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Ryanodine receptor type 2 heart

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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/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
#2
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/28216082/semi-automated-program-for-analysis-of-local-ca-2-spark-release-with-application-for-classification-of-heart-cell-type
#3
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/28126160/role-of-nod1-in-heart-failure-progression-via-regulation-of-ca-2-handling
#4
Almudena Val-Blasco, María Jose G M Piedras, Gema Ruiz-Hurtado, Natalia Suarez, Patricia Prieto, Silvia Gonzalez-Ramos, Nieves Gómez-Hurtado, Carmen Delgado, Laetitia Pereira, Gemma Benito, Carlos Zaragoza, Nieves Domenech, María Generosa Crespo-Leiro, Daniel Vasquez-Echeverri, Gabriel Nuñez, Eduardo Lopez-Collazo, Lisardo Boscá, María Fernández-Velasco
BACKGROUND: Heart failure (HF) is a complex syndrome associated with a maladaptive innate immune system response that leads to deleterious cardiac remodeling. However, the underlying mechanisms of this syndrome are poorly understood. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune sensor involved in cardiovascular diseases. OBJECTIVES: This study evaluated the role of NOD1 in HF progression. METHODS: NOD1 was examined in human failing myocardium and in a post-myocardial infarction (PMI) HF model evaluated in wild-type (wt-PMI) and Nod1(-/-) mice (Nod1(-/-)-PMI)...
January 31, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28077437/sensitized-signalling-between-l-type-ca2-channels-and-ryanodine-receptors-in-the-absence-or-inhibition-of-fkbp12-6-in-cardiomyocytes
#5
Yan-Ting Zhao, Yun-Bo Guo, Lei Gu, Xue-Xin Fan, Hua-Qian Yang, Zheng Chen, Peng Zhou, Qi Yuan, Guang-Ju Ji, Shi-Qiang Wang
AIMS: The heart contraction is controlled by the Ca(2+)-induced Ca(2+ )release (CICR) between L-type Ca(2+ )channels and ryanodine receptors (RyRs). The FK506-binding protein FKBP12.6 binds to RyR subunits, but its role in stabilizing RyR function has been debated for long. Recent reports of high-resolution RyR structure show that the HD2 domain that binds to the SPRY2 domain of neighbouring subunit in FKBP-bound RyR1 is detached and invisible in FKBP-null RyR2. The present study was to test the consequence of FKBP12...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/27987400/an-insertion-deletion-polymorphism-within-3-utr-of-ryr2-modulates-sudden-unexplained-death-risk-in-chinese-populations
#6
Shouyu Wang, Zhixiang Zhang, Ya Yang, Chaoqun Wang, Ruiyang Tao, Shuxiang Hu, Zhixia Yin, Qing Zhang, Lijuan Li, Yan He, Shaohua Zhu, Chengtao Li, Suhua Zhang, Jianhua Zhang, Lihui Sheng, Fangyu Wu, Bin Luo, Yuzhen Gao
Sudden unexplained death (SUD) constitutes a part of the overall sudden death that can not be underestimated. Over the last years, genetic testing on SUD has revealed that inherited channelopathies might play important roles in the pathophysiology of this disease. Ryanodine receptor type-2 (RYR2) is a kind of ion channel extensively distributed in the sarcoplasmic reticulum (SR) of myocardium. Studies on RYR2 have suggested that either dysfunction or abnormal expression of it could lead to arrhythmia, which may cause cardiac arrest...
December 9, 2016: Forensic Science International
https://www.readbyqxmd.com/read/27864509/loss-of-%C3%AE-adrenergic-stimulated-phosphorylation-of-cav1-2-channels-on-ser1700-leads-to-heart-failure
#7
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)...
December 6, 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
#8
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 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown. OBJECTIVE: To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction. METHODS AND RESULTS: Pharmacological inhibition of phosphodiesterase 2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor activation in healthy mice...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/27760414/junctophilin-2-gene-therapy-rescues-heart-failure-by-normalizing-ryr2-mediated-ca-2-release
#9
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
#10
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...
November 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27729468/speg-striated-muscle-preferentially-expressed-protein-kinase-is-essential-for-cardiac-function-by-regulating-junctional-membrane-complex-activity
#11
Ann P Quick, Qiongling Wang, Leonne E Philippen, Giselle Barreto-Torres, David Y Chiang, David Beavers, Guoliang Wang, Maha Khalid, Julia O Reynolds, Hannah M Campbell, Jordan Showell, Mark D McCauley, Arjen Scholten, Xander H T Wehrens
RATIONALE: Junctional membrane complexes (JMCs) 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 SPEG (striated muscle preferentially expressed protein kinase) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. METHODS AND RESULTS: Proteomic analysis of immunoprecipitated JMC proteins ryanodine receptor type 2 and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/27708056/structural-basis-for-the-gating-mechanism-of-the-type-2-ryanodine-receptor-ryr2
#12
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
#13
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
#14
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 laboratorySUBJECTS:: Male wild type and transgenic miceINTERVENTIONS:: We induced sepsis in mice using the colon ascendens stent peritonitis model...
April 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/27585747/regulation-of-sarcoplasmic-reticulum-ca-2-release-by-serine-threonine-phosphatases-in-the-heart
#15
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...
December 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
#16
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
#17
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
#18
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
#19
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
#20
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
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