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https://www.readbyqxmd.com/read/28700936/alternative-splicing-of-p-q-type-ca-2-channels-shapes-presynaptic-plasticity
#1
Agnes Thalhammer, Andrea Contestabile, Yaroslav S Ermolyuk, Teclise Ng, Kirill E Volynski, Tuck Wah Soong, Yukiko Goda, Lorenzo A Cingolani
Alternative splicing of pre-mRNAs is prominent in the mammalian brain, where it is thought to expand proteome diversity. For example, alternative splicing of voltage-gated Ca(2+) channel (VGCC) α1 subunits can generate thousands of isoforms with differential properties and expression patterns. However, the impact of this molecular diversity on brain function, particularly on synaptic transmission, which crucially depends on VGCCs, is unclear. Here, we investigate how two major splice isoforms of P/Q-type VGCCs (Cav2...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28675819/anti-neuronal-autoantibodies-in-both-drug-responsive-and-resistant-focal-seizures-with-unknown-cause
#2
Gokcen Gozubatik-Celik, Cigdem Ozkara, Canan Ulusoy, Aysegul Gunduz, Sakir Delil, Naz Yeni, Erdem Tuzun
BACKGROUND: and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients. METHOD: Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies...
June 17, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28669898/relevance-of-tissue-specific-subunit-expression-in-channelopathies
#3
REVIEW
Hartwig Seitter, Alexandra Koschak
Channelopathies are a diverse group of human disorders that are caused by mutations in genes coding for ion channels or channel-regulating proteins. Several dozen channelopathies have been identified that involve both non-excitable cells as well as electrically active tissues like brain, skeletal and smooth muscle or the heart. In this review, we start out from the general question which ion channel genes are expressed tissue-selectively. We mined the human gene expression database Human Protein Atlas (HPA) for tissue-enriched ion channel genes and found 85 genes belonging to the ion channel families...
June 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28662295/%C3%AE-9-containing-nicotinic-acetylcholine-receptors-and-the-modulation-of-pain
#4
REVIEW
Arik J Hone, Denis Servent, J Michael McIntosh
Neuropathic pain is a complex and debilitating syndrome for which there are few effective pharmacological treatments. Opioid-based medications are initially effective for acute pain but tolerance to their analgesic effects quickly develops and long-term use often leads to physical dependence and addiction. Furthermore, neuropathic pain is generally resistant to non-steroidal anti-inflammatory drugs. Other classes of medications including antidepressants, antiepileptics, and voltage-gated calcium channel (VGCC) inhibitors are only partially effective in most patients, may be associated with significant side effects, and have few disease modifying effects on the underlying pathology...
June 29, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646556/injury-induced-maladaption-and-dysregulation-of-calcium-channel-alpha-2-delta-subunit-proteins-and-its-contribution-to-neuropathic-pain-development
#5
REVIEW
Nian Gong, John Park, Z David Luo
Voltage gated calcium channels (VGCCs) play important roles in physiological functions including modulations of neurotransmitter release, neuronal network activities, intracellular signaling pathways, and gene expression. Some pathological conditions, including nerve injuries, can cause dysregulation of VGCCs and their subunits. This in turn can lead to functional maladaption of VGCCs and their subunits, which can contribute to development of disorders such as pain sensations. This review summarized recent findings related to maladaptive changes of dysregulated VGCC alpha-2-delta-1 subunit (Cav α2 δ1 ) with a focus on exploration of mechanisms underlying contribution of Cav α2 δ1 to pain signal transduction...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28634208/ligand-and-voltage-gated-ca-2-channels-differentially-regulate-the-mode-of-vesicular-neuropeptide-release-in-mammalian-sensory-neurons
#6
Yeshi Wang, Qihui Wu, Meiqin Hu, Bin Liu, Zuying Chai, Rong Huang, Yuan Wang, Huadong Xu, Li Zhou, Lianghong Zheng, Changhe Wang, Zhuan Zhou
Neuropeptides released from dorsal root ganglion (DRG) neurons play essential roles in the neurotransmission of sensory inputs, including those underlying nociception and pathological pain. Neuropeptides are released from intracellular vesicles through two modes: a partial release mode called "kiss-and-run" (KAR) and a full release mode called "full fusion-like" (FFL). Using total internal reflection fluorescence (TIRF) microscopy, we traced the release of pH-sensitive green fluorescent protein-tagged neuropeptide Y (pHluorin-NPY) from individual dense-core vesicles in the soma and axon of single DRG neurons after Ca(2+) influx through either voltage-gated Ca(2+) channels (VGCCs) or ligand-gated transient receptor potential vanilloid 1 (TRPV1) channels...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28629730/synergistic-antinociceptive-effect-of-a-calcium-channel-blocker-and-a-trpv1-blocker-in-an-acute-pain-model-in-mice
#7
Manuella R Palhares, Juliana F Silva, Marcio Junior S Rezende, Duana C Santos, Cláudio A Silva-Junior, Márcia H Borges, Juliano Ferreira, Marcus V Gomez, Célio J Castro-Junior
AIMS: Extensive evidence supports a role for voltage-gated calcium channels (VGCC) and TRPV1 receptors in pain transmission and modulation. We investigated the profile of analgesic interaction between Phα1β toxin (a VGCC blocker) and SB366791 (selective TRPV1 antagonist) in a model of acute pain induced by capsaicin. Changes in body temperature induced by combination regimens were also evaluated. MAIN METHODS: Isobolographic approach with a fixed dose-ratio of combined drugs was used to determine whether antinociceptive interaction of Phα1β and SB366791 are subadditive, additive or synergic...
August 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28608304/lambert-eaton-myasthenic-syndrome-lems-a-rare-autoimmune-presynaptic-disorder-often-associated-with-cancer
#8
REVIEW
Benedikt Schoser, Bruno Eymard, Joe Datt, Renato Mantegazza
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder that is related to the loss of functional P/Q-type voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals. Up to 60% of cases occur as a paraneoplastic disorder (SCLC-LEMS), most commonly in association with small cell lung cancer. The remaining cases have an idiopathic non-tumor etiology but are associated with underlying autoimmune disease (NT-LEMS). Patients with LEMS invariably experience progressive proximal muscle weakness, often accompanied by general fatigue and autonomic symptoms...
June 12, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28603637/t-type-voltage-gated-ca-2-channels-do-not-contribute-to-the-negative-feedback-regulation-of-myogenic-tone-in-murine-superior-epigastric-arteries
#9
Brendan Mullan, Jessica Pettis, William F Jackson
T-type voltage-gated Ca(2+) channels (CaV3.2 VGCC) have been hypothesized to control spontaneous transient outward currents (STOCs) through large-conductance Ca(2+)-activated K(+) channels (BKCa), and contribute to the negative-feedback regulation of myogenic tone. We tested this hypothesis in superior epigastric arteries (SEAs) isolated from male C57BL/6 mice. SEAs were isolated and enzymatically dissociated to obtain single smooth muscle cells (SMCs) for whole-cell recording of paxilline-sensitive (PAX, 1 μmol/L) STOCs at -30 mV, or cannulated and studied by pressure myography (80 cm H2O, 37°C)...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28587927/the-%C3%AE-4-subunit-of-the-voltage-gated-calcium-channel-cacnb4-regulates-the-rate-of-cell-proliferation-in-chinese-hamster-ovary-cells
#10
Mohamad Rima, Marwa Daghsni, Stephan De Waard, Nathalie Gaborit, Ziad Fajloun, Michel Ronjat, Yasuo Mori, Juan L Brusés, Michel De Waard
The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β4) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities...
June 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28576969/redox-regulation-of-the-yeast-voltage-gated-ca-2-channel-homolog-cch1p-by-glutathionylation-of-specific-cysteine-residues
#11
Avinash Chandel, Anand K Bachhawat
Cch1p, the yeast homolog of the pore-forming subunit α1 of the mammalian voltage-gated Ca(2+) channel (VGCC), is located on the plasma membrane and mediates the redox-dependent influx of Ca(2+) Cch1p is known to undergo both rapid activation (after oxidative stress and or a change to high pH) and slow activation (after ER stress and mating pheromone activation), but the mechanism of activation is not known. We demonstrate here that both the fast activation (exposure to pH 8-8.5 or treatment with H2O2) and the slow activation (treatment with tunicamycin or α-factor) are mediated through a common redox-dependent mechanism...
July 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28526335/the-spider-toxin-ph%C3%AE-1%C3%AE-recombinant-possesses-strong-analgesic-activity
#12
Flavia Karine Rigo, Gabriela Trevisan, Samira Dal-Toé De Prá, Marta Nascimento Cordeiro, Marcia Helena Borges, Juliana Figueiredo Silva, Flavia Viana Santa Cecilia, Alessandra Hubner de Souza, Gabriela de Oliveira Adamante, Alessandra Marcon Milioli, Célio José de Castro Junior, Juliano Ferreira, Marcus Vinicius Gomez
The native Phα1β - a Voltage-Gated Calcium Channel (VGCC) blocker - and its Recombinant Version - were both tested in rodent pain models with an intraplantar injections of capsaicin or formalin, a chronic constriction injury, and melanoma cancer related pain. The formalin nociceptive behaviour in the neurogenic phase was not affected by the toxin pre-treatments, while in the inflammatory phase, Phα1β and the Recombinant form caused a significant reduction. The nociception that was triggered by capsaicin, an agonist of the TRPV1 vanilloid receptor, was totally blocked by 100 pmol/site, i...
July 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#13
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled G protein-coupled receptors can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels (VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin 1(syt1) for binding sites on t-SNARE...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28510727/alternative-splicing-in-the-c-terminal-tail-of-cav2-1-is-essential-for-preventing-a-neurological-disease-in-mice
#14
Tomonori Aikawa, Takaki Watanabe, Taisuke Miyazaki, Takayasu Mikuni, Minoru Wakamori, Miyano Sakurai, Hidenori Aizawa, Nobutaka Ishizu, Masahiko Watanabe, Masanobu Kano, Hidehiro Mizusawa, Kei Watase
Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in the brain, MPI and MPc. These isoforms differ in their splice acceptor sites; human MPI is translated into a polyglutamine tract associated with spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop codon, resulting in a shorter cytoplasmic tail.To gain insight into the functional role of the AS in vivo and whether modulating the splice patterns at this locus can be a potential therapeutic strategy for SCA6, here we created knockin mice that exclusively express MPc by inserting the splice-site mutation...
May 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28456310/deltamethrin-affects-the-expression-of-voltage-gated-calcium-channel-%C3%AE-1-subunits-and-the-locomotion-egg-laying-foraging-behavior-of-caenorhabditis-elegans
#15
Rune Zeng, Xing Yu, Xing Tan, Shan Ye, Zhong Ding
Deltamethrin belongs to the class of synthetic pyrethroids, which are being widely used as insecticides in agricultural practices. Voltage-gated sodium channels (VGSCs) are the primary targets of these chemicals for toxicity to insects. Caenorhabditis elegans (C. elegans) does not have VGSCs but is susceptible to deltamethrin. Recent findings have suggested that pyrethroids can affect voltage-gated calcium channels (VGCCs). However, it remains elusive whether deltamethrin induces toxicity to C. elegans via modulating the activity of VGCCs...
May 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28438566/t-type-voltage-gated-calcium-channels-are-involved-in-endothelium-dependent-relaxation-of-mice-pulmonary-artery
#16
Guillaume Gilbert, Arnaud Courtois, Mathilde Dubois, Laure-Anne Cussac, Thomas Ducret, Philippe Lory, Roger Marthan, Jean-Pierre Savineau, Jean-François Quignard
In pulmonary arterial endothelial cells, Ca(2+) channels and intracellular Ca(2+) concentration ([Ca(2+)]i) control the release of vasorelaxant factors such as nitric oxide and are involved in the regulation of pulmonary arterial blood pressure. The present study was undertaken to investigate the implication of T-type voltage-gated Ca(2+) channels (T-VGCCs, Cav3.1 channel) in the endothelium-dependent relaxation of intrapulmonary arteries. Relaxation was quantified by means of a myograph in wild type and Cav3...
August 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28435258/quantum-dots-modulate-intracellular-ca-2-level-in-lung-epithelial-cells
#17
Huijuan Yin, Jacopo M Fontana, Johan Solandt, Johnny Israelsson Jussi, Hao Xu, Hjalmar Brismar, Ying Fu
While adverse effects of nanoparticles on lung health have previously been proposed, few studies have addressed the direct effects of nanoparticle exposure on the airway epithelium. In this work, we examine the response of the pulmonary airway to nanoparticles by measuring intracellular Ca(2+) concentration ([Ca(2+)]i) in the Calu-3 epithelial layer stimulated by 3-mercaptopropionic-acid (3MPA) coated CdSe-CdS/ZnS core-multishell quantum dots (QDs). Simultaneous transient transepithelial electrical resistance (TEER) decrease and global [Ca(2+)]i increase in Calu-3 epithelial layer, accompanied by cell displacements, contraction, and expansion, were observed under QD deposition...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28434782/dimeric-isoxazolyl-1-4-dihydropyridines-have-enhanced-binding-at-the-multi-drug-resistance-transporter
#18
Scott A Steiger, Chun Li, Donald S Backos, Philip Reigan, N R Natale
A series of dimeric isoxazolyl-1,4-dihydropyridines (IDHPs) were prepared by click chemistry and examined for their ability to bind the multi-drug resistance transporter (MDR-1), a member of the ATP-binding cassette superfamily (ABC). Eight compounds in the present study exhibited single digit micromolar binding to this efflux transporter. One monomeric IDHP m-Br-1c, possessed submicromolar binding of 510nM at MDR-1. Three of the dimeric IDHPs possessed <1.5µM activity, and 4b and 4c were observed to have superior binding selectivity compared to their corresponding monomers verses the voltage gated calcium channel (VGCC)...
April 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28432032/neuronal-excitation-and-permeabilization-by-200-ns-pulsed-electric-field-an-optical-membrane-potential-study-with-fluovolt-dye
#19
Andrei G Pakhomov, Iurii Semenov, Maura Casciola, Shu Xiao
Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca(2+) signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1ms...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28348377/bilirubin-augments-ca-2-load-of-developing-bushy-neurons-by-targeting-specific-subtype-of-voltage-gated-calcium-channels
#20
Min Liang, Xin-Lu Yin, Hai-Bo Shi, Chun-Yan Li, Xin-Yi Li, Ning-Ying Song, Hao-Song Shi, Yi Zhao, Lu-Yang Wang, Shan-Kai Yin
Neonatal brain is particularly vulnerable to pathological levels of bilirubin which elevates and overloads intracellular Ca(2+), leading to neurotoxicity. However, how voltage-gated calcium channels (VGCCs) are functionally involved in excess calcium influx remains unknown. By performing voltage-clamp recordings from bushy cells in the ventral cochlear nucleus (VCN) in postnatal rat pups (P4-17), we found the total calcium current density was more than doubled over P4-17, but the relative weight of VGCC subtypes changed dramatically, being relatively equal among T, L, N, P/Q and R-type at P4-6 to predominantly L, N, R over T and P/Q at P15-17...
March 27, 2017: Scientific Reports
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