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Voltage Gated Calcium Channels

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https://www.readbyqxmd.com/read/29429937/a-calmodulin-c-lobe-ca2-dependent-switch-governs-kv7-channel-function
#1
Aram Chang, Fayal Abderemane-Ali, Greg L Hura, Nathan D Rossen, Rachel E Gate, Daniel L Minor
Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation...
February 6, 2018: Neuron
https://www.readbyqxmd.com/read/29427102/spinocerebellum-ataxia-type-6-molecular-mechanisms-and-calcium-channel-genetics
#2
Xiaofei Du, Christopher Manuel Gomez
Spinocerebellar ataxia (SCA) type 6 is an autosomal dominant disease affecting cerebellar degeneration. Clinically, it is characterized by pure cerebellar dysfunction, slowly progressive unsteadiness of gait and stance, slurred speech, and abnormal eye movements with late onset. Pathological findings of SCA6 include a diffuse loss of Purkinje cells, predominantly in the cerebellar vermis. Genetically, SCA6 is caused by expansion of a trinucleotide CAG repeat in the last exon of longest isoform CACNA1A gene on chromosome 19p13...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29414872/suramin-induced-neurotoxicity-preclinical-models-and-neuroprotective-strategies
#3
David von der Ahe, Petra Huehnchen, Mustafa Balkaya, Sarah Peruzzaro, Matthias Endres, Wolfgang Boehmerle
Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed to investigate suramin-induced neuropathy with a focus on calcium (Ca2+) homeostasis as a potential pathomechanism. Adult C57Bl/6 mice treated with a single injection of 250 mg/kg bodyweight suramin developed locomotor and sensory deficits, which were confirmed by electrophysiological measurements showing a predominantly sensory axonal-demyelinating polyneuropathy...
February 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29411265/rare-risk-variants-identification-by-identity-by-descent-mapping-and-whole-exome-sequencing-implicates-neuronal-development-pathways-in-schizophrenia-and-bipolar-disorder
#4
C Salvoro, S Bortoluzzi, A Coppe, G Valle, E Feltrin, M L Mostacciuolo, G Vazza
Schizophrenia (SCZ) and bipolar disorder (BPD) are highly heritable disorders with an estimated co-heritability of 68%. Hundreds of common alleles have been implicated, but recently a role for rare, high-penetrant variants has been also suggested in both disorders. This study investigated a familial cohort of SCZ and BPD patients from a closed population sample, where the high recurrence of the disorders and the homogenous genetic background indicate a possible enrichment in rare risk alleles. A total of 230 subjects (161 cases, 22 unaffected relatives, and 47 controls) were genetically investigated through an innovative strategy that integrates identity-by-descent (IBD) mapping and whole-exome sequencing (WES)...
February 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29410612/nav1-9-potentiates-oxidized-phospholipid-induced-trp-responses-only-under-inflammatory-conditions
#5
Corinna Martin, Carolin Stoffer, Milad Mohammadi, Julian Hugo, Enrico Leipold, Beatrice Oehler, Heike L Rittner, Robert Blum
Oxidized phospholipids (OxPL) like oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) were recently identified as novel proalgesic targets in acute and chronic inflammatory pain. These endogenous chemical irritants are generated in inflamed tissue and mediate their pain-inducing function by activating the transient receptor potential channels TRPA1 and TRPV1 expressed in sensory neurons. Notably, prototypical therapeutics interfering with OxPL were shown to inhibit TRP channel activation and pain behavior...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29397554/the-role-of-intralipid-emulsion-in-the-rat-model-of-digoxin-intoxication
#6
Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Rohat Ak, Kemal Aygun, Ali Sahiner, Engin Sumer, Adnan Somay, Ozge Ecmel Onur
Although the mechanism of action is not well known, intravenous lipid emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that, ILE probably separates the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high-dose free fatty acids activating the voltage-gated calcium channels in the myocytes. In this study, effects of ILE treatment on digoxin overdose were searched in an animal model in terms of cardiac side effects and survival...
February 3, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29392225/effect-of-the-spider-toxin-tx3-3-on-spinal-processing-of-sensory-information-in-naive-and-neuropathic-rats-an-in-vivo-electrophysiological-study
#7
Gerusa D Dalmolin, Kirsty Bannister, Leonor Gonçalves, Shafaq Sikandar, Ryan Patel, Marta do Nascimento Cordeiro, Marcus Vinícius Gomez, Juliano Ferreira, Anthony H Dickenson
Introduction: Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives: In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL)...
July 2017: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/29386498/-a-retrospective-study-of-the-effects-of-3-4-diaminopyridine-treatment-in-lambert-eaton-myasthenic-syndrome
#8
Ryoji Naganuma, Ichiro Yabe, Ikuko Takahashi, Masaaki Matsushima, Takahiro Kano, Hidenao Sasaki
In this independent clinical study, we analyzed retrospectively the clinical features of 9 cases (6 male and 3 female) of Lambert-Eaton myasthenic syndrome that were administered 3,4-diaminopyridine (3,4-DAP). Four cases showed no cancer and 5 cases had small cell lung carcinoma. Seven cases were positive for anti voltage-gated calcium channel antibodies. Activities of daily living (ADL) were improved by 3,4-DAP in 8 cases that showed mainly weakness of the extremities, but did not improve ADL in 1 case with cerebellar ataxia of paraneoplastic cerebellar degeneration (PCD)...
January 31, 2018: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/29386119/ip3-receptor-dependent-cytoplasmic-ca2-signals-are-tightly-controlled-by-cav%C3%AE-3
#9
Anouar Belkacemi, Xin Hui, Barbara Wardas, Matthias W Laschke, Ulrich Wissenbach, Michael D Menger, Peter Lipp, Andreas Beck, Veit Flockerzi
Voltage-gated calcium channels (Cavs) are major Ca2+ entry pathways in excitable cells. Their β subunits facilitate membrane trafficking of the channel's ion-conducting α1 pore and modulate its gating properties. We report that one β subunit, β3, reduces Ca2+ release following stimulation of phospholipase C-coupled receptors and inositol 1,4,5-trisphosphate (IP3) formation. This effect requires the SH3-HOOK domain of Cavβ3, includes physical β3/IP3 receptor interaction, and prevails when agonist-induced IP3 formation is bypassed by photolysis of caged IP3...
January 30, 2018: Cell Reports
https://www.readbyqxmd.com/read/29385621/outgroup-emotion-processing-in-the-vacc-is-modulated-by-childhood-trauma-and-cacna1c-risk-variant
#10
Johannes T Krautheim, Benjamin Straube, Udo Dannlowski, Martin Pyka, Henriette Schneider-Hassloff, Rebecca Drexler, Axel Krug, Jens Sommer, Marcella Rietschel, Stephanie H Witt, Tilo Kircher
A high frequency of outgroup contact - as experienced by urban dwellers and migrants - possibly increases schizophrenia risk. This risk might be further amplified by genetic and environmental risk factors, such as the A-allele of rs1006737 within the Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) gene and Childhood Interpersonal Trauma (CIT). Both have been related to ventral anterior cingulate cortex (vACC) functioning. We investigated vACC functioning, during ingroup and outgroup emotion perception in relation to rs1006737 and CIT...
January 29, 2018: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/29382081/n-salicyloyltryptamine-an-n-benzoyltryptamine-analogue-induces-vasorelaxation-through-activation-of-the-no-sgc-pathway-and-reduction-of-calcium-influx
#11
Robson Cavalcante Veras, Darizy Flávia Silva, Lorena Soares Bezerra, Valéria Lopes de Assis, Walma Pereira de Vasconcelos, Maria do Carmo Alustau, José George Ferreira de Albuquerque, Fabíola Fialho Furtado, Islania Giselia de Albuquerque Araújo, Fátima de Lourdes Assunção Araújo de Azevedo, Thais Porto Ribeiro, José Maria Barbosa-Filho, Stanley Juan Chavez Gutierrez, Isac Almeida Medeiros
Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on smooth muscles. In this study, we investigated the ability of N-salicyloyltryptamine (STP) to produce vasorelaxation and determined its underlying mechanisms of action. Isolated rat mesenteric arteries with and without functional endothelium were studied in an isometric contraction system in the presence or absence of pharmacological inhibitors. Amperometric experiments were used to measure the nitric oxide (NO) levels in CD31+ cells using flow cytometry...
January 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29378016/a-phase-i-randomized-double-blind-laser-evoked-potential-study-to-evaluate-the-analgesic-antihyperalgesic-effect-of-asp9226-a-state-dependent-n-type-voltage-gated-calcium-channel-inhibitor-in-healthy-male-subjects
#12
Klaus Schaffler, Weizhong He, Paul Passier, Katherine Tracy, Allam Fakhoury, Jeffrey Paul
Objective: Evaluate the analgesic/antihyperalgesic effects of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects. Design: Randomized, double-blind, double-dummy, placebo- and active comparator-controlled crossover study. Setting: HPR Dr. Schaffler GmbH, Munich, Germany. Subject: Healthy male subjects aged 18-55 years. Methods: Twenty-four eligible subjects were randomly assigned to one of four treatment sequences and received single doses of ASP9226 (30 mg or 50 mg), pregabalin (150 mg), or placebo during four treatment periods...
January 25, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29371604/swell1-is-a-glucose-sensor-regulating-%C3%AE-cell-excitability-and-systemic-glycaemia
#13
Chen Kang, Litao Xie, Susheel K Gunasekar, Anil Mishra, Yanhui Zhang, Saachi Pai, Yiwen Gao, Ashutosh Kumar, Andrew W Norris, Samuel B Stephens, Rajan Sah
Insulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling...
January 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29364071/regulation-of-eag-by-calcium-calmodulin-controls-presynaptic-excitability-in-drosophila
#14
Peter Bronk, Elena A Kuklin, Srinivas Gorur-Shandilya, Chang Liu, Timothy D Wiggin, Martha L Reed, Eve Marder, Leslie C Griffith
Drosophila ether-à-go-go (eag) is the founding member of a large family of voltage-gated K+ channels, the KCNH family, which includes Kv10, 11 and 12, (Ganetzky et al. 1999). Concurrent binding of calcium/calmodulin (Ca2+/CaM) to N- and C-terminal sites inhibits mammalian EAG1 channels at sub-micromolar Ca2+ concentrations (Schonherr et al. 2000), likely by causing pore constriction (Whicher and MacKinnon 2016). Although the Drosophila EAG channel was believed to be Ca2+-insensitive (Schonherr et al. 2000), both the N- and C-terminal sites are conserved...
January 24, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29363593/stac-proteins-associate-to-the-iq-domain-of-cav1-2-and-inhibit-calcium-dependent-inactivation
#15
Marta Campiglio, Pierre Costé de Bagneaux, Nadine J Ortner, Petronel Tuluc, Filip Van Petegem, Bernhard E Flucher
The adaptor proteins STAC1, STAC2, and STAC3 represent a newly identified family of regulators of voltage-gated calcium channel (CaV) trafficking and function. The skeletal muscle isoform STAC3 is essential for excitation-contraction coupling and its mutation causes severe muscle disease. Recently, two distinct molecular domains in STAC3 were identified, necessary for its functional interaction with CaV1.1: the C1 domain, which recruits STAC proteins to the calcium channel complex in skeletal muscle triads, and the SH3-1 domain, involved in excitation-contraction coupling...
January 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29363587/intracellular-cavity-of-sensor-domain-controls-allosteric-gating-of-trpa1-channel
#16
Lucie Zimova, Viktor Sinica, Anna Kadkova, Lenka Vyklicka, Vlastimil Zima, Ivan Barvik, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is a temperature-sensitive ion channel activated by various pungent and irritant compounds that can produce pain in humans. Its activation involves an allosteric mechanism whereby electrophilic agonists evoke interactions within cytosolic domains and open the channel pore through an integrated nexus formed by intracellular membrane proximal regions that are densely packed beneath the lower segment of the S1-S4 sensor domain. Studies indicate that this part of the channel may contain residues that form a water-accessible cavity that undergoes changes in solvation during channel gating...
January 23, 2018: Science Signaling
https://www.readbyqxmd.com/read/29362759/a-simple-microfluidic-platform-for-the-partial-treatment-of-insuspendable-tissue-samples-with-orientation-control
#17
Anthony Fan, Alireza Tofangchi, Matthew De Venecia, Taher Saif
Microfluidic devices have extensively been applied to study biological samples, including single cells. Exploiting laminar flows on a small scale, microfluidics allow for the selective and partial exposure of samples to various chemical treatments. Traditionally, suspendable samples are first flowed into formed microchannels and are allowed to adhere to the channel floor randomly with no control over sample placement or orientation, before being subjected to partial treatment. This severely limits the choice of samples and the extent of sample preparations...
January 24, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29358363/serotonin-disinhibits-a-caenorhabditis-elegans-sensory-neuron-by-suppressing-ca-dependent-negative-feedback
#18
Paul D E Williams, Jeffrey A Zahratka, Matthew Rodenbeck, Jason Wanamaker, Hilary Linzie, Bruce A Bamber
Neuromodulators such as serotonin (5-HT) alter neuronal excitability and synaptic strengths, and define different behavioral states. Neuromodulator-dependent changes in neuronal activity patterns are frequently measured using calcium reporters, since calcium imaging can easily be performed on intact functioning nervous systems. With only 302 neurons, the nematode Caenorhabditis elegans provides a relatively simple, yet powerful, system to understand neuromodulation at the level of individual neurons. C. elegans hermaphrodites are repelled by 1-octanol, and the initiation of these aversive responses are potentiated by 5-HT...
January 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29356177/proline-rich-transmembrane-protein-2-negative-paroxysmal-kinesigenic-dyskinesia-clinical-and-genetic-analyses-of-163-patients
#19
Wo-Tu Tian, Xiao-Jun Huang, Xiao Mao, Qing Liu, Xiao-Li Liu, Sheng Zeng, Xia-Nan Guo, Jun-Yi Shen, Yang-Qi Xu, Hui-Dong Tang, Xiao-Meng Yin, Mei Zhang, Wei-Guo Tang, Xiao-Rong Liu, Bei-Sha Tang, Sheng-Di Chen, Li Cao
BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. OBJECTIVE: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel...
January 22, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29355786/upregulation-of-calcium-channel-alpha-2-delta-1-subunit-in-dorsal-horn-contributes-to-spinal-cord-injury-induced-tactile-allodynia
#20
Kazuki Kusuyama, Toshiya Tachibana, Hiroki Yamanaka, Masamichi Okubo, Shinichi Yoshiya, Koichi Noguchi
BACKGROUND CONTEX: Spinal cord injury (SCI) commonly results not only in motor paralysis but also in the emergence of neuropathic pain, both of which can impair the quality of life for SCI patients. In the clinical field, it is well known that pregabalin, which binds to the voltage-gated calcium channel α2δ-1subunit has therapeutic effects on neuropathic pain after SCI. A Previous study has demonstrated that SCI increased α2δ-1 in L4-6 dorsal spinal cord of SCI rats by Western blot analysis and that the increase of α2δ-1 was correlated with tactile allodynia of the hind paw...
January 16, 2018: Spine Journal: Official Journal of the North American Spine Society
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