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Calcium channel subunit

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https://www.readbyqxmd.com/read/27900342/cacna1c-protecting-young-hippocampal-neurons-in-the-adult-brain
#1
Héctor De Jesús-Cortés, Anjali M Rajadhyaksha, Andrew A Pieper
Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.(1,2) Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, the CACNA1C gene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27878303/neuroprotective-effects-of-vitexin-against-isoflurane-induced-neurotoxicity-by-targeting-the-trpv1-and-nr2b-signaling-pathways
#2
Linlin Chen, Bin Zhang, Shiqiang Shan, Xin Zhao
Vitexin is a bioactive compound extracted from hawthorn leaves, which reduces blood pressure and has anti‑inflammatory and potential anticancer effects. However, the mechanisms underlying the protective effects of vitexin against isoflurane‑induced neurotoxicity remain elusive. Therefore, the aim of the present study was to investigate these mechanisms further. Sprague Dawley rats received 1.4% isoflurane in a 100% oxygen environment for 2 h. Human PC12 pheochromocytoma neurosecretory cells were exposed to 2% isoflurane for 12 h before they were treated with 1, 10 or 100 µM vitexin for a further 24 h...
November 16, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27872869/dynamic-association-of-calcium-channel-subunits-at-the-cellular-membrane
#3
Andreas Voigt, Romy Freund, Jennifer Heck, Markus Missler, Gerald J Obermair, Ulrich Thomas, Martin Heine
High voltage gated calcium channels (VGCCs) are composed of at least three subunits, one pore forming [Formula: see text]-subunit, an intracellular [Formula: see text]-variant, and a mostly extracellular [Formula: see text]-variant. Interactions between these subunits determine the kinetic properties of VGCCs. It is unclear whether these interactions are stable over time or rather transient. Here, we used single-molecule tracking to investigate the surface diffusion of [Formula: see text]- and [Formula: see text]-subunits at the cell surface...
October 2016: Neurophotonics
https://www.readbyqxmd.com/read/27866326/the-neuroprotective-peptide-poly-arginine-12-r12-reduces-cell-surface-levels-of-nmda-nr2b-receptor-subunit-in-cortical-neurons-investigation-into-the-involvement-of-endocytic-mechanisms
#4
Gabriella MacDougall, Ryan S Anderton, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx...
November 20, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27859335/extracellular-protons-enable-activation-of-the-calcium-dependent-chloride-channel-tmem16a-ano1
#5
Silvia Cruz-Rangel, José J De Jesus-Pérez, Iván A Aréchiga-Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola
TMEM16A (ANO1), the pore forming subunit of a Ca(2+) -dependent Cl(-) channel (CaCC), is activated by direct, voltage-dependent, binding of intracellular Ca(2+) . Endogenous CaCCs are regulated by extracellular protons; however, the molecular basis of such regulation remains unidentified. Here, we evaluated the effects of different extracellular proton concentrations ([H(+) ]o ) on mouse TMEM16A expressed in HEK-293 cells using whole-cell and inside-out patch clamp recordings. We found that increasing the [H(+) ]o from 10(-10) to 10(-5...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27853054/expression-of-cyp11b2-in-aldosterone-producing-adrenocortical-adenoma-regulatory-mechanisms-and-clinical-significance
#6
Yasuhiro Nakamura, Yuto Yamazaki, Yuta Tezuka, Fumitoshi Satoh, Hironobu Sasano
Aldosterone-producing adrenocortical adenoma (APA) is responsible for the majority of cases clinically diagnosed as primary aldosteronism. Aldosterone synthase (CYP11B2) is one of the enzymes that play essential roles in aldosterone synthesis and is involved in the pathogenesis of APA. Recent studies have demonstrated that various factors and regulators influence the expression and function of CYP11B2 in APA. In particular, somatic mutations, such as gain-of-function and loss-of-function mutations, have been identified in several genes, each of which encodes a pivotal protein that affects the calcium signaling pathway, the expression of CYP11B2, and aldosterone production...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27848217/pregabalin-for-the-treatment-of-drug-and-alcohol-withdrawal-symptoms-a-comprehensive-review
#7
REVIEW
Rainer Freynhagen, Miroslav Backonja, Stephan Schug, Gavin Lyndon, Bruce Parsons, Stephen Watt, Regina Behar
Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted...
November 16, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27831563/tissue-type-plasminogen-activator-controls-neuronal-death-by-raising-surface-dynamics-of-extrasynaptic-nmda-receptors
#8
Flavie Lesept, Arnaud Chevilley, Julie Jezequel, Laurent Ladépêche, Richard Macrez, Margaux Aimable, Sophie Lenoir, Thomas Bertrand, Laëtitia Rubrecht, Pascale Galea, Laurent Lebouvier, Karl-Uwe Petersen, Yannick Hommet, Eric Maubert, Carine Ali, Laurent Groc, Denis Vivien
N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). To date, the roles and dynamics of the NTD of the GluN1 subunit in NMDAR allosteric signaling remain poorly understood...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27826230/ampa-receptors-are-involved-in-store-operated-calcium-entry-and-interact-with-stim-proteins-in-rat-primary-cortical-neurons
#9
Joanna Gruszczynska-Biegala, Maria Sladowska, Jacek Kuznicki
The process of store-operated calcium entry (SOCE) leads to refilling the endoplasmic reticulum (ER) with calcium ions (Ca(2+)) after their release into the cytoplasm. Interactions between (ER)-located Ca(2+) sensors (stromal interaction molecule 1 [STIM1] and STIM2) and plasma membrane-located Ca(2+) channel-forming protein (Orai1) underlie SOCE and are well described in non-excitable cells. In neurons, however, SOCE appears to be more complex because of the importance of Ca(2+) influx via voltage-gated or ionotropic receptor-operated Ca(2+) channels...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27810048/patient-specific-and-genome-edited-induced-pluripotent-stem-cell-derived-cardiomyocytes-elucidate-single-cell-phenotype-of-brugada-syndrome
#10
Ping Liang, Karim Sallam, Haodi Wu, Yingxin Li, Ilanit Itzhaki, Priyanka Garg, Ying Zhang, Vittavat Vermglinchan, Feng Lan, Mingxia Gu, Tingyu Gong, Yan Zhuge, Chunjiang He, Antje D Ebert, Veronica Sanchez-Freire, Jared Churko, Shijun Hu, Arun Sharma, Chi Keung Lam, Melvin M Scheinman, Donald M Bers, Joseph C Wu
BACKGROUND: Brugada syndrome (BrS), a disorder associated with characteristic electrocardiogram precordial ST-segment elevation, predisposes afflicted patients to ventricular fibrillation and sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to a lack of adequate human cellular models of the disorder. OBJECTIVES: The objective of this study was to examine single cell mechanism of Brugada syndrome using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)...
November 8, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27806289/vulnerability-of-purkinje-cells-generated-from-spinocerebellar-ataxia-type-6-patient-derived-ipscs
#11
Yoshihito Ishida, Hideshi Kawakami, Hiroyuki Kitajima, Ayaka Nishiyama, Yoshiki Sasai, Haruhisa Inoue, Keiko Muguruma
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27800483/tocotrienol-rich-tocomin-attenuates-oxidative-stress-and-improves-endothelium-dependent-relaxation-in-aortae-from-rats-fed-a-high-fat-western-diet
#12
Saher F Ali, Jason C D Nguyen, Trisha A Jenkins, Owen L Woodman
We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study, we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high-fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat) or control rat chow (standard diet, 6% fat) for 12 weeks. Tocomin (40 mg/kg/day sc) or its vehicle (peanut oil) was administered for the last 4 weeks of the feeding regime...
2016: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27799318/independent-activation-of-ion-conduction-pores-in-the-double-barreled-calcium-activated-chloride-channel-tmem16a
#13
Novandy K Lim, Andy K M Lam, Raimund Dutzler
The TMEM16 proteins constitute a family of membrane proteins with unusual functional breadth, including lipid scramblases and Cl(-) channels. Members of both these branches are activated by Ca(2+), acting from the intracellular side, and probably share a common architecture, which was defined in the recent structure of the lipid scramblase nhTMEM16. The structural features of subunits and the arrangement of Ca(2+)-binding sites in nhTMEM16 suggest that the dimeric protein harbors two locations for catalysis that are independent with respect to both activation and lipid conduction...
November 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27798183/%C3%AE-2%C3%AE-2-controls-the-function-and-trans-synaptic-coupling-of-cav1-3-channels-in-mouse-inner-hair-cells-and-is-essential-for-normal-hearing
#14
Barbara Fell, Stephanie Eckrich, Kerstin Blum, Tobias Eckrich, Dietmar Hecker, Gerald J Obermair, Stefan Münkner, Veit Flockerzi, Bernhard Schick, Jutta Engel
: The auxiliary subunit α2δ2 modulates the abundance and function of voltage-gated calcium channels. Here we show that α2δ2 mRNA is expressed in neonatal and mature hair cells. A functional α2δ2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds. Otoacoustic emissions were not impaired pointing to normal outer hair cell function. Peak Ca(2+) and Ba(2+) currents of mature du/du inner hair cells (IHCs) were reduced by 30-40%, respectively, and gating properties, such as the voltage of half-maximum activation and voltage sensitivity, were altered, indicating that Cav1...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27798131/cocaine-exposure-enhances-the-activity-of-ventral-tegmental-area-dopamine-neurons-via-calcium-impermeable-nmdars
#15
Meaghan Creed, Jennifer Kaufling, Giulia R Fois, Marion Jalabert, Tifei Yuan, Christian Lüscher, Francois Georges, Camilla Bellone
: Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting activity of VTA dopamine neurons, and that these increases persist for 7 d...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27787949/pasireotide-prevents-nuclear-factor-of-activated-t-cells-nuclear-translocation-and-acts-as-a-protective-agent-in-aminoglycoside-induced-auditory-hair-cell-loss
#16
Daniel Bodmer, Adrijana Perkovic, Marijana Sekulic-Jablanovic, Matthew B Wright, Vesna Petkovic
Hearing impairment is a global health problem with a high socioeconomic impact. Damage to auditory hair cells (HCs) in the inner ear as a result of aging, disease, trauma, or toxicity, underlies the majority of cases of sensorineural hearing loss. Previously we demonstrated that the Ca(2+) -sensitive neuropeptide, somatostatin (SST), and an analog, octreotide, protect HCs from gentamicin-induced cell death in vitro. Aminoglycosides such as gentamicin trigger a calcium ion influx (Ca(2+) ) that activates pro-apoptotic signaling cascades in HCs...
October 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27782881/proteolytic-maturation-of-%C3%AE-2%C3%AE-represents-a-checkpoint-for-activation-and-neuronal-trafficking-of-latent-calcium-channels
#17
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
https://www.readbyqxmd.com/read/27780862/the-orai1-store-operated-calcium-channel-functions-as-a-hexamer
#18
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
https://www.readbyqxmd.com/read/27768059/determination-of-the-relative-cell-surface-and-total-expression-of-recombinant-ion-channels-using-flow-cytometry
#19
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
https://www.readbyqxmd.com/read/27764657/synaptic-suppression-of-axon-regeneration
#20
Jessica M Meves, Binhai Zheng
In this issue of Neuron, Tedeschi et al. (2016) describe the voltage-gated calcium channel subunit alpha2delta2 as a developmental switch from axon elongation to synapse formation and transmission that doubles as a suppressor of axon regeneration, providing a molecular clue for the synaptic stabilization hypothesis of CNS regeneration failure.
October 19, 2016: Neuron
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