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Voltage-dependent calcium channels

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https://www.readbyqxmd.com/read/29330545/de-novo-bk-channel-variant-causes-epilepsy-by-affecting-voltage-gating-but-not-ca2-sensitivity
#1
Xia Li, Sibylle Poschmann, Qiuyun Chen, Walid Fazeli, Nelly Jouayed Oundjian, Francesca M Snoeijen-Schouwenaars, Oliver Fricke, Erik-Jan Kamsteeg, Marjolein Willemsen, Qing Kenneth Wang
Epilepsy is one of the most common neurological diseases and it causes profound morbidity and mortality. We identified the first de novo variant in KCNMA1 (c.2984 A > G (p.(N995S)))-encoding the BK channel-that causes epilepsy, but not paroxysmal dyskinesia, in two independent families. The c.2984 A > G (p.(N995S)) variant markedly increased the macroscopic potassium current by increasing both the channel open probability and channel open dwell time. The c.2984 A > G (p.(N995S)) variant did not affect the calcium sensitivity of the channel...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29317246/presynaptic-calcium-channels
#2
REVIEW
Sumiko Mochida
At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca2+ entry through voltage-gated Ca2+ (CaV) channels triggers neurotransmitter release from the active zone. Presynaptic Ca2+ channels form a large signaling complex, which targets synaptic vesicles to Ca2+ channels for efficient release and mediates Ca2+ channel regulation. The presynaptic CaV2 channel family (comprising CaV2.1, CaV2.2 and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are the target of regulatory proteins for channel modulation...
January 6, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29306662/ciguatoxins-activate-the-calcineurin-signalling-pathway-in-yeasts-potential-for-development-of-an-alternative-detection-tool
#3
Hélène Martin-Yken, Camille Gironde, Sylvain Derick, Hélène Taiana Darius, Christophe Furger, Dominique Laurent, Mireille Chinain
Ciguatoxins (CTXs) are lipid-soluble polyether compounds produced by dinoflagellates from the genus Gambierdiscus spp. typically found in tropical and subtropical zones. This endemic area is however rapidly expanding due to environmental perturbations, and both toxic Gambierdiscus spp. and ciguatoxic fishes have been recently identified in the North Atlantic Ocean (Madeira and Canary islands) and Mediterranean Sea. Ciguatoxins bind to Voltage Gated Sodium Channels on the membranes of sensory neurons, causing Ciguatera Fish Poisoning (CFP) in humans, a disease characterized by a complex array of gastrointestinal, neurological, neuropsychological, and cardiovascular symptoms...
January 4, 2018: Environmental Research
https://www.readbyqxmd.com/read/29305813/a-simultaneous-mixed-effects-pharmacokinetic-model-for-nefopam-n-desmethylnefopam-and-nefopam-n-oxide-in-human-plasma-and-urine
#4
Aravind Mittur
BACKGROUND AND OBJECTIVE: Nefopam is a non-opioid, non-steroidal, central analgesic thought to act via multiple mechanisms including potent inhibition of serotonin-norepinephrine reuptake and modulation of voltage-sensitive calcium and sodium channels. There has been a resurgence in its use for postoperative pain and neuropathic pain. Dosing route-dependent metabolism and clinical effects have been described following intravenous and oral nefopam. N-desmethylnefopam and nefopam N-oxide are metabolites of clinical interest...
January 5, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29301136/assessment-of-the-airway-smooth-muscle-relaxant-effect-of-drotaverine
#5
Zoltán Patai, András Guttman, Endre G Mikus
BACKGROUND: Drotaverine, a type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor, blocks the degradation of 3',5'-cyclic adenosine monophosphate. However, published receptor binding data showed that drotaverin also binds to the L-type voltage-operated calcium channel (L-VOCC). Based on these molecular mechanisms of action, a direct and indirect (by blocking the constrictor response) relaxant effect on airway smooth muscle can be predicted, which has not yet been assessed. SUMMARY: Accordingly, drotaverine and reference agents were tested both on the histamine-, methacholine-, or KCl-induced contraction response and on precontracted guinea pig tracheal preparations...
January 4, 2018: Pharmacology
https://www.readbyqxmd.com/read/29277655/phosphatidylinositol-4-5-bisphosphate-cholesterol-and-fatty-acids-modulate-the-calcium-activated-chloride-channel-tmem16a-ano1
#6
José J De Jesús-Pérez, Silvia Cruz-Rangel, Ángeles E Espino-Saldaña, Ataúlfo Martínez-Torres, Zhiqiang Qu, H Criss Hartzell, Nancy E Corral-Fernandez, Patricia Pérez-Cornejo, Jorge Arreola
The TMEM16A-mediated Ca2+-activated Cl- current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca2+...
December 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29246857/new-cav2-calcium-channel-gating-modifiers-with-agonist-activity-and-therapeutic-potential-to-treat-neuromuscular-disease
#7
Man Wu, Hayley V White, Blake Boehm, Christopher J Meriney, Kaylan Kerrigan, Michael Frasso, Mary Liang, Erika M Gotway, Madeleine Wilcox, Jon W Johnson, Peter Wipf, Stephen D Meriney
Voltage-gated calcium channels (VGCCs) are critical regulators of many cellular functions, including the activity-dependent release of chemical neurotransmitter from nerve terminals. At nerve terminals, the Cav2 family of VGCCs are closely positioned with neurotransmitter-containing synaptic vesicles. The relationship between calcium ions and transmitter release is such that even subtle changes in calcium flux through VGCCs have a strong influence on the magnitude of transmitter released. Therefore, modulators of the calcium influx at nerve terminals have the potential to strongly affect transmitter release at synapses...
December 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29230810/trauma-exposure-interacts-with-the-genetic-risk-of-bipolar-disorder-in-alcohol-misuse-of-us-soldiers
#8
R Polimanti, J Kaufman, H Zhao, H R Kranzler, R J Ursano, R C Kessler, M B Stein, J Gelernter
OBJECTIVE: To investigate whether trauma exposure moderates the genetic correlation between substance use disorders and psychiatric disorders, we tested whether trauma exposure modifies the association of genetic risks for mental disorders with alcohol misuse and nicotine dependence (ND) symptoms. METHODS: High-resolution polygenic risk scores (PRSs) were calculated for 10 732 US Army soldiers (8346 trauma-exposed and 2386 trauma-unexposed) based on genome-wide association studies of bipolar disorder (BD), major depressive disorder, and schizophrenia...
December 11, 2017: Acta Psychiatrica Scandinavica
https://www.readbyqxmd.com/read/29228786/oxidative-stress-induces-disruption-of-the-axon-initial-segment
#9
Kareem Clark, Brooke A Sword, Jeffrey L Dupree
The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear...
November 2017: ASN Neuro
https://www.readbyqxmd.com/read/29217581/structure-of-the-human-trpm4-ion-channel-in-a-lipid-nanodisc
#10
Henriette E Autzen, Alexander G Myasnikov, Melody G Campbell, Daniel Asarnow, David Julius, Yifan Cheng
Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage dependent manner, but unlike many other TRP channels is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3Å resolution as determined by single particle electron cryo-microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium binding site within the intracellular side of the S1-S4 domain...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29216332/voltage-dependent-calcium-channel-signaling-mediates-gabaa-receptor-induced-migratory-activation-of-dendritic-cells-infected-by-toxoplasma-gondii
#11
Sachie Kanatani, Jonas M Fuks, Einar B Olafsson, Linda Westermark, Benedict Chambers, Manuel Varas-Godoy, Per Uhlén, Antonio Barragan
The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon T. gondii-infection, γ-aminobutyric acid (GABA)/GABAA receptor signaling triggers a hypermigratory phenotype in dendritic cells (DCs) by unknown signal transduction pathways. Here, we demonstrate that calcium (Ca2+) signaling in DCs is indispensable for T. gondii-induced DC hypermotility and transmigration in vitro. We report that activation of GABAA receptors by GABA induces transient Ca2+ entry in DCs...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29214743/gc-ms-ms-detects-potential-pregabalin-abuse-in-susceptible-subjects-hair
#12
Federica Ianni, Kyriaki Aroni, Alessio Gili, Roccaldo Sardella, Mauro Bacci, Massimo Lancia, Benedetto Natalini, Cristiana Gambelunghe
Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage-dependent calcium channels. It is recognized as efficacious in pathologies such as epilepsy, neuropathic pain and anxiety disorders. Since pregabalin prescriptions have increased worldwide, reports of its abuse have been accumulating, mainly in patients with opioid abuse disorders. The present study investigated potential pregabalin abuse by means of hair analysis, a matrix that provides valuable retrospective information. Half of the pool of 280 susceptible patients had been occasional drug users and were being monitored for driving licence renewals...
December 7, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29213100/altered-spontaneous-calcium-signaling-of-in-situ-chondrocytes-in-human-osteoarthritic-cartilage
#13
Xiaoyuan Gong, Wenbin Xie, Bin Wang, Lingchuan Gu, Fuyou Wang, Xiang Ren, Cheng Chen, Liu Yang
Intracellular calcium ([Ca2+]i) signaling is an essential universal secondary messenger in articular chondrocytes. However, little is known about its spatiotemporal features in the context of osteoarthritis (OA). Herein, by examining the cartilage samples collected from patients undergoing knee arthroscopic surgery, we investigated the spatiotemporal features of spontaneous [Ca2+]i signaling in in situ chondrocytes at different OA stages. Our data showed zonal dependent spontaneous [Ca2+]i signaling in healthy cartilage samples under 4 mM calcium environment...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29200901/the-bifunctional-effect-of-propofol-on-thromboxane-agonist-u46619-induced-vasoconstriction-in-isolated-human-pulmonary-artery
#14
Ning Hao, Wang Zhaojun, Sujuan Kuang, Guangyan Zhang, Chunyu Deng, Jue Ma, Jianxiu Cui
Propofol is known to cause vasorelaxation of several systemic vascular beds. However, its effect on the pulmonary vasculature remains controversial. In the present study, we investigated the effects of propofol on human pulmonary arteries obtained from patients who had undergone surgery. Arterial rings were mounted in a Multi-Myograph system for measurement of isometric forces. U46619 was used to induce sustained contraction of the intrapulmonary arteries, and propofol was then applied (in increments from 10-300 µM)...
November 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29198756/cav2-2-gates-calcium-independent-but-voltage-dependent-secretion-in-mammalian-sensory-neurons
#15
Zuying Chai, Changhe Wang, Rong Huang, Yuan Wang, Xiaoyu Zhang, Qihui Wu, Yeshi Wang, Xi Wu, Lianghong Zheng, Chen Zhang, Wei Guo, Wei Xiong, Jiuping Ding, Feipeng Zhu, Zhuan Zhou
Action potential induces membrane depolarization and triggers intracellular free Ca2+ concentration (Ca2+)-dependent secretion (CDS) via Ca2+ influx through voltage-gated Ca2+ channels. We report a new type of somatic exocytosis triggered by the action potential per se-Ca2+-independent but voltage-dependent secretion (CiVDS)-in dorsal root ganglion neurons. Here we uncovered the molecular mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their linker. Specifically, the voltage-gated N-type Ca2+ channel (CaV2...
November 23, 2017: Neuron
https://www.readbyqxmd.com/read/29186814/alternative-splicing-of-l-type-cav1-2-calcium-channels-implications-in-cardiovascular-diseases
#16
REVIEW
(no author information available yet)
L-type Cav1.2 calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alteration of Cav1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands Cav1.2 channel structures to modify function, pharmacological and biophysical property such as calcium/voltage-dependent inactivation (C/VDI), or to influence its post-translational modulation by interacting proteins such as Galectin-1...
November 24, 2017: Genes
https://www.readbyqxmd.com/read/29180451/molecular-mimicking-of-c-terminal-phosphorylation-tunes-the-surface-dynamics-of-cav1-2-calcium-channels-in-hippocampal-neurons
#17
Alessandra Folci, Angela Steinberger, Boram Lee, Ruslan Stanika, Susanne Scheruebel, Marta Campiglio, Claudia Ramprecht, Brigitte Pelzmann, Johannes W Hell, Gerald J Obermair, Martin Heine, Valentina Di Biase
L-type voltage gated CaV1.2 calcium channels (CaV1.2) are key regulators of neuronal excitability, synaptic plasticity, and excitation-transcription coupling. Surface exposed CaV1.2 distributes in clusters along the dendrites of hippocampal neurons. A permanent exchange between stably clustered and laterally diffusive extra-clustered channels maintains steady-state levels of CaV1.2 at dendritic signaling domains. A dynamic equilibrium between anchored and diffusive receptors is a common feature among ion channels and is crucial to modulate signaling transduction...
November 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29179637/cone-dystrophy-and-ectopic-synaptogenesis-in-a-cacna1f-loss-of-function-model-of-congenital-stationary-night-blindness-csnb2a
#18
D M Waldner, N C Giraldo Sierra, S Bonfield, L Nguyen, I S Dimopoulos, Y Sauvé, W K Stell, N T Bech-Hansen
Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal disorder, characterized by phenotypically variable signs and symptoms of impaired vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming α1F subunit of a L-type voltage-gated calcium channel, Cav1.4. Mouse models of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f-knockout mice show an apparent lack of visual function, gradual retinal degeneration, and disruption of photoreceptor synaptic terminals...
November 28, 2017: Channels
https://www.readbyqxmd.com/read/29167165/long-term-high-altitude-hypoxia-influences-pulmonary-arterial-l-type-calcium-channel-mediated-ca-2-signals-and-contraction-in-fetal-and-adult-sheep
#19
Christine Shen, Monica Romero, Alexander Brunelle, Craig Wolfe, Abigail Dobyns, Michael Francis, Mark S Taylor, Jose Puglisi, Lawrence D Longo, Lubo Zhang, Christopher G Wilson, Sean M Wilson
Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca(2+) signaling is important during the development of LTH induced pulmonary hypertension. In the present study we tested the hypothesis that L-type Ca(2+) channels, which are voltage-dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in post-natal maturation and in response to LTH. Pulmonary arteries were isolated from fetal or adult sheep maintained at low- or high-altitude (3,801 m) for >100 days...
November 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29167062/mechanistic-insights-into-the-detection-of-free-fatty-and-bile-acids-by-ileal-glucagon-like-peptide-1-secreting-cells
#20
Deborah A Goldspink, Van B Lu, Lawrence J Billing, Pierre Larraufie, Gwen Tolhurst, Fiona M Gribble, Frank Reimann
OBJECTIVES: The aim of this study was to investigate the electrical properties of ileal Glucagon-like peptide 1 (GLP-1) secreting L-cells using murine organoid cultures and the electrophysiological and intracellular signaling pathways recruited following activation of the Gαq-coupled free fatty acid receptors FFA1 and Gαs-coupled bile acid receptors GPBAR1. METHODS: Experiments were performed using ileal organoids generated from mice transgenically expressing fluorescent reporters (Epac2-camps and GCaMP3) under control of the proglucagon promoter...
November 11, 2017: Molecular Metabolism
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