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chloride channel activators

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https://www.readbyqxmd.com/read/29331508/compartmentalized-crosstalk-of-cftr-and-tmem16a-ano1-through-epac1-and-adcy1
#1
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29329909/the-signaling-role-for-chloride-in-the-bidirectional-communication-between-neurons-and-astrocytes
#2
REVIEW
Corinne S Wilson, Alexander A Mongin
It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl-) fluxes via the inhibitory GABAA and glycine receptors. Here, we discuss the putative contribution of Cl- fluxes and intracellular Cl- to other forms of information transfer in the CNS, namely the bidirectional communication between neurons and astrocytes. The manuscript (i) summarizes the generic functions of Cl- in cellular physiology, (ii) recaps molecular identities and properties of Cl- transporters and channels in neurons and astrocytes, and (iii) analyzes emerging studies implicating Cl- in the modulation of neuroglial communication...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29326302/role-of-clc-k-and-barttin-in-low-potassium-induced-sodium-chloride-cotransporter-activation-and-hypertension-in-mouse-kidney
#3
Naohiro Nomura, Wakana Shoda, Yuanlong Wang, Shintaro Mandai, Taisuke Furusho, Daiei Takahashi, Moko Zeniya, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
The sodium-chloride cotransporter (NCC) has been identified as a key molecule regulating potassium balance. The mechanisms of NCC regulation during low extracellular potassium concentrations have been studied in vitro. These studies have shown that hyperpolarization increased chloride efflux, leading to the activation of chloride-sensitive WNK kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC. However, this mechanism was not studied in vivo Previously, we developed the barttin hypomorphic mouse ( Bsndneo/neo mice), expressing very low levels of barttin and ClC-K channels, because barttin is an essential ß-subunit of ClC-K...
January 11, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29310825/potassium-intake-modulates-the-thiazide-sensitive-sodium-chloride-cotransporter-ncc-activity-via-the-kir4-1-potassium-channel
#4
Ming-Xiao Wang, Catherina A Cuevas, Xiao-Tong Su, Peng Wu, Zhong-Xiuzi Gao, Dao-Hong Lin, James A McCormick, Chao-Ling Yang, Wen-Hui Wang, David H Ellison
Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of potassium diet on NCC. High potassium intake inhibited the basolateral 40 pS potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice...
January 6, 2018: Kidney International
https://www.readbyqxmd.com/read/29304792/aberrant-use-and-poor-quality-of-trypanocides-a-risk-for-drug-resistance-in-south-western-ethiopia
#5
T Tekle, G Terefe, T Cherenet, H Ashenafi, K G Akoda, A Teko-Agbo, J Van Den Abbeele, G Gari, P-H Clausen, A Hoppenheit, R C Mattioli, R Peter, T Marcotty, G Cecchi, V Delespaux
BACKGROUND: Trypanocidal drugs have been used to control African animal trypanosomosis for several decades. In Ethiopia, these drugs are available from both authorized (legal) and unauthorized (illegal) sources but documentation on utilization practices and quality of circulating products is scanty. This study looked at the practices of trypanocidal drug utilization by farmers and the integrity of active ingredient in trypanocides sold in Gurage zone, south western Ethiopia. The surveys were based on a structured questionnaire and drug quality determination of commonly used brands originating from European and Asian companies and sold at both authorized and unauthorized markets...
January 5, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/29301784/trpv4-transient-receptor-potential-vanilloid-4-channel-dependent-negative-feedback-mechanism-regulates-gq-protein-coupled-receptor-induced-vasoconstriction
#6
Kwangseok Hong, Eric L Cope, Leon J DeLalio, Corina Marziano, Brant E Isakson, Swapnil K Sonkusare
OBJECTIVE: Several physiological stimuli activate smooth muscle cell (SMC) GqPCRs (Gq protein-coupled receptors) to cause vasoconstriction. As a protective mechanism against excessive vasoconstriction, SMC GqPCR stimulation invokes endothelial cell vasodilatory signaling. Whether Ca2+ influx in endothelial cells contributes to the regulation of GqPCR-induced vasoconstriction remains unknown. Ca2+ influx through TRPV4 (transient receptor potential vanilloid 4) channels is a key regulator of endothelium-dependent vasodilation...
January 4, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29286076/activation-of-transient-receptor-potential-vanilloid-1-protects-the-heart-against-apoptosis-in-ischemia-reperfusion-injury-through-upregulating-the-pi3k-akt-signaling-pathway
#7
Xiao-Xue Jiang, Guan-Yu Liu, Han Lei, Zuo-Ling Li, Qing-Ping Feng, Wei Huang
Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel and a molecular integrator of noxious stimuli. TRPV1 activation confers cardiac protection against ischemia/reperfusion (I/R) injury. The present study aimed to investigate whether the cardioprotective effects of TRPV1 were associated with the inhibition of apoptosis via the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) and extracellular signal‑regulated protein kinase 1/2 (ERK1/2) signaling pathways. Briefly, the hearts of TRPV1 knockout (TRPV1‑/‑) or wild‑type (WT) mice were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion in a Langendorff apparatus in the presence or absence of the PI3K inhibitor, LY294002...
December 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29283974/the-role-of-distal-tubule-and-collecting-duct-sodium-reabsorption-in-sunitinib-induced-hypertension
#8
Jeannine Witte, Josephine Lampe, Anna Koenen, Ines Urbaneck, Antje Steinbach, Rainer Rettig, Olaf Grisk
OBJECTIVE: Antiangiogenic receptor tyrosine kinase inhibitors (RTKI) induce arterial hypertension which may limit their use. Renal fractional sodium excretion (FENa) is reduced in early RTKI-induced hypertension, whereas fractional lithium excretion is unaltered. Therefore, we tested the hypothesis that activated distal tubule and collecting duct sodium reabsorption contributes to RTKI-induced hypertension. METHODS: Amiloride-sensitive and hydrochlorothiazide (HCTZ)-sensitive fractional sodium reabsorption (FRNa) and renal epithelial sodium channel (ENaC) as well as sodium chloride cotransporter (NCC) abundances were determined in sunitinib-treated and control rats...
December 27, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29277655/phosphatidylinositol-4-5-bisphosphate-cholesterol-and-fatty-acids-modulate-the-calcium-activated-chloride-channel-tmem16a-ano1
#9
José J De Jesús-Pérez, Silvia Cruz-Rangel, Ángeles E Espino-Saldaña, Ataúlfo Martínez-Torres, Zhiqiang Qu, H Criss Hartzell, Nancy E Corral-Fernandez, Patricia Pérez-Cornejo, Jorge Arreola
The TMEM16A-mediated Ca2+-activated Cl- current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca2+...
December 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29273736/vglut1-functions-as-a-glutamate-proton-exchanger-with-chloride-channel-activity-in-hippocampal-glutamatergic-synapses
#10
Magalie Martineau, Raul E Guzman, Christoph Fahlke, Jürgen Klingauf
Glutamate is the major excitatory transmitter in the vertebrate nervous system. To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and mechanism of glutamate uptake in intact neurons are still largely unknown. Here, we show by live-cell imaging with pH- and chloride-sensitive fluorescent probes in cultured hippocampal neurons of wild-type and VGLUT1-deficient mice that in SVs VGLUT functions as a glutamate/proton exchanger associated with a channel-like chloride conductance...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29259251/bkip-1-an-auxiliary-subunit-critical-to-slo-1-function-inhibits-slo-2-potassium-channel-in-vivo
#11
Long-Gang Niu, Ping Liu, Yuan Shui, Roger Mailler, Zhao-Wen Wang, Bojun Chen
Auxiliary subunits are often needed to tailor K+ channel functional properties and expression levels. Many auxiliary subunits have been identified for mammalian Slo1, a high-conductance K+ channel gated by voltage and Ca2+. Experiments with heterologous expression systems show that some of the identified Slo1 auxiliary subunits can also regulate other Slo K+ channels. However, it is unclear whether a single auxiliary subunit may regulate more than one Slo channel in native tissues. BKIP-1, an auxiliary subunit of C...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29236691/activation-mechanism-of-the-calcium-activated-chloride-channel-tmem16a-revealed-by-cryo-em
#12
Cristina Paulino, Valeria Kalienkova, Andy K M Lam, Yvonne Neldner, Raimund Dutzler
The calcium-activated chloride channel TMEM16A is a ligand-gated anion channel that opens in response to an increase in intracellular Ca2+ concentration. The protein is broadly expressed and contributes to diverse physiological processes, including transepithelial chloride transport and the control of electrical signalling in smooth muscles and certain neurons. As a member of the TMEM16 (or anoctamin) family of membrane proteins, TMEM16A is closely related to paralogues that function as scramblases, which facilitate the bidirectional movement of lipids across membranes...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29236684/cryo-em-structures-of-the-tmem16a-calcium-activated-chloride-channel
#13
Shangyu Dang, Shengjie Feng, Jason Tien, Christian J Peters, David Bulkley, Marco Lolicato, Jianhua Zhao, Kathrin Zuberbühler, Wenlei Ye, Lijun Qi, Tingxu Chen, Charles S Craik, Yuh Nung Jan, Daniel L Minor, Yifan Cheng, Lily Yeh Jan
Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29235532/investigation-of-the-effects-of-the-cftr-potentiator-ivacaftor-on-human-p-glycoprotein-abcb1
#14
Swathi Lingam, Nopnithi Thonghin, Robert C Ford
Ivacaftor is a potentiator of the CFTR chloride channel and is in worldwide clinical use for the chronic treatment of cystic fibrosis in patients. There is evidence that the bioavailability of ivacaftor in the body may be influenced by the multi-drug exporter P-glycoprotein. Here we have employed purified and reconstituted P-glycoprotein to study its interaction with ivacaftor as well as the ability of the drug to compete with a known transported substrate of the protein. We find that ivacaftor stimulates the ATPase activity of the purified protein and can compete with the transport of the fluorescent substrate Hoechst 33342...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29231977/dids-inhibits-overexpression-bak1-induced-mitochondrial-apoptosis-through-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway
#15
Xiayun Yang, Shusheng Tang, Daowen Li, Xiaohong Yu, Fuyun Wang, Xilong Xiao
Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1-induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1-induced apoptosis through GSK3β/β-catenin signaling pathway...
December 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29229864/cytoplasmic-cl-couples-membrane-remodeling-to-epithelial-morphogenesis
#16
Mu He, Wenlei Ye, Won-Jing Wang, Eirish S Sison, Yuh Nung Jan, Lily Yeh Jan
Chloride is the major free anion in the extracellular space (>100 mM) and within the cytoplasm in eukaryotes (10 ∼ 20 mM). Cytoplasmic Cl- level is dynamically regulated by Cl- channels and transporters. It is well established that movement of Cl- across the cell membrane is coupled with cell excitability through changes in membrane potential and with water secretion. However, whether cytoplasmic Cl- plays additional roles in animal development and tissue homeostasis is unknown. Here we use genetics, cell biological and pharmacological tools to demonstrate that TMEM16A, an evolutionarily conserved calcium-activated chloride channel (CaCC), regulates cytoplasmic Cl- homeostasis and promotes plasma membrane remodeling required for mammalian epithelial morphogenesis...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29200904/taurine-relaxes-human-radial-artery-through-potassium-channel-opening-action
#17
Kemal Gokhan Ulusoy, Erkan Kaya, Kubilay Karabacak, Melik Seyrek, İbrahim Duvan, Vedat Yildirim, Oguzhan Yildiz
The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, 30 µM) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride (10 µM to 10 mM)-induced contractions was investigated...
November 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29190973/clca4-inhibits-bladder-cancer-cell-proliferation-migration-and-invasion-by-suppressing-the-pi3k-akt-pathway
#18
Teng Hou, Lijie Zhou, Longwang Wang, Gallina Kazobinka, Xiaoping Zhang, Zhaohui Chen
Calcium activated chloride channel A4 (CLCA4), a tumor suppressor, was shown to contribute to the progression of several human cancers, while its role in bladder carcinoma remains unclear. In this study, we showed CLCA4 expression was down-regulated in bladder carcinoma tissues and cells compared to adjacent non-tumor tissues and normal urothelial cells. Low CLCA4 expression was correlated with larger tumor size, advanced tumor stage, and poor prognosis in bladder carcinoma patients. Overexpression of CLCA4 profoundly attenuated the proliferation, growth, migratory and invasive capabilities of bladder cancer cells, whereas CLCA4 knockdown had the opposite effect...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187363/trpv4-heats-up-ano1-dependent-exocrine-gland-fluid-secretion
#19
Sandra Derouiche, Yasunori Takayama, Masataka Murakami, Makoto Tominaga
Several ion channels and transporters regulate fluid secretion in salivary and lacrimal glands. In salivary glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increasing intracellular calcium concentrations...
November 29, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29185178/vasorelaxant-activities-and-the-underlying-pharmacological-mechanisms-of-gynura-procumbens-merr-leaf-extracts-on-rat-thoracic-aorta
#20
Zafar Iqbal, Idris Bello, Mohd Zaini Asmawi, Majed Ahmed Al-Mansoub, Ashfaq Ahmad, Qaiser Jabeen, Yam Mun Fei
Previous studies have investigated the cardiovascular activity of Gynura procumbens Merr. single-solvent extracts. The objective of this study was to evaluate the in vitro vasorelaxant properties and the underlying pharmacological mechanisms of serial extracts and fractions of Gynura procumbens (GP). The leaves of GP were serially extracted with petroleum ether, chloroform, methanol and water using the maceration method. Suspended aortic ring preparations were pre-contracted with phenylephrine (PE 1 µM), followed by cumulative addition of GP extracts (0...
November 28, 2017: Inflammopharmacology
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