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"ryanodine receptor" OR "ryr" OR "ryr2"

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https://www.readbyqxmd.com/read/28316073/arrhythmic-effects-of-epac-mediated-ryanodine-receptor-activation-in-langendorff-perfused-murine-hearts-are-associated-with-reduced-conduction-velocity
#1
Mengye Li, Sandeep Hothi, Samantha C Salvage, Kamalan Jeevaratnam, Andrew A Grace, Christopher L-H Huang
Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct Epac (exchange protein directly activated by cAMP)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential recordings demonstrated that initial steady (8-Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention...
March 18, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28303572/intracellular-calcium-release-channels-an-update
#2
Gaetano Santulli, Ryutaro Nakashima, Qi Yuan, Andrew R Marks
Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are calcium (Ca(2+) ) release channels on the endo/sarcoplasmic reticulum (ER/SR). Here we summarize the latest advances in the field, describing the recently discovered mechanistic roles of intracellular Ca(2+) release channels in the regulation of mitochondrial fitness and endothelial function, providing novel therapeutic options for the treatment of heart failure, hypertension, and diabetes mellitus. This article is protected by copyright...
March 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28292875/in-vivo-ca-2-dynamics-induced-by-ca-2-injection-in-individual-rat-skeletal-muscle-fibers
#3
Mario Wakizaka, Hiroaki Eshima, Yoshinori Tanaka, Hideki Shirakawa, David C Poole, Yutaka Kano
In contrast to cardiomyocytes, store overload-induced calcium ion (Ca(2+)) release (SOICR) is not considered to constitute a primary Ca(2+) releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage-induced Ca(2+) release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca(2+) concentration ([Ca(2+)]i) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca(2+) microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca(2+)]i dynamics following Ca(2+) injection would be amplified and fiber contraction facilitated by SOICR...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28290972/malignant-hyperthermia-susceptibility-and-fitness-for-duty
#4
Michael A Lee, Erin B McGlinch, Maria C McGlinch, John F Capacchione
INTRODUCTION: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28289592/associations-of-biochemical-changes-and-maternal-traits-with-mutation-1843-c-t-in-the-ryr1-gene-as-a-common-cause-for-porcine-stress-syndrome
#5
Z T Popovski, B Tanaskovska, E Miskoska-Milevska, S Andonov, S Domazetovska
Stress syndrome is usually caused by a mutation in the ryanodine receptor gene (ryr1) and it is widely studied in humans and swine populations. The protein product of this gene plays a crucial role in the regulation of calcium transport in muscle cells. A G>T mutation in the human ryr1 gene, which results in the replacement of a conserved arginine at position 614 where a leucine occurs at the same position as the previously identified Arg→Cys mutation reported in all cases of porcine stress syndrome (PSS)...
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28277227/-red-yeast-rice-induced-muscular-injuries-analysis-of-french-pharmacovigilance-database-and-literature-review
#6
Christelle Philibert, Virginie Bres, Marie-Josèphe Jean-Pastor, Claire Guy, Bénédicte Lebrun-Vignes, Perrine Robin, Véronique Pinzani, Dominique Hillaire-Buys
Red yeast rice (RYR) is a dietary supplement containing monacolins obtained by fermentation of Monascus purpureus strains. Because of its structural homology with lovastatin, monacolin K inhibits HMG-CoA reductase and shows hypocholesterolemic properties comparable to synthetic statins. We studied all cases of myopathy involving RYR reported in the French national pharmacovigilance database (6 cases) and in scientific literature (9 cases). Among these cases, 9 showed elevated creatine kinase, 3 rhabdomyolysis and 2 myalgia...
October 27, 2016: Thérapie
https://www.readbyqxmd.com/read/28269792/ryr1-related-myopathies-clinical-histopathologic-and-genetic-heterogeneity-among-17-patients-from-a-portuguese-tertiary-centre
#7
Raquel Samões, Jorge Oliveira, Ricardo Taipa, Teresa Coelho, Márcio Cardoso, Ana Gonçalves, Rosário Santos, Manuel Melo Pires, Manuela Santos
BACKGROUND: Pathogenic variants in ryanodine receptor type 1 (RYR1) gene are an important cause of congenital myopathy. The clinical, histopathologic and genetic spectrum is wide. OBJECTIVE: Review a group of the patients diagnosed with ryanodinopathy in a tertiary centre from North Portugal, as an attempt to define some phenotypical patterns that may help guiding future diagnosis. METHODS: Patients were identified from the database of the reference centre for Neuromuscular Disorders in North Portugal...
2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28260211/respiratory-muscle-contractile-inactivity-induced-by-mechanical-ventilation-in-piglets-leads-to-leaky-ryanodine-receptors-and-diaphragm-weakness
#8
Stefan Matecki, Boris Jung, Nathalie Saint, Valerie Scheuermann, Samir Jaber, Alain Lacampagne
Respiratory muscle contractile inactivity during mechanical ventilation (MV) induces diaphragm muscle weakness, a condition referred to as ventilator-induced diaphragmatic dysfunction (VIDD). Although VIDD pathophysiological mechanisms are still not fully understood, it has been recently suggested that remodeling of the sarcoplasmic reticulum (SR) calcium release channel/ryanodine receptors (RyR1) in the diaphragm is a proximal mechanism of VIDD. Here, we used piglets, a large animal model of VIDD that is more relevant to human pathophysiology, to determine whether RyR1 alterations are observed in the presence of diaphragm weakness...
March 4, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28257063/red-yeast-rice
#9
Thu Nguyen, Mitchell Karl, Antonello Santini
Red yeast rice (RYR), produced by the fermentation of the Monascus purpureus mold, has been used for a long time in Asian cuisine and traditional medicine. It consists of multiple bioactive substances, including monacolins, which potentially can be used as a nutraceutical. Monacolin K, which is chemically identical to lovastatin, has been recognized as responsible for the cholesterolreducing effect of this compound. While the European Food Safety Authority maintains that the use of monacolin K from RYR preparations of at least 10 mg can produce a normal blood cholesterol level, the United States Food and Drug Administration considers monacolin K, due to its similarity with lovastatin, an unapproved drug, and therefore marketing of products that label the monacolin content is prohibited...
March 1, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#10
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
February 24, 2017: Peptides
https://www.readbyqxmd.com/read/28237968/nationwide-experience-of-catecholaminergic-polymorphic-ventricular-tachycardia-caused-by-ryr2-mutations
#11
Anders Krogh Broendberg, Jens Cosedis Nielsen, Jesper Bjerre, Lisbeth Noerum Pedersen, Jens Kristensen, Finn Lund Henriksen, Henning Bundgaard, Henrik Kjaerulf Jensen
OBJECTIVE: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. METHODS: The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives...
February 25, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28237334/functional-involvement-of-protein-kinase-c-rho-kinase-and-trpc3-decreases-while-plc-increases-with-advancement-of-pregnancy-in-mediating-oxytocin-induced-myometrial-contractions-in-water-buffaloes-bubalus-bubalis
#12
Abhishek Sharma, Udayraj P Nakade, Soumen Choudhury, Satish Kumar Garg
Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28228260/chemotherapy-induced-ca-2-release-stimulates-breast-cancer-stem-cell-enrichment
#13
Haiquan Lu, Ivan Chen, Larissa A Shimoda, Youngrok Park, Chuanzhao Zhang, Linh Tran, Huimin Zhang, Gregg L Semenza
Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor 1 (HIF-1) and HIF-2. Knockdown of GSTO1 expression abrogates carboplatin-induced BCSC enrichment, decreases tumor initiation and metastatic capacity, and delays tumor recurrence after chemotherapy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226201/genomewide-association-study-of-alcohol-dependence-identifies-risk-loci-altering-ethanol-response-behaviors-in-model-organisms
#14
Amy E Adkins, Laura M Hack, Tim B Bigdeli, Vernell S Williamson, G Omari McMichael, Mohammed Mamdani, Alexis Edwards, Fazil Aliev, Robin F Chan, Poonam Bhandari, Richard C Raabe, Joseph T Alaimo, GinaMari G Blackwell, Arden A Moscati, Ryan S Poland, Benjamin Rood, Diana G Patterson, Dermot Walsh, John B Whitfield, Gu Zhu, Grant W Montgomery, Anjali K Henders, Nicholas G Martin, Andrew C Heath, Pamela A F Madden, Josef Frank, Monika Ridinger, Norbert Wodarz, Michael Soyka, Peter Zill, Marcus Ising, Markus M Nöthen, Falk Kiefer, Marcella Rietschel, Joel Gelernter, Richard Sherva, Ryan Koesterer, Laura Almasy, Hongyu Zhao, Henry R Kranzler, Lindsay A Farrer, Brion S Maher, Carol A Prescott, Danielle M Dick, Silviu A Bacanu, Laura D Mathies, Andrew G Davies, Vladimir I Vladimirov, Mike Grotewiel, M Scott Bowers, Jill C Bettinger, Bradley T Webb, Michael F Miles, Kenneth S Kendler, Brien P Riley
BACKGROUND: Alcohol Dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms to assess the role of orthologous genes in ethanol response behaviors. We tested one primate-specific gene for expression differences in case/control post-mortem brain tissue...
February 22, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28216082/semi-automated-program-for-analysis-of-local-ca-2-spark-release-with-application-for-classification-of-heart-cell-type
#15
Moran Davoodi, Sofia Segal, Noa Kirschner Peretz, David Kamoun, Yael Yaniv
Local Ca(2+) spark releases are essential to the Ca(2+) cycling process. Thus, they play an important role in ventricular and atrial cell contraction, as well as in sinoatrial cell automaticity. Characterizing their properties in healthy cells from different regions in the heart can reveal the basic biophysical differences among these regions. We designed a semi-automatic Matlab Graphical User Interface (called Sparkalyzer) to characterize parameters of Ca(2+) spark release from any major cardiac tissue, as recorded in line-scan mode with a confocal laser-scanning microscope...
February 9, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28209802/doublet-stimulation-increases-ca-2-binding-to-troponin-c-to-ensure-rapid-force-development-in-skeletal-muscle
#16
Anthony J Bakker, Tanya R Cully, Catherine D Wingate, Christopher J Barclay, Bradley S Launikonis
Fast-twitch skeletal muscle fibers are often exposed to motor neuron double discharges (≥200 Hz), which markedly increase both the rate of contraction and the magnitude of the resulting force responses. However, the mechanism responsible for these effects is poorly understood, likely because of technical limitations in previous studies. In this study, we measured cytosolic Ca(2+) during doublet activation using the low-affinity indicator Mag-Fluo-4 at high temporal resolution and modeled the effects of doublet stimulation on sarcoplasmic reticulum (SR) Ca(2+) release, binding of Ca(2+) to cytosolic buffers, and force enhancement in fast-twitch fibers...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28209766/glycosylated-chromogranin-a-in-heart-failure-implications-for-processing-and-cardiomyocyte-calcium-homeostasis
#17
Anett Hellebø Ottesen, Cathrine R Carlson, William E Louch, Mai Britt Dahl, Ragnhild A Sandbu, Rune Forstrøm Johansen, Hilde Jarstadmarken, Magnar Bjørås, Arne Didrik Høiseth, Jon Brynildsen, Ivar Sjaastad, Mats Stridsberg, Torbjørn Omland, Geir Christensen, Helge Røsjø
BACKGROUND: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function. METHODS AND RESULTS: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands...
February 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28202948/identification-of-pathogenic-variants-in-genes-related-to-channelopathy-and-cardiomyopathy-in-korean-sudden-cardiac-arrest-survivors
#18
Ju Sun Song, Jong-Sun Kang, Young-Eun Kim, Seung-Jung Park, Kyoung-Min Park, June Huh, June Soo Kim, Hana Cho, Chang-Seok Ki, Young Keun On
Pathogenic variants in genes related to channelopathy and cardiomyopathy are the most common cause of sudden unexplained cardiac death. However, few reports have investigated the frequency and/or spectrum of pathogenic variants in these genes in Korean sudden cardiac arrest survivors. This study aimed to investigate the causative genetic variants of cardiac-associated genes in Korean sudden cardiac arrest survivors. We performed exome sequencing followed by filtering and validation of variants in 100 genes related to channelopathy and cardiomyopathy in 19 Korean patients who survived sudden cardiac arrest...
February 16, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#19
Zeting Yuan, Aili Cao, Hua Liu, Henjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28181690/calcium-mediated-cellular-triggered-activity-in-atrial-fibrillation
#20
Dobromir Dobrev, Xander H T Wehrens
Although atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, the basic mechanisms underlying this disorder remain incompletely understood. During the past decade or so, it has become clear that alterations in intracellular Ca(2+) handling may play a role in the pathogenesis of AF. Studies in small and large animal models, as well as atrial samples from patients with different forms of AF have implicated ryanodine receptor type 2 (RyR2) dysfunction and enhanced spontaneous Ca(2+) release events from the sarcoplasmic reticulum (SR) as a potential cause of proarrhythmic cellular ectopic (triggered) activity in AF...
February 9, 2017: Journal of Physiology
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