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https://www.readbyqxmd.com/read/29327607/up-regulation-of-cav3-1-expression-in-sh-sy5y-cells-induced-by-lidocaine-hydrochloride
#1
Qin Gong, Xianjie Wen, Heng Li, Jian He, Yunhua Wang, Huiping Wu, Hanbing Wang, Xiaoping Wang
BACKGROUND: Neurotoxicity induced by the local anaesthetics has aroused concern. A previous study has shown that an overload of intracellular calcium was involved in the neurotoxic effect. Cav3.1 is one of the low-voltage-activated (LVA) calcium channels which play a key point to regulate the intracellular calcium ion level. This study aimed to investigate the changes of the Cav3.1 expression in the SH-SY5Y cells treated with lidocaine hydrochloride. METHODS: The SH-SY5Y cells were treated with different concentrations of lidocaine hydrochloride(1 mM, 5 mM and 10 mM, namely L1 group, L5 group and L10 group) and different exposure times (1 h,12 h and 24 h), respectively...
January 12, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29326130/inward-rectifier-potassium-channels-kir2-x-and-caveolin-3-domain-specific-interaction-implications-for-purkinje-cell-dependent-ventricular-arrhythmias
#2
Ravi Vaidyanathan, Hanora Van Ert, Kazi T Haq, Stefano Morotti, Samuel Esch, Elise C McCune, Eleonora Grandi, Lee L Eckhardt
BACKGROUND: In human cardiac ventricle, IK1 is mainly comprised Kir2.1, but Kir2.2 and Kir2.3 heterotetramers occur and modulate IK1. Long-QT syndrome-9-associated CAV3 mutations cause decreased Kir2.1 current density, but Kir2.x heterotetramers have not been studied. Here, we determine the effect of long-QT syndrome-9-CAV3 mutation F97C on Kir2.x homo- and heterotetramers and model-associated arrhythmia mechanisms. METHODS AND RESULTS: Super-resolution microscopy, co-immunoprecipitation, cellular electrophysiology, on-cell Western blotting, and simulation of Purkinje and ventricular myocyte mathematical models were used...
January 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29311306/mechanism-specific-assay-design-facilitates-the-discovery-of-nav1-7-selective-inhibitors
#3
Tania Chernov-Rogan, Tianbo Li, Gang Lu, Henry Verschoof, Kuldip Khakh, Steven W Jones, Maureen H Beresini, Chang Liu, Daniel F Ortwine, Steven J McKerrall, David H Hackos, Daniel Sutherlin, Charles J Cohen, Jun Chen
Many ion channels, including Nav1.7, Cav1.3, and Kv1.3, are linked to human pathologies and are important therapeutic targets. To develop efficacious and safe drugs, subtype-selective modulation is essential, but has been extremely difficult to achieve. We postulate that this challenge is caused by the poor assay design, and investigate the Nav1.7 membrane potential assay, one of the most extensively employed screening assays in modern drug discovery. The assay uses veratridine to activate channels, and compounds are identified based on the inhibition of veratridine-evoked activities...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29304398/generation-of-human-induced-pluripotent-stem-cells-euraci001-a-euraci002-a-euraci003-a-from-peripheral-blood-mononuclear-cells-of-three-patients-carrying-mutations-in-the-cav3-gene
#4
Viviana Meraviglia, Patrizia Benzoni, Sara Landi, Carmen Murano, Marianna Langione, Benedetta M Motta, Serena Baratto, Rosamaria Silipigni, Marina Di Segni, Peter P Pramstaller, Dario DiFrancesco, Elisabetta Gazzerro, Andrea Barbuti, Alessandra Rossini
Caveolinopathies are a heterogeneous family of genetic pathologies arising from alterations of the caveolin-3 gene (CAV3), encoding for the isoform specifically constituting muscle caveolae. Here, by reprogramming peripheral blood mononuclear cells, we report the generation of induced pluripotent stem cells (iPSCs) from three patients carrying the ΔYTT deletion, T78K and W101C missense mutations in caveolin-3. iPSCs displayed normal karyotypes and all the features of pluripotent stem cells in terms of morphology, specific marker expression and ability to differentiate in vitro into the three germ layers...
December 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29274077/increasing-t-type-calcium-channel-activity-by-%C3%AE-adrenergic-stimulation-contributes-to-%C3%AE-adrenergic-regulation-of-heart-rates
#5
Yingxin Li, Xiaoxiao Zhang, Chen Zhang, Xiaoying Zhang, Ying Li, Zhao Qi, Christopher Szeto, Mingxin Tang, Yizhi Peng, Jeffery D Molkentin, Steven R Houser, Mingxing Xie, Xiongwen Chen
OBJECTIVE: Cav3.1 (α1G ) T-type Ca2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular nodal (AVN) cells and contributes to heart rate genesis and AV conduction. However, its role in heart rate (HR) regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear, which is the topic of this study. METHODS AND RESULTS: L- (ICa-L ) and T-type (ICa-T ) Ca2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice...
December 23, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29262379/dexamethasone-induced-upregulation-of-cav3-2-t-type-ca2-channels-in-rat-cardiac-myocytes
#6
D Falcón, R González-Montelongo, E Sánchez de Rojas-de Pedro, A Ordóñez, J Ureña, A Castellano
Glucocorticoids are widely used to treat acute and chronic diseases. Unfortunately, their therapeutic use is associated with severe side effects. Glucocorticoids are known to regulate several ion channels in cardiac myocytes, including voltage-dependent Ca2+ channels. Low-voltage-activated T-type Ca2+ channels are expressed in ventricular myocytes during the fetal and perinatal period, but are practically absent in the adult. However, these channels can be re-expressed in adult cardiomyocytes under some pathological conditions...
December 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29231014/-correlation-between-genetic-variants-and-polymorphism-of-caveolin-and-sudden-unexplained-death
#7
F Y Wu, X H Tang, L L Gai, X P Kong, B Hao, E W Huang, H Shi, L H Sheng, L Quan, S P Liu, B Luo
OBJECTIVES: To explore the genetic variation sites of caveolin (CAV) and their correlation with sudden unexplained death (SUD). METHODS: The blood samples were collected from SUD group (71 cases), coronary artery disease (CAD) group (62 cases) and control group (60 cases), respectively. The genome DNA were extracted and sequencing was performed directly by amplifying gene coding region and exon-intron splicing region of CAV1 and CAV3 using PCR...
April 2017: Fa Yi Xue za Zhi
https://www.readbyqxmd.com/read/29213100/altered-spontaneous-calcium-signaling-of-in-situ-chondrocytes-in-human-osteoarthritic-cartilage
#8
Xiaoyuan Gong, Wenbin Xie, Bin Wang, Lingchuan Gu, Fuyou Wang, Xiang Ren, Cheng Chen, Liu Yang
Intracellular calcium ([Ca2+]i) signaling is an essential universal secondary messenger in articular chondrocytes. However, little is known about its spatiotemporal features in the context of osteoarthritis (OA). Herein, by examining the cartilage samples collected from patients undergoing knee arthroscopic surgery, we investigated the spatiotemporal features of spontaneous [Ca2+]i signaling in in situ chondrocytes at different OA stages. Our data showed zonal dependent spontaneous [Ca2+]i signaling in healthy cartilage samples under 4 mM calcium environment...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207174/calcium-channels-are-involved-in-ephb-ephrinb-reverse-signaling%C3%A2-induced-apoptosis-in-a-rat-chronic-ocular-hypertension-model
#9
Lingdan Dong, Xianglin Cheng, Long Zhou, Yanhong Hu
Erythropoietin-producing hepatocyte receptor B (EphB)/ephrinB reverse signaling has been revealed to be activated in chronic ocular hypertension (COH) by increasing the apoptosis of retinal ganglion cells (RGCs). However, the exact mechanism is not well understood. The present study investigated the involvement of Ca2+ channels in the apoptosis of RGCs induced by EphB/ephrinB reverse signaling in a rat CHO model, which was established by cauterizing 3 out of the 4 episcleral veins. The expression levels of four voltage‑gated Ca2+ channel subunits (Cav3...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29206848/caveolin-3-promotes-glycometabolism-growth-and-proliferation-in-muscle-cells
#10
Lina Shang, Tingting Chen, Yufeng Deng, Yiyuan Huang, Yuanheng Huang, Jing Xian, Wensheng Lu, Lihui Yang, Qin Huang
OBJECTIVE: Caveolin-3 (CAV3) protein is known to be expressed specifically in various myocytes, but its physiological function remains unclear. CAV3, located at the cell membrane, may promote the sensitivity of the Akt signaling pathway, which is closely related to glucose metabolism and to cell growth and proliferation. METHODS: The CAV3 gene was stably transfected into C2C12 muscle cells, and the effects were evaluated by biochemical assays, WB and confocal microscopy for the observation of cellular glucose metabolism, growth and proliferation, and the effect of CAV3 on the Akt signaling pathway with no insulin stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/29167643/post-inflammatory-ileitis-induces-non-neuronal-purinergic-signaling-adjustments-of-cholinergic-neurotransmission-in-the-myenteric-plexus
#11
Cátia Vieira, Fátima Ferreirinha, Maria T Magalhães-Cardoso, Isabel Silva, Patrícia Marques, Paulo Correia-de-Sá
Uncoupling between ATP overflow and extracellular adenosine formation changes purinergic signaling in post-inflammatory ileitis. Adenosine neuromodulation deficits were ascribed to feed-forward inhibition of ecto-5'-nucleotidase/CD73 by high extracellular adenine nucleotides in the inflamed ileum. Here, we hypothesized that inflammation-induced changes in cellular density may also account to unbalance the release of purines and their influence on [(3)H]acetylcholine release from longitudinal muscle-myenteric plexus preparations of the ileum of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-treated rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29165691/estradiol-protects-proopiomelanocortin-neurons-against-insulin-resistance
#12
Jian Qiu, Martha A Bosch, Cecilia Meza, Uyen-Vy Navarro, Casey C Nestor, Edward J Wagner, Oline K Rønnekleiv, Martin J Kelly
Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Since 17β-estradiol (E2) augments the excitability of the anorexigenic POMC neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male but not in DIO female mice...
November 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/29158021/gold-nanoparticles-potentiate-cav-channel-currents-in-rat-tail-artery-myocytes
#13
Fabio Fusi, Giampietro Sgaragli, Massimo Valoti
This study was designed to unveil effects of 5-nm sized, polyvinylpyrrolidone-coated gold nanoparticles (AuNPs) on vascular CaV1.2 and CaV3.1 channels. Ba(2+) currents through both channels (IBa1.2 and IBa3.1) were recorded in single myocytes isolated from the rat tail main artery by means of the whole-cell patch-clamp method. AuNPs increased IBa1.2 and IBa3.1 amplitude in a concentration- and Vh-dependent manner. Neither the voltage dependence of inactivation and activation curves nor inactivation and activation kinetics were affected by AuNPs...
November 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29129814/zinc-deficiency-promotes-cystitis-related-bladder-pain-by-enhancing-function-and-expression-of-cav3-2-in-mice
#14
Tomoka Ozaki, Junki Matsuoka, Maho Tsubota, Shiori Tomita, Fumiko Sekiguchi, Takeshi Minami, Atsufumi Kawabata
Cav3.2 T-type Ca(2+) channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Cav3.2, and enhanced by H2S that interacts with zinc. Cav3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Cav3.2 activity by H2S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Cav3...
November 10, 2017: Toxicology
https://www.readbyqxmd.com/read/29115500/roles-and-mechanisms-of-trpc3-and-the-plc%C3%AE-pkc-cpi-17-signaling-pathway-in-regulating-parturition
#15
Jing Chen, Dongming Zheng, Hong Cui, Sishi Liu, Lijuan Zhang, Caixia Liu
The aim of the current study was to investigate the role of phospholipase C (PLC)γ/protein kinase C (PKC)/C‑kinase‑activated protein phosphatase‑1 (CPI‑17) signaling pathways in uterine smooth muscle during parturition. Samples of uterine tissue were collected from pregnant patients who underwent a caesarean section for preterm delivery, full‑term delivery with labor onset, full‑term delivery without labor onset, and from a non‑pregnant control group undergoing surgery for cervical intraepithelial neoplasia III...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29082441/deletion-of-t-type-calcium-channels-cav3-1-or-cav3-2-attenuates-endothelial-dysfunction-in-aging-mice
#16
Anne D Thuesen, Kenneth Andersen, Kristina S Lyngsø, Mark Burton, Charlotte Brasch-Andersen, Paul M Vanhoutte, Pernille B L Hansen
Impairment of endothelial function with aging is accompanied by reduced nitric oxide (NO) production. T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels contribute to the endothelial dysfunction of aging. Endothelial function was determined in mesenteric arteries (perfusion) and aortae (isometric contraction) of young and old wild-type (WT), Cav3.1, and Cav3.2 knockout mice. NO production was measured by fluorescence imaging in mesenteric arteries...
October 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29074257/discovery-and-evaluation-of-cav3-2-selective-t-type-calcium-channel-blockers
#17
Olivier Bezençon, Luboš Remeň, Sylvia Richard, Catherine Roch, Melanie Kessler, Eric A Ertel, Richard Moon, Jacques Mawet, Thomas Pfeifer, Bruno Capeleto
We identified and characterized a series of pyrrole amides as potent, selective Cav3.2-blockers. This series culminated with the identification of pyrrole amides 13b and 26d, with excellent potencies and/or selectivities toward the Cav3.1- and Cav3.3-channels. These compounds display poor physicochemical and DMPK properties, making their use difficult for in vivo applications. Nevertheless, they are well-suited for in vitro studies.
September 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29073181/modulation-of-t-type-ca2-channels-by-lavender-and-rosemary-extracts
#18
Chaymae El Alaoui, Jean Chemin, Taoufiq Fechtali, Philippe Lory
Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs)...
2017: PloS One
https://www.readbyqxmd.com/read/29066309/discovery-and-evaluation-of-cav3-1-selective-t-type-calcium-channel-blockers
#19
Olivier Bezençon, Luboš Remeň, Sylvia Richard, Catherine Roch, Melanie Kessler, Richard Moon, Jacques Mawet, Eric A Ertel, Thomas Pfeifer, Bruno Capeleto
We identified and characterized a series of pyrazole amides as potent, selective Cav3.1-blockers. This series culminated with the identification of pyrazole amides 5a and 12d, with excellent potencies and/or selectivities toward the Cav3.2- and Cav3.3-channels. This compound displays poor DMPK properties, making its use difficult for in vivo applications. Nevertheless, this compound as well as analogous ones are well-suited for in vitro studies.
October 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29052595/corrigendum-hydrogen-sulfide-induced-itch-requires-activation-of-cav3-2-t-type-calcium-channel-in-mice
#20
Xue-Long Wang, Bin Tian, Ya Huang, Xiao-Yan Peng, Li-Hua Chen, Jun-Cheng Li, Tong Liu
This corrects the article DOI: 10.1038/srep16768.
October 20, 2017: Scientific Reports
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