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https://www.readbyqxmd.com/read/27914790/sarcoplasmic-reticulum-ca-2-mg-2-k-and-cl-concentrations-adjust-quickly-as-heart-rate-changes
#1
Claudio Berti, Vilmos Zsolnay, Thomas R Shannon, Michael Fill, Dirk Gillespie
During systole, Ca(2+) is released from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) while, simultaneously, other ions (specifically K(+), Mg(2+), and Cl(-)) provide counter-ion flux. These ions move back into the SR during diastole through the SERCA pump and SR K(+) and Cl(-) channels. In homeostasis, all ion concentrations in different cellular regions (e.g., junctional and non-junctional SR, dyadic cleft, and cytosol) are the same at the beginning and end of the cardiac cycle. Here, we used an equivalent circuit compartment model of the SR and the surrounding cytoplasm to understand the heart rate dependence of SR ion homeostasis...
November 30, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#2
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27866274/ryanodine-receptor-type-3-does-not-contribute-to-contractions-in-the-mouse-myometrium-regardless-of-pregnancy
#3
Katsuhito Matsuki, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine...
November 20, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27865358/low-daily-dose-of-3-mg-monacolin-k-from-ryr-reduces-the-concentration-of-ldl-c-in-a-randomized-placebo-controlled-intervention
#4
Tina Heinz, Jan Philipp Schuchardt, Katharina Möller, Peyman Hadji, Andreas Hahn
Hypercholesterolemia and elevated homocysteine concentrations are associated with cardiovascular risk. Previous studies have demonstrated a cholesterol-lowering effect of red yeast rice (RYR) supplements which contained 5 to 10 mg of monacolin K. We hypothesized that the intake of a low monacolin K dose may likewise reduce low-density lipoprotein-cholesterol (LDL-C) and other plasma lipids. In secondary analyses, we tested the homocysteine lowering effect of folic acid, which was also included in the study preparation...
October 2016: Nutrition Research
https://www.readbyqxmd.com/read/27845250/ryanodine-receptor-point-mutations-confer-diamide-insecticide-resistance-in-tomato-leafminer-tuta-absoluta-lepidoptera-gelechiidae
#5
Emmanouil Roditakis, Denise Steinbach, Gerald Moritz, Emmanouil Vasakis, Marianna Stavrakaki, Aris Ilias, Lidia García-Vidal, María Del Rosario Martínez-Aguirre, Pablo Bielza, Evangelia Morou, Jefferson E Silva, Wellington M Silva, Ηerbert A A Siqueira, Sofia Iqbal, Bartlomiej J Troczka, Martin S Williamson, Chris Bass, Anastasia Tsagkarakou, John Vontas, Ralf Nauen
Insect ryanodine receptors (RyR) are the molecular target-site for the recently introduced diamide insecticides. Diamides are particularly active on Lepidoptera pests, including tomato leafminer, Tuta absoluta (Lepidoptera: Gelechiidae). High levels of diamide resistance were recently described in some European populations of T. absoluta, however, the mechanisms of resistance remained unknown. In this study the molecular basis of diamide resistance was investigated in a diamide resistant strain from Italy (IT-GELA-SD4), and additional resistant field populations collected in Greece, Spain and Brazil...
November 12, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27802169/junctophilin-2-in-the-nanoscale-organisation-and-functional-signalling-of-ryanodine-receptor-clusters-in-cardiomyocytes
#6
Michelle L Munro, Isuru D Jayasinghe, Qiongling Wang, Ann Quick, Wei Wang, David Baddeley, Xander H T Wehrens, Christian Soeller
Signalling nanodomains requiring close contact between the plasma membrane and internal compartments, known as 'junctions', are fast communication hubs within excitable cells such as neurones and muscle. Here, we have examined two transgenic murine models probing the role of junctophilin-2, a membrane-tethering protein crucial for the formation and molecular organisation of sub-microscopic junctions in ventricular muscle cells of the heart. Quantitative single-molecule localisation microscopy showed that junctions in animals producing above-normal levels of junctophilin-2 were enlarged, allowing the re-organisation of the primary functional protein within it, the ryanodine receptor (RyR; in this paper, we use RyR to refer to the myocardial isoform RyR2)...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27798190/a-feed-forward-mechanism-involving-the-nox-complex-and-ryr-mediated-ca2-release-during-axonal-specification
#7
Carlos Wilson, Ernesto Muñoz-Palma, Daniel R Henríquez, Ilaria Palmisano, M Tulio Núñez, Simone Di Giovanni, Christian González-Billault
: Physiological levels of ROS support neurite outgrowth and axonal specification, but the mechanisms by which ROS are able to shape neurons remain unknown. Ca(2+), a broad intracellular second messenger, promotes both Rac1 activation and neurite extension. Ca(2+) release from the endoplasmic reticulum, mediated by both the IP3R1 and ryanodine receptor (RyR) channels, requires physiological ROS levels that are mainly sustained by the NADPH oxidase (NOX) complex. In this work, we explore the contribution of the link between NOX and RyR-mediated Ca(2+) release toward axonal specification of rat hippocampal neurons...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27789712/the-cytoplasmic-region-of-inner-helix-s6-is-an-important-determinant-of-cardiac-ryanodine-receptor-channel-gating
#8
Bo Sun, Wenting Guo, Xixi Tian, Jinjing Yao, Lin Zhang, Ruiwu Wang, S R Wayne Chen
The ryanodine receptor (RyR) channel pore is formed by four S6 inner helices with its intracellular gate located at the S6 helix bundle crossing region. The cytoplasmic region of the extended S6 helix is held by the U-motif of the Central domain, and is thought to control the opening and closing of the S6 helix bundle. However, the functional significance of the S6 cytoplasmic region in channel gating is unknown. Here we assessed the role of the S6 cytoplasmic region in the function of cardiac RyR (RyR2) via structure-guided site-directed mutagenesis...
October 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27776230/the-combination-of-in-silico-and-in%C3%A2-vivo-approaches-for-the-investigation-of-disrupting-effects-of-tris-2-chloroethyl-phosphate-tcep-toward-core-receptors-of-zebrafish
#9
Yang Wu, Guanyong Su, Song Tang, Wei Liu, Zhiyuan Ma, Xinmei Zheng, Hongling Liu, Hongxia Yu
Tris (2-chloroethyl) phosphate (TCEP), a substitute for brominated flame retardants (FRs) that have been phased out of use, is frequently detected in aqueous environments. However, previous studies on its endocrine disrupting effects have mainly focused on terrestrial mammals. Here, to comprehensively evaluate the potential adverse effects of TCEP on aquatic vertebrates, zebrafish was used as a model to examine developmental phenotypes. The underlying mechanisms of toxicity of TCEP were further explored using in silico and in vivo approaches...
October 21, 2016: Chemosphere
https://www.readbyqxmd.com/read/27771553/correction-of-impaired-calmodulin-binding-to-ryr2-as-a-novel-therapy-for-lethal-arrhythmia-in-the-pressure-overloaded-heart-failure
#10
Takayoshi Kato, Takeshi Yamamoto, Yoshihide Nakamura, Takuma Nanno, Go Fukui, Yoko Sufu, Yoriomi Hamada, Takako Maeda, Shigehiko Nishimura, Hironori Ishiguchi, Wakako Murakami, Masakazu Fukuda, Xiaojuan Xu, Akihiro Hino, Makoto Ono, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Noritaka Koseki, Hiroyuki Kyushiki, Masafumi Yano
BACKGROUND: Calmodulin (CaM) is a key modulator of the channel gating function of the ryanodine receptor (RyR). OBJECTIVE: The purpose of this study was to investigate the pathogenic role of RyR-bound CaM in diastolic Ca(2+) leakage from the sarcoplasmic reticulum and arrhythmogenesis in pressure-overloaded heart failure. METHODS: Pressure overload was induced in 12-week-old mice by transverse aortic constriction (TAC) using a 27-gauge needle...
October 19, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27760856/high-throughput-screens-to-discover-small-molecule-modulators-of-ryanodine-receptor-calcium-release-channels
#11
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27739779/nonlinear-onset-of-calcium-wave-propagation-in-cardiac-cells
#12
Yohannes Shiferaw
Spontaneous calcium (Ca) waves in cardiac myocytes are known to underlie a wide range of cardiac arrhythmias. However, it is not understood which physiological parameters determine the onset of waves. In this study, we explore the relationship between Ca signaling between ion channels and the nucleation of Ca waves. In particular, we apply a master equation approach to analyze the stochastic interaction between neighboring clusters of ryanodine receptor (RyR) channels. Using this analysis, we show that signaling between clusters can be described as a barrier hopping process with exponential sensitivity to system parameters...
September 2016: Physical Review. E
https://www.readbyqxmd.com/read/27733687/enhanced-cytosolic-ca2-activation-underlies-a-common-defect-of-central-domain-cardiac-ryanodine-receptor-mutations-linked-to-arrhythmias
#13
Zhichao Xiao, Wenting Guo, Bo Sun, Donald J Hunt, Jinhong Wei, Yingjie Liu, Yundi Wang, Ruiwu Wang, Peter P Jones, Thomas G Back, S R Wayne Chen
Recent three-dimensional structural studies reveal that the central domain of ryanodine receptor (RyR) serves as a transducer that converts long-range conformational changes into the gating of the channel pore. Interestingly, the central domain encompasses one of the mutation hotspots (corresponding to amino acid residues 3778-4201) that contains a number of cardiac RyR (RyR2) mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) and atrial fibrillation (AF). However, the functional consequences of these central domain RyR2 mutations are not well understood...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27717822/inhibiting-c-jun-n-terminal-kinase-partially-attenuates-caffeine-dependent-cell-death-without-alleviating-the-caffeine-induced-reduction-in-mitochondrial-respiration-in-c2c12-skeletal-myotubes
#14
R M Downs, M A Hughes, S T Kinsey, M C Johnson, B L Baumgarner
Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far there is little information available regarding the toxicity of caffeine in skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this study was to further elucidate the pathways by which caffeine increased cell death and reduced mitochondrial respiration...
October 4, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27708056/structural-basis-for-the-gating-mechanism-of-the-type-2-ryanodine-receptor-ryr2
#15
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/27687475/structures-of-the-colossal-ryr1-calcium-release-channel
#16
Oliver B Clarke, Wayne A Hendrickson
Ryanodine receptors (RyRs) are intracellular cation channels that mediate the rapid and voluminous release of Ca(2+) from the sarcoplasmic reticulum (SR) as required for excitation-contraction coupling in cardiac and skeletal muscle. Understanding of the architecture and gating of RyRs has advanced dramatically over the past two years, due to the publication of high resolution cryo-electron microscopy (cryoEM) reconstructions and associated atomic models of multiple functional states of the skeletal muscle receptor, RyR1...
August 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27671094/a-guide-to-the-3d-structure-of-the-ryanodine-receptor-type-1-by-cryoem
#17
Montserrat Samsó
Signal transduction by the ryanodine receptor (RyR) is essential in many excitable cells including all striated contractile cells and some types of neurons. While its transmembrane domain is a classic tetrameric, six-transmembrane cation channel, the cytoplasmic domain is uniquely large and complex, hosting a multiplicity of specialized domains. The overall outline and substructure readily recognizable by electron microscopy make RyR a geometrically well-behaved specimen. Hence, for the last two decades, the 3D structural study of the RyR has tracked closely the technological advances in electron microscopy, cryo-electron microscopy (cryoEM), and computerized 3D reconstruction...
September 27, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27659710/emerging-pathways-driving-early-synaptic-pathology-in-alzheimer-s-disease
#18
Clark A Briggs, Shreaya Chakroborty, Grace E Stutzmann
The current state of the AD research field is highly dynamic is some respects, while seemingly stagnant in others. Regarding the former, our current lack of understanding of initiating disease mechanisms, the absence of effective treatment options, and the looming escalation of AD patients is energizing new research directions including a much-needed re-focusing on early pathogenic mechanisms, validating novel targets, and investigating relevant biomarkers, among other exciting new efforts to curb disease progression and foremost, preserve memory function...
September 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27650424/antiarrhythmic-effects-of-dantrolene-in-human-diseased-cardiomyocytes
#19
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/27641745/cannabinoid-signalling-inhibits-sarcoplasmic-ca-2-release-and-regulates-excitation-contraction-coupling-in-mammalian-skeletal-muscle
#20
Tamás Oláh, Dóra Bodnár, Adrienn Tóth, János Vincze, János Fodor, Barbara Reischl, Adrienn Kovács, Olga Ruzsnavszky, Beatrix Dienes, Péter Szentesi, Oliver Friedrich, László Csernoch
Marijuana was found to cause muscle weakness, but it is unknown whether it affects the muscles directly, or modulates only the motor control of the central nervous system. Although the presence of CB1 cannabinoid receptors (CB1R) - responsible for the psychoactive effects of the drug in the brain - have recently been shown in skeletal muscle, it is unclear how CB1R-mediated signalling affects the contraction and Ca²⁺ homeostasis of mammalian skeletal muscle. Here we demonstrate that in vitro CB1R activation increased muscle fatigability, decreased the Ca(2+) -sensitivity of the contractile apparatus, but did not alter the amplitude of single twitch contractions...
September 19, 2016: Journal of Physiology
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