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kca3.1

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https://www.readbyqxmd.com/read/28331181/multi-walled-carbon-nanotubes-act-as-a-chemokine-and-recruit-macrophages-by-activating-the-plc-ip3-crac-channel-signaling-pathway
#1
Hui Li, Xiao-Qiu Tan, Li Yan, Bo Zeng, Jie Meng, Hai-Yan Xu, Ji-Min Cao
The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28280458/jmv5656-a-novel-derivative-of-tlqp-21-triggers-the-activation-of-a-calcium-dependent-potassium-outward-current-in-microglial-cells
#2
Ilaria Rivolta, Anna Binda, Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Vittorio Locatelli, Antonio Torsello
TLQP-21 (TLQPPASSRRRHFHHALPPAR) is a multifunctional peptide that is involved in the control of physiological functions, including feeding, reproduction, stress responsiveness, and general homeostasis. Despite the huge interest in TLQP-21 biological activity, very little is known about its intracellular mechanisms of action. In microglial cells, TLQP-21 stimulates increases of intracellular Ca(2+) that may activate functions, including proliferation, migration, phagocytosis and production of inflammatory molecules...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28248292/potassium-channels-kv1-3-and-kca3-1-cooperatively-and-compensatorily-regulate-antigen-specific-memory-t-cell-functions
#3
Eugene Y Chiang, Tianbo Li, Surinder Jeet, Ivan Peng, Juan Zhang, Wyne P Lee, Jason DeVoss, Patrick Caplazi, Jun Chen, Søren Warming, David H Hackos, Susmith Mukund, Christopher M Koth, Jane L Grogan
Voltage-gated Kv1.3 and Ca(2+)-dependent KCa3.1 are the most prevalent K(+) channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3...
March 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28245384/-effects-of-tram-34-on-proliferation-and-invasion-of-leukemia-cell-line-hl-60
#4
Tian-Hua Jiang, Zhi-Gang Huang
OBJECTIVE: To investigate the effects of KCa3.1 channel inhibitor TRAM-34 on the proliferation and invasion of leukemia cell line HL-60. METHODS: HL-60 cells at logarithmic growth phase exposed to TRAM-34 at the final concentration of 25, 50, 75 and 100 nmol/L were used as experimental group. The HL-60 cells of control group was cultured in 10% fetal bovine serum-RPMI 1640. The proliferation inhibition rate of TRAM-34 on HL-60 cells was detected by adding MTT solution after 24, 48 and 72 h culture...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28212804/potassium-channels-in-regulation-of-vascular-smooth-muscle-contraction-and-growth
#5
W F Jackson
Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca(2+) channels (VGCC), Ca(2+) influx through VGCC, intracellular Ca(2+), and VSM contraction. Membrane potential also affects release of Ca(2+) from internal stores and the Ca(2+) sensitivity of the contractile machinery such that K(+) channels participate in all aspects of regulation of VSM contraction...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28197106/inhibition-of-intermediate-conductance-calcium-activated-k-channel-kca3-1-and-fibroblast-mitogenesis-by-%C3%AE-linolenic-acid-and-alterations-of-channel-expression-in-the-lysosomal-storage-disorders-fabry-disease-and-niemann-pick-c
#6
Aida Oliván-Viguera, Javier Lozano-Gerona, Laura López de Frutos, Jorge J Cebolla, Pilar Irún, Edgar Abarca-Lachen, Ana J García-Malinis, Ángel Luis García-Otín, Yolanda Gilaberte, Pilar Giraldo, Ralf Köhler
The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K(+)-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28126850/structural-insights-into-the-atomistic-mechanisms-of-action-of-small-molecule-inhibitors-targeting-the-kca3-1-channel-pore
#7
Hai M Nguyen, Vikrant Singh, Brandon Pressly, David Paul Jenkins, Heike Wulff, Vladimir Yarov-Yarovoy
The calcium-activated potassium channel KCa3.1 constitutes an attractive pharmacological target for immunosuppression, fibroproliferative disorders, atherosclerosis and stroke. However, there currently is no available crystal structure of this medically relevant channel that could be used for structure-assisted drug design. Using the Rosetta molecular modeling suite we generated a molecular model of the KCa3.1 pore and tested the model by first confirming previously mapped binding sites and visualizing the mechanism of TRAM-34, senicapoc and NS6180 inhibition at the atomistic level...
January 26, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28062499/role-of-kca3-1-channels-in-macrophage-polarization-and-its-relevance-in-atherosclerotic-plaque-instability
#8
Rende Xu, Chenguang Li, Yizhe Wu, Li Shen, Jianying Ma, Juying Qian, Junbo Ge
OBJECTIVE: Emerging evidence indicates that proinflammatory macrophage polarization imbalance plays a key role in atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in macrophage polarization is unknown. This study investigates the potential role of KCa3.1 in transcriptional regulation in macrophage polarization and its relationship to plaque instability...
February 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28060543/inhibition-of-the-kca3-1-channel-alleviates-established-pulmonary-fibrosis-in-a-large-animal-model
#9
Louise Organ, Barbara Bacci, Emmanuel Koumoundouros, Wayne G Kimpton, Chrishan S Samuel, Cameron J Nowell, Peter Bradding, Katy M Roach, Glen Westall, Jade Jaffar, Ken J Snibson
Idiopathic pulmonary fibrosis is a chronic progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca2+-activated KCa3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF. Pharmacological inhibition of IPF-derived fibroblasts is able to somewhat prevent TGF-βand bFGF-dependent profibrotic responses. In the current study, we investigated whether blockade of the KCa3...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28028617/calcium-gated-k-channels-of-the-kca1-1-and-kca3-1-type-couple-intracellular-ca-2-signals-to-membrane-hyperpolarization-in-mesenchymal-stromal-cells-from-the-human-adipose-tissue
#10
Michail V Tarasov, Marina F Bystrova, Polina D Kotova, Olga A Rogachevskaja, Veronika Y Sysoeva, Stanislav S Kolesnikov
Electrogenesis in mesenchymal stromal cells (MSCs) remains poorly understood. Little is known about ion channels active in resting MSCs and activated upon MSC stimulation, particularly, by agonists mobilizing Ca(2+) in the MSC cytoplasm. A variety of Ca(2+)-gated ion channels may couple Ca(2+) signals to polarization of the plasma membrane. Here, we studied MSCs from the human adipose tissue and found that in cells responsive to ATP and adenosine with Ca(2+) transients or exhibiting spontaneous Ca(2+) oscillations, Ca(2+) bursts were associated with hyperpolarization mediated by Ca(2+)-gated K(+) channels...
December 27, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#11
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27876619/inhibition-of-the-potassium-channel-kca3-1-by-senicapoc-reverses-tactile-allodynia-in-rats-with-peripheral-nerve-injury
#12
Roland G W Staal, Tanzilya Khayrullina, Hong Zhang, Scott Davis, Shaun M Fallon, Manuel Cajina, Megan E Nattini, Andrew Hu, Hua Zhou, Suresh Babu Poda, Stevin Zorn, Gamini Chandrasena, Elena Dale, Brian Cambpell, Lars Christian Biilmann Rønn, Gordon Munro, Thomas Mӧller
Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca(2+)- activated K(+) channel, KCa3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of KCa3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent KCa3...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27826710/the-action-of-smooth-muscle-cell-potassium-channels-in-the-pathology-of-pulmonary-arterial-hypertension
#13
REVIEW
Yasunobu Hayabuchi
Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and pathological conditions. The deep involvement of these channels in the onset and exacerbation of pulmonary arterial hypertension (PAH) also continues to be revealed. In 2013, KCNK3 (TASK1), which encodes a type of two-pore domain potassium channel, was shown to be a predisposing gene for PAH by genetic mutation, and it was added to the PAH classification at the Fifth World Symposium on Pulmonary Hypertension (Nice International Conference)...
January 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/27789963/herg1-positivity-and-glut-1-negativity-identifies-high-risk-tnm-stage-i-and-ii-colorectal-cancer-patients-regardless-of-adjuvant-chemotherapy
#14
Leonardo Muratori, Giulia Petroni, Lorenzo Antonuzzo, Luca Boni, Jessica Iorio, Elena Lastraioli, Gianluca Bartoli, Luca Messerini, Francesco Di Costanzo, Annarosa Arcangeli
BACKGROUND: The identification of early-stage colorectal cancer (CRC) with high risk of progression is one major clinical challenge, mainly due to lack of validated biomarkers. The aims of the present study were to analyze the prognostic impact of three molecular markers belonging to the ion channels and transporters family: the ether-à-go-go-related gene 1 (hERG1) and the calcium-activated KCa3.1 potassium channels, as well as the glucose transporter 1 (Glut-1); and to define the impact of adjuvant chemotherapy in conjunction with the abovementioned biomarkers, in a cohort of radically resected stage I-III CRC patients...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27752766/kca3-1-ik-modulates-pancreatic-cancer-cell-migration-invasion-and-proliferation-anomalous-effects-on-tram-34
#15
B Bonito, D R P Sauter, A Schwab, M B A Djamgoz, I Novak
In the recent decades, ion channels became the focus of cancer biologists, as many channels are overexpressed in tumour tissue and functionally they are linked to abnormal cell behaviour with processes including apoptosis, chemo- and radioresistance, proliferation and migration. KCa3.1 is a Ca(2+)-activated K(+) channel that plays a central role in tumour progression in many cancer types. Therefore, the aim of the present study was to investigate KCa3.1 expression in pancreatic cancer cells and assess possible implications to disease progression...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27696527/differential-kv1-3-kca3-1-and-kir2-1-expression-in-classically-and-alternatively-activated-microglia
#16
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
January 2017: Glia
https://www.readbyqxmd.com/read/27592222/protective-role-of-ace2-ang-1-7-mas-in-myocardial-fibrosis-by-downregulating-kca3-1-channel-via-erk1-2-pathway
#17
Li-Ping Wang, Su-Jing Fan, Shu-Min Li, Xiao-Jun Wang, Jun-Ling Gao, Xiu-Hong Yang
The intermediate-conductance Ca(2+)-activated K(+) (KCa3.1) channel plays a vital role in myocardial fibrosis induced by angiotensin (Ang) II. However, as the antagonists of Ang II, the effect of angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis on KCa3.1 channel during myocardial fibrosis remains unknown. This study was designed to explore the function of KCa3.1 channel in the cardioprotective role of ACE2-Ang-(1-7)-Mas. Wild-type (WT) mice, hACE2 transgenic mice (Tg), and ACE2 deficiency mice (ACE2(-/-)) were administrated with Ang II by osmotic mini-pumps...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27577886/minimally-modified-ldl-induced-impairment-of-endothelium-dependent-relaxation-in-small-mesenteric-arteries-of-mice
#18
Gen Chen, Jun-Jie Wang, Cang-Bao Xu, Lei Cao, Jie Lin, Xu-Ping Qing, Si-Yu Liu, En-Qi Liu, Jie Li
Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultramicrostructure of mesenteric vascular beds was investigated using a transmission electron microscope...
September 1, 2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27567685/kca3-1-constitutes-a-pharmacological-target-for-astrogliosis-associated-with-alzheimer-s-disease
#19
Mengni Yi, Panpan Yu, Qin Lu, Herbert M Geller, Zhihua Yu, Hongzhuan Chen
Alzheimer's disease (AD) is the most common type of dementia and is characterized by a progression from decline of episodic memory to a global impairment of cognitive function. Astrogliosis is a hallmark feature of AD, and reactive gliosis has been considered as an important target for intervention in various neurological disorders. We previously found in astrocyte cultures that the expression of the intermediate conductance calcium-activated potassium channel KCa3.1 was increased in reactive astrocytes induced by TGF-β, while pharmacological blockade or genetic deletion of KCa3...
October 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27549144/role-of-kca3-1-channels-in-cns-diseases-a-concise-review
#20
Sinoy Sugunan, Sreekala S Nampoothiri, Tanya Garg, Rajanikant G Krishnamurthy
KCa3.1 protein is part of a heterotetrameric voltage-independent potassium channel, the activity of which depends on the intracellular calcium binding to calmodulin. KCa3.1 is immensely significant in regulating immune responses and primarily expressed in cells of hematopoietic lineage. It is one of the attractive pharmacological targets that are known to inhibit neuroinflammation. KCa3.1 blockers mediate neuroprotection through multiple mechanisms, such as by targeting microglia-mediated neuronal killing. KCa3...
August 22, 2016: CNS & Neurological Disorders Drug Targets
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