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Wenqin Hu, Bruce P Bean
Voltage-dependent conductances not only drive action potentials but also help regulate neuronal resting potential. We found differential regulation of resting potential in the proximal axon of layer 5 pyramidal neurons compared to the soma. Axonal resting potential was more negative than the soma, reflecting differential control by multiple voltage-dependent channels, including sodium channels, Cav3 channels, Kv7 channels, and HCN channels. Kv7 current is highly localized to the axon and HCN current to the soma and dendrite...
March 3, 2018: Neuron
Aleksi Suo, Allison Childers, Adrijana D'Silva, Lars F Petersen, Shannon Otsuka, Michelle Dean, Haocheng Li, Emeka K Enwere, Brant Pohorelic, Alexander Klimowicz, Ivana A Souza, Jawed Hamid, Gerald W Zamponi, DGwyn Bebb
Introduction: Voltage-gated calcium channels (VGCC) have been found to be differentially expressed in several different tumor types, but their role in tumor growth, malignant invasion, metastases and impact on clinical outcomes has not been clarified. Materials and Methods: From a cohort database of 193 patients with early-stage NSCLC, 163 formalin-fixed paraffin-embedded specimens were available for analysis to construct tissue microarrays. Cav3.1 protein expression was detected using fluorescence immunohistochemistry, and quantified using automated image acquisition and analysis...
February 2, 2018: Oncotarget
Lu Zhang, Hongli Yin, Lei Jiao, Tianyi Liu, Yuqiu Gao, Yingchun Shao, Yuanyuan Zhang, Hongli Shan, Ying Zhang, Baofeng Yang
BACKGROUND/AIMS: Cardiac fibrosis is an important cardiac remodeling event that can ultimately lead to the development of severe arrhythmia and heart failure. MicroRNAs (miRNAs) are involved in the pathogenesis of many cardiovascular diseases. Here, we aimed to investigate the effects of caveolin-3 (Cav3) on the pathogenesis of cardiac fibrosis and the underlying molecular mechanisms. METHODS: Cav3 expression was decreased in cardiac fibrosis in vivo and in vitro model...
February 21, 2018: Cellular Physiology and Biochemistry
Ana Laura Sanchez-Sandoval, Zazil Herrera Carrillo, Clara Estela Díaz Velásquez, Dulce María Delgadillo, Heriberto Manuel Rivera, Juan Carlos Gomora
Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3...
2018: PloS One
Ji-Woon Kim, Hyun Ah Oh, Sung Hoon Lee, Ki Chan Kim, Pyung Hwa Eun, Mee Jung Ko, Edson Luck T Gonzales, Hana Seung, Seonmin Kim, Geon Ho Bahn, Chan Young Shin
T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3...
February 21, 2018: Biomolecules & Therapeutics
Maho Tsubota, Yasumasa Okawa, Yuhei Irie, Mariko Maeda, Tomoka Ozaki, Fumiko Sekiguchi, Hiroyasu Ishikura, Atsufumi Kawabata
Hydrogen sulfide (H2 S) formed by cystathionine-γ-lyase (CSE) enhances the activity of Cav 3.2 T-type Ca2+ channels, contributing to the bladder pain accompanying hemorrhagic cystitis caused by systemic administration of cyclophosphamide (CPA) in mice. Given clinical and fundamental evidence for the involvement of the substance P/NK1 receptor systems in bladder pain syndrome (BPS)/interstitial cystitis (IC), we created an intravesical substance P-induced bladder pain model in mice and analyzed the possible involvement of the CSE/Cav 3...
January 31, 2018: Neuropharmacology
Chen Jing, Zheng Dongming, Cui Hong, Na Quan, Liu Sishi, Liu Caixia
BACKGROUND/AIMS: To detect the expression of the TRPC3 channel protein in the tissues of women experiencing preterm labor and investigate its interaction with T lymphocytes, providing a theoretical basis for the clinical prevention of threatened preterm labor and the development of drug-targeted therapy. METHODS: Forty-seven women experiencing preterm labor and 47 women experiencing normal full-term labor were included in this study. All included women underwent delivery via cesarean section; uterine samples were obtained at delivery...
January 22, 2018: Cellular Physiology and Biochemistry
Kuihao Chen, Dongchuan Zuo, Sho-Ya Wang, Haijun Chen
Spontaneous rhythmic action potential or pacemaking activity of pacemaker cells controls rhythmic signaling such as heartbeat. The mechanism underlying the origin of pacemaking activity is not well understood. In this study, we created human embryonic kidney (HEK) 293 cells that show pacemaking activity through heterologous expression of strong inward rectifier K+ channels (Kir2.1), hyperpolarization-activated cyclic nucleotide-gated nonselective cation channels (HCN2), and voltage-gated Na+ or Ca2+ channels (Nav1...
January 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
O Maiques, C Barceló, A Panosa, J Pijuan, J L Orgaz, I Rodriguez-Hernandez, C Matas-Nadal, G Tell, R Vilella, A Fabra, Puig S, V Sanz-Moreno, X Matias-Guiu, C Canti, J Herreros, R M Marti, A Macià
Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma progression. Importantly, TTCC pharmacological blockers reduce proliferation and deregulate autophagy leading to apoptosis. Here, we analyze the role of autophagy during migration/invasion of melanoma cells. TTCC Cav3...
January 31, 2018: Pigment Cell & Melanoma Research
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
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
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
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
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
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
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
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
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...
February 2018: Molecular Medicine Reports
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
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
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