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("ryanodine receptor" OR "ryr" OR "ryr2") AND ("heart" OR "cardiac")

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https://www.readbyqxmd.com/read/28736243/from-insulin-synthesis-to-secretion-alternative-splicing-of-type-2-ryanodine-receptor-gene-is-essential-for-insulin-secretion-in-pancreatic-%C3%AE-cells
#1
Hiroshi Okamoto, Shin Takasawa, Yasuhiko Yamamoto
Increases in the intracellular Ca(2+) concentration in pancreatic islets, resulting from the its mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca(2+) mobilizing second messenger synthesized from NAD(+) by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75...
July 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28731153/altered-profile-of-mrna-expression-in-atrioventricular-node-of-streptozotocin%C3%A2-induced-diabetic-rats
#2
Frank Christopher Howarth, Khatija Parekh, Petrilla Jayaprakash, Edward Samuel Inbaraj, Murat Oz, Halina Dobrzynski, Thomas Edward Adrian
Prolonged action potential duration, reduced action potential firing rate, upstroke velocity and rate of diastolic depolarization have been demonstrated in atrioventricular node (AVN) cells from streptozotocin (STZ)‑induced diabetic rats. To further clarify the molecular basis of these electrical disturbances, the mRNA profiles encoding a variety of proteins associated with the generation and conduction of electrical activity in the AVN, were evaluated in the STZ‑induced diabetic rat heart. Expression of mRNA was measured in AVN biopsies using reverse transcription‑quantitative polymerase chain reaction techniques...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713282/the-n-terminal-region-of-the-ryanodine-receptor-affects-channel-activation
#3
Andrea Faltinova, Nataša Tomaskova, Marián Antalik, Jozef Sevcik, Alexandra Zahradnikova
Mutations in the cardiac ryanodine receptor (RyR2), the ion channel responsible for release of calcium ions from intracellular stores into cytoplasm, are the cause of several inherited cardiac arrhythmias. At the molecular level, disease symptoms can be mimicked by domain peptides from mutation-prone regions of RyR2 that bind to RyR2 and activate it. Here we show that the domain peptide DPcpvtN2, corresponding to the central helix of the N-terminal region of RyR2, activates the RyR2 channel. Structural modeling of interaction between DPcpvtN2 and the N-terminal region of RyR2 in the closed and open conformation provided three plausible structures of the complex...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28702845/regulation-of-cardiac-ca-2-and-ion-channels-by-shear-mechanotransduction
#4
REVIEW
Joon-Chul Kim, Min-Jeong Son, Jun Wang, Sun-Hee Woo
Cardiac contraction is controlled by a Ca(2+) signaling sequence that includes L-type Ca(2+) current-gated opening of Ca(2+) release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca(2+) signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses...
July 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28691539/investigational-antiarrhythmic-agents-promising-drugs-in-early-clinical-development
#5
Jordi Heijman, Shokoufeh Ghezelbash, Dobromir Dobrev
Although there have been important technological advances for the treatment of cardiac arrhythmias (e.g., catheter ablation technology), antiarrhythmic drugs (AADs) remain the cornerstone therapy for the majority of patients with arrhythmias. Most of the currently available AADs were coincidental findings and did not result from a systematic development process based on known arrhythmogenic mechanisms and specific targets. During the last 20 years, our understanding of cardiac electrophysiology and fundamental arrhythmia mechanisms has increased significantly, resulting in the identification of new potential targets for mechanism-based antiarrhythmic therapy...
July 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28687594/reduced-threshold-for-store-overload-induced-ca-2-release-is-a-common-defect-of-ryr1-mutations-associated-with-malignant-hyperthermia-and-central-core-disease
#6
Wenqian Chen, Andrea Koop, Yingjie Liu, Wenting Guo, Jinhong Wei, Ruiwu Wang, David H MacLennan, Robert T Dirksen, S R Wayne Chen
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), while mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding RyR isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process known as store-overload induced Ca(2+) release (SOICR)...
July 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28670363/verapamil-suppresses-cardiac-alternans-and-ventricular-arrhythmias-in-acute-myocardial-ischemia-via-ryanodine-receptor-inhibition
#7
Yu-Lei Deng, Jun-Yan Zhao, Ji-Hua Yao, Qiang Tang, Le Zhang, Hong-Lian Zhou, Cun-Tai Zhang, Jia-Gao Lv, Xiao-Qing Quan
T-wave alternans (TWA) is a potent arrhythmia substrate under the conditions of acute myocardial ischemia. Abnormal intracellular calcium cycling contributes to the genesis of cardiac alternans. Ryanodine receptor (RyR) is a pivotal Ca(2+) cycling protein central to Ca(2+) signaling in the heart. Here, we investigated the potential role of RyR in cardiac alternans and ventricular arrhythmias in acute myocardial ischemia. Transmembrane action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contraction force in the arterially perfused left ventricular wedge preparations...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#8
Ying Yang, Xiqing Rong, Xue Lv, Wenbing Jiang, Yuan Yang, Dongwu Lai, Shiming Xu, Guosheng Fu
AIM: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction. METHODS: We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28657075/bioinspired-onion-epithelium-like-structure-promotes-the-maturation-of-cardiomyocytes-derived-from-human-pluripotent-stem-cells
#9
Cong Xu, Li Wang, Yue Yu, Fangchao Yin, Xiaoqing Zhang, Lei Jiang, Jianhua Qin
Organized cardiomyocyte alignment is critical to maintain the mechanical properties of the heart. In this study, we present a new and simple strategy to fabricate a biomimetic microchip designed with an onion epithelium-like structure and investigate the guided behavior of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) on the substrate. The hiPSC-CMs were observed to be confined by the three dimensional surficial features morphologically, analogous to the in vivo microenvironment, and exhibited an organized anisotropic alignment on the onion epithelium-like structure with good beating function...
June 28, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28638869/reducing-toxicity-and-increasing-efficiency-aconitine-with-liquiritin-and-glycyrrhetinic-acid-regulate-calcium-regulatory-proteins-in-rat-myocardial-cell
#10
Yuyan Zhang, Li Yu, Weifeng Jin, Hongjing Fan, Min Li, Tianmei Zhou, Haitong Wan, Jiehong Yang
BACKGROUND: Compatibility of Radix Aconiti Carmichaeli and Liquorice is known to treat heart diseases such as heart failure and cardiac arrhythmias. This work answers the question that whether the active components (Aconitine, Liquiritin and Glycyrrhetinic Acid) of Radix Aconiti Carmichaeli and Liquorice could result in regulating intracellular calcium homeostasis and calcium cycling, and thereby verifies the therapeutic material basis. MATERIALS AND METHODS: The myocardial cells were divided into twelve groups randomly as control group, Aconitine group, nine different dose groups that orthogonal combined with Aconitine, Liquiritin and Glycyrrhetinic Acid, and Verapamil group...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
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
#11
Luis A 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+) signaling, 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/28630041/dysregulated-zn-2-homeostasis-impairs-cardiac-type-2-ryanodine-receptor-and-mitsugumin-23-functions-leading-to-sarcoplasmic-reticulum-ca-2-leakage
#12
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
#13
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/28617952/systolic-ca-2-i-regulates-diastolic-levels-in-rat-ventricular-myocytes
#14
Rajiv Sankaranarayanan, Kornél Kistamás, David J Greensmith, Luigi A Venetucci, David A Eisner
KEY POINTS: For the heart to function as a pump, intracellular calcium concentration ([Ca(2+) ]i ) must increase during systole to activate contraction and then fall, during diastole, to allow the myofilaments to relax and the heart to refill with blood. The present study investigates the control of diastolic [Ca(2+) ]i in rat ventricular myocytes. We show that diastolic [Ca(2+) ]i is increased by manoeuvres that decrease sarcoplasmic reticulum function. This is accompanied by a decrease of systolic [Ca(2+) ]i such that the time-averaged [Ca(2+) ]i remains constant...
June 15, 2017: Journal of Physiology
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
#15
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/28587810/subcellular-localization-of-na-k-atpase-isoforms-in-ventricular-myocytes
#16
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
#17
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/28573136/effects-of-wenxin-keli-on-cardiac-hypertrophy-and-arrhythmia-via-regulation-of-the-calcium-calmodulin-dependent-kinase-ii-signaling-pathway
#18
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
#19
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/28566627/analysis-of-clinical-efficacy-and-adverse-effects-of-%C3%AE-blocking-agents-used-clinically-for-chronic-heart-failure
#20
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
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