, as occurs by defective components of the dystrophin-glycoprotein complex that are directly or indirectly involved in linking the cytoskeleton to the surrounding basement membrane (Ervasti et al., 1990; Duclos et al., 1998). Alternatively, the cell could have a defective plasma membrane ...
the neurotransmitter substance for muscle contraction and is released at neuromuscular junctions diffuses across the synapses and binds to the receptor sites on the sarcolemma ...
3) Ca2+ channels in SR membrane situated directly opposite t-tubules are Ca2+ release channels (the RYRs). The RYRs and SHPRs are coupled together and physically link the t tubules and SR ...
Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The DMDmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD), presenting the same molecular and protein defect as seen in humans with the disease. However, this mouse is not useful for clinical trials, because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene and displays a severe phenotype. To help elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein complex in muscle sarcolemma, we generated double-mutant mice for the dystrophin and LARGE proteins. The new DMDmdx/Largemyd mouse model is viable and shows a severe phenotype that is associated with the lack of dystrophin in muscle. ...
Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one
The PUFAs act by stabilizing electrically every cardiac myocyte by modulating conductance of ion channels in the sarcolemma, particularly the fast, voltage-dependent sodium current and the L-type calcium currents, though other ion currents are also affected. Work in progress suggests that the primary site of action of the PUFAs may be on the phospholipid bilayer of the heart cells in the microdomains through which the ion channels penetrate the membrane bilayer in juxtaposition with the ion channels rather than directly on the channel protein itself ...
T-tubule structural abnormalities in myotubularin morphant muscle.T-tubule (vertical arrows) and sarcoplasmic reticulum (angled arrows) abnormalities as demonst
We show here that talin 1 is crucial for the maintenance of integrin attachment sites at MTJs. Tln1HSA-CREko mice were viable and fertile, but suffered from a progressive myopathy. Whereas integrins and some of their effectors such as FAK, Ilk and vinculin still were localized to muscle attachment sites at costameres and MTJs, MTJs showed structural abnormalities. Defects in the ultrastructure of MTJs, such as decreased interdigitations of muscle and tendon and retraction of myofilaments from electron-dense plaques at the plasma membrane, indicate that in the absence of talin 1 the mechanical connection of actin filaments and integrins at the MTJ was compromised. By contrast, sarcolemmal integrity was largely maintained. Defects in skeletal muscle were prominent in 6- to 7-month-old mice, and were only occasionally noted in 1- to 2-month-old animals, suggesting that the defects were caused by mechanical failure of MTJs under duress. In agreement with this finding, isolated muscle fibers from 7 ...
The costamere or dystrophin-associated protein complex (DAPC) is a structural-functional component of skeletal muscle cells which, according to original descriptions in the early 1980s (which are generally still accepted), are sub-sarcolemmal protein assemblies circumferentially aligned in register with the Z-disk of peripheral myofibrils. They physically couple force-generating sarcomeres with the sarcolemma in striated muscle cells and are thus considered the "Achilles heel", i.e. the key vulnerable point of the muscle which is defective in many myopathies. [1] The DAPC contains various macromolecules such as dystroglycans which are responsible for linking the DAPC to extracellular proteins; collagen and laminin for example. Therefore it is one of the features of the sarcolemma which helps to couple the sarcomere to the extracellular connective tissue. Desmin protein may also bind to the DAPC, and regions of it are known to be involved in signaling. ...
This gene encodes dystrobrevin beta, a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and dystrobrevin alpha and beta. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin. [provided by RefSeq, Mar 2016] ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes dystrobrevin beta, a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and dystrobrevin alpha and beta. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin. [provided by RefSeq, Mar 2016 ...
In skeletal muscle, an accumulation of lipid droplets (LDs) in the subsarcolemmal space is associated with insulin resistance, but the underlying mechanism is not clear. We aimed to investigate how the size, number and location of LDs are associated with insulin sensitivity and muscle fiber types, and are regulated by aerobic training and treatment with an erythropoiesis-stimulating agent (ESA) in healthy young untrained males. LD analyses were performed by quantitative transmission electron microscopy and insulin sensitivity was assessed by a hyperinsulinemic euglycemic clamp. At baseline, we found that only the diameter (and not the number) of individual subsarcolemmal LDs was negatively associated with insulin sensitivity (R2 = 0.20, P = 0.03, n = 29). Despite 34% (P = 0.004) fewer LDs, the diameter of individual subsarcolemmal LDs was 20% (P = 0.0004) larger in type 2 fibers than in type 1 fibers. Furthermore, aerobic training decreased the size of subsarcolemmal LDs in the type 2fibers, and ...
It is believed that in embryonic cardiomyocytes the myocardial contraction is predominantly dependent on transsarcolemmal Ca2+ influx (26, 36). Therefore, it is expected that in embryonic cardiomyocytes, NCX might be a prominent Ca2+ remover and even more important than SERCA. However, it has been recently shown that in murine embryonic cardiomyocytes 8.5-9.5 days old, the majority of Ca2+ removal (∼74%) is accomplished by SERCA (32). The studies on mESCMs showed that the SERCA is the major Ca2+ remover in 17-day-old mESCMs (16). Here, we provided evidence showing that the contribution of SERCA to Ca2+ removal is upregulated with the time of mESCMs differentiation, accompanied with a downregulation of NCX to Ca2+ removal, a similar pattern as reported by Kapur and Banach (16). The functional changes with differentiation also coincide with the gene expression pattern of SERCA and NCX during embryonic development (21, 32) or mESCMs differentiation (12). Moreover, our data demonstrated that ...
Dysferlin兔多克隆抗体(ab15108)可与狗, 人样本反应并经WB, IHC, ICC/IF实验严格验证,被3篇文献引用并得到3个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
TY - JOUR. T1 - Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. AU - Matsumura, Kiichiro. AU - Ervasti, James M.. AU - Ohlendieck, Kay. AU - Kahl, Steven D.. AU - Campbell, Kevin P.. PY - 1992/1/1. Y1 - 1992/1/1. N2 - DYSTROPHIN is associated with a complex of muscle membrane (sarcolemmal) glycoproteins that provide a linkage to the extracellular matrix protein, laminin1-8. The absence of dystrophin leads to a dramatic reduction of the dystrophin-associated proteins (156DAG, 59DAP, 50DAG, 43DAG and 35DAG) in the sarcolemma of patients with Duchenne muscular dystrophy and mdx mice 2,6-8. Here we demonstrate that dystrophin-related protein (DRP, utrophin), an autosomal homologue of dystrophin9,17, is associated with an identical or antigenically similar complex of sarcolemmal proteins and that DRP and the dystrophin/DRP-associated proteins colocalize to the neuromuscular junction in Duchenne muscular dystrophy and mdx muscle. The DRP and ...
Sarcoglycan is a multimeric, integral membrane glycoprotein complex that associates with dystrophin. Mutations in individual sarcoglycan subunits have been identified in inherited forms of muscular dystrophy. To evaluate the contributions of sarcoglycan and dystrophin to muscle membrane stability and muscular dystrophy, we compared muscle lacking specific sarcoglycans or dystrophin. Here we report that mice lacking (delta)-sarcoglycan developed muscular dystrophy and cardiomyopathy similar to mice lacking (gamma)-sarcoglycan. However, unlike muscle lacking (gamma)-sarcoglycan, (delta)-sarcoglycan-deficient muscle was sensitive to eccentric contraction-induced disruption of the plasma membrane. In the absence of (delta)-sarcoglycan, (alpha)-, (beta)- and (gamma)-sarcoglycan were undetectable, while dystrophin was expressed at normal levels. In contrast, without (gamma)-sarcoglycan, reduced levels of (alpha)-, (beta)- and (delta)-sarcoglycan were expressed, glycosylated and formed a complex with ...
FUNCTION: Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix. May play a role in the maintenance of striated muscle membrane stability (By similarity ...
A brief reminder of the benefits of bicarbonate: Regulation of hydrogen ions (H + ) or pH within homeostatic concentrations is critical for proper physiological function. The factors contributing to the change in muscle pH seen during intense exercise are numerous and the role of each factor remains hotly debated. However, classically it is believed that a large contributor of H + is through the accumulation of lactate produced from glycolysis. Next to internal buffers, which are exhausted relatively quickly, the shuttling of H + and lactate across the sarcolemma is also believed to play an important role in the maintenance of pH during intense exercise. This is due to the extracellular buffering capacity HCO3 - which is believed to promote the efflux of H + from active muscles ( Hollidge-Horvat. 2000; Bishop. 2004 ...