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Annebel R De Vleeschauwer, Xiaocui Zhou, David J Lefebvre, Annabelle Garnier, Fleur Watier, Charly Pignon, Sandrine A Lacour, Stephan Zientara, Labib Bakkali-Kassimi, Kris De Clercq, Bernard Klonjkowski
Vaccination is a key element in the control of foot-and-mouth disease (FMD). The majority of the antigenic sites that induce protective immune responses are localized on the FMD virus (FMDV) capsid that is formed by four virus-encoded structural proteins, VP1 to VP4. In the present study, recombinant canine adenovirus type 2 (CAV2)-based FMD vaccines, Cav-P1/3C R° and Cav-VP1 R°, respectively expressing the structural P1 precursor protein along with the non-structural 3C protein or expressing the structural VP1 protein of the FMDV strain O/FRA/1/2001, were evaluated as novel vaccines against FMD...
March 12, 2018: Vaccine
Haowen Liu, Lei Li, Wei Wang, Jihong Gong, Xiaofei Yang, Zhitao Hu
The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release...
February 27, 2018: Cell Reports
Fang-Xiong Zhang, Vinicius M Gadotti, Ivana A Souza, Lina Chen, Gerald W Zamponi
Cavα2δ subunits contribute to the cell-surface expression of Cav2 calcium channels. Upregulation of Cavα2δ-1 in dorsal root ganglion neurons occurs after nerve injury and results in an increased synaptic abundance of Cav2.2 channels in the spinal dorsal horn, thus enhancing the transmission of pain signals. Here, we report that large conductance calcium-activated potassium (BK) channels interact with the Cavα2δ subunit. Coexpression of BK channels with the Cav2 calcium channels reduces their cell-surface expression and whole-cell current density by competing the Cavα2δ subunit away from the Cav2 complex...
February 20, 2018: Cell Reports
Che Chuan Wang, Jinn Rung Kuo, Shu Kuei Huang, Su Jane Wang
AMN082 is a selective metabotropic glutamate mGlu7 receptor agonist reported to exhibit antidepressant activity. Considering that excessive glutamate release is involved in the pathogenesis of depression, the effect of N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082) on glutamate release in rat cerebrocortical nerve terminals and the possible underlying mechanism were investigated. In this study, we observed here that AMN082 inhibited 4-aminopyridine-evoked glutamate release and this phenomenon was blocked by the metabotropic glutamate mGlu7 receptor antagonist MMPIP...
January 29, 2018: European Journal of Pharmacology
Parviz Daniel Hejazi Pastor, Xiaofei Du, Sarah Fazal, Andre N Davies, Christopher M Gomez
We have discovered that the P/Q-type voltage-gated Ca2+ channel (VGCC) gene, CACNA1A, encodes both the α1A (Cav2.1) subunit and a newly recognized transcription factor, α1ACT, by means of a novel internal ribosomal entry site (IRES) within the α1A C-terminal coding region. α1ACT, when mutated with an expansion of the polyglutamine tract in the C-terminus, gives rise to spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A gene would result in the loss of the essential Cav2.1 channel, the IRES controlling α1ACT expression is an excellent target for selective silencing of α1ACT as a therapeutic intervention for SCA6...
January 26, 2018: Cerebellum
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
Yuanlong Song, Miaomiao Zhang, Xiaoqing Tao, Zifen Xu, Yunjie Zheng, Minjie Zhu, Liangpin Zhang, Jinhan Qiao, Linlin Gao
The dissociated dorsal root ganglion (DRG) neurons with or without culture were widely used for investigation of their electrophysiological properties. The culture procedures, however, may alter the properties of these neurons and the effects are not clear. In the present study, we recorded the action potentials (AP) and the voltage-gated Na+, K+, and Ca2+ currents with patch clamp technique and measured the mRNA of Nav1.6-1.9 and Cav2.1-2.2 with real-time PCR technique from acutely dissociated and 1-day (1-d) cultured DRG neurons...
January 19, 2018: Journal of Physiology and Biochemistry
Sascha Kopp, Jayashree Sahana, Tawhidul Islam, Asbjørn Graver Petersen, Johann Bauer, Thomas J Corydon, Herbert Schulz, Kathrin Saar, Norbert Huebner, Lasse Slumstrup, Stefan Riwaldt, Markus Wehland, Manfred Infanger, Ronald Luetzenberg, Daniela Grimm
Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine (RPM). After 24 hours (h) the cells grew either adherently within a monolayer (AD) or within multicellular spheroids (MCS). AD and MCS populations were separately harvested, their cellular differences were determined performing qPCR on genes, which were differently expressed in AD and MCS cells. Gene array technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h. Furthermore, the capability to form multicellular spheroids in vitro was compared with the intracellular distribution of NF-kappaB (NFκB) p65...
January 17, 2018: Scientific Reports
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
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
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
Cheng-Wei Lu, Chi-Feng Hung, Wei-Horng Jean, Tzu-Yu Lin, Shu-Kuei Huang, Su-Jane Wang
Lycopene is a natural dietary carotenoid that was reported to exhibit a 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 Ca2+ concentration elevation. The inhibitory effect of lycopene on 4-AP-evoked glutamate release was markedly reduced in the presence of the Cav 2...
December 7, 2017: Canadian Journal of Physiology and Pharmacology
Jessica R Thomas, Jussara Hagen, Daniel Soh, Amy Lee
Voltage-gated Cav 2.1 (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 Cav 2.1 α1 subunit, most notably to a consensus CaM-binding IQ-like (IQ) domain. Closely related Cav 2.2 (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 Cav 2...
January 2, 2018: Journal of General Physiology
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
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
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
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
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
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
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
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