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chloride channel activators

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https://www.readbyqxmd.com/read/28109183/chloride-ion-transport-and-overexpression-of-tmem16a-in-a-guinea-pig-asthma-model
#1
Mitsuko Kondo, Mayoko Tsuji, Kaori Hara, Ken Arimura, Osamitsu Yagi, Etsuko Tagaya, Kiyoshi Takeyama, Jun Tamaoki
BACKGROUND: TMEM16A, a Ca-activated Cl channel, regulates various physiological functions such as mucin secretion. However, the role of TMEM16A in hypersecretion in asthma is not fully understood. OBJECTIVE: The aim of this study is to evaluate Cl ion transport via TMEM16A and determine the localization of TMEM16A in a guinea pig asthma model. METHODS: Guinea pigs were sensitized with OVA ip. on Day 1 and Day 8. On Day 22, we assessed OVA challenge-induced Cl ion transport in the sensitized tracheas ex vivo in an Ussing chamber, compared with the non-sensitized tracheas...
January 21, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28099811/nanomolar-potency-aminophenyl-1-3-5-triazine-activators-of-the-cystic-fibrosis-transmembrane-conductance-regulator-cftr-chloride-channel-for-pro-secretory-therapy-of-dry-eye-diseases
#2
Sujin Lee, Puay-Wah Phuan, Christian M Felix, Joseph-Anthony Tan, Marc H Levin, Alan S Verkman
Dry eye disorders are a significant health problem for which limited therapeutic options are available. CFTR is a major pro-secretory chloride channel at the ocular surface. We previously identified, by high-throughput screening, aminophenyl-1,3,5-triazine CFTRact-K089 (1) that activated CFTR with EC50 ~250 nM, which when delivered topically increased tear fluid secretion in mice and showed efficacy in an experimental dry eye model. Here, functional analysis of aminophenyl-1,3,5-triazine analogs elucidated structure-activity relationships for CFTR activation and identified substantially more potent analogs than 1...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#3
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28093304/chloride-conducting-light-activated-channel-gtacr2-can-produce-both-cessation-of-firing-and-generation-of-action-potentials-in-cortical-neurons-in-response-to-light
#4
A Y Malyshev, M V Roshchin, G R Smirnova, D A Dolgikh, P M Balaban, M A Ostrovsky
Optogenetics is a powerful technique in neuroscience that provided a great success in studying the brain functions during the last decade. Progress of optogenetics crucially depends on development of new molecular tools. Light-activated cation-conducting channelrhodopsin2 was widely used for excitation of cells since the emergence of optogenetics. In 2015 a family of natural light activated chloride channels GtACR was identified which appeared to be a very promising tool for using in optogenetics experiments as a cell silencer...
January 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28088107/gaas-laser-therapy-reestablishes-the-morphology-of-the-nmj-and-nachrs-after-injury-due-to-bupivacaine
#5
Cristiane Neves Alessi Pissulin, Paula Aiello Tomé de Souza Castro, Flávio Codina, Carina Guidi Pinto, Ivan Jose Vechetti-Junior, Selma Maria Michelin Matheus
BACKGROUND: Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle...
December 22, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28074656/atomistic-modeling-of-ion-conduction-through-the-voltage-sensing-domain-of-the-shaker-k-ion-channel
#6
Mona L Wood, J Alfredo Freites, Francesco Tombola, Douglas J Tobias
Voltage-sensing domains (VSDs) are modular membrane protein units that sense changes in the membrane electrostatic potential, and through conformational changes, regulate a specific function. The VSDs of voltage-dependent K+, Na+, and Ca2+ channels do not conduct ions under physiological conditions, but they can become ion-permeable under pathological conditions through mutations in the voltage sensor, particularly of basic residues (mostly arginines) in the S4 helix. Relatively little is known about the underlying mechanisms of conduction through VSDs...
January 11, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28071216/disinhibition-of-the-rat-prelimbic-cortex-promotes-serotonergic-activation-of-the-dorsal-raphe-nucleus-and-panicolytic-like-behavioral-effects
#7
Paula Sm Yamashita, Ailton Spiacci, James E Hassel, Christopher A Lowry, Helio Zangrossi
Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28067240/cd8-t-cells-stimulate-na-cl-co-transporter-ncc-in-distal-convoluted-tubules-leading-to-salt-sensitive-hypertension
#8
Yunmeng Liu, Tonya M Rafferty, Sung W Rhee, Jessica S Webber, Li Song, Benjamin Ko, Robert S Hoover, Beixiang He, Shengyu Mu
Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28056803/de-novo-transcriptome-and-expression-profile-analyses-of-the-asian-corn-borer-ostrinia-furnacalis-reveals-relevant-flubendiamide-response-genes
#9
Li Cui, Changhui Rui, Daibin Yang, Zhenying Wang, Huizhu Yuan
BACKGROUND: The Asian corn borer (ACB), Ostrinia furnacalis (Guenée), has become the most damaging insect pest of corn in Asia. However, the lack of genome or transcriptome information heavily hinders our further understanding of ACB in every aspect at a molecular level and on a genome-wide scale. Here, we used the Ion Torrent Personal Genome Machine (PGM) Sequencer to explore the ACB transcriptome and to identify relevant genes in response to flubendiamide, showing high selective activity against ACB...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28053034/simultaneous-loss-of-nckx4-and-cng-channel-desensitization-impairs-olfactory-sensitivity
#10
Christopher H Ferguson, Haiqing Zhao
: In vertebrate olfactory sensory neurons (OSNs), Ca(2+) plays key roles in both mediating and regulating the olfactory response. Ca(2+) enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca(2+)-activated chloride channel to amplify the response. Ca(2+) also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca(2+)/calmodulin (CaM), to reduce the response...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28046119/permeation-mechanisms-in-the-tmem16b-calcium-activated-chloride-channels
#11
Simone Pifferi
TMEM16A and TMEM16B encode for Ca2+-activated Cl- channels (CaCC) and are expressed in many cell types and play a relevant role in many physiological processes. Here, I performed a site-directed mutagenesis study to understand the molecular mechanisms of ion permeation of TMEM16B. I mutated two positive charged residues R573 and K540, respectively located at the entrance and inside the putative channel pore and I measured the properties of wild-type and mutant TMEM16B channels expressed in HEK-293 cells using whole-cell and excised inside-out patch clamp experiments...
2017: PloS One
https://www.readbyqxmd.com/read/28045581/overexpression-of-the-pp2a-c5-gene-confers-increased-salt-tolerance-in-arabidopsis-thaliana
#12
Rongbin Hu, Yinfeng Zhu, Guoxin Shen, Hong Zhang
Protein phosphatase 2A (PP2A) was shown to play important roles in biotic and abiotic stress signaling pathways in plants. PP2A is made of three subunits: a scaffolding subunit A, a regulatory subunit B, and a catalytic subunit C. It is believed that the B subunit recognizes specific substrates and the C subunit directly acts on the selected substrates, whereas the A subunit brings a B subunit and a C subunit together to form a specific PP2A holoenzyme. Because there are multiple isoforms for each PP2A subunit, there could be hundreds of novel PP2A holoenzymes in plants...
January 3, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28040564/role-of-potassium-channels-in-chlorogenic-acid-induced-apoptotic-volume-decrease-and-cell-cycle-arrest-in-candida-albicans
#13
JiEun Yun, Dong Gun Lee
BACKGROUND: Chlorogenic acid (CRA) is an abundant phenolic compound in the human diet. CRA has a potent antifungal effect, inducing cell death in Candida albicans. However, there are no further studies to investigate the antifungal mechanism of CRA, associated with ion channels. METHODS: To evaluate the inhibitory effects on CRA-induced cell death, C. albicans cells were pretreated with potassium and chloride channel blockers, separately. Flow cytometry was carried out to detect several hallmarks of apoptosis, such as cell cycle arrest, caspase activation, and DNA fragmentation, after staining of the cells with SYTOX green, FITC-VAD-FMK, and TUNEL...
December 28, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28027799/regulation-of-epithelial-ion-transport-in-exocrine-glands-by-store-operated-ca-2-entry
#14
REVIEW
Axel R Concepcion, Stefan Feske
Store-operated Ca(2+) entry (SOCE) is a conserved mechanism of Ca(2+) influx that regulates Ca(2+) signaling in many cell types. SOCE is activated by depletion of endoplasmic reticulum (ER) Ca(2+) stores in response to physiological agonist stimulation. After it was first postulated by J.W. Putney Jr. in 1986, SOCE has been described in a large number of non-excitable cell types including secretory cells of different exocrine glands. Here we discuss the mechanisms by which SOCE controls salt and fluid secretion in exocrine glands, with a special focus on eccrine sweat glands...
December 21, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28027400/elevated-intracellular-na-concentrations-in-developing-spinal-neurons
#15
Casie Lindsly, Carlos Gonzalez-Islas, Peter Wenner
Over 25 years ago it was first reported that intracellular chloride levels (Cl(-)in ) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with disease and neural injury. While there is some evidence that intracellular sodium levels (Na(+)in ) change during the development of non-neural cells, it has largely been assumed that Na(+)in is the same in developing and mature neurons...
December 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28017617/mir-263a-regulates-enac-to-maintain-osmotic-and-intestinal-stem-cell-homeostasis-in-drosophila
#16
Kevin Kim, Ruei-Jiun Hung, Norbert Perrimon
Proper regulation of osmotic balance and response to tissue damage is crucial in maintaining intestinal stem cell (ISC) homeostasis. We found that Drosophila miR-263a downregulates the expression of epithelial sodium channel (ENaC) subunits in enterocytes (ECs) to maintain osmotic and ISC homeostasis. In the absence of miR-263a, the intraluminal surface of the intestine displays dehydration-like phenotypes, Na(+) levels are increased in ECs, stress pathways are activated in ECs, and ISCs overproliferate. Furthermore, miR-263a mutants have increased bacterial load and expression of antimicrobial peptides...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28011945/orexin-a-modulates-ins-1e-cell-proliferation-and-insulin-secretion-via-extracellular-signal-regulated-kinase-and-transient-receptor-potential-channels
#17
M Skrzypski, N Khajavi, S Mergler, M Billert, D Szczepankiewicz, T Wojciechowicz, K W Nowak, M Z Strowski
Orexins A (OXA) and B (OXB) control energy homeostasis by regulating food intake, energy expenditure and sleep-wake cycle. Several studies showed that OXA stimulates insulin secretion and proliferation of beta cells. However, mechanisms of action are still not well understood. Here, we investigated whether ERK and transient receptor potential channels (TRPs) play a role in mediating the effect of OXA on cell growth, insulin production, and secretion using the established INS-1E cell line. Cell proliferation was measured using BrdU assay...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28006700/detection-of-different-microenvironments-and-lactobacillus-sakei-biotypes-in-ventricina-a-traditional-fermented-sausage-from-central-italy
#18
Patrizio Tremonte, Elena Sorrentino, Gianfranco Pannella, Luca Tipaldi, Marina Sturchio, Armando Masucci, Lucia Maiuro, Raffaele Coppola, Mariantonietta Succi
The present study evaluated the physico-chemical and microbiological features of Ventricina, considering for the first time the presence of different compartments deriving from the technology of production. In fact meat pieces (pork muscle and fat cut into cubes of about 10-20cm(3)), mixed with other ingredients and then stuffed into pig bladder, are still distinguishable at the end of the ripening. They appear delimited on the outside by the casing and inside by thin layers consisting of spices (mainly red pepper powder), salt and meat juices...
February 2, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/28002411/structure-of-a-clc-chloride-ion-channel-by-cryo-electron-microscopy
#19
Eunyong Park, Ernest B Campbell, Roderick MacKinnon
CLC proteins transport chloride (Cl(-)) ions across cellular membranes to regulate muscle excitability, electrolyte movement across epithelia, and acidification of intracellular organelles. Some CLC proteins are channels that conduct Cl(-) ions passively, whereas others are secondary active transporters that exchange two Cl(-) ions for one H(+). The structural basis underlying these distinctive transport mechanisms is puzzling because CLC channels and transporters are expected to share the same architecture on the basis of sequence homology...
December 21, 2016: Nature
https://www.readbyqxmd.com/read/27999941/extracellular-phosphates-enhance-activities-of-voltage-gated-proton-channels-and-production-of-reactive-oxygen-species-in-murine-osteoclast-like-cells
#20
Guangshuai Li, Katsuyuki Miura, Miyuki Kuno
Osteoclasts are highly differentiated bone-resorbing cells and play a significant role in bone remodelling. In the resorption pit, inorganic phosphate (Pi) concentrations increase because of degradation of hydroxyapatite. We studied effects of extracellular Pi on voltage-gated H(+) channels in osteoclast-like cells derived from a macrophage cell line (RAW264). Extracellular Pi (1.25-20 mM) increased the H(+) channel currents dose dependently and reversibly. The Pi-induced increases were attenuated by removal of extracellular Na(+) and by phosphonoformic acid, a blocker of Na(+)-dependent Pi transporters...
December 21, 2016: Pflügers Archiv: European Journal of Physiology
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