Read by QxMD icon Read

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

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: Here, we investigated 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. RESULTS: TAC operation for 8 weeks produced a significant increase in the left ventricular end-diastolic diameter, and frequent occurrence of lethal arrhythmias after infusion of epinephrine and caffeine in TAC mice...
October 19, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Naokata Sumitomo
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by emotions or exercise in patients without organic heart disease and may be polymorphic or bidirectional in nature. The prognosis of CPVT is not good, and therefore prevention of sudden death is of utmost importance. Genetic variants of CPVT include RyR2, CASQ2, CALM2, TRD, and possibly KCNJ2 and ANK2 gene mutations. Hypotheses that suggest the causes of CPVT include weakened binding of FKBP12.6 and RyR2, a store overload-induced Ca(2+) release (SOICR), unzipping of intramolecular domain interactions in RyR2, and molecular and functional abnormalities caused by mutations in the CASQ2 gene...
October 2016: Journal of Arrhythmia
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
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...
October 8, 2016: International Journal of Cardiology
Steven Hunt, Paul Hopkins, Nazeem Nanjee, Karen Schwander, Donald Kohan, D C Rao, Gordon Williams
OBJECTIVE: Identify the earliest hormonal, electrolyte and gene expression responses to a saline infusion before compensatory mechanisms are activated and relate these responses to delayed sodium excretion. DESIGN AND METHOD: 233 normotensive subjects with a strong positive family history of hypertension, ages 21-65, were studied on a low sodium diet before, during and after a 2-hour, 2-liter saline infusion. Plasma and urine hormones of the renin-angiotensin-aldosterone, catecholamine, uric acid, kallikrein, and cortisol pathways, microalbumin, and urine and plasma electrolytes were measured...
September 2016: Journal of Hypertension
Przemysław B Radwański, Hsiang-Ting Ho, Rengasayee Veeraraghavan, Lucia Brunello, Bin Liu, Andriy E Belevych, Sathya D Unudurthi, Michael A Makara, Silvia G Priori, Pompeo Volpe, Antonis A Armoundas, Wolfgang H Dillmann, Bjorn C Knollmann, Peter J Mohler, Thomas J Hund, Sándor Györke
BACKGROUND: Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca(2+) and Na(+) handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive. METHODS AND RESULTS: We performed functional and structural studies to assess Ca(2+) and Na(+) signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT...
June 2016: JACC. Basic to Translational Science
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
Yong Xie, Zhen-Jie Gu, Mao-Xiong Wu, Tu-Cheng Huang, Jing-Song Ou, Huiping-Son Ni, Mao-Huan Lin, Wo-Liang Yuan, Jing-Feng Wang, Yang-Xin Chen
AIMS: Adverse cardiovascular effects induced by peroxisome proliferator activator receptor-γ (PPAR-γ) activation were observed in clinical setting. But the underlying mechanism is unclear. Now, transgenic mice with cardiac specific peroxisome proliferator activator receptor-γ overexpression (TG-PPAR-γ) were used to explore the possible mechanisms. MATERIALS AND METHODS: Cardiac tissues from TG-PPAR-γ mice, a PPAR-γ over-expressing human cardiomyocyte line AC16 cell, and PPAR-γ agonist-treated primary cardiomyocytes were used to evaluate the expression of cardiac calcium regulatory proteins as sarcoplasmic reticulum Ca(2+) ATPase, Na(+)/Ca(2+)exchanger 1, ryanodine receptor 2 and phospholamban...
October 13, 2016: Life Sciences
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
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUNDS: -Tissue engineering enables the generation of functional human cardiac tissue using cells derived in vitro in combination with biocompatible materials. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electrical pacing on the maturation of hiPSC-derived cardiac tissues. METHODSS: -Cardiomyocytes derived from hiPSCs were used to generate collagen-based bioengineered human cardiac tissue...
October 13, 2016: Circulation
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
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...
October 12, 2016: Journal of Biological Chemistry
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
Donald M Bers
No abstract text is available yet for this article.
October 7, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Wei Peng, Huaizong Shen, Jianping Wu, Wenting Guo, Xiaojing Pan, Ruiwu Wang, S R Wayne Chen, Nieng Yan
RyR2 is a high-conductance intracellular 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 breathing motion of the overall cytoplasmic region resulted from the interdomain movements of amino-terminal domains (NTDs), Helical domains, and Handle domains, whereas little intradomain shifts are observed in these armadillo repeats-containing domains...
September 22, 2016: Science
Saptarshi Mukherjee, N Lowri Thomas, Alan J Williams
The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel's selectivity filter and its ability to alter gating, with most studies involving prokaryotic K(+) channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K(+) channels makes unambiguous interpretation of data from single channel recordings difficult...
October 5, 2016: Scientific Reports
Hanting Yang, Miaohui Hu, Jianli Guo, Xiaomin Ou, Tanxi Cai, Zhenfeng Liu
Intracellular Ca(2+) signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca(2+) from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca(2+) through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen...
October 3, 2016: Nature
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: -Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: -We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: -Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban (PLN), calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM compared to controls...
September 29, 2016: Circulation
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
James Bailey, Ross P Berkeley
A 13-year-old girl had a witnessed loss of consciousness after a scuffle with another student at school and was found in ventricular fibrillation at the time of arrival of emergency medical services personnel. The patient was successfully defibrillated in the field and was transported to the emergency department as a presumed "traumatic arrest". The patient's initial electrocardiogram was remarkable for a prolonged QT interval, and it was discovered that multiple family members had died of cardiac events as young adults...
September 23, 2016: Pediatric Emergency Care
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"