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https://www.readbyqxmd.com/read/29317246/presynaptic-calcium-channels
#1
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/29277284/alcohol-withdrawal-upregulates-mrna-encoding-for-cav2-1-%C3%AE-1-subunit-in-the-rat-inferior-colliculus
#2
Jamila Newton, Shubhankar Suman, Luli R Akinfiresoye, Kamal Datta, David M Lovinger, Prosper N'Gouemo
We previously reported increased current density through P-type voltage-gated Ca2+ channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased P-type channel current is currently unknown. Here, we probe changes in mRNA and protein expression of the pore-forming CaV2.1-α1 (P/Q-type) subunits in IC neurons during the course of alcohol withdrawal-induced seizures (AWSs). Rats received three daily doses of ethanol or the vehicle every 8 h for 4 consecutive days...
February 2018: Alcohol
https://www.readbyqxmd.com/read/29242712/corrigendum-conditional-knockout-of-cav2-1-disrupts-the-accuracy-of-spatial-recognition-of-ca1-place-cells-and-spatial-contextual-recognition-behavior
#3
Dahee Jung, Yu J Hwang, Hoon Ryu, Masanobu Kano, Kenji Sakimura, Jeiwon Cho
[This corrects the article on p. 214 in vol. 10, PMID: 27857685.].
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29216442/lycopene-depresses-glutamate-release-through-inhibition-of-voltage-dependent-ca-sup-2-sup-entry-and-protein-kinase-c-in-rat-cerebrocortical-nerve-terminals
#4
Cheng-Wei Lu, Chi-Feng Hung, Wei-Horng Jean, Tzu-Yu Lin, Shu-Kuei Huang, Su Jane Wang
Lycopene is a natural dietary carotenoid which was reported to exhibit neuroprotective profile. Considering that excitotoxicity and cell death induced by glutamate are involved in many brain disorders, the effect of lycopene on glutamate release in rat cerebrocortical nerve terminals and the possible mechanism involved in such effect was investigated. We observed here that lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and intrasynaptosomal Ca <sup>2+<sup> concentration elevation...
December 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29208674/molecular-moieties-masking-ca2-dependent-facilitation-of-voltage-gated-cav2-2-ca2-channels
#5
Jessica R Thomas, Jussara Hagen, Daniel Soh, Amy Lee
Voltage-gated Cav2.1 (P/Q-type) Ca2+ channels undergo Ca2+-dependent inactivation (CDI) and facilitation (CDF), both of which contribute to short-term synaptic plasticity. Both CDI and CDF are mediated by calmodulin (CaM) binding to sites in the C-terminal domain of the Cav2.1 α1 subunit, most notably to a consensus CaM-binding IQ-like (IQ) domain. Closely related Cav2.2 (N-type) channels display CDI but not CDF, despite overall conservation of the IQ and additional sites (pre-IQ, EF-hand-like [EF] domain, and CaM-binding domain) that regulate CDF of Cav2...
December 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29177691/differential-association-of-gabab-receptors-with-their-effector-ion-channels-in-purkinje-cells
#6
Rafael Luján, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis de la Ossa, Bernhard Bettler, Kevin Wickman, Masahiko Watanabe, Ryuichi Shigemoto, Yugo Fukazawa
Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines...
November 25, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29163057/synchronicity-and-rhythmicity-of-purkinje-cell-firing-during-generalized-spike-and-wave-discharges-in-a-natural-mouse-model-of-absence-epilepsy
#7
Lieke Kros, Sander Lindeman, Oscar H J Eelkman Rooda, Pavithra Murugesan, Lorenzo Bina, Laurens W J Bosman, Chris I De Zeeuw, Freek E Hoebeek
Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29104244/a-multi-locus-genetic-risk-score-for-primary-open-angle-glaucoma-poag-variants-is-associated-with-poag-risk-in-a-mediterranean-population-inverse-correlations-with-plasma-vitamin-c-and-e-concentrations
#8
Vicente Zanon-Moreno, Carolina Ortega-Azorin, Eva M Asensio-Marquez, Jose J Garcia-Medina, Maria D Pinazo-Duran, Oscar Coltell, Jose M Ordovas, Dolores Corella
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS)...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29089769/identification-of-a-novel-cacna1a-mutation-in-a-chinese-family-with-autosomal-recessive-progressive-myoclonic-epilepsy
#9
Yudan Lv, Zan Wang, Chang Liu, Li Cui
BACKGROUND: Progressive myoclonic epilepsy (PME) is a heterogeneous neurodegenerative disorder, which is commonly manifested with refractory seizures and neurologic deterioration. The prognosis of PME is poor, so early diagnosis of PME is critical. The aim of our study is to identify the novel pathogenic gene in a Chinese family with PME, which may be helpful in future. SUBJECTS AND METHODS: A three-generation consanguineous Chinese Han family with PME was recruited...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29067356/cell-specific-rna-binding-protein-rbfox2-regulates-cav2-2-mrna-exon-composition-and-cav2-2-current-size
#10
Summer E Allen, Cecilia P Toro, Arturo Andrade, Eduardo J López-Soto, Sylvia Denome, Diane Lipscombe
The majority of multiexon mammalian genes contain alternatively spliced exons that have unique expression patterns in different cell populations and that have important cell functions. The expression profiles of alternative exons are controlled by cell-specific splicing factors that can promote exon inclusion or exon skipping but with few exceptions we do not know which specific splicing factors control the expression of alternatively spliced exons of known biological function. Many ion channel genes undergo extensive alternative splicing including Cacna1b that encodes the voltage-gated CaV2...
September 2017: ENeuro
https://www.readbyqxmd.com/read/29065889/injury-induced-expression-of-caveolar-proteins-in-human-kidney-tubules-role-of-megakaryoblastic-leukemia-1
#11
Krzysztof M Krawczyk, Jennifer Hansson, Helén Nilsson, Katarzyna K Krawczyk, Karl Swärd, Martin E Johansson
BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined. METHODS: Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3 and cavin 1-4) and examined by electron microscopy...
October 24, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-cav-channels
#12
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low-voltage activated (LVA, CaV3.1-3.3)...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28972185/calmodulin-regulates-cav3-t-type-channels-at-their-gating-brake
#13
Jean Chemin, Valentina Taiakina, Arnaud Monteil, Michael Piazza, Wendy Guan, Robert F Stephens, Ashraf Kitmitto, Zhiping P Pang, Annette C Dolphin, Edward Perez-Reyes, Thorsten Dieckmann, Joseph Guy Guillemette, J David Spafford
Calcium (Cav1 and Cav2) and sodium channels possess homologous CaM-binding motifs, known as IQ motifs in their C-termini, which associate with calmodulin (CaM), a universal calcium sensor. Cav3 T-type channels, which serve as pacemakers of the mammalian brain and heart, lack a C-terminal IQ motif. We illustrate that T-type channels associate with CaM using co-immunoprecipitation experiments and single particle cryo-electron microscopy. We demonstrate that protostome invertebrate (LCav3) and human Cav3.1, Cav3...
September 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28957379/involvement-of-parkin-in-the-ubiquitin-proteasome-system-mediated-degradation-of-n-type-voltage-gated-ca2-channels
#14
Lizbeth Grimaldo, Alejandro Sandoval, Edgar Garza-López, Ricardo Felix
N-type calcium (CaV2.2) channels are widely expressed in the brain and the peripheral nervous system, where they play important roles in the regulation of transmitter release. Although CaV2.2 channel expression levels are precisely regulated, presently little is known regarding the molecules that mediate its synthesis and degradation. Previously, by using a combination of biochemical and functional analyses, we showed that the complex formed by the light chain 1 of the microtubule-associated protein 1B (LC1-MAP1B) and the ubiquitin-proteasome system (UPS) E2 enzyme UBE2L3, may interact with the CaV2...
2017: PloS One
https://www.readbyqxmd.com/read/28946818/bicistronic-cacna1a-gene-expression-in-neurons-derived-from-spinocerebellar-ataxia-type-6-patient-induced-pluripotent-stem-cells
#15
Carlo Bavassano, Andreas Eigentler, Ruslan Stanika, Gerald J Obermair, Sylvia Boesch, Georg Dechant, Roxana Nat
Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative disorder that is caused by a CAG trinucleotide repeat expansion in the CACNA1A gene. As one of the few bicistronic genes discovered in the human genome, CACNA1A encodes not only the α1A subunit of the P/Q type voltage-gated Ca(2+) channel CaV2.1 but also the α1ACT protein, a 75 kDa transcription factor sharing the sequence of the cytoplasmic C-terminal tail of the α1A subunit. Isoforms of both proteins contain the polyglutamine (polyQ) domain that is expanded in SCA6 patients...
November 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28930822/five-years-experience-on-3-4-diaminopyridine-phosphate-in-lambert-eaton-syndrome-case-reports
#16
Simona Portaro, Teresa Brizzi, Stefano Sinicropi, Alberto Cacciola, Maria Cristina De Cola, Alessia Bramanti, Demetrio Milardi, Antonino Lupica, Placido Bramanti, Antonio Toscano, Carmelo Rodolico
RATIONALE: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. PATIENT CONCERNS: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28880874/discovery-and-mode-of-action-of-a-novel-analgesic-%C3%AE-toxin-from-the-african-spider-ceratogyrus-darlingi
#17
Silmara R Sousa, Joshua S Wingerd, Andreas Brust, Christopher Bladen, Lotten Ragnarsson, Volker Herzig, Jennifer R Deuis, Sebastien Dutertre, Irina Vetter, Gerald W Zamponi, Glenn F King, Paul F Alewood, Richard J Lewis
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 of 1318 pmol/g) and inhibited human Cav2.2 (IC50 2.6 μM) but not Cav1.3 or Cav3.1 (IC50 > 30 μM) in fluorimetric assays...
2017: PloS One
https://www.readbyqxmd.com/read/28878269/caveolin-1-protects-retinal-ganglion-cells-against-acute-ocular-hypertension-injury-via-modulating-microglial-phenotypes-and-distribution-and-activating-akt-pathway
#18
Liwei Zhang, Jiazhou Xu, Ran Liu, Wei Chen, Qishan Chen, Wenjie Hu, Lan Zhou, Ruting Zhang, Hongping Xu, Dongyue Lin, Xuri Li, Zhongshu Tang
Glaucoma, a group of eye diseases, causes gradual loss of retinal ganglion cells (RGCs) and ultimately results in irreversible blindness. Studies of the underlying mechanisms of glaucoma and clinical trial are far from satisfactory. Results from a genome-wide association study have suggested that the CAV1/CAV2 locus is associated with glaucoma, but this association and its potential underlying mechanisms need to be confirmed and further explored. Here, we studied the function of caveolin-1 (Cav1) in an acute ocular hypertension glaucoma model...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837380/cav2-channel-subtype-expression-in-rat-sympathetic-neurons-is-selectively-regulated-by-%C3%AE-2%C3%AE-subunits
#19
Mallory B Scott, Paul J Kammermeier
Type two voltage gated calcium (CaV2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability (1) . Mechanisms that regulate CaV2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express CaV2.2 and CaV2.3 (2) . We noted previously that heterologous expression of CaV2...
August 24, 2017: Channels
https://www.readbyqxmd.com/read/28832686/additive-effects-of-genetic-variants-associated-with-intraocular-pressure-in-primary-open-angle-glaucoma
#20
Fumihiko Mabuchi, Nakako Mabuchi, Yoichi Sakurada, Seigo Yoneyama, Kenji Kashiwagi, Hiroyuki Iijima, Zentaro Yamagata, Mitsuko Takamoto, Makoto Aihara, Takeshi Iwata, Kazuhide Kawase, Yukihiro Shiga, Koji M Nishiguchi, Toru Nakazawa, Mineo Ozaki, Makoto Araie
To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2...
2017: PloS One
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