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CaV2.2

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https://www.readbyqxmd.com/read/28167673/ubiquitin-ligase-rnf138-promotes-episodic-ataxia-type-2-associated-aberrant-degradation-of-human-cav2-1-p-q-type-calcium-channels
#1
Ssu-Ju Fu, Chung-Jiuan Jeng, Chia-Hao Ma, Yi-Jheng Peng, Chi-Ming Lee, Ya-Ching Fang, Yi-Ching Lee, Sung-Chun Tang, Meng-Chun Hu, Chih-Yung Tang
: Voltage-gated CaV2.1 channels comprise a pore-forming α1A (CaV2.1) subunit with auxiliary α2δ and β subunits. CaV2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding CaV2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of CaV2.1 wild-type (WT) protein expression via aberrant proteasomal degradation...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28161890/homology-guided-mutational-analysis-reveals-the-functional-requirements-for-antinociceptive-specificity-of-crmp2-derived-peptides
#2
Aubin Moutal, Wennan Li, Yue Wang, Weina Ju, Shizhen Luo, Song Cai, Liberty François-Moutal, Samantha Perez-Miller, Jackie Hu, Erik T Dustrude, Todd W Vanderah, Vijay Gokhale, May Khanna, Rajesh Khanna
BACKGROUND AND PURPOSE: N-type voltage-gated calcium (CaV2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Despite CaV2.2 antagonism being recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and are often mired by numerous side-effects. Collapsin response mediator protein 2 (CRMP2) targets CaV2.2 to the sensory neuron membrane, and allosterically modulates Cav2...
February 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28145504/honeybee-locomotion-is-impaired-by-am-cav3-low-voltage-activated-ca-2-channel-antagonist
#3
M Rousset, C Collet, T Cens, F Bastin, V Raymond, I Massou, C Menard, J-B Thibaud, M Charreton, M Vignes, M Chahine, J C Sandoz, P Charnet
Voltage-gated Ca(2+) channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca(2+) channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143451/distinct-prostate-cancer-related-mrna-cargo-in-extracellular-vesicle-subsets-from-prostate-cell-lines
#4
Elisa Lázaro-Ibáñez, Taral R Lunavat, Su Chul Jang, Carmen Escobedo-Lucea, Jorge Oliver-De La Cruz, Pia Siljander, Jan Lötvall, Marjo Yliperttula
BACKGROUND: Multiple types of extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs), are released by all cells constituting part of the cellular EV secretome. The bioactive cargo of EVs can be shuffled between cells and consists of lipids, metabolites, proteins, and nucleic acids, including multiple RNA species from non-coding RNAs to messenger RNAs (mRNAs). In this study, we hypothesized that the mRNA cargo of EVs could differ based on the EV cellular origin and subpopulation analyzed...
February 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28132918/ciproxifan-a-histamine-h3-receptor-antagonist-and-inverse-agonist-presynaptically-inhibits-glutamate-release-in-rat-hippocampus
#5
Cheng-Wei Lu, Tzu-Yu Lin, Chia-Ying Chang, Shu-Kuei Huang, Su-Jane Wang
Ciproxifan is an H3 receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Cav2...
January 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28131838/phospholipase-c-dependent-hydrolysis-of-phosphatidylinositol-4-5-bisphosphate-underlies-agmatine-induced-suppression-of-n-type-ca-2-channel-in-rat-celiac-ganglion-neurons
#6
Young-Hwan Kim, Ji-Hyun Jeong, Duck-Sun Ahn, Seungsoo Chung
Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (ICav2.2) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited ICav2.2 in a VI manner. The agmatine-induced inhibition of the ICav2...
January 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28127114/cacna1b-cav2-2-overexpression-and-its-association-with-clinicopathologic-characteristics-and-unfavorable-prognosis-in-non-small-cell-lung-cancer
#7
Xiaoyu Zhou, Wei Wang, Shu Zhang, Xudong Wang, Zhiyuan Tang, Jun Gu, Jun Li, Jianan Huang
CACNA1B (Cav2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (Cav2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated...
2017: Disease Markers
https://www.readbyqxmd.com/read/28122853/caveolin-2-a-facultative-marker-of-unfavourable-prognosis-in-long-term-patency-rate-of-internal-thoracic-artery-grafts-used-in-coronary-artery-bypass-grafting-preliminary-report
#8
Agnieszka Malinska, Zuzanna Podemska, Patrycja Sujka-Kordowska, Wojciech Witkiewicz, Michal Nowicki, Bartlomiej Perek, Martin Witt
OBJECTIVES: Intimal hyperplasia leading to graft failure in patients undergoing coronary artery bypass grafting (CABG) is related to vascular smooth muscle cells (SMCs) proliferation. SMCs respond to a variety of mediators, the most important of which is platelet-derived growth factor (PDGF). The platelet-derived growth factor-induced cellular response has been shown to be mediated by caveolins. The aim of this study was to analyze CAV1-3 expression in internal thoracic artery (ITA) grafts used in CABG and correlate their expression with graft occlusion...
January 25, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28117367/the-sorting-receptor-rer1-controls-purkinje-cell-function-via-voltage-gated-sodium-channels
#9
Christina Valkova, Lutz Liebmann, Andreas Krämer, Christian A Hübner, Christoph Kaether
Rer1 is a sorting receptor in the early secretory pathway that controls the assembly and the cell surface transport of selected multimeric membrane protein complexes. Mice with a Purkinje cell (PC) specific deletion of Rer1 showed normal polarization and differentiation of PCs and normal development of the cerebellum. However, PC-specific loss of Rer1 led to age-dependent motor deficits in beam walk, ladder climbing and gait. Analysis of brain sections revealed a specific degeneration of PCs in the anterior cerebellar lobe in old animals...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115484/target-cell-type-dependent-differences-in-ca2-channel-function-underlie-distinct-release-probabilities-at-hippocampal-glutamatergic-terminals
#10
Tímea Éltes, Tekla Kirizs, Zoltan Nusser, Noemi Holderith
: Target cell type-dependent differences in presynaptic release probability (Pr) and short-term plasticity are intriguing features of cortical microcircuits that increase the computational power of neuronal networks. Here we tested the hypothesis that different voltage-gated Ca(2+) channel densities in presynaptic active zones (AZs) underlie different Pr Two-photon Ca(2+) imaging, triple immunofluorescent labeling and three-dimensional electron microscopic (EM) reconstruction of rat CA3 pyramidal cell axon terminals revealed approximately 1...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#11
F Agosti, S Cordisco Gonzalez, V Martinez Damonte, M J Tolosa, N Di Siervi, H B Schioth, C Davio, M Perello, J Raingo
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (CaV2...
January 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28092651/long-lasting-antinociceptive-effects-of-green-light-in-acute-and-chronic-pain-in-rats
#12
Mohab M Ibrahim, Amol Patwardhan, Kerry B Gilbraith, Aubin Moutal, Xiaofang Yang, Lindsey A Chew, Tally Largent-Milnes, T Philip Malan, Todd W Vanderah, Frank Porreca, Rajesh Khanna
Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain...
February 2017: Pain
https://www.readbyqxmd.com/read/28007571/multiple-nickel-sensitive-targets-elicit-cardiac-arrhythmia-in-isolated-mouse-hearts-after-pituitary-adenylate-cyclase-activating-polypeptide-mediated-chronotropy
#13
Etienne E Tevoufouet, Erastus N Nembo, Fabian Distler, Felix Neumaier, Jürgen Hescheler, Filomain Nguemo, Toni Schneider
The pituitary adenylate cyclase-activating polypeptide (PACAP)-27 modulates various biological processes, from the cellular level to function specification. However, the cardiac actions of this neuropeptide are still under intense studies. Using control (+|+) and mice lacking (-|-) either R-type (Cav2.3) or T-type (Cav3.2) Ca(2+) channels, we investigated the effects of PACAP-27 on cardiac activity of spontaneously beating isolated perfused hearts. Superfusion of PACAP-27 (20nM) caused a significant increase of baseline heart frequency in Cav2...
December 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#14
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27847332/intralipid-protects-the-heart-in-late-pregnancy-against-ischemia-reperfusion-injury-via-caveolin2-stat3-gsk-3%C3%AE-pathway
#15
Jingyuan Li, Gregoire Ruffenach, Georgios Kararigas, Christine M Cunningham, Negar Motayagheni, Neusha Barakai, Soban Umar, Vera Regitz-Zagrosek, Mansoureh Eghbali
BACKGROUND: We recently demonstrated that the heart of late pregnant (LP) rodents is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant rodents. Lipids, particularly polyunsaturated fatty acids, have received special attention in the field of cardiovascular research. Here, we explored whether Intralipid (ITLD) protects the heart against I/R injury in LP rodents and investigated the mechanisms underlying this protection. METHODS AND RESULTS: In-vivo female LP rat hearts or ex-vivo isolated Langendorff-perfused LP mouse hearts were subjected to ischemia followed by reperfusion with PBS or ITLD (one bolus of 5mg/kg of 20% in in-vivo and 1% in ex-vivo)...
November 12, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27843503/review-cav2-3-r-type-voltage-gated-ca-2-channels-functional-implications-in-convulsive-and-non-convulsive-seizure-activity
#16
Carola Wormuth, Andreas Lundt, Christina Henseler, Ralf Müller, Karl Broich, Anna Papazoglou, Marco Weiergräber
BACKGROUND: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca(2+) channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca(2+) channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2...
2016: Open Neurology Journal
https://www.readbyqxmd.com/read/27799552/calcium-sensor-regulation-of-the-cav2-1-ca2-channel-contributes-to-long-term-potentiation-and-spatial-learning
#17
Evanthia Nanou, Todd Scheuer, William A Catterall
Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca(2+) type 2.1 (CaV2.1) channels. However, the contribution of regulation of CaV2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of CaV2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
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
#18
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/27720444/calcium-calmodulin-dependent-serine-protein-kinase-cask-modulates-the-l-type-calcium-current
#19
Sabine Nafzger, Jean-Sebastien Rougier
AIM: The L-type voltage-gated calcium channel Cav1.2 mediates the calcium influx into cells upon membrane depolarization. The list of cardiopathies associated to Cav1.2 dysfunctions highlights the importance of this channel in cardiac physiology. Calcium/calmodulin-dependent serine protein kinase (CASK), expressed in cardiac cells, has been identified as a regulator of Cav2.2 channels in neurons, but no experiments have been performed to investigate its role in Cav1.2 regulation. METHODS AND RESULTS: Full length or the distal C-terminal truncated of the pore-forming Cav1...
October 5, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27671655/rim-binding-protein-2-regulates-release-probability-by-fine-tuning-calcium-channel-localization-at-murine-hippocampal-synapses
#20
M Katharina Grauel, Marta Maglione, Suneel Reddy-Alla, Claudia G Willmes, Marisa M Brockmann, Thorsten Trimbuch, Tanja Rosenmund, Maria Pangalos, Gülçin Vardar, Alexander Stumpf, Alexander M Walter, Benjamin R Rost, Britta J Eickholt, Volker Haucke, Dietmar Schmitz, Stephan J Sigrist, Christian Rosenmund
The tight spatial coupling of synaptic vesicles and voltage-gated Ca(2+) channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca(2+) channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2-deficient murine hippocampal neurons in cultures and slices...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
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