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

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https://www.readbyqxmd.com/read/28550171/%C3%AE-adrenergic-receptor-stimulation-inhibits-proarrhythmic-alternans-in-post-infarction-border-zone-cardiomyocytes-a-computational-analysis
#1
Jakub Tomek, Blanca Rodriguez, Gil Bub, Jordi Heijman
The border zone (BZ) of viable myocardium adjacent to an infarct undergoes extensive autonomic and electrical remodelling and is prone to repolarisation alternans-induced cardiac arrhythmias. BZ remodelling processes may promote or inhibit calcium and/or repolarisation alternans and may differentially affect ventricular arrhythmogenesis. Here, we employed a detailed computational model of the canine ventricular cardiomyocyte to study the determinants of alternans in the BZ and their regulation by β-adrenergic receptor (βAR) stimulation...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28549333/endoplasmic-reticulum-er-stress-and-camp-pka-pathway-mediated-zn-induced-hepatic-lipolysis
#2
Yu-Feng Song, Christer Hogstrand, Chuan-Chuan Wei, Kun Wu, Ya-Xiong Pan, Zhi Luo
The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway...
May 23, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28547000/whole-exome-sequencing-of-a-patient-with-suspected-mitochondrial-myopathy-reveals-novel-compound-heterozygous-variants-in-ryr1
#3
Patrick R Blackburn, Duygu Selcen, Jennifer M Gass, Jessica L Jackson, Sarah Macklin, Margot A Cousin, Nicole J Boczek, Eric W Klee, Elliot L Dimberg, Kathleen D Kennelly, Paldeep S Atwal
BACKGROUND: Pathogenic variants in ryanodine receptor 1 (RYR1, MIM# 180901) are the cause of congenital myopathy with fiber-type disproportion, malignant hyperthermia susceptibility type 1, central core disease of muscle, multiminicore disease and other congenital myopathies. METHODS: We present a patient with global developmental delay, hypotonia, myopathy, joint hypermobility, and multiple other systemic complaints that were noted early in life. Later she was found to have multiple bone deformities involving her spine, with severe scoliosis that was corrected surgically...
May 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28538150/lanthanides-report-calcium-sensor-in-the-vestibule-of-ryanodine-receptor
#4
Sándor Sárközi, István Komáromi, István Jóna, János Almássy
Ca(2+) regulates ryanodine receptor's (RyR) activity through an activating and an inhibiting Ca(2+)-binding site located on the cytoplasmic side of the RyR channel. Their altered sensitivity plays an important role in the pathology of malignant hyperthermia and heart failure. We used lanthanide ions (Ln(3+)) as probes to investigate the Ca(2+) sensors of RyR, because they specifically bind to Ca(2+)-binding proteins and they are impermeable to the channel. Eu(3+)'s and Sm(3+)'s action was tested on single RyR1 channels reconstituted into planar lipid bilayers...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28536695/cardiac-protection-of-valsartan-on-juvenile-rats-with-heart-failure-by-inhibiting-activity-of-camkii-via-attenuating-phosphorylation
#5
Yao Wu, Feifei Si, Xiaojuan Ji, Kunfeng Jiang, Sijie Song, Qijian Yi
Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload. Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28536302/a-cryo-em-based-model-of-phosphorylation-and-fkbp12-6-mediated-allosterism-of-the-cardiac-ryanodine-receptor
#6
Sonali Dhindwal, Joshua Lobo, Vanessa Cabra, Demetrio J Santiago, Ashok R Nayak, Kelly Dryden, Montserrat Samsó
Type 2 ryanodine receptors (RyR2s) are calcium channels that play a vital role in triggering cardiac muscle contraction by releasing calcium from the sarcoplasmic reticulum into the cytoplasm. Several cardiomyopathies are associated with the abnormal functioning of RyR2. We determined the three-dimensional structure of rabbit RyR2 in complex with the regulatory protein FKBP12.6 in the closed state at 11.8 Å resolution using cryo-electron microscopy and built an atomic model of RyR2. The heterogeneity in the data set revealed two RyR2 conformations that we proposed to be related to the extent of phosphorylation of the P2 domain...
May 23, 2017: Science Signaling
https://www.readbyqxmd.com/read/28536299/new-connections-how-to-become-more-flexible-and-open-up
#7
Wei Wong
Cryo-EM-generated structures provide insight into how RyR2 is gated and how phosphorylation may affect the activation process.
May 23, 2017: Science Signaling
https://www.readbyqxmd.com/read/28528672/physiology-and-pharmacology-of-ryanodine-receptor-calcium-release-channels
#8
Angela F Dulhunty, Philip G Board, Nicole A Beard, Marco G Casarotto
Ryanodine receptor (RyR) ion channels are essential for skeletal and cardiac muscle function. Their knockout leads to perinatal death from respiratory and cardiac failure. Acquired changes or mutations in the protein cause debilitating skeletal myopathy and cardiac arrhythmia which can be deadly. Knowledge of the pharmacology of RyR channels is central to developing effective and specific treatments of these myopathies. The ion channel is a >2.2MDa homotetamer with distinct structural and functional characteristics giving rise to a myriad of regulatory sites that are potential therapeutic targets...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28527222/functional-characterization-of-c-terminal-ryanodine-receptor-1-variants-associated-with-central-core-disease-or-malignant-hyperthermia
#9
Remai Parker, Anja H Schiemann, Elaine Langton, Terasa Bulger, Neil Pollock, Andrew Bjorksten, Robyn Gillies, David Hutchinson, Richard Roxburgh, Kathryn M Stowell
BACKGROUND: Central core disease and malignant hyperthermia are human disorders of skeletal muscle resulting from aberrant Ca2+ handling. Most malignant hyperthermia and central core disease cases are associated with amino acid changes in the type 1 ryanodine receptor (RyR1), the skeletal muscle Ca2+-release channel. Malignant hyperthermia exhibits a gain-of-function phenotype, and central core disease results from loss of channel function. For a variant to be classified as pathogenic, functional studies must demonstrate a correlation with the pathophysiology of malignant hyperthermia or central core disease...
May 15, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28512623/ca-2-microdomains-in-t-lymphocytes
#10
REVIEW
Insa M A Wolf, Andreas H Guse
Early Ca(2+) signaling is characterized by occurrence of Ca(2+) microdomains formed by opening of single or clusters of Ca(2+) channels, thereby initiating first signaling and subsequently activating global Ca(2+) signaling mechanisms. However, only few data are available focusing on the first seconds and minutes of Ca(2+) microdomain formation and related signaling pathways in activated T-lymphocytes. In this review, we condense current knowledge on Ca(2+) microdomain formation in T-lymphocytes and early Ca(2+) signaling, function of Ca(2+) microdomains, and microdomain organization...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28509762/beetroot-juice-increases-human-muscle-force-without-changing-ca2-handling-proteins
#11
Jamie Whitfield, Daniel Gamu, George J F Heigenhauser, Luc J C van Loon, Lawrence L Spriet, A Russell Tupling, Graham P Holloway
Dietary inorganic nitrate (NO3) supplementation improves skeletal muscle (SkM) contractile efficiency, and while rodent literature has suggested improvements in calcium handling or redox modifications as likely explanations, the direct mechanism-of-action in humans remains unknown. PURPOSE: To examine the effects of 7-d of beetroot juice (BRJ) supplementation on SkM contractile characteristics and function. METHODS: Recreationally active males (n=8) underwent transcutaneous electrical muscle stimulation of the vastus lateralis for evaluation of contractile characteristics before (pre) and after (post) 7-d of BRJ supplementation (280 mL/day, ~26 mmol NO3)...
May 15, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28508509/investigating-the-inter-subunit-subdomain-interactions-and-motions-relevant-to-disease-mutations-in-the-n-terminal-domain-of-ryanodine-receptors-by-molecular-dynamics-simulation
#12
Wenjun Zheng, Zheng Liu
The ryanodine receptors (RyR) are essential to calcium signaling in striated muscles, and numerous disease mutations have been identified in two RyR isoforms, RyR1 in skeletal muscle and RyR2 in cardiac muscle. A deep understanding of the activation/regulation mechanisms of RyRs has been hampered by the shortage of high-resolution structures and dynamic information for this giant tetrameric complex in different functional states. Toward elucidating the molecular mechanisms of disease mutations in RyRs, we performed molecular dynamics simulation of the N-terminal domain (NTD) which is not only the best-resolved structural component of RyRs, but also a hotspot of disease mutations...
May 15, 2017: Proteins
https://www.readbyqxmd.com/read/28506910/omecamtiv-mecarbil-activates-ryanodine-receptors-from-canine-cardiac-but-not-skeletal-muscle
#13
Péter Nánási, Marta Gaburjakova, Jana Gaburjakova, János Almássy
Due to the limited results achieved in the clinical treatment of heart failure, a new inotropic strategy of myosin motor activation has been developed. The lead molecule of myosin activator agents is omecamtiv mecarbil, which binds directly to the heavy chain of the cardiac β-myosin and enhances cardiac contractility by lengthening the lifetime of the acto-myosin complex and increasing the number of the active force-generating cross-bridges. In the absence of relevant data, the effect of omecamtiv mecarbil on canine cardiac ryanodine receptors (RyR 2) has been investigated in the present study by measuring the electrical activity of single RyR 2 channels incorporated into planar lipid bilayer...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28506554/selective-dopamine-receptor-4-activation-mediates-the-hippocampal-neuronal-calcium-response-via-ip3-and-ryanodine-receptors
#14
Ya-Li Wang, Jian-Gang Wang, Fang-Li Guo, Xia-Huan Gao, Dan-Dan Zhao, Lin Zhang, Jian-Zhi Wang, Cheng-Biao Lu
Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD)...
May 12, 2017: Brain Research
https://www.readbyqxmd.com/read/28506253/genome-wide-identification-of-lncrnas-associated-with-chlorantraniliprole-resistance-in-diamondback-moth-plutella-xylostella-l
#15
Bin Zhu, Manyu Xu, Haiyan Shi, Xiwu Gao, Pei Liang
BACKGROUND: Long noncoding RNAs (lncRNAs) are now considered important regulatory factors, with a variety of biological functions in many species including insects. Some lncRNAs have the ability to show rapid responses to diverse stimuli or stress factors and are involved in responses to insecticide. However, there are no reports to date on the characterization of lncRNAs associated with chlorantraniliprole resistance in Plutella xylostella. RESULTS: Nine RNA libraries constructed from one susceptible (CHS) and two chlorantraniliprole-resistant P...
May 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28499500/ca-2-release-channels-join-the-resolution-revolution
#16
REVIEW
Ran Zalk, Andrew R Marks
Ryanodine receptors (RyRs) are calcium release channels expressed in the sarcoendoplasmic reticula of many cell types including cardiac and skeletal muscle cells. In recent years Ca(2+) leak through RyRs has been implicated as a major contributor to the development of diseases including heart failure, muscle myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of multiple functional states have clarified longstanding questions including the architecture of the transmembrane (TM) pore and cytoplasmic domains, the location and architecture of the channel gate, ligand-binding sites, and the gating mechanism...
May 9, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28497395/cardio-protective-effects-of-qishen-granule-on-sarcoplasmic-reticulum-ca-2-handling-in-heart-failure-rats
#17
Ling-Hui Lu, Chun Li, Qi-Yan Wang, Qian Zhang, Yi Zhang, Hui Meng, Yong Wang, Wei Wang
OBJECTIVES: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca(2+) handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28487634/ryr2-mediated-ca-2-release-and-mitochondrial-ros-generation-partake-in-the-synaptic-dysfunction-caused-by-amyloid-%C3%AE-peptide-oligomers
#18
Carol D SanMartín, Pablo Veloso, Tatiana Adasme, Pedro Lobos, Barbara Bruna, Jose Galaz, Alejandra García, Steffen Hartel, Cecilia Hidalgo, Andrea C Paula-Lima
Amyloid β peptide oligomers (AβOs), toxic aggregates with pivotal roles in Alzheimer's disease, trigger persistent and low magnitude Ca(2+) signals in neurons. We reported previously that these Ca(2+) signals, which arise from Ca(2+) entry and subsequent amplification by Ca(2+) release through ryanodine receptor (RyR) channels, promote mitochondrial network fragmentation and reduce RyR2 expression. Here, we examined if AβOs, by inducing redox sensitive RyR-mediated Ca(2+) release, stimulate mitochondrial Ca(2+)-uptake, ROS generation and mitochondrial fragmentation, and also investigated the effects of the antioxidant N-acetyl cysteine (NAC) and the mitochondrial antioxidant EUK-134 on AβOs-induced mitochondrial dysfunction...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28487342/calcium-calmodulin-dependent-protein-kinase-ii-activity-persists-during-chronic-%C3%AE-adrenoceptor-blockade-in-experimental-and-human-heart-failure
#19
Matthias Dewenter, Stefan Neef, Christiane Vettel, Simon Lämmle, Christina Beushausen, Laura C Zelarayan, Sylvia Katz, Albert von der Lieth, Stefanie Meyer-Roxlau, Silvio Weber, Thomas Wieland, Samuel Sossalla, Johannes Backs, Joan H Brown, Lars S Maier, Ali El-Armouche
BACKGROUND: Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF...
May 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28484388/aging-impairs-hippocampal-dependent-recognition-memory-and-ltp-and-prevents-the-associated-ryr-up-regulation
#20
Alejandra Arias-Cavieres, Tatiana Adasme, Gina Sánchez, Pablo Muñoz, Cecilia Hidalgo
Recognition memory comprises recollection judgment and familiarity, two different processes that engage the hippocampus and the perirhinal cortex, respectively. Previous studies have shown that aged rodents display defective recognition memory and alterations in hippocampal synaptic plasticity. We report here that young rats efficiently performed at short-term (5 min) and long-term (24 h) hippocampus-associated object-location tasks and perirhinal cortex-related novel-object recognition tasks. In contrast, aged rats successfully performed the object-location and the novel-object recognition tasks only at short-term...
2017: Frontiers in Aging Neuroscience
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