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Calcium channel

Sharon M Moe
Calcium is an important ion in cell signaling, hormone regulation, and bone health. Its regulation is complex and intimately connected to that of phosphate homeostasis. Both ions are maintained at appropriate levels to maintain the extracellular to intracellular gradients, allow for mineralization of bone, and to prevent extra skeletal and urinary calcification. The homeostasis involves the target organs intestine, parathyroid glands, kidney, and bone. Multiple hormones converge to regulate the extracellular calcium level: parathyroid hormone, vitamin D (principally 25(OH)D or 1,25(OH)2D), fibroblast growth factor 23, and α-klotho...
September 15, 2016: Comprehensive Physiology
Devasena Ponnalagu, Harpreet Singh
Mitochondria are the "power house" of a cell continuously generating ATP to ensure its proper functioning. The constant production of ATP via oxidative phosphorylation demands a large electrochemical force that drives protons across the highly selective and low-permeable mitochondrial inner membrane. Besides the conventional role of generating ATP, mitochondria also play an active role in calcium signaling, generation of reactive oxygen species (ROS), stress responses, and regulation of cell-death pathways...
October 26, 2016: Handbook of Experimental Pharmacology
Jihui Seo, Jeehye Maeng, Hwa-Jung Kim
The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [³H]dopamine release in concentration- and time-dependent manners...
October 24, 2016: International Journal of Molecular Sciences
Ivan Kadurin, Laurent Ferron, Simon W Rothwell, James O Meyer, Leon R Douglas, Claudia S Bauer, Beatrice Lana, Wojciech Margas, Orpheas Alexopoulos, Manuela Nieto-Rostro, Wendy S Pratt, Annette C Dolphin
The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ...
October 26, 2016: ELife
M Koselski, A Olszewska, A Hordyjewska, T Małecka-Massalska, K Trebacz
Patch clamp recordings carried out in the inside-out configuration revealed activity of three kinds of channels: nonselective cation channels, small-conductance K(+) channels, and large-conductance anion channels. The nonselective cation channels did not distinguish between Na(+) and K(+). The unitary conductance of these channels reached 28 pS in a symmetrical concentration of 200 mM NaCl. A lower value of this parameter was recorded for the small-conductance K(+) channels and in a 50-fold gradient of K(+) (200 mM/4 mM) it reached 8 pS...
October 26, 2016: Physiological Research
I M Fuentes, J A Christianson
Ion channels are expressed throughout the gastrointestinal system and regulate nearly every aspect of digestion, including fluid secretion and absorption, motility, and visceral sensitivity. It is therefore not surprising that in the setting of functional bowel disorders, such as irritable bowel syndrome (IBS), ion channels are often altered in terms of expression level and function and are a target of pharmacological intervention. This is particularly true of their role in driving abdominal pain through visceral hypersensitivity (VH), which is the main reason IBS patients seek medical care...
November 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Xiangyu Cai, Yandong Zhou, Robert M Nwokonko, Natalia A Loktionova, Xianming Wang, Ping Xin, Mohamed Trebak, Youjun Wang, Donald L Gill
Orai channels mediate store-operated Ca2+ signals crucial in regulating transcription in many cell types, and implicated in numerous immunological and inflammatory disorders. Despite their central importance, controversy surrounds the basic subunit structure of Orai channels, several biochemical and biophysical studies suggesting a tetrameric structure yet crystallographic evidence indicating a hexamer. We systematically investigated the subunit configuration of the functional Orai1 channel, generating a series of tdTomato-tagged concatenated Orai1 channel constructs (dimers to hexamers) expressed in CRISPR-derived Orai1-knockout HEK cells, stably expressing STIM1-YFP...
October 25, 2016: Journal of Biological Chemistry
François Seghers, Xavier Yerna, Nadège Zanou, Olivier Devuyst, Rudi Vennekens, Bernd Nilius, Philippe Gailly
The renin - angiotensin system is a crucial blood pressure regulation system. It consists of a hormonal cascade where the rate-limiting enzyme is renin, which is secreted in blood flow by renal juxtaglomerular (JG) cells in response to low pressure in the renal afferent arteriole. In contrast, an increase in blood pressure results in a decreased renin secretion. This is accompanied by a transitory increase in [Ca(2+) ]i of JG cells. The inverse relationship between [Ca(2+) ]i and renin secretion has been called the "calcium paradox" of renin release...
October 25, 2016: Journal of Physiology
Chia-Wen Hsu, Jui-Hua Hsieh, Ruili Huang, Dirk Pijnenburg, Thai Khuc, Jon Hamm, Jinghua Zhao, Caitlin Lynch, Rinie van Beuningen, Xiaoqing Chang, Rene Houtman, Menghang Xia
Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches...
October 20, 2016: Toxicology and Applied Pharmacology
George L Bakris, John M Burkart, Eric D Weinhandl, Peter A McCullough, Michael A Kraus
Hypertension is a cardinal feature of end-stage renal disease (ESRD). Hypertensive nephropathy is the primary cause of ESRD for nearly 30% of patients, and the prevalence of hypertension is >85% in new patients with ESRD. In contemporary hemodialysis (HD) patients, mean predialysis systolic blood pressure (SBP) is nearly 150mmHg, and about 70%, 50%, and 40% use β-blockers, calcium channel blockers, and renin-angiotensin system inhibitors, respectively. Predialysis SBP generally exhibits a U-shaped association with mortality risk...
November 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Kirilka Mladenova, Svetla D Petrova, Tonya D Andreeva, Veselina Moskova-Doumanova, Tanya Topouzova-Hristova, Yuri Kalvachev, Konstantin Balashev, Shomi S Bhattacharya, Christina Chakarova, Zdravko Lalchev, Jordan A Doumanov
Human bestrophin-1 (hBest1) is a transmembrane calcium-activated chloride channel protein - member of the bestrophin family of anion channels, predominantly expressed in the membrane of retinal pigment epithelium (RPE) cells. Mutations in the protein cause ocular diseases, named Bestrophinopathies. Here, we present the first Fourier transform infrared (FTIR) study of the secondary structure elements of hBest1, π/A isotherms and hysteresis, Brewster angle microscopy (BAM) and atomic force microscopy (AFM) visualization of the aggregation state of protein molecules dispersed as Langmuir and Langmuir-Blodgett films...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Junting Huang, Gerald W Zamponi
Calcium entry via voltage gated calcium channels mediates a wide range of physiological functions, whereas calcium channel dysregulation has been associated with numerous pathophysiological conditions. There are myriad cell signaling pathways that act on voltage gated calcium channels to fine tune their activities and to regulate their cell surface expression. These regulatory mechanisms include the activation of G protein-coupled receptors and downstream phosphorylation events, and their control over calcium channel trafficking through direct physical interactions...
October 18, 2016: Current Opinion in Pharmacology
Katrin Feldbauer, Jan Schlegel, Juliane Weissbecker, Frank Sauer, Phillip G Wood, Ernst Bamberg, Ulrich Terpitz
An optochemokine tandem was developed to control the release of calcium from endosomes into the cytosol by light and to analyze the internalization kinetics of G-protein coupled receptors (GPCRs) by electrophysiology. A previously constructed rhodopsin tandem was re-engineered to combine the light-gated Ca2+-permeable cation channel Channelrhodopsin-2(L132C), CatCh, with the chemokine receptor CXCR4 in a functional tandem protein tCXCR4/CatCh. The GPCR was used as a shuttle protein to displace CatCh from the plasma membrane into intracellular areas...
2016: PloS One
Benoîte Bourdin, Emilie Segura, Marie-Philippe Tétreault, Sylvie Lesage, Lucie Parent
Inherited or de novo mutations in cation-selective channels may lead to sudden cardiac death. Alteration in the plasma membrane trafficking of these multi-spanning transmembrane proteins, with or without change in channel gating, is often postulated to contribute significantly in this process. It has thus become critical to develop a method to quantify the change of the relative cell surface expression of cardiac ion channels on a large scale. Herein, a detailed protocol is provided to determine the relative total and cell surface expression of cardiac L-type calcium channels CaV1...
September 28, 2016: Journal of Visualized Experiments: JoVE
Derek Garden, Arianna Rinaldi, Matthew F Nolan
The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neurones in the inferior olive integrate synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs...
October 21, 2016: Journal of Physiology
Alessandro Rubini, Vincenzo Catena, Daniele Del Monte, Gerardo Bosco
CONTEXT: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle. OBJECTIVE: To investigate possible effects of nifedipine on respiratory mechanics in the rat. METHODS: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine. RESULTS: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Young Joon Kwon, Marni J Falk, Michael J Bennett
CLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric-onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis of CLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of CLN3 deficiency suggested that FDA-approved calcium channel antagonists may have therapeutic value...
October 20, 2016: Journal of Inherited Metabolic Disease
Stefano Fiorucci, Angela Zampella, Giuseppe Cirino, Mariarosaria Bucci, Eleonora Distrutti
Bile acids are end product of cholesterol metabolism generated in the liver and released in the intestine. In addition to their role in nutrient absorption, bile acids are increasingly recognized as regulatory signals which exert their function beyond the intestine by activating a network of membrane and nuclear receptors. The best characterized of these bile acid activated receptors, GPBAR1 (also known as TGR5) and the Farnesosid-x-receptor (FXR) have also been detected in the vascular system and their activation mediate the vasodilatory effects of bile acids in the systemic and splanchnic circulation...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Jay S Naik, Jessica M Osmond, Benjimen R Walker, Nancy L Kanagy
Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtansferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large conductance Ca(2+)-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Donal Melanaphy, Christpher D Johnson, Maxim Kustov, Connall Watson, Lyudmyla Borysova, Theodore Burdyga, Alexander V Zholos
Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold sensing role in sensory neurons, it is expressed and functional in several non-neuronal tissues, including vasculature. We previously demonstrated that menthol causes vasoconstriction and vasodilatation in isolated arteries, depending on vascular tone. Here we investigated calcium's role in responses mediated by TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology and ratiometric Ca(2+) recording...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
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