Control of acetylcholine receptors in skeletal muscle

1989 ◽  
Vol 8 (3) ◽  
pp. 333-335
Author(s):  
Veit Witzemann
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptors

Trophic effect of iron-bound transferrin on acetylcholine receptors in rat skeletal muscle in vivo

1983 ◽  
Vol 38 (3) ◽  
pp. 303-307 ◽  
Author(s):  
Keiji Wada ◽  
Satoshi Ueno ◽  
Takanori Hazama ◽  
Hiro-O Yoshikawa ◽  
Saburo Ogasahara ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptors ◽  
Rat Skeletal Muscle ◽  
Trophic Effect

scholarly journals MyoScreen, a High-Throughput Phenotypic Screening Platform Enabling Muscle Drug Discovery

2018 ◽  
Vol 23 (8) ◽  
pp. 790-806 ◽  
Author(s):  
Joanne Young ◽  
Yoran Margaron ◽  
Mathieu Fernandes ◽  
Eve Duchemin-Pelletier ◽  
Joris Michaud ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Throughput ◽  
Acetylcholine Receptors ◽  
Calcium Release ◽  
Screening Strategy ◽  
Adult Skeletal Muscle ◽  
New Chemical Entities ◽  
Drug Treatments ◽  
Screening Platform

Despite the need for more effective drug treatments to address muscle atrophy and disease, physiologically accurate in vitro screening models and higher information content preclinical assays that aid in the discovery and development of novel therapies are lacking. To this end, MyoScreen was developed: a robust and versatile high-throughput high-content screening (HT/HCS) platform that integrates a physiologically and pharmacologically relevant micropatterned human primary skeletal muscle model with a panel of pertinent phenotypic and functional assays. MyoScreen myotubes form aligned, striated myofibers, and they show nerve-independent accumulation of acetylcholine receptors (AChRs), excitation–contraction coupling (ECC) properties characteristic of adult skeletal muscle and contraction in response to chemical stimulation. Reproducibility and sensitivity of the fully automated MyoScreen platform are highlighted in assays that quantitatively measure myogenesis, hypertrophy and atrophy, AChR clusterization, and intracellular calcium release dynamics, as well as integrating contractility data. A primary screen of 2560 compounds to identify stimulators of myofiber regeneration and repair, followed by further biological characterization of two hits, validates MyoScreen for the discovery and testing of novel therapeutics. MyoScreen is an improvement of current in vitro muscle models, enabling a more predictive screening strategy for preclinical selection of the most efficacious new chemical entities earlier in the discovery pipeline process.

A novel alpha conotoxin (α-PIB) isolated from C. purpurascens is selective for skeletal muscle nicotinic acetylcholine receptors

Toxicon ◽  
2007 ◽  
Vol 49 (8) ◽  
pp. 1193-1199 ◽  
Author(s):  
Estuardo López-Vera ◽  
Richard B. Jacobsen ◽  
Michael Ellison ◽  
Baldomero M. Olivera ◽  
Russell W. Teichert
Keyword(s):  
Skeletal Muscle ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine

scholarly journals Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy

2016 ◽  
Vol 113 (11) ◽  
pp. 3060-3065 ◽  
Author(s):  
Eleonora Palma ◽  
Jorge Mauricio Reyes-Ruiz ◽  
Diego Lopergolo ◽  
Cristina Roseti ◽  
Cristina Bertollini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Motor Neurons ◽  
Acetylcholine Receptors ◽  
New Drugs ◽  
Clinical Effects ◽  
Pharmacological Targets ◽  
Clinical Conditions ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy. By microtransplanting muscle membranes from selected ALS patients into Xenopus oocytes, we show that PEA reduces the desensitization of acetylcholine-evoked currents after repetitive neurotransmitter application (i.e., rundown). The same effect was observed using muscle samples from denervated (non-ALS) control patients. The expression of human recombinant α1β1γδ (γ-AChRs) and α1β1εδ AChRs (ε-AChRs) in Xenopus oocytes revealed that PEA selectively affected the rundown of ACh currents in ε-AChRs. A clear up-regulation of the α1 subunit in muscle from ALS patients compared with that from non-ALS patients was found by quantitative PCR, but no differential expression was found for other subunits. Clinically, ALS patients treated with PEA showed a lower decrease in their forced vital capacity (FVC) over time as compared with untreated ALS patients, suggesting that PEA can enhance pulmonary function in ALS. In the present work, data were collected from a cohort of 76 ALS patients and 17 denervated patients. Our results strengthen the evidence for the role of skeletal muscle in ALS pathogenesis and pave the way for the development of new drugs to hamper the clinical effects of the disease.

scholarly journals Thymic B lymphocyte clones from patients with myasthenia gravis secrete monoclonal striational autoantibodies reacting with myosin, alpha actinin, or actin.

1986 ◽  
Vol 164 (4) ◽  
pp. 1043-1059 ◽  
Author(s):  
C L Williams ◽  
V A Lennon
Keyword(s):  
Skeletal Muscle ◽  
Epithelial Cells ◽  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
B Lymphocyte ◽  
High Yield ◽  
Thymic Epithelial Cells ◽  
Anchoring Proteins ◽  
Mucosal Cells

Striational autoantibodies (StrAb), which react with elements of skeletal muscle cross-striations, occur frequently in patients with thymoma associated with myasthenia gravis (MG). Dissociated thymic lymphocytes from 22 of 72 MG patients secreted StrAb when cultured with PWM. A high yield of EBV-transformed B cell lines was established from thymus, thymoma, and peripheral blood of seven patients with MG, but clones secreting StrAb arose only from the three patients who had StrAb in their sera. The monoclonal StrAb bound to A bands or I bands in skeletal muscle of human, rat, and frog. One bound to mitochondria in addition to myofibrillar I bands. None bound to nuclei, smooth muscle, or gastric mucosal cells. In immunoblot analyses and ELISAs the monoclonal StrAb bound to muscle and nonmuscle isotypes of myosin, alpha actinin, and/or actin. All bound to contractile proteins common to thymus and muscle, and one selectively immunostained epithelial cells of the thymic medulla. From these antigenic specificities we suggest that StrAb might arise as an immune response directed against the cytoskeletal anchoring proteins associated with nicotinic acetylcholine receptors in thymic epithelial cells undergoing neoplastic transformation to thymoma.

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