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ryanodine receptor

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https://www.readbyqxmd.com/read/28636428/fk506-binding-proteins-12-and-12-6-fkbps-as-regulators-of-cardiac-ryanodine-receptors-insights-from-new-functional-and-structural-knowledge
#1
Luis Alberto Gonano, Peter P Jones
Ryanodine Receptors (RyRs) are intracellular Ca(2+) channels that mediate Ca(2+) flux from the sarco(endo)plasmic reticulum in many cell types. The interaction of RyRs with FK506-binding proteins (FKBPs) has been proposed as an important regulatory mechanism, where the loss of this interaction leads to channel dysfunction. In the heart, phosphorylation of RyR has been suggested to disrupt the RyR-FKBP interaction promoting altered Ca(2+) signalling, heart failure and arrhythmias. However, the functional result of FKBP interaction with RyR and how this interaction is regulated remains highly controversial...
June 21, 2017: Channels
https://www.readbyqxmd.com/read/28631341/evaluation-of-flubendiamide-induced-mitochondrial-dysfunction-and-metabolic-changes-in-helicoverpa-armigera-hubner
#2
Bharat Nareshkumar, Shaik Mohammad Akbar, Hari Chand Sharma, Senigala K Jayalakshmi, Kuruba Sreeramulu
Phthalic acid diamide insecticides are the most effective insecticides used against most of the lepidopteran pests including Helicoverpa armigera, a polyphagous pest posing threat to several crops worldwide. The present studies were undertaken to understand different target sites and their interaction with insect ryanodine receptors (RyR). Bioassays indicated that flubendiamide inhibited the larval growth in dose-dependent manner with LD50 value of 0.72 μM, and at 0.8 μM larval growth decreased by about 88%...
June 20, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28631094/post-translational-remodeling-of-ryanodine-receptor-induces-calcium-leak-leading-to-alzheimer-s-disease-like-pathologies-and-cognitive-deficits
#3
Alain Lacampagne, Xiaoping Liu, Steven Reiken, Renaud Bussiere, Albano C Meli, Inger Lauritzen, Andrew F Teich, Ran Zalk, Nathalie Saint, Ottavio Arancio, Charlotte Bauer, Fabrice Duprat, Clark A Briggs, Shreaya Chakroborty, Grace E Stutzmann, Michael L Shelanski, Frederic Checler, Mounia Chami, Andrew R Marks
The mechanisms underlying ryanodine receptor (RyR) dysfunction associated with Alzheimer disease (AD) are still not well understood. Here, we show that neuronal RyR2 channels undergo post-translational remodeling (PKA phosphorylation, oxidation, and nitrosylation) in brains of AD patients, and in two murine models of AD (3 × Tg-AD, APP (+/-) /PS1 (+/-)). RyR2 is depleted of calstabin2 (KFBP12.6) in the channel complex, resulting in endoplasmic reticular (ER) calcium (Ca(2+)) leak. RyR-mediated ER Ca(2+) leak activates Ca(2+)-dependent signaling pathways, contributing to AD pathogenesis...
June 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28630041/dysregulated-zn-2-homeostasis-impairs-cardiac-type-2-ryanodine-receptor-and-mitsugumin-23-functions-leading-to-sarcoplasmic-reticulum-ca-2-leakage
#4
Benedict Reilly-O'Donnell, Gavin B Robertson, Angela Karumbi, Connor McIntyre, Wojciech Bal, Miyuki Nishi, Hiroshi Takeshima, Alan J Stewart, Samantha J Pitt
Aberrant Zn2+-homeostasis is associated with dysregulated intracellular Ca2+ release resulting in chronic heart failure. In the failing heart, a small population of cardiac ryanodine receptors (RyR2) display sub-conductance state gating leading to Ca2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn2+ in shaping intracellular Ca2+ release in cardiac muscle...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28620067/allele-specific-silencing-of-mutant-mrna-rescues-ultrastructural-and-arrhythmic-phenotype-in-mice-carriers-of-the-r4496c-mutation-in-the-ryanodine-receptor-gene-ryr2
#5
Rossana Bongianino, Marco Denegri, Andrea Mazzanti, Francesco Lodola, Alessandra Vollero, Simona Boncompagni, Silvia Fasciano, Giulia Rizzo, Damiano Mangione, Serena Barbaro, Alessia Di Fonso, Carlo Napolitano, Alberto Auricchio, Feliciano Protasi, Silvia G Priori
Rationale: Mutations in the cardiac Ryanodine Receptor gene (RYR2) cause dominant Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a leading cause of sudden death in apparently healthy individuals exposed to emotions or physical exercise. Objective: We investigated the efficacy of allele specific silencing by RNA interference to prevent CPVT phenotypical manifestations in our dominant CPVT mice model carriers of the heterozygous mutation R4496C in RYR2Methods and Results: We developed an in vitro mRNA and protein-based assays to screen multiple siRNAs for their ability to selectively silence mutant RYR2-R4496C mRNA over the corresponding wild-type (WT) allele...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28618061/electrical-storm-in-a-patient-with-duchenne-muscular-dystrophy-cardiomyopathy-triggered-by-abrupt-%C3%AE-blocker-interruption
#6
Nikolaos Fragakis, Melani Sotiriadou, Lydia Krexi, Vassilios Vassilikos
We present a case of a young man with Duchenne muscular dystrophy cardiomyopathy (DMDC) having an implantable cardioverter defibrillator for secondary prevention, who presented with electrical storm shortly after β-blocker interruption. The patient was stabilized and remained free of ventricular arrhythmias soon after reinitiating b-adrenoreceptor antagonists. The present case highlights the importance of sympathetic blockage in patients with DMDC due to existing pathophysiology of excess diastolic Ca(2+) leak from sarcoplasmic reticulum as a result of ryanodine receptor dysfunction...
June 15, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28614084/propofol-affects-neurodegeneration-and-neurogenesis-by-regulation-of-autophagy-via-effects-on-intracellular-calcium-homeostasis
#7
Hui Qiao, Yun Li, Zhendong Xu, Wenxian Li, Zhijian Fu, Yuezhi Wang, Alexander King, Huafeng Wei
BACKGROUND: In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. METHODS: The dose-response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays...
June 14, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28612155/the-role-of-spatial-organization-of-ca-2-release-sites-in-the-generation-of-arrhythmogenic-diastolic-ca-2-release-in-myocytes-from-failing-hearts
#8
Andriy E Belevych, Hsiang-Ting Ho, Ingrid M Bonilla, Radmila Terentyeva, Karsten E Schober, Dmitry Terentyev, Cynthia A Carnes, Sándor Györke
In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca(2+) waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca(2+) imaging were applied to study spatially defined Ca(2+) handling in ventricular myocytes isolated from normal (control) and failing canine hearts...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28592421/clustering-of-ca-2-transients-in-interstitial-cells-of-cajal-defines-slow-wave-duration
#9
Bernard T Drumm, Grant W Hennig, Matthew J Battersby, Erin K Cunningham, Tae Sik Sung, Sean M Ward, Kenton M Sanders, Salah A Baker
Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca(2+)-activated Cl(-) channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca(2+) regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca(2+) transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca(2+) sensor, GCaMP3, in ICC...
June 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28587810/subcellular-localization-of-na-k-atpase-isoforms-in-ventricular-myocytes
#10
Garrick K Yuen, Samuel Galice, Donald M Bers
The sodium/potassium ATPase (NKA) is essential for establishing the normal intracellular [Na(+)] and [K(+)] and transmembrane gradients that are essential for many cellular functions, including cardiac electrophysiology and contractility. Different NKA isoforms exhibit differential expression levels, cellular localization, and function in different tissues and species. Prior work has indicated that the NKA-α1 isoform is quantitatively predominant in cardiac myocytes, but that the α2 isoform is preferentially concentrated in the transverse tubules (TT), possibly at junctions with the sarcoplasmic reticulum (SR) where α2 may preferentially modulate cardiac contractility...
June 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28584051/ion-pulling-simulations-provide-insights-into-the-mechanisms-of-channel-opening-of-the-skeletal-muscle-ryanodine-receptor
#11
David D Mowrey, Le Xu, Yingwu Mei, Daniel A Pasek, Gerhard Meissner, Nikolay V Dokholyan
The type 1 ryanodine receptor (RyR1) mediates Ca(2+) release from the sarcoplasmic reticulum to initiate skeletal muscle contraction and is associated with muscle diseases, malignant hyperthermia, and central core disease. To better understand RyR1 channel function, we investigated the molecular mechanisms of channel gating and ion permeation. An adequate model of channel gating requires accurate, high-resolution models of both open and closed states of the channel. To this end, we generated an open-channel RyR1 model using molecular simulations to pull Ca(2+) through the pore constriction site of a closed-channel RyR1 structure determined at 3...
June 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28576866/heat-induced-calcium-leakage-causes-mitochondrial-damage-in-caenorhabditis-elegans-body-wall-muscles
#12
Kenta Momma, Takashi Homma, Ruri Isaka, Surabhi Sudevan, Atsushi Higashitani
Acute onset of organ failure in heatstroke is triggered by rhabdomyolysis of skeletal muscle. To gain insight into heat-induced muscle breakdown, we investigated alterations of Ca(2+) homeostasis and mitochondrial morphology in vivo in body-wall muscles of Caenorhabditis elegans exposed to elevated temperature. Heat stress for 3h at 35°C increased the concentration of free cytosolic Ca(2+), and led to mitochondrial fragmentation and subsequent dysfunction in the muscle cells. A similar mitochondrial fragmentation phenotype is induced in the absence of heat stress by treatment with a calcium ionophore, ionomycin...
June 1, 2017: Genetics
https://www.readbyqxmd.com/read/28573136/effects-of-wenxin-keli-on-cardiac-hypertrophy-and-arrhythmia-via-regulation-of-the-calcium-calmodulin-dependent-kinase-ii-signaling-pathway
#13
Xinyu Yang, Yu Chen, Yanda Li, Xiaomeng Ren, Yanwei Xing, Hongcai Shang
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28572573/protein-tyrosine-phosphatase-1b-is-a-mediator-of-cyclic-adp-ribose-induced-ca-2-signaling-in-ventricular-myocytes
#14
Seon-Ah Park, Bing-Zhe Hong, Ki-Chan Ha, Uh-Hyun Kim, Myung-Kwan Han, Yong-Geun Kwak
Cyclic ADP-ribose (cADPR) releases Ca(2+) from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca(2+) (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca(2+) ([Ca(2+)]i) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA)...
June 2, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28570539/monitoring-er-sr-calcium-release-with-the-targeted-ca2-sensor-catcher
#15
Florence N Reddish, Cassandra L Miller, Rakshya Gorkhali, Jenny J Yang
Intracellular calcium (Ca(2+)) transients evoked by extracellular stimuli initiate a multitude of biological processes in living organisms. At the center of intracellular calcium release are the major intracellular calcium storage organelles, the endoplasmic reticulum (ER) and the more specialized sarcoplasmic reticulum (SR) in muscle cells. The dynamic release of calcium from these organelles is mediated by the ryanodine receptor (RyR) and the inositol 1,4,5-triphosphate receptor (IP3R) with refilling occurring through the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump...
May 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28568606/coupling-of-excitation-to-ca-2-release-is-modulated-by-dysferlin
#16
Valeriy Lukyanenko, Joaquin M Muriel, Robert J Bloch
Dysferlin concentrates in the transverse tubules of skeletal muscle and stabilizes Ca(2+) transients when muscle fibres are subjected to osmotic shock injury (OSI). We show here that voltage-induced Ca(2+) transients elicited in dysferlin-null A/J myofibers are smaller than control A/WySnJ fibres. Regional expression of Venus-dysferlin chimeras in A/J fibres restores the full amplitude of the Ca(2+) transients and protects against OSI. We also show that drugs that target ryanodine receptors (RyR1: dantrolene, tetracaine, S107) and L-type Ca(2+) channels (LTCC: nifedipine, verapamil, diltiazem) prevent the decrease in Ca(2+) transients in A/J fibres following OSI...
June 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28566627/analysis-of-clinical-efficacy-and-adverse-effects-of-%C3%AE-blocking-agents-used-clinically-for-chronic-heart-failure
#17
Risa Takayanagi, Kaori Fujito, Koji Kimura, Yasuhiko Yamada
Clinical efficacy and adverse effects of the β-blocking agents, carvedilol, bisoprolol, and metoprolol were analyzed theoretically, and then compared quantitatively, for the purpose of determining their proper use for chronic heart failure. Initially, we evaluated occupancy binding to the β1 and β2 receptors (Фss(β1) and Фss(β2)) by these drugs. Thereafter, we examined the relationship between Фss(β1) values and left ventricular ejection fraction (LVEF) increase rate to determine efficacy. The result showed that the efficacy with carvedilol could be attained with a lower Фss(β1) value than the others...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28561738/oxidative-stress-induces-stem-cell-proliferation-via-trpa1-ryr-mediated-ca-2-signaling-in-the-drosophila-midgut
#18
Chiwei Xu, Junjie Luo, Li He, Craig Montell, Norbert Perrimon
Precise regulation of stem cell activity is crucial for tissue homeostasis and necessary to prevent overproliferation. In the Drosophila adult gut, high levels of reactive oxygen species (ROS) has been detected with different types of tissue damage, and oxidative stress has been shown to be both necessary and sufficient to trigger intestinal stem cell (ISC) proliferation. However, the connection between oxidative stress and mitogenic signals remains obscure. In a screen for genes required for ISC proliferation in response to oxidative stress, we identified two regulators of cytosolic Ca(2+) levels, transient receptor potential A1 (TRPA1) and ryanodine receptor (RyR)...
May 31, 2017: ELife
https://www.readbyqxmd.com/read/28550171/%C3%AE-adrenergic-receptor-stimulation-inhibits-proarrhythmic-alternans-in-post-infarction-border-zone-cardiomyocytes-a-computational-analysis
#19
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/28547000/whole-exome-sequencing-of-a-patient-with-suspected-mitochondrial-myopathy-reveals-novel-compound-heterozygous-variants-in-ryr1
#20
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
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