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https://www.readbyqxmd.com/read/28731505/calcium-calmodulin-dependent-kinase-2-camkii-mediates-epac-induced-spontaneous-transient-outward-currents-stocs-in-rat-vascular-smooth-muscle
#1
Edward S A Humphries, Tomoko Kamishima, John M Quayle, Caroline Dart
Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)-sensitive release channels on the peripheral sarcoplasmic reticulum. Resultant Ca(2+) sparks activate plasma membrane Ca(2+) -activated K(+) (BKCa ) channels, evoking spontaneous transient outward currents (STOCs) that hyperpolarize the cell and reduce voltage-dependent Ca(2+) entry. In this study we investigate the mechanism by which Epac increases STOC activity...
July 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28731153/altered-profile-of-mrna-expression-in-atrioventricular-node-of-streptozotocin%C3%A2-induced-diabetic-rats
#2
Frank Christopher Howarth, Khatija Parekh, Petrilla Jayaprakash, Edward Samuel Inbaraj, Murat Oz, Halina Dobrzynski, Thomas Edward Adrian
Prolonged action potential duration, reduced action potential firing rate, upstroke velocity and rate of diastolic depolarization have been demonstrated in atrioventricular node (AVN) cells from streptozotocin (STZ)‑induced diabetic rats. To further clarify the molecular basis of these electrical disturbances, the mRNA profiles encoding a variety of proteins associated with the generation and conduction of electrical activity in the AVN, were evaluated in the STZ‑induced diabetic rat heart. Expression of mRNA was measured in AVN biopsies using reverse transcription‑quantitative polymerase chain reaction techniques...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28727921/effect-of-lysophosphatidylglycerol-on-intracellular-free-ca2-concentration-in-a10-vascular-smooth-muscle-cells
#3
Ying Zhang, Jing-Dian Zhang, Ming-Qin Zhu, Ming Zhang, Yan-Jun Xu, Li Cui, Naranjan S Dhalla
Although plasma levels of lysophosphatidylglycerol (LPG) are increased in hypertension, its role in the pathogenesis of vascular defects is not clear. In view of the importance of Ca2+-overload in causing vascular smooth muscle (VSM) dysfunction, the action of LPG on [Ca2+]i in cultured A10 VSM cell line was examined by using Fura 2-AM acetoxymethyl ester technique. LPG was found to induce a concentration-dependent increase in [Ca2+]i in VSM cells. This change was dependent both on the extracellular and intracellular Ca2+ sources as it was reduced by 30% by EGTA, an extracellular Ca2+ chelator, and 70% by tharpsigargin, a sarcoplasmic reticulum (SR) Ca2+-pump inhibitor...
July 20, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28716970/prolonged-force-depression-after-mechanically-demanding-contractions-is-largely-independent-of-ca-2-and-reactive-oxygen-species
#4
Sigitas Kamandulis, Felipe de Souza Leite, Andres Hernández, Abram Katz, Marius Brazaitis, Joseph D Bruton, Tomas Venckunas, Nerijus Masiulis, Dalia Mickeviciene, Nerijus Eimantas, Andrejus Subocius, Dilson E Rassier, Albertas Skurvydas, Niklas Ivarsson, Håkan Westerblad
Increased production of reactive oxygen/nitrogen species (ROS) and impaired cellular Ca(2+) handling are implicated in the prolonged low-frequency force depression (PLFFD) observed in skeletal muscle after both metabolically and mechanically demanding exercise. Metabolically demanding high-intensity exercise can induce PLFFD accompanied by ROS-dependent fragmentation of the sarcoplasmic reticulum Ca(2+) release channels, the ryanodine receptor (RyR)-1. We tested whether similar changes occur after mechanically demanding eccentric contractions...
July 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28713282/the-n-terminal-region-of-the-ryanodine-receptor-affects-channel-activation
#5
Andrea Faltinova, Nataša Tomaskova, Marián Antalik, Jozef Sevcik, Alexandra Zahradnikova
Mutations in the cardiac ryanodine receptor (RyR2), the ion channel responsible for release of calcium ions from intracellular stores into cytoplasm, are the cause of several inherited cardiac arrhythmias. At the molecular level, disease symptoms can be mimicked by domain peptides from mutation-prone regions of RyR2 that bind to RyR2 and activate it. Here we show that the domain peptide DPcpvtN2, corresponding to the central helix of the N-terminal region of RyR2, activates the RyR2 channel. Structural modeling of interaction between DPcpvtN2 and the N-terminal region of RyR2 in the closed and open conformation provided three plausible structures of the complex...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713161/functional-expression-of-the-ca-2-signaling-machinery-in-human-embryonic-stem-cells
#6
Ji-Jun Huang, Yi-Jie Wang, Min Zhang, Peng Zhang, He Liang, Hua-Jun Bai, Xiu-Jian Yu, Huang-Tian Yang
Emerging evidence suggests that Ca(2+) signals are important for the self-renewal and differentiation of human embryonic stem cells (hESCs). However, little is known about the physiological and pharmacological properties of the Ca(2+)-handling machinery in hESCs. In this study we used RT-PCR and Western blotting to analyze the expression profiles of genes encoding Ca(2+)-handling proteins; we also used confocal Ca(2+) imaging and pharmacological approaches to determine the contribution of the Ca(2+)-handling machinery to the regulation of Ca(2+) signaling in hESCs...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28709993/intracellular-calcium-release-through-ip3r-or-ryr-contributes-to-secondary-axonal-degeneration
#7
Ben C Orem, Nicolas Pelisch, Joshua Williams, Jacqueline M Nally, David P Stirling
Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca(2+) store mediated intra-axonal Ca(2+) release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model...
July 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28702845/regulation-of-cardiac-ca-2-and-ion-channels-by-shear-mechanotransduction
#8
REVIEW
Joon-Chul Kim, Min-Jeong Son, Jun Wang, Sun-Hee Woo
Cardiac contraction is controlled by a Ca(2+) signaling sequence that includes L-type Ca(2+) current-gated opening of Ca(2+) release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca(2+) signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses...
July 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28701513/the-prion-protein-regulates-glutamate-mediated-ca-2-entry-and-mitochondrial-ca-2-accumulation-in-neurons
#9
Agnese De Mario, Caterina Peggion, Maria Lina Massimino, Francesca Viviani, Angela Castellani, Marta Giacomello, Dmitry Lim, Alessandro Bertoli, Maria Catia Sorgato
The prion protein, PrP(C), whose conformational misfolding originates deadly prions, has a still unclarified cellular function despite decades of intensive research. Following our recent finding that PrP(C) limits Ca(2+) entry via store-operated Ca(2+) channels in neurons, we investigated whether the protein could also control the activity of ionotropic glutamate receptors (iGluRs). To this end, we compared local Ca(2+) movements in primary cerebellar granule neurons and cortical neurons, expressing, or not, PrP(C), transduced with genetically encoded Ca(2+) probes...
July 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28691539/investigational-antiarrhythmic-agents-promising-drugs-in-early-clinical-development
#10
Jordi Heijman, Shokoufeh Ghezelbash, Dobromir Dobrev
Although there have been important technological advances for the treatment of cardiac arrhythmias (e.g., catheter ablation technology), antiarrhythmic drugs (AADs) remain the cornerstone therapy for the majority of patients with arrhythmias. Most of the currently available AADs were coincidental findings and did not result from a systematic development process based on known arrhythmogenic mechanisms and specific targets. During the last 20 years, our understanding of cardiac electrophysiology and fundamental arrhythmia mechanisms has increased significantly, resulting in the identification of new potential targets for mechanism-based antiarrhythmic therapy...
July 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28687594/reduced-threshold-for-store-overload-induced-ca-2-release-is-a-common-defect-of-ryr1-mutations-associated-with-malignant-hyperthermia-and-central-core-disease
#11
Wenqian Chen, Andrea Koop, Yingjie Liu, Wenting Guo, Jinhong Wei, Ruiwu Wang, David H MacLennan, Robert T Dirksen, S R Wayne Chen
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), while mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding RyR isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process known as store-overload induced Ca(2+) release (SOICR)...
July 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28674006/clusters-of-calcium-release-channels-harness-the-ising-phase-transition-to-confine-their-elementary-intracellular-signals
#12
Anna V Maltsev, Victor A Maltsev, Michael D Stern
Intracellular Ca signals represent a universal mechanism of cell function. Messages carried by Ca are local, rapid, and powerful enough to be delivered over the thermal noise. A higher signal-to-noise ratio is achieved by a cooperative action of Ca release channels such as IP3 receptors or ryanodine receptors arranged in clusters (release units) containing a few to several hundred release channels. The channels synchronize their openings via Ca-induced Ca release, generating high-amplitude local Ca signals known as puffs in neurons and sparks in muscle cells...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28672269/underlying-mechanisms-preserving-coronary-basal-tone-and-no-mediated-relaxation-in-obesity-involvement-of-%C3%AE-1-subunit-mediated-upregulation-of-bkca-channels
#13
Belén Climent, Ana Sánchez, Laura Moreno, Francisco Pérez-Vizcaíno, Albino García-Sacristán, Luis Rivera, Dolores Prieto
BACKGROUND AND AIMS: The impact of obesity on vasomotor regulation of coronary arteries and its underlying mechanisms are not completely understood and, in particular, the role of BKCa channels in the NO-mediated coronary vasodilation in obesity remains to be elucidated. METHODS: The effects of selective blockade of BKCa channel was tested on nitric oxide (NO)-mediated vasodilator responses of coronary arteries from lean and obese Zucker rats (LZR and OZR, respectively) by means of simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence and tension in endothelium-denuded coronary arteries mounted in microvascular myographs...
June 23, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28670363/verapamil-suppresses-cardiac-alternans-and-ventricular-arrhythmias-in-acute-myocardial-ischemia-via-ryanodine-receptor-inhibition
#14
Yu-Lei Deng, Jun-Yan Zhao, Ji-Hua Yao, Qiang Tang, Le Zhang, Hong-Lian Zhou, Cun-Tai Zhang, Jia-Gao Lv, Xiao-Qing Quan
T-wave alternans (TWA) is a potent arrhythmia substrate under the conditions of acute myocardial ischemia. Abnormal intracellular calcium cycling contributes to the genesis of cardiac alternans. Ryanodine receptor (RyR) is a pivotal Ca(2+) cycling protein central to Ca(2+) signaling in the heart. Here, we investigated the potential role of RyR in cardiac alternans and ventricular arrhythmias in acute myocardial ischemia. Transmembrane action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contraction force in the arterially perfused left ventricular wedge preparations...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28669775/investigation-of-the-contribution-of-ryr-target-site-mutations-in-diamide-resistance-by-crispr-cas9-genome-modification-in-drosophila
#15
Vassilis Douris, Kyriaki-Maria Papapostolou, Aris Ilias, Emmanuel Roditakis, Styliani Kounadi, Maria Riga, Ralf Nauen, John Vontas
Diamide insecticides are used widely against lepidopteran pests, acting as potent activators of insect Ryanodine Receptors (RyRs) and thus inducing muscle contraction and eventually death. However, resistant phenotypes have recently evolved in the field, associated with the emergence of target site resistance mutations (G4946E/V and I4790M). We investigated the frequency of the mutations found in a resistant population of Tuta absoluta from Greece (G4946V ~79% and I4790M ~21%) and the associated diamide resistance profile: there are very high levels of resistance against chlorantraniliprole (9329-fold) and flubendiamide (4969-fold), but moderate levels against cyantraniliprole (191-fold)...
June 29, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#16
Ying Yang, Xiqing Rong, Xue Lv, Wenbing Jiang, Yuan Yang, Dongwu Lai, Shiming Xu, Guosheng Fu
AIM: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction. METHODS: We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28659760/mecp2-mediates-experience-dependent-transcriptional-upregulation-of-ryanodine-receptor-type-3
#17
Rodrigo F Torres, Cecilia Hidalgo, Bredford Kerr
Mecp2 is a DNA methylation reader that plays a critical role in experience-dependent plasticity. Increasing evidence supports a role for epigenetic modifications in activity-induced gene expression. Hence, candidate genes related to such phenomena are of great interest. Ryanodine receptors are intracellular calcium channels that contribute to hippocampal synaptic plasticity, dendritic spine remodeling, and participate in learning and memory processes. Here we exposed mice to the enriched environment (EE) paradigm, which through increased stimulation induces experience dependent-plasticity, to explore a role for methyl-cytosines, and Mecp2 in directing Ryanodine receptor 3 (Ryr3) transcriptional activity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28655610/neuropeptide-s-nps-is-a-neuropeptide-with-cellular-actions-in-arousal-and-anxiety-related-nuclei-functional-implications-for-effects-of-nps-on-wakefulness-and-mood
#18
Vincenzo Roncacè, Filip Souza Polli, Minella Zojicic, Kristi Anne Kohlmeier
Neuropeptide S (NPS) is a peptide recently recognized to be present in the CNS, and believed to play a role in vigilance and mood control, as behavioral studies have shown it promotes arousal and has an anxiolytic effect. Although NPS precursor is found in very few neurons, NPS positive fibers are present throughout the brain stem. Given the behavioral actions of this peptide and the wide innervation pattern, we examined the cellular effects of NPS within two brain stem nuclei known to play a critical role in anxiety and arousal: the dorsal raphe (DR) and laterodorsal tegmentum (LDT)...
June 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28653141/physiology-and-pathophysiology-of-excitation-contraction-coupling-the-functional-role-of-ryanodine-receptor
#19
Gaetano Santulli, Daniel R Lewis, Andrew R Marks
Calcium (Ca(2+)) release from intracellular stores plays a key role in the regulation of skeletal muscle contraction. The type 1 ryanodine receptors (RyR1) is the major Ca(2+) release channel on the sarcoplasmic reticulum (SR) of myocytes in skeletal muscle and is required for excitation-contraction (E-C) coupling. This article explores the role of RyR1 in skeletal muscle physiology and pathophysiology.
June 26, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28638869/reducing-toxicity-and-increasing-efficiency-aconitine-with-liquiritin-and-glycyrrhetinic-acid-regulate-calcium-regulatory-proteins-in-rat-myocardial-cell
#20
Yuyan Zhang, Li Yu, Weifeng Jin, Hongjing Fan, Min Li, Tianmei Zhou, Haitong Wan, Jiehong Yang
BACKGROUND: Compatibility of Radix Aconiti Carmichaeli and Liquorice is known to treat heart diseases such as heart failure and cardiac arrhythmias. This work answers the question that whether the active components (Aconitine, Liquiritin and Glycyrrhetinic Acid) of Radix Aconiti Carmichaeli and Liquorice could result in regulating intracellular calcium homeostasis and calcium cycling, and thereby verifies the therapeutic material basis. MATERIALS AND METHODS: The myocardial cells were divided into twelve groups randomly as control group, Aconitine group, nine different dose groups that orthogonal combined with Aconitine, Liquiritin and Glycyrrhetinic Acid, and Verapamil group...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
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