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TRPC4

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https://www.readbyqxmd.com/read/29273760/urotensin-ii-induced-store-operated-ca2-entry-contributes-to-glomerular-mesangial-cell-proliferation-and-extracellular-matrix-protein-production-under-high-glucose-conditions
#1
Hitesh Soni, Adebowale Adebiyi
Glomerular mesangial cell (GMC) proliferation and matrix expansion are pathological hallmarks of a wide range of kidney diseases, including diabetic nephropathy. Although the circulating level of peptide hormone urotensin II (UII) and kidney tissue expression of UII and UII receptors (UTR) are increased in diabetic nephropathy, it remains unclear whether UII regulates GMC growth and extracellular matrix (ECM) accumulation. In this study, we tested the hypothesis that UII-induced Ca2+ signaling controls GMC proliferation and ECM production under normal and high glucose conditions...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29247460/identification-of-an-englerin-a-analogue-which-antagonizes-englerin-a-at-trpc1-4-5-channels
#2
Hussein N Rubaiy, Tobias Seitz, Sven Hahn, Axel Choidas, Peter Habenberger, Bert Klebl, Klaus Dinkel, Peter Nussbaumer, Herbert Waldmann, Mathias Christmann, David J Beech
BACKGROUND AND PURPOSE: (-)-Englerin A (EA) is a potent cytotoxic agent against renal cell carcinoma cells. It achieves its effects by activation of TRPC4/TRPC1 heteromeric channels. It is also an agonist at channels formed by the related protein, TRPC5. Here we sought an EA analogue which might enable better understanding of these EA effects. EXPERIMENTAL APPROACH: Renal cell carcinoma A498 cells and HEK 293 cells overexpressing TRPC4 or TRPC5 were studied by intracellular Ca2+ measurement or whole-cell patch-clamp...
December 16, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29242169/c60-fullerenes-disrupt-cellular-signalling-leading-to-trpc4-and-trpc6-channels-opening-by-the-activation-of-muscarinic-receptors-and-g-proteins-in-small-intestinal-smooth-muscles
#3
Dariia O Dryn, Mariia I Melnyk, Lina T Al Kury, Yuriy I Prylutskyy, Uwe Ritter, Alexander V Zholos
The effect of water-soluble pristine C60 fullerene nanoparticles (C60NPs) on receptor-operated cation channels formed by TRPC4/C6 proteins in ileal smooth muscle cells was investigated for the first time. Activation of these channels subsequent to acetylcholine binding to the expressed in these cells M2 and M3 muscarinic receptors represents the key event in the parasympathetic control of gastrointestinal smooth muscle motility and cholinergic excitation-contraction coupling. Experiments were performed on single collagenase-dispersed mouse ileal myocytes using patch-clamp techniques with symmetrical 125mM Cs+ solutions and [Ca2+]i 'clamped' at 100nM in order to isolate the muscarinic cation current (mICAT)...
December 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29209034/na-entry-through-heteromeric-trpc4-c1-channels-mediates-englerin-a-induced-cytotoxicity-in-synovial-sarcoma-cells
#4
Katsuhiko Muraki, Kaori Ohnishi, Akiho Takezawa, Hiroka Suzuki, Noriyuki Hatano, Yukiko Muraki, Nurasyikin Hamzah, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, David J Beech
The sesquiterpene (-)Englerin A (EA) is an organic compound from the plant Phyllanthus engleri which acts via heteromeric TRPC4/C1 channels to cause cytotoxicity in some types of cancer cell but not normal cells. Here we identified selective cytotoxicity of EA in human synovial sarcoma cells (SW982 cells) and investigated the mechanism. EA induced cation channel current (Icat) in SW982 cells with biophysical characteristics of heteromeric TRPC4/C1 channels. Inhibitors of homomeric TRPC4 channels were weak inhibitors of the Icat and EA-induced cytotoxicity whereas a potent inhibitor of TRPC4/C1 channels (Pico145) strongly inhibited Icat and cytotoxicity...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29198958/inhalation-anaesthetic-isoflurane-inhibits-the-muscarinic-cation-current-and-carbachol-induced-gastrointestinal-smooth-muscle-contractions
#5
Dariia Dryn, Jialie Luo, Mariia Melnyk, Alexander Zholos, Hongzhen Hu
Gastrointestinal tract motility may be demoted significantly after surgery operations at least in part due to anaesthetic agents, but there is no comprehensive explanation of the molecular mechanism(s) of such adverse effects. Anesthetics are known to interact with various receptors and ion channels including several subtypes of transient receptor potential (TRP) channels. Two members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are Ca2+-permeable cation channels involved in visceral smooth muscle contractility induced by acetylcholine, the primary excitatory neurotransmitter in the gut...
November 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28978766/trpc5-is-required-for-the-no-dependent-increase-in-dendritic-ca-2-and-gaba-release-from-chick-retinal-amacrine-cells
#6
John Wesley Maddox, Nikka Khorsandi, Evanna L Gleason
GABAergic signaling from amacrine cells (ACs) is a fundamental aspect of visual signal processing in the inner retina. We have previously shown that nitric oxide (NO) can elicit release of GABA independently from activation of voltage-gated Ca(2+) channels in cultured retinal ACs. This voltage-independent quantal GABA release relies on a Ca(2+) influx mechanism with pharmacological characteristics consistent with the involvement of transient receptor potential canonical (TRPC) channels TRPC4 and/or TRPC5. To determine the identity of these channels, we evaluate the ability of NO to elevate dendritic Ca(2+) and to stimulate GABA release from cultured ACs under conditions known to alter the function of TRPC4 and 5...
October 4, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28900930/cardiac-remodeling-and-disease-soce-and-trpc-signaling-in-cardiac-pathology
#7
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca(2+) entry (SOCE) in cardiomyocytes. There is increasing evidence that the TRPC isoforms TRPC1 and TRPC4 might fulfill the function as SOCs, in concert with or in parallel to the key players of SOCE, Orai1, and STIM1. Several other isoforms, e.g., TRPC3, TRPC6, and TRPC7, might rather associate to receptor-activated diacylglycerol (DAG)-sensitive ion channels. However, the exact activation mode has not been elucidated yet, given the characteristic of TRPC channels to heteromerize to unpredictable ion channel assemblies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#8
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#9
Holger Beckmann, Julia Richter, Kerstin Hill, Nicole Urban, Horst Lemoine, Michael Schaefer
The transient receptor potential canonical channel 5 (TRPC5) is a Ca(2+)-permeable ion channel, which is predominantly expressed in the brain. TRPC5-deficient mice exhibit a reduced innate fear response and impaired motor control. In addition, outgrowth of hippocampal and cerebellar neurons is retarded by TRPC5. However, pharmacological evidence of TRPC5 function on cellular or organismic levels is sparse. Thus, there is still a need for identifying novel and efficient TRPC5 channel modulators. We, therefore, screened compound libraries and identified the glucocorticoid methylprednisolone and N-[3-(adamantan-2-yloxy)propyl]-3-(6-methyl-1,1-dioxo-2H-1λ(6),2,4-benzothiadiazin-3-yl)propanamide (BTD) as novel TRPC5 activators...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28790178/heteromeric-channels-formed-by-trpc1-trpc4-and-trpc5-define-hippocampal-synaptic-transmission-and-working-memory
#10
Jenny Bröker-Lai, Astrid Kollewe, Barbara Schindeldecker, Jörg Pohle, Vivan Nguyen Chi, Ilka Mathar, Raul Guzman, Yvonne Schwarz, Alan Lai, Petra Weißgerber, Herbert Schwegler, Alexander Dietrich, Martin Both, Rolf Sprengel, Andreas Draguhn, Georg Köhr, Bernd Fakler, Veit Flockerzi, Dieter Bruns, Marc Freichel
Canonical transient receptor potential (TRPC) channels influence various neuronal functions. Using quantitative high-resolution mass spectrometry, we demonstrate that TRPC1, TRPC4, and TRPC5 assemble into heteromultimers with each other, but not with other TRP family members in the mouse brain and hippocampus. In hippocampal neurons from Trpc1/Trpc4/Trpc5-triple-knockout (Trpc1/4/5(-/-)) mice, lacking any TRPC1-, TRPC4-, or TRPC5-containing channels, action potential-triggered excitatory postsynaptic currents (EPSCs) were significantly reduced, whereas frequency, amplitude, and kinetics of quantal miniature EPSC signaling remained unchanged...
September 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28697491/trpc1-trpc3-and-trpc4-in-rat-orofacial-structures
#11
Masatoshi Fujita, Tadasu Sato, Takehiro Yajima, Eiji Masaki, Hiroyuki Ichikawa
TRPC (transient receptor potential cation channel subfamily C) members are nonselective monovalent cation channels and control Ca2+ inflow. In this study, immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and craniofacial structures to elucidate their distribution and function in the peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A double immunofluorescence method revealed that small to medium-sized TG neurons co-expressed TRPCs and calcitonin gene-related peptide...
July 12, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28672825/maitotoxin-is-a-potential-selective-activator-of-the-endogenous-transient-receptor-potential-canonical-type-1-channel-in-xenopus-laevis-oocytes
#12
Pedro L Flores, Emma Rodríguez, Estrella Zapata, Roxana Carbó, José María Farías, Martín Martínez
Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels...
June 25, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28636132/trpc1-and-trpc3-dependent-ca-2-signaling-in-mouse-cortical-astrocytes-affects-injury-evoked-astrogliosis-in-vivo
#13
Thabet Belkacemi, Alexander Niermann, Laura Hofmann, Ulrich Wissenbach, Lutz Birnbaumer, Petra Leidinger, Christina Backes, Eckart Meese, Andreas Keller, Xianshu Bai, Anja Scheller, Frank Kirchhoff, Stephan E Philipp, Petra Weissgerber, Veit Flockerzi, Andreas Beck
Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca(2+) . Transient receptor potential canonical (TRPC) channels may contribute to Ca(2+) influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells...
September 2017: Glia
https://www.readbyqxmd.com/read/28627017/functional-expression-of-calcium-permeable-canonical-transient-receptor-potential-4-containing-channels-promotes-migration-of-medulloblastoma-cells
#14
Wei-Chun Wei, Wan-Chen Huang, Yu-Ping Lin, Esther B E Becker, Olaf Ansorge, Veit Flockerzi, Daniele Conti, Giovanna Cenacchi, Maike D Glitsch
KEY POINTS: The proton sensing ovarian cancer G protein coupled receptor 1 (OGR1, aka GPR68) promotes expression of the canonical transient receptor potential channel subunit TRPC4 in normal and transformed cerebellar granule precursor (DAOY) cells. OGR1 and TRPC4 are prominently expressed in healthy cerebellar tissue throughout postnatal development and in primary cerebellar medulloblastoma tissues. Activation of TRPC4-containing channels in DAOY cells, but not non-transformed granule precursor cells, results in prominent increases in [Ca(2+) ]i and promotes cell motility in wound healing and transwell migration assays...
August 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28613228/rna-seq-reveals-transcriptomic-differences-in-inflamed-and-noninflamed-intestinal-mucosa-of-crohn-s-disease-patients-compared-with-normal-mucosa-of-healthy-controls
#15
Sung Noh Hong, Je-Gun Joung, Joon Seol Bae, Chan Soo Lee, Ja Seol Koo, Soo Jung Park, Jong Pil Im, You Sun Kim, Ji Won Kim, Woong Yang Park, Young-Ho Kim
BACKGROUND: Aberrant gene expression in the gut mucosa might contribute to the initiation and progression of Crohn's disease (CD). RNA sequencing (RNA-seq) provides precise measurements of expression levels of transcripts and their isoforms. The aim of this study was to use RNA-seq to investigate transcriptomic differences and identify significantly differentially expressed transcripts in inflamed and noninflamed intestinal mucosa of CD patients. METHODS: RNA-seq was performed on 13 pairs of inflamed and noninflamed intestinal mucosa from 13 CD patients and on sex-matched normal mucosa of 13 healthy controls...
July 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28566634/effect-of-docosahexaenoic-acid-on-voltage-independent-ca-2-entry-pathways-in-cultured-vascular-smooth-muscle-cells-stimulated-with-5-hydroxytryptamine
#16
Takuji Machida, Akina Onoguchi, Kenji Iizuka, Sayuri Ishibashi, Mikiko Yutani, Masahiko Hirafuji
We previously reported that docosahexaenoic acid (DHA) inhibits an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in cultured rat vascular smooth muscle cells (VSMCs) through a mechanism involving mainly voltage-dependent Ca(2+) channels; however, the effect of DHA on voltage-independent pathways, such as store-operated and receptor-operated Ca(2+) entry, and Ca(2+) entry through Na(+)/Ca(2+) exchanger (NCX), has not been clarified. In the present study, we investigated the effect of DHA treatment on the expression of transient receptor potential canonical (TRPC) channels, capacitative Ca(2+) entry, and Ca(2+) entry through NCX in rat cultured VSMCs stimulated with 5-hydroxytryptamine (5-HT)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28522036/transient-receptor-potential-trp-channel-function-in-the-reproductive-axis
#17
REVIEW
Viktoria Götz, Sen Qiao, Andreas Beck, Ulrich Boehm
Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic-pituitary-gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28499580/transient-receptor-potential-trp-channels-as-molecular-targets-in-lung-toxicology-and-associated-diseases
#18
REVIEW
Alexander Dietrich, Dirk Steinritz, Thomas Gudermann
The lungs as the gateways of our body to the external environment are essential for gas exchange. They are also exposed to toxicants from two sides, the airways and the vasculature. Apart from naturally produced toxic agents, millions of human made chemicals were produced since the beginning of the industrial revolution whose toxicity still needs to be determined. While the knowledge about toxic substances is increasing only slowly, a paradigm shift regarding the proposed mechanisms of toxicity at the plasma membrane emerged...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28455787/elevated-expression-of-trpc4-in-cortical-lesions-of-focal-cortical-dysplasia-ii-and-tuberous-sclerosis-complex
#19
Lu-Kang Wang, Xin Chen, Chun-Qing Zhang, Chao Liang, Yu-Jia Wei, Jiong Yue, Shi-Yong Liu, Hui Yang
Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC) are well-known causes of chronic refractory epilepsy in children. Canonical transient receptor potential channels (TRPCs) are non-selective cation channels that are commonly activated by phospholipase C (PLC) stimulation. Previous studies found that TRPC4 may participate in the process of epileptogenesis. This study aimed to examine the expression and distribution of TRPC4 in FCD II (n = 24) and TSC (n = 11) surgical specimens compared with that in age-matched autopsy control samples (n = 12)...
June 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#20
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Ying Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters, but understanding of these channels remains inadequate. Here we focus on transient receptor potential canonical 4 and 5 proteins (TRPC4 and TRPC5), which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested, including in epilepsy, innate fear, pain, and cardiac remodeling, but limitations in tools to probe these channels have restricted progress...
May 19, 2017: Journal of Biological Chemistry
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