keyword
MENU ▼
Read by QxMD icon Read
search

Ryr1

keyword
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#1
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27866274/ryanodine-receptor-type-3-does-not-contribute-to-contractions-in-the-mouse-myometrium-regardless-of-pregnancy
#2
Katsuhito Matsuki, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine...
November 20, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27857962/functional-analysis-of-ryr1-variants-linked-to-malignant-hyperthermia
#3
Jeremy Stephens, Anja H Schiemann, Cornelia Roesl, Dorota Miller, Sean Massey, Neil Pollock, Terasa Bulger, Kathryn Stowell
Malignant hyperthermia manifests as a rapid and sustained rise in temperature in response to pharmacological triggering agents, e.g. inhalational anesthetics and the muscle relaxant suxamethonium. Other clinical signs include an increase in end-tidal CO2, increased O2 consumption, as well as tachycardia, and if untreated a malignant hyperthermia episode can result in death. The metabolic changes are caused by dysregulation of skeletal muscle Ca(2+) homeostasis, resulting from a defective ryanodine receptor Ca(2+) channel, which resides in the sarcoplasmic reticulum and controls the flux of Ca(2+) ions from intracellular stores to the cytoplasm...
April 2016: Temperature: Multidisciplinary Biomedical Journal
https://www.readbyqxmd.com/read/27855725/review-of-ryr1-pathway-and-associated-pathomechanisms
#4
REVIEW
Jessica W Witherspoon, Katherine G Meilleur
Ryanodine receptor isoform-1 (RyR1) is a major calcium channel in skeletal muscle important for excitation-contraction coupling. Mutations in the RYR1 gene yield RyR1 protein dysfunction that manifests clinically as RYR1-related congenital myopathies (RYR1-RM) and/or malignant hyperthermia susceptibility (MHS). Individuals with RYR1-RM and/or MHS exhibit varying symptoms and severity. The symptoms impair quality of life and put patients at risk for early mortality, yet the cause of varying severity is not well understood...
November 17, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27854207/long-term-oral-dantrolene-improved-muscular-symptoms-in-a-malignant-hyperthermia-susceptible-individual
#5
Brian N Butala, Audry Kang, Jasmeen Guron, Barbara W Brandom
This case report describes a female with p.Lys4876Arg amino acid change in the ryanodine receptor type 1 (RYR1) and a sibling who died of malignant hyperthermia (MH) during anesthesia. After her diagnosis as MH susceptible, this patient was administered low-dose dantrolene daily for greater than 25 years for treatment of chronic muscle spasm and pain in her lower extremities and back limiting sleep. Her creatine phosphokinase (CPK) was as high as 2390 IU/L during labor and 900 IU at rest. With 25 mg dantrolene daily, muscle cramps were eliminated, and sleep was improved...
March 3, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27854153/genetic-factors-affecting-pork-quality-halothane-and-rendement-napole-genes
#6
Ramon Cesar D Salas, Claro N Mingala
The most common pork quality problems are pale, soft, and exudative (PSE) and acid pork (AP). PSE is associated with the expression of recessive halothane (Hal) allele Hal(n). Recessive Hal pigs (Hal(nn)) have defective Ca(2+) release channels (CRC) or Ryanodine Receptors (RYR1) within the sarcoplasmic reticulum that allow uncontrolled release of Ca(2+) in response to stress. Abnormal lactic acid metabolism caused by stress prior to slaughter leads to the sudden drop in postmortem muscle pH producing the PSE pork...
November 17, 2016: Animal Biotechnology
https://www.readbyqxmd.com/read/27851958/alternative-splicing-of-four-trafficking-genes-regulates-myofiber-structure-and-skeletal-muscle-physiology
#7
Jimena Giudice, James A Loehr, George G Rodney, Thomas A Cooper
During development, transcriptional and post-transcriptional networks are coordinately regulated to drive organ maturation. Alternative splicing contributes by producing temporal-specific protein isoforms. We previously found that genes undergoing splicing transitions during mouse postnatal heart development are enriched for vesicular trafficking and membrane dynamics functions. Here, we show that adult trafficking isoforms are also expressed in adult skeletal muscle and hypothesize that striated muscle utilizes alternative splicing to generate specific isoforms required for function of adult tissue...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27832566/sequencing-of-genes-involved-in-the-movement-of-calcium-across-human-skeletal-muscle-sarcoplasmic-reticulum-continuing-the-search-for-genes-associated-with-malignant-hyperthermia
#8
A R Bjorksten, R L Gillies, B M Hockey, D Du Sart
The genetic basis of malignant hyperthermia (MH) is not fully characterised and likely involves more than just the currently classified mutations in the gene encoding the skeletal muscle ryanodine receptor (<i>RYR1</i>) and the gene encoding the α1 subunit of the dihydropyridine receptor (<i>CACNA1S</i>). In this paper we sequence other genes involved in calcium trafficking within skeletal muscle in patients with positive in vitro contracture tests, searching for alternative genes associated with MH...
November 2016: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/27812757/counter-flow-suggests-transport-of-dantrolene-and-5-oh-dantrolene-by-the-organic-anion-transporters-2-oat2-and-3-oat3
#9
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
Dantrolene is the only available drug for the treatment of malignant hyperthermia, a life-threatening inborn sensitivity of the ryanodine receptor (RyR1) in skeletal muscles to volatile anesthetics. Dantrolene is metabolized in the liver to 5-OH dantrolene. Both compounds are zwitterions or net negatively charged. Here, we investigated interactions of dantrolene and 5-OH dantrolene with solute carrier (SLC) family members occurring in skeletal muscle cells, hepatocytes, and renal proximal tubule cells. SLC22A8 (organic anion transporter 3, OAT3) was very sensitive to both compounds exhibiting IC50 values of 0...
November 3, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27793347/the-mammalian-skeletal-muscle-dhpr-has-larger-ca-2-conductance-and-is-phylogenetically-ancient-to-the-early-ray-finned-fish-sterlet-acipenser-ruthenus
#10
Kai Schrötter, Anamika Dayal, Manfred Grabner
The L-type Ca(2+) channel or dihydropyridine receptor (DHPR) in vertebrate skeletal muscle is responsible for sensing sarcolemmal depolarizations and transducing this signal to the sarcoplasmic Ca(2+) release channel RyR1 via conformational coupling to initiate muscle contraction. During this excitation-contraction (EC) coupling process there is a slow Ca(2+) current through the mammalian DHPR which is fully missing in euteleost fishes. In contrast to ancestral evolutionary stages where skeletal muscle EC coupling is still depended on Ca(2+)-induced Ca(2+)-release (CICR), it is possible that the DHPR Ca(2+) conductivity during mammalian (conformational) EC coupling was retained as an evolutionary remnant (vestigiality)...
October 23, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27760856/high-throughput-screens-to-discover-small-molecule-modulators-of-ryanodine-receptor-calcium-release-channels
#11
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27708434/clinical-relevance-and-molecular-phenotypes-in-gastric-cancer-of-tp53-mutations-and-gene-expressions-in-combination-with-other-gene-mutations
#12
Sungjin Park, Jinhyuk Lee, Yon Hui Kim, Jaheun Park, Jung-Woog Shin, Seungyoon Nam
While altered TP53 is the most frequent mutation in gastric cancer (GC), its association with molecular or clinical phenotypes (e.g., overall survival, disease-free survival) remains little known. To that end, we can use genome-wide approaches to identify altered genes significantly related to mutated TP53. Here, we identified significant differences in clinical outcomes, as well as in molecular phenotypes, across specific GC tumor subpopulations, when combining TP53 with other signaling networks, including WNT and its related genes NRXN1, CTNNB1, SLITRK5, NCOR2, RYR1, GPR112, MLL3, MTUS2, and MYH6...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27708273/the-sensitivity-of-exome-sequencing-in-identifying-pathogenic-mutations-for-lgmd-in-the-united-states
#13
Hemakumar M Reddy, Kyung-Ah Cho, Monkol Lek, Elicia Estrella, Elise Valkanas, Michael D Jones, Satomi Mitsuhashi, Basil T Darras, Anthony A Amato, Hart Gw Lidov, Catherine A Brownstein, David M Margulies, Timothy W Yu, Mustafa A Salih, Louis M Kunkel, Daniel G MacArthur, Peter B Kang
The current study characterizes a cohort of limb-girdle muscular dystrophy (LGMD) in the United States using whole-exome sequencing. Fifty-five families affected by LGMD were recruited using an institutionally approved protocol. Exome sequencing was performed on probands and selected parental samples. Pathogenic mutations and cosegregation patterns were confirmed by Sanger sequencing. Twenty-two families (40%) had novel and previously reported pathogenic mutations, primarily in LGMD genes, and also in genes for Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, congenital myopathy, myofibrillar myopathy, inclusion body myopathy and Pompe disease...
October 6, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27696487/the-core-skeletal-muscle-ryanodine-receptor-calcium-release-complex
#14
A F Dulhunty, L Wei-LaPierre, M G Casarotto, N A Beard
The core skeletal muscle ryanodine receptor (RyR1) calcium release complex extends through three compartments of the muscle fibre, linking the extracellular environment through the cytoplasmic junctional gap to the lumen of the internal sarcoplasmic reticulum (SR) calcium store. The protein complex is essential for skeletal excitation-contraction (EC-) coupling and skeletal muscle function. Its importance is highlighted by perinatal death if any one of the EC-coupling components are missing and by myopathies associated with mutation of any of the proteins...
October 1, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27687475/structures-of-the-colossal-ryr1-calcium-release-channel
#15
Oliver B Clarke, Wayne A Hendrickson
Ryanodine receptors (RyRs) are intracellular cation channels that mediate the rapid and voluminous release of Ca(2+) from the sarcoplasmic reticulum (SR) as required for excitation-contraction coupling in cardiac and skeletal muscle. Understanding of the architecture and gating of RyRs has advanced dramatically over the past two years, due to the publication of high resolution cryo-electron microscopy (cryoEM) reconstructions and associated atomic models of multiple functional states of the skeletal muscle receptor, RyR1...
August 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27663056/ryr1-related-rhabdomyolysis-a-common-but-probably-underdiagnosed-manifestation-of-skeletal-muscle-ryanodine-receptor-dysfunction
#16
N C Voermans, M Snoeck, H Jungbluth
Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a common cause of exertional rhabdomyolysis, accounting for up to 30% of rhabdomyolysis episodes in otherwise healthy individuals. Common triggers are exercise and heat and, less frequently, viral infections, alcohol and drugs. Most subjects are normally strong and have no personal or family history of malignant hyperthermia...
October 2016: Revue Neurologique
https://www.readbyqxmd.com/read/27662087/structural-basis-for-gating-and-activation-of-ryr1
#17
Amédée des Georges, Oliver B Clarke, Ran Zalk, Qi Yuan, Kendall J Condon, Robert A Grassucci, Wayne A Hendrickson, Andrew R Marks, Joachim Frank
The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca(2+)) release channel required for skeletal muscle contraction. Here, we present cryo-EM reconstructions of RyR1 in multiple functional states revealing the structural basis of channel gating and ligand-dependent activation. Binding sites for the channel activators Ca(2+), ATP, and caffeine were identified at interdomain interfaces of the C-terminal domain. Either ATP or Ca(2+) alone induces conformational changes in the cytoplasmic assembly ("priming"), without pore dilation...
September 22, 2016: Cell
https://www.readbyqxmd.com/read/27646467/hypermetabolism-in-b-lymphocytes-from-malignant-hyperthermia-susceptible-individuals
#18
Kerstin Hoppe, Guido Hack, Frank Lehmann-Horn, Karin Jurkat-Rott, Scott Wearing, Alberto Zullo, Antonella Carsana, Werner Klingler
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca(2+) release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B-lymphocytes, this study investigated whether cellular metabolism of native B-lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4-chloro-m-cresol (4-CmC) was used to challenge native B-lymphocytes in a real-time, metabolic assay based on a pH-sensitive silicon biosensor chip...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27621462/stac3-has-a-direct-role-in-skeletal-muscle-type-excitation-contraction-coupling-that-is-disrupted-by-a-myopathy-causing-mutation
#19
Alexander Polster, Benjamin R Nelson, Eric N Olson, Kurt G Beam
In skeletal muscle, conformational coupling between CaV1.1 in the plasma membrane and type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum (SR) is thought to underlie both excitation-contraction (EC) coupling Ca(2+) release from the SR and retrograde coupling by which RyR1 increases the magnitude of the Ca(2+) current via CaV1.1. Recent work has shown that EC coupling fails in muscle from mice and fish null for the protein Stac3 (SH3 and cysteine-rich domain 3) but did not establish the functional role of Stac3 in the CaV1...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27616680/intra-familial-variability-associated-with-recessive-ryr1-mutation-diagnosed-prenatally-by-exome-sequencing
#20
Jillian Casey, Karen Flood, Sean Ennis, Emma Doyle, Michael Farrell, Sally Ann Lynch
OBJECTIVE: To determine the underlying molecular aetiology in a non-consanguineous Irish family who have had three fetal losses because of a primary myopathy characterised by fetal akinesia, arthrogryposis multiplex, bilateral pulmonary hypoplasia and reduced muscle bulk. METHODS: Fetal DNA extracted from amniotic cells was whole genome amplified and subjected to whole exome sequencing. RESULTS: Whole exome sequencing identified compound heterozygous variants in RYR1 as the cause of the lethal myopathy in this family...
November 2016: Prenatal Diagnosis
keyword
keyword
46183
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"