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https://www.readbyqxmd.com/read/28028837/a-novel-mechanism-of-tandem-activation-of-ryanodine-receptors-by-cytosolic-and-sr-luminal-ca-during-excitation-contraction-coupling-in-atrial-myocytes
#1
Joshua T Maxwell, Lothar A Blatter
In atrial myocytes Ca release during excitation-contraction coupling (ECC) is strikingly different from ventricular myocytes. In many species atrial myocytes lack a transverse tubule system, dividing the sarcoplasmic reticulum (SR) Ca store into the peripheral subsarcolemmnal junctional (j-SR) and the much more abundant central non-junctional (nj-SR) SR. Action potential (AP)-induced Ca entry activates Ca-induced Ca release (CICR) from j-SR ryanodine receptor (RyR) Ca release channels. Peripheral elevation of [Ca]i initiates CICR from nj-SR and sustains propagation of CICR to the cell centre...
December 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27994552/exercise-training-attenuates-right-ventricular-remodeling-in-rats-with-pulmonary-arterial-stenosis
#2
Brunno Lemes de Melo, Stella S Vieira, Ednei L Antônio, Luís F N Dos Santos, Leslie A Portes, Regiane S Feliciano, Helenita A de Oliveira, José A Silva, Paulo de Tarso C de Carvalho, Paulo J F Tucci, Andrey J Serra
Introduction: Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27992670/dissection-of-the-effects-of-quercetin-on-mouse-myocardium
#3
Michel Santana Santos, Evaleide Diniz de Oliveira, Artur Santos-Miranda, Jader Santos Cruz, Antônio Nei Santana Gondim, José Evaldo Rodrigues de Menezes-Filho, Diego Santos de Souza, Leidiane Pinho-da-Silva, Itamar Couto Guedes de Jesus, Danilo Roman-Campos, Silvia Guatimosim, Aline Lara, Eduardo Antônio Conde-Garcia, Carla Maria Lins de Vasconcelos
Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased ICa,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V0...
December 19, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27991906/hepatic-stimulator-substance-inhibits-calcium-overflow-through-the-mitochondria-associated-membrane-compartment-during-nonalcoholic-steatohepatitis
#4
Fan Xiao, Jing Zhang, Can Zhang, Wei An
Nonalcoholic fatty liver disease is considered a disorder of the endoplasmic reticulum (ER) and mitochondria. Recent studies have shown that the ER and mitochondrial membranes overlap by 15-20%, a region referred to as the 'mitochondria-associated ER membrane' (MAM). Some proteins, including sarco/ER calcium ATPase (SERCA), are located in the MAM and have an important role in Ca(2+) signaling and homeostasis between the ER and the mitochondria. Our previous study showed that hepatic stimulator substance (HSS) inhibits the ER stress induced by reactive oxygen species, thus reducing mitochondrial damage...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27979982/role-of-calpain-in-eccentric-contraction-induced-proteolysis-of-ca2-regulatory-proteins-and-force-depression-in-rat-fast-twitch-skeletal-muscle
#5
Keita Kanzaki, Daiki Watanabe, Mai Kuratani, Takashi Yamada, Satoshi Matsunaga, Masanobu Wada
The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca(2+)-regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200-repeated ECC in situ and excised immediately (recovery 0) or 3 days (recovery 3) after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during 3 days of recovery. Tetanic force was markedly reduced at recovery 0 and remained reduced at recovery 3...
December 15, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27939335/calcium-signalling-induced-by-in-vitro-exposure-to-silicium-dioxide-nanoparticles-in-rat-pulmonary-artery-smooth-muscle-cells
#6
Virginie Dubes, Thibaud Parpaite, Thomas Ducret, Jean-François Quignard, Stéphane Mornet, Nora Reinhardt, Isabelle Baudrimont, Mathilde Dubois, Véronique Freund-Michel, Roger Marthan, Bernard Muller, Jean-Pierre Savineau, Arnaud Courtois
The development and use of nanomaterials, especially engineered nanoparticles (NP), is expected to provide many benefits. But at the same time the development of such materials is also feared because of their potential human health risks. Indeed, NP display some characteristics similar to ultrafine environmental particles which are known to exert deleterious cardiovascular effects including pro-hypertensive ones. In this context, the effect of NP on calcium signalling, whose deregulation is often involved in hypertensive diseases, remain poorly described...
January 15, 2017: Toxicology
https://www.readbyqxmd.com/read/27923914/widespread-control-of-calcium-signaling-by-a-family-of-serca-inhibiting-micropeptides
#7
Douglas M Anderson, Catherine A Makarewich, Kelly M Anderson, John M Shelton, Svetlana Bezprozvannaya, Rhonda Bassel-Duby, Eric N Olson
Micropeptides function as master regulators of calcium-dependent signaling in muscle. Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), the membrane pump that promotes muscle relaxation by taking up Ca(2+) into the sarcoplasmic reticulum, is directly inhibited by three muscle-specific micropeptides: myoregulin (MLN), phospholamban (PLN), and sarcolipin (SLN). The widespread and essential function of SERCA across diverse cell types has raised questions as to how SERCA is regulated in cells that lack MLN, PLN, and SLN...
December 6, 2016: Science Signaling
https://www.readbyqxmd.com/read/27914790/sarcoplasmic-reticulum-ca-2-mg-2-k-and-cl-concentrations-adjust-quickly-as-heart-rate-changes
#8
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
#9
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/27872020/niclosamide-ethanolamine-inhibits-artery-constriction
#10
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...
January 2017: 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
#11
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...
December 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
#12
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/27815070/direct-detection-of-serca-calcium-transport-and-small-molecule-inhibition-in-giant-unilamellar-vesicles
#13
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
#14
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/27776889/a-new-target-for-parkinson-s-disease-small-molecule-serca-activator-cdn1163-ameliorates-dyskinesia-in-6-ohda-lesioned-rats
#15
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...
January 1, 2017: Bioorganic & Medicinal Chemistry
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
#16
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
#17
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/27731980/sarcolipin-promotes-uncoupling-of-the-serca-ca-2-pump-by-inducing-a-structural-rearrangement-in-the-energy-transduction-domain
#18
Joseph M Autry, David D Thomas, L Michel Espinoza-Fonseca
We have performed microsecond (μs) molecular dynamics simulation (MDS) to identify structural mechanisms for sarcolipin (SLN) uncoupling of Ca(2+) transport from ATP hydrolysis for the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). SLN regulates muscle metabolism and energy expenditure to provide resistance against diet-induced obesity and extreme cold. MDS demonstrated that the cytosolic domain of SLN induces a salt bridge-mediated structural rearrangement in the energy-transduction domain of SERCA. We propose that this structural change uncouples SERCA by perturbing Ca(2+) occlusion at residue E309 in transport site II, thus facilitating Ca(2+) backflux to the cytosol...
November 8, 2016: Biochemistry
https://www.readbyqxmd.com/read/27729868/the-autonomic-nervous-system-regulates-the-heart-rate-through-camp-pka-dependent-and-independent-coupled-clock-pacemaker-cell-mechanisms
#19
Joachim Behar, Ambhighainath Ganesan, Jin Zhang, Yael Yaniv
Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation)...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27694578/redox-assisted-regulation-of-ca2-homeostasis-in-the-endoplasmic-reticulum-by-disulfide-reductase-erdj5
#20
Ryo Ushioda, Akitoshi Miyamoto, Michio Inoue, Satoshi Watanabe, Masaki Okumura, Ken-Ichi Maegawa, Kaiku Uegaki, Shohei Fujii, Yasuko Fukuda, Masataka Umitsu, Junichi Takagi, Kenji Inaba, Katsuhiko Mikoshiba, Kazuhiro Nagata
Calcium ion (Ca(2+)) is an important second messenger that regulates numerous cellular functions. Intracellular Ca(2+) concentration ([Ca(2+)]i) is strictly controlled by Ca(2+) channels and pumps on the endoplasmic reticulum (ER) and plasma membranes. The ER calcium pump, sarco/endoplasmic reticulum calcium ATPase (SERCA), imports Ca(2+) from the cytosol into the ER in an ATPase activity-dependent manner. The activity of SERCA2b, the ubiquitous isoform of SERCA, is negatively regulated by disulfide bond formation between two luminal cysteines...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
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