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ryanodine receptor

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https://www.readbyqxmd.com/read/28527222/functional-characterization-of-c-terminal-ryanodine-receptor-1-variants-associated-with-central-core-disease-or-malignant-hyperthermia
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28484012/metaplasticity-mechanisms-restore-plasticity-and-associativity-in-an-animal-model-of-alzheimer-s-disease
#13
Qin Li, Sheeja Navakkode, Martin Rothkegel, Tuck Wah Soong, Sreedharan Sajikumar, Martin Korte
Dynamic regulation of plasticity thresholds in a neuronal population is critical for the formation of long-term plasticity and memory and is achieved by mechanisms such as metaplasticity. Metaplasticity tunes the synapses to undergo changes that are necessary prerequisites for memory storage under physiological and pathological conditions. Here we discovered that, in amyloid precursor protein (APP)/presenilin-1 (PS1) mice (age 3-4 mo), a prominent mouse model of Alzheimer's disease (AD), late long-term potentiation (LTP; L-LTP) and its associative plasticity mechanisms such as synaptic tagging and capture (STC) were impaired already in presymptomatic mice...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28481020/activation-of-ryanodine-receptors-is-required-for-pka-mediated-downregulation-of-a-type-k-channels-in-rat-hippocampal-neurons
#14
Yoon-Sil Yang, Sang-Chan Jeon, Moon-Suk Kang, Seon-Hee Kim, Su-Yong Eun, Soo-Hee Jin, Sung-Cherl Jung
A-type K(+) channels (IA channels) contribute to learning and memory mechanisms by regulating neuronal excitabilities in the CNS, and their expression level is targeted by Ca(2+) influx via synaptic NMDA receptors (NMDARs) during long-term potentiation (LTP). However, it is not clear how local synaptic Ca(2+) changes induce IA downregulation throughout the neuron, extending from the active synapse to the soma. In this study, we tested if two major receptors of endoplasmic reticulum (ER), ryanodine (RyRs), and IP3 (IP3 R) receptors, are involved in Ca(2+) -mediated IA downregulation in cultured hippocampal neurons of rats...
May 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28476922/sarcolemmal-distribution-of-ica-and-incx-and-ca-autoregulation-in-mouse-ventricular-myocytes
#15
Hanne C Gadeberg, Cherrie H T Kong, Simon M Bryant, Andrew F James, Clive H Orchard
The balance of Ca influx and efflux regulates the Ca load of cardiac myocytes, a process known as autoregulation. Previous work has shown that Ca influx, via L-type Ca current (ICa), and efflux, via Na-Ca exchange (NCX), occur predominantly at t-tubules; however the role of t-tubules in autoregulation is unknown. We therefore investigated the sarcolemmal distribution of ICa and INCX, and autoregulation, in mouse ventricular myocytes using whole cell voltage-clamp and simultaneous Ca measurement in intact and detubulated (DT) cells...
May 5, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28476886/amyloid-%C3%AE-production-is-regulated-by-%C3%AE-2-adrenergic-signaling-mediated-post-translational-modifications-of-the-ryanodine-receptor
#16
Renaud Bussiere, Alain Lacampagne, Steven Reiken, Xiaoping Liu, Valerie Scheuerman, Ran Zalk, Cécile Martin, Frederic Checler, Andrew R Marks, Mounia Chami
Alteration of ryanodine receptor (RyR)-mediated calcium (Ca(2+)) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca(2+) release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe)...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28476660/%C3%AE-adrenergic-induced-sr-ca-2-leak-is-mediated-by-an-epac-nos-pathway
#17
Laëtitia Pereira, Dan J Bare, Samuel Galice, Thomas R Shannon, Donald M Bers
Cardiac β-adrenergic receptors (β-AR) and Ca(2+)-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca(2+) signaling. Elevated diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca(2+) leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1)...
May 2, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28473402/post-myocardial-infarction-t-tubules-form-enlarged-branched-structures-with-dysregulation-of-junctophilin-2-and-bridging-integrator-1-bin-1
#18
Christian Pinali, Nadim Malik, J Bernard Davenport, Laurence J Allan, Lucy Murfitt, Mohammad M Iqbal, Mark R Boyett, Elizabeth J Wright, Rachel Walker, Yu Zhang, Halina Dobryznski, Cathy M Holt, Ashraf Kitmitto
BACKGROUND: Heart failure is a common secondary complication following a myocardial infarction (MI), characterized by impaired cardiac contraction and t-tubule (t-t) loss. However, post-MI nano-scale morphological changes to the remaining t-ts are poorly understood. METHOD AND RESULTS: We utilized a porcine model of MI, using a nonlethal microembolization method to generate controlled microinfarcts. Using serial block face scanning electron microscopy, we report that post-MI, after mild left-ventricular dysfunction has developed, t-ts are not only lost in the peri-infarct region, but also the remnant t-ts form enlarged, highly branched disordered structures, containing a dense intricate inner membrane...
May 4, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28470044/chemical-synthesis-of-ryanodine-and-20-deoxyspiganthine
#19
Chen Xu, Arthur Han, Scott C Virgil, Sarah E Reisman
(+)-Ryanodine is a natural product modulator of ryanodine receptors, important intracellular calcium ion channels that play a critical role in signal transduction leading to muscle movement and synaptic transmission. Chemical derivatization of (+)-ryanodine has demonstrated that certain peripheral structural modifications can alter its pharmacology, and that the pyrrole-2-carboxylate ester is critical for high affinity binding to ryanodine receptors. However, the structural variation of available ryanodine analogues has been limited by the challenge of site-specific functionalization of semisynthetic intermediates, such as (+)-ryanodol...
April 26, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28469494/studying-dyadic-structure-function-relationships-a-review-of-current-modeling-approaches-and-new-insights-into-ca-2-mis-handling
#20
Mary M Maleckar, Andrew G Edwards, William E Louch, Glenn T Lines
Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes...
2017: Clinical Medicine Insights. Cardiology
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