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https://www.readbyqxmd.com/read/28522367/qrs-t-wave-and-calcium-alternans-in-a-type-i-diabetic-mouse-model-for-spontaneous-post-myocardial-infarction-ventricular-tachycardia-a-mechanism-for-the-antiarrhythmic-effect-of-statins
#1
Hongwei Jin, Charles M Welzig, Mark Aronovitz, Farzad Noubary, Robert Blanton, Bo Wang, Mohammad Rajab, Alfred Albano, Mark S Link, Sami F Noujaim, Ho-Jin Park, Jonas B Galper
BACKGROUND: The incidence of sudden arrhythmic death is markedly increased in diabetics. OBJECTIVE: Develop a mouse model for Post MI VT in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. METHODS: EKG transmitters were implanted in wild type (WT), placebo and pravastatin treated Type I diabetic Akita mice, MIs induced by coronary ligation, Ca(2+) transients studied by optical mapping, Ca(2+) transients and sparks in left VM (VM) by the Ionoptix system and confocal microscopy...
May 15, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28384221/kchip2-regulates-the-cardiac-ca2-transient-and-myocyte-contractility-by-targeting-ryanodine-receptor-activity
#2
Drew M Nassal, Xiaoping Wan, Haiyan Liu, Kenneth R Laurita, Isabelle Deschênes
Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss...
2017: PloS One
https://www.readbyqxmd.com/read/28332202/calcium-signalling-silencing-in-atrial-fibrillation
#3
Maura Greiser
Subcellular calcium signalling silencing is a novel and distinct cellular and molecular adaptive response to rapid cardiac activation. Calcium signalling silencing develops during short-term sustained rapid atrial activation as seen clinically during paroxysmal atrial fibrillation (AF). It is the first 'anti-arrhythmic' adaptive response in the setting of AF and appears to counteract the maladaptive changes that lead to intracellular Ca(2+) signalling instability and Ca(2+) -based arrhythmogenicity. Calcium signalling silencing results in a failed propagation of the [Ca(2+) ]i signal to the myocyte centre both in patients with AF and in a rabbit model...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28329187/bumped-kinase-inhibitors-for-therapy-of-cryptosporidiosis
#4
Matthew A Hulverson, Sumiti Vinayak, Ryan Choi, Deborah A Schaefer, Alejandro Castellanos-Gonzalez, Rama S R Vidadala, Carrie F Brooks, Gillian T Herbert, Dana P Betzer, Grant R Whitman, Hayley N Sparks, Samuel L M Arnold, Kasey L Rivas, Lynn K Barrett, A Clinton White, Maly Dustin J, Michael W Riggs, Boris Striepen, Wesley C Van Voorhis, Kayode K Ojo
Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) are leading candidates for treatment of cryptosporidiosis diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity of the first generation anti-Cryptosporidium BKIs triggered further testing for efficacy. A luminescence assay adapted for high-throughput screening was used to measure inhibitory activities of BKIs on in vitro C. parvum. Furthermore, neonatal and interferon-γ knockout mouse models of C...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28279675/synchronism-in-mitochondrial-ros-flashes-membrane-depolarization-and-calcium-sparks-in-human-carcinoma-cells
#5
Andrey V Kuznetsov, Sabzali Javadov, Valdur Saks, Raimund Margreiter, Michael Grimm
Mitochondria are major producers of reactive oxygen species (ROS) in many cells including cancer cells. However, complex interrelationships between mitochondrial ROS (mitoROS), mitochondrial membrane potential (ΔΨm) and Ca(2+) are not completely understood. Using human carcinoma cells, we further highlight biphasic ROS dynamics: - gradual mitoROS increase followed by mitoROS flash. Also, we demonstrate heterogeneity in rates of mitoROS generation and flash initiation time. Comparing mitochondrial and near-extra-mitochondrial signals, we show that mechanisms of mitoROS flashes in single mitochondria, linked to mitochondrial permeability transition pore opening (ΔΨm collapse) and calcium sparks, may involve flash triggering by certain levels of external ROS released from the same mitochondria...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28209766/glycosylated-chromogranin-a-in-heart-failure-implications-for-processing-and-cardiomyocyte-calcium-homeostasis
#6
Anett Hellebø Ottesen, Cathrine R Carlson, William E Louch, Mai Britt Dahl, Ragnhild A Sandbu, Rune Forstrøm Johansen, Hilde Jarstadmarken, Magnar Bjørås, Arne Didrik Høiseth, Jon Brynildsen, Ivar Sjaastad, Mats Stridsberg, Torbjørn Omland, Geir Christensen, Helge Røsjø
BACKGROUND: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function. METHODS AND RESULTS: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands...
February 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28169003/increased-calcium-leak-associated-with-reduced-calsequestrin-expression-in-hyperthyroid-cardiomyocytes
#7
David R de Alba-Aguayo, Natalia Pavón, Martha Mercado-Morales, Miyamin Miranda-Saturnino, Mavil López-Casamichana, Agustin Guerrero-Hernández, Angelica Rueda
INTRODUCTION: Calcium (Ca(2+)) leak during cardiac diastole is chiefly mediated by intracellular Ca(2+) channel/Ryanodine Receptors. Increased diastolic Ca(2+) leak has been proposed as the mechanism underlying the appearance of hereditary arrhythmias. However, little is known about alterations in diastolic Ca(2+) leak and the specific roles played by key intracellular Ca(2+)-handling proteins in hyperthyroidism, a known arrhythmogenic condition. AIM: We sought to determine whether there were modifications in diastolic Ca(2+) leak, based on the recording of Ca(2+) sparks and Ca(2+) waves; we also investigated changes in the expression and activity of key Ca(2+) handling proteins, including ryanodine receptors, Sarco-Endoplasmic Reticulum Ca(2+) ATPase pump and calsequestrin in isolated left-ventricular cardiomyocytes isolated from hyperthyroid rats...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/27992670/dissection-of-the-effects-of-quercetin-on-mouse-myocardium
#8
Michel Santana Santos, Evaleide Diniz Oliveira, Artur Santos-Miranda, Jader Santos Cruz, Antônio Nei Santana Gondim, José Evaldo Rodrigues Menezes-Filho, Diego Santos Souza, Leidiane Pinho-da-Silva, Itamar Couto Guedes Jesus, Danilo Roman-Campos, Silvia Guatimosim, Aline Lara, Eduardo Antônio Conde-Garcia, Carla Maria Lins 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...
June 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27959915/numerical-approach-to-spatial-deterministic-stochastic-models-arising-in-cell-biology
#9
James C Schaff, Fei Gao, Ye Li, Igor L Novak, Boris M Slepchenko
Hybrid deterministic-stochastic methods provide an efficient alternative to a fully stochastic treatment of models which include components with disparate levels of stochasticity. However, general-purpose hybrid solvers for spatially resolved simulations of reaction-diffusion systems are not widely available. Here we describe fundamentals of a general-purpose spatial hybrid method. The method generates realizations of a spatially inhomogeneous hybrid system by appropriately integrating capabilities of a deterministic partial differential equation solver with a popular particle-based stochastic simulator, Smoldyn...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27882934/macrophage-dependent-il-1%C3%AE-production-induces-cardiac-arrhythmias-in-diabetic-mice
#10
Gustavo Monnerat, Micaela L Alarcón, Luiz R Vasconcellos, Camila Hochman-Mendez, Guilherme Brasil, Rosana A Bassani, Oscar Casis, Daniela Malan, Leonardo H Travassos, Marisa Sepúlveda, Juan Ignacio Burgos, Martin Vila-Petroff, Fabiano F Dutra, Marcelo T Bozza, Claudia N Paiva, Adriana Bastos Carvalho, Adriana Bonomo, Bernd K Fleischmann, Antonio Carlos Campos de Carvalho, Emiliano Medei
Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27815365/xanthohumol-modulates-calcium-signaling-in-rat-ventricular-myocytes-possible-antiarrhythmic-properties
#11
Juan Jose Arnaiz-Cot, Lars Cleemann, Martin Morad
Cardiac arrhythmia is a major cause of mortality in cardiovascular pathologies. A host of drugs targeted to sarcolemmal Na(+), Ca(2+), and K(+) channels has had limited success clinically. Recently, Ca(2+) signaling has been target of pharmacotherapy based on finding that leaky ryanodine receptors elevate local Ca(2+) concentrations causing membrane depolarizations that trigger arrhythmias. In this study, we report that xanthohumol, an antioxidant extracted from hops showing therapeutic effects in other pathologies, suppresses aberrant ryanodine receptor Ca(2+) release...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27802169/junctophilin-2-in-the-nanoscale-organisation-and-functional-signalling-of-ryanodine-receptor-clusters-in-cardiomyocytes
#12
Michelle L Munro, Isuru D Jayasinghe, Qiongling Wang, Ann Quick, Wei Wang, David Baddeley, Xander H T Wehrens, Christian Soeller
Signalling nanodomains requiring close contact between the plasma membrane and internal compartments, known as 'junctions', are fast communication hubs within excitable cells such as neurones and muscle. Here, we have examined two transgenic murine models probing the role of junctophilin-2, a membrane-tethering protein crucial for the formation and molecular organisation of sub-microscopic junctions in ventricular muscle cells of the heart. Quantitative single-molecule localisation microscopy showed that junctions in animals producing above-normal levels of junctophilin-2 were enlarged, allowing the re-organisation of the primary functional protein within it, the ryanodine receptor (RyR; in this paper, we use RyR to refer to the myocardial isoform RyR2)...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27762397/a-unified-theory-of-calcium-alternans-in-ventricular-myocytes
#13
Zhilin Qu, Michael B Liu, Michael Nivala
Intracellular calcium (Ca(2+)) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca(2+) cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca(2+) alternans. Two mechanisms of Ca(2+) alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca(2+) release and uptake, and the other on refractoriness and other properties of Ca(2+) sparks...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27738055/a-novel-calcium-dependent-kinase-inhibitor-bumped-kinase-inhibitor-1517-cures-cryptosporidiosis-in-immunosuppressed-mice
#14
Alejandro Castellanos-Gonzalez, Hayley Sparks, Samantha Nava, Wenlin Huang, Zhongsheng Zhang, Kasey Rivas, Matthew A Hulverson, Lynn K Barrett, Kayode K Ojo, Erkang Fan, Wesley C Van Voorhis, Arthur Clinton White
Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium-dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKIs) that selectively target CDPK1...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27729468/speg-striated-muscle-preferentially-expressed-protein-kinase-is-essential-for-cardiac-function-by-regulating-junctional-membrane-complex-activity
#15
Ann P Quick, Qiongling Wang, Leonne E Philippen, Giselle Barreto-Torres, David Y Chiang, David Beavers, Guoliang Wang, Maha Khalid, Julia O Reynolds, Hannah M Campbell, Jordan Showell, Mark D McCauley, Arjen Scholten, Xander H T Wehrens
RATIONALE: Junctional membrane complexes (JMCs) 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 SPEG (striated muscle preferentially expressed protein kinase) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. METHODS AND RESULTS: Proteomic analysis of immunoprecipitated JMC proteins ryanodine receptor type 2 and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/27711080/adeno-associated-virus-mediated-casq2-delivery-rescues-phenotypic-alterations-in-a-patient-specific-model-of-recessive-catecholaminergic-polymorphic-ventricular-tachycardia
#16
Francesco Lodola, Diego Morone, Marco Denegri, Rossana Bongianino, Hiroko Nakahama, Lucia Rutigliano, Rosanna Gosetti, Giulia Rizzo, Alessandra Vollero, Michelangelo Buonocore, Carlo Napolitano, Gianluigi Condorelli, Silvia G Priori, Elisa Di Pasquale
Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse model of the disease homozygous carrier of the R33Q mutation. In the present study, we investigated the efficacy of the virally mediated gene therapy in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs) obtained from a patient carrying the homozygous CASQ2-G112+5X mutation...
October 6, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27612843/titanium-dental-implant-surfaces-obtained-by-anodic-spark-deposition-from-the-past-to-the-future
#17
REVIEW
Milena R Kaluđerović, Joachim P Schreckenbach, Hans-Ludwig Graf
Commercial titanium-based dental implants are obtained applying various methods such as machining, acid etching, anodization, plasma spraying, grit blasting or combination techniques yielding materials with smooth or micro-roughened surfaces. Those techniques are used to optimize the surface properties and to maximize biocompatibility and bioactivity with bone tissue. Present review is focused on the material surfaces obtained by anodic spark deposition (ASD). From the early 1980s till present, the results of numerous studies have shown that anodically oxidized surfaces with different dopants express a positive effect on osteoblasts behavior in vitro and osseointegration in vivo...
December 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/27377851/modeling-na-ca-2-exchange-in-the-heart-allosteric-activation-spatial-localization-sparks-and-excitation-contraction-coupling
#18
Lulu Chu, Joseph L Greenstein, Raimond L Winslow
The cardiac sodium (Na(+))/calcium (Ca(2+)) exchanger (NCX1) is an electrogenic membrane transporter that regulates Ca(2+) homeostasis in cardiomyocytes, serving mainly to extrude Ca(2+) during diastole. The direction of Ca(2+) transport reverses at membrane potentials near that of the action potential plateau, generating an influx of Ca(2+) into the cell. Therefore, there has been great interest in the possible roles of NCX1 in cardiac Ca(2+)-induced Ca(2+) release (CICR). Interest has been reinvigorated by a recent super-resolution optical imaging study suggesting that ~18% of NCX1 co-localize with ryanodine receptor (RyR2) clusters, and ~30% of additional NCX1 are localized to within ~120nm of the nearest RyR2...
July 1, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27368417/a-novel-mouse-model-of-the-aged-brain-over-expression-of-the-l-type-voltage-gated-calcium-channel-cav1-3
#19
Jamie N Krueger, Shannon J Moore, Rachel Parent, Brandon C McKinney, Amy Lee, Geoffrey G Murphy
The aged population is growing rapidly, which has sparked tremendous interest in elucidating mechanisms of aging in both the body and the brain. Animal models have become an indispensable tool in biomedical science, but because of the cost and extended timeframe associated with aging animals to appropriate time points, studies that rely on using aged animals are often not feasible. Somewhat surprisingly, there are relatively few animal models that have been specifically engineered to mimic physiological changes known to occur during "normal" aging...
March 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27347901/role-of-mitochondria-in-cerebral-vascular-function-energy-production-cellular-protection-and-regulation-of-vascular-tone
#20
David W Busija, Ibolya Rutkai, Somhrita Dutta, Prasad V Katakam
Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms...
2016: Comprehensive Physiology
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