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https://www.readbyqxmd.com/read/28923351/functionally-redundant-control-of-cardiac-hypertrophic-signaling-by-inositol-1-4-5-trisphosphate-receptors
#1
M Iveth Garcia, Anja Karlstaedt, Jessica J Chen, Javier Amione-Guerra, Keith A Youker, Heinrich Taegtmeyer, Darren Boehning
Calcium plays an integral role to many cellular processes including contraction, energy metabolism, gene expression, and cell death. The inositol 1, 4, 5-trisphosphate receptor (IP3R) is a calcium channel expressed in cardiac tissue. There are three IP3R isoforms encoded by separate genes. In the heart, the IP3R-2 isoform is reported to being most predominant with regards to expression levels and functional significance. The functional roles of IP3R-1 and IP3R-3 in the heart are essentially unexplored despite measureable expression levels...
September 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28919880/non-mammalian-vertebrates-distinct-models-to-assess-the-role-of-ion-gradients-in-energy-expenditure
#2
REVIEW
Caroline E Geisler, Kyle P Kentch, Benjamin J Renquist
Animals store metabolic energy as electrochemical gradients. At least 50% of mammalian energy is expended to maintain electrochemical gradients across the inner mitochondrial membrane (H(+)), the sarcoplasmic reticulum (Ca(++)), and the plasma membrane (Na(+)/K(+)). The potential energy of these gradients can be used to perform work (e.g., transport molecules, stimulate contraction, and release hormones) or can be released as heat. Because ectothermic species adapt their body temperature to the environment, they are not constrained by energetic demands that are required to maintain a constant body temperature...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28916620/the-anthracycline-metabolite-doxorubicinol-abolishes-ryr2-sensitivity-to-physiological-changes-in-luminal-ca-2-through-an-interaction-with-calsequestrin
#3
Amy Hanna, Alexander Lam, Chris Thekkedam, Hermia Willemse, Angela Fay Dulhunty, Nicole Beard
The chemotherapeutic anthracycline metabolite doxorubicinol (doxOL) has been shown to interact with and disrupt the function of the cardiac ryanodine receptor Ca2+ release channel (RyR2) in the sarcoplasmic reticulum (SR) membrane and the SR Ca2+ binding protein calsequestrin2 (CSQ2). Normal increases in RyR2 activity in response to increasing diastolic SR [Ca2+] are influenced by CSQ2 and are disrupted in arrhythmic conditions. Therefore we explored the action of doxOL on RyR2's response to changes in luminal [Ca2+] seen during diastole...
September 15, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28913625/calcium-release-dependent-inactivation-precedes-formation-of-the-tubular-system-in-developing-rat-cardiac-myocytes
#4
Katarina Macková, Alexandra Zahradníková, Matej Hoťka, Barbora Hoffmannová, Ivan Zahradník, Alexandra Zahradníková
Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes...
September 14, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28912570/a-focus-on-extracellular-ca-2-entry-into-skeletal-muscle
#5
REVIEW
Chung-Hyun Cho, Jin Seok Woo, Claudio F Perez, Eun Hui Lee
The main task of skeletal muscle is contraction and relaxation for body movement and posture maintenance. During contraction and relaxation, Ca(2+) in the cytosol has a critical role in activating and deactivating a series of contractile proteins. In skeletal muscle, the cytosolic Ca(2+) level is mainly determined by Ca(2+) movements between the cytosol and the sarcoplasmic reticulum. The importance of Ca(2+) entry from extracellular spaces to the cytosol has gained significant attention over the past decade...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28904083/assessing-the-effects-of-mitofusin-2-deficiency-in-the-adult-heart-using-3d-electron-tomography
#6
Siavash Beikoghli Kalkhoran, Andrew R Hall, Ian J White, Jackie Cooper, Qiao Fan, Sang-Bing Ong, Sauri Hernández-Reséndiz, Hector Cabrera-Fuentes, Kroekkiat Chinda, Bibhas Chakraborty, Gerald W Dorn, Derek M Yellon, Derek J Hausenloy
The effects of mitofusin 2 (MFN2) deficiency, on mitochondrial morphology and the mitochondria-junctional sarcoplasmic reticulum (jSR) complex in the adult heart, have been previously investigated using 2D electron microscopy, an approach which is unable to provide a 3D spatial assessment of these imaging parameters. Here, we use 3D electron tomography to show that MFN2-deficient mitochondria are larger in volume, more elongated, and less rounded; have fewer mitochondria-jSR contacts, and an increase in the distance between mitochondria and jSR, when compared to WT mitochondria...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28900933/neurological-and-motor-disorders-trpc-in-the-skeletal-muscle
#7
Sophie Saüc, Maud Frieden
Transient receptor potential canonical (TRPC) channels belong to the large family of TRPs that are mostly nonselective cation channels with a great variety of gating mechanisms. TRPC are composed of seven members that can all be activated downstream of agonist-induced phospholipase C stimulation, but some members are also stretch-activated and/or are part of the store-operated Ca(2+) entry (SOCE) pathway. Skeletal muscles generate contraction via an explosive increase of cytosolic Ca(2+) concentration resulting almost exclusively from sarcoplasmic reticulum Ca(2+) channel opening...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900922/tissue-specificity-the-role-of-organellar-membrane-nanojunctions-in-smooth-muscle-ca-2-signaling
#8
Nicola Fameli, A Mark Evans, Cornelis van Breemen
In this chapter we examine the importance of cytoplasmic nanojunctions-nanometer scale appositions between organellar membranes including the molecular transporters therein-to the cell signaling machinery, with specific reference to Ca(2+) transport and signaling in vascular smooth muscle and endothelial cells. More specifically, we will consider the extent to which quantitative modeling may aid in the development of our understanding of these processes. Testament to the requirement for such approaches lies in the fact that recent studies have provided evermore convincing evidence in support of the view that cytoplasmic nanospaces may be as significant to the process of Ca(2+) signaling as the Ca(2+) transporters, release channels, and Ca(2+)-storing organelles themselves...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28894423/%C3%AE-adrenergic-inhibition-prevents-action-potential-and-calcium-handling-changes-during-regional-myocardial-ischemia
#9
Shannon R Murphy, Lianguo Wang, Zhen Wang, Philip Domondon, Di Lang, Beth A Habecker, Rachel C Myles, Crystal M Ripplinger
β-adrenergic receptor (β-AR) blockers may be administered during acute myocardial infarction (MI), as they reduce energy demand through negative chronotropic and inotropic effects and prevent ischemia-induced arrhythmogenesis. However, the direct effects of β-AR blockers on ventricular electrophysiology and intracellular Ca(2+) handling during ischemia remain unknown. Using optical mapping of transmembrane potential (with RH237) and sarcoplasmic reticulum (SR) Ca(2+) (with the low-affinity indicator Fluo-5N AM), the effects of 15 min of regional ischemia were assessed in isolated rabbit hearts (n = 19)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28889952/ormdl3-upregulates-airway-smooth-muscle-proliferation-contraction-and-ca-2-oscillations-in-asthma
#10
Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael Sanderson, David H Broide
BACKGROUND: Airway hyperresponsiveness (AHR) is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. OBJECTIVE: We investigated whether increased ASM expression of ORMDL3, a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro, as well as influenced airway contractility and calcium flux in ASM in precision cut lung slices from WT and hORMDL3(Zp3-Cre) mice (which express increased levels of human ORMDL3)...
September 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28886186/the-cardiac-calsequestrin-gene-transcription-is-modulated-at-the-promoter-by-nfat-and-mef-2-transcription-factors
#11
Rafael Estrada-Avilés, Gabriela Rodríguez, Angel Zarain-Herzberg
Calsequestrin-2 (CASQ2) is the main Ca2+-binding protein inside the sarcoplasmic reticulum of cardiomyocytes. Previously, we demonstrated that MEF-2 and SRF binding sites within the human CASQ2 gene (hCASQ2) promoter region are functional in neonatal cardiomyocytes. In this work, we investigated if the calcineurin/NFAT pathway regulates hCASQ2 expression in neonatal cardiomyocytes. The inhibition of NFAT dephosphorylation with CsA or INCA-6, reduced both the luciferase activity of hCASQ2 promoter constructs (-3102/+176 bp and -288/+176 bp) and the CASQ2 mRNA levels in neonatal rat cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28883413/the-ca-2-influx-through-the-mammalian-skeletal-muscle-dihydropyridine-receptor-is-irrelevant-for-muscle-performance
#12
Anamika Dayal, Kai Schrötter, Yuan Pan, Karl Föhr, Werner Melzer, Manfred Grabner
Skeletal muscle excitation-contraction (EC) coupling is initiated by sarcolemmal depolarization, which is translated into a conformational change of the dihydropyridine receptor (DHPR), which in turn activates sarcoplasmic reticulum (SR) Ca(2+) release to trigger muscle contraction. During EC coupling, the mammalian DHPR embraces functional duality, as voltage sensor and L-type Ca(2+) channel. Although its unique role as voltage sensor for conformational EC coupling is firmly established, the conventional function as Ca(2+) channel is still enigmatic...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28874726/remarkable-plasticity-of-na-k-atpase-ca-2-atpase-and-serca-contributes-to-muscle-disuse-atrophy-resistance-in-hibernating-daurian-ground-squirrels
#13
Quanling Guo, Xin Mi, Xiaoyong Sun, Xiaoyu Li, Weiwei Fu, Shenhui Xu, Qi Wang, Yasir Arfat, Huiping Wang, Hui Chang, Yunfang Gao
We investigated cytosolic calcium (Ca(2+)) and sarcoplasmic reticulum Ca(2+) regulation in skeletal muscle fibers of hibernating Daurian ground squirrels (Spermophilus dauricus), non-hibernating hindlimb-unloaded (HLU) squirrels, and HLU rats to clarify the molecular mechanisms involved in preventing muscle atrophy in hibernators. The Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the soleus muscle (SOL) of squirrels were maintained in hibernation, decreased during interbout arousal (IB-A), and increased to autumn/pre-hibernation (AUT/Pre-H) levels in torpor after interbout arousal (Post-IBA), whereas activities in the extensor digitorum longus muscle (EDL) were stable during hibernation, but increased during post-hibernation (Post-H)...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872460/deficiency-in-kelch-protein-klhl31-causes-congenital-myopathy-in-mice
#14
James B Papizan, Glynnis A Garry, Svetlana Brezprozvannaya, John R McAnally, Rhonda Bassel-Duby, Ning Liu, Eric N Olson
Maintenance of muscle structure and function depends on the precise organization of contractile proteins into sarcomeres and coupling of the contractile apparatus to the sarcoplasmic reticulum (SR), which serves as the reservoir for calcium required for contraction. Several members of the Kelch superfamily of proteins, which modulate protein stability as substrate-specific adaptors for ubiquitination, have been implicated in sarcomere formation. The Kelch protein Klhl31 is expressed in a muscle-specific manner under control of the transcription factor MEF2...
September 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28870220/the-type-vi-adenylyl-cyclase-protects-cardiomyocytes-from-%C3%AE-adrenergic-stress-by-a-pka-stat3-dependent-pathway
#15
Yu-Shuo Wu, Chien-Chang Chen, Chen-Li Chien, Hsing-Lin Lai, Si-Tse Jiang, Yong-Cyuan Chen, Lin-Ping Lai, Wei-Fan Hsiao, Wen-Pin Chen, Yijuang Chern
BACKGROUND: The type VI adenylyl cyclase (AC6) is a main contributor of cAMP production in the heart. The amino acid (aa) sequence of AC6 is highly homologous to that of another major cardiac adenylyl cyclase, AC5, except for its N-terminus (AC6-N, aa 1-86). Activation of AC6, rather than AC5, produces cardioprotective effects against heart failure, while the underlying mechanism remains to be unveiled. Using an AC6-null (AC6(-/-)) mouse and a knockin mouse with AC6-N deletion (AC6 (ΔN/ΔN)), we aimed to investigate the cardioprotective mechanism of AC6 in the heart...
September 4, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28863192/e2-er-%C3%AE-inhibit-iso-induced-cardiac-cellular-hypertrophy-by-suppressing-ca2-calcineurin-signaling
#16
Cheng-Yen Tsai, Wei-Wen Kuo, Marthandam Asokan Shibu, Yueh-Min Lin, Chien-Nam Liu, Yi-Hui Chen, Cecilia-Hsuan Day, Chia-Yao Shen, Vijaya Padma Viswanadha, Chih-Yang Huang
Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast...
2017: PloS One
https://www.readbyqxmd.com/read/28861149/posttranslational-modifications-of-calcium-calmodulin-dependent-protein-kinase-ii%C3%AE-and-its-downstream-signaling-in-human-failing-hearts
#17
Tomas Rajtik, Eva Goncalvesova, Zoltan V Varga, Przemyslaw Leszek, Mariusz Kusmierczyk, Michal Hulman, Jan Kyselovic, Peter Ferdinandy, Adriana Adameova
BACKGROUND: In human failing hearts (HF) of different origin (coronary artery disease-CAD, dilated-DCM, restrictive and hypertrophic cardiomyopathy-OTHER), we investigated the active forms of Ca(2+)/calmodulin-dependent protein kinase IIδ (p-Thr(287)-CaMKIIδ, oxMet(281/282)-CaMKIIδ) and their role in phenotypes of the disease. METHODS AND RESULTS: Although basic diagnostic and clinical markers indicating the attenuated cardiac contractility and remodeling were comparable in HF groups, CaMKIIδ-mediated axis was different...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28859968/dipeptidyl-peptidase-4-independent-cardiac-dysfunction-links-saxagliptin-to-heart-failure
#18
Chintan N Koyani, Ewald Kolesnik, Gerald Wölkart, Niroj Shrestha, Susanne Scheruebel, Christopher Trummer, Klaus Zorn-Pauly, Astrid Hammer, Petra Lang, Helga Reicher, Heinrich Maechler, Klaus Groschner, Bernd Mayer, Peter P Rainer, Harald Sourij, Wolfgang Sattler, Ernst Malle, Brigitte Pelzmann, Dirk von Lewinski
Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca(2+)/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca(2+)-ATPase 2a axis and Na(+)-Ca(2+) exchanger function in Ca(2+) extrusion...
August 30, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28859079/a-computational-model-of-spatio-temporal-cardiac-intracellular-calcium-handling-with-realistic-structure-and-spatial-flux-distribution-from-sarcoplasmic-reticulum-and-t-tubule-reconstructions
#19
Michael A Colman, Christian Pinali, Andrew W Trafford, Henggui Zhang, Ashraf Kitmitto
Intracellular calcium cycling is a vital component of cardiac excitation-contraction coupling. The key structures responsible for controlling calcium dynamics are the cell membrane (comprising the surface sarcolemma and transverse-tubules), the intracellular calcium store (the sarcoplasmic reticulum), and the co-localisation of these two structures to form dyads within which calcium-induced-calcium-release occurs. The organisation of these structures tightly controls intracellular calcium dynamics. In this study, we present a computational model of intracellular calcium cycling in three-dimensions (3-D), which incorporates high resolution reconstructions of these key regulatory structures, attained through imaging of tissue taken from the sheep left ventricle using serial block face scanning electron microscopy...
August 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28858645/simulation-study-of-the-ionic-mechanisms-underlying-torsade-de-pointes-in-a-2d-cardiac-tissue
#20
Ponnuraj Kirthi Priya, M Ramasubba Reddy
BACKGROUND: To understand the ionic mechanism behind the genesis of Torsade de Pointes (TdP) occurring with long QT syndrome 2 (LQTS2) in a remodelled transmural tissue. METHODS: The TP06 model is used to simulate the electrical activity of cells in a 2D transmural ventricular model. LQTS2 is realised by reducing the potassium current (IKr) to 0.5 in each cell. Each cell of the tissue is remodelled by increasing the conductance of calcium current (GCaL). The above two factors make the cells prone to early after depolarizations (EADs) development...
August 24, 2017: Computers in Biology and Medicine
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