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Cav2.1

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https://www.readbyqxmd.com/read/27857685/conditional-knockout-of-cav2-1-disrupts-the-accuracy-of-spatial-recognition-of-ca1-place-cells-and-spatial-contextual-recognition-behavior
#1
Dahee Jung, Yu J Hwang, Hoon Ryu, Masanobu Kano, Kenji Sakimura, Jeiwon Cho
Hippocampal pyramidal neurons play an essential role in processing spatial information as implicated with its place-dependent firing. Although, previous slice physiology studies have reported that voltage gated calcium channels contribute to spike shapes and corresponding firing rate in the hippocampus, the roles of P/Q type calcium channels (Cav2.1) underlying neural activity in behaving mice have not been well-investigated. To determine physiological and behavioral roles of Cav2.1, we conducted place cell recordings in CA1 and hippocampus dependent learning/memory tasks using mice lacking Cav2...
2016: Frontiers in Behavioral Neuroscience
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
#2
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
#3
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/27806289/vulnerability-of-purkinje-cells-generated-from-spinocerebellar-ataxia-type-6-patient-derived-ipscs
#4
Yoshihito Ishida, Hideshi Kawakami, Hiroyuki Kitajima, Ayaka Nishiyama, Yoshiki Sasai, Haruhisa Inoue, Keiko Muguruma
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27799552/calcium-sensor-regulation-of-the-cav2-1-ca2-channel-contributes-to-long-term-potentiation-and-spatial-learning
#5
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/27671655/rim-binding-protein-2-regulates-release-probability-by-fine-tuning-calcium-channel-localization-at-murine-hippocampal-synapses
#6
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
https://www.readbyqxmd.com/read/27581393/neural-cell-proliferation-and-survival-in-the-hippocampus-of-adult-cav-2-1-calcium-ion-channel-mutant-mice
#7
Fikru Nigussie, Pei-San Huang, Kris Lukauskis, Bhupinder Bawa, Eid Moussa, Louise C Abbott
Tottering mutant mice carry a mutation in the pore-forming subunit (α1A) of CaV2.1 (P/Q-type) voltage-gated calcium ion (Ca(2+)) channels resulting in reduced neuronal Ca(2+) current density. We assessed male tottering mice for spatial learning using the Morris water maze. Tottering mice performed worse than wild type mice, suggesting abnormal hippocampal function. Because Ca(2+) influx via voltage-dependent Ca(2+) channels regulates neuronal survival and function, we assessed hippocampus volume and cell density using hematoxylin and eosin stained serial sections...
November 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27537197/similar-gabaa-receptor-subunit-composition-in-somatic-and-axon-initial-segment-synapses-of-hippocampal-pyramidal-cells
#8
Katalin Kerti-Szigeti, Zoltan Nusser
Hippocampal pyramidal cells (PCs) express many GABAAR subunit types and receive GABAergic inputs from distinct interneurons. Previous experiments revealed input-specific differences in α1 and α2 subunit densities in perisomatic synapses, suggesting distinct IPSC decay kinetics. However, IPSC decays evoked by axo-axonic, parvalbumin- or cholecystokinin-expressing basket cells were found to be similar. Using replica immunogold labeling, here we show that all CA1 PC somatic and AIS synapses contain the α1, α2, β1, β2, β3 and γ2 subunits...
2016: ELife
https://www.readbyqxmd.com/read/27489103/the-cav%C3%AE-subunit-protects-the-i-ii-loop-of-the-voltage-gated-calcium-channel-cav2-2-from-proteasomal-degradation-but-not-oligoubiquitination
#9
Karen M Page, Simon W Rothwell, Annette C Dolphin
CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598-9611)...
September 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27468821/redistribution-of-cav2-1-channels-and-calcium-ions-in-nerve-terminals-following-end-to-side-neurorrhaphy-ionic-imaging-analysis-by-tof-sims
#10
Chiung-Hui Liu, Hung-Ming Chang, To-Jung Tseng, Chyn-Tair Lan, Li-You Chen, Su-Chung Youn, Jian-Jr Lee, Fu-Der Mai, Jui-Feng Chou, Wen-Chieh Liao
The P/Q-type voltage-dependent calcium channel (Cav2.1) in the presynaptic membranes of motor nerve terminals plays an important role in regulating Ca(2+) transport, resulting in transmitter release within the nervous system. The recovery of Ca(2+)-dependent signal transduction on motor end plates (MEPs) and innervated muscle may directly reflect nerve regeneration following peripheral nerve injury. Although the functional significance of calcium channels and the levels of Ca(2+) signalling in nerve regeneration are well documented, little is known about calcium channel expression and its relation with the dynamic Ca(2+) ion distribution at regenerating MEPs...
November 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27430911/baicalein-a-constituent-of-scutellaria-baicalensis-reduces-glutamate-release-and-protects-neuronal-cell-against-kainic-acid-induced-excitotoxicity-in-rats
#11
Yi Chang, Cheng Wei Lu, Tzu Yu Lin, Shu Kuei Huang, Su Jane Wang
Interest in the health benefits of flavonoids, particularly their effects on neurodegenerative disease, is increasing. This study evaluated the role of baicalein, a flavonoid compound isolated from the traditional Chinese medicine Scutellaria baicalensis, in glutamate release and glutamate neurotoxicity in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), baicalein inhibits depolarization-induced glutamate release, and this phenomenon is prevented by chelating the extracellular Ca[Formula: see text] ions and blocking presynaptic Cav2...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27378904/stimulation-of-synaptic-vesicle-exocytosis-by-the-mental-disease-gene-disc1-is-mediated-by-n-type-voltage-gated-calcium-channels
#12
Willcyn Tang, Jervis Vermal Thevathasan, Qingshu Lin, Kim Buay Lim, Keisuke Kuroda, Kozo Kaibuchi, Marcel Bilger, Tuck Wah Soong, Marc Fivaz
Lesions and mutations of the DISC1 (Disrupted-in-schizophrenia-1) gene have been linked to major depression, schizophrenia, bipolar disorder and autism, but the influence of DISC1 on synaptic transmission remains poorly understood. Using two independent genetic approaches-RNAi and a DISC1 KO mouse-we examined the impact of DISC1 on the synaptic vesicle (SV) cycle by population imaging of the synaptic tracer vGpH in hippocampal neurons. DISC1 loss-of-function resulted in a marked decrease in SV exocytic rates during neuronal stimulation and was associated with reduced Ca(2+) transients at nerve terminals...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27375432/characterization-of-a-synaptic-vesicle-binding-motif-on-the-distal-cav2-2-channel-c-terminal
#13
Sabiha R Gardezi, Arup R Nath, Qi Li, Elise F Stanley
Neurotransmitter is released from synaptic vesicles (SVs) that are gated to fuse with the presynaptic membrane by calcium ions that enter through voltage-gated calcium channels (CaVs). There is compelling evidence that SVs associate closely with the CaVs but the molecular linking mechanisms remain poorly understood. Using a cell-free, synaptic vesicle-pull-down assay method (SV-PD) we have recently demonstrated that SVs can bind both to the intact CaV2.2 channel and also to a fusion protein comprising the distal third, C3 segment, of its long C-terminal...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27347934/echinacoside-inhibits-glutamate-release-by-suppressing-voltage-dependent-ca-2-entry-and-protein-kinase-c-in-rat-cerebrocortical-nerve-terminals
#14
Cheng Wei Lu, Tzu Yu Lin, Shu Kuei Huang, Su Jane Wang
The glutamatergic system may be involved in the effects of neuroprotectant therapies. Echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Herba Cistanche, has neuroprotective effects. This study investigated the effects of echinacoside on 4-aminopyridine-evoked glutamate release in rat cerebrocortical nerve terminals (synaptosomes). Echinacoside inhibited Ca(2+)-dependent, but not Ca(2+)-independent, 4-aminopyridine-evoked glutamate release in a concentration-dependent manner...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27346147/loss-of-inhibition-by-brain-natriuretic-peptide-over-p2x3-receptors-contributes-to-enhanced-spike-firing-of-trigeminal-ganglion-neurons-in-a-mouse-model-of-familial-hemiplegic-migraine-type-1
#15
Anna Marchenkova, Arn M J M van den Maagdenberg, Andrea Nistri
Purinergic P2X3 receptors (P2X3Rs) play an important role in pain pathologies, including migraine. In trigeminal neurons, P2X3Rs are constitutively downregulated by endogenous brain natriuretic peptide (BNP). In a mouse knock-in (KI) model of familial hemiplegic migraine type-1 with upregulated calcium CaV2.1 channel function, trigeminal neurons exhibit hyperexcitability with gain-of-function of P2X3Rs and their deficient BNP-mediated inhibition. We studied whether the absent BNP-induced control over P2X3Rs activity in KI cultures may be functionally expressed in altered firing activity of KI trigeminal neurons...
September 7, 2016: Neuroscience
https://www.readbyqxmd.com/read/27297022/ethnic-specific-association-of-the-cav1-cav2-locus-with-primary-open-angle-glaucoma
#16
Shi Song Rong, Li Jia Chen, Christopher K S Leung, Kenji Matsushita, Liyun Jia, Atsuya Miki, Sylvia W Y Chiang, Pancy O S Tam, Noriyasu Hashida, Alvin L Young, Motokazu Tsujikawa, Mingzhi Zhang, Ningli Wang, Kohji Nishida, Chi Pui Pang
A single-nucleotide polymorphism (SNP) rs4236601 at the CAV1/CAV2 locus is associated with primary open-angle glaucoma (POAG). Rs4236601 is common in Caucasians but rare in East Asians. Here we conducted a haplotype-tagging SNP analysis followed by replication in a total of 848 POAG cases and 1574 controls drawn from 3 cities in China and 1 city in Japan. Two SNPs, rs4236601 (odds ratio [OR] = 6.25; P = 0.0086) and a tagging-SNP rs3801994 (OR = 1.32; P = 0.042), were associated with POAG in the Hong Kong Chinese cohort after age and gender adjustments...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27260834/a-cav2-1-n-terminal-fragment-relieves-the-dominant-negative-inhibition-by-an-episodic-ataxia-2-mutant
#17
Shehrazade Dahimene, Karen M Page, Manuela Nieto-Rostro, Wendy S Pratt, Marianna D'Arco, Annette C Dolphin
Episodic ataxia 2 (EA2) is an autosomal dominant disorder caused by mutations in the gene CACNA1A that encodes the pore-forming CaV2.1 calcium channel subunit. The majority of EA2 mutations reported so far are nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous expression of wild-type CaV2.1, together with truncated constructs that mimic EA2 mutants, significantly suppressed wild-type calcium channel function, indicating that the truncated protein produces a dominant-negative effect (Jouvenceau et al...
September 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27245500/mechanism-of-direct-cav2-2-channel-block-by-the-%C3%AE%C2%BA-opioid-receptor-agonist-u50488h
#18
Géza Berecki, Leonid Motin, David J Adams
U50488H is a benzeneacetamide κ-opioid receptor (κ-OR) agonist analgesic, widely used for investigating the pharmacology of G protein-coupled κ-ORs. However, U50488H is also known to directly block various voltage-gated ion channels in a G protein-independent manner. We investigated the direct actions of U50488H on various high voltage-activated (HVA) and low voltage-activated (LVA) neuronal Ca(2+) channels heterologously expressed in human embryonic kidney (HEK293) cells. U50488H inhibited HVA rat Cav1...
October 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27242426/lrrk2-regulates-voltage-gated-calcium-channel-function
#19
Cade Bedford, Catherine Sears, Maria Perez-Carrion, Giovanni Piccoli, Steven B Condliffe
Voltage-gated Ca(2+) (CaV) channels enable Ca(2+) influx in response to membrane depolarization. CaV2.1 channels are localized to the presynaptic membrane of many types of neurons where they are involved in triggering neurotransmitter release. Several signaling proteins have been identified as important CaV2.1 regulators including protein kinases, G-proteins and Ca(2+) binding proteins. Recently, we discovered that leucine rich repeat kinase 2 (LRRK2), a protein associated with inherited Parkinson's disease, interacts with specific synaptic proteins and influences synaptic transmission...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27228562/enos-activity-in-cav1-knockout-mouse-eyes
#20
Yuan Lei, Maomao Song, Jihong Wu, Chao Xing, Xinghuai Sun
PURPOSE: To investigate endothelial nitric oxide synthase (eNOS) activity and the response of conventional outflow facility to nitric oxide donors and a nitric oxide synthase (NOS) inhibitor in caveolin-1 (CAV1) knockout (KO) mice. METHODS: Intraocular pressure (IOP) was measured in both CAV1 KO and wild-type (WT) mice by rebound tonometry. The expressions of caveolin-2 (CAV2), eNOS, eNOS-phospho Ser1177, eNOS-phospho Thr495, Akt, Akt-phospho Ser473, and nitrotyrosin were measured by Western blot analysis...
May 1, 2016: Investigative Ophthalmology & Visual Science
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