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https://www.readbyqxmd.com/read/28439630/myriocin-treatment-of-cf-lung-infection-and-inflammation-complex-analyses-for-enigmatic-lipids
#1
Anna Caretti, Michele Vasso, Fabiola Tecla Bonezzi, Andrea Gallina, Marco Trinchera, Alice Rossi, Raffaella Adami, Josefina Casas, Monica Falleni, Delfina Tosi, Alessandra Bragonzi, Riccardo Ghidoni, Cecilia Gelfi, Paola Signorelli
Our aim was to use quantitative and qualitative analyses to gain further insight into the role of ceramide in cystic fibrosis (CF). Sphingolipid ceramide is a known inflammatory mediator, and its accumulation in inflamed lung has been reported in different types of emphysema, chronic obstructive pulmonary disease and CF. CF is caused by a mutation of the chloride channel and associated with hyperinflammation of the respiratory airways and high susceptibility to ongoing infections. We have previously demonstrated that de novo ceramide synthesis is enhanced in lung inflammation and sustains Pseudomonas aeruginosa pulmonary infection in a CF murine model...
April 24, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28439239/development-of-automated-patch-clamp-technique-to-investigate-cftr-chloride-channel-function
#2
Arnaud Billet, Lionel Froux, John W Hanrahan, Frederic Becq
The chloride (Cl(-)) channel cystic fibrosis transmembrane conductance regulator (CFTR) is defective in cystic fibrosis (CF), and mutation of its encoding gene leads to various defects such as retention of the misfolded protein in the endoplasmic reticulum, reduced stability at the plasma membrane, abnormal channel gating with low open probability, and thermal instability, which leads to inactivation of the channel at physiological temperature. Pharmacotherapy is one major therapeutic approach in the CF field and needs sensible and fast tools to identify promising compounds...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28437476/clc-3-chloride-channel-mediates-the-role-of-parathyroid-hormone-1-34-on-osteogenic-differentiation-of-osteoblasts
#3
Xiaolin Lu, Yin Ding, Qiannan Niu, Shijie Xuan, Yan Yang, Yulong Jin, Huan Wang
INTRODUCTION: Different concentrations of parathyroid hormone [1-34] (PTH [1-34]) can have totally opposite effects on osteoblasts. Intermittent stimulation with PTH can significantly increase bone mineral density in vitro, mainly through the protein kinase A (PKA) signaling pathway, which phosphorylates runt-related transcription factor 2 (Runx2). The ClC-3 chloride channel, an important anion channel, can also promote osteogenesis via the Runx2 pathway based on recent studies. The purpose of our study, therefore, is to research whether the ClC-3 chloride channel has an effect on PTH osteodifferentiation in MC3T3-E1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28435971/-mechanisms-underlying-rat-coronary-arterial-vasoconstriction-induced-by-blockade-of-inward-rectifier-potassium-channels-with-bacl2
#4
Fang-Wen Fan, Ze-Fang He, Meng Shi, Rong Yang, Xiao-Min Hou, Yu Liu, Ming-Sheng Zhang
In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier K(+) channels (Kir) with BaCl2, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl2- induced contraction on intracellular Ca(2+) ([Ca(2+)]i) release and extracellular Ca(2+) ([Ca(2+)]o) influx was studied by Ca(2+) deprivation and restoration. The mechanisms underlying BaCl2-induced RCA contraction were investigated with specific inhibitors. BaCl2 (0...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#5
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28429370/the-role-of-charged-residues-in-independent-glycine-receptor-folding-domains-for-intermolecular-interactions-and-ion-channel-function
#6
Georg Langlhofer, Carmen Villmann
Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead to non-functionality of GlyRs. The missing part that contains the TM3-4 loop, TM4, and C-terminal sequences is essential for pentameric receptor arrangements. In vitro coexpressions of GlyRα1 truncated N-domains and C- domains were able to restore ion channel function. An ionic interaction between both domains was hypothesised as the underlying mechanism...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429004/binding-site-opening-by-loop-c-shift-and-chloride-ion-pore-interaction-in-the-gabaa-receptor-model
#7
M A Michałowski, S Kraszewski, J W Mozrzymas
GABAA receptors (GABAARs) are crucial in mediating inhibition in the adult mammalian brain. Although the kinetics of this receptor has been extensively studied, the molecular picture of interactions occurring at various channel conformations remains elusive. While electrophysiology combined with mutagenesis sheds light on the role of specific residues, ultrastructural studies reveal static structures which, in the case of GABAARs, are limited to the β3 homomer. To take advantage of the newest crystal structures of cys-loop receptors, a homology model of α1β2γ2 GABAAR in the unbound closed state was built using a template of the homomeric glycine receptor in the closed state...
April 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28428744/mutational-analysis-at-intersubunit-interfaces-of-an-anionic-glutamate-receptor-reveals-a-key-interaction-important-for-channel-gating-by-ivermectin
#8
Nurit Degani-Katzav, Revital Gortler, Marina Weissman, Yoav Paas
The broad-spectrum anthelmintic drug ivermectin (IVM) activates and stabilizes an open-channel conformation of invertebrate chloride-selective glutamate receptors (GluClRs), thereby causing a continuous inflow of chloride ions and sustained membrane hyperpolarization. These effects suppress nervous impulses and vital physiological processes in parasitic nematodes. The GluClRs are pentamers. Homopentameric receptors assembled from the Caenorhabditis elegans (C. elegans) GluClα (GLC-1) subunit can inherently respond to IVM but not to glutamate (the neurotransmitter)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28428070/no-production-and-potassium-channels-activation-induced-by-crotalus-durissus-cascavella-underlie-mesenteric-artery-relaxation
#9
S S Santos, R L C Jesus, L O Simões, W P Vasconcelos, I A Medeiros, R C Veras, L L Casais-E-Silva, D F Silva
Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001-30 μg/mL) on phenylephrine (Phe; 10 μM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47...
April 18, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28426183/mass-production-of-cell-laden-calcium-alginate-particles-with-centrifugal-force
#10
Yuya Morimoto, Maiko Onuki, Shoji Takeuchi
This paper describes a centrifuge-based device for oil-free and mass production of calcium-alginate (Ca-alginate) particles. The device is composed of four components: a tank with a glass capillary for forming sodium alginate droplets, a collecting bath with calcium chloride (CaCl2 ) solution, a waste liquid box, and a bypass channel bridged between the collecting bath and the waste liquid box. When the device is centrifuged, extra CaCl2 solution in the collecting bath is delivered to the waste liquid box to maintain the appropriate liquid level of CaCl2 solution for the production of monodisperse Ca-alginate particles...
April 20, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28422190/current-carried-by-the-slc26-family-member-prestin-does-not-flow-through-the-transporter-pathway
#11
Jun-Ping Bai, Iman Moeini-Naghani, Sheng Zhong, Fang-Yong Li, Shumin Bian, Fred J Sigworth, Joseph Santos-Sacchi, Dhasakumar Navaratnam
Prestin in the lateral membrane of outer hair cells, is responsible for electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin's voltage sensitivity is influenced by intracellular chloride. A regulator of intracellular chloride is a stretch-sensitive, non-selective conductance within the lateral membrane, GmetL. We determine that prestin itself possesses a stretch-sensitive, non-selective conductance that is largest in the presence of thiocyanate ions. This conductance is independent of the anion transporter mechanism...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420732/modulation-of-tmem16a-channel-activity-by-the-von-willebrand-factor-type-a-vwa-domain-of-the-calcium-activated-chloride-channel-regulator-1-clca1
#12
Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Colin G Nichols, Tom J Brett
Calcium-activated chloride channels (CaCCs) are key players in transepithelial ion transport and fluid secretion, smooth muscle constriction, neuronal excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel at the cell surface, but the exact mechanism is unknown. Here, we demonstrate that the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal fragment is necessary and sufficient for this interaction...
April 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28419445/activation-of-clc-3-chloride-channel-by-17%C3%AE-estradiol-relies-on-the-estrogen-receptor-%C3%AE-expression-in-breast-cancer
#13
Haifeng Yang, Lianshun Ma, Yawei Wang, Wanhong Zuo, Bingxue Li, Yaping Yang, Yehui Chen, Lixin Chen, Liwei Wang, Linyan Zhu
Although extensively studied, the mechanisms by which estrogen promotes breast cancer growth remain to be fully elucidated. Tamoxifen, an antiestrogen to treat ERα+ breast cancer, is also a high-affinity blocker of the chloride channels. In this study, we explored the involvement of the chloride channels in the action of estrogen in breast cancer. We found that 17β-estradiol (17β-E2) concentration-dependently activated the chloride currents in ERα+ breast cancer MCF-7 cells. Extracellular hypertonic challenge and chloride channel blockers, NPPB and DIDS inhibited the 17β-E2-activated chloride currents...
April 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28416372/effects-of-bilobalide-ginkgolide-b-and-picrotoxinin-on-gabaa-receptor-modulation-by-structurally-diverse-positive-modulators
#14
Chiu Chin Ng, Rujee K Duke, Tina Hinton, Graham A R Johnston
Anxiolytics and anticonvulsants generally positively modulate the action of GABA, whereas many convulsants (including the chloride channel blocker picrotoxinin) negatively modulate the action of GABA on GABAA receptors. Like picrotoxinin, bilobalide and ginkgolide B, active constituents of Ginkgo biloba, have been shown to negatively modulate the action of GABA at α1β2γ2L GABAA receptors. However, unlike picrotoxinin, bilobalide and ginkgolide B are not known to cause convulsions. We have assessed the action of bilobalide, ginkgolide B and picrotoxinin on a range of GABAA modulators (etomidate, loreclezole, propofol, thiopentone sodium, diazepam, and allopregnanolone), using two-electrode voltage clamp electrophysiology at recombinant α1β2γ2L GABAA receptors expressed in Xenopus oocytes...
April 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28415833/molecular-characterization-and-biodiversity-of-a-putative-chlorotoxin-from-the-iranian-yellow-scorpion-odontobuthus-doriae
#15
Maryam Naderi Soorki, Amir Jalali, Hamid Galehdari
BAckground: Chloride channels have already been over-expressed in the different types of cancer. Chlorotoxins, as the blocking agent of these channels, have been indicated to be an effective drug against tumors. In this study, we characterized a putative chlorotoxin from a cDNA library of the venom glands obtained from the Iranian scorpion Odontobuthus doriae. Methods: A cDNA library was constructed from venom gland transcriptome of six scorpions. The cDNA encoding Odontobuthus doriae chlorotoxin was isolated from the library, and its putative peptide was characterized by some bioinformatics software such as protein blast, SignalP4...
April 18, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28413263/intensified-microwave-assisted-n-acylation-procedure-synthesis-and-activity-evaluation-of-trpc3-channel-agonists-with-a-1-3-dihydro-2h-benzo-d-imidazol-2-one-core
#16
Gema Guedes de la Cruz, Barbora Svobodova, Michaela Lichtenegger, Oleksandra Tiapko, Klaus Groschner, Toma Glasnov
Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H-benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed. Compared to the few conventional protocols, a drastic reduction in processing time from ca. 2 days down to 10 minutes was achieved accompanied by significantly improved product yields. The robustness of the method was confirmed by 18 additional examples including aromatic, aliphatic, and heterocyclic amines and acids...
April 2017: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry
https://www.readbyqxmd.com/read/28412580/a-non-toxic-dose-of-cobalt-chloride-blocks-hair-cells-of-the-zebrafish-lateral-line
#17
William J Stewart, Jacob L Johansen, James C Liao
Experiments on the flow-sensitive lateral line system of fishes have provided important insights into the function and sensory transduction of vertebrate hair cells. A common experimental approach has been to pharmacologically block lateral line hair cells and measure how behavior changes. Cobalt chloride (CoCl2) blocks the lateral line by inhibiting calcium movement through the membrane channels of hair cells, but high concentrations can be toxic, making it unclear whether changes in behavior are due to a blocked lateral line or poor health...
April 12, 2017: Hearing Research
https://www.readbyqxmd.com/read/28411554/emodin-suppresses-the-nasopharyngeal-carcinoma-cells-by-targeting-the-chloride-channels
#18
Lianshun Ma, Yaping Yang, Zizhang Yin, Mei Liu, Liwei Wang, Lixin Chen, Linyan Zhu, Haifeng Yang
Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry...
April 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28398517/depolarization-causes-the-formation-of-a-ternary-complex-between-glialcam-mlc1-and-clc-2-in-astrocytes-implications-in-megalencephalic-leukoencephalopathy
#19
Sònia Sirisi, Xabier Elorza-Vidal, Tanit Arnedo, Mercedes Armand-Ugón, Gerard Callejo, Xavier Capdevila-Nortes, Tania López-Hernández, Uwe Schulte, Alejandro Barrallo-Gimeno, Virginia Nunes, Xavier Gasull, Raúl Estévez
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy caused by mutations in either MLC1 or GLIALCAM. GlialCAM is necessary for the correct targeting of MLC1, but also for the targeting of the Cl- channel ClC-2. Furthermore, GlialCAM modifies ClC-2 functional properties in vitro. However, in vivo studies in GlialCAM-/- mice have shown that the modification of ClC-2 activity only occurs in oligodendrocytes, despite GlialCAM and ClC-2 being expressed in astrocytes. Thus, the relationship between GlialCAM, MLC1 and ClC-2 in astrocytes is unknown...
April 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28396087/high-performance-separation-of-quaternary-amines-using-microchip-non-aqueous-electrophoresis-coupled-with-contactless-conductivity-detection
#20
Roger Cardoso Moreira, Marilia Sousa Lopes, Iris Medeiros Junior, Wendell K T Coltro
This study describes the development of an analytical methodology for the separation of quaternary amines using non-aqueous microchip electrophoresis (NAME) coupled with capacitively coupled contactless conductivity detection (C(4)D). All experiments were performed using a commercial microchip electrophoresis system consisting of a C(4)D detector, a high-voltage sequencer and a microfluidic platform to assemble a glass microchip with integrated sensing electrodes. The detection parameters were optimized and the best response was reached applying a 700-kHz sinusoidal wave with 14Vpp excitation voltage...
March 27, 2017: Journal of Chromatography. A
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