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Ryanodine receptor type 2 heart

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https://www.readbyqxmd.com/read/27864509/loss-of-%C3%AE-adrenergic-stimulated-phosphorylation-of-cav1-2-channels-on-ser1700-leads-to-heart-failure
#1
Linghai Yang, Dao-Fu Dai, Can Yuan, Ruth E Westenbroek, Haijie Yu, Nastassya West, Horacio O de la Iglesia, William A Catterall
L-type Ca(2+) currents conducted by voltage-gated calcium channel 1.2 (CaV1.2) initiate excitation-contraction coupling in the heart, and altered expression of CaV1.2 causes heart failure in mice. Here we show unexpectedly that reducing β-adrenergic regulation of CaV1.2 channels by mutation of a single PKA site, Ser1700, in the proximal C-terminal domain causes reduced contractile function, cardiac hypertrophy, and heart failure without changes in expression, localization, or function of the CaV1.2 protein in the mutant mice (SA mice)...
November 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27799254/phosphodiesterase-2-protects-against-catecholamine-induced-arrhythmia-and-preserves-contractile-function-after-myocardial-infarction
#2
Christiane Vettel, Marta Lindner, Matthias Dewenter, Kristina Lorenz, Constanze Schanbacher, Merle Riedel, Simon Lämmle, Simone Meinecke, Fleur E Mason, Samuel Sossalla, Andreas Geerts, Michael Hoffmann, Frank Wunder, Fabian J Brunner, Thomas Wieland, Hind Mehel, Sarah Karam, Patrick Lechêne, Jérôme Leroy, Grégoire Vandecasteele, Michael Wagner, Rodolphe Fischmeister, Ali El-Armouche
RATIONALE: Phosphodiesterase 2 (PDE2) is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyses cAMP. Myocardial PDE2 is upregulated in human heart failure (HF), but its role in the heart is unknown. OBJECTIVE: To explore the role of PDE2 in cardiac function, propensity to arrhythmia and in myocardial infarction. METHODS AND RESULTS: Pharmacological inhibition of PDE2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor (β-AR) activation in healthy mice...
October 31, 2016: Circulation Research
https://www.readbyqxmd.com/read/27760414/junctophilin-2-gene-therapy-rescues-heart-failure-by-normalizing-ryr2-mediated-ca-2-release
#3
Julia O Reynolds, Ann P Quick, Qiongling Wang, David L Beavers, Leonne E Philippen, Jordan Showell, Giselle Barreto-Torres, Donna J Thuerauf, Shirin Doroudgar, Christopher C Glembotski, Xander H T Wehrens
BACKGROUND: Junctophilin-2 (JPH2) is the primary structural protein for the coupling of transverse (T)-tubule associated cardiac L-type Ca channels and type-2 ryanodine receptors on the sarcoplasmic reticulum within junctional membrane complexes (JMCs) in cardiomyocytes. Effective signaling between these channels ensures adequate Ca-induced Ca release required for normal cardiac contractility. Disruption of JMC subcellular domains, a common feature of failing hearts, has been attributed to JPH2 downregulation...
December 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27737323/thyroxine-increases-serca2-and-ryr2-gene-expression-in-heart-failure-rats-with-euthyroid-sick-syndrome
#4
Fábio V G Campanha, Denise Perone, Dijon H S de Campos, Renata de A M Luvizotto, Maria T De Síbio, Miriane de Oliveira, Regiane M C Olimpio, Fernanda C F Moretto, Carlos R Padovani, Gláucia M F S Mazeto, Antonio C Cicogna, Célia R Nogueira
Objective: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups...
October 10, 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27729468/striated-muscle-preferentially-expressed-protein-kinase-speg-is-essential-for-cardiac-function-by-regulating-junctional-membrane-complex-activity
#5
Ann P Quick, Qiongling Wang, Leonne E Philippen, Giselle Barreto-Torres, David Y Chiang, David L Beavers, Guoliang Wang, Maha Khalid, Julia O Reynolds, Hannah M Campbell, Jordan Showell, Mark D McCauley, Arjen Scholten, Xander H Wehrens
RATIONALE: Junctional membrane complexes (JMC) in myocytes are critical microdomains, in which excitation-contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein striated muscle preferentially expressed gene (SPEG) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. MMethods and Results: Proteomic analysis of immunoprecipatated JMC-proteins ryanodine receptor type-2 (RyR2) and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins...
October 11, 2016: Circulation Research
https://www.readbyqxmd.com/read/27708056/structural-basis-for-the-gating-mechanism-of-the-type-2-ryanodine-receptor-ryr2
#6
Wei Peng, Huaizong Shen, Jianping Wu, Wenting Guo, Xiaojing Pan, Ruiwu Wang, S R Wayne Chen, Nieng Yan
RyR2 is a high-conductance intracellular calcium (Ca(2+)) channel that controls the release of Ca(2+) from the sarco(endo)plasmic reticulum of a variety of cells. Here, we report the structures of RyR2 from porcine heart in both the open and closed states at near-atomic resolutions determined using single-particle electron cryomicroscopy. Structural comparison reveals a breathing motion of the overall cytoplasmic region resulted from the interdomain movements of amino-terminal domains (NTDs), Helical domains, and Handle domains, whereas almost no intradomain shifts are observed in these armadillo repeats-containing domains...
October 21, 2016: Science
https://www.readbyqxmd.com/read/27650424/antiarrhythmic-effects-of-dantrolene-in-human-diseased-cardiomyocytes
#7
Nico Hartmann, Steffen Pabel, Jonas Herting, Felix Schatter, André Renner, Jan Gummert, Hanna Schotola, Bernhard C Danner, Lars S Maier, Norbert Frey, Gerd Hasenfuss, Thomas H Fischer, Samuel Sossalla
BACKGROUND: Cardiac type 2 ryanodine receptors (RyR2s) play a pivotal role in cellular electrophysiology and contractility. Increased RyR2-mediated diastolic sarcoplasmic reticulum (SR) Ca(2+) release is linked to heart failure (HF) and arrhythmias. Dantrolene, a drug used for the treatment of malignant hyperthermia, is known to stabilize RyRs in skeletal muscle. OBJECTIVE: The purpose of this study was to investigate the effects of dantrolene on arrhythmogenic triggers and contractile function in human atrial fibrillation (AF) and HF cardiomyocytes (CM)...
September 17, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27648519/calcium-calmodulin-protein-kinase-ii-dependent-ryanodine-receptor-phosphorylation-mediates-cardiac-contractile-dysfunction-associated-with-sepsis
#8
Marisa Sepúlveda, Luis A Gonano, Manuel Viotti, Malena Morell, Paula Blanco, Micaela López Alarcón, Isalira Peroba Ramos, Adriana Bastos Carvalho, Emiliano Medei, Martín Vila Petroff
OBJECTIVES: Sepsis is associated with cardiac contractile dysfunction attributed to alterations in Ca handling. We examined the subcellular mechanisms involved in sarcoplasmic reticulum Ca loss that mediate altered Ca handling and contractile dysfunction associated with sepsis. DESIGN: Randomized controlled trial. SETTING: Research laboratory SUBJECTS:: Male wild type and transgenic mice INTERVENTIONS:: We induced sepsis in mice using the colon ascendens stent peritonitis model...
September 19, 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27585747/regulation-of-sarcoplasmic-reticulum-ca-2-release-by-serine-threonine-phosphatases-in-the-heart
#9
Dmitry Terentyev, Shanna Hamilton
The amount and timing of Ca(2+) release from the sarcoplasmic reticulum (SR) during cardiac cycle are the main determinants of cardiac contractility. Reversible phosphorylation of the SR Ca(2+) release channel, ryanodine receptor type 2 (RyR2) is the central mechanism of regulation of Ca(2+) release in cardiomyocytes. Three major serine-threonine phosphatases including PP1, PP2A and PP2B (calcineurin) have been implicated in modulation of RyR2 function. Changes in expression levels of these phosphatases, their activity and targeting to the RyR2 macromolecular complex were demonstrated in many animal models of cardiac disease and humans and are implicated in cardiac arrhythmia and heart failure...
August 29, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27529477/nitric-oxide-synthase-1-modulates-basal-and-%C3%AE-adrenergic-stimulated-contractility-by-rapid-and-reversible-redox-dependent-s-nitrosylation-of-the-heart
#10
Alejandra Z Vielma, Luisa León, Ignacio C Fernández, Daniel R González, Mauricio P Boric
S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC...
2016: PloS One
https://www.readbyqxmd.com/read/27496868/inositol-1-4-5-trisphosphate-mediated-sarcoplasmic-reticulum-mitochondrial-crosstalk-influences-adenosine-triphosphate-production-via-mitochondrial-ca2-uptake-through-the-mitochondrial-ryanodine-receptor-in-cardiac-myocytes
#11
Lea K Seidlmayer, Johannes Kuhn, Annette Berbner, Paula-Anahi Arias-Loza, Tatjana Williams, Mathias Kaspar, Martin Czolbe, Jennifer Q Kwong, Jeffery D Molkentin, Katrin Gertrud Heinze, Elena N Dedkova, Oliver Ritter
AIMS: Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac myocytes are typically associated with the development of cardiac hypertrophy, arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3 receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to determine whether IP3-induced Ca(2+ )release affects mitochondrial function and determine the underlying mechanisms. METHODS AND RESULTS: We compared the effects of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation, respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP) generation...
October 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27402669/camkii-dependent-phosphorylation-regulates-basal-cardiac-pacemaker-function-via-modulation-of-local-ca2-releases
#12
Yue Li, Syevda Sirenko, Daniel R Riordon, Dongmei Yang, Harold Spurgeon, Edward G Lakatta, Tatiana M Vinogradova
Spontaneous beating of the heart pacemaker, the sinoatrial node, is generated by sinoatrial node cells (SANC) due to gradual change of the membrane potential called diastolic depolarization (DD). Spontaneous, submembrane local Ca(2+) releases (LCR) from ryanodine receptors (RyR) occur during late DD and activate an inward Na(+)/Ca(2+)exchange current to boost the DD rate and fire an action potential (AP). Here we studied the extent of basal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation and the role of basal CaMKII-dependent protein phosphorylation in generation of LCRs and regulation of normal automaticity of intact rabbit SANC...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27402292/roselle-polyphenols-exert-potent-negative-inotropic-effects-via-modulation-of-intracellular-calcium-regulatory-channels-in-isolated-rat-heart
#13
Yi-Cheng Lim, Siti Balkis Budin, Faizah Othman, Jalifah Latip, Satirah Zainalabidin
Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study...
July 11, 2016: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/27377851/modeling-na-ca-2-exchange-in-the-heart-allosteric-activation-spatial-localization-sparks-and-excitation-contraction-coupling
#14
Lulu Chu, Joseph L Greenstein, Raimond L Winslow
The cardiac sodium (Na(+))/calcium (Ca(2+)) exchanger (NCX1) is an electrogenic membrane transporter that regulates Ca(2+) homeostasis in cardiomyocytes, serving mainly to extrude Ca(2+) during diastole. The direction of Ca(2+) transport reverses at membrane potentials near that of the action potential plateau, generating an influx of Ca(2+) into the cell. Therefore, there has been great interest in the possible roles of NCX1 in cardiac Ca(2+)-induced Ca(2+) release (CICR). Interest has been reinvigorated by a recent super-resolution optical imaging study suggesting that ~18% of NCX1 co-localize with ryanodine receptor (RyR2) clusters, and ~30% of additional NCX1 are localized to within ~120nm of the nearest RyR2...
July 1, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27350214/genomic-structure-expression-and-association-study-of-the-porcine-fsd2
#15
Kyu-Sang Lim, Kyung-Tai Lee, Si-Woo Lee, Han-Ha Chai, Gulwon Jang, Ki-Chang Hong, Tae-Hun Kim
The fibronectin type III and SPRY domain containing 2 (FSD2) on porcine chromosome 7 is considered a candidate gene for pork quality, since its two domains, which were present in fibronectin and ryanodine receptor. The fibronectin type III and SPRY domains were first identified in fibronectin and ryanodine receptor, respectively, which are candidate genes for meat quality. The aim of this study was to elucidate the genomic structure of FSD2 and functions of single nucleotide polymorphisms (SNPs) within FSD2 that are related to meat quality in pigs...
September 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27332123/ultrastructural-analysis-of-self-associated-ryr2s
#16
Vanessa Cabra, Takashi Murayama, Montserrat Samsó
In heart, type-2 ryanodine receptor (RyR2) forms discrete supramolecular clusters in the sarcoplasmic reticulum known as calcium release units (CRUs), which are responsible for most of the Ca(2+) released for muscle contraction. To learn about the substructure of the CRU, we sought to determine whether RyR2s have the ability to self-associate in the absence of other factors and if so, whether they do it in a specific manner. Purified RyR2 was negatively stained and imaged on the transmission electron microscope, and RyR2 particles closely associated were further analyzed using bias-free multivariate statistical analysis and classification...
June 21, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27226555/s100a1-protein-does-not-compete-with-calmodulin-for-ryanodine-receptor-binding-but-structurally-alters-the-ryanodine-receptor%C3%A2-calmodulin-complex
#17
Robyn T Rebbeck, Florentin R Nitu, David Rohde, Patrick Most, Donald M Bers, David D Thomas, Razvan L Cornea
S100A1 has been suggested as a therapeutic agent to enhance myocyte Ca(2+) cycling in heart failure, but its molecular mode of action is poorly understood. Using FRET, we tested the hypothesis that S100A1 directly competes with calmodulin (CaM) for binding to intact, functional ryanodine receptors type I (RyR1) and II (RyR2) from skeletal and cardiac muscle, respectively. Our FRET readout provides an index of acceptor-labeled CaM binding near donor-labeled FKBP (FK506-binding protein 12.6) on the cytoplasmic domain of RyR in isolated sarcoplasmic reticulum vesicles...
July 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26904356/ryr2-qq2958-genotype-and-risk-of-malignant-ventricular-arrhythmias
#18
Francesca Galati, Antonio Galati, Serafina Massari
Ventricular arrhythmias are one of the most common causes of death in developed countries. The use of implantable cardiac defibrillators is the most effective treatment to prevent sudden cardiac death. To date, the ejection fraction is the only approved clinical variable used to determine suitability for defibrillator placement in subjects with heart failure. The purpose of this study was to assess whether genetic polymorphisms found in the ryanodine receptor type 2 (Q2958R) and histidine-rich calcium-binding protein (S96A) might serve as markers for arrhythmias...
2016: Cardiology Research and Practice
https://www.readbyqxmd.com/read/26827896/ryanodine-receptor-sensitivity-governs-the-stability-and-synchrony-of-local-calcium-release-during-cardiac-excitation-contraction-coupling
#19
Andrew P Wescott, M Saleet Jafri, W J Lederer, George S B Williams
Calcium-induced calcium release is the principal mechanism that triggers the cell-wide [Ca(2+)]i transient that activates muscle contraction during cardiac excitation-contraction coupling (ECC). Here, we characterize this process in mouse cardiac myocytes with a novel mathematical action potential (AP) model that incorporates realistic stochastic gating of voltage-dependent L-type calcium (Ca(2+)) channels (LCCs) and sarcoplasmic reticulum (SR) Ca(2+) release channels (the ryanodine receptors, RyR2s). Depolarization of the sarcolemma during an AP stochastically activates the LCCs elevating subspace [Ca(2+)] within each of the cell's 20,000 independent calcium release units (CRUs) to trigger local RyR2 opening and initiate Ca(2+) sparks, the fundamental unit of triggered Ca(2+) release...
March 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/26786159/l-type-cav1-3-channels-regulate-ryanodine-receptor-dependent-ca2-release-during-sino-atrial-node-pacemaker-activity
#20
Angelo Giovanni Torrente, Pietro Mesirca, Patricia Neco, Riccardo Rizzetto, Stefan Dubel, Christian Barrere, Martina Sinegger-Brauns, Joerg Striessnig, Sylvain Richard, Joël Nargeot, Ana Maria Gomez, Matteo Elia Mangoni
AIMS: Sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that is still not completely understood. Recent studies highlighted the importance of intracellular Ca(2+) ([Ca(2+)]i) dynamics during SAN pacemaker activity. Nevertheless, the functional role of voltage-dependent L-type Ca(2+) channels in controlling SAN [Ca(2+)]i release is largely unexplored. Since Cav1.3 is the predominant L-type Ca(2+) channel isoform in SAN cells, we studied [Ca(2+)]i dynamics in isolated cells and ex vivo SAN preparations explanted from wild-type (WT) and Cav1...
March 1, 2016: Cardiovascular Research
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