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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/27899691/high-throughput-spectral-and-lifetime-based-fret-screening-in-living-cells-to-identify-small-molecule-effectors-of-serca
#2
Tory M Schaaf, Kurt C Peterson, Benjamin D Grant, Prachi Bawaskar, Samantha Yuen, Ji Li, Joseph M Muretta, Gregory D Gillispie, David D Thomas
A robust high-throughput screening (HTS) strategy has been developed to discover small-molecule effectors targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA), based on a fluorescence microplate reader that records both the nanosecond decay waveform (lifetime mode) and the complete emission spectrum (spectral mode), with high precision and speed. This spectral unmixing plate reader (SUPR) was used to screen libraries of small molecules with a fluorescence resonance energy transfer (FRET) biosensor expressed in living cells...
November 29, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#3
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27872214/effects-of-prolonged-anoxia-on-electrical-activity-of-the-heart-in-crucian-carp-carassius-carassius
#4
Elisa Tikkanen, Jaakko Haverinen, Stuart Egginton, Minna Hassinen, Matti Vornanen
The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant Crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 to 4.1±0.29 bpm (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored...
November 21, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27872020/niclosamide-ethanolamine-inhibits-artery-constriction
#5
Shan-Liang Li, Jie Yan, Yan-Qiu Zhang, Chang-Lin Zhen, Ming-Yu Liu, Jing Jin, Jin-Lai Gao, Xiao-Lin Xiao, Xin Shen, Yu Tai, Nan Hu, Xin-Zi Zhang, Zhi-Jie Sun, De-Li Dong
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system...
November 18, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27862060/effect-of-bafilomycin-and-naadp-on-membrane-associated-atpases-and-respiration-of-isolated-mitochondria-of-the-murine-nemeth-kellner-lymphoma
#6
V Hreniukh, S Bychkova, O Kulachkovsky, A Babsky
: The goal of the study was to estimate the effect of a selective V-type H(+) -ATPase inhibitor bafilomycin A1 and nicotinic acid adenine dinucleotide phosphate (NAADP) on energetic processes in NK/Ly cell by directly measuring the respiration of isolated mitochondria and ATPase activities. NAADP (7 μM) increased the activity of Na(+) /K(+) -ATPase in the postmitochondrial fraction of NK/Ly cells, but lower concentration of NAADP decreased it (0.1 and 1 μM). The increase the activity of plasma membrane Ca(2)(+) ATPase (PMCA) under NAADP application (1 and 7 μM) was observed...
November 8, 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27861123/tecrl-a-new-life-threatening-inherited-arrhythmia-gene-associated-with-overlapping-clinical-features-of-both-lqts-and-cpvt
#7
Harsha D Devalla, Roselle Gélinas, Elhadi H Aburawi, Abdelaziz Beqqali, Philippe Goyette, Christian Freund, Marie-A Chaix, Rafik Tadros, Hui Jiang, Antony Le Béchec, Jantine J Monshouwer-Kloots, Tom Zwetsloot, Georgios Kosmidis, Frédéric Latour, Azadeh Alikashani, Maaike Hoekstra, Jurg Schlaepfer, Christine L Mummery, Brian Stevenson, Zoltan Kutalik, Antoine Af de Vries, Léna Rivard, Arthur Am Wilde, Mario Talajic, Arie O Verkerk, Lihadh Al-Gazali, John D Rioux, Zahurul A Bhuiyan, Robert Passier
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation...
December 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27856713/effect-of-increased-and-maintained-frequency-of-speed-endurance-training-on-performance-and-muscle-adaptations-in-runners
#8
Casper Skovgaard, Nicki Winfield Almquist, Jens Bangsbo
The aim of the study was, in runners accustomed to speed endurance training (SET), to examine the effect of increased and maintained frequency of SET on performance and muscular adaptations. After familiarization (FAM) to SET, eighteen male (n=14) and female (n=4) runners (VO2-max: 57.3±3.4 ml·min(-1); mean±SD) completed twenty sessions of maintained low-frequency (LF; every fourth day; n=7) or high-frequency (HF; every second day; n=11) SET (intervention period; INT). Before FAM as well as before and after INT, subjects completed a series of running tests and a biopsy from m...
November 17, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27856611/loss-of-akap150-promotes-pathological-remodelling-and-heart-failure-propensity-by-disrupting-calcium-cycling-and-contractile-reserve
#9
Lei Li, Jing Li, Benjamin M Drum, Yi Chen, Haifeng Yin, Xiaoyun Guo, Stephen W Luckey, Merle L Gilbert, G Stanley McKnight, John D Scott, L Fernando Santana, Qinghang Liu
AIMS: Impaired Ca(2 + )cycling and myocyte contractility are a hallmark of heart failure triggered by pathological stress such as hemodynamic overload. The A-Kinase anchoring protein AKAP150 has been shown to coordinate key aspects of adrenergic regulation of Ca(2+ )cycling and excitation-contraction in cardiomyocytes. However, the role of the AKAP150 signalling complexes in the pathogenesis of heart failure has not been investigated. METHODS AND RESULTS: Here we examined how AKAP150 signalling complexes impact Ca(2+ )cycling, myocyte contractility, and heart failure susceptibility following pathological stress...
November 17, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27853260/the-synthetic-antimicrobial-peptide-19-2-5-attenuates-septic-cardiomyopathy-and-prevents-down-regulation-of-serca2-in-polymicrobial-sepsis
#10
Lukas Martin, Klemens Horst, Fausto Chiazza, Silvia Oggero, Massimo Collino, Klaus Brandenburg, Frank Hildebrand, Gernot Marx, Christoph Thiemermann, Tobias Schuerholz
An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca(2+)-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves outcome in sepsis. Thus, we investigated whether the administration of the synthetic antimicrobial peptide Pep2.5 may attenuate the cardiac dysfunction in murine polymicrobial sepsis through regulating SERCA2 expression...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816525/enhanced-nucleoplasmic-ca-2-signaling-in-ventricular-myocytes-from-young-hypertensive-rats
#11
Jelena Plačkić, Sebastian Preissl, Yulia Nikonova, Florentina Pluteanu, Lutz Hein, Jens Kockskämper
Arterial hypertension causes left ventricular (LV) myocyte hypertrophy. Alterations in nuclear Ca(2+) may be involved in regulation of histone acetylation, transcription and hypertrophy. Regulation of nuclear Ca(2+) in hypertension, however, is unknown. Therefore, we elucidated cellular mechanisms underlying nuclear Ca(2+) regulation in LV myocytes from hypertensive versus normotensive rats and evaluated possible consequences for Ca(2+)-dependent regulation of histone acetylation. LV myocytes and myocyte nuclei were isolated from young spontaneously hypertensive rats (SHR) shortly after development of hypertension...
November 3, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27815070/direct-detection-of-serca-calcium-transport-and-small-molecule-inhibition-in-giant-unilamellar-vesicles
#12
Tengfei Bian, Joseph M Autry, Denise Casemore, Ji Li, David D Thomas, Gaohong He, Chengguo Xing
We have developed a charge-mediated fusion method to reconstitute the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) in giant unilamellar vesicles (GUV). Intracellular Ca(2+) transport by SERCA controls key processes in human cells such as proliferation, signaling, and contraction. Small-molecule effectors of SERCA are urgently needed as therapeutics for Ca(2+) dysregulation in human diseases including cancer, diabetes, and heart failure. Here we report the development of a method for efficiently reconstituting SERCA in GUV, and we describe a streamlined protocol based on optimized parameters (e...
December 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27802489/prolongation-of-relaxation-time-in-extraocular-muscles-with-brain-derived-neurotrophic-factor-in-adult-rabbit
#13
Krysta R Nelson, Shanlee M Stevens, Linda K McLoon
Purpose: We tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM). Methods: One week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27792751/a-decoy-peptide-targeted-to-protein-phosphatase-1-attenuates-degradation-of-serca2a-in-vascular-smooth-muscle-cells
#14
Seung Pil Jang, Jae Gyun Oh, Dong Hoon Kang, Ju Young Kang, Sang Won Kang, Roger J Hajjar, Woo Jin Park
Neointimal growth in the injured vasculature is largely facilitated by the proliferation of vascular smooth muscle cells (VSMC), which associates with reduced sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. The gene transfer-mediated restoration of the SERCA2a level thus attenuates neointimal growth and VSMC proliferation. We previously reported that a peptide targeted to protein phosphatase 1, ψPLB-SE, normalizes SERCA2a activity in cardiomyocytes. In this study, we found that ψPLB-SE attenuated neointimal growth in balloon-injured rat carotid arteries, and the proliferation and migration of VSMC cultured in high-serum media (synthetic conditions)...
2016: PloS One
https://www.readbyqxmd.com/read/27780728/serca2a-was-serotonylated-and-may-regulate-sino-atrial-node-pacemaker-activity
#15
Qingjie Wang, Dong Wang, Gaoliang Yan, Yong Qiao, Ling Sun, Boqian Zhu, Xin Wang, Chengchun Tang
The modulation of sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that is still not completely understood. Recent studies highlighted the importance of protein serotonylation by intracellular 5-HT during varies physiological actions. Nevertheless, the functional role of protein serotonylation in controlling SAN automaticity is largely unexplored. In this study, we screened the cardiomyocytes proteins and found that sarco(endo)plasmic reticulum Ca ATPase type 2a (SERCA2a) can be serotonylated...
October 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27776889/a-new-target-for-parkinson-s-disease-small-molecule-serca-activator-cdn1163-ameliorates-dyskinesia-in-6-ohda-lesioned-rats
#16
Russell Dahl
Endoplasmic reticulum (ER) stress is intimately linked to Parkinson's disease (PD) pathophysiology. Disrupted intracellular calcium homeostasis is a major cause of the ER stress seen in dopaminergic neurons, leading to the cell death and subsequent loss of movement and coordination in patients. Dysfunctional calcium handling proteins play a major role in the promulgation of ER stress in PD. Specifically, compromised sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) has been identified as a major cause of ER stress and neuron loss in PD...
October 12, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27761848/dexamethasone-induced-cardiac-deterioration-is-associated-with-both-calcium-handling-abnormalities-and-calcineurin-signaling-pathway-activation
#17
Fabiana de Salvi Guimarães, Wilson Max Almeida Monteiro de Moraes, Luis Henrique Marchesi Bozi, Pâmela R Souza, Ednei Luiz Antonio, Danilo Sales Bocalini, Paulo José Ferreira Tucci, Daniel Araki Ribeiro, Patricia Chakur Brum, Alessandra Medeiros
Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days...
October 19, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27747855/r%C3%A3-%C3%A5-nice-zale%C3%A5-ne-od-p%C3%A5-ci-w-uk%C3%A5-adzie-%C3%A5-ylnym-serca-potencjalne-wyt%C3%A5-umaczenie-dla-r%C3%A3-%C3%A5-nic-w-odpowiedzi-na-terapi%C3%A4-resynchronizuj%C3%A4-ca
#18
Agnieszka Młynarska, Rafał Młynarski, Krzysztof S Gołba, Maciej Sosnowski
BACKGROUND: We hypothesized that small differences in the anatomy of the coronary venous tree might be one of the factors responsible for the differences in the respond for cardiac resynchronization depending on a patient's gender. METHODS: The cardiac computed tomography scans with retrospective gating were performed on 315 subjects (aged 58.3 ± 11.6; 117 women) according to the clinical criteria. The standard protocol for coronary arteries was used during scanning...
October 17, 2016: Kardiologia Polska
https://www.readbyqxmd.com/read/27747307/neuronal-na-channels-are-integral-components-of-pro-arrhythmic-na-ca-2-signaling-nanodomain-that-promotes-cardiac-arrhythmias-during-%C3%AE-adrenergic-stimulation
#19
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
https://www.readbyqxmd.com/read/27747100/altered-left-ventricular-ion-channel-transcriptome-in-a-high-fat-fed-rat-model-of-obesity-insight-into-obesity-induced-arrhythmogenesis
#20
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
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