Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains.

Science.gov (United States)

Garcia-Olivares, Jennie; Alekov, Alexi; Boroumand, Mohammad Reza; Begemann, Birgit; Hidalgo, Patricia; Fahlke, Christoph

2008-11-15

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability.

Evidence for a role of GABA- and glutamate-gated chloride channels in olfactory memory.

Science.gov (United States)

Boumghar, Katia; Couret-Fauvel, Thomas; Garcia, Mikael; Armengaud, Catherine

2012-11-01

In the honeybee, we investigated the role of transmissions mediated by GABA-gated chloride channels and glutamate-gated chloride channels (GluCls) of the mushroom bodies (MBs) on olfactory learning using a single-trial olfactory conditioning paradigm. The GABAergic antagonist picrotoxin (PTX) or the GluCl antagonist L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) was injected alone or in combination into the α-lobes of MBs. PTX impaired early long-term olfactory memory when injected before conditioning or before testing. L-trans-PDC alone induced no significant effect on learning and memory but induced a less specific response to the conditioned odor. When injected before PTX, L-trans-PDC was able to modulate PTX effects. These results emphasize the role of MB GABA-gated chloride channels in consolidation processes and strongly support that GluCls are involved in the perception of the conditioned stimulus.

Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels

DEFF Research Database (Denmark)

Lynagh, Timothy; Cromer, Brett A.; Dufour, Vanessa

2014-01-01

Pharmacological targeting of glutamate-gated chloride channels (GluCls) is a potent anthelmintic strategy, evidenced by macrocyclic lactones that eliminate numerous roundworm infections by activating roundworm GluCls. Given the recent identification of flatworm GluCls and the urgent need for drugs...

The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

DEFF Research Database (Denmark)

Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina

2004-01-01

, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION......Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone...... for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride...

CFTR chloride channel as a molecular target of anthraquinone compounds in herbal laxatives

Science.gov (United States)

Yang, Hong; Xu, Li-na; He, Cheng-yan; Liu, Xin; Fang, Rou-yu; Ma, Tong-hui

2011-01-01

Aim: To clarify whether CFTR is a molecular target of intestinal fluid secretion caused by the anthraquinone compounds from laxative herbal plants. Methods: A cell-based fluorescent assay to measure I− influx through CFTR chloride channel. A short-circuit current assay to measure transcellular Cl− current across single layer FRT cells and freshly isolated colon mucosa. A closed loop experiment to measure colon fluid secretion in vivo. Results: Anthraquinone compounds rhein, aloe-emodin and 1,8-dihydroxyanthraquinone (DHAN) stimulated I− influx through CFTR chloride channel in a dose-dependent manner in the presence of physiological concentration of cAMP. In the short-circuit current assay, the three compound enhanced Cl− currents in epithelia formed by CFTR-expressing FRT cells with EC50 values of 73±1.4, 56±1.7, and 50±0.5μmol/L, respectively, and Rhein also enhanced Cl− current in freshly isolated rat colonic mucosa with a similar potency. These effects were completely reversed by the CFTR selective blocker CFTRinh-172. In in vivo closed loop experiments, rhein 2 mmol/L stimulated colonic fluid accumulation that was largely blocked by CFTRinh-172. The anthraquinone compounds did not elevate cAMP level in cultured FRT cells and rat colonic mucosa, suggesting a direct effect on CFTR activity. Conclusion: Natural anthraquinone compounds in vegetable laxative drugs are CFTR potentiators that stimulated colonic chloride and fluid secretion. Thus CFTR chloride channel is a molecular target of vegetable laxative drugs. PMID:21602836

Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents

Science.gov (United States)

Moroni, Mirko; Biro, Istvan; Giugliano, Michele; Vijayan, Ranjit; Biggin, Philip C.; Beato, Marco; Sivilotti, Lucia G.

2011-01-01

In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mM). Our main finding is that glycine and GABA receptors “sense” chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation-selective, or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage-dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane. PMID:21976494

The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels.

Science.gov (United States)

Ozoe, Yoshihisa; Asahi, Miho; Ozoe, Fumiyo; Nakahira, Kunimitsu; Mita, Takeshi

2010-01-01

A structurally unique isoxazoline class compound, A1443, exhibits antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. This isoxazoline compound inhibits specific binding of the gamma-aminobutyric acid (GABA) receptor channel blocker [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) to housefly-head membranes, with an IC(50) value of 455pM. In contrast, the IC(50) value in rat-brain membranes is>10muM. To study the mode of action of this isoxazoline, we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively. Two-electrode voltage clamp electrophysiology was used to confirm that A1443 blocks GABA- and glutamate-induced chloride currents in Xenopus oocytes expressing MdGBCl or MdGluCl channels, with IC(50) values of 5.32 and 79.9 nM, respectively. Blockade by A1443 was observed in A2'S-MdGBCl and S2'A-MdGluCl mutant channels at levels similar to those of the respective wild-types, and houseflies expressing A2'S-MdGBCl channels were as susceptible to A1443 as standard houseflies. These findings indicate that A1443 is a novel and specific blocker of insect ligand-gated chloride channels. Copyright 2009 Elsevier Inc. All rights reserved.

The novel isoxazoline ectoparasiticide lotilaner (Credelio™: a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls

Directory of Open Access Journals (Sweden)

Lucien Rufener

2017-11-01

Full Text Available Abstract Background The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA-gated chloride channels (GABACls and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls. Lotilaner (Credelio™, a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. Methods In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the successful gene identification, cDNA cloning and functional expression in Xenopus oocytes of Drosohpila melanogaster (wild type and dieldrin/fipronil-resistant forms, Lepeophtheirus salmonis (an ectoparasite copepod crustacean of salmon, Rhipicephalus microplus and Canis lupus familiaris GABACls. Automated Xenopus oocyte two-electrode voltage clamp electrophysiology was used to assess GABACls functionality and to compare ion channel inhibition by lotilaner with that of established insecticides addressing GABACls as targets. Results In these assays, we demonstrated that lotilaner is a potent non-competitive antagonist of insects (fly GABACls. No cross-resistance with dieldrin or fipronil resistance mutations was detected, suggesting that lotilaner might bind to a site at least partly different from the one bound by known GABACl blockers. Using co-application experiments, we observed that lotilaner antagonism differs significantly from the classical open channel blocker fipronil. We finally confirmed for the first time that isoxazoline compounds are not only powerful antagonists of GABACls of acari (ticks but also of crustaceans (sea lice, while no activity on a dog GABAA receptor was observed up to a concentration of 10 μM. Conclusions Together, these results demonstrate that lotilaner is a non-competitive antagonist specific to invertebrate’s γ-aminobutyric acid-gated chloride channels (GABACls. They contribute to our understanding of the mode of

The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls).

Science.gov (United States)

Rufener, Lucien; Danelli, Vanessa; Bertrand, Daniel; Sager, Heinz

2017-11-01

The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls). Lotilaner (Credelio™), a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the successful gene identification, cDNA cloning and functional expression in Xenopus oocytes of Drosohpila melanogaster (wild type and dieldrin/fipronil-resistant forms), Lepeophtheirus salmonis (an ectoparasite copepod crustacean of salmon), Rhipicephalus microplus and Canis lupus familiaris GABACls. Automated Xenopus oocyte two-electrode voltage clamp electrophysiology was used to assess GABACls functionality and to compare ion channel inhibition by lotilaner with that of established insecticides addressing GABACls as targets. In these assays, we demonstrated that lotilaner is a potent non-competitive antagonist of insects (fly) GABACls. No cross-resistance with dieldrin or fipronil resistance mutations was detected, suggesting that lotilaner might bind to a site at least partly different from the one bound by known GABACl blockers. Using co-application experiments, we observed that lotilaner antagonism differs significantly from the classical open channel blocker fipronil. We finally confirmed for the first time that isoxazoline compounds are not only powerful antagonists of GABACls of acari (ticks) but also of crustaceans (sea lice), while no activity on a dog GABA A receptor was observed up to a concentration of 10 μM. Together, these results demonstrate that lotilaner is a non-competitive antagonist specific to invertebrate's γ-aminobutyric acid-gated chloride channels (GABACls). They contribute to our understanding of the mode of action of this new ectoparasiticide compound.

Adrenomedullin increases the short-circuit current in the rat prostate: Receptors, chloride channels, the effects of cAMP and calcium ions and implications on fluid secretion.

Science.gov (United States)

Liao, S B; Cheung, K H; Cheung, M P L; Wong, P F; O, W S; Tang, F

2014-05-01

In this study, we have investigated the effects of adrenomedullin on chloride and fluid secretion in the rat prostate. The presence of adrenomedullin (ADM) in rat prostate was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with an enzyme-linked assay for ADM. The effects of ADM on fluid secretion were studied by short-circuit current technique in a whole mount preparation of the prostate in an Ussing chamber. The results indicated that the ADM level was higher in the ventral than the dorso-lateral prostate and the major molecular species was the active peptide. ADM increased the short-circuit current through both the cAMP- and calcium-activated chloride channels in the ventral lobe, but only through the calcium-activated channels in the dorso-lateral lobe. These stimulatory effects were blocked by the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP8-37. We conclude that ADM may regulate prostatic fluid secretion through the chloride channels, which may affect the composition of the seminal plasma bathing the spermatozoa and hence fertility. © 2014 American Society of Andrology and European Academy of Andrology.

A proton-activated, outwardly rectifying chloride channel in human umbilical vein endothelial cells

International Nuclear Information System (INIS)

Ma Zhiyong; Zhang Wei; Chen Liang; Wang Rong; Kan Xiaohong; Sun Guizhen; Liu Chunxi; Li Li; Zhang Yun

2008-01-01

Extracellular acidic pH-activated chloride channel I Cl,acid , has been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to characterize I Cl,acid in human umbilical vein endothelial cells(HUVECs). The activation and deactivation of the current rapidly and repeatedly follows the change of the extracellular solution at pH 4.3, with the threshold pH 5.3. In addition, at very positive potentials, the current displays a time-dependent facilitation. pH-response relationship for I Cl,acid revealed that EC 50 is pH 4.764 with a threshold pH value of pH 5.3 and nH of 14.545. The current can be blocked by the Cl - channel inhibitor DIDS (100 μM). In summary, for the first time we report the presence of proton-activated, outwardly rectifying chloride channel in HUVECs. Because an acidic environment can develop in local myocardium under pathological conditions such as myocardial ischemia, I Cl,acid would play a role in regulation of EC function under these pathological conditions

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

Energy Technology Data Exchange (ETDEWEB)

Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

2014-04-18

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

International Nuclear Information System (INIS)

Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

2014-01-01

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections

Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

Science.gov (United States)

Qi, Yanmei; Mair, Norbert; Kummer, Kai K.; Leitner, Michael G.; Camprubí-Robles, María; Langeslag, Michiel; Kress, Michaela

2018-01-01

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception. PMID:29479306

Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

Directory of Open Access Journals (Sweden)

Yanmei Qi

2018-02-01

Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception.

Gene expression in Listeria monocytogenes exposed to sublethal concentration of benzalkonium chloride.

Science.gov (United States)

Tamburro, Manuela; Ripabelli, Giancarlo; Vitullo, Monia; Dallman, Timothy James; Pontello, Mirella; Amar, Corinne Francoise Laurence; Sammarco, Michela Lucia

2015-06-01

In this study, tolerance at sublethal concentration of benzalkonium chloride and transcription levels of mdrL, ladR, lde, sigB and bcrABC genes in Listeria monocytogenes strains were evaluated. Viable cells reduction occurred in 45% of strains and clinical isolates showed lower sensitivity than isolates from foods. An increased transcription of an efflux system encoding gene was found in 60% of strains, and simultaneous mdrL overexpression and ladR underexpression occurred in 30% of isolates. A significant association between reduced benzalkonium chloride activity and both mdrL and sigB overexpression was observed; sigB expression also correlated with both mdrL and ladR genes. The bcrABC gene was only found in six strains, all isolated from foods and sensitive to benzalkonium chloride, and in four strains an underexpression was observed. Disinfection at sublethal concentration was less effective in clinical isolates, and mdrL and sigB expression was significantly affected by disinfection. Further insights are needed to understand the adaptation to benzalkonium chloride and to evaluate whether changes in gene expression could affect the L. monocytogenes virulence traits and persistence in the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibition of the voltage-dependent chloride channel of Torpedo electric organ by diisopropylfluorophosphate and its reversal by oximes

International Nuclear Information System (INIS)

Abalis, I.M.; Chiang, P.K.; Wirtz, R.A.; Andre, R.G.

1986-01-01

Diisopropylfluorophosphate (DFP), a potent organophosphate inhibitor of cholinesterases, was found to inhibit the specific binding of [ 35 S]t-butylbicyclophosphorothionate (TBPS), specific chloride channels ligand, to the electric organ membranes of Torpedo, with a Ki of 21 +/- 3 μM. The binding sites of [ 35 S]TBPS in the Torpedo membranes were found not to be GABA receptors or nicotinic acetylcholine receptors as previously described. Interestingly, a stimulation of the binding of [ 35 S]TBPS was observed in the presence of atropine and three oximes, monopyridinium oxime 2-PAM, bispyridinium bis-oxime TMB-4 and H-oxime HI-6. The maximal stimulation was 300-500% of control, after which, the stimulation was reversed at higher concentrations. The three oximes protected by more than 95% the inhibition by 1 mM DFP of the binding of [ 35 S]TBPS to the voltage-dependent chloride channel. However, atropine protected only 20% of the inhibited channel. These results, thus, suggest that the protection against the toxic effects of DFP or other anticholinesterase agents by the tested oximes may not be solely a result of the reactivation of cholinesterases but also the protection of the voltage-dependent chloride channel

The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls)

OpenAIRE

Rufener, Lucien; Danelli, Vanessa; Bertrand, Daniel; Sager, Heinz

2017-01-01

Background The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls). Lotilaner (Credelio™), a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. Methods In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the success...

Cloning and functional expression of a plant voltage-dependent chloride channel.

Science.gov (United States)

Lurin, C; Geelen, D; Barbier-Brygoo, H; Guern, J; Maurel, C

1996-01-01

Plant cell membrane anion channels participate in basic physiological functions, such as cell volume regulation and signal transduction. However, nothing is known about their molecular structure. Using a polymerase chain reaction strategy, we have cloned a tobacco cDNA (CIC-Nt1) encoding a 780-amino acid protein with several putative transmembrane domains. CIC-Nt1 displays 24 to 32% amino acid identity with members of the animal voltage-dependent chloride channel (CIC) family, whose archetype is CIC-0 from the Torpedo marmorata electric organ. Injection of CIC-Nt1 complementary RNA into Xenopus oocytes elicited slowly activating inward currents upon membrane hyperpolarization more negative than -120 mV. These currents were carried mainly by anions, modulated by extracellular anions, and totally blocked by 10 mM extracellular calcium. The identification of CIC-Nt1 extends the CIC family to higher plants and provides a molecular probe for the study of voltage-dependent anion channels in plants. PMID:8624442

Differential distribution of glutamate- and GABA-gated chloride channels in the housefly Musca domestica.

Science.gov (United States)

Kita, Tomo; Ozoe, Fumiyo; Azuma, Masaaki; Ozoe, Yoshihisa

2013-09-01

l-Glutamic acid (glutamate) mediates fast inhibitory neurotransmission by affecting glutamate-gated chloride channels (GluCls) in invertebrates. The molecular function and pharmacological properties of GluCls have been well studied, but not much is known about their physiological role and localization in the insect body. The distribution of GluCls in the housefly (Musca domestica L.) was thus compared with the distribution of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls). Quantitative PCR and ligand-binding experiments indicate that the GluCl and GABACl transcripts and proteins are predominantly expressed in the adult head. Intense GluCl immunostaining was detected in the lamina, leg motor neurons, and legs of adult houseflies. The GABACl (Rdl) immunostaining was more widely distributed, and was found in the medulla, lobula, lobula plate, mushroom body, antennal lobe, and ellipsoid body. The present findings suggest that GluCls have physiological roles in different tissues than GABACls. Copyright © 2013 Elsevier Ltd. All rights reserved.

CLC channel function and dysfunction in health and disease

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Gabriel eStölting

2014-10-01

Full Text Available CLC channels and transporters are expressed in most tissues and fulfill diverse functions. There are four human CLC channels, ClC-1, ClC-2, ClC-Ka and ClC-Kb, and five CLC transporters, ClC-3 through -7. Some of the CLC channels additionally associate with accessory subunits. Whereas barttin is mandatory for the functional expression of CLC-K, GlialCam is a facultative subunit of ClC-2 which modifies gating and thus increases the functional variability within the CLC family. Isoform-specific ion conduction and gating properties optimize distinct CLC channels for their cellular tasks. ClC-1 preferentially conducts at negative voltages, and the resulting inward rectification provides a large resting chloride conductance without interference with the muscle action potential. Exclusive opening at voltages negative to the chloride reversal potential allows for ClC-2 to regulate intracellular chloride concentrations. ClC-Ka and ClC-Kb are equally suited for inward and outward currents to support transcellular chloride fluxes. Every human CLC channel gene has been linked to a genetic disease, and studying these mutations has provided much information about the physiological roles and the molecular basis of CLC channel function. Mutations in the gene encoding ClC-1 cause myotonia congenita, a disease characterized by sarcolemmal hyperexcitability and muscle stiffness. Loss-of-function of ClC-Kb/barttin channels in patients suffering from Bartter syndrome identified the determinants of chloride conductances in the limb of Henle. Mutations in CLCN2 were found in patients with CNS disorders but the functional role of this isoform is still not understood. Recent links between ClC-1 and epilepsy and ClC-Ka and heart failure suggested novel cellular functions of these proteins. This review aims to survey the knowledge about physiological and pathophysiological functions of human CLC channels in the light of recent discoveries from biophysical, physiological

Salt Sensitive Tet-Off-Like Systems to Knockdown Primordial Germ Cell Genes for Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus.

Science.gov (United States)

Li, Hanbo; Su, Baofeng; Qin, Guyu; Ye, Zhi; Alsaqufi, Ahmed; Perera, Dayan A; Shang, Mei; Odin, Ramjie; Vo, Khoi; Drescher, David; Robinson, Dalton; Zhang, Dan; Abass, Nermeen; Dunham, Rex A

2017-05-31

Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus . Two primordial germ cell (PGC) marker genes, nanos and dead end , were targeted for knockdown, and an off-target gene, vasa , was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS) and zebrafish racemase (Rm), were each coupled with four knockdown strategies: ds-sh RNA targeting the 5' end (N1) or 3' end (N2) of channel catfish nanos , full-length cDNA sequence of channel catfish nanos for overexpression (cDNA) and ds-sh RNA targeting channel catfish dead end (DND). Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P₁ fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P₁ fish, most F₁ individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F₂ or F₃ are needed for evaluation.

Adrenomedullin increases the short-circuit current in the mouse seminal vesicle: actions on chloride secretion.

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Liao, S B; Cheung, K H; O, W S; Tang, Fai

2014-08-01

Adrenomedullin (ADM) may regulate seminal vesicle fluid secretion, and this may affect sperm quality. In this study, we investigated the effect of ADM on chloride secretion in the mouse seminal vesicle. The presence of ADM in mouse seminal vesicle was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with enzyme-linked assay for ADM. The effects of ADM on chloride secretion were studied by short-circuit current technique in a whole-mount preparation of mouse seminal vesicle in an Ussing chamber. The effects of specific ADM and calcitonin gene-related peptide (CGRP) receptor antagonists were investigated. Whether the ADM effect depended on the cAMP- and/or calcium-activated chloride channel was also studied using specific chloride channel blockers. The results showed that ADM was present in seminal vesicle epithelial cells. The major molecular species was precursor in the mouse seminal vesicle. ADM increased short-circuit current through the calcium-activated chloride channel in mouse seminal vesicle, and CGRP receptor was involved. We conclude that ADM may regulate chloride and fluid secretion from the seminal vesicle, which may affect the composition of the seminal plasma bathing the sperm and, hence, fertility. © 2014 by the Society for the Study of Reproduction, Inc.

CLC-Nt1, a putative chloride channel protein of tobacco, co-localizes with mitochondrial membrane markers.

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Lurin, C; Güclü, J; Cheniclet, C; Carde, J P; Barbier-Brygoo, H; Maurel, C

2000-06-01

The voltage-dependent chloride channel (CLC) family of membrane proteins has cognates in animals, yeast, bacteria and plants, and chloride-channel activity has been assigned to most of the animal homologues. Lack of evidence of CLC functions in plants prompted us to characterize the cellular localization of the tobacco CLC-Nt1 protein. Specific polyclonal antibodies were raised against an N-terminal polypeptide of CLC-Nt1. These antibodies were used to probe membrane proteins prepared by various cell-fractionation methods. These included aqueous two-phase partitioning (for plasma membranes), free-flow electrophoresis (for vacuolar and plasma membranes), intact vacuole isolation, Percoll-gradient centrifugation (for plastids and mitochondria) and stepped, linear, sucrose-density-gradient centrifugation (for mitochondria). Each purified membrane fraction was characterized with specific marker enzyme activities or antibodies. Our studies ruled out the possibility that the major cell localization of CLC-Nt1 was the vacuolar or plasma membranes, the endoplasmic reticulum, the Golgi apparatus or the plastids. In contrast, we showed that the tobacco CLC-Nt1 specifically co-localized with the markers of the mitochondrial inner membrane, cytochrome c oxidase and NAD9 protein. CLC-Nt1 may correspond to the inner membrane anion channel ('IMAC') described previously in animal and plant mitochondria.

Salt Sensitive Tet-Off-Like Systems to Knockdown Primordial Germ Cell Genes for Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus

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Hanbo Li

2017-05-01

Full Text Available Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC marker genes, nanos and dead end, were targeted for knockdown, and an off-target gene, vasa, was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS and zebrafish racemase (Rm, were each coupled with four knockdown strategies: ds-sh RNA targeting the 5′ end (N1 or 3′ end (N2 of channel catfish nanos, full-length cDNA sequence of channel catfish nanos for overexpression (cDNA and ds-sh RNA targeting channel catfish dead end (DND. Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P1 fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P1 fish, most F1 individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F2 or F3 are needed for evaluation.

Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series.

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O'Brien, Catherine E; Anderson, Paula J; Stowe, Cindy D

2010-03-01

To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF). This case series describes the use of lubiprostone for the treatment of constipation in 3 adults with CF (mean +/- SD length of therapy 17.3 +/- 1.5 mo). All 3 patients were prescribed lubiprostone 24 microg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients. CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (ClC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF. Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

pH-modulation of chloride channels from the sarcoplasmic reticulum of skeletal muscle.

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Kourie, J I

1999-01-01

The understanding of the role of cytoplasmic pH in modulating sarcoplasmic reticulum (SR) ion channels involved in Ca2+ regulation is important for the understanding of the function of normal and adversely affected muscles. The dependency of the SR small chloride (SCl) channel from rabbit skeletal muscle on cytoplasmic pH (pHcis) and luminal pH (pHtrans) was investigated using the lipid bilayer-vesicle fusion technique. Low pHcis 6.75-4.28 modifies the operational mode of this multiconductance channel (conductance levels between 5 and 75 pS). At pHcis 7.26-7.37 the channel mode is dominated by the conductance and kinetics of the main conductance state (65-75 pS) whereas at low pHcis 6.75-4.28 the channel mode is dominated by the conductance and kinetics of subconductance states (5-40 pS). Similarly, low pHtrans 4.07, but not pHtrans 6.28, modified the activity of SCl channels. The effects of low pHcis are pronounced at 10(-3) and 10(-4) M [Ca2+]cis but are not apparent at 10(-5) M [Ca2+]cis, where the subconductances of the channel are already prominent. Low pHcis-induced mode shift in the SCl channel activity is due to modification of the channel proteins that cause the uncoupling of the subconductance states. The results in this study suggest that low pHcis can modify the functional properties of the skeletal SR ion channels and hence contribute, at least partly, to the malfunction in the contraction-relaxation mechanism in skeletal muscle under low cytoplasmic pH levels.

Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut Microbiota and Host Chloride Channels.

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Zhang, Yong; Kang, Chao; Wang, Xiao-Lan; Zhou, Min; Chen, Meng-Ting; Zhu, Xiao-Hui; Liu, Kai; Wang, Bin; Zhang, Qian-Yong; Zhu, Jun-Dong; Mi, Man-Tian

2018-03-01

In recent decades, the association among diet, gut microbiota, and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study is to identify that the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota. An AOM/DSS (azoxymethan/dextran sodium sulfate) model is established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influence the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota display different degrees of chemically induced tumorigenesis. Mechanism analysis reveals that gut microbiota-associated chloride channels participated in colon tumorigenesis. Gut microbiota changes occur in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Osmoregulated Chloride Currents in Hemocytes from Mytilus galloprovincialis.

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Monica Bregante

Full Text Available We investigated the biophysical properties of the transport mediated by ion channels in hemocytes from the hemolymph of the bivalve Mytilus galloprovincialis. Besides other transporters, mytilus hemocytes possess a specialized channel sensitive to the osmotic pressure with functional properties similar to those of other transport proteins present in vertebrates. As chloride fluxes may play an important role in the regulation of cell volume in case of modifications of the ionic composition of the external medium, we focused our attention on an inwardly-rectifying voltage-dependent, chloride-selective channel activated by negative membrane potentials and potentiated by the low osmolality of the external solution. The chloride channel was slightly inhibited by micromolar concentrations of zinc chloride in the bath solution, while the antifouling agent zinc pyrithione did not affect the channel conductance at all. This is the first direct electrophysiological characterization of a functional ion channel in ancestral immunocytes of mytilus, which may bring a contribution to the understanding of the response of bivalves to salt and contaminant stresses.

Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole-cell oscillations in smooth muscle cells

DEFF Research Database (Denmark)

Jacobsen, Jens Christian; Aalkjær, Christian; Nilsson, Holger

2007-01-01

waves sweeping through the cytoplasm when the SR is stimulated to release calcium. A rise in cyclic guanosine monophosphate (cGMP) leads to the experimentally observed transition from waves to whole-cell calcium oscillations. At the same time membrane potential starts to oscillate and the frequency...... approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes uniform opening of L-type calcium...... onset of oscillations in membrane potential within the individual cell may underlie sudden intercellular synchronization and the appearance of vasomotion. Key words: Vasomotion, Chloride channel, cGMP, Mathematical model, Calcium waves....

Salt, chloride, bleach, and innate host defense

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Wang, Guoshun; Nauseef, William M.

2015-01-01

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979

Salt, chloride, bleach, and innate host defense.

Science.gov (United States)

Wang, Guoshun; Nauseef, William M

2015-08-01

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.

Oxidation promotes insertion of the CLIC1 chloride intracellular channel into the membrane.

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Goodchild, Sophia C; Howell, Michael W; Cordina, Nicole M; Littler, Dene R; Breit, Samuel N; Curmi, Paul M G; Brown, Louise Jennifer

2009-12-01

Members of the chloride intracellular channel (CLIC) family exist primarily as soluble proteins but can also auto-insert into cellular membranes to form ion channels. While little is known about the process of CLIC membrane insertion, a unique feature of mammalian CLIC1 is its ability to undergo a dramatic structural metamorphosis between a monomeric glutathione-S-transferase homolog and an all-helical dimer upon oxidation in solution. Whether this oxidation-induced metamorphosis facilitates CLIC1 membrane insertion is unclear. In this work, we have sought to characterise the role of oxidation in the process of CLIC1 membrane insertion. We examined how redox conditions modify the ability of CLIC1 to associate with and insert into the membrane using fluorescence quenching studies and a sucrose-loaded vesicle sedimentation assay to measure membrane binding. Our results suggest that oxidation of monomeric CLIC1, in the presence of membranes, promotes insertion into the bilayer more effectively than the oxidised CLIC1 dimer.

CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease.

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Jentsch, Thomas J; Pusch, Michael

2018-07-01

CLC anion transporters are found in all phyla and form a gene family of eight members in mammals. Two CLC proteins, each of which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory β-subunits for function. CLC proteins come in two flavors: anion channels and anion/proton exchangers. Structures of these two CLC protein classes are surprisingly similar. Extensive structure-function analysis identified residues involved in ion permeation, anion-proton coupling and gating and led to attractive biophysical models. In mammals, ClC-1, -2, -Ka/-Kb are plasma membrane Cl - channels, whereas ClC-3 through ClC-7 are 2Cl - /H + -exchangers in endolysosomal membranes. Biological roles of CLCs were mostly studied in mammals, but also in plants and model organisms like yeast and Caenorhabditis elegans. CLC Cl - channels have roles in the control of electrical excitability, extra- and intracellular ion homeostasis, and transepithelial transport, whereas anion/proton exchangers influence vesicular ion composition and impinge on endocytosis and lysosomal function. The surprisingly diverse roles of CLCs are highlighted by human and mouse disorders elicited by mutations in their genes. These pathologies include neurodegeneration, leukodystrophy, mental retardation, deafness, blindness, myotonia, hyperaldosteronism, renal salt loss, proteinuria, kidney stones, male infertility, and osteopetrosis. In this review, emphasis is laid on biophysical structure-function analysis and on the cell biological and organismal roles of mammalian CLCs and their role in disease.

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

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Tien, Jason; Peters, Christian J; Wong, Xiu Ming; Cheng, Tong; Jan, Yuh Nung; Jan, Lily Yeh; Yang, Huanghe

2014-01-01

TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sensors of this channel are still lacking. By aligning distantly related calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of all conserved acidic residues thought to be exposed to the cytoplasm, we identify four acidic amino acids as putative calcium-binding residues. Alterations of the charge, polarity, and size of amino acid side chains at these sites alter the ability of different divalent cations to activate the channel. Furthermore, TMEM16A mutant channels containing double cysteine substitutions at these residues are sensitive to the redox potential of the internal solution, providing evidence for their physical proximity and solvent accessibility. DOI: http://dx.doi.org/10.7554/eLife.02772.001 PMID:24980701

[Application of Brownian dynamics to the description of transmembrane ion flow as exemplified by the chloride channel of glycine receptor].

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Boronovskiĭ, S E; Nartsissov, Ia R

2009-01-01

Using the Brownian dynamics of the movement of hydrated ion in a viscous water solution, a mathematical model has been built, which describes the transport of charged particles through a single protein pore in a lipid membrane. The dependences of transmembrane ion currents on ion concentrations in solution have been obtained. It was shown that, if the geometry of a membrane pore is identical to that of the inner part of the glycine receptor channel and there is no ion selectivity, then the values of both chloride and sodium currents are not greater than 0.5 pA at the physiological concentrations of these ions. If local charge heterogeneity caused by charged amino acid residues of transmembrane protein segments is included into the model calculations, the chloride current increases to about 3.7 pA, which exceeds more than seven times the value for sodium ions under the conditions of the complex channel geometry in the range of physiological concentrations of ions in the solution. The model takes changes in the density of charge distribution both inside the channel and near the protein surface into account. The alteration of pore geometry can be also considered as a parameter at the researcher's option. Thus, the model appears as an effective tool for the description of transmembrane currents for other types of membrane channels.

A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series

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Rashid Ban Mousa

2013-01-01

Full Text Available Abstract Introduction Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case presentation Case 1 is the 12-year-old daughter (index patient of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1, whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG located in exon 15 (c.1225C>T of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T. Case 2 is the 16-year-old son (brother of the index patient of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride

A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series.

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Rashid, Ban Mousa; Rashid, Nawshirwan Gafoor; Schulz, Ansgar; Lahr, Georgia; Nore, Beston Faiek

2013-01-09

Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case 1 is the 12-year-old daughter (index patient) of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1), whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T).Case 2 is the 16-year-old son (brother of the index patient) of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride channel 7 gene in this patient (Case 2). The missense

Differential involvement of glutamate-gated chloride channel splice variants in the olfactory memory processes of the honeybee Apis mellifera.

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Démares, Fabien; Drouard, Florian; Massou, Isabelle; Crattelet, Cindy; Lœuillet, Aurore; Bettiol, Célia; Raymond, Valérie; Armengaud, Catherine

2014-09-01

Glutamate-gated chloride channels (GluCl) belong to the cys-loop ligand-gated ion channel superfamily and their expression had been described in several invertebrate nervous systems. In the honeybee, a unique gene amel_glucl encodes two alternatively spliced subunits, Amel_GluCl A and Amel_GluCl B. The expression and differential localization of those variants in the honeybee brain had been previously reported. Here we characterized the involvement of each variant in olfactory learning and memory processes, using specific small-interfering RNA (siRNA) targeting each variant. Firstly, the efficacy of the two siRNAs to decrease their targets' expression was tested, both at mRNA and protein levels. The two proteins showed a decrease of their respective expression 24h after injection. Secondly, each siRNA was injected into the brain to test whether or not it affected olfactory memory by using a classical paradigm of conditioning the proboscis extension reflex (PER). Amel_GluCl A was found to be involved only in retrieval of 1-nonanol, whereas Amel_GluCl B was involved in the PER response to 2-hexanol used as a conditioned stimulus or as new odorant. Here for the first time, a differential behavioral involvement of two highly similar GluCl subunits has been characterized in an invertebrate species. Copyright © 2014 Elsevier Inc. All rights reserved.

Cryo-EM structures of the TMEM16A calcium-activated chloride channel.

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Dang, Shangyu; Feng, Shengjie; Tien, Jason; Peters, Christian J; Bulkley, David; Lolicato, Marco; Zhao, Jianhua; Zuberbühler, Kathrin; Ye, Wenlei; Qi, Lijun; Chen, Tingxu; Craik, Charles S; Jan, Yuh Nung; Minor, Daniel L; Cheng, Yifan; Jan, Lily Yeh

2017-12-21

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. Here we present de novo atomic structures of the transmembrane domains of mouse TMEM16A in nanodiscs and in lauryl maltose neopentyl glycol as determined by single-particle electron cryo-microscopy. These structures reveal the ion permeation pore and represent different functional states. The structure in lauryl maltose neopentyl glycol has one Ca 2+ ion resolved within each monomer with a constricted pore; this is likely to correspond to a closed state, because a CaCC with a single Ca 2+ occupancy requires membrane depolarization in order to open (C.J.P. et al., manuscript submitted). The structure in nanodiscs has two Ca 2+ ions per monomer and its pore is in a closed conformation; this probably reflects channel rundown, which is the gradual loss of channel activity that follows prolonged CaCC activation in 1 mM Ca 2+ . Our mutagenesis and electrophysiological studies, prompted by analyses of the structures, identified ten residues distributed along the pore that interact with permeant anions and affect anion selectivity, as well as seven pore-lining residues that cluster near pore constrictions and regulate channel gating. Together, these results clarify the basis of CaCC anion conduction.

Dynamic [Cl-]i measurement with chloride sensing quantum dots nanosensor in epithelial cells

International Nuclear Information System (INIS)

Wang Yuchi; Mao Hua; Wong, Lid B

2010-01-01

We have synthesized a chloride sensing quantum dots (QD) nanosensor, Cl-QD, for the dynamic measurements of chloride ion concentration in the millimolar range, a sensitivity that is applicable to most physiological intracellular chloride ion concentration ([Cl - ] i ) measurements in epithelial cells. The Cl-QD is synthesized by conjugating an anion receptor, 1-(2-mercapto-ethyl)-3-phenyl-thiourea (MEPTU) to a water soluble CdSe/ZnS QD at an emission wavelength of 620 nm. Upon binding of chloride ions to the Cl-QD, a photo-induced electron transfer mechanism caused the fluorescence of the QD to quench. This resulted in an inversely proportional relationship between the chloride ion concentration and the fluorescence intensity of the Cl-QD. We have utilized this Cl-QD to measure [Cl - ] i in T84 and CF-PAC cultured cells, with either the C1C-2 or CFTR chloride channels being manipulated by pharmacological chloride channel activators and inhibitors. Activations of C1C-2 and CFTR chloride channels in T84 by the respective lubiprostone and genistein caused predictive increases in the fluorescence of the Cl-QD, i.e., a decrease of [Cl - ] i . Conversely, glibenclamide, a chloride channel inhibitor, applied to the CF-PAC cells caused a predictable decrease in the fluorescence of Cl-QD due to the increase of [Cl - ] i . These are the first data in using QD-based chloride ion sensors for dynamic measurements of intracellular chloride ion concentrations in epithelial cells.

Paramecium BBS genes are key to presence of channels in Cilia

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Valentine Megan

2012-09-01

Full Text Available Abstract Background Changes in genes coding for ciliary proteins contribute to complex human syndromes called ciliopathies, such as Bardet-Biedl Syndrome (BBS. We used the model organism Paramecium to focus on ciliary ion channels that affect the beat form and sensory function of motile cilia and evaluate the effects of perturbing BBS proteins on these channels. Methods We used immunoprecipitations and mass spectrometry to explore whether Paramecium proteins interact as in mammalian cells. We used RNA interference (RNAi and swimming behavior assays to examine the effects of BBS depletion on ciliary ion channels that control ciliary beating. Combining RNA interference and epitope tagging, we examined the effects of BBS depletion of BBS 7, 8 and 9 on the location of three channels and a chemoreceptor in cilia. Results We found 10 orthologs of 8 BBS genes in P. tetraurelia. BBS1, 2, 4, 5, 7, 8 and 9 co-immunoprecipitate. While RNAi reduction of BBS 7 and 9 gene products caused loss and shortening of cilia, RNAi for all BBS genes except BBS2 affected patterns of ciliary motility that are governed by ciliary ion channels. Swimming behavior assays pointed to loss of ciliary K+ channel function. Combining RNAi and epitope tagged ciliary proteins we demonstrated that a calcium activated K+ channel was no longer located in the cilia upon depletion of BBS 7, 8 or 9, consistent with the cells’ swimming behavior. The TRPP channel PKD2 was also lost from the cilia. In contrast, the ciliary voltage gated calcium channel was unaffected by BBS depletion, consistent with behavioral assays. The ciliary location of a chemoreceptor for folate was similarly unperturbed by the depletion of BBS 7, 8 or 9. Conclusions The co-immunoprecipitation of BBS 1,2,4,5,7,8, and 9 suggests a complex of BBS proteins. RNAi for BBS 7, 8 or 9 gene products causes the selective loss of K+ and PKD2 channels from the cilia while the critical voltage gated calcium channel and a

Unique contributions of an arginine side chain to ligand recognition in a glutamate-gated chloride channel

DEFF Research Database (Denmark)

Lynagh, Timothy; Komnatnyy, Vitaly V; Pless, Stephan A

2017-01-01

Glutamate recognition by neurotransmitter receptors often relies on arginine (Arg) residues in the binding site, leading to the assumption that charge-charge interactions underlie ligand recognition. However, assessing the precise chemical contribution of Arg side chains to protein function......-gated chloride channel from the nematode Haemonchus contortus. Our data unveil a surprisingly small contribution of charge at a conserved arginine side chain previously suggested to form a salt bridge with the ligand, glutamate. Instead, our data show that Arg contributes crucially to ligand sensitivity via...

Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?

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Sacchi, Oscar; Rossi, Maria Lisa; Canella, Rita; Fesce, Riccardo

2011-02-25

The permeability of the nicotinic channel (nAChR) at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC) I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh), were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV) resulted in a change of the synaptic potassium/sodium permeability ratio (P(K)/P(Na)) from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh), by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn)) and of the EPSC decay time constant. Reduction of [Cl(-)](o) to 18 mM resulted in a change of P(K)/P(Na) from 1.57 (control) to 2.26, associated with a reversible shift of E(ACh) by about -10 mV. Application of 200 nM αBgTx evoked P(K)/P(Na) and g(syn) modifications similar to those observed in reduced [Cl(-)](o). The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K)/P(Na) changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization), while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.

Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?

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Oscar Sacchi

Full Text Available The permeability of the nicotinic channel (nAChR at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh, were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV resulted in a change of the synaptic potassium/sodium permeability ratio (P(K/P(Na from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh, by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn and of the EPSC decay time constant. Reduction of [Cl(-](o to 18 mM resulted in a change of P(K/P(Na from 1.57 (control to 2.26, associated with a reversible shift of E(ACh by about -10 mV. Application of 200 nM αBgTx evoked P(K/P(Na and g(syn modifications similar to those observed in reduced [Cl(-](o. The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K/P(Na changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization, while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.

The Arabidopsis thylakoid chloride channel AtCLCe functions in chloride homeostasis and regulation of photosynthetic electron transport

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Andrei eHerdean

2016-02-01

Full Text Available Chloride ions can be translocated across cell membranes through Cl− channels or Cl−/H+ exchangers. The thylakoid-located member of the Cl− channel CLC family in Arabidopsis thaliana (AtCLCe was hypothesized to play a role in photosynthetic regulation based on the initial photosynthetic characterization of clce mutant lines. The reduced nitrate content of Arabidopsis clce mutants suggested a role in regulation of plant nitrate homeostasis. In this study, we aimed to further investigate the role of AtCLCe in the regulation of ion homeostasis and photosynthetic processes in the thylakoid membrane. We report that the size and composition of proton motive force were mildly altered in two independent Arabidopsis clce mutant lines. Most pronounced effects in the clce mutants were observed on the photosynthetic electron transport of dark-adapted plants, based on the altered shape and associated parameters of the polyphasic OJIP kinetics of chlorophyll a fluorescence induction. Other alterations were found in the kinetics of state transition and in the macro-organisation of photosystem II supercomplexes, as indicated by circular dichroism measurements. Pre-treatment with KCl but not with KNO3 restored the wild-type photosynthetic phenotype. Analyses by transmission electron microscopy revealed a bow-like arrangement of the thylakoid network and a large thylakoid-free stromal region in chloroplast sections from the dark-adapted clce plants. Based on these data, we propose that AtCLCe functions in Cl− homeostasis after transition from light to dark, which affects chloroplast ultrastructure and regulation of photosynthetic electron transport.

Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole-cell oscillations in smooth muscle cells

DEFF Research Database (Denmark)

Jacobsen, Jens Christian; Aalkjær, Christian; Nilsson, Holger

2007-01-01

approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes uniform opening of L-type calcium...... channels on the cell surface stimulating synchronized release of SR-calcium and inducing the shift from waves to whole-cell oscillations. The effect of the channel is therefore to couple the processes of the SR with those of the membrane. We hypothesize that the shift in oscillatory mode and the associated...

[Channels: a new way to revisit pathology].

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Fournier, Emmanuel

2014-02-01

Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties.

An evolutionarily conserved gene family encodes proton-selective ion channels.

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Tu, Yu-Hsiang; Cooper, Alexander J; Teng, Bochuan; Chang, Rui B; Artiga, Daniel J; Turner, Heather N; Mulhall, Eric M; Ye, Wenlei; Smith, Andrew D; Liman, Emily R

2018-03-02

Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3 , and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Mechanisms underlying KCNQ1channel cell volume sensitivity

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Hammami, Sofia

Cells are constantly exposed to changes in cell volume during cell metabolism, nutrient uptake, cell proliferation, cell migration and salt and water transport. In order to cope with these perturbations, potassium channels in line with chloride channels have been shown to be likely contributors...... to the process of cell volume adjustments. A great diversity of potassium channels being members of either the 6TM, 4 TM or 2 TM K+ channel gene family have been shown to be strictly regulated by small, fast changes in cell volume. However, the precise mechanism underlying the K+ channel sensitivity to cell...... volume alterations is not yet fully understood. The KCNQ1 channel belonging to the voltage gated KCNQ family is considered a precise sensor of volume changes. The goal of this thesis was to elucidate the mechanism that induces cell volume sensitivity. Until now, a number of investigators have implicitly...

Salmon lice (Lepeophtheirus salmonis) showing varying emamectin benzoate susceptibilities differ in neuronal acetylcholine receptor and GABA-gated chloride channel mRNA expression.

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Carmichael, Stephen N; Bron, James E; Taggart, John B; Ireland, Jacqueline H; Bekaert, Michaël; Burgess, Stewart Tg; Skuce, Philip J; Nisbet, Alasdair J; Gharbi, Karim; Sturm, Armin

2013-06-18

Caligid copepods, also called sea lice, are fish ectoparasites, some species of which cause significant problems in the mariculture of salmon, where the annual cost of infection is in excess of €300 million globally. At present, caligid control on farms is mainly achieved using medicinal treatments. However, the continued use of a restricted number of medicine actives potentially favours the development of drug resistance. Here, we report transcriptional changes in a laboratory strain of the caligid Lepeophtheirus salmonis (Krøyer, 1837) that is moderately (~7-fold) resistant to the avermectin compound emamectin benzoate (EMB), a component of the anti-salmon louse agent SLICE® (Merck Animal Health). Suppression subtractive hybridisation (SSH) was used to enrich transcripts differentially expressed between EMB-resistant (PT) and drug-susceptible (S) laboratory strains of L. salmonis. SSH libraries were subjected to 454 sequencing. Further L. salmonis transcript sequences were available as expressed sequence tags (EST) from GenBank. Contiguous sequences were generated from both SSH and EST sequences and annotated. Transcriptional responses in PT and S salmon lice were investigated using custom 15 K oligonucleotide microarrays designed using the above sequence resources. In the absence of EMB exposure, 359 targets differed in transcript abundance between the two strains, these genes being enriched for functions such as calcium ion binding, chitin metabolism and muscle structure. γ-aminobutyric acid (GABA)-gated chloride channel (GABA-Cl) and neuronal acetylcholine receptor (nAChR) subunits showed significantly lower transcript levels in PT lice compared to S lice. Using RT-qPCR, the decrease in mRNA levels was estimated at ~1.4-fold for GABA-Cl and ~2.8-fold for nAChR. Salmon lice from the PT strain showed few transcriptional responses following acute exposure (1 or 3 h) to 200 μg L-1 of EMB, a drug concentration tolerated by PT lice, but toxic for S lice

Participation of GABAA Chloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture

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Juan Francisco Rodríguez-Landa

2013-01-01

Full Text Available Human amniotic fluid and a mixture of eight fatty acids (FAT-M identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg% produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement of γ-aminobutyric acid-A (GABAA receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, three GABAA receptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg, GABAA benzodiazepine antagonist flumazenil (5 mg/kg, and noncompetitive GABAA chloride channel antagonist picrotoxin (1 mg/kg. The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. The GABAA antagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects through GABAA receptor chloride channels.

Ion channel gene expressions in infertile men: A case-control study

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Serkan Carkci

2017-12-01

Full Text Available Background: Infertility is described as not receiving pregnancy despite unprotected and regular sexual intercourse in a 1 yr period. It is detected by 15% of the couples. Male and female factor in the etiology may be detected in similar rates. Objective: The present study aims to investigate ion channel gene expression in semen samples of infertile male compared with fertile men. Materials and Methods: A total of 150 men who applied to the urology clinic due to infertility were divided into five equal groups: asthenozoospermia, oligozoospermia, oligoasthenoteratozoospermia, teratozoospermia, and normozoospermia (control. All paticipants were evaluated with Cation Channel Spermia (CatSper 1, 2, 3, 4, Proton Voltage Gated Ion Channel1 (Hv1, Potassium Channel Subfamily U1 (KCNU1, and transmembrane protein (TMEM16A gene expression in semen samples. Results: “CatSper1, 4, HV1, KCNU1, and TMEM16A gene expression were detected higher in the oligozoospermia group compared to the controls. CatSper1, 2, 3, 4, KCNU1, and TMEM16A gene expression in the asthenozoospermia group and CatSper1, 2, 3, 4, KCNU1, and TMEM16A gene expression in the teratozoospermia group were detected lower compared to the controls. CatSper1, 4, HV1, and TMEM16A gen expression were higher in the oligoasthenoteratozoospermia men than the controls while CatSper3 gen expression was detected as lower.” Conclusion: It was detected that these ion channels have an effect on sperm progressive motility and morphology. It may be considered that mutations in these ion channels may result in infertility

Subunit Stoichiometry of Human Muscle Chloride Channels

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Fahlke, Christoph; Knittle, Timothy; Gurnett, Christina A.; Campbell, Kevin P.; George, Alfred L.

1997-01-01

Voltage-gated Cl? channels belonging to the ClC family appear to function as homomultimers, but the number of subunits needed to form a functional channel is controversial. To determine subunit stoichiometry, we constructed dimeric human skeletal muscle Cl? channels in which one subunit was tagged by a mutation (D136G) that causes profound changes in voltage-dependent gating. Sucrose-density gradient centrifugation experiments indicate that both monomeric and dimeric hClC-1 channels in their ...

An L319F mutation in transmembrane region 3 (TM3) selectively reduces sensitivity to okaramine B of the Bombyx mori l-glutamate-gated chloride channel.

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Furutani, Shogo; Okuhara, Daiki; Hashimoto, Anju; Ihara, Makoto; Kai, Kenji; Hayashi, Hideo; Sattelle, David B; Matsuda, Kazuhiko

2017-10-01

Okaramines produced by Penicillium simplicissimum AK-40 activate l-glutamate-gated chloride channels (GluCls) and thus paralyze insects. However, the okaramine binding site on insect GluCls is poorly understood. Sequence alignment shows that the equivalent of residue Leucine319 of the okaramine B sensitive Bombyx mori (B. mori) GluCl is a phenylalanine in the okaramine B insensitive B. mori γ-aminobutyric acid-gated chloride channel of the same species. This residue is located in the third transmembrane (TM3) region, a location which in a nematode GluCl is close to the ivermectin binding site. The B. mori GluCl containing the L319F mutation retained its sensitivity to l-glutamate, but responses to ivermectin were reduced and those to okaramine B were completely blocked.

Expanded functional diversity of shaker K(+ channels in cnidarians is driven by gene expansion.

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Timothy Jegla

Full Text Available The genome of the cnidarian Nematostella vectensis (starlet sea anemone provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K(+ channel gene family: Shaker (Kv1, Shaw (Kv3 and Shal (Kv4. In order to better understand the physiological significance of these voltage-gated K(+ channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K(+ channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct "silent" or "regulatory" phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2 family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages.

Differential gene expression of cardiac ion channels in human dilated cardiomyopathy.

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Maria Micaela Molina-Navarro

Full Text Available BACKGROUND: Dilated cardiomyopathy (DCM is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function. METHODS AND RESULTS: Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT. The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples validated the gene expression of SCN2B (p < 0.0001, KCNJ5 (p < 0.05, KCNJ8 (p < 0.05, CLIC2 (p < 0.05, and CACNB2 (p < 0.05. Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work. CONCLUSION: This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches.

A remarkably stable TipE gene cluster: evolution of insect Para sodium channel auxiliary subunits

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Li Jia

2011-11-01

Full Text Available Abstract Background First identified in fruit flies with temperature-sensitive paralysis phenotypes, the Drosophila melanogaster TipE locus encodes four voltage-gated sodium (NaV channel auxiliary subunits. This cluster of TipE-like genes on chromosome 3L, and a fifth family member on chromosome 3R, are important for the optional expression and functionality of the Para NaV channel but appear quite distinct from auxiliary subunits in vertebrates. Here, we exploited available arthropod genomic resources to trace the origin of TipE-like genes by mapping their evolutionary histories and examining their genomic architectures. Results We identified a remarkably conserved synteny block of TipE-like orthologues with well-maintained local gene arrangements from 21 insect species. Homologues in the water flea, Daphnia pulex, suggest an ancestral pancrustacean repertoire of four TipE-like genes; a subsequent gene duplication may have generated functional redundancy allowing gene losses in the silk moth and mosquitoes. Intronic nesting of the insect TipE gene cluster probably occurred following the divergence from crustaceans, but in the flour beetle and silk moth genomes the clusters apparently escaped from nesting. Across Pancrustacea, TipE gene family members have experienced intronic nesting, escape from nesting, retrotransposition, translocation, and gene loss events while generally maintaining their local gene neighbourhoods. D. melanogaster TipE-like genes exhibit coordinated spatial and temporal regulation of expression distinct from their host gene but well-correlated with their regulatory target, the Para NaV channel, suggesting that functional constraints may preserve the TipE gene cluster. We identified homology between TipE-like NaV channel regulators and vertebrate Slo-beta auxiliary subunits of big-conductance calcium-activated potassium (BKCa channels, which suggests that ion channel regulatory partners have evolved distinct lineage

Chloride equilibrium potential in salamander cones

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Bryson Eric J

2004-12-01

Full Text Available Abstract Background GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca and then determined the reversal potential for the current component that was inhibited by the Cl- channel blocker, niflumic acid. With this method, ECl was found to average -46 mV. In a complementary approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by depolarization with elevated concentrations of K+. The membrane potentials produced by the various high K+ solutions were measured in separate current clamp experiments. Consistent with electrophysiological experiments, MEQ fluorescence measurements indicated that ECl was below -36 mV. Conclusions The results of this study indicate that ECl is close to the dark resting potential. This will minimize the impact of chloride-dependent presynaptic mechanisms in cone terminals involving GABAa receptors, glutamate transporters and ICl(Ca.

Digital gene expression analysis of Microsporum canis exposed to berberine chloride.

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Chen-Wen Xiao

Full Text Available Berberine, a natural isoquinoline alkaloid of many medicinal herbs, has an active function against a variety of microbial infections including Microsporum canis (M. canis. However, the underlying mechanisms are poorly understood. To study the effect of berberine chloride on M. canis infection, a Digital Gene Expression (DGE tag profiling was constructed and a transcriptome analysis of the M. canis cellular responses upon berberine treatment was performed. Illumina/Hisseq sequencing technique was used to generate the data of gene expression profile, and the following enrichment analysis of Gene Ontology (GO and Pathway function were conducted based on the data of transcriptome. The results of DGE showed that there were 8476945, 14256722, 7708575, 5669955, 6565513 and 9303468 tags respectively, which was obtained from M. canis incubated with berberine or control DMSO. 8,783 genes were totally mapped, and 1,890 genes have shown significant changes between the two groups. 1,030 genes were up-regulated and 860 genes were down-regulated (P<0.05 in berberine treated group compared to the control group. Besides, twenty-three GO terms were identified by Gene Ontology functional enrichment analysis, such as calcium-transporting ATPase activity, 2-oxoglutarate metabolic process, valine catabolic process, peroxisome and unfolded protein binding. Pathway significant enrichment analysis indicated 6 signaling pathways that are significant, including steroid biosynthesis, steroid hormone biosynthesis, Parkinson's disease, 2,4-Dichlorobenzoate degradation, and tropane, piperidine and Isoquinoline alkaloid biosynthesis. Among these, eleven selected genes were further verified by qRT-PCR. Our findings provide a comprehensive view on the gene expression profile of M. canis upon berberine treatment, and shed light on its complicated effects on M. canis.

A Lys-Trp cation-π interaction mediates the dimerization and function of the chloride intracellular channel protein 1 transmembrane domain.

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Peter, Bradley; Polyansky, Anton A; Fanucchi, Sylvia; Dirr, Heini W

2014-01-14

Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can exist either as a soluble monomer or in an integral membrane form. The oligomerization of the transmembrane domain (TMD) remains speculative despite it being implicated in pore formation. The extent to which electrostatic and van der Waals interactions drive folding and association of the dimorphic TMD is unknown and is complicated by the requirement of interactions favorable in both aqueous and membrane environments. Here we report a putative Lys37-Trp35 cation-π interaction and show that it stabilizes the dimeric form of the CLIC1 TMD in membranes. A synthetic 30-mer peptide comprising a K37M TMD mutant was examined in 2,2,2-trifluoroethanol, sodium dodecyl sulfate micelles, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes using far-ultraviolet (UV) circular dichroism, fluorescence, and UV absorbance spectroscopy. Our data suggest that Lys37 is not implicated in the folding, stability, or membrane insertion of the TMD peptide. However, removal of this residue impairs the formation of dimers and higher-order oligomers. This is accompanied by a 30-fold loss of chloride influx activity, suggesting that dimerization modulates the rate of chloride conductance. We propose that, within membranes, individual TMD helices associate via a Lys37-mediated cation-π interaction to form active dimers. The latter findings are also supported by results of modeling a putative TMD dimer conformation in which Lys37 and Trp35 form cation-π pairs at the dimer interface. Dimeric helix bundles may then associate to form fully active ion channels. Thus, within a membrane-like environment, aromatic interactions involving a polar lysine side chain provide a thermodynamic driving force for helix-helix association.

Molecular Cloning and Sequencing of Hemoglobin-Beta Gene of Channel Catfish, Ictalurus Punctatus Rafinesque

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: Hemoglobin-y gene of channel catfish , lctalurus punctatus, was cloned and sequenced . Total RNA from head kidneys was isolated, reverse transcribed and amplified . The sequence of the channel catfish hemoglobin-y gene consists of 600 nucleotides . Analysis of the nucleotide sequence reveals one o...

Emerging role of cystic fibrosis transmembrane conductance regulator- an epithelial chloride channel in gastrointestinal cancers

Institute of Scientific and Technical Information of China (English)

Yuning Hou; Xiaoqing Guan; Zhe Yang; Chunying Li

2016-01-01

Cystic fibrosis transmembrane conductance regulator(CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers.

Chloride regulates afferent arteriolar contraction in response to depolarization

DEFF Research Database (Denmark)

Hansen, P B; Jensen, B L; Skott, O

1998-01-01

-Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit...... afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel...... antagonist diltiazem (10(-6) mol/L) abolished K+-induced contractions. Bicarbonate did not modify the sensitivity to chloride. Norepinephrine (10(-6) mol/L) induced full contraction in depolarized vessels even in the absence of chloride. Iodide and nitrate were substituted for chloride with no inhibitory...

Functional modulation of cerebral gamma-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl beta-carboline-3-carboxylate: Presence of independent binding site for ethyl beta-carboline-3-carboxylate

Energy Technology Data Exchange (ETDEWEB)

Taguchi, J.; Kuriyama, K. (Kyoto Prefectural Univ. of Medicine (Japan))

1990-05-01

Effect of ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/chloride ion channel complex was studied. Beta-CCE noncompetitively and competitively inhibited (3H)flunitrazepam binding to benzodiazepine receptor, but not (3H)muscimol binding to GABAA receptor as well as t-(3H)butylbicycloorthobenzoate (( 3H) TBOB) binding to chloride ion channel, in particulate fraction of the mouse brain. Ro15-1788 also inhibited competitively (3H) flunitrazepam binding. On the other hand, the binding of beta-(3H)CCE was inhibited noncompetitively and competitively by clonazepam and competitively by Ro15-1788. In agreement with these results, benzodiazepines-stimulated (3H)muscimol binding was antagonized by beta-CCE and Ro15-1788. Gel column chromatography for the solubilized fraction from cerebral particulate fraction by 0.2% sodium deoxycholate (DOC-Na) in the presence of 1 M KCl indicated that beta-(3H)CCE binding site was eluted in the same fraction (molecular weight, 250,000) as the binding sites for (3H)flunitrazepam, (3H)muscimol and (3H)TBOB. GABA-stimulated 36Cl- influx into membrane vesicles prepared from the bovine cerebral cortex was stimulated and attenuated by flunitrazepam and beta-CCE, respectively. These effects of flunitrazepam and beta-CCE on the GABA-stimulated 36Cl- influx were antagonized by Ro15-1788. The present results suggest that the binding site for beta-CCE, which resides on GABAA receptor/benzodiazepine receptor/chloride ion channel complex, may be different from that for benzodiazepine. Possible roles of beta-CCE binding site in the allosteric inhibitions on benzodiazepine binding site as well as on the functional coupling between chloride ion channel and GABAA receptor are also suggested.

GmCLC1 Confers Enhanced Salt Tolerance through Regulating Chloride Accumulation in Soybean

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Peipei Wei

2016-07-01

Full Text Available The family of chloride channel proteins that mediate Cl- transportation play vital roles in plant nutrient supply, cellular action potential and turgor pressure adjustment, stomatal movement, hormone signal recognition and transduction, Cl- homeostasis, and abiotic and biotic stress tolerance. The anionic toxicity, mainly caused by chloride ions (Cl-, on plants under salt stress remains poorly understood. In this work, we investigated the function of soybean Cl-/H+ antiporter GmCLC1 under salt stress in transgenic Arabidopsis thaliana, soybean, and yeast. We found that GmCLC1 enhanced salt tolerance in transgenic A. thaliana by reducing the Cl- accumulation in shoots and hence released the negative impact of salt stress on plant growth. Overexpression of GmCLC1 in the hairy roots of soybean sequestered more Cl- in their roots and transferred less Cl- to their shoots, leading to lower relative electrolyte leakage values in the roots and leaves. When either the soybean GmCLC1 or the yeast chloride transporter gene, GEF1, was transformed into the yeast gef1 mutant, and then treated with different chloride salts (MnCl2, KCl, NaCl, enhanced survival rate was observed. The result indicates that GmCLC1 and GEF1 exerted similar effects on alleviating the stress of diverse chloride salts on the yeast gef1 mutant. Together, this work suggests a protective function of GmCLC1 under Cl- stress.

Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.

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Wei, Feng; Yan, Li-Min; Su, Tao; He, Na; Lin, Zhi-Jian; Wang, Jie; Shi, Yi-Wu; Yi, Yong-Hong; Liao, Wei-Ping

2017-08-01

Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

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Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis

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Blackman, Scott M.; Raraigh, Karen S.; Corvol, Harriet; Rommens, Johanna M.; Pace, Rhonda G.; Boelle, Pierre-Yves; McGready, John; Sosnay, Patrick R.; Strug, Lisa J.; Knowles, Michael R.; Cutting, Garry R.

2016-01-01

Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation. Objectives: To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. Methods: A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling. Measurements and Main Results: Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H2 = 0; 95% confidence interval, 0.0–0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%). Conclusions: Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker

Expression analysis of the CLCA gene family in mouse and human with emphasis on the nervous system

NARCIS (Netherlands)

M. Piirsoo (Marko); D. Meijer (Daniëlle); T. Timmusk (Tnis)

2009-01-01

textabstractBackground. Members of the calcium-activated chloride channel (CLCA) gene family have been suggested to possess a variety of functions including cell adhesion and tumor suppression. Expression of CLCA family members has mostly been analyzed in non-neural tissues. Here we describe the

Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

DEFF Research Database (Denmark)

Hoffmann, Else Kay; Sørensen, Belinda Halling; Sauter, Daniel Rafael Peter

2015-01-01

to be an essential component of both VRAC and VSOAC. Reduced VRAC and VSOAC activities are seen in drug resistant cancer cells. ANO1 is a calcium-activated chloride channel expressed on the plasma membrane of e.g. secretory epithelia. ANO1 is amplified and highly expressed in a large number of carcinomas. The gene...... functions as well as their role in cancer and drug resistance....

Myotonia congenita-associated mutations in chloride channel-1 affect zebrafish body wave swimming kinematics.

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Cheng, Wei; Tian, Jing; Burgunder, Jean-Marc; Hunziker, Walter; Eng, How-Lung

2014-01-01

Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1). Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in human patients suffering from myotonia congenita. We developed video analytic tools that are able to provide precise quantitative measurements of movement abnormalities in order to analyse the effect of these CLCN1 mutations on adult transgenic zebrafish swimming. Two new parameters for body-wave kinematics of swimming reveal changes in body curvature and tail offset in transgenic zebrafish expressing the disease-associated CLCN1 mutants, presumably due to their effect on muscle function. The capability of the developed video analytic tool to distinguish wild-type from transgenic zebrafish could provide a useful asset to screen for compounds that reverse the disease phenotype, and may be applicable to other movement disorders besides myotonia congenita.

Myotonia congenita-associated mutations in chloride channel-1 affect zebrafish body wave swimming kinematics.

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Wei Cheng

Full Text Available Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1. Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in human patients suffering from myotonia congenita. We developed video analytic tools that are able to provide precise quantitative measurements of movement abnormalities in order to analyse the effect of these CLCN1 mutations on adult transgenic zebrafish swimming. Two new parameters for body-wave kinematics of swimming reveal changes in body curvature and tail offset in transgenic zebrafish expressing the disease-associated CLCN1 mutants, presumably due to their effect on muscle function. The capability of the developed video analytic tool to distinguish wild-type from transgenic zebrafish could provide a useful asset to screen for compounds that reverse the disease phenotype, and may be applicable to other movement disorders besides myotonia congenita.

Support for calcium channel gene defects in autism spectrum disorders

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Lu Ake Tzu-Hui

2012-12-01

Full Text Available Abstract Background Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD. Calcium channel genes (CCG contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis. Methods A total of 2,176 single-nucleotide polymorphisms (SNP (703 genotyped and 1,473 imputed covering the genes that encode the α1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP. SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel. Results Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations. Conclusions These associations support a role for common CCG SNPs in ASD.

Topology of transmembrane channel-like gene 1 protein.

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Labay, Valentina; Weichert, Rachel M; Makishima, Tomoko; Griffith, Andrew J

2010-10-05

Mutations of transmembrane channel-like gene 1 (TMC1) cause hearing loss in humans and mice. TMC1 is the founding member of a family of genes encoding proteins of unknown function that are predicted to contain multiple transmembrane domains. The goal of our study was to define the topology of mouse TMC1 expressed heterologously in tissue culture cells. TMC1 was retained in the endoplasmic reticulum (ER) membrane of five tissue culture cell lines that we tested. We used anti-TMC1 and anti-HA antibodies to probe the topologic orientation of three native epitopes and seven HA epitope tags along full-length TMC1 after selective or complete permeabilization of transfected cells with digitonin or Triton X-100, respectively. TMC1 was present within the ER as an integral membrane protein containing six transmembrane domains and cytosolic N- and C-termini. There is a large cytoplasmic loop, between the fourth and fifth transmembrane domains, with two highly conserved hydrophobic regions that might associate with or penetrate, but do not span, the plasma membrane. Our study is the first to demonstrate that TMC1 is a transmembrane protein. The topologic organization revealed by this study shares some features with that of the shaker-TRP superfamily of ion channels.

Chloride is essential for contraction of afferent arterioles after agonists and potassium

DEFF Research Database (Denmark)

Jensen, B L; Ellekvist, Peter; Skøtt, O

1997-01-01

to norepinephrine, angiotensin II (ANG II), and potassium were measured after chloride depletion and compared with controls. Chloride depletion did not change arteriolar diameters, but the response to norepinephrine was markedly reduced when chloride was substituted with gluconate (n = 6) or isethionate (n = 6......). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular......A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses...

Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

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Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

2015-08-01

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

Chloride channel inhibition by a red wine extract and a synthetic small molecule prevents rotaviral secretory diarrhoea in neonatal mice

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Ko, Eun-A; Jin, Byung-Ju; Namkung, Wan; Ma, Tonghui; Thiagarajah, Jay R.; Verkman, A. S.

2014-01-01

Background Rotavirus is the most common cause of severe secretory diarrhoea in infants and young children globally. The rotaviral enterotoxin, NSP4, has been proposed to stimulate calcium-activated chloride channels (CaCC) on the apical plasma membrane of intestinal epithelial cells. We previously identified red wine and small molecule CaCC inhibitors. Objective To investigate the efficacy of a red wine extract and a synthetic small molecule, CaCCinh-A01, in inhibiting intestinal CaCCs and rotaviral diarrhoea. Design Inhibition of CaCC-dependent current was measured in T84 cells and mouse ileum. The effectiveness of an orally administered wine extract and CaCCinh-A01 in inhibiting diarrhoea in vivo was determined in a neonatal mouse model of rotaviral infection. Results Screening of ~150 red wines revealed a Cabernet Sauvignon that inhibited CaCC current in T84 cells with IC50 at a ~1:200 dilution, and higher concentrations producing 100% inhibition. A >1 kdalton wine extract prepared by dialysis, which retained full inhibition activity, blocked CaCC current in T84 cells and mouse intestine. In rotavirus-inoculated mice, oral administration of the wine extract prevented diarrhoea by inhibition of intestinal fluid secretion without affecting rotaviral infection. The wine extract did not inhibit the cystic fibrosis chloride channel (CFTR) in cell cultures, nor did it prevent watery stools in neonatal mice administered cholera toxin, which activates CFTR-dependent fluid secretion. CaCCinh-A01 also inhibited rotaviral diarrhoea. Conclusions Our results support a pathogenic role for enterocyte CaCCs in rotaviral diarrhoea and demonstrate the antidiarrhoeal action of CaCC inhibition by an alcohol-free, red wine extract and by a synthetic small molecule. PMID:24052273

Renin release from permeabilized juxtaglomerular cells is stimulated by chloride but not by low calcium

DEFF Research Database (Denmark)

Jensen, B L; Skøtt, O

1994-01-01

of chloride channels followed by a drop in the intracellular chloride concentration. The stimulation caused by the high calcium concentration may be a toxic effect or may be due to stimulation of the fusion between granules and cell membrane in a way analogous to other secretory cells....

Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression

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Krishna Samanta

2015-07-01

Full Text Available In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relatively simple topology, suggesting it fulfills a more fundamental role in cell biology than simply orchestrating compartmentalized responses. Here, we have compared the ability of store-operated Ca2+ release-activated Ca2+ (CRAC channels confined to PM microdomains with a similar number of dispersed CRAC channels to activate transcription factors, which subsequently increase nuclear gene expression. For similar levels of channel activity, we find that channel confinement is considerably more effective in stimulating gene expression. Our results identify a long-range signaling advantage to the tight evolutionary conservation of channel clustering and reveal that CRAC channel aggregation increases the strength, fidelity, and reliability of the general process of excitation-transcription coupling.

Structure of the CLC-1 chloride channel from Homo sapiens.

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Park, Eunyong; MacKinnon, Roderick

2018-05-29

CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.

Prompt and delayed Coulomb explosion of doubly ionized hydrogen chloride molecules in intense femtosecond laser fields

Science.gov (United States)

Ma, Junyang; Li, Hui; Lin, Kang; Song, Qiying; Ji, Qinying; Zhang, Wenbin; Li, Hanxiao; Sun, Fenghao; Qiang, Junjie; Lu, Peifen; Gong, Xiaochun; Zeng, Heping; Wu, Jian

2018-06-01

We experimentally investigate the dissociative double ionization of hydrogen chloride (HCl) molecules in intense femtosecond laser pulses. In addition to the prompt dissociation channels which occur on femtosecond timescales, long-lived hydrogen chloride dications which Coulomb-explode in flight towards the detector are clearly identified in the photoion-photoion coincidence spectrum. Different pathways leading to these prompt and delayed dissociation channels involving various bound and repulsive states of the HCl dication are discussed based on the observed kinetic energy release and momentum distributions. Our results indicate that the specific features of the HCl dication potential energy curves are responsible for the generation of the delayed fragmentation channels, which are expected to be general processes for the hydrogen halides.

Gene-expression changes in cerium chloride-induced injury of mouse hippocampus.

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Zhe Cheng

Full Text Available Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl(3 for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl(3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl(3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure.

Identification and functional expression of a glutamate- and avermectin-gated chloride channel from Caligus rogercresseyi, a southern Hemisphere sea louse affecting farmed fish.

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Isabel Cornejo

2014-09-01

Full Text Available Parasitic sea lice represent a major sanitary threat to marine salmonid aquaculture, an industry accounting for 7% of world fish production. Caligus rogercresseyi is the principal sea louse species infesting farmed salmon and trout in the southern hemisphere. Most effective control of Caligus has been obtained with macrocyclic lactones (MLs ivermectin and emamectin. These drugs target glutamate-gated chloride channels (GluCl and act as irreversible non-competitive agonists causing neuronal inhibition, paralysis and death of the parasite. Here we report the cloning of a full-length CrGluClα receptor from Caligus rogercresseyi. Expression in Xenopus oocytes and electrophysiological assays show that CrGluClα is activated by glutamate and mediates chloride currents blocked by the ligand-gated anion channel inhibitor picrotoxin. Both ivermectin and emamectin activate CrGluClα in the absence of glutamate. The effects are irreversible and occur with an EC(50 value of around 200 nM, being cooperative (n(H = 2 for ivermectin but not for emamectin. Using the three-dimensional structure of a GluClα from Caenorabditis elegans, the only available for any eukaryotic ligand-gated anion channel, we have constructed a homology model for CrGluClα. Docking and molecular dynamics calculations reveal the way in which ivermectin and emamectin interact with CrGluClα. Both drugs intercalate between transmembrane domains M1 and M3 of neighbouring subunits of a pentameric structure. The structure displays three H-bonds involved in this interaction, but despite similarity in structure only of two these are conserved from the C. elegans crystal binding site. Our data strongly suggest that CrGluClα is an important target for avermectins used in the treatment of sea louse infestation in farmed salmonids and open the way for ascertaining a possible mechanism of increasing resistance to MLs in aquaculture industry. Molecular modeling could help in the design of new

Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of electrical signaling in vertebrates

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Zhong Tao P

2007-07-01

Full Text Available Abstract Background Action potential generation in excitable cells such as myocytes and neurons critically depends on voltage-gated sodium channels. In mammals, sodium channels exist as macromolecular complexes that include a pore-forming alpha subunit and 1 or more modulatory beta subunits. Although alpha subunit genes have been cloned from diverse metazoans including flies, jellyfish, and humans, beta subunits have not previously been identified in any non-mammalian species. To gain further insight into the evolution of electrical signaling in vertebrates, we investigated beta subunit genes in the teleost Danio rerio (zebrafish. Results We identified and cloned single zebrafish gene homologs for beta1-beta3 (zbeta1-zbeta3 and duplicate genes for beta4 (zbeta4.1, zbeta4.2. Sodium channel beta subunit loci are similarly organized in fish and mammalian genomes. Unlike their mammalian counterparts, zbeta1 and zbeta2 subunit genes display extensive alternative splicing. Zebrafish beta subunit genes and their splice variants are differentially-expressed in excitable tissues, indicating tissue-specific regulation of zbeta1-4 expression and splicing. Co-expression of the genes encoding zbeta1 and the zebrafish sodium channel alpha subunit Nav1.5 in Chinese Hamster Ovary cells increased sodium current and altered channel gating, demonstrating functional interactions between zebrafish alpha and beta subunits. Analysis of the synteny and phylogeny of mammalian, teleost, amphibian, and avian beta subunit and related genes indicated that all extant vertebrate beta subunits are orthologous, that beta2/beta4 and beta1/beta3 share common ancestry, and that beta subunits are closely related to other proteins sharing the V-type immunoglobulin domain structure. Vertebrate sodium channel beta subunit genes were not identified in the genomes of invertebrate chordates and are unrelated to known subunits of the para sodium channel in Drosophila. Conclusion The

Adrenomedullin increased the short-circuit current in the pig oviduct through chloride channels via the CGRP receptor: mediation by cAMP and calcium ions but not by nitric oxide.

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Liao, S B; Cheung, K H; Cheung, M P L; To, Y T; O, W S; Tang, F

2013-10-01

The oviduct serves as a site for the fertilization of the ovum and the transport of the conceptus down to the uterus for implantation. In this study, we investigated the presence of adrenomedullin (ADM) and its receptor component proteins in the pig oviduct. The effect of ADM on oviductal secretion, the specific receptor, and the mechanisms involved were also investigated. The presence of ADM and its receptor component proteins in the pig oviduct were confirmed using immunostaining. Short-circuit current (I(sc)) technique was employed to study chloride ion secretion in the oviductal epithelium. ADM increased I(sc) through cAMP- and calcium-activated chloride channels, and this effect could be inhibited by the CGRP receptor antagonist, hCGRP8-37. In contrast, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME), could not block the effect of ADM on I(sc). In summary, ADM may increase oviductal fluid secretion via chloride secretion independent of the nitric oxide pathway for the transport of sperm and the conceptus.

Ion channels in glioblastoma.

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Molenaar, Remco J

2011-01-01

Glioblastoma is the most common primary brain tumor with the most dismal prognosis. It is characterized by extensive invasion, migration, and angiogenesis. Median survival is only 15 months due to this behavior, rendering focal surgical resection ineffective and adequate radiotherapy impossible. At this moment, several ion channels have been implicated in glioblastoma proliferation, migration, and invasion. This paper summarizes studies on potassium, sodium, chloride, and calcium channels of glioblastoma. It provides an up-to-date overview of the literature that could ultimately lead to new therapeutic targets.

Time-resolved energy transfer from single chloride-terminated nanocrystals to graphene

International Nuclear Information System (INIS)

Ajayi, O. A.; Wong, C. W.; Anderson, N. C.; Wolcott, A.; Owen, J. S.; Cotlet, M.; Petrone, N.; Hone, J.; Gu, T.; Gesuele, F.

2014-01-01

We examine the time-resolved resonance energy transfer of excitons from single n-butyl amine-bound, chloride-terminated nanocrystals to two-dimensional graphene through time-correlated single photon counting. The radiative biexponential lifetime kinetics and blinking statistics of the individual surface-modified nanocrystal elucidate the non-radiative decay channels. Blinking modification as well as a 4× reduction in spontaneous emission were observed with the short chloride and n-butylamine ligands, probing the energy transfer pathways for the development of graphene-nanocrystal nanophotonic devices

Time-resolved energy transfer from single chloride-terminated nanocrystals to graphene

Energy Technology Data Exchange (ETDEWEB)

Ajayi, O. A., E-mail: oaa2114@columbia.edu, E-mail: cww2104@columbia.edu; Wong, C. W., E-mail: oaa2114@columbia.edu, E-mail: cww2104@columbia.edu [Optical Nanostructures Laboratory, Center for Integrated Science and Engineering, Solid-State Science and Engineering, Columbia University, New York, New York 10027 (United States); Department of Mechanical Engineering, Columbia University, New York, New York 10027 (United States); Anderson, N. C.; Wolcott, A.; Owen, J. S. [Department of Chemistry, Columbia University, New York, New York 10027 (United States); Cotlet, M. [Brookhaven National Laboratory, Upton, New York, New York 11973 (United States); Petrone, N.; Hone, J. [Department of Mechanical Engineering, Columbia University, New York, New York 10027 (United States); Gu, T.; Gesuele, F. [Optical Nanostructures Laboratory, Center for Integrated Science and Engineering, Solid-State Science and Engineering, Columbia University, New York, New York 10027 (United States)

2014-04-28

We examine the time-resolved resonance energy transfer of excitons from single n-butyl amine-bound, chloride-terminated nanocrystals to two-dimensional graphene through time-correlated single photon counting. The radiative biexponential lifetime kinetics and blinking statistics of the individual surface-modified nanocrystal elucidate the non-radiative decay channels. Blinking modification as well as a 4× reduction in spontaneous emission were observed with the short chloride and n-butylamine ligands, probing the energy transfer pathways for the development of graphene-nanocrystal nanophotonic devices.

KCNN Genes that Encode Small-Conductance Ca2+-Activated K+ Channels Influence Alcohol and Drug Addiction.

Science.gov (United States)

Padula, Audrey E; Griffin, William C; Lopez, Marcelo F; Nimitvilai, Sudarat; Cannady, Reginald; McGuier, Natalie S; Chesler, Elissa J; Miles, Michael F; Williams, Robert W; Randall, Patrick K; Woodward, John J; Becker, Howard C; Mulholland, Patrick J

2015-07-01

Small-conductance Ca(2+)-activated K(+) (KCa2) channels control neuronal excitability and synaptic plasticity, and have been implicated in substance abuse. However, it is unknown if genes that encode KCa2 channels (KCNN1-3) influence alcohol and drug addiction. In the present study, an integrative functional genomics approach shows that genetic datasets for alcohol, nicotine, and illicit drugs contain the family of KCNN genes. Alcohol preference and dependence QTLs contain KCNN2 and KCNN3, and Kcnn3 transcript levels in the nucleus accumbens (NAc) of genetically diverse BXD strains of mice predicted voluntary alcohol consumption. Transcript levels of Kcnn3 in the NAc negatively correlated with alcohol intake levels in BXD strains, and alcohol dependence enhanced the strength of this association. Microinjections of the KCa2 channel inhibitor apamin into the NAc increased alcohol intake in control C57BL/6J mice, while spontaneous seizures developed in alcohol-dependent mice following apamin injection. Consistent with this finding, alcohol dependence enhanced the intrinsic excitability of medium spiny neurons in the NAc core and reduced the function and protein expression of KCa2 channels in the NAc. Altogether, these data implicate the family of KCNN genes in alcohol, nicotine, and drug addiction, and identify KCNN3 as a mediator of voluntary and excessive alcohol consumption. KCa2.3 channels represent a promising novel target in the pharmacogenetic treatment of alcohol and drug addiction.

Properties of Single K+ and Cl− Channels in Asclepias tuberosa Protoplasts 1

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Schauf, Charles L.; Wilson, Kathryn J.

1987-01-01

Potassium and chloride channels were characterized in Asclepias tuberosa suspension cell derived protoplasts by patch voltage-clamp. Whole-cell currents and single channels in excised patches had linear instantaneous current-voltage relations, reversing at the Nernst potentials for K+ and Cl−, respectively. Whole cell K+ currents activated exponentially during step depolarizations, while voltage-dependent Cl− channels were activated by hyperpolarizations. Single K+ channel conductance was 40 ± 5 pS with a mean open time of 4.5 milliseconds at 100 millivolts. Potassium channels were blocked by Cs+ and tetraethylammonium, but were insensitive to 4-aminopyridine. Chloride channels had a single-channel conductance of 100 ± 17 picosiemens, mean open time of 8.8 milliseconds, and were blocked by Zn2+ and ethacrynic acid. Whole-cell Cl− currents were inhibited by abscisic acid, and were unaffected by indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid. Since internal and external composition can be controlled, patch-clamped protoplasts are ideal systems for studying the role of ion channels in plant physiology and development. Images Fig. 5 PMID:16665712

Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking.

Science.gov (United States)

Stölting, Gabriel; Bungert-Plümke, Stefanie; Franzen, Arne; Fahlke, Christoph

2015-12-18

ClC-K chloride channels are crucial for auditory transduction and urine concentration. Mutations in CLCNKB, the gene encoding the renal chloride channel hClC-Kb, cause Bartter syndrome type III, a human genetic condition characterized by polyuria, hypokalemia, and alkalosis. In recent years, several Bartter syndrome-associated mutations have been described that result in truncations of the intracellular carboxyl terminus of hClC-Kb. We here used a combination of whole-cell patch clamp, confocal imaging, co-immunoprecipitation, and surface biotinylation to study the functional consequences of a frequent CLCNKB mutation that creates a premature stop codon at Trp-610. We found that W610X leaves the association of hClC-Kb and the accessory subunit barttin unaffected, but impairs its regulation by barttin. W610X attenuates hClC-Kb surface membrane insertion. Moreover, W610X results in hClC-Kb channel opening in the absence of barttin and prevents further barttin-mediated activation. To describe how the carboxyl terminus modifies the regulation by barttin we used V166E rClC-K1. V166E rClC-K1 is active without barttin and exhibits prominent, barttin-regulated voltage-dependent gating. Electrophysiological characterization of truncated V166E rClC-K1 demonstrated that the distal carboxyl terminus is necessary for slow cooperative gating. Since barttin modifies this particular gating process, channels lacking the distal carboxyl-terminal domain are no longer regulated by the accessory subunit. Our results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin. The loss-of-activation of truncated hClC-Kb channels in heterologous expression systems fully explains the reduced basolateral chloride conductance in affected kidneys and the clinical symptoms of Bartter syndrome patients. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking*

Science.gov (United States)

Stölting, Gabriel; Bungert-Plümke, Stefanie; Franzen, Arne; Fahlke, Christoph

2015-01-01

ClC-K chloride channels are crucial for auditory transduction and urine concentration. Mutations in CLCNKB, the gene encoding the renal chloride channel hClC-Kb, cause Bartter syndrome type III, a human genetic condition characterized by polyuria, hypokalemia, and alkalosis. In recent years, several Bartter syndrome-associated mutations have been described that result in truncations of the intracellular carboxyl terminus of hClC-Kb. We here used a combination of whole-cell patch clamp, confocal imaging, co-immunoprecipitation, and surface biotinylation to study the functional consequences of a frequent CLCNKB mutation that creates a premature stop codon at Trp-610. We found that W610X leaves the association of hClC-Kb and the accessory subunit barttin unaffected, but impairs its regulation by barttin. W610X attenuates hClC-Kb surface membrane insertion. Moreover, W610X results in hClC-Kb channel opening in the absence of barttin and prevents further barttin-mediated activation. To describe how the carboxyl terminus modifies the regulation by barttin we used V166E rClC-K1. V166E rClC-K1 is active without barttin and exhibits prominent, barttin-regulated voltage-dependent gating. Electrophysiological characterization of truncated V166E rClC-K1 demonstrated that the distal carboxyl terminus is necessary for slow cooperative gating. Since barttin modifies this particular gating process, channels lacking the distal carboxyl-terminal domain are no longer regulated by the accessory subunit. Our results demonstrate that the carboxyl terminus of hClC-Kb is not part of the binding site for barttin, but functionally modifies the interplay with barttin. The loss-of-activation of truncated hClC-Kb channels in heterologous expression systems fully explains the reduced basolateral chloride conductance in affected kidneys and the clinical symptoms of Bartter syndrome patients. PMID:26453302

Pharmacovigilance database search discloses ClC-K channels as a novel target of the AT1 receptor blockers valsartan and olmesartan.

Science.gov (United States)

Imbrici, Paola; Tricarico, Domenico; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio; Lograno, Marcello Diego; Conte, Diana; Liantonio, Antonella

2017-07-01

Human ClC-K chloride channels are highly attractive targets for drug discovery as they have a variety of important physiological functions and are associated with genetic disorders. These channels are crucial in the kidney as they control chloride reabsorption and water diuresis. In addition, loss-of-function mutations of CLCNKB and BSND genes cause Bartter's syndrome (BS), whereas CLCNKA and CLCNKB gain-of-function polymorphisms predispose to a rare form of salt sensitive hypertension. Both disorders lack a personalized therapy that is in most cases only symptomatic. The aim of this study was to identify novel ClC-K ligands from drugs already on the market, by exploiting the pharmacological side activity of drug molecules available from the FDA Adverse Effects Reporting System database. We searched for drugs having a Bartter-like syndrome as a reported side effect, with the assumption that BS could be causatively related to the block of ClC-K channels. The ability of the selected BS-causing drugs to bind and block ClC-K channels was then validated through an integrated experimental and computational approach based on patch clamp electrophysiology in HEK293 cells and molecular docking simulations. Valsartan and olmesartan were able to block ClC-Ka channels and the molecular requirements for effective inhibition of these channels have been identified. These results suggest additional mechanisms of action for these sartans further to their primary AT 1 receptor antagonism and propose these compounds as leads for designing new potent ClC-K ligands. © 2017 The British Pharmacological Society.

The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1.

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Bo Yang

Full Text Available Breaking the balance between proliferation and differentiation in animal cells can lead to cancer, but the mechanisms maintaining this balance remain largely undefined. The calcium activated chloride channel A1 (CLCA1 is a member of the calcium sensitive chloride conductance family of proteins and is expressed mainly in the colon, small intestine and appendix. We show that CLCA1 plays a functional role in differentiation and proliferation of Caco-2 cells and of intestinal tissue. Caco-2 cells spontaneously differentiate either in confluent culture or when treated with butyrate, a molecule present naturally in the diet. Here, we compared CLCA1 expressional levels between patients with and without colorectal cancer (CRC and determined the functional role of CLCA1 in differentiation and proliferation of Caco-2 cells. We showed that: 1 CLCA1 and CLCA4 expression were down-regulated significantly in CRC patients; 2 CLCA1 expression was up-regulated in Caco-2 cells induced to differentiate by confluent culture or by treatment with sodium butyrate (NaBT; 3 Knockdown of CLCA1 with siRNA significantly inhibited cell differentiation and promoted cell proliferation in Caco-2 confluent cultures, and 4 In Caco-2 3D culture, suppression of CLCA1 significantly increased cell proliferation and compromised NaBT-induced inhibition of proliferation. In conclusion, CLCA1 may contribute to promoting spontaneous differentiation and reducing proliferation of Caco-2 cells and may be a target of NaBT-induced inhibition of proliferation and therefore a potential diagnostic marker for CRC prognosis.

The Drosophila gene CheB42a is a novel modifier of Deg/ENaC channel function.

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Yehuda Ben-Shahar

2010-02-01

Full Text Available Degenerin/epithelial Na(+ channels (DEG/ENaC represent a diverse family of voltage-insensitive cation channels whose functions include Na(+ transport across epithelia, mechanosensation, nociception, salt sensing, modification of neurotransmission, and detecting the neurotransmitter FMRFamide. We previously showed that the Drosophila melanogaster Deg/ENaC gene lounge lizard (llz is co-transcribed in an operon-like locus with another gene of unknown function, CheB42a. Because operons often encode proteins in the same biochemical or physiological pathway, we hypothesized that CHEB42A and LLZ might function together. Consistent with this hypothesis, we found both genes expressed in cells previously implicated in sensory functions during male courtship. Furthermore, when coexpressed, LLZ coprecipitated with CHEB42A, suggesting that the two proteins form a complex. Although LLZ expressed either alone or with CHEB42A did not generate ion channel currents, CHEB42A increased current amplitude of another DEG/ENaC protein whose ligand (protons is known, acid-sensing ion channel 1a (ASIC1a. We also found that CHEB42A was cleaved to generate a secreted protein, suggesting that CHEB42A may play an important role in the extracellular space. These data suggest that CHEB42A is a modulatory subunit for sensory-related Deg/ENaC signaling. These results are consistent with operon-like transcription of CheB42a and llz and explain the similar contributions of these genes to courtship behavior.

CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.

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Tang, Tiantian; Lang, Xueting; Xu, Congfei; Wang, Xiaqiong; Gong, Tao; Yang, Yanqing; Cui, Jun; Bai, Li; Wang, Jun; Jiang, Wei; Zhou, Rongbin

2017-08-04

The NLRP3 inflammasome can sense different pathogens or danger signals, and has been reported to be involved in the development of many human diseases. Potassium efflux and mitochondrial damage are both reported to mediate NLRP3 inflammasome activation, but the underlying, orchestrating signaling events are still unclear. Here we show that chloride intracellular channels (CLIC) act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation. NLRP3 agonists induce potassium efflux, which causes mitochondrial damage and ROS production. Mitochondrial ROS then induces the translocation of CLICs to the plasma membrane for the induction of chloride efflux to promote NEK7-NLRP3 interaction, inflammasome assembly, caspase-1 activation, and IL-1β secretion. Thus, our results identify CLICs-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation.The NLRP3 inflammasome is key to the regulation of innate immunity against pathogens or stress, but the underlying signaling regulation is still unclear. Here the authors show that chloride intracellular channels (CLIC) interface between mitochondria stress and inflammasome activation to modulate inflammatory responses.

Ultrastructural Observation of the Skin Chloride Cells of Japanese Flounder Paralichthys olivaceus and Turbot Scophthamus maximus Larvae

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

The ultrastructures of skin chloride cells in cultured Japanese flounder and turbot larvae in metamorphosis, which grow in the same feeding conditions, are examined with a transmission electron microscope. These developed skin chloride cells were shaped like flattened ellipsoids and similar in morphology and ultrastructure to typical chloride cells of euryhaline fish gill. They locate in the epidermis and contract with the extra and interior environment through the apical pit and narrow channels. The cytoplasm of cell is full of numerous mitochondria and a ramifying network of tubules. The degeneration of skin chloride cells is observed with development of Japanese flounder larvae. Skin chloride cells of turbot are less developmental than those of Japanese flounder in the same developmental stage.

Electric organ discharge diversification in mormyrid weakly electric fish is associated with differential expression of voltage-gated ion channel genes.

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Nagel, Rebecca; Kirschbaum, Frank; Tiedemann, Ralph

2017-03-01

In mormyrid weakly electric fish, the electric organ discharge (EOD) is used for species recognition, orientation and prey localization. Produced in the muscle-derived adult electric organ, the EOD exhibits a wide diversity across species in both waveform and duration. While certain defining EOD characteristics can be linked to anatomical features of the electric organ, many factors underlying EOD differentiation are yet unknown. Here, we report the differential expression of 13 Kv1 voltage-gated potassium channel genes, two inwardly rectifying potassium channel genes, two previously studied sodium channel genes and an ATPase pump in two sympatric species of the genus Campylomormyrus in both the adult electric organ and skeletal muscle. Campylomormyrus compressirostris displays a basal EOD, largely unchanged during development, while C. tshokwe has an elongated, putatively derived discharge. We report an upregulation in all Kv1 genes in the electric organ of Campylomormyrus tshokwe when compared to both skeletal muscle and C. compressirostris electric organ. This pattern of upregulation in a species with a derived EOD form suggests that voltage-gated potassium channels are potentially involved in the diversification of the EOD signal among mormyrid weakly electric fish.

46 CFR 151.50-34 - Vinyl chloride (vinyl chloride monomer).

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Vinyl chloride (vinyl chloride monomer). 151.50-34... chloride (vinyl chloride monomer). (a) Copper, aluminum, magnesium, mercury, silver, and their alloys shall... equipment that may come in contact with vinyl chloride liquid or vapor. (b) Valves, flanges, and pipe...

Polyvinyl chloride resin

International Nuclear Information System (INIS)

Kim, Hong Jae

1976-06-01

This book contains polyvinyl chloride resin industry with present condition such as plastic industry and polyvinyl chloride in the world and Japan, manufacture of polyvinyl chloride resin ; suspension polymerization and solution polymerization, extruding, injection process, hollow molding vinyl record, vacuum forming, polymer powders process, vinyl chloride varnish, vinyl chloride latex, safety and construction on vinyl chloride. Each chapter has descriptions on of process and kinds of polyvinyl chloride resin.

Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

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Vandewauw Ine

2013-02-01

Full Text Available Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG in the head and from a string of dorsal root ganglia (DRG located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.

Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

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Sammeta V Raju

Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

Exposure of Daphnia magna to trichloroethylene (TCE) and vinyl chloride (VC): evaluation of gene transcription, cellular activity, and life-history parameters.

Science.gov (United States)

Houde, Magali; Douville, Mélanie; Gagnon, Pierre; Sproull, Jim; Cloutier, François

2015-06-01

Trichloroethylene (TCE) is a ubiquitous contaminant classified as a human carcinogen. Vinyl chloride (VC) is primarily used to manufacture polyvinyl chloride and can also be a degradation product of TCE. Very few data exist on the toxicity of TCE and VC in aquatic organisms particularly at environmentally relevant concentrations. The aim of this study was to evaluate the sub-lethal effects (10 day exposure; 0.1; 1; 10 µg/L) of TCE and VC in Daphnia magna at the gene, cellular, and life-history levels. Results indicated impacts of VC on the regulation of genes related to glutathione-S-transferase (GST), juvenile hormone esterase (JHE), and the vitelline outer layer membrane protein (VMO1). On the cellular level, exposure to 0.1, 1, and 10 µg/L of VC significantly increased the activity of JHE in D. magna and TCE increased the activity of chitinase (at 1 and 10 µg/L). Results for life-history parameters indicated a possible tendency of TCE to affect the number of molts at the individual level in D. magna (p=0.051). Measurement of VG-like proteins using the alkali-labile phosphates (ALP) assay did not show differences between TCE treated organisms and controls. However, semi-quantitative measurement using gradient gel electrophoresis (213-218 kDa) indicated significant decrease in VG-like protein levels following exposure to TCE at all three concentrations. Overall, results indicate effects of TCE and VC on genes and proteins related to metabolism, reproduction, and growth in D. magna. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Transmembrane helical interactions in the CFTR channel pore.

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Jhuma Das

2017-06-01

Full Text Available Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF. Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants. Several CFTR homology models have been developed using bacterial ABC transporters as templates but these have low sequence similarity to CFTR and are not ion channels. Here, we refine an earlier model in an outward (OWF and develop an inward (IWF facing model employing an integrated experimental-molecular dynamics simulation (200 ns approach. Our IWF structure agrees well with a recently solved cryo-EM structure of a CFTR IWF state. We utilize cysteine cross-linking to verify positions and orientations of residues within trans-membrane helices (TMHs of the OWF conformation and to reconstruct a physiologically relevant pore structure. Comparison of pore profiles of the two conformations reveal a radius sufficient to permit passage of hydrated Cl- ions in the OWF but not the IWF model. To identify structural determinants that distinguish the two conformations and possible rearrangements of TMHs within them responsible for channel gating, we perform cross-linking by bifunctional reagents of multiple predicted pairs of cysteines in TMH 6 and 12 and 6 and 9. To determine whether the effects of cross-linking on gating observed are the result of switching of the channel from open to close state, we also treat the same residue pairs with monofunctional reagents in separate experiments. Both types of reagents prevent ion currents indicating that pore blockage is primarily responsible.

5,5'-Dithio-bis(2-nitrobenzoic acid) modification of cysteine improves the crystal quality of human chloride intracellular channel protein 2

International Nuclear Information System (INIS)

Mi Wei; Li Lanfen; Su Xiaodong

2008-01-01

Structural studies of human chloride intracellular channel protein 2 (CLIC2) had been hampered by the problem of generating suitable crystals primarily due to the protein containing exposed cysteines. Several chemical reagents were used to react with the cysteines on CLIC2 in order to modify the redox state of the protein. We have obtained high quality crystals that diffracted to better than 2.5 A at a home X-ray source by treating the protein with 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB). After solving the crystal structure of CLIC2, we found that the DTNB had reacted with the Cys 114 , and made CLIC2 in a homogenous oxidized state. This study demonstrated that the DTNB modification drastically improved the crystallization of CLIC2, and it implied that this method may be useful for other proteins containing exposed cysteines in general

Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene Affecting Human Bone Formation

DEFF Research Database (Denmark)

Brum, A M; Leije, M; J, Schreuders-Koedam

2017-01-01

is diminished and more adipocytes are seen in the bone marrow, suggesting a shift in MSC lineage commitment. Identification of specific factors that stimulate osteoblast differentiation from human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this study was to identify novel genes...... an in vivo human bone formation model in which hMSCs lentivirally transduced with the CLIC3 overexpression construct were loaded onto a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD-SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression led to a 15...

Ion channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration.

Science.gov (United States)

Franklin, Brandon M; Voss, S Randal; Osborn, Jeffrey L

2017-08-01

Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K V 2.1, K V 2.2, L-type Ca V channels and H/K ATPases) or completely (GlyR, GABA A R, K V 1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in tail muscle and mesenchymal regions. Inhibition of anoctamin 1/2 also altered the post-amputation transcriptional response of p44/42 MAPK signaling pathway genes, including decreased expression of erk1/erk2. We also found that complete inhibition via voltage gated K + channel blockade was associated with diminished phagocyte recruitment to the amputation site. The identification of H + pumps as required for axolotl tail regeneration supports findings in Xenopus and Planaria models, and more generally, the conservation of ion channels as regulators of tissue regeneration. This study provides a preliminary framework for an in-depth investigation of the mechanistic role of ion channels and their potential involvement in regulating cellular proliferation and other processes essential to wound healing, appendage regeneration, and tissue repair. Copyright © 2017 Elsevier B.V. All rights reserved.

Mutations on M3 helix of Plutella xylostella glutamate-gated chloride channel confer unequal resistance to abamectin by two different mechanisms.

Science.gov (United States)

Wang, Xingliang; Puinean, Alin M; O Reilly, Andrias O; Williamson, Martin S; Smelt, Charles L C; Millar, Neil S; Wu, Yidong

2017-07-01

Abamectin is one of the most widely used avermectins for agricultural pests control, but the emergence of resistance around the world is proving a major threat to its sustained application. Abamectin acts by directly activating glutamate-gated chloride channels (GluCls) and modulating other Cys-loop ion channels. To date, three mutations occurring in the transmembrane domain of arthropod GluCls are associated with target-site resistance to abamectin: A309V in Plutella xylostella GluCl (PxGluCl), G323D in Tetranychus urticae GluCl1 (TuGluCl1) and G326E in TuGluCl3. To compare the effects of these mutations in a single system, A309V/I/G and G315E (corresponding to G323 in TuGluCl1 and G326 in TuGluCl3) substitutions were introduced individually into the PxGluCl channel. Functional analysis using Xenopus oocytes showed that the A309V and G315E mutations reduced the sensitivity to abamectin by 4.8- and 493-fold, respectively. In contrast, the substitutions A309I/G show no significant effects on the response to abamectin. Interestingly, the A309I substitution increased the channel sensitivity to glutamate by one order of magnitude (∼12-fold). Analysis of PxGluCl homology models indicates that the G315E mutation interferes with abamectin binding through a steric hindrance mechanism. In contrast, the structural consequences of the A309 mutations are not so clear and an allosteric modification of the binding site is the most likely mechanism. Overall the results show that both A309V and G315E mutations may contribute to target-site resistance to abamectin and may be important for the future prediction and monitoring of abamectin resistance in P. xylostella and other arthropod pests. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

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Linghan Jia

Full Text Available Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

Investigation of Endogenous Retrovirus Sequences in the Neighborhood of Genes Up-regulated in a Neuroblastoma Model after Treatment with Hypoxia-Mimetic Cobalt Chloride.

Science.gov (United States)

Brütting, Christine; Narasimhan, Harini; Hoffmann, Frank; Kornhuber, Malte E; Staege, Martin S; Emmer, Alexander

2018-01-01

Human endogenous retroviruses (ERVs) have been found to be associated with different diseases, e.g., multiple sclerosis (MS). Most human ERVs integrated in our genome are not competent to replicate and these sequences are presumably silent. However, transcription of human ERVs can be reactivated, e.g., by hypoxia. Interestingly, MS has been linked to hypoxia since decades. As some patterns of demyelination are similar to white matter ischemia, hypoxic damage is discussed. Therefore, we are interested in the association between hypoxia and ERVs. As a model, we used human SH-SY5Y neuroblastoma cells after treatment with the hypoxia-mimetic cobalt chloride and analyzed differences in the gene expression profiles in comparison to untreated cells. The vicinity of up-regulated genes was scanned for endogenous retrovirus-derived sequences. Five genes were found to be strongly up-regulated in SH-SY5Y cells after treatment with cobalt chloride: clusterin, glutathione peroxidase 3, insulin-like growth factor 2, solute carrier family 7 member 11, and neural precursor cell expressed developmentally down-regulated protein 9. In the vicinity of these genes we identified large (>1,000 bp) open reading frames (ORFs). Most of these ORFs showed only low similarities to proteins from retro-transcribing viruses. However, we found very high similarity between retrovirus envelope sequences and a sequence in the vicinity of neural precursor cell expressed developmentally down-regulated protein 9. This sequence encodes the human endogenous retrovirus group FRD member 1, the encoded protein product is called syncytin 2. Transfection of syncytin 2 into the well-characterized Ewing sarcoma cell line A673 was not able to modulate the low immunostimulatory activity of this cell line. Future research is needed to determine whether the identified genes and the human endogenous retrovirus group FRD member 1 might play a role in the etiology of MS.

Point mutations in the transmembrane region of the clic1 ion channel selectively modify its biophysical properties.

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Stefania Averaimo

Full Text Available Chloride intracellular Channel 1 (CLIC1 is a metamorphic protein that changes from a soluble cytoplasmic protein into a transmembrane protein. Once inserted into membranes, CLIC1 multimerises and is able to form chloride selective ion channels. Whilst CLIC1 behaves as an ion channel both in cells and in artificial lipid bilayers, its structure in the soluble form has led to some uncertainty as to whether it really is an ion channel protein. CLIC1 has a single putative transmembrane region that contains only two charged residues: arginine 29 (Arg29 and lysine 37 (Lys37. As charged residues are likely to have a key role in ion channel function, we hypothesized that mutating them to neutral alanine to generate K37A and R29A CLIC1 would alter the electrophysiological characteristics of CLIC1. By using three different electrophysiological approaches: i single channel Tip-Dip in artificial bilayers using soluble recombinant CLIC1, ii cell-attached and iii whole-cell patch clamp recordings in transiently transfected HEK cells, we determined that the K37A mutation altered the single-channel conductance while the R29A mutation affected the single-channel open probability in response to variation in membrane potential. Our results show that mutation of the two charged amino acids (K37 and R29 in the putative transmembrane region of CLIC1 alters the biophysical properties of the ion channel in both artificial bilayers and cells. Hence these charged residues are directly involved in regulating its ion channel activity. This strongly suggests that, despite its unusual structure, CLIC1 itself is able to form a chloride ion channel.

Subdued, a TMEM16 family Ca²⁺-activated Cl⁻channel in Drosophila melanogaster with an unexpected role in host defense.

Science.gov (United States)

Wong, Xiu Ming; Younger, Susan; Peters, Christian J; Jan, Yuh Nung; Jan, Lily Y

2013-11-05

TMEM16A and TMEM16B are calcium-activated chloride channels (CaCCs) with important functions in mammalian physiology. Whether distant relatives of the vertebrate TMEM16 families also form CaCCs is an intriguing open question. Here we report that a TMEM16 family member from Drosophila melanogaster, Subdued (CG16718), is a CaCC. Amino acid substitutions of Subdued alter the ion selectivity and kinetic properties of the CaCC channels heterologously expressed in HEK 293T cells. This Drosophila channel displays characteristics of classic CaCCs, thereby providing evidence for evolutionarily conserved biophysical properties in the TMEM16 family. Additionally, we show that knockout flies lacking subdued gene activity more readily succumb to death caused by ingesting the pathogenic bacteria Serratia marcescens, suggesting that subdued has novel functions in Drosophila host defense. DOI: http://dx.doi.org/10.7554/eLife.00862.001.

Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

DEFF Research Database (Denmark)

Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

2018-01-01

- with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

Cobalt chloride administration in athletes: a new perspective in blood doping?

Science.gov (United States)

Lippi, G; Franchini, M; Guidi, G C

2005-11-01

Blood doping is an illegal and unfair way of enhancing athletic performance by increasing the oxygen carrying capacity of the blood. Currently used methods usually involve stimulation of erythropoiesis. Gene therapy targeting the hypoxia inducible factor pathway may be an attractive alternative to traditional blood doping techniques. Hypoxia activates a large number of genes with essential roles in cell and tissue adaptation to low oxygen. Cobalt chloride is a well established chemical inducer of hypoxia-like responses such as erythropoiesis. Cobalt supplementation is not banned and therefore would not be detected by current anti-doping testing. Although there is as yet no direct or anecdotal evidence of cobalt chloride administration to athletes, its use should be warned against as being not only unfair but potentially dangerous.

Cerium(terbium, erbium)chloride-choline chloride aqueous systems

International Nuclear Information System (INIS)

Gajfutdinova, R.K.; Zhuravlev, E.F.; Bikbaeva, G.G.; Domrachev, V.N.; Vanskova, G.I.

1985-01-01

To clarify the effect of rare earth nature on mutual solubility of rare earth salts and amines the solubility of solid phases in the systems, consisting of choline chloride, water and cerium, terbium, erbium chlorides, has been studied. It is established, that solubility isotherms of all the systems, testify to the formation of new solid phases of the composition: Ce(Tb, Er)xCl 3 x2C 5 H 14 ONClx3H 2 O. Individuality of new solid phases is proved by DTA method, the composition is confirmed by chemical analysis and data of PMR spectra, for choline chloride and its complexes with rare earth chlorides of the given composition PMR and IR spectra are studied

[3H]PN200-110 and [3H]ryanodine binding and reconstitution of ion channel activity with skeletal muscle membranes

International Nuclear Information System (INIS)

Hamilton, S.L.; Alvarez, R.M.; Fill, M.; Hawkes, M.J.; Brush, K.L.; Schilling, W.P.; Stefani, E.

1989-01-01

Skeletal muscle membranes derived either from the tubular (T) network or from the sarcoplasmic reticulum (SR) were characterized with respect to the binding of the dihydropyridine, [ 3 H]PN200-110, and the alkaloid, [ 3 H]ryanodine; polypeptide composition; and ion channel activity. Conditions for optimizing the binding of these radioligands are discussed. A bilayer pulsing technique is described and is used to examine the channels present in these membranes. Fusion of T-tubule membranes into bilayers revealed the presence of chloride channels and dihydropyridine-sensitive calcium channels with three distinct conductances. The dihydropyridine-sensitive channels were further characterized with respect to their voltage dependence. Pulsing experiments indicated that two different populations of dihydropyridine-sensitive channels existed. Fusion of heavy SR vesicles revealed three different ion channels; the putative calcium release channel, a potassium channel, and a chloride channel. Thus, this fractionation procedure provides T-tubules and SR membranes which, with radioligand binding and single channel recording techniques, provide a useful tool to study the characteristics of skeletal muscle ion channels and their possible role in excitation-contraction coupling

Characterization of the chicken inward rectifier K+ channel IRK1/Kir2.1 gene

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Locke Emily

2004-11-01

Full Text Available Abstract Background Inward rectifier potassium channels (IRK contribute to the normal function of skeletal and cardiac muscle cells. The chick inward rectifier K+ channel cIRK1/Kir2.1 is expressed in skeletal muscle, heart, brain, but not in liver; a distribution similar but not identical to that of mouse Kir2.1. We set out to explore regulatory domains of the cIRK1 promoter that enhance or inhibit expression of the gene in different cell types. Results We cloned and characterized the 5'-flanking region of cIRK1. cIRK1 contains two exons with splice sites in the 5'-untranslated region, a structure similar to mouse and human orthologs. cIRK1 has multiple transcription initiation sites, a feature also seen in mouse. However, while the chicken and mouse promoter regions share many regulatory motifs, cIRK1 possesses a GC-richer promoter and a putative TATA box, which appears to positively regulate gene expression. We report here the identification of several candidate cell/tissue specific cIRK1 regulatory domains by comparing promoter activities in expressing (Qm7 and non-expressing (DF1 cells using in vitro transcription assays. Conclusion While multiple transcription initiation sites and the combinatorial function of several domains in activating cIRK1 expression are similar to those seen in mKir2.1, the cIRK1 promoter differs by the presence of a putative TATA box. In addition, several domains that regulate the gene's expression differentially in muscle (Qm7 and fibroblast cells (DF1 were identified. These results provide fundamental data to analyze cIRK1 transcriptional mechanisms. The control elements identified here may provide clues to the tissue-specific expression of this K+ channel.

Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

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Ovcaric Mick

2005-09-01

Full Text Available Abstract Background Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. Methods The present association study tested whether length variations in the second (more 3' polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO. In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. Results Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090. Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05. The prevalence of the long CAG repeat (>19 repeats did not reach statistical significance in migraineurs (P = 0.15, nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively, or between MA vs MO (P = 0.40. Conclusion This association study provides no evidence that length variations of the second polyglutamine array in

Barium chloride induces redox status unbalance, upregulates cytokine genes expression and confers hepatotoxicity in rats-alleviation by pomegranate peel.

Science.gov (United States)

Elwej, Awatef; Grojja, Yousri; Ghorbel, Imen; Boudawara, Ons; Jarraya, Raoudha; Boudawara, Tahia; Zeghal, Najiba

2016-04-01

The present study was performed to establish the therapeutic efficacy of pomegranate peel against barium chloride induced liver injury. Adult rats were divided into four groups of six animals each: group I, serving as controls, received distilled water; group II received by their drinking water 67 ppm of BaCl2; group III received both 67 ppm of BaCl2 by the same way than group II and 5 % of pomegranate peel (PP) via diet; group IV received 5 % of PP. Analysis by HPLC/MS of PP showed its rich composition in flavonoids such as gallic acid, castalin, hyperin, quercitrin, syringic acid, and quercetin. The protective effects of pomegranate peel against hepatotoxicity induced by barium chloride were assessed using biochemical parameters and histological studies. Exposure of rats to barium caused oxidative stress in the liver as evidenced by an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOHs), H2O2 and advanced oxidation protein product (AOPP) levels, and lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities, a decrease in catalase (CAT) and glutathione peroxidase (GPx) activities, glutathion (GSH), non-protein thiol (NPSH), vitamin C levels, and Mn-SOD gene expression. Liver total MT levels, MT-1, and MT-2 and pro-inflammatory cytokine genes expression like TNF-α, IL-1β and IL-6 were increased. Pomegranate peel, supplemented in the diet of barium-treated rats, showed an improvement of all the parameters indicated above.The present work provided ethnopharmacological relevance of pomegranate peel against the toxic effects of barium, suggesting its beneficial role as a potential antioxidant.

Sequence Alterations of I(Ks Potassium Channel Genes in Kazakhstani Patients with Atrial Fibrillation

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Ainur Akilzhanova

2014-12-01

Full Text Available Introduction. Atrial fibrillation (AF is the most common sustained arrhythmia, and it results in significant morbidity and mortality. However, the pathogenesis of AF remains unclear to date. Recently, more pieces of evidence indicated that AF is a multifactorial disease resulting from the interaction between environmental factors and genetics. Recent studies suggest that genetic mutation of the slow delayed rectifier potassium channel (I(Ks may underlie AF.Objective. To investigate sequence alterations of I(Ks potassium channel genes KCNQ1, KCNE1 and KCNE2 in Kazakhstani patients with atrial fibrillation.Methods. Genomic DNA of 69 cases with atrial fibrillation and 27 relatives were analyzed for mutations in all protein-coding exons and their flanking splice site regions of the genes KCNQ1 (NM_000218.2 and NM_181798.1, KCNE1 (NM_000219.2, and KCNE2 (NM_172201.1 using bidirectional sequencing on the ABI 3730xL DNA Analyzer (Applied Biosystems, Foster City, CA, USA.Results. In total, a disease-causing mutation was identified in 39 of the 69 (56.5% index cases. Of these, altered sequence variants in the KCNQ1 gene accounted for 14.5% of the mutations, whereas a KCNE1 mutation accounted for 43.5% of the mutations and KCNE2 mutation accounted for 1.4% of the mutations. The majority of the distinct mutations were found in a single case (80%, whereas 20% of the mutations were observed more than once. We found two sequence variants in KCNQ1 exon 13 (S546S G1638A and exon 16 (Y662Y, C1986T in ten patients (14.5%. In KCNE1 gene in exon 3 mutation, S59G A280G was observed in 30 of 69 patients (43.5% and KCNE2 exon 2 T10K C29A in 1 patient (1.4%. Genetic cascade screening of 27 relatives to the 69 index cases with an identified mutation revealed 26.9% mutation carriers  who were at risk of cardiac events such as syncope or sudden unexpected death.Conclusion. In this cohort of Kazakhstani index cases with AF, a disease-causing mutation was identified in

Effects of transgenic sterilization constructs and their repressor compounds on hatch, developmental rate and early survival of electroporated channel catfish embryos and fry.

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Su, Baofeng; Shang, Mei; Li, Chao; Perera, Dayan A; Pinkert, Carl A; Irwin, Michael H; Peatman, Eric; Grewe, Peter; Patil, Jawahar G; Dunham, Rex A

2015-04-01

Channel catfish (Ictalurus punctatus) embryos were electroporated with sterilization constructs targeting primordial germ cell proteins or with buffer. Some embryos then were treated with repressor compounds, cadmium chloride, copper sulfate, sodium chloride or doxycycline, to prevent expression of the transgene constructs. Promoters included channel catfish nanos and vasa, salmon transferrin (TF), modified yeast Saccharomyces cerevisiae copper transport protein (MCTR) and zebrafish racemase (RM). Knock-down systems were the Tet-off (nanos and vasa constructs), MCTR, RM and TF systems. Knock-down genes included shRNAi targeting 5' nanos (N1), 3' nanos (N2) or dead end (DND), or double-stranded nanos RNA (dsRNA) for overexpression of nanos mRNA. These constructs previously were demonstrated to knock down nanos, vasa and dead end, with the repressors having variable success. Exogenous DNA affected percentage hatch (% hatch), as all 14 constructs, except for the TF dsRNA, TF N1 (T), RM DND (C), vasa DND (C), vasa N1 (C) and vasa N2 (C), had lower % hatch than the control electroporated with buffer. The MCTR and RM DND (T) constructs resulted in delayed hatch, and the vasa and nanos constructs had minimal effects on time of hatch (P nanos constructs, doxycycline greatly delayed hatch (P < 0.05). Adverse effects of the transgenes and repressors continued for several treatments for the first 6 days after hatch, but only in a few treatments during the next 10 days. Repressors and gene expression impacted the yield of putative transgenic channel catfish fry, and need to be considered and accounted for in the hatchery phase of producing transgenically sterilized catfish fry and their fertile counterparts. This fry output should be considered to ensure that sufficient numbers of transgenic fish are produced for future applications and for defining repressor systems that are the most successful.

Loss of functional K+ channels encoded by ether-à-go-go-related genes in mouse myometrium prior to labour onset

Science.gov (United States)

Greenwood, I A; Yeung, S Y; Tribe, R M; Ohya, S

2009-01-01

There is a growing appreciation that ion channels encoded by the ether-à-go-go-related gene family have a functional impact in smooth muscle in addition to their accepted role in cardiac myocytes and neurones. This study aimed to assess the expression of ERG1–3 (KCNH1–3) genes in the murine myometrium (smooth muscle layer of the uterus) and determine the functional impact of the ion channels encoded by these genes in pregnant and non-pregnant animals. Quantitative RT-PCR did not detect message for ERG2 and 3 in whole myometrial tissue extracts. In contrast, message for two isoforms of mERG1 were readily detected with mERG1a more abundant than mERG1b. In isometric tension studies of non-pregnant myometrium, the ERG channel blockers dofetilide (1 μm), E4031 (1 μm) and Be-KM1 (100 nm) increased spontaneous contractility and ERG activators (PD118057 and NS1643) inhibited spontaneous contractility. In contrast, neither ERG blockade nor activation had any effect on the inherent contractility in myometrium from late pregnant (19 days gestation) animals. Moreover, dofetilide-sensitive K+ currents with distinctive ‘hooked’ kinetics were considerably smaller in uterine myocytes from late pregnant compared to non-pregnant animals. Expression of mERG1 isoforms did not alter throughout gestation or upon delivery, but the expression of genes encoding auxillary subunits (KCNE) were up-regulated considerably. This study provides the first evidence for a regulation of ERG-encoded K+ channels as a precursor to late pregnancy physiological activity. PMID:19332483

Severe manifestation of Bartter syndrome Type IV caused by a novel insertion mutation in the BSND gene.

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de Pablos, Augusto Luque; García-Nieto, Victor; López-Menchero, Jesús C; Ramos-Trujillo, Elena; González-Acosta, Hilaria; Claverie-Martín, Félix

2014-05-01

Bartter syndrome Type IV is a rare subtype of the Bartter syndromes that leads to both severe renal salt wasting and sensorineural deafness. This autosomal recessive disease is caused by mutations in the gene encoding barttin, BSND, an essential subunit of the ClC-K chloride channels expressed in renal and inner ear epithelia. Patients differ in the severity of renal symptoms, which appears to depend on the modification of channel function by the mutant barttin. To date, only a few BSND mutations have been reported, most of which are missense or nonsense mutations. In this study, we report the identification of the first insertion mutation, p.W102Vfs*7, in the BSND gene of a newborn girl with acute clinical symptoms including early-onset chronic renal failure. The results support previous data indicating that mutations that are predicted to abolish barttin expression are associated with a severe phenotype and early onset renal failure.

Chloride ingress prediction

DEFF Research Database (Denmark)

Frederiksen, Jens Mejer; Geiker, Mette Rica

2008-01-01

Prediction of chloride ingress into concrete is an important part of durability design of reinforced concrete structures exposed to chloride containing environment. This paper presents experimentally based design parameters for Portland cement concretes with and without silica fume and fly ash...... in marine atmospheric and submersed South Scandinavian environment. The design parameters are based on sequential measurements of 86 chloride profiles taken over ten years from 13 different types of concrete. The design parameters provide the input for an analytical model for chloride profiles as function...... of depth and time, when both the surface chloride concentration and the diffusion coefficient are allowed to vary in time. The model is presented in a companion paper....

EBIO, an agent causing maintained epithelial chloride secretion by co-ordinate actions at both apical and basolateral membranes.

Science.gov (United States)

MacVinish, L J; Keogh, J; Cuthbert, A W

2001-01-01

The effect of 1-ethyl-2-benzimidazolone (EBIO) on electrogenic chloride secretion in murine colonic and nasal epithelium was investigated by the short-circuit technique. In the colon, EBIO produces a sustained current increase in the presence of amiloride, which is sensitive to furosemide. In nasal epithelium EBIO causes only a small, transient current increase. Sustained increases in current were obtained in response to forskolin in both epithelia. To examine the mechanisms by which EBIO increases chloride secretion, the effects on intracellular mediators were measured in colonic crypts. There was no effect on [Ca(2+)]i but cAMP content was increased, more so in the presence of IBMX, indicating a direct effect on adenylate cyclase. In colonic epithelia in which the apical surface was permeabilized by nystatin, and the tissue subjected to an apical to basolateral K(+) gradient, EBIO caused a current increase that was entirely sensitive to charybdotoxin (ChTX). In similarly permeabilized colons Br-cAMP caused a current increase that was entirely sensitive to 293B. Thus EBIO increases chloride secretion in the colon by coordinated actions at both the apical and basolateral faces of the cells. These include direct and indirect actions on Ca(2+)-sensitive and cAMP-sensitive K(+) channels respectively, and indirect actions on the basolateral cotransporter and apical CFTR chloride channels via cAMP. In CF colonic epithelia EBIO did not evoke chloride secretion. It is not clear why the nasal epithelium responds poorly to EBIO whereas it gives a sustained response to the related compound chlorzoxazone.

Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

International Nuclear Information System (INIS)

Wang, Hailong; Cheng, Xiaolin

2011-01-01

The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential of mean force (PMF) profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel is open for a sodium ion to transport, but presents a ∼10 kcal/mol free energy barrier for a chloride ion, which arises primarily from the unfavorable interactions with a ring of negatively charged glutamate residues (E-2) at the intracellular end and a ring of hydrophobic residues (I9) in the middle of the transmembrane domain. Our collective findings further suggest that the charge selection mechanism can, to a large extent, be attributed to the narrow intracellular end and a ring of glutamate residues in this position their strong negative electrostatics and ability to bind cations. By contrast, E19 at the extracellular entrance only plays a minor role in ion selectivity of GLIC. In addition to electrostatics, both ion hydration and protein dynamics are found to be crucial for ion conduction as well, which explains why a chloride ion experiences a much greater barrier than a sodium ion in the hydrophobic region of the pore.

Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression

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Mats Wiedemann

2015-10-01

Full Text Available The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight. In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h, the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

Cell swelling activates separate taurine and chloride channels in Ehrlich mouse ascites tumor cells

DEFF Research Database (Denmark)

Lambert, Ian Henry; Hoffmann, Else Kay

1994-01-01

The taurine efflux from Ehrlich ascites tumor cells is stimulated by hypotonic cell swelling. The swelling-activated taurine efflux is unaffected by substitution of gluconate for extracellular Cl– but inhibited by addition of MK196 (anion channel blocker) and 4,4 -diisothiocyanostilbene-2......,2 -disulfonic acid (DIDS; anion channel and anion exchange blocker) and by depolarization of the cell membrane. This is taken to indicate that taurine does not leave the osmotically swollen Ehrlich cells in exchange for extracellular Cl–, i.e., via the anion exchanger but via a MK196- and DIDS-sensitive channel...... that is potential dependent. An additional stimulation of the swelling-activated taurine efflux is seen after addition of arachidonic acid and oleic acid. Cell swelling also activates a Mini Cl– channel. The Cl– efflux via this Cl– channel, in contrast to the swelling-activated taurine efflux, is unaffected by DIDS...

Chloride Test

Science.gov (United States)

... metabolic acidosis ) or when a person hyperventilates (causing respiratory alkalosis ). A decreased level of blood chloride (called hypochloremia) ... disease , emphysema or other chronic lung diseases (causing respiratory ... metabolic alkalosis). An increased level of urine chloride can indicate ...

Expression of Genes Involved in Iron and Sulfur Respiration in a Novel Thermophilic Crenarchaeon Isolated from Acid-Sulfate-Chloride Geothermal Systems

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Kozubal, M.; Macur, R.; Inskeep, W. P.

2007-12-01

Acidic geothermal springs within Yellowstone National Park (YNP) provide an excellent opportunity to study microbial populations and their relationship with geochemical processes such as redox cycling and biomineralization of iron. Fourteen acid-sulfate-chloride (ASC) and acid-sulfate (AS) geothermal springs located in (YNP) have been extensively characterized for aqueous chemistry, solid phase mineral deposition and microbial diversity and distribution. The oxidation of Fe(II) with oxygen as an electron acceptor is exergonic under these conditions, consequently, Fe(II) may be an important electron donor driving primary production in ASC and AS habitats, and products of biomineralization (e.g. Fe[III]-oxides of varying crystallinity and structure, as well as jarosite in some cases) are common in the outflow channels of these environments. Recently, we isolated a novel Metallosphaera-like microorganism (Metallosphaera strain MK1) from an ASC spring in Norris Geyser Basin, YNP. Clone libraries (16S rRNA gene) from multiple sites suggest that microorganisms closely related to strain MK1 (between 98-100 percent similarity) dominate many spring locations between 55-80 C. The in situ abiotic oxidation rate of Fe(II) has been shown to be very slow in these systems and Metallosphaera strain MK1 has been directly implicated in biotic Fe(II) oxidation. Metallosphaera strain MK1 has been submitted for full genome sequencing and is yielding gene sequences related to the terminal oxidases SOXABC and SOXM super-complex. In addition, sequences from a recently characterized terminal oxidase FOX complex involved in Fe(II) and pyrite oxidation from Sulfolobus metallicus have been found in Metallosphaera strain MK1. A protein complex analogous to Metallosphaera sedula has been identified in strain MK1 and this complex has also been expressed in cells grown on pyrite and Fe(II). Other sequences identified in Metallosphaera strain MK1 that are involved in respiration are the TQO

Activation of AMPK inhibits cholera toxin stimulated chloride secretion in human and murine intestine.

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Ailín C Rogers

Full Text Available Increased intestinal chloride secretion through chloride channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR, is one of the major molecular mechanisms underlying enterotoxigenic diarrhea. It has been demonstrated in the past that the intracellular energy sensing kinase, the AMP-activated protein kinase (AMPK, can inhibit CFTR opening. We hypothesized that pharmacological activation of AMPK can abrogate the increased chloride flux through CFTR occurring during cholera toxin (CTX mediated diarrhea. Chloride efflux was measured in isolated rat colonic crypts using real-time fluorescence imaging. AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK. In order to substantiate our findings on the whole tissue level, short-circuit current (SCC was monitored in human and murine colonic mucosa using Ussing chambers. Furthermore, fluid accumulation was measured in excised intestinal loops. CTX and forskolin (FSK significantly increased chloride efflux in isolated colonic crypts. The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin. In human and mouse mucosal sheets, CTX and FSK increased SCC. AICAR and metformin inhibited the secretagogue induced rise in SCC, thereby confirming the findings made in isolated crypts. Moreover, AICAR decreased CTX stimulated fluid accumulation in excised intestinal segments. The present study suggests that pharmacological activation of AMPK effectively reduces CTX mediated increases in intestinal chloride secretion, which is a key factor for intestinal water accumulation. AMPK activators may therefore represent a supplemental treatment strategy for acute diarrheal illness.

Chloride channels in the plasma membrane of a foetal Drosophila cell line, S2

DEFF Research Database (Denmark)

Asmild, Margit; Willumsen, Niels J.

2000-01-01

S2 cells, Cl- Channels, Expression system, Drosophila, Inward rectifier, Outward rectifier, Patch clamp......S2 cells, Cl- Channels, Expression system, Drosophila, Inward rectifier, Outward rectifier, Patch clamp...

Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

DEFF Research Database (Denmark)

Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders

2010-01-01

Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migrai...

40 CFR 61.65 - Emission standard for ethylene dichloride, vinyl chloride and polyvinyl chloride plants.

Science.gov (United States)

2010-07-01

... dichloride, vinyl chloride and polyvinyl chloride plants. 61.65 Section 61.65 Protection of Environment... AIR POLLUTANTS National Emission Standard for Vinyl Chloride § 61.65 Emission standard for ethylene dichloride, vinyl chloride and polyvinyl chloride plants. An owner or operator of an ethylene dichloride...

Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis.

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Fenton, Robert A; Poulsen, Søren B; de la Mora Chavez, Samantha; Soleimani, Manoocher; Dominguez Rieg, Jessica A; Rieg, Timo

2017-08-01

The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3 loxloxCre) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3 loxloxCre mice, while urine osmolality and GFR were significantly lower. Water deprivation revealed a small urinary concentrating defect in NHE3 loxloxCre mice on a control diet, exaggerated on low sodium chloride. Ten days of low or high sodium chloride diet did not affect plasma sodium in control mice; however, NHE3 loxloxCre mice were susceptible to low sodium chloride (about -4 mM) or high sodium chloride intake (about +2 mM) versus baseline, effects without differences in plasma aldosterone between groups. Blood pressure was significantly lower in NHE3 loxloxCre mice and was sodium chloride sensitive. In control mice, the expression of the sodium/phosphate co-transporter Npt2c was sodium chloride sensitive. However, lack of tubular NHE3 blunted Npt2c expression. Alterations in the abundances of sodium/chloride cotransporter and its phosphorylation at threonine 58 as well as the abundances of the α-subunit of the epithelial sodium channel, and its cleaved form, were also apparent in NHE3 loxloxCre mice. Thus, renal NHE3 is required to maintain blood pressure and steady-state plasma sodium levels when dietary sodium chloride intake is modified. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chloride flux in phagocytes.

Science.gov (United States)

Wang, Guoshun

2016-09-01

Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)-H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium-lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of nutrient restriction and re-feeding on calpain family genes in skeletal muscle of channel catfish (Ictalurus punctatus.

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Elena Preziosa

Full Text Available BACKGROUND: Calpains, a superfamily of intracellular calcium-dependent cysteine proteases, are involved in the cytoskeletal remodeling and wasting of skeletal muscle. Calpains are generated as inactive proenzymes which are activated by N-terminal autolysis induced by calcium-ions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we characterized the full-length cDNA sequences of three calpain genes, clpn1, clpn2, and clpn3 in channel catfish, and assessed the effect of nutrient restriction and subsequent re-feeding on the expression of these genes in skeletal muscle. The clpn1 cDNA sequence encodes a protein of 704 amino acids, Clpn2 of 696 amino acids, and Clpn3 of 741 amino acids. Phylogenetic analysis of deduced amino acid sequences indicate that catfish Clpn1 and Clpn2 share a sequence similarity of 61%; catfish Clpn1 and Clpn3 of 48%, and Clpn2 and Clpn3 of only 45%. The domain structure architectures of all three calpain genes in channel catfish are similar to those of other vertebrates, further supported by strong bootstrap values during phylogenetic analyses. Starvation of channel catfish (average weight, 15-20 g for 35 days influenced the expression of clpn1 (2.3-fold decrease, P<0.05, clpn2 (1.3-fold increase, P<0.05, and clpn3 (13.0-fold decrease, P<0.05, whereas the subsequent refeeding did not change the expression of these genes as measured by quantitative real-time PCR analysis. Calpain catalytic activity in channel catfish skeletal muscle showed significant differences only during the starvation period, with a 1.2- and 1.4- fold increase (P<0.01 after 17 and 35 days of starvation, respectively. CONCLUSION/SIGNIFICANCE: We have assessed that fasting and refeeding may provide a suitable experimental model to provide us insight into the role of calpains during fish muscle atrophy and how they respond to changes in nutrient supply.

Ca2+-dependent K+ Channels in Exocrine Salivary Glands

Science.gov (United States)

Catalán, Marcelo A.; Peña-Munzenmayer, Gaspar; Melvin, James E.

2014-01-01

In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca2+-dependent K+ channels take part in key functions including membrane potential regulation, fluid movement and K+ secretion in exocrine glands. Two K+ channels have been identified in exocrine salivary glands: 1) a Ca2+-activated K+ channel of intermediate single channel conductance encoded by the KCNN4 gene; and, 2) a voltage- and Ca2+-dependent K+ channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca2+-dependent K+ channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca2+-dependent K+ channels by protein-protein interactions that may significantly impact exocrine gland physiology. PMID:24559652

dyschronic, a Drosophila homolog of a deaf-blindness gene, regulates circadian output and Slowpoke channels.

Directory of Open Access Journals (Sweden)

James E C Jepson

Full Text Available Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc. dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause of deaf-blindness in humans. Whirlin and other Usher proteins are expressed in the mammalian central nervous system, yet their function in the CNS has not been investigated. We show that DYSC is expressed in major neuronal tracts and regulates expression of the calcium-activated potassium channel SLOWPOKE (SLO, an ion channel also required in the circadian output pathway. SLO and DYSC are co-localized in the brain and control each other's expression post-transcriptionally. Co-immunoprecipitation experiments demonstrate they form a complex, suggesting they regulate each other through protein-protein interaction. Furthermore, electrophysiological recordings of neurons in the adult brain show that SLO-dependent currents are greatly reduced in dysc mutants. Our work identifies a Drosophila homolog of a deaf-blindness gene as a new component of the circadian output pathway and an important regulator of ion channel expression, and suggests novel roles for Usher proteins in the mammalian nervous system.

Anion channels: master switches of stress responses.

Science.gov (United States)

Roelfsema, M Rob G; Hedrich, Rainer; Geiger, Dietmar

2012-04-01

During stress, plant cells activate anion channels and trigger the release of anions across the plasma membrane. Recently, two new gene families have been identified that encode major groups of anion channels. The SLAC/SLAH channels are characterized by slow voltage-dependent activation (S-type), whereas ALMT genes encode rapid-activating channels (R-type). Both S- and R-type channels are stimulated in guard cells by the stress hormone ABA, which leads to stomatal closure. Besides their role in ABA-dependent stomatal movement, anion channels are also activated by biotic stress factors such as microbe-associated molecular patterns (MAMPs). Given that anion channels occur throughout the plant kingdom, they are likely to serve a general function as master switches of stress responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of Chloride-Ion Adsorption Agent on Chloride Ions in Concrete and Mortar

Directory of Open Access Journals (Sweden)

Gai-Fei Peng

2014-04-01

Full Text Available The influence of a chloride-ion adsorption agent (Cl agent in short, composed of zeolite, calcium aluminate hydrate and calcium nitrite, on the ingress of chloride ions into concrete and mortar has been experimentally studied. The permeability of concrete was measured, and the chloride ion content in mortar was tested. The experimental results reveal that the Cl agent could adsorb chloride ions effectively, which had penetrated into concrete and mortar. When the Cl agent was used at a dosage of 6% by mass of cementitious materials in mortar, the resistance to the penetration of chloride ions could be improved greatly, which was more pronounced when a combination of the Cl agent and fly ash or slag was employed. Such an effect is not the result of the low permeability of the mortar, but might be a result of the interaction between the Cl agent and the chloride ions penetrated into the mortar. There are two possible mechanisms for the interaction between the Cl agent and chloride ion ingress. One is the reaction between calcium aluminate hydrate in the Cl agent and chloride ions to form Friedel’s salt, and the other one is that calcium aluminate hydrate reacts with calcium nitrite to form AFm during the early-age hydration of mortar and later the NO2− in AFm is replaced by chloride ions, which then penetrate into the mortar, also forming Friedel’s salt. More research is needed to confirm the mechanisms.

Chloride test - blood

Science.gov (United States)

Serum chloride test ... A greater-than-normal level of chloride is called hyperchloremia. It may be due to: Carbonic anhydrase inhibitors (used to treat glaucoma) Diarrhea Metabolic acidosis Respiratory alkalosis (compensated) Renal ...

Chloride in diet

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/002417.htm Chloride in diet To use the sharing features on this page, please enable JavaScript. Chloride is found in many chemicals and other substances ...

Mercuric chloride poisoning

Science.gov (United States)

... page: //medlineplus.gov/ency/article/002474.htm Mercuric chloride poisoning To use the sharing features on this page, please enable JavaScript. Mercuric chloride is a very poisonous form of mercury. It ...

Chloride removal from vitrification offgas

Energy Technology Data Exchange (ETDEWEB)

Slaathaug, E.J. [Westinghouse Hanford Co., Richland, WA (United States)

1995-06-01

This study identified and investigated techniques of selectively purging chlorides from the low-level waste (LLW) vitrification process with the purge stream acceptable for burial on the Hanford Site. Chlorides will be present in high concentration in several individual feeds to the LLW Vitrification Plant. The chlorides are highly volatile in combustion type melters and are readily absorbed by wet scrubbing of the melter offgas. The Tank Waste Remediation System (TWRS) process flow sheets show that the resulting chloride rich scrub solution is recycled back to the melter. The chlorides must be purged from the recycle loop to prevent the buildup of excessively high chloride concentrations.

Chloride removal from vitrification offgas

International Nuclear Information System (INIS)

Slaathaug, E.J.

1995-01-01

This study identified and investigated techniques of selectively purging chlorides from the low-level waste (LLW) vitrification process with the purge stream acceptable for burial on the Hanford Site. Chlorides will be present in high concentration in several individual feeds to the LLW Vitrification Plant. The chlorides are highly volatile in combustion type melters and are readily absorbed by wet scrubbing of the melter offgas. The Tank Waste Remediation System (TWRS) process flow sheets show that the resulting chloride rich scrub solution is recycled back to the melter. The chlorides must be purged from the recycle loop to prevent the buildup of excessively high chloride concentrations

Amine and Titanium (IV Chloride, Boron (III Chloride or Zirconium (IV Chloride-Promoted Baylis-Hillman Reactions

Directory of Open Access Journals (Sweden)

Shi-Cong Cui

2001-10-01

Full Text Available The Baylis-Hillman reactions of various aryl aldehydes with methyl vinyl ketone at temperatures below -20oC using Lewis acids such as titanium (IV chloride, boron (III chloride or zirconium (IV chloride in the presence of a catalytic amount of selected amines used as a Lewis bases afford the chlorinated compounds 1 as the major product in very high yields. Acrylonitrile can also undergo the same reaction to give the corresponding chlorinated product in moderate yield. A plausible reaction mechanism is proposed. However, if the reaction was carried out at room temperature (ca. 20oC, then the Z-configuration of the elimination product 3, derived from 1, was formed as the major product.

Exterior Site Occupancy Infers Chloride-Induced Proton Gating in a Prokaryotic Homolog of the ClC Chloride Channel

Science.gov (United States)

Bostick, David L.; Berkowitz, Max L.

2004-01-01

The ClC family of anion channels mediates the efficient, selective permeation of Cl− across the biological membranes of living cells under the driving force of an electrochemical gradient. In some eukaryotes, these channels are known to exhibit a unique gating mechanism, which appears to be triggered by the permeant Cl− anion. We infer details of this gating mechanism by studying the free energetics of Cl− occupancy in the pore of a prokaryotic ClC homolog. These free energetics were gleaned from 30 ns of molecular dynamics simulation on an ∼133,000-atom system consisting of a hydrated membrane embedded StClC transporter. The binding sites for Cl− in the transporter were determined for the cases where the putative gating residue, Glu148, was protonated and unprotonated. When the glutamate gate is protonated, Cl− favorably occupies an exterior site, Sext, to form a queue of anions in the pore. However, when the glutamate gate is unprotonated, Cl− cannot occupy this site nor, consequently, pass through the pore. An additional, previously undetected, site was found in the pore near the outer membrane that exists regardless of the protonation state of Glu148. Although this suggests that, for the prokaryotic homolog, protonation of Glu148 may be the first step in transporting Cl− at the expense of H+ transport in the opposite direction, an evolutionary argument might suggest that Cl− opens the ClC gate in eukaryotic channels by inducing the conserved glutamate's protonation. During an additional 20 ns free dynamics simulation, the newly discovered outermost site, Sout, and the innermost site, Sint, were seen to allow spontaneous exchange of Cl− ions with the bulk electrolyte while under depolarization conditions. PMID:15345547

Chloride Transport in Heterogeneous Formation

Science.gov (United States)

Mukherjee, A.; Holt, R. M.

2017-12-01

The chloride mass balance (CMB) is a commonly-used method for estimating groundwater recharge. Observations of the vertical distribution of pore-water chloride are related to the groundwater infiltration rates (i.e. recharge rates). In CMB method, the chloride distribution is attributed mainly to the assumption of one dimensional piston flow. In many places, however, the vertical distribution of chloride will be influenced by heterogeneity, leading to horizontal movement of infiltrating waters. The impact of heterogeneity will be particularly important when recharge is locally focused. When recharge is focused in an area, horizontal movement of chloride-bearing waters, coupled with upward movement driven by evapotranspiration, may lead to chloride bulges that could be misinterpreted if the CMB method is used to estimate recharge. We numerically simulate chloride transport and evaluate the validity of the CMB method in highly heterogeneous systems. This simulation is conducted for the unsaturated zone of Ogallala, Antlers, and Gatuna (OAG) formations in Andrews County, Texas. A two dimensional finite element model will show the movement of chloride through heterogeneous systems. We expect to see chloride bulges not only close to the surface but also at depths characterized by horizontal or upward movement. A comparative study of focused recharge estimates in this study with available recharge data will be presented.

Electrochemical Chloride extraction using external electrodes?

DEFF Research Database (Denmark)

Ottosen, Lisbeth M.; Pedersen, Anne Juul

2006-01-01

Electrochemical methods for the removal of chloride from concrete have been developed and the methods are primarily designed for situations where corrosion has started due to an increased chloride concentration in the vicinity of the reinforcement. In these methods the reinforcement is used...... as the cathode. However, some unwanted side effects can occur, including alkali-silica reaction and in some cases hydrogen embrittlement. It is also suggested also to use electrochemical chloride extraction in a preventive way in constructions where chloride induced corrosion is likely to be a problem after...... a period of time, i.e. remove the chlorides before the chloride front reaches the reinforcement. If the chlorides are removed from outer few centimetres from the surface, the chloride will not reach the reinforcement and cause damage. By using the electrochemical chloride removal in this preventive way...

Draft genome sequence of chloride-tolerant Leptospirillum ferriphilum Sp-Cl from industrial bioleaching operations in northern Chile.

Science.gov (United States)

Issotta, Francisco; Galleguillos, Pedro A; Moya-Beltrán, Ana; Davis-Belmar, Carol S; Rautenbach, George; Covarrubias, Paulo C; Acosta, Mauricio; Ossandon, Francisco J; Contador, Yasna; Holmes, David S; Marín-Eliantonio, Sabrina; Quatrini, Raquel; Demergasso, Cecilia

2016-01-01

Leptospirillum ferriphilum Sp-Cl is a Gram negative, thermotolerant, curved, rod-shaped bacterium, isolated from an industrial bioleaching operation in northern Chile, where chalcocite is the major copper mineral and copper hydroxychloride atacamite is present in variable proportions in the ore. This strain has unique features as compared to the other members of the species, namely resistance to elevated concentrations of chloride, sulfate and metals. Basic microbiological features and genomic properties of this biotechnologically relevant strain are described in this work. The 2,475,669 bp draft genome is arranged into 74 scaffolds of 74 contigs. A total of 48 RNA genes and 2,834 protein coding genes were predicted from its annotation; 55 % of these were assigned a putative function. Release of the genome sequence of this strain will provide further understanding of the mechanisms used by acidophilic bacteria to endure high osmotic stress and high chloride levels and of the role of chloride-tolerant iron-oxidizers in industrial bioleaching operations.

Factors influencing chloride deposition in a coastal hilly area and application to chloride deposition mapping

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H. Guan

2010-05-01

Full Text Available Chloride is commonly used as an environmental tracer for studying water flow and solute transport in the environment. It is especially useful for estimating groundwater recharge based on the commonly used chloride mass balance (CMB method. Strong spatial variability in chloride deposition in coastal areas is one difficulty encountered in appropriately applying the method. A high-resolution bulk chloride deposition map in the coastal region is thus needed. The aim of this study is to construct a chloride deposition map in the Mount Lofty Ranges (MLR, a coastal hilly area of approximately 9000 km² spatial extent in South Australia. We examined geographic (related to coastal distance, orographic, and atmospheric factors that may influence chloride deposition, using partial correlation and regression analyses. The results indicate that coastal distance, elevation, as well as terrain aspect and slope, appear to be significant factors controlling chloride deposition in the study area. Coastal distance accounts for 70% of spatial variability in bulk chloride deposition, with elevation, terrain aspect and slope an additional 15%. The results are incorporated into a de-trended residual kriging model (ASOADeK to produce a 1 km×1 km resolution bulk chloride deposition and concentration maps. The average uncertainty of the deposition map is about 20–30% in the western MLR, and 40–50% in the eastern MLR. The maps will form a useful basis for examining catchment chloride balance for the CMB application in the study area.

Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel*

Science.gov (United States)

Chen, Jeffery; Guo, Jun; Yang, Tonghua; Li, Wentao; Lamothe, Shawn M.; Kang, Yudi; Szendrey, John A.; Zhang, Shetuan

2015-01-01

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K+ conditions. In the present study, we addressed whether hERG internalization occurs under normal K+ conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K+-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell-surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K+ exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K+ medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane-bound hERG channels. PMID:26152716

21 CFR 184.1297 - Ferric chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ferric chloride. 184.1297 Section 184.1297 Food and... Substances Affirmed as GRAS § 184.1297 Ferric chloride. (a) Ferric chloride (iron (III) chloride, FeC13, CAS Reg. No. 7705-08-0) may be prepared from iron and chlorine or from ferric oxide and hydrogen chloride...

A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

Directory of Open Access Journals (Sweden)

Vargas-Alarcon Gilberto

2012-02-01

Full Text Available Abstract Background A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM; and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7 act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. Methods We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ. Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. Results The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036 mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88 than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002 and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001. Conclusion In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that

ATP sensitive potassium channels in the skeletal muscle functions : involvement of the KCNJ11(Kir6.2 gene in the determination of Warner Bratzer shear force

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Domenico eTricarico

2016-05-01

Full Text Available The ATP-sensitive K+-channels (KATP are distributed in the tissues coupling metabolism with K+ ions efflux. KATP subunits are encoded by KCNJ8 (Kir6.1, KCNJ11 (Kir6.2, ABCC8 (SUR1 and ABCC9 (SUR2 genes, alternative RNA splicing give rise to SUR variants that confer distinct physiological properties on the channel. An high expression/activity of the sarco-KATP channel is observed in various rat fast-twitch muscles, characterized by elevated muscle strength, while a low expression/activity is observed in the slow-twitch muscles characterized by reduced strength and frailty. Down-regulation of the KATP subunits of fast-twitch fibres is found in conditions characterized by weakness and frailty. KCNJ11 gene knockout mice have reduced glycogen, lean phenotype, lower body fat, and weakness. KATP channel is also a sensor of muscle atrophy. The KCNJ11 gene is located on BTA15, close to a QTL for meat tenderness, it has also a role in glycogen storage, a key mechanism of the postmortem transformation of muscle into meat. The role of KCNJ11 gene in muscle function may underlie an effect of KCNJ11 genotypes on meat tenderness, as recently reported. The fiber phenotype and genotype are important in livestock production science. Quantitative traits including meat production and quality are influenced both by environment and genes. Molecular markers can play an important role in the genetic improvement of animals through breeding strategies. Many factors influence the muscle Warner-Bratzler shear force including breed, age, feeding, the biochemical and functional parameters. The role of KCNJ11gene and related genes on muscle tenderness will be discussed in the present review.

On the Capacity of the Dirty Paper Channel with Fast Fading and Discrete Channel States

OpenAIRE

Rini, Stefano; Shitz, Shlomo Shamai

2016-01-01

The "writing dirty paper" capacity result crucially dependents on the perfect channel knowledge at the transmitter as the presence of even a small uncertainty in the channel realization gravely hampers the ability of the transmitter to pre-code its transmission against the channel state. This is particularly disappointing as it implies that interference pre-coding in practical systems is effective only when the channel estimates at the users have very high precision, a condition which is gene...

Dynamic electrochemical measurement of chloride ions

NARCIS (Netherlands)

Abbas, Yawar; de Graaf, Derk B.; Olthuis, Wouter; van den Berg, Albert

2016-01-01

This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver chloride electrode is used extensively for potentiometric measurement of chloride ions concentration in electrolyte. In this measurement,

Reaction of calcium chloride with alkali metal chlorides in melts

International Nuclear Information System (INIS)

Savin, V.D.; Mikhajlova, N.P.

1984-01-01

Thermochemical characteristics of CaCl 2 reaction with sodium, potassium, rubidium and cesium chlorides in melts at 890 deg C are determined. The values of formation enthalpies of infinitely diluted by CaCl 2 solutions (ΔH) in the chloride row increase from -22 in NaCl to -47 kJ/mol of CaCl 2 in CsCl. With increasing the concentration of calcium chloride in the solution the ΔH values decrease. The regularities of separation from the solution of the CaCl 2 -CsCl system at 890 deg C of the CaCl 2 x CsCl in solid are studied. Formation enthalpies under the given conditions constitutes -70+-3 kJ/mol

Association of chloride intracellular channel 4 and Indian hedgehog proteins with survival of patients with pancreatic ductal adenocarcinoma.

Science.gov (United States)

Zou, Qiong; Yang, Zhulin; Li, Daiqiang; Liu, Ziru; Yuan, Yuan

2016-12-01

Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question. Immunohistochemistry of CLIC4 and Ihh was performed with EnVision ™ in 106 pancreatic ductal adenocarcinoma specimens, 35 paracancer samples (2 cm away from the tumour, when possible or available), 55 benign lesions and 13 normal tissue samples. CLIC4 and Ihh expression in pancreatic ductal adenocarcinoma were significantly higher than in paracancer tissue and benign lesions (CLIC4: P = 0.009 and Ihh: P Ihh: P = 0.0001 respectively). CLIC4 and Ihh expression was negative in normal pancreatic tissues. The expression of CLIC4 and Ihh was associated significantly with tumour grade, lymph node metastasis, tumour invasion and poor overall survival. Thus CLIC4 and Ihh could serve as biological markers for the progression, metastasis and/or invasiveness of pancreatic ductal adenocarcinoma. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Facile Preparation of Chloride-Conducting Membranes : First Step towards a Room-Temperature Solid-State Chloride-Ion Battery

NARCIS (Netherlands)

Gschwind, Fabienne; Steinle, Dominik; Sandbeck, Daniel; Schmidt, Celine; von Hauff, Elizabeth

2016-01-01

Three types of chloride-conducting membranes based on polyvinyl chloride, commercial gelatin, and polyvinyldifluoride-hexafluoropolymer are introduced in this report. The polymers are mixed with chloride-containing salts, such as tetrabutylammonium chloride, and cast to form membranes. We studied

Phycodnavirus potassium ion channel proteins question the virus molecular piracy hypothesis.

Directory of Open Access Journals (Sweden)

Kay Hamacher

Full Text Available Phycodnaviruses are large dsDNA, algal-infecting viruses that encode many genes with homologs in prokaryotes and eukaryotes. Among the viral gene products are the smallest proteins known to form functional K(+ channels. To determine if these viral K(+ channels are the product of molecular piracy from their hosts, we compared the sequences of the K(+ channel pore modules from seven phycodnaviruses to the K(+ channels from Chlorella variabilis and Ectocarpus siliculosus, whose genomes have recently been sequenced. C. variabilis is the host for two of the viruses PBCV-1 and NY-2A and E. siliculosus is the host for the virus EsV-1. Systematic phylogenetic analyses consistently indicate that the viral K(+ channels are not related to any lineage of the host channel homologs and that they are more closely related to each other than to their host homologs. A consensus sequence of the viral channels resembles a protein of unknown function from a proteobacterium. However, the bacterial protein lacks the consensus motif of all K(+ channels and it does not form a functional channel in yeast, suggesting that the viral channels did not come from a proteobacterium. Collectively, our results indicate that the viruses did not acquire their K(+ channel-encoding genes from their current algal hosts by gene transfer; thus alternative explanations are required. One possibility is that the viral genes arose from ancient organisms, which served as their hosts before the viruses developed their current host specificity. Alternatively the viral proteins could be the origin of K(+ channels in algae and perhaps even all cellular organisms.

Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis.

Science.gov (United States)

McGlothlin, Joel W; Chuckalovcak, John P; Janes, Daniel E; Edwards, Scott V; Feldman, Chris R; Brodie, Edmund D; Pfrender, Michael E; Brodie, Edmund D

2014-11-01

Members of a gene family expressed in a single species often experience common selection pressures. Consequently, the molecular basis of complex adaptations may be expected to involve parallel evolutionary changes in multiple paralogs. Here, we use bacterial artificial chromosome library scans to investigate the evolution of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin (TTX), which blocks Nav's, arresting action potentials in nerves and muscle. Some Thamnophis populations have evolved resistance to extremely high levels of TTX. Previous work has identified amino acid sites in the skeletal muscle sodium channel Nav1.4 that confer resistance to TTX and vary across populations. We identify parallel evolution of TTX resistance in two additional Nav paralogs, Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system and should thus be exposed to ingested TTX. Each paralog contains at least one TTX-resistant substitution identical to a substitution previously identified in Nav1.4. These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle. In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier. We also report the exon-intron structure of six Nav paralogs, the first such analysis for snake genes. Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Electrochemical chloride extraction of a beam polluted by chlorides after 40 years in the sea

OpenAIRE

BOUTEILLER, Véronique; LAPLAUD, André; MALOULA, Aurélie; MORELLE, René Stéphane; DUCHESNE, Béatrice; MORIN, Mathieu

2006-01-01

A beam element, naturally polluted by chlorides after 40 years of a marine tidal exposure, has been treated by electrochemical chloride extraction. The chloride profiles, before and after treatment, show that free chlorides are extrated with an efficiency of 70 % close to the steel, 50 % in the intermediate cover and only 5 % at the concrete surface. From the electrochemical characterizations (before, after, 1, 2 and 17 months after treatment), the steel potential values can, semehow, indicat...

Sorption of sulphur dioxide in calcium chloride and nitrate chloride liquids

International Nuclear Information System (INIS)

Trzepierczynska, I.; Gostomczyk, M.A.

1989-01-01

Flue gas desulphurization via application of suspensions has one inherent disadvantage: fixation of sulphur dioxide is very poor. This should be attributed to the low content of calcium ions which results from the solubility of the sorbing species. The solubility of sparingly soluble salts (CaO, CaCO 3 ) may be increased by decreasing the pH of the solution; yet, there is a serious limitation in this method: the corrosivity of the scrubber. The objective of this paper was to assess the sorbing capacity of two soluble calcium salts, calcium chloride and calcium nitrate, as a function of calcium ion concentration in the range of 20 to 82 kg/m 3 . It has been found that sorbing capacity increases with the increasing calcium ion concentration until the calcium concentration in the calcium chloride solution reaches the level of 60 kg/m 3 which is equivalent to the chloride ion content of ∼ 110 kg/m 3 . Addition of calcium hydroxide to the solutions brings about an increase in the sorbing capacity up to 1.6 kg/m 3 and 2.2 kg/m 3 for calcium chloride and calcium nitrate, respectively, as a result of the increased sorbent alkalinity. The sorption capacity of the solutions is considerably enhanced by supplementing them by acetate ions (2.8 to 13.9 kg/m 3 ). Increase in the sorption capacity of calcium nitrate solutions enriched with calcium acetate was approximately 30% as high as that of the chloride solutions enriched with calcium acetate was approximately 30% as high as that of the chloride solutions supplemented in the same way. (author). 12 refs, 7 refs, 4 tabs

21 CFR 173.375 - Cetylpyridinium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Cetylpyridinium chloride. 173.375 Section 173.375... CONSUMPTION Specific Usage Additives § 173.375 Cetylpyridinium chloride. Cetylpyridinium chloride (CAS Reg. No....1666 of this chapter, at a concentration of 1.5 times that of cetylpyridinium chloride. (c) The...

21 CFR 184.1622 - Potassium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in infant...

Temperature dependence of diffusion coefficients of trivalent uranium ions in chloride and chloride-fluoride melts

International Nuclear Information System (INIS)

Komarov, V.E.; Borodina, N.P.

1981-01-01

Diffusion coefficients of U 3+ ions are measured by chronopotentiometric method in chloride 3LiCl-2KCl and in mixed chloride fluoride 3LiCl(LiF)-2KCl melts in the temperature range 633-1235 K. It is shown It is shown that experimental values of diffusion-coefficients are approximated in a direct line in lg D-1/T coordinate in chloride melt in the whole temperature range and in chloride-fluoride melt in the range of 644-1040 K. Experimental values of diffusion coefficients diviate from Arrhenius equation in the direction of large values in chloride-fluoride melt at further increase of temperature up to 1235 K. Possible causes of such a diviation are considered [ru

GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions.

Science.gov (United States)

Lin, Guo-Wang; Lu, Ping; Zeng, Tao; Tang, Hui-Ling; Chen, Yong-Hong; Liu, Shu-Jing; Gao, Mei-Mei; Zhao, Qi-Hua; Yi, Yong-Hong; Long, Yue-Sheng

2017-02-01

Abnormal expressions of sodium channel SCN1A and SCN3A genes alter neural excitability that are believed to contribute to the pathogenesis of epilepsy, a long-term risk of recurrent seizures. Ketogenic diet (KD), a high-fat and low-carbohydrate treatment for difficult-to-control (refractory) epilepsy in children, has been suggested to reverse gene expression patterns. Here, we reveal a novel role of GAPDH on the posttranscriptional regulation of mouse Scn1a and Scn3a expressions under seizure and KD conditions. We show that GAPDH binds to a conserved region in the 3' UTRs of human and mouse SCN1A and SCN3A genes, which decreases and increases genes' expressions by affecting mRNA stability through SCN1A 3' UTR and SCN3A 3' UTR, respectively. In seizure mice, the upregulation and phosphorylation of GAPDH enhance its binding to the 3' UTR, which lead to downregulation of Scn1a and upregulation of Scn3a. Furthermore, administration of KD generates β-hydroxybutyric acid which rescues the abnormal expressions of Scn1a and Scn3a by weakening the GAPDH's binding to the element. Taken together, these data suggest that GAPDH-mediated expression regulation of sodium channel genes may be associated with epilepsy and the anticonvulsant action of KD. Copyright © 2016 Elsevier Ltd. All rights reserved.

21 CFR 184.1138 - Ammonium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ammonium chloride. 184.1138 Section 184.1138 Food... Specific Substances Affirmed as GRAS § 184.1138 Ammonium chloride. (a) Ammonium chloride (NH4Cl, CAS Reg. No. 12125-02-9) is produced by the reaction of sodium chloride and an ammonium salt in solution. The...

21 CFR 184.1426 - Magnesium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Magnesium chloride. 184.1426 Section 184.1426 Food... Specific Substances Affirmed as GRAS § 184.1426 Magnesium chloride. (a) Magnesium chloride (MgC12·6H2O, CAS... hydrochloric acid solution and crystallizing out magnesium chloride hexahydrate. (b) The ingredient meets the...

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

Science.gov (United States)

Kaczmarek, Leonard K; Aldrich, Richard W; Chandy, K George; Grissmer, Stephan; Wei, Aguan D; Wulff, Heike

2017-01-01

A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium. This article describes the molecular relationships between these channels and provides an introduction to their functional properties. It also introduces a new nomenclature that differentiates between calcium- and sodium-activated potassium channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Synthesis of aminocarbonyl N-acylhydrazones by a three-component reaction of isocyanides, hydrazonoyl chlorides, and carboxylic acids.

Science.gov (United States)

Giustiniano, Mariateresa; Meneghetti, Fiorella; Mercalli, Valentina; Varese, Monica; Giustiniano, Francesco; Novellino, Ettore; Tron, Gian Cesare

2014-10-17

A novel one-pot multicomponent synthesis of α-aminocarbonyl N-acylhydrazones starting from readily available hydrazonoyl chlorides, isocyanides, and carboxylic acids is reported. The strategy exploits the ability of the carboxylic acid as a third component to suppress all competing reactions between nitrile imines and isocyanides, channeling the course of the reaction toward the formation of this novel class of compounds.

Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1.

Science.gov (United States)

Achilonu, Ikechukwu; Fanucchi, Sylvia; Cross, Megan; Fernandes, Manuel; Dirr, Heini W

2012-02-07

Chloride intracellular channel proteins exist in both a soluble cytosolic form and a membrane-bound form. The mechanism of conversion between the two forms is not properly understood, although one of the contributing factors is believed to be the variation in pH between the cytosol (~7.4) and the membrane (~5.5). We systematically mutated each of the three histidine residues in CLIC1 to an alanine at position 74 and a phenylalanine at positions 185 and 207. We examined the effect of the histidine-mediated pH dependence on the structure and global stability of CLIC1. None of the mutations were found to alter the global structure of the protein. However, the stability of H74A-CLIC1 and H185F-CLIC1, as calculated from the equilibrium unfolding data, is no longer dependent on pH because similar trends are observed at pH 7.0 and 5.5. The crystal structures show that the mutations result in changes in the local hydrogen bond coordination. Because the mutant total free energy change upon unfolding is not different from that of the wild type at pH 7.0, despite the presence of intermediates that are not seen in the wild type, we propose that it may be the stability of the intermediate state rather than the native state that is dependent on pH. On the basis of the lower stability of the intermediate in the H74A and H185F mutants compared to that of the wild type, we conclude that both His74 and His185 are involved in triggering the pH changes to the conformational stability of wild-type CLIC1 via their protonation, which stabilizes the intermediate state.

Removal of chloride from MSWI fly ash.

Science.gov (United States)

Chen, Wei-Sheng; Chang, Fang-Chih; Shen, Yun-Hwei; Tsai, Min-Shing; Ko, Chun-Han

2012-10-30

The high levels of alkali chloride and soluble metal salts present in MSWI fly ash is worth noting for their impact on the environment. In addition, the recycling or reuse of fly ash has become an issue because of limited landfill space. The chloride content in fly ash limits its application as basis for construction materials. Water-soluble chlorides such as potassium chloride (KCl), sodium chloride (NaCl), and calcium chloride hydrate (CaCl(2) · 2H(2)O) in fly ash are easily washed away. However, calcium chloride hydroxide (Ca(OH)Cl) might not be easy to leach away at room temperature. The roasting and washing-flushing processes were applied to remove chloride content in this study. Additionally, air and CO(2) were introduced into the washing process to neutralize the hazardous nature of chlorides. In comparison with the water flushing process, the roasting process is more efficient in reducing the process of solid-liquid separation and drying for the reuse of Cl-removed fly ash particles. In several roasting experiments, the removal of chloride content from fly ash at 1050°C for 3h showed the best results (83% chloride removal efficiency). At a solid to liquid ratio of 1:10 the water-flushing process can almost totally remove water-soluble chloride (97% chloride removal efficiency). Analyses of mineralogical change also prove the efficiency of the fly ash roasting and washing mechanisms for chloride removal. Copyright © 2012 Elsevier B.V. All rights reserved.

21 CFR 184.1193 - Calcium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium chloride. 184.1193 Section 184.1193 Food... Specific Substances Affirmed as GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be commercially...

Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

Directory of Open Access Journals (Sweden)

Wei Wang

2017-01-01

Full Text Available Chloride intracellular channel 1 (CLIC1 is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM database using structure-based virtual screening and molecular dynamics (MD simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.

Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A).

Science.gov (United States)

Truong, Eric C; Phuan, Puay W; Reggi, Amanda L; Ferrera, Loretta; Galietta, Luis J V; Levy, Sarah E; Moises, Alannah C; Cil, Onur; Diez-Cecilia, Elena; Lee, Sujin; Verkman, Alan S; Anderson, Marc O

2017-06-08

Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells, and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure-activity studies indicated the importance of benzene substituted as 2- or 4-methyl, or 4-fluoro, and defined the significance of thiophene substituents and size of the cycloalkylthiophene core. The most potent compound (10bm), which contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC 50 of ∼30 nM, ∼3.6-fold more potent than the most potent previously reported TMEM16A inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp analysis. AACTs may be useful as pharmacological tools to study TMEM16A function and as potential drug development candidates.

Determination of chloride in MOX samples using chloride ion selective electrode

Energy Technology Data Exchange (ETDEWEB)

Govindan, R; Das, D K; Mallik, G K; Sumathi, A; Patil, Sangeeta; Raul, Seema; Bhargava, V K; Kamath, H S [Bhabha Atomic Research Centre, Tarapur (India). Advanced Fuel Fabrication Facility

1997-09-01

The chloride present in the MOX fuel is separated from the matrix by pyrohydrolysis at a temperature of 950 {+-} 50 degC and is then analyzed by chloride ion selective electrode (Cl-ISE). The range covered is 0.4-4 ppm with a precision of better than {+-}5% R.S.D. (author). 4 refs., 1 tab.

Ca²⁺-dependent K⁺ channels in exocrine salivary glands.

Science.gov (United States)

Catalán, Marcelo A; Peña-Munzenmayer, Gaspar; Melvin, James E

2014-06-01

In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+) channels take part in key functions including membrane potential regulation, fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of intermediate single channel conductance encoded by the KCNN4 gene, and (2) a voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels by protein-protein interactions that may significantly impact exocrine gland physiology. Published by Elsevier Ltd.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

Science.gov (United States)

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Pharmacokinetics of vinyl chloride in the rat

International Nuclear Information System (INIS)

Bolt, H.M.; Laib, R.J.; Kappus, H.; Buchter, A.

1977-01-01

When rats are exposed to [ 14 C]vinyl chloride in a closed system, the vinyl chloride present in the atmosphere equilibrates with the animals' organism within 15 min. The course of equilibration could be determined using rats which had been given 6-nitro-1,2,3-benzothiadiazole. This compound completely blocks metabolism of vinyl chloride. The enzymes responsible for metabolism of vinyl chloride are saturated at an atmospheric concentration of vinyl chloride of 250 ppm. Pharmacokinetic analysis shows that no significant cumulation of vinyl chloride or its major metabolites is to be expected on repeated administration of vinyl chlorides. This may be consistent with the theory that a reactive, shortly living metabolite which occurs in low concentration only, may be responsible for the toxic effects of vinyl chloride

Laboratory investigation of electro-chemical chloride extraction from concrete with penetrated chloride

NARCIS (Netherlands)

Polder, R.B.; Hondel, A.W.M. van den

2002-01-01

Chloride extraction of concrete is a short-term electrochemical treatment against corrosion of reinforcing steel. The aim is to remove chloride ions from the concrete cover in order to reinstate passive behaviour. Physically sound concrete is left in place. To make this method more predictable and

Endocochlear potential depends on Cl- channels: Mechanism underlying deafness in Bartter syndrome IV

NARCIS (Netherlands)

G. Rickheit (Gesa); H. Maier (Hannes); N. Strenzke (Nicola); C.E. Andreescu (Corina); C.I. de Zeeuw (Chris); A. Muenscher (Adrian); A.A. Zdebik (Anselm); T.J. Jentsch (Thomas)

2008-01-01

textabstractHuman Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a β-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in

Assessment of Correlation between Sweat Chloride Levels and Clinical Features of Cystic Fibrosis Patients.

Science.gov (United States)

Raina, Manzoor A; Khan, Mosin S; Malik, Showkat A; Raina, Ab Hameed; Makhdoomi, Mudassir J; Bhat, Javed I; Mudassar, Syed

2016-12-01

Cystic Fibrosis (CF) is an autosomal recessive disorder and the incidence of this disease is undermined in Northern India. The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease. The aim of this prospective study was to elucidate the relationship of sweat chloride levels with clinical features and pattern of CF. A total of 182 patients, with clinical features of CF were included in this study for quantitative measurement of sweat chloride. Sweat stimulation and collection involved pilocarpine iontophoresis based on the Gibson and Cooks methodology. The quantitative estimation of chloride was done by Schales and Schales method with some modifications. Cystic Fibrosis Trans Membrane Conductance Regulator (CFTR) mutation status was recorded in case of patients with borderline sweat chloride levels to correlate the results and for follow-up. Out of 182 patients having clinical features consistent with CF, borderline and elevated sweat chloride levels were present in 9 (5%) and 41 (22.5%) subjects respectively. Elevated sweat chloride levels were significantly associated with wheeze, Failure To Thrive (FTT), history of CF in Siblings, product of Consanguineous Marriage (CM), digital clubbing and steatorrhoea on univariate analysis. On multivariate analysis only wheeze, FTT and steatorrhoea were found to be significantly associated with elevated sweat chloride levels (p<0.05). Among the nine borderline cases six cases were positive for at least two CFTR mutations and rest of the three cases were not having any mutation in CFTR gene. The diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Sweat testing is a gold standard for diagnosis of CF patients as genetic mutation profile being heterozygous and unlikely to become diagnostic test.

Major Channels Involved In Neuropsychiatric Disorders And Therapeutic Perspectives

Directory of Open Access Journals (Sweden)

Paola eImbrici

2013-05-01

Full Text Available Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders or schizophrenia. Moreover, point mutations in calcium, sodium and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium and potassium channels in bipolar disorder, schizophrenia and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.

Chloride Ingress in Concrete with Different Age at Time of First Chloride Exposure

DEFF Research Database (Denmark)

Hansen, Esben Østergaard; Iskau, Martin Riis; Hasholt, Marianne Tange

2016-01-01

Concrete structures cast in spring have longer time to hydrate and are therefore denser and more resistant to chloride ingress when first subjected to deicing salts in winter than structures cast in autumn. Consequently, it is expected that a spring casting will have a longer service life....... This hypothesis is investigated in the present study by testing drilled cores from concrete cast in 2012 and 2013 on the Svendborgsund Bridge. The cores are subject to petrographic examination and mapping of chloride profiles. Moreover, chloride migration coefficients have been measured. The study shows...

Producing ammonium chloride from coal or shale

Energy Technology Data Exchange (ETDEWEB)

Christenson, O L

1921-02-25

Process of producing ammonium chloride consists of mixing the substance to be treated with a chloride of an alkali or alkaline earth metal, free silica, water and free hydrochloric acid, heating the mixture until ammonium chloride distills off and collecting the ammonium chloride.

Calculated Third Order Rate Constants for Interpreting the Mechanisms of Hydrolyses of Chloroformates, Carboxylic Acid Halides, Sulfonyl Chlorides and Phosphorochloridates

Directory of Open Access Journals (Sweden)

T. William Bentley

2015-05-01

Full Text Available Hydrolyses of acid derivatives (e.g., carboxylic acid chlorides and fluorides, fluoro- and chloroformates, sulfonyl chlorides, phosphorochloridates, anhydrides exhibit pseudo-first order kinetics. Reaction mechanisms vary from those involving a cationic intermediate (SN1 to concerted SN2 processes, and further to third order reactions, in which one solvent molecule acts as the attacking nucleophile and a second molecule acts as a general base catalyst. A unified framework is discussed, in which there are two reaction channels—an SN1-SN2 spectrum and an SN2-SN3 spectrum. Third order rate constants (k3 are calculated for solvolytic reactions in a wide range of compositions of acetone-water mixtures, and are shown to be either approximately constant or correlated with the Grunwald-Winstein Y parameter. These data and kinetic solvent isotope effects, provide the experimental evidence for the SN2-SN3 spectrum (e.g., for chloro- and fluoroformates, chloroacetyl chloride, p-nitrobenzoyl p-toluenesulfonate, sulfonyl chlorides. Deviations from linearity lead to U- or V-shaped plots, which assist in the identification of the point at which the reaction channel changes from SN2-SN3 to SN1-SN2 (e.g., for benzoyl chloride.

21 CFR 173.400 - Dimethyldialkylammonium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Dimethyldialkylammonium chloride. 173.400 Section... HUMAN CONSUMPTION Specific Usage Additives § 173.400 Dimethyldialkylammonium chloride. Dimethyldialkylammonium chloride may be safely used in food in accordance with the following prescribed conditions: (a...

Functional characterization of a prokaryotic Kir channel.

Science.gov (United States)

Enkvetchakul, Decha; Bhattacharyya, Jaya; Jeliazkova, Iana; Groesbeck, Darcy K; Cukras, Catherine A; Nichols, Colin G

2004-11-05

The Kir gene family encodes inward rectifying K+ (Kir) channels that are widespread and critical regulators of excitability in eukaryotic cells. A related gene family (KirBac) has recently been identified in prokaryotes. While a crystal structure of one member, Kir-Bac1.1, has been solved, there has been no functional characterization of any KirBac gene products. Here we present functional characterization of KirBac1.1 reconstituted in liposomes. Utilizing a 86Rb+ uptake assay, we demonstrate that KirBac1.1 generates a K+ -selective permeation path that is inhibited by extraliposomal Ba2+ and Ca2+ ions. In contrast to KcsA (an acid-activated bacterial potassium channel), KirBac1.1 is inhibited by extraliposomal acid (pKa approximately 6). This characterization of KirBac1.1 activity now paves the way for further correlation of structure and function in this model Kir channel.

Microbial reductive dehalogenation of vinyl chloride

Science.gov (United States)

Spormann, Alfred M [Stanford, CA; Muller, Jochen A [Baltimore, MD; Rosner, Bettina M [Berlin, DE; Von Abendroth, Gregory [Nannhein, DE; Meshulam-Simon, Galit [Los Altos, CA; McCarty, Perry L [Stanford, CA

2011-11-22

Compositions and methods are provided that relate to the bioremediation of chlorinated ethenes, particularly the bioremediation of vinyl chloride by Dehalococcoides-like organisms. An isolated strain of bacteria, Dehalococcoides sp. strain VS, that metabolizes vinyl chloride is provided; the genetic sequence of the enzyme responsible for vinyl chloride dehalogenation; methods of assessing the capability of endogenous organisms at an environmental site to metabolize vinyl chloride; and a method of using the strains of the invention for bioremediation.

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

Science.gov (United States)

Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

2017-10-15

Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels ( I h currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal , Lefty , and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

21 CFR 522.1862 - Sterile pralidoxime chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile pralidoxime chloride. 522.1862 Section 522....1862 Sterile pralidoxime chloride. (a) Chemical name. 2-Formyl-1-methylpyridinium chloride oxime. (b) Specifications. Sterile pralidoxime chloride is packaged in vials. Each vial contains 1 gram of sterile...

49 CFR 173.322 - Ethyl chloride.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must be...

Preparation of pure anhydrous rare earth chlorides

International Nuclear Information System (INIS)

Bel'kova, N.L.; Slastenova, N.M.; Batyaev, I.M.; Solov'ev, M.A.

1979-01-01

A method has been suggested for obtaining extra-pure anhydrous REE chlorides by chloridizing corresponding oxalates by chlorine in a fluid bed, the chloridizing agents being diluted by an inert gas in a ratio of 2-to-1. The method is applicable to the manufacture of quality chlorides not only of light, but also of heavy REE. Neodymium chloride has an excited life of tau=30 μs, this evidencing the absence of the damping impurities

Crystal field influence on vibration spectra: anhydrous uranyl chloride and dihydroxodiuranyl chloride tetrahydrate

International Nuclear Information System (INIS)

Perrin, Andre; Caillet, Paul

1976-01-01

Vibrational spectra of anhydrous uranyl chloride UO 2 Cl 2 and so called basic uranyl chloride: dihydroxodiuranyl chloride tetrahydrate /UO 2 (OH) 2 UO 2 /Cl 2 (H 2 O) 4 are reported. Factor group method analysis leads for the first time to complete and comprehensive interpretation of their spectra. Two extreme examples of crystal field influence on vibrational spectra are pointed out: for UO 2 Cl 2 , one is unable to explain spectra without taking into account all the elements of primitive crystalline cell, whilst for dihydroxodiuranyl dichloride tetrahydrate the crystal packing has very little effect on vibrational spectra [fr

Chloride Transport in Undersea Concrete Tunnel

Directory of Open Access Journals (Sweden)

Yuanzhu Zhang

2016-01-01

Full Text Available Based on water penetration in unsaturated concrete of underwater tunnel, a diffusion-advection theoretical model of chloride in undersea concrete tunnel was proposed. The basic parameters including porosity, saturated hydraulic conductivity, chloride diffusion coefficient, initial water saturation, and moisture retention function of concrete specimens with two water-binder ratios were determined through lab-scale experiments. The variation of chloride concentration with pressuring time, location, solution concentration, initial saturation, hydraulic pressure, and water-binder ratio was investigated through chloride transport tests under external water pressure. In addition, the change and distribution of chloride concentration of isothermal horizontal flow were numerically analyzed using TOUGH2 software. The results show that chloride transport in unsaturated concrete under external water pressure is a combined effect of diffusion and advection instead of diffusion. Chloride concentration increased with increasing solution concentration for diffusion and increased with an increase in water pressure and a decrease in initial saturation for advection. The dominant driving force converted with time and saturation. When predicting the service life of undersea concrete tunnel, it is suggested that advection is taken into consideration; otherwise the durability tends to be unsafe.

21 CFR 582.3845 - Stannous chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Stannous chloride. 582.3845 Section 582.3845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL....3845 Stannous chloride. (a) Product. Stannous chloride. (b) Tolerance. This substance is generally...

7 CFR 58.434 - Calcium chloride.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Calcium chloride. 58.434 Section 58.434 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.434 Calcium chloride. Calcium chloride, when used, shall meet the requirements of the Food...

21 CFR 582.6193 - Calcium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium chloride. 582.6193 Section 582.6193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This substance is generally...

Anion-sensitive regions of L-type CaV1.2 calcium channels expressed in HEK293 cells.

Directory of Open Access Journals (Sweden)

Norbert Babai

2010-01-01

Full Text Available L-type calcium currents (I(Ca are influenced by changes in extracellular chloride, but sites of anion effects have not been identified. Our experiments showed that CaV1.2 currents expressed in HEK293 cells are strongly inhibited by replacing extracellular chloride with gluconate or perchlorate. Variance-mean analysis of I(Ca and cell-attached patch single channel recordings indicate that gluconate-induced inhibition is due to intracellular anion effects on Ca(2+ channel open probability, not conductance. Inhibition of CaV1.2 currents produced by replacing chloride with gluconate was reduced from approximately 75%-80% to approximately 50% by omitting beta subunits but unaffected by omitting alpha(2delta subunits. Similarly, gluconate inhibition was reduced to approximately 50% by deleting an alpha1 subunit N-terminal region of 15 residues critical for beta subunit interactions regulating open probability. Omitting beta subunits with this mutant alpha1 subunit did not further diminish inhibition. Gluconate inhibition was unchanged with expression of different beta subunits. Truncating the C terminus at AA1665 reduced gluconate inhibition from approximately 75%-80% to approximately 50% whereas truncating it at AA1700 had no effect. Neutralizing arginines at AA1696 and 1697 by replacement with glutamines reduced gluconate inhibition to approximately 60% indicating these residues are particularly important for anion effects. Expressing CaV1.2 channels that lacked both N and C termini reduced gluconate inhibition to approximately 25% consistent with additive interactions between the two tail regions. Our results suggest that modest changes in intracellular anion concentration can produce significant effects on CaV1.2 currents mediated by changes in channel open probability involving beta subunit interactions with the N terminus and a short C terminal region.

Chloride removal from plutonium alloy

International Nuclear Information System (INIS)

Holcomb, H.P.

1983-01-01

SRP is evaluating a program to recover plutonium from a metallic alloy that will contain chloride salt impurities. Removal of chloride to sufficiently low levels to prevent damaging corrosion to canyon equipment is feasible as a head-end step following dissolution. Silver nitrate and mercurous nitrate were each successfully used in laboratory tests to remove chloride from simulated alloy dissolver solution containing plutonium. Levels less than 10 ppM chloride were achieved in the supernates over the precipitated and centrifuged insoluble salts. Also, less than 0.05% loss of plutonium in the +3, +4, or +6 oxidation states was incurred via precipitate carrying. These results provide impetus for further study and development of a plant-scale process to recover plutonium from metal alloy at SRP

21 CFR 173.255 - Methylene chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methylene chloride. 173.255 Section 173.255 Food... Solvents, Lubricants, Release Agents and Related Substances § 173.255 Methylene chloride. Methylene chloride may be present in food under the following conditions: (a) In spice oleoresins as a residue from...

21 CFR 182.8252 - Choline chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Choline chloride. 182.8252 Section 182.8252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized as...

21 CFR 582.5446 - Manganese chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Manganese chloride. 582.5446 Section 582.5446 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5446 Manganese chloride. (a) Product. Manganese chloride. (b) Conditions of use. This...

21 CFR 582.5252 - Choline chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Choline chloride. 582.5252 Section 582.5252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This...

21 CFR 582.5622 - Potassium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium chloride. 582.5622 Section 582.5622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use. This...

21 CFR 582.1193 - Calcium chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium chloride. 582.1193 Section 582.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1193 Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This substance...

Skeletal Muscle Na+ Channel Disorders

Directory of Open Access Journals (Sweden)

Dina eSimkin

2011-10-01

Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

21 CFR 582.5985 - Zinc chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is...

21 CFR 182.8985 - Zinc chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc chloride. 182.8985 Section 182.8985 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is generally recognized as safe when used in...

21 CFR 172.180 - Stannous chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Stannous chloride. 172.180 Section 172.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Preservatives § 172.180 Stannous chloride. The food additive stannous chloride may be safely used for color...

Overexpression of afsR and Optimization of Metal Chloride to Improve Lomofungin Production in Streptomyces lomondensis S015.

Science.gov (United States)

Wang, Wei; Wang, Huasheng; Hu, Hongbo; Peng, Huasong; Zhang, Xuehong

2015-05-01

As a global regulatory gene in Streptomyces, afsR can activate the biosynthesis of many secondary metabolites. The effect of afsR on the biosynthesis of a phenazine metabolite, lomofungin, was studied in Streptomyces lomondensis S015. There was a 2.5-fold increase of lomofungin production in the afsR-overexpressing strain of S. lomondensis S015 N1 compared with the wild-type strain. Meanwhile, the transcription levels of afsR and two important genes involved in the biosynthesis of lomofungin (i.e., phzC and phzE) were significantly upregulated in S. lomondensis S015 N1. The optimization of metal chlorides was investigated to further increase the production of lomofungin in the afsR-overexpressing strain. The addition of different metal chlorides to S. lomondensis S015 N1 cultivations showed that CaCl2, FeCl2, and MnCl2 led to an increase in lomofungin biosynthesis. The optimum concentrations of these metal chlorides were obtained using response surface methodology. CaCl2 (0.04 mM), FeCl2 (0.33 mM), and MnCl2 (0.38 mM) gave a maximum lomofungin production titer of 318.0 ± 10.7 mg/l, which was a 4.1-fold increase compared with that of S. lomondensis S015 N1 without the addition of a metal chloride. This work demonstrates that the biosynthesis of phenazine metabolites can be induced by afsR. The results also indicate that metal chlorides addition might be a simple and useful strategy for improving the production of other phenazine metabolites in Streptomyces.

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

OpenAIRE

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant.The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques o...

Ropivacaine-Induced Contraction Is Attenuated by Both Endothelial Nitric Oxide and Voltage-Dependent Potassium Channels in Isolated Rat Aortae

Directory of Open Access Journals (Sweden)

Seong-Ho Ok

2013-01-01

Full Text Available This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, the neuronal NOS inhibitor Nω-propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP, the calcium-activated potassium channel inhibitor tetraethylammonium (TEA, the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, Nω-propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

Novel transcripts of the estrogen receptor α gene in channel catfish

Science.gov (United States)

Patino, Reynaldo; Xia, Zhenfang; Gale, William L.; Wu, Chunfa; Maule, Alec G.; Chang, Xiaotian

2000-01-01

Complementary DNA libraries from liver and ovary of an immature female channel catfish were screened with a homologous ERα cDNA probe. The hepatic library yielded two new channel catfish ER cDNAs that encode N-terminal ERα variants of different sizes. Relative to the catfish ERα (medium size; 581 residues) previously reported, these new cDNAs encode Long-ERα (36 residues longer) and Short-ERα (389 residues shorter). The 5′-end of Long-ERα cDNA is identical to that of Medium-ERα but has an additional 503-bp segment with an upstream, in-frame translation-start codon. Recombinant Long-ERα binds estrogen with high affinity (Kd = 3.4 nM), similar to that previously reported for Medium-ERα but lower than reported for catfish ERβ. Short-ERα cDNA encodes a protein that lacks most of the receptor protein and does not bind estrogen. Northern hybridization confirmed the existence of multiple hepatic ERα RNAs that include the size range of the ERα cDNAs obtained from the libraries as well as additional sizes. Using primers for RT-PCR that target locations internal to the protein-coding sequence, we also established the presence of several ERα cDNA variants with in-frame insertions in the ligand-binding and DNA-binding domains and in-frame or out-of-frame deletions in the ligand-binding domain. These internal variants showed patterns of expression that differed between the ovary and liver. Further, the ovarian library yielded a full-length, ERα antisense cDNA containing a poly(A) signal and tail. A limited survey of histological preparations from juvenile catfish by in situ hybridization using directionally synthesized cRNA probes also suggested the expression of ERα antisense RNA in a tissue-specific manner. In conclusion, channel catfish seemingly have three broad classes of ERα mRNA variants: those encoding N-terminal truncated variants, those encoding internal variants (including C-terminal truncated variants), and antisense mRNA. The sense variants may

21 CFR 184.1446 - Manganese chloride.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Manganese chloride. 184.1446 Section 184.1446 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Specific Substances Affirmed as GRAS § 184.1446 Manganese chloride. (a) Manganese chloride (MnCl2·4H2O, CAS...

Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC Gene in Aedes albopictus.

Directory of Open Access Journals (Sweden)

Jiabao Xu

2016-05-01

Full Text Available Aedes albopictus is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr. Previous studies reported various mutations in the voltage-gated sodium channel (VGSC gene, but the spatial distribution of kdr mutations in Ae. albopictus has not been systematically examined, and the association between kdr mutation and phenotypic resistance has not been established.A total of 597 Ae. albopictus individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between kdr mutations and phenotypic resistance was tested.A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S was detected in southern China and Florida, USA with a frequency ranging from 9.5-22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between kdr mutations with deltamethrin resistance was established in these two populations.Two novel kdr

Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC) Gene in Aedes albopictus.

Science.gov (United States)

Xu, Jiabao; Bonizzoni, Mariangela; Zhong, Daibin; Zhou, Guofa; Cai, Songwu; Li, Yiji; Wang, Xiaoming; Lo, Eugenia; Lee, Rebecca; Sheen, Roger; Duan, Jinhua; Yan, Guiyun; Chen, Xiao-Guang

2016-05-01

Aedes albopictus is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). Previous studies reported various mutations in the voltage-gated sodium channel (VGSC) gene, but the spatial distribution of kdr mutations in Ae. albopictus has not been systematically examined, and the association between kdr mutation and phenotypic resistance has not been established. A total of 597 Ae. albopictus individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between kdr mutations and phenotypic resistance was tested. A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T) was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S) was detected in southern China and Florida, USA with a frequency ranging from 9.5-22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between kdr mutations with deltamethrin resistance was established in these two populations. Two novel kdr mutations, I1532T

Downregulation of Kv7.4 channel activity in primary and secondary hypertension

DEFF Research Database (Denmark)

Jepps, Thomas Andrew; Chadha, Preet S; Davis, Alison J

2011-01-01

Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of...... structurally different activators of Kv7.2 through Kv7.5 channels (BMS-204352, S-1, and retigabine) on blood vessels from normotensive and hypertensive animals.......Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of 3...

Method for preparation of melts of alkali metal chlorides with highly volatile polyvalent metal chlorides

International Nuclear Information System (INIS)

Salyulev, A.B.; Kudyakov, V.Ya.

1990-01-01

A method for production of alkali metal (Cs, Rb, K) chloride melts with highly volatile polyvalent metal chlorides is suggested. The method consists, in saturation of alkali metal chlorides, preheated to the melting point, by volatile component vapours (titanium tetrachloride, molybdenum or tantalum pentachloride) in proportion, corresponding to the composition reguired. The saturation is realized in an evacuated vessel with two heating areas for 1-1.5 h. After gradual levelling of temperature in both areas the product is rapidly cooled. 1 fig.; 1 tab

CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

Science.gov (United States)

Blaisdell, Carol J; Howard, Timothy D; Stern, Augustus; Bamford, Penelope; Bleecker, Eugene R; Stine, O Colin

2004-01-01

Background Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity. PMID:15507145

CLC-2 single nucleotide polymorphisms (SNPs as potential modifiers of cystic fibrosis disease severity

Directory of Open Access Journals (Sweden)

Bleecker Eugene R

2004-10-01

Full Text Available Abstract Background Cystic fibrosis (CF lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1 > 70% and Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity.

Determination of Chloride Content in Cementitious Materials : From Fundamental Aspects to Application of Ag/AgCl Chloride Sensors

NARCIS (Netherlands)

Pargar, F.; Koleva, D.A.; van Breugel, K.

2017-01-01

This paper reports on the advantages and drawbacks of available test methods for the determination of chloride content in cementitious materials in general, and the application of Ag/AgCl chloride sensors in particular. The main factors that affect the reliability of a chloride sensor are presented.

Calcium-Activated Cl- Channel: Insights on the Molecular Identity in Epithelial Tissues.

Science.gov (United States)

Rottgen, Trey S; Nickerson, Andrew J; Rajendran, Vazhaikkurichi M

2018-05-10

Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca 2+ -activated Cl − secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca 2+ -activated Cl − channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca 2+ -sensitivity of the channel. This review will also discuss the role of TMEM16A in epithelial physiology and potential associated-pathophysiology. This will include discussion of developed knockout models that have provided much needed insight on the functional localization of TMEM16A in several epithelial tissues. Finally, this review will examine the implications of the identification of TMEM16A as it pertains to potential novel therapies in several pathologies.

Synthesis and characterization of N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chloride for potential application in gene delivery.

Science.gov (United States)

Xiao, Bo; Wan, Ying; Wang, Xiaoyu; Zha, Qichen; Liu, Haoming; Qiu, Zhiye; Zhang, Shengmin

2012-03-01

A series of N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chloride (HTCC) samples with various degrees of quaternization ranging from 12.4 to 43.7% was synthesized. The structures and properties of HTCC were investigated by FT-IR, (1)H NMR, conductometric titration and XRD analysis. It was found that HTCC had a more amorphous structure than chitosan. HTCC samples showed significantly lower cytotoxicity than polyethyleneimine in HepG2 and HeLa cell lines. The samples spontaneously formed complexes with pGL3 luciferase plasmid. These complexes had desirable particle sizes (160-300 nm) and zeta potentials (10.8-18.7 mV) when the weight ratios of HTCC to plasmid altered in the range of 3:1-20:1. In vitro gene transfection results indicated that HTCC had significantly high transfection efficiency compared with chitosan for delivering pGL3 luciferase plasmid to HeLa cells. The results suggest that HTCC could be a promising non-viral vector for safe and efficient DNA delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin

DEFF Research Database (Denmark)

Lynagh, Timothy; Lynch, Joseph W.

2012-01-01

Ivermectin is an anthelmintic drug that works by inhibiting neuronal activity and muscular contractility in arthropods and nematodes. It works by activating glutamate-gated chloride channels (GluClRs) at nanomolar concentrations. These receptors, found exclusively in invertebrates, belong to the ...... to the neurotransmitter binding site, thus suggesting a mechanism by which ivermectin potentiates neurotransmitter-gated currents. Together, this information provides new insights into the mechanisms of action of this important drug.......) to its site. Several lines of evidence suggest that ivermectin opens the channel pore via a structural change distinct from that induced by the neurotransmitter agonist. Conformational changes occurring at locations distant from the pore can be probed using voltage-clamp fluorometry (VCF), a technique...

Genetic disorders of transporters/channels in the inner ear and their relation to the kidney.

NARCIS (Netherlands)

Peters, T.A.; Monnens, L.A.H.; Cremers, C.W.R.J.; Curfs, J.H.A.J.

2004-01-01

Inner ear physiology is reviewed with emphasis on features common to renal physiology. Genetic disorders in transporters/channels for chloride (ClC-K), bicarbonate (Cl(-)/HCO(3)(-) exchanger), protons (H(+)-ATPase), sodium (ENaC, NKKC1, NBC3, NHE3), potassium (KCNQ1/KCNE1, Kcc4), and water (AQP4) in

Micellar solubilization in strongly interacting binary surfactant systems. [Binary surfactant systems of: dodecyltrimethylammonium chloride + sodium dodecyl sulfate; benzyldimethyltetradecylammonium chloride + tetradecyltrimethylammonium chloride

Energy Technology Data Exchange (ETDEWEB)

Treiner, C. (Universite Pierre et Marie Curie, Paris (France)); Nortz, M.; Vaution, C. (Faculte de Pharmacie de Paris-sud, Chatenay-Malabry (France))

1990-07-01

The apparent partition coefficient P of barbituric acids between micelles and water has been determined in mixed binary surfactant solutions from solubility measurements in the whole micellar composition range. The binary systems chosen ranged from the strongly interacting system dodecyltrimethylammonium chloride + sodium dodecyl sulfate to weakly interacting systems such as benzyldimethyltetradecylammonium chloride + tetradecyltrimethyammonium chloride. In all cases studied, mixed micelle formation is unfavorable to micellar solubilization. A correlation is found between the unlike surfactants interaction energy, as measured by the regular solution parameter {beta} and the solute partition coefficient change upon surfactant mixing. By use of literature data on micellar solubilization in binary surfactant solutions, it is shown that the change of P for solutes which are solubilized by surface adsorption is generally governed by the sign and amplitude of the interaction parameter {beta}.

Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

DEFF Research Database (Denmark)

Jensen, B L; Skøtt, O

1996-01-01

or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate....... Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated...

Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat.

Science.gov (United States)

Schuhmacher, Laura-Nadine; Smith, Ewan St John

2016-12-13

Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

Thallium-201 chloride dynamic analysis using thallium-201 chloride and sodium iodide-131 thyroid subtraction scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Morimoto, Setsuo; Hiraki, Yoshio; Togami, Izumi [Okayama Univ. (Japan). School of Medicine

1984-10-01

The mechanism of /sup 201/Tl chloride accumulation is unclear in thyroid gland and thyroid tumor. This report examines 108 patients that received thyroid scintigraphy examinations with both /sup 201/Tl chloride and sodium /sup 131/I. The patients were diagnosed clinically and histologically whenever possible. The ROI were obtained by subtraction imaging with both isotopes and by subtraction positive and negative areas of imaging. Dynamic curves were obtained for /sup 201/Tl chloride per square unit of each ROI. The dynamic curve in the radioiodide-accumulated area was examined. The data indicate that the clearance rate of /sup 201/Tl chloride (T/sub 15/) was correlated with the sodium /sup 131/I uptake rate at 24 h (r=0.70).

Modified chloride diffusion model for concrete under the coupling effect of mechanical load and chloride salt environment

Science.gov (United States)

Lei, Mingfeng; Lin, Dayong; Liu, Jianwen; Shi, Chenghua; Ma, Jianjun; Yang, Weichao; Yu, Xiaoniu

2018-03-01

For the purpose of investigating lining concrete durability, this study derives a modified chloride diffusion model for concrete based on the odd continuation of boundary conditions and Fourier transform. In order to achieve this, the linear stress distribution on a sectional structure is considered, detailed procedures and methods are presented for model verification and parametric analysis. Simulation results show that the chloride diffusion model can reflect the effects of linear stress distribution of the sectional structure on the chloride diffusivity with reliable accuracy. Along with the natural environmental characteristics of practical engineering structures, reference value ranges of model parameters are provided. Furthermore, a chloride diffusion model is extended for the consideration of multi-factor coupling of linear stress distribution, chloride concentration and diffusion time. Comparison between model simulation and typical current research results shows that the presented model can produce better considerations with a greater universality.

Enthalpic interactions of N-glycylglycine with xylitol in aqueous sodium chloride and potassium chloride solutions at T = 298.15 K

International Nuclear Information System (INIS)

Liu Min; Wang Lili; Zhu Lanying; Li Hui; Sun Dezhi; Di Youying; Li Linwei

2010-01-01

The mixing enthalpies of N-glycylglycine with xylitol and their respective enthalpies of dilution in aqueous sodium chloride and potassium chloride solutions have been determined by using flow-mix isothermal microcalorimetry at the temperature of 298.15 K. These experimental results have been used to determine the heterotactic enthalpic interaction coefficients (h xy , h xxy , and h xyy ) according to the McMillan-Mayer theory. It has been found that the heterotactic enthalpic pairwise interaction coefficients h xy between N-glycylglycine and xylitol in aqueous sodium chloride and potassium chloride solutions are negative and become less negative with an increase in the molality of sodium chloride or potassium chloride. The results are discussed in terms of solute-solute and solute-solvent interactions.

Enthalpic interactions of N-glycylglycine with xylitol in aqueous sodium chloride and potassium chloride solutions at T = 298.15 K

Energy Technology Data Exchange (ETDEWEB)

Liu Min, E-mail: panpanliumin@163.co [College of Chemistry and Chemical Engineering, Liao Cheng University, Liaocheng, Shandong 252059 (China); Wang Lili [College of Chemistry and Chemical Engineering, Liao Cheng University, Liaocheng, Shandong 252059 (China); Zhu Lanying [College of Life Science and Bioengineering, Liao Cheng University, Liaocheng, Shandong 252059 (China); Li Hui; Sun Dezhi; Di Youying; Li Linwei [College of Chemistry and Chemical Engineering, Liao Cheng University, Liaocheng, Shandong 252059 (China)

2010-07-15

The mixing enthalpies of N-glycylglycine with xylitol and their respective enthalpies of dilution in aqueous sodium chloride and potassium chloride solutions have been determined by using flow-mix isothermal microcalorimetry at the temperature of 298.15 K. These experimental results have been used to determine the heterotactic enthalpic interaction coefficients (h{sub xy}, h{sub xxy}, and h{sub xyy}) according to the McMillan-Mayer theory. It has been found that the heterotactic enthalpic pairwise interaction coefficients h{sub xy} between N-glycylglycine and xylitol in aqueous sodium chloride and potassium chloride solutions are negative and become less negative with an increase in the molality of sodium chloride or potassium chloride. The results are discussed in terms of solute-solute and solute-solvent interactions.

Renal abnormalities in congenital chloride diarrhea

International Nuclear Information System (INIS)

Al-Hamad, Nadia M.; Al-Eisa, Amal A.

2004-01-01

Congenital chloride diarrhea CLD is a rare autosomal recessive disorder caused by a defect in the chloride/ bicarbonate exchange in the ileum and colon. It is characterized by watery diarrhea, abdominal distension, hypochloremic hypokalemic metabolic alkalosis with high fecal content of chloride >90 mmol/l. We report 3 patients with CLD associated with various renal abnormalities including chronic renal failure secondary to renal hypoplasia, nephrocalcinosis and congenital nephrotic syndrome. (author)

TRPV6 channels.

Science.gov (United States)

Fecher-Trost, Claudia; Weissgerber, Petra; Wissenbach, Ulrich

2014-01-01

TRPV6 (former synonyms ECAC2, CaT1, CaT-like) displays several specific features which makes it unique among the members of the mammalian Trp gene family (1) TRPV6 (and its closest relative, TRPV5) are the only highly Ca(2+)-selective channels of the entire TRP superfamily (Peng et al. 1999; Wissenbach et al. 2001; Voets et al. 2004). (2) Translation of Trpv6 initiates at a non-AUG codon, at ACG, located upstream of the annotated AUG, which is not used for initiation (Fecher-Trost et al. 2013). The ACG codon is nevertheless decoded by methionine. Not only a very rare event in eukaryotic biology, the full-length TRPV6 protein existing in vivo comprises an amino terminus extended by 40 amino acid residues compared to the annotated truncated TRPV6 protein which has been used in most studies on TRPV6 channel activity so far. (In the following numbering occurs according to this full-length protein, with the numbers of the so far annotated truncated protein in brackets). (3) Only in humans a coupled polymorphism of Trpv6 exists causing three amino acid exchanges and resulting in an ancestral Trpv6 haplotype and a so-called derived Trpv6 haplotype (Wissenbach et al. 2001). The ancestral allele encodes the amino acid residues C197(157), M418(378) and M721(681) and the derived alleles R197(157), V418(378) and T721(681). The ancestral haplotype is found in all species, the derived Trpv6 haplotype has only been identified in humans, and its frequency increases with the distance to the African continent. Apparently the Trpv6 gene has been a strong target for selection in humans, and its derived variant is one of the few examples showing consistently differences to the orthologues genes of other primates (Akey et al. 2004, 2006; Stajich and Hahn 2005; Hughes et al. 2008). (4) The Trpv6 gene expression is significantly upregulated in several human malignancies including the most common cancers, prostate and breast cancer (Wissenbach et al. 2001; Zhuang et al. 2002; Fixemer et al

Study on the chloride migration coefficient obtained following different Rapid Chloride Migration (RCM) test guidelines

NARCIS (Netherlands)

Spiesz, P.R.; Brouwers, H.J.H.; Uzoegbo, H.C.; Schmidt, W.

2013-01-01

This work presents the differences in the available Rapid Chloride Migration (RCM) test guidelines, and their influence on the values of the chloride migration coefficients DRCM, obtained following these guidelines. It is shown that the differences between the guidelines are significant and concern

Mapping the spatial distribution of chloride deposition across Australia

Science.gov (United States)

Davies, P. J.; Crosbie, R. S.

2018-06-01

The high solubility and conservative behaviour of chloride make it ideal for use as an environmental tracer of water and salt movement through the hydrologic cycle. For such use the spatial distribution of chloride deposition in rainfall at a suitable scale must be known. A number of authors have used point data acquired from field studies of chloride deposition around Australia to construct relationships to characterise chloride deposition as a function of distance from the coast; these relationships have allowed chloride deposition to be interpolated in different regions around Australia. In this paper we took this a step further and developed a chloride deposition map for all of Australia which includes a quantification of uncertainty. A previously developed four parameter model of chloride deposition as a function of distance from the coast for Australia was used as the basis for producing a continental scale chloride deposition map. Each of the four model parameters were made spatially variable by creating parameter surfaces that were interpolated using a pilot point regularisation approach within a parameter estimation software. The observations of chloride deposition were drawn from a literature review that identified 291 point measurements of chloride deposition over a period of 80 years spread unevenly across all Australian States and Territories. A best estimate chloride deposition map was developed from the resulting surfaces on a 0.05 degree grid. The uncertainty in the chloride deposition map was quantified as the 5th and 95th percentile of 1000 calibrated models produced via Null Space Monte Carlo analysis and the spatial variability of chloride deposition across the continent was consistent with landscape morphology. The temporal variability in chloride deposition on a decadal scale was investigated in the Murray-Darling Basin, this highlighted the need for long-term monitoring of chloride deposition if the uncertainty of the continental scale map is

BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

Science.gov (United States)

Gao, Mingyong; Lu, Paul; Lynam, Dan; Bednark, Bridget; Campana, W. Marie; Sakamoto, Jeff; Tuszynski, Mark

2016-12-01

Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.

Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

Science.gov (United States)

Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

2016-07-01

The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

Relation between chloride exchange diffusion and a conductive chloride pathway across the isolated skin of the toad (Bufo bufo)

DEFF Research Database (Denmark)

Kristensen, P; Larsen, Erik Hviid

1978-01-01

Substitution of chloride in the outside bathing medium of the toad skin with bromide, iodide, nitrate and sulphate leads to a reduction in the apparent exchange diffusion of chloride across this tissue, and also to a reduction of the chloride current recorded during hyperpolarization. A series...

Channel opening of γ-aminobutyric acid receptor from rat brain: molecular mechanisms of the receptor responses

International Nuclear Information System (INIS)

Cash, D.J.; Subbarao, K.

1987-01-01

The function of γ-aminobutyric acid (GABA) receptors, which mediate transmembrane chloride flux, can be studied by use of 36 Cl - isotope tracer with membrane from mammalian brain by quench-flow technique, with reaction times that allow resolution of the receptor desensitization rates from the ion flux rates. The rates of chloride exchange into the vesicles in the absence and presence of GABA were characterized with membrane from rat cerebral cortex. Unspecific 36 Cl - influx was completed in three phases of ca. 3% (t/sub 1/2/ = 0.6 s), 56% (t/sub 1/2 = 82 s), and 41% (t/sub 1/2 = 23 min). GABA-mediated, specific chloride exchange occurred with 6.5% of the total vesicular internal volume. The GABA-dependent 36 Cl - influx proceeded in two phases, each progressively slowed by desensitization. The measurements supported the presence of two distinguishable active GABA receptors on the same membrane mediating chloride exchange into the vesicles. The half-response concentrations were similar for both receptors. The two receptors were present in the activity ratio of ca. 4/1, similar to the ratio of low affinity to high-affinity GABA sites found in ligand binding experiments. The desensitization rates have a different dependence on GABA concentration than the channel-opening equilibria. For both receptors, the measurements over a 2000-fold GABA concentration range required a minimal mechanism involving the occupation of both of the two GABA binding sites for significant channel opening; then the receptors were ca. 80% open. Similarly for both receptors, desensitization was mediated by a different pair of binding sites, although desensitization with only one ligand molecule bound could occur at a 20-fold slower rate

Identification of an alternative knockdown resistance (kdr)-like mutation, M918L, and a novel mutation, V1010A, in the Thrips tabaci voltage-gated sodium channel gene.

Science.gov (United States)

Wu, Meixiang; Gotoh, Hiroki; Waters, Timothy; Walsh, Douglas B; Lavine, Laura Corley

2014-06-01

Knockdown resistance (kdr) has been identified as a main mechanism against pyrethroid insecticides in many arthropod pests including in the onion thrips, Thrips tabaci. To characterize and identify pyrethroid-resistance in onion thrips in Washington state, we conducted insecticide bioassays and sequenced a region of the voltage gated sodium channel gene from several different T. tabaci populations. Field collected Thrips tabaci were found to have large variations in resistance to the pyrethroid insecticide lambda-cyhalothrin. We identified two single nucleotide substitutions in our analysis of a partial sequence of the T. tabaci voltage-gated sodium channel gene. One mutation resulted in the non-synonymous substitution of methionine with leucine (M918L), which is well known to be responsible for super knockdown resistance in some pest species. Another non-synonymous substitution, a valine (GTT) to alanine (GCT) replacement at amino acid 1010 (V1010A) was identified in our study and was associated with lambda-cyhalothrin resistance. We have characterized a known kdr mutation and identified a novel mutation in the voltage-gated sodium channel gene of Thrips tabaci associated with resistance to lambda-cyhalothrin. This gene region and these mutations are expected to be useful in the development of a diagnostic test to detect kdr resistance in many onion thrips populations. © 2013 Society of Chemical Industry.

Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion

Science.gov (United States)

House, Carrie D.; Vaske, Charles J.; Schwartz, Arnold M.; Obias, Vincent; Frank, Bryan; Luu, Truong; Sarvazyan, Narine; Irby, Rosalyn; Strausberg, Robert L.; Hales, Tim G.; Stuart, Joshua M.; Lee, Norman H.

2010-01-01

Voltage-gated Na+ channels (VGSCs) have been implicated in the metastatic potential of human breast, prostate and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Nav1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiological recordings. Na+ channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by siRNAs specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, where there was strong Nav1.5 protein staining in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion. PMID:20651255

Ion channels in plants.

Science.gov (United States)

Hedrich, Rainer

2012-10-01

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

Synthesis of carbon-14 labelled ethyl chloride

International Nuclear Information System (INIS)

Kanski, R.

1976-01-01

A new efficient method of synthesis of ethyl chloride (1,2- 14 C), based on the Ba 14 CO 3 and dry hydrogen chloride as starting materials has been developed and described. Addition of the hydrogen chloride to ethylene (1,2- 14 C), obtained from Ba 14 CO 3 , has been carried out in the presence of the AlCl 3 as catalyst. The outlined method leads to ethyl chloride (1,2- 14 C) of high specific activity. The radiochemical yield of the reaction based on the activity of barium carbonate used was 72%. (author)

[Bartter syndrome, severe rare orphan kidney disease: a step towards therapy through pharmacogenetic and epidemiological studies].

Science.gov (United States)

Conte, Elena; Imbrici, Paola; Sahbani, Dalila; Liantonio, Antonella; Conte, Diana

2018-05-01

Bartter syndromes (BS) types 1-5 are rare salt-losing tubulopathies presenting with overlapping clinical phenotypes including marked salt wasting and hypokalemia leading to polyuria, polydipsia, volume contraction, muscle weakness and growth retardation. These diseases are due to an impairment of sodium, potassium, chloride reabsorption caused by mutations in genes encoding for ion channel or transporters expressed in specific nephron tubule segments. Particularly, BS type 3 is a clinically heterogeneous form caused by mutations in CLCNKB gene which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. Specific therapy for BS is lacking and the only pharmacotherapy up today available is purely symptomatic and characterized by limiting side effects. The improvement of our understanding of the phenotype/genotype correlation and of the precise pathogenic mechanisms associated with BS type 3 as well as the pharmacological characterization of ClC-K chloride channels are fundamental to design therapies tailored upon patients' mutation. This mini review focused on recent studies representing relevant forward steps in the field as well as noteworthy examples of how basic and clinical research can cooperate to gain insight into the pathophysiology of this renal channelopathy, paving the way for a personalized therapy. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Ion channel electrophysiology via integrated planar patch-clamp chip with on-demand drug exchange.

Science.gov (United States)

Chen, Chang-Yu; Tu, Ting-Yuan; Jong, De-Shien; Wo, Andrew M

2011-06-01

Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays. Copyright © 2011 Wiley Periodicals, Inc.

A new sodium channel {alpha}-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2

Energy Technology Data Exchange (ETDEWEB)

Beckers, M.C.; Ernst, E.; Gros, P. [McGill Univ., Montreal (Canada)

1996-08-15

We have used a total of 27 AXB/BXA recombinant inbred mouse strains to determine the chromosomal location of a newly identified gene encoding an {alpha}-subunit isoform of the sodium channel from Schwann cells, Scn9a. Linkage analysis established that Scn9a mapped to the proximal segment of mouse chromosome 2. The segregation of restriction fragment length polymorphisms in 145 progeny from a Mus spretus x C57BL/6J backcross indicates that Scn9a is very tightly linked to Scn1a (gene encoding the type I sodium channel {alpha}-subunit of the brain) and forms part of a cluster of four Scna genes located on mouse chromosome 2. 17 refs., 1 fig., 3 tabs.

Chloride sensing by WNK1 kinase involves inhibition of autophosphorylation

Science.gov (United States)

Piala, Alexander T.; Moon, Thomas M.; Akella, Radha; He, Haixia; Cobb, Melanie H.; Goldsmith, Elizabeth J.

2014-01-01

WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase. Here, we found that chloride stabilizes the inactive conformation of WNK1, preventing kinase autophosphorylation and activation. Crystallographic studies of inactive WNK1 in the presence of chloride revealed that chloride binds directly to the catalytic site, providing a basis for the unique position of the catalytic lysine. Mutagenesis of the chloride binding site rendered the kinase less sensitive to inhibition of autophosphorylation by chloride, validating the binding site. Thus, these data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation. PMID:24803536

A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.

Science.gov (United States)

Ghosh, Borna; Tsao, Tzu-Wei; Czajkowski, Cynthia

2017-10-01

Pentameric ligand-gated ion channels (pLGICs) are the targets of several clinical and endogenous allosteric modulators including anesthetics and neurosteroids. Molecular mechanisms underlying allosteric drug modulation are poorly understood. Here, we constructed a chimeric pLGIC by fusing the extracellular domain (ECD) of the proton-activated, cation-selective bacterial channel GLIC to the transmembrane domain (TMD) of the human ρ1 chloride-selective GABA A R, and tested the hypothesis that drug actions are regulated locally in the domain that houses its binding site. The chimeric channels were proton-gated and chloride-selective demonstrating the GLIC ECD was functionally coupled to the GABAρ TMD. Channels were blocked by picrotoxin and inhibited by pentobarbital, etomidate and propofol. The point mutation, ρ TMD W328M, conferred positive modulation and direct gating by pentobarbital. The data suggest that the structural machinery mediating general anesthetic modulation resides in the TMD. Proton-activation and neurosteroid modulation of the GLIC-ρ chimeric channels, however, did not simply mimic their respective actions on GLIC and GABAρ revealing that across domain interactions between the ECD and TMD play important roles in determining their actions. Proton-induced current responses were biphasic suggesting that the chimeric channels contain an additional proton sensor. Neurosteroid modulation of the GLIC-ρ chimeric channels by the stereoisomers, 5α-THDOC and 5β-THDOC, were swapped compared to their actions on GABAρ indicating that positive versus negative neurosteroid modulation is not encoded solely in the TMD nor by neurosteroid isomer structure but is dependent on specific interdomain connections between the ECD and TMD. Our data reveal a new mechanism for shaping neurosteroid modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Slack, Slick, and Sodium-Activated Potassium Channels

Science.gov (United States)

Kaczmarek, Leonard K.

2013-01-01

The Slack and Slick genes encode potassium channels that are very widely expressed in the central nervous system. These channels are activated by elevations in intracellular sodium, such as those that occur during trains of one or more action potentials, or following activation of nonselective cationic neurotransmitter receptors such as AMPA receptors. This review covers the cellular and molecular properties of Slack and Slick channels and compares them with findings on the properties of sodium-activated potassium currents (termed KNa currents) in native neurons. Human mutations in Slack channels produce extremely severe defects in learning and development, suggesting that KNa channels play a central role in neuronal plasticity and intellectual function. PMID:24319675

Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations.

Directory of Open Access Journals (Sweden)

Bryan D Moyer

Full Text Available BACKGROUND: Using fungiform (FG and circumvallate (CV taste buds isolated by laser capture microdissection and analyzed using gene arrays, we previously constructed a comprehensive database of gene expression in primates, which revealed over 2,300 taste bud-associated genes. Bioinformatics analyses identified hundreds of genes predicted to encode multi-transmembrane domain proteins with no previous association with taste function. A first step in elucidating the roles these gene products play in gustation is to identify the specific taste cell types in which they are expressed. METHODOLOGY/PRINCIPAL FINDINGS: Using double label in situ hybridization analyses, we identified seven new genes expressed in specific taste cell types, including sweet, bitter, and umami cells (TRPM5-positive, sour cells (PKD2L1-positive, as well as other taste cell populations. Transmembrane protein 44 (TMEM44, a protein with seven predicted transmembrane domains with no homology to GPCRs, is expressed in a TRPM5-negative and PKD2L1-negative population that is enriched in the bottom portion of taste buds and may represent developmentally immature taste cells. Calcium homeostasis modulator 1 (CALHM1, a component of a novel calcium channel, along with family members CALHM2 and CALHM3; multiple C2 domains; transmembrane 1 (MCTP1, a calcium-binding transmembrane protein; and anoctamin 7 (ANO7, a member of the recently identified calcium-gated chloride channel family, are all expressed in TRPM5 cells. These proteins may modulate and effect calcium signalling stemming from sweet, bitter, and umami receptor activation. Synaptic vesicle glycoprotein 2B (SV2B, a regulator of synaptic vesicle exocytosis, is expressed in PKD2L1 cells, suggesting that this taste cell population transmits tastant information to gustatory afferent nerve fibers via exocytic neurotransmitter release. CONCLUSIONS/SIGNIFICANCE: Identification of genes encoding multi-transmembrane domain proteins

Preparation of Carbon-Chitosan-Polyvinyl Chloride (CC-PVC) Material and its Application to Electrochemical Degradation of Methylene Blue in Sodium Chloride Solution

Science.gov (United States)

Riyanto; Prawidha, A. D.

2018-01-01

Electrochemical degradation of methylene blue using Carbon-Chitosan-Polyvinyl Chloride (CC-PVC) electrode in sodium chloride have been done. The aim of this work was to degradation of methylene blue using Carbon-Chitosan-Polyvinyl Chloride (CC-PVC). Carbon chitosan composite electrode was preparing by Carbon and Chitosan powder and PVC in 4 mL tetrahydrofuran (THF) solvent and swirled flatly to homogeneous followed by drying in an oven at 100 °C for 3 h. The mixture was placed in stainless steel mould and pressed at 10 ton/cm2. Sodium chloride was used electrolyte solution. The effects of the current and electrolysis time were investigated using spectrophotometer UV-Visible. The experimental results showed that the carbon-chitosan composite electrode have higher effect in the electrochemical degradation of methylene blue in sodium chloride. Based on UV-visible spectra analysis shows current and electrolysis time has high effect to degradation of methylene blue in sodium chloride. Chitosan and polyvinyl chloride can strengthen the bond between the carbons so that the material has the high stability and conductivity. As conclusions is Carbon-Chitosan-Polyvinyl Chloride (CC-PVC) electrode have a high electrochemical activity for degradation of methylene blue in sodium chloride.

Buried chloride stereochemistry in the Protein Data Bank.

Science.gov (United States)

Carugo, Oliviero

2014-09-23

Despite the chloride anion is involved in fundamental biological processes, its interactions with proteins are little known. In particular, we lack a systematic survey of its coordination spheres. The analysis of a non-redundant set (pairwise sequence identity chloride anion shows that the first coordination spheres of the chlorides are essentially constituted by hydrogen bond donors. Amongst the side-chains positively charged, arginine interacts with chlorides much more frequently than lysine. Although the most common coordination number is 4, the coordination stereochemistry is closer to the expected geometry when the coordination number is 5, suggesting that this is the coordination number towards which the chlorides tend when they interact with proteins. The results of these analyses are useful in interpreting, describing, and validating new protein crystal structures that contain chloride anions.

Chloride Blood Test: MedlinePlus Lab Test Information

Science.gov (United States)

... this page: https://medlineplus.gov/labtests/chloridebloodtest.html Chloride Blood Test To use the sharing features on this page, please enable JavaScript. What is a Chloride Blood Test? A chloride blood test measures the ...

Atmospheric chloride: Its implication for foliar uptake and damage

Science.gov (United States)

McWilliams, E. L.; Sealy, R. L.

Atmospheric chloride is inversely related to distance from the Texas coast; r2 = 0.86. Levels of atmospheric chloride are higher in the early summer than in the winter because of salt storms. Leaf chloride l'evels of Tillandsia usneoides L. (Spanish moss) reflect the atmospheric chloride levels; r2 = 0.78. The importance of considering the effect of atmospheric chloride on leaf damage to horticultural crops is discussed.

Simple Ion Channels: From Structure to Electrophysiology and Back

Science.gov (United States)

Pohorille, Andrzej

2018-01-01

A reliable way to establish whether our understanding of a channel is satisfactory is to reproduce its measured ionic conductance over a broad range of applied voltages in computer simulations. In molecular dynamics (MD), this can be done by way of applying an external electric field to the system and counting the number of ions that traverse the channel per unit time. Since this approach is computationally very expensive, we have developed a markedly more efficient alternative in which MD is combined with the electrodiffusion (ED) equation. In this approach, the assumptions of the ED equation can be rigorously tested, and the precision and consistency of the calculated conductance can be determined. We have demonstrated that the full current/voltage dependence and the underlying free energy profile for a simple channel can be reliably calculated from equilibrium or non-equilibrium MD simulations at a single voltage. To carry out MD simulations, a structural model of a channel has to be assumed, which is an important constraint, considering that high-resolution structures are available for only very few simple channels. If the comparison of calculated ionic conductance with electrophysiological data is satisfactory, it greatly increases our confidence that the structure and the function are described sufficiently accurately. We examined the validity of the ED for several channels embedded in phospholipid membranes - four naturally occurring channels: trichotoxin, alamethicin, p7 from hepatitis C virus (HCV) and Vpu from the HIV-1 virus, and a synthetic, hexameric channel, formed by a 21-residue peptide that contains only leucine and serine. All these channels mediate transport of potassium and chloride ions. It was found that the ED equation is satisfactory for these systems. In some of them experimental and calculated electrophysiological properties are in good agreement, whereas in others there are strong indications that the structural models are incorrect.

Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

International Nuclear Information System (INIS)

Duncan, L; Shelmerdine, H; Hughes, M P; Coley, H M; Huebner, Y; Labeed, F H

2008-01-01

Dielectrophoresis (DEP)-the motion of particles in non-uniform AC fields-has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K + and Ca 2+ levels were extremely similar between sensitive and resistant lines, levels of Cl - were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function. (note)

Influence of chloride admixtures on cement matrix durability

International Nuclear Information System (INIS)

Sheikh, I.A.; Zamorani, E.; Serrini, G.

1989-01-01

The influence of various inorganic salts, as chloride admixtures to Portland cement, on the mechanical properties and the durability of the matrix has been studied. The salts used in this study are chromium, nickel and cadmium chlorides. Improved compressive strength values are obtained which have been correlated to the stable metal hydroxide formation in high pH environment. Under static water conditions at 50 0 C, hydrolyzed chloride ions exhibit adverse effects on the matrix durability through rapid release of calcium as calcium chloride in the initial period of leaching. On the contrary, enhanced matrix durability is obtained on long term leaching in the case of cement containing chromium chloride

[Forensic Analysis for 54 Cases of Suxamethonium Chloride Poisoning].

Science.gov (United States)

Zhao, Y F; Zhao, B Q; Ma, K J; Zhang, J; Chen, F Y

2017-08-01

To observe and analyze the performance of forensic science in the cases of suxa- methonium chloride poisoning, and to improve the identification of suxamethonium chloride poisoning. Fifty-four cases of suxamethonium chloride poisoning were collected. The rules of determination of suxamethonium chloride poisoning were observed by the retrospective analysis of pathological and toxicological changes as well as case features. The pathological features of suxamethonium chloride poisoning were similar to the general changes of sudden death, which mainly included acute pulmonary congestion and edema, and partly showed myocardial disarray and fracture. Suxamethonium chloride could be detected in the heart blood of all cases and in skin tissue of part cases. Suxa-methonium chloride poisoning has the characteristics with fast death and covert means, which are difficult to rescue and easily miss inspection. For the cases of sudden death or suspicious death, determination of suxamethonium chloride should be taken as a routine detection index to prevent missing inspection. Copyright© by the Editorial Department of Journal of Forensic Medicine

Growth and characterization of magnesium chloride and lanthanum chloride doped strontium tartrate crystals - gel method

International Nuclear Information System (INIS)

Kalaiarasi, S.; Jaikumar, D.

2014-01-01

Growth of single crystals of doped strontium tartrate by controlled diffusion of strontium chloride into the silica gel charged with tartaric acid at room temperature is narrated. In this study, we synthesized magnesium chloride (5% and 10%) doped strontium tartrate crystals and Lanthanum chloride (5%, 10% and 15%) doped strontium tartrate crystals are grown. The crystal structure of the compound crystals was confirmed by single crystal X-ray diffraction. The Fourier transform infrared spectrum of pure and doped crystals are recorded and analyzed. The UV-Vis-NIR spectrum analysis reveals that the optical study of the grown crystals. The second harmonic generation efficiency was measured by using Kurtz powder technique with Nd:YAG laser of wavelength 1064 nm. (author)

KATP Channels in the Cardiovascular System.

Science.gov (United States)

Foster, Monique N; Coetzee, William A

2016-01-01

KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease. Copyright © 2016 the American Physiological Society.

Atomistic Modeling of Ion Conduction through the Voltage-Sensing Domain of the Shaker K+ Ion Channel.

Science.gov (United States)

Wood, Mona L; Freites, J Alfredo; Tombola, Francesco; Tobias, Douglas J

2017-04-20

Voltage-sensing domains (VSDs) sense changes in the membrane electrostatic potential and, through conformational changes, regulate a specific function. The VSDs of wild-type voltage-dependent K + , Na + , and Ca 2+ channels do not conduct ions, but they can become ion-permeable through pathological mutations in the VSD. Relatively little is known about the underlying mechanisms of conduction through VSDs. The most detailed studies have been performed on Shaker K + channel variants in which ion conduction through the VSD is manifested in electrophysiology experiments as a voltage-dependent inward current, the so-called omega current, which appears when the VSDs are in their resting state conformation. Only monovalent cations appear to permeate the Shaker VSD via a pathway that is believed to be, at least in part, the same as that followed by the S4 basic side chains during voltage-dependent activation. We performed μs-time scale atomistic molecular dynamics simulations of a cation-conducting variant of the Shaker VSD under applied electric fields in an experimentally validated resting-state conformation, embedded in a lipid bilayer surrounded by solutions containing guanidinium chloride or potassium chloride. Our simulations provide insights into the Shaker VSD permeation pathway, the protein-ion interactions that control permeation kinetics, and the mechanism of voltage-dependent activation of voltage-gated ion channels.

Channel sialic acids limit hERG channel activity during the ventricular action potential.

Science.gov (United States)

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Voltage-gated sodium channels: action players with many faces

NARCIS (Netherlands)

Koopmann, Tamara T.; Bezzina, Connie R.; Wilde, Arthur A. M.

2006-01-01

Voltage-gated sodium channels are responsible for the upstroke of the action potential and thereby play an important role in propagation of the electrical impulse in excitable tissues like muscle, nerve and the heart. Duplication of the sodium channels encoding genes during evolution generated the

Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys.

Science.gov (United States)

Christ, George J; Andersson, Karl-Erik; Williams, Koudy; Zhao, Weixin; D'Agostino, Ralph; Kaplan, Jay; Aboushwareb, Tamer; Yoo, James; Calenda, Giulia; Davies, Kelvin P; Sellers, Rani S; Melman, Arnold

2009-12-01

Despite the advent of effective oral therapies for erectile dysfunction (ED), many patients are not successfully treated, and side effects have been documented. To further evaluate the potential utility of naked DNA-based gene transfer as an attractive treatment option for ED. The effects of gene transfer on erectile function and sexual behavior were evaluated in eight male cynomolgus monkeys with ED secondary to moderately severe, diet-induced atherosclerosis. Following establishment of baseline characteristics, animals were subjected to intracavernous injection of a smooth-muscle-specific gene transfer vector (pSMAA-hSlo) encoding the pore-forming subunit of the human large-conductance, calcium-sensitive potassium channel (Maxi-K). For the sexual behavior studies, 2 wk of baseline data were obtained, and then animals were placed in the presence of estrogen-implanted females (n=2) three times per week for 30 min, and sexual behavior was recorded. The intracavernous pressure response to papaverine injection was also monitored. Dramatic changes in erectile function and sexual behavior were observed after intracorporal gene transfer. The frequency of partial (6±2 to 10±2) and full (2±1.5 to 5±1.4) erections were significantly increased, with a parallel 2-3-fold increase in the duration of the observed erections. The frequency and latency of ejaculation were increased and decreased, respectively. Frequency and duration of grooming by the female were increased, and the latency decreased. Increased latency and decreased frequency of body contact was also observed, and this is characteristic of the typical drop in consort intimacy that occurs after mating in most macaque species. In addition, an increased responsiveness to intracavernous papaverine injection was observed. The data indicate that intracorporal Maxi-K-channel gene transfer enhances erectile capacity and sexual behavior; the data imply that increased erectile function per se may lead to increased sexual

Properties of silver chloride track detectors

International Nuclear Information System (INIS)

Dmitriev, V.D.; Kocherov, N.P.; Novikova, N.R.; Perfilov, N.A.

1976-01-01

The experiments on preparation of silver chloride track detectors and their properties are described. The results of X-ray structural analysis and data on sensitivity to charged particles and actinic light of silver chloride crystals, doped with several elements, are presented. (orig.) [de

Plant Natural compounds with antibacterial activity towards common pathogens of pond-cultured channel catfish (Ictalurus punctatus).

Science.gov (United States)

Schrader, Kevin K

2010-07-01

The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds as potential therapeutants. Chelerythrine chloride and ellagic acid were the most toxic toward E. ictaluri, with 24-h IC50 of 7.3 mg/L and 15.1 mg/L, respectively, and MIC of 2.1 mg/L and 6.5 mg/L, respectively. Chelerythrine chloride, ellagic acid, β-glycyrrhetinic acid, sorgoleone, and wogonin were the most toxic towards two genomovars of F. columnare, and wogonin had the strongest antibacterial activity (MIC = 0.3 mg/L).

Chloride Ingress into Concrete under Water Pressure

DEFF Research Database (Denmark)

Lund, Mia Schou; Sander, Lotte Braad; Grelk, Bent

2011-01-01

The chloride ingress into concrete under water pressures of 100 kPa and 800 kPa have been investigated by experiments. The specimens were exposed to a 10% NaCl solution and water mixture. For the concrete having w/c = 0.35 the experimental results show the chloride diffusion coefficient at 800 k......Pa (～8 atm.) is 12 times greater than at 100 kPa (～1 atm.). For w/c = 0.45 and w/c = 0.55 the chloride diffusion coefficients are 7 and 3 times greater. This means that a change in pressure highly influences the chloride ingress into the concrete and thereby the life length models for concrete structures....

Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation.

Directory of Open Access Journals (Sweden)

Chaowalit Yuajit

Full Text Available Cyst enlargement in polycystic kidney disease (PKD involves cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR chloride channel. This study aimed to investigate an inhibitory effect and detailed mechanisms of steviol and its derivatives on cyst growth using a cyst model in Madin-Darby canine kidney (MDCK cells. Among 4 steviol-related compounds tested, steviol was found to be the most potent at inhibiting MDCK cyst growth. Steviol inhibition of cyst growth was dose-dependent; steviol (100 microM reversibly inhibited cyst formation and cyst growth by 72.53.6% and 38.2±8.5%, respectively. Steviol at doses up to 200 microM had no effect on MDCK cell viability, proliferation and apoptosis. However, steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK epithelia, measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged treatment (24 h with steviol (100 microM also strongly inhibited forskolin-stimulated apical chloride current, in part by reducing CFTR protein expression in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect of steviol on CFTR protein expression. Immunofluorescence studies demonstrated that prolonged treatment (24 h with steviol (100 microM markedly reduced CFTR expression at the plasma membrane. Taken together, the data suggest that steviol retards MDCK cyst progression in two ways: first by directly inhibiting CFTR chloride channel activity and second by reducing CFTR expression, in part, by promoting proteasomal degradation of CFTR. Steviol and related compounds therefore represent drug candidates for treatment of polycystic kidney disease.

Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units

DEFF Research Database (Denmark)

Larsen, Erik Hviid; Gabriel, S. E.; Stutts, M. J.

1996-01-01

The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath...

Hydrolysis of cupric chloride in aqueous ammoniacal ammonium chloride solutions

Directory of Open Access Journals (Sweden)

Limpo, J. L.

1995-06-01

Full Text Available Cupric solubility in the CuCl₂-NH₄Cl-NH₃-H₂O system for chloride concentrations lower than 4 molal in the temperature range 25-60 °C was studied. The experimental results show that for chloride concentration between 3.0 and 1.0 molal the cupric solubility is determined by the solubility of the cupric hydroxychloride Cu(OH_1.5Cl_0.5. For a chloride concentration value of 4.0 molal, there are two cupric compounds, the hydroxychloride Cu(OH_1.5Cl_0.5 or the diammine chloride Cu(NH₃₂Cl₂, on which the solubility of Cu(II depends, according to the temperature and the value of the ratio [NH₃]_Total/[Cu]_Total.

Se estudia la solubilidad del Cu(II en el sistema CuCl₂-NH₄Cl-NH₃-H₂O para concentraciones de cloruro inferiores a 4 molal en el intervalo de temperaturas 25-60 °C. Los resultados experimentales muestran que, para concentraciones de cloruros comprendidas entre 3,0 y 1,0 molal, la solubilidad cúprica viene determinada por la solubilidad del hidroxicloruro cúprico, Cu(OH_1.5Cl_0.5. Para concentraciones de cloruro 4,0 molal, existen dos compuestos cúpricos, el hidroxicloruro, Cu(OH_1.5Cl_0.5 o el cloruro de diamina, Cu(NH₃₂Cl₂, de los que, de acuerdo con la temperatura y con el valor de la relación [NH₃]_Total/[Cu]_Total depende la solubilidad del Cu(II.

29 CFR 1926.1152 - Methylene chloride.

Science.gov (United States)

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Methylene chloride. 1926.1152 Section 1926.1152 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Methylene chloride. Note: The requirements applicable to construction employment under this section are...

29 CFR 1915.1052 - Methylene chloride.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Methylene chloride. 1915.1052 Section 1915.1052 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1052 Methylene chloride. Note: The requirements applicable to shipyard employment under this...

cAMP and forskolin decrease γ-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes

International Nuclear Information System (INIS)

Heuschneider, G.; Schwartz, R.D.

1989-01-01

The effects of the cyclic nucleotide cAMP on γ-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N 6 , O 2' -dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36 Cl - uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner. The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the γ-aminobutyric acid-gated Cl - channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36 Cl - uptake and generated cAMP with similar potencies. Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl - channel directly. The data suggest that γ-aminobutyric acid (GABA A ) receptor function in brain can be regulated by cAMP-dependent phosphorylation

Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea.

Science.gov (United States)

Höglund, P; Sormaala, M; Haila, S; Socha, J; Rajaram, U; Scheurlen, W; Sinaasappel, M; de Jonge, H; Holmberg, C; Yoshikawa, H; Kere, J

2001-09-01

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by defective intestinal electrolyte absorption, resulting in voluminous osmotic diarrhea with high chloride content. A variety of mutations in the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or DRA) are responsible for the disease. Since the identification of the SLC26A3 gene and the determination of its genomic structure, altogether three founder and 17 private mutations have been characterized within miscellaneous ethnic groups. We screened for mutations in seven unrelated families with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven novel mutations including two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two previously identified mutations were also found. This is the first report of rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for the two rearrangements may include repetitive elements and palindromic-like sequences. The increasingly wide diversity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene may not be rare events. Copyright 2001 Wiley-Liss, Inc.

Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro

International Nuclear Information System (INIS)

Kunert-Radek, J.; Stepien, H.; Lyson, K.; Pawlikowski, M.; Radek, A.

1989-01-01

The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [ 3 H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that varapamil (10 4 -10 5 M) and nimodipine (10 4 -10 6 M) significantly inhibited the [ 3 H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by stimultancous addition of calcium chloride (5x10 3 M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blokade of specific voltage-dependent calcium channels. (author)

Thermochemistry of certain rare earth and ammonium double chlorides

International Nuclear Information System (INIS)

Usubaliev, D.U.; Abramtsev, V.A.; Kydynov, M.K.; Vilyaev, A.N.

1987-01-01

In a calorimeter with isothermal casing at 25 deg C dissolution enthalpies of double chlorides of rare earths and ammonium LnCl 3 x2NH 4 Cl (Ln=La, Sm) and LnCl 3 x3NH 4 Cl (Ln=Gd, Tb, Ho) in water, as well as dissolution enthalpy of rare earth chlorides in solution of ammonium chloride and NH 4 Cl in solution of rare earth chloride, have been measured. Formation enthalpies, standard formation enthalpies, dissociation enthalpies of the above-mentioned double chlorides are calculated

Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH.

Science.gov (United States)

Pinelli, Laurent; Nissant, Antoine; Edwards, Aurélie; Lourdel, Stéphane; Teulon, Jacques; Paulais, Marc

2016-09-01

ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. © 2016 Pinelli et al.

21 CFR 177.1950 - Vinyl chloride-ethylene copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vinyl chloride-ethylene copolymers. 177.1950... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1950 Vinyl chloride-ethylene copolymers. The vinyl chloride-ethylene copolymers identified in paragraph (a) of this section may be safely...

Chlorides behavior in raw fly ash washing experiments

International Nuclear Information System (INIS)

Zhu Fenfen; Takaoka, Masaki; Oshita, Kazuyuki; Kitajima, Yoshinori; Inada, Yasuhiro; Morisawa, Shinsuke; Tsuno, Hiroshi

2010-01-01

Chloride in fly ash from municipal solid waste incinerators (MSWIs) is one of the obstructive substances in recycling fly ash as building materials. As a result, we have to understand the behavior of chlorides in recycling process, such as washing. In this study, we used X-ray absorption near edge structure (XANES) and X-ray diffraction (XRD) to study the chloride behavior in washed residue of raw fly ash (RFA). We found that a combination of XRD and XANES, which is to use XRD to identify the situation of some compounds first and then process XANES data, was an effective way to explain the chlorides behavior in washing process. Approximately 15% of the chlorine in RFA was in the form of NaCl, 10% was in the form of KCl, 51% was CaCl 2 , and the remainder was in the form of Friedel's salt. In washing experiments not only the mole percentage but also the amount of soluble chlorides including NaCl, KCl and CaCl 2 decreases quickly with the increase of liquid to solid (L/S) ratio or washing frequency. However, those of insoluble chlorides decrease slower. Moreover, Friedel's salt and its related compound (11CaO.7Al 2 O 3 .CaCl 2 ) were reliable standards for the insoluble chlorides in RFA, which are strongly related to CaCl 2 . Washing of RFA promoted the release of insoluble chlorides, most of which were in the form of CaCl 2 .

Abnormal chloride homeostasis in the substancia nigra pars reticulata contributes to locomotor deficiency in a model of acute liver injury.

Directory of Open Access Journals (Sweden)

Yan-Ling Yang

Full Text Available BACKGROUND: Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. METHODS: Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE. The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. RESULTS: In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. CONCLUSION: Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure.

29 CFR 1915.1017 - Vinyl chloride.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Vinyl chloride. 1915.1017 Section 1915.1017 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1017 Vinyl chloride. Note: The requirements applicable to shipyard employment under this section...

29 CFR 1926.1117 - Vinyl chloride.

Science.gov (United States)

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Vinyl chloride. 1926.1117 Section 1926.1117 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... chloride. Note: The requirements applicable to construction work under this section are identical to those...

Mass transport and chloride ion complexes in occluded cell

International Nuclear Information System (INIS)

Tsuru, T.; Hashimoto, K.; Nishikata, A.; Haruyama, S.

1989-01-01

Changes in the transport and the concentration of ions in a model occluded cell are traced during galvanostatic anodic polarization of a mild steel and a stainless steel. Apparent transport numbers of anions and cations, which were estimated from chemical analysis of solution, were different from those calculated from known mobility data. At the initial stage of the polarization, the transport number of chloride ion was almost unity, and then decreased gradually. For the mild steel, the concentration of total chloride ion accumulated in the occluded compartment increased with the anodic charge passed, and the amount of chloride ion complexed with cations also increased. The chloride complex was estimated as FeCl + . For SUS304 stainless steel, the total chloride ion increased, however, the free chloride ion, which responded to an Ag/AgCl electrode remained approximately 2 mol/dm 3 . Therefore, most of the chloride ions transferred into the occluded cell formed complex ions, such as CrCl n 3-n . The number of chloride ion coordinated to ferrous and chromic ions was estimated from the data fo mass transport for the case of the mild steel and the stainless steel. (author) 9 refs., 14 figs

Anodic Behavior of Alloy 22 in Calcium Chloride and in Calcium Chloride Plus Calcium Nitrate Brines

International Nuclear Information System (INIS)

Evans, K.J.; Day, S.D.; Ilevbare, G.O.; Whalen, M.T.; King, K.J.; Hust, G.A.; Wong, L.L.; Estill, J.C.; Rebak, R.B.

2003-01-01

Alloy 22 (UNS N60622) is a nickel-based alloy, which is extensively used in aggressive industrial applications, especially due to its resistance to localized corrosion and stress corrosion cracking in high chloride environments. The purpose of this work was to characterize the anodic behavior of Alloy 22 in concentrated calcium chloride (CaCl 2 ) brines and to evaluate the inhibitive effect of nitrate, especially to localized corrosion. Standard electrochemical tests such as polarization resistance and cyclic polarization were used. Results show that the corrosion potential of Alloy 22 was approximately -360 mV in the silver-silver chloride (SSC) scale and independent of the tested temperature. Cyclic polarization tests showed that Alloy 22 was mainly susceptible to localized attack in 5 M CaCl 2 at 75 C and higher temperatures. The addition of nitrate in a molar ratio of chloride to nitrate equal to 10 increased the onset of localized corrosion to approximately 105 C. The addition of nitrate to the solution also decreased the uniform corrosion rate and the passive current of the alloy

Bartter syndrome Type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation

NARCIS (Netherlands)

Westland, R.; Hack, W.W.; van der Horst, H.J.; Uittenbogaard, L.B.; van Hagen, J.M.; van der Valk, P.; Kamsteeg, E.J.; Heuvel, L.P.W.J. van den; van Wijk, J.A.

2012-01-01

Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2

Ion Channels of Pituitary Gonadotrophs and Their Roles in Signaling and Secretion

Directory of Open Access Journals (Sweden)

Stanko S. Stojilkovic

2017-06-01

Full Text Available Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM. These cells also express the hyperpolarization-activated and cyclic nucleotide-gated cation channels at the PM, as well as GABAA, nicotinic, and purinergic P2X channels gated by γ-aminobutyric acid (GABA, acetylcholine (ACh, and ATP, respectively. Activation of these channels leads to initiation or amplification of the pacemaking activity, facilitation of calcium influx, and activation of the exocytic pathway. Gonadotrophs also express calcium-conducting channels at the endoplasmic reticulum membranes gated by inositol trisphosphate and intracellular calcium. These channels are activated potently by hypothalamic gonadotropin-releasing hormone (GnRH and less potently by several paracrine calcium-mobilizing agonists, including pituitary adenylate cyclase-activating peptides, endothelins, ACh, vasopressin, and oxytocin. Activation of these channels causes oscillatory calcium release and a rapid gonadotropin release, accompanied with a shift from tonic firing of single APs to periodic bursting type of electrical activity, which accounts for a sustained calcium signaling and gonadotropin secretion. This review summarizes our current understanding of ion channels as signaling molecules in gonadotrophs, the role of GnRH and paracrine agonists in their gating, and the cross talk among channels.

Process for making rare earth metal chlorides

International Nuclear Information System (INIS)

Kruesi, P.R.

1981-01-01

An uncombined metal or a metal compound such as a sulfide, oxide, carbonate or sulfate is converted in a liquid salt bath to the corresponding metal chloride by reacting it with chlorine gas or a chlorine donor. The process applies to metals of groups 1b, 2a, 2b, 3a, 3b, 4a, 5a and 8 of the periodic table and to the rare earth metals. The chlorine donor may be ferric or sulfur chloride. The liquid fused salt bath is made up of chlorides of alkali metals, alkaline earth metals, ammonia, zinc and ferric iron. Because the formed metal chlorides are soluble in the liquid fused salt bath, they can be recovered by various conventional means

Crystal structures of salicylideneguanylhydrazinium chloride and its copper(II) and cobalt(III) chloride complexes

International Nuclear Information System (INIS)

Chumakov, Yu. M.; Tsapkov, V. I.; Bocelli, G.; Antosyak, B. Ya.; Shova, S. G.; Gulea, A. P.

2006-01-01

The crystal structures of salicylideneguanylhydrazinium chloride hydrate hemiethanol solvate (I), salicylideneguanylhydrazinium trichloroaquacuprate(II) (II), and bis(salicylideneguanylhydrazino)cobalt(III) chloride trihydrate (III) are determined using X-ray diffraction. The structures of compounds I, II, and III are solved by direct methods and refined using the least-squares procedure in the anisotropic approximation for the non-hydrogen atoms to the final factors R = 0.0597, 0.0212, and 0.0283, respectively. In the structure of compound I, the monoprotonated molecules and chlorine ions linked by hydrogen bonds form layers aligned parallel to the (010) plane. In the structure of compound II, the salicylaldehyde guanylhydrazone cations and polymer chains consisting of trichloroaquacuprate(II) anions are joined by an extended three-dimensional network of hydrogen bonds. In the structure of compound III, the [Co(LH) 2 ] + cations, chloride ions, and molecules of crystallization water are linked together by a similar network

Gene knockout of the KCNJ8-encoded Kir6.1 K(ATP) channel imparts fatal susceptibility to endotoxemia.

Science.gov (United States)

Kane, Garvan C; Lam, Chen-Fuh; O'Cochlain, Fearghas; Hodgson, Denice M; Reyes, Santiago; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Katusic, Zvonimir S; Terzic, Andre

2006-11-01

Sepsis, the systemic inflammatory response to infection, imposes a high demand for bodily adaptation, with the cardiovascular response a key determinant of outcome. The homeostatic elements that secure cardiac tolerance in the setting of the sepsis syndrome are poorly understood. Here, in a model of acute septic shock induced by endotoxin challenge with Escherichia coli lipopolysaccharide (LPS), knockout of the KCNJ8 gene encoding the vascular Kir6.1 K(ATP) channel pore predisposed to an early and profound survival disadvantage. The exaggerated susceptibility provoked by disruption of this stress-responsive sensor of cellular metabolism was linked to progressive deterioration in cardiac activity, ischemic myocardial damage, and contractile dysfunction. Deletion of KCNJ8 blunted the responsiveness of coronary vessels to cytokine- or metabolic-mediated vasodilation necessary to support myocardial perfusion in the wild-type (WT), creating a deficit in adaptive response in the Kir6.1 knockout. Application of a K(ATP) channel opener drug improved survival in the endotoxic WT but had no effect in the Kir6.1 knockout. Restoration of the dilatory capacity of coronary vessels was required to rescue the Kir6.1 knockout phenotype and reverse survival disadvantage in lethal endotoxemia. Thus, the Kir6.1-containing K(ATP) channel, by coupling vasoreactivity with metabolic demand, provides a vital feedback element for cardiovascular tolerance in endotoxic shock.

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

DEFF Research Database (Denmark)

Hedley, Paula L; Haundrup, Ole; Andersen, Paal S

2011-01-01

The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere...... as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic...

Estimating Anthropogenic Emissions of Hydrogen Chloride and Fine Particulate Chloride in China

Science.gov (United States)

Fu, X.; Wang, T.; Wang, S.; Zhang, L.

2017-12-01

Nitryl chloride (ClNO2) can significantly impact the atmospheric photochemistry via photolysis and subsequent reactions of chlorine radical with other gases. The formation of ClNO2 in the atmosphere is sensitive to the emissions of chlorine-containing particulates from oceanic and anthropogenic sources. For China, the only available anthropogenic chlorine emission inventory was compiled for the year 1990 with a coarse resolution of 1 degree. In this study, we developed an up-to-date anthropogenic inventory of hydrogen chloride (HCl) and fine particulate chloride (Cl-) emissions in China for the year 2014, including coal burning, industrial processes, biomass burning and waste burning. Bottom-up and top-down methodologies were combined. Detailed local data (e.g. Cl content in coal, control technologies, etc.) were collected and applied. In order to improve the spatial resolution of emissions, detailed point source information were collected for coal-fired power plants, cement factories, iron & steel factories and waste incineration factories. Uncertainties of this emission inventory and their major causes were analyzed using the Monte Carlo method. This work enables better quantification of the ClNO2 production and impact over China.

The transient outward current in mice lacking the potassium channel gene Kv1.4

Science.gov (United States)

London, Barry; Wang, Dao W; Hill, Joseph A; Bennett, Paul B

1998-01-01

The transient outward current (Ito) plays a prominent role in the repolarization phase of the cardiac action potential. Several K+ channel genes, including Kv1.4, are expressed in the heart, produce rapidly inactivating currents when heterologously expressed, and may be the molecular basis of Ito.We engineered mice homozygous for a targeted disruption of the K+ channel gene Kv1.4 and compared Ito in wild-type (Kv1.4+/+), heterozygous (Kv1.4+/-) and homozygous ‘knockout’ (Kv1.4−/−) mice. Kv1.4 RNA was truncated in Kv1.4−/− mice and protein expression was absent.Adult myocytes isolated from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice had large rapidly inactivating outward currents. The peak current densities at 60 mV (normalized by cellular capacitance, in pA pF−1; means ± s.e.m.) were 53.8 ± 5.3, 45.3 ± 2.2 and 44.4 ± 2.8 in cells from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice, respectively (P mice.The voltage dependence and time course of inactivation were not changed by targeted disruption of Kv1.4. The mean best-fitting V½ (membrane potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/− and Kv1.4−/− mice were -53.5 ± 3.7, -51.1 ± 2.6 and -54.2 ± 2.4 mV, respectively. The slope factors (k) were -10.1 ± 1.4, -8.8 ± 1.4 and -9.5 ± 1.2 mV, respectively. The fast time constants for development of inactivation at -30 mV were 27.8 ± 2.2, 26.2 ± 5.1 and 19.6 ± 2.1 ms in Kv1.4+/+, Kv1.4+/− and Kv1.4−/− myocytes, respectively. At +30 mV, they were 35.5 ± 2.6, 30.0 ± 2.1 and 28.7 ± 1.6 ms, respectively. The time constants for the rapid phase of recovery from inactivation at -80 mV were 32.5 ± 8.2, 23.3 ± 1.8 and 39.0 ± 3.7 ms, respectively.Nearly the entire inactivating component as well as more than 60 % of the steady-state outward current was eliminated by 1 mm 4-aminopyridine in Kv1.4+/+, Kv1.4+/− and Kv1.4−/− myocytes.Western blot analysis of heart membrane extracts showed no significant

Bone marrow scintigraphy with 111In-chloride

International Nuclear Information System (INIS)

Fujishima, Mamoru; Hiraki, Yoshio; Takeda, Yoshihiro; Kohno, Yoshihiro; Niiya, Harutaka; Aono, Kaname; Yorimitsu, Seiichi; Takahashi, Isao

1988-01-01

Bone marrow scintigraphy with indium chloride ( 111 In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1) in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2) in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3) in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4) four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5) in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific. (author)

Chlorides behavior in raw fly ash washing experiments.

Science.gov (United States)

Zhu, Fenfen; Takaoka, Masaki; Oshita, Kazuyuki; Kitajima, Yoshinori; Inada, Yasuhiro; Morisawa, Shinsuke; Tsuno, Hiroshi

2010-06-15

Chloride in fly ash from municipal solid waste incinerators (MSWIs) is one of the obstructive substances in recycling fly ash as building materials. As a result, we have to understand the behavior of chlorides in recycling process, such as washing. In this study, we used X-ray absorption near edge structure (XANES) and X-ray diffraction (XRD) to study the chloride behavior in washed residue of raw fly ash (RFA). We found that a combination of XRD and XANES, which is to use XRD to identify the situation of some compounds first and then process XANES data, was an effective way to explain the chlorides behavior in washing process. Approximately 15% of the chlorine in RFA was in the form of NaCl, 10% was in the form of KCl, 51% was CaCl(2), and the remainder was in the form of Friedel's salt. In washing experiments not only the mole percentage but also the amount of soluble chlorides including NaCl, KCl and CaCl(2) decreases quickly with the increase of liquid to solid (L/S) ratio or washing frequency. However, those of insoluble chlorides decrease slower. Moreover, Friedel's salt and its related compound (11CaO.7Al(2)O(3).CaCl(2)) were reliable standards for the insoluble chlorides in RFA, which are strongly related to CaCl(2). Washing of RFA promoted the release of insoluble chlorides, most of which were in the form of CaCl(2). Copyright 2010 Elsevier B.V. All rights reserved.

Characterization of GABA/sub A/ receptor-mediated 36chloride uptake in rat brain synaptoneurosomes

International Nuclear Information System (INIS)

Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

1987-01-01

γ-Aminobutyric acid (GABA) receptor-mediated 36 chloride ( 36 Cl - ) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated 36 Cl - uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated 36 Cl - uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated 36 Cl - uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br - >Cl - ≥NO 3 - >I - ≥SCN - >>C 3 H 5 OO - ≥ClO 4 - >F - , consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl - channel. 43 references, 4 figures, 3 tables

Alkali metal and ammonium chlorides in water and heavy water (binary systems)

CERN Document Server

Cohen-Adad, R

1991-01-01

This volume surveys the data available in the literature for solid-fluid solubility equilibria plus selected solid-liquid-vapour equilibria, for binary systems containing alkali and ammonium chlorides in water or heavy water. Solubilities covered are lithium chloride, sodium chloride, potassium chloride, rubidium chloride, caesium chloride and ammonium chloride in water and heavy water.

Studies on the mercuric chloride resistance of Staphylococcus aureus

Energy Technology Data Exchange (ETDEWEB)

Vaczi, L; Fodor, M; Milch, H; Rethy, A

1962-01-01

Among 409 pathogenic Staph. aureus strains 34% have been found to be sensitive, and 66% resistant, to mercuric chloride. The incidence of mercuric chloride resistant cultures among antibiotic sensitive staphylococci was 20%; among strains resistant to penicillin or to more than one antibiotic, 70%. Mercuric chloride resistant organisms occurred chiefly among phage group I and untypable strains; they were especially common among the so called epidemic strains of phage group I, and among cultures resistant to 4-6 antibiotics. In mercuric chloride sensitivity a thirtyfold, in merthiolate sensitivity only a two-fold difference has been revealed among the strains. The sulfydryl group content of mercuric chloride resistant organisms was only 1 1/2 times higher than that of sensitive bacteria. As to p-chlor mercuric benzoate binding capacity, a twofold difference was found between mercuric chloride sensitive and resistant staphylococci. The differences in the mercuric chloride resistance of various staphylococcal strains might be due to differences in the chemical structure of the cell surface. 9 references, 1 figure, 6 tables.

Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients.

Science.gov (United States)

Marshall-Gradisnik, Sonya; Johnston, Samantha; Chacko, Anu; Nguyen, Thao; Smith, Peter; Staines, Donald

2016-12-01

Objective The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca 2+ ) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients. Methods A total of 11 CFS/ME patients (aged 31.82 ± 5.50 years) and 11 non-fatigued controls (aged 33.91 ± 5.06 years) were included. Flow cytometric protocols were used to determine B cell purity, followed by SNP and genotype analysis for 21 mammalian TRP ion channel genes and nine mammalian ACh receptor genes. SNP association and genotyping analysis were performed using ANOVA and PLINK analysis software. Results Seventy-eight SNPs were identified in nicotinic and muscarinic acetylcholine receptor genes in the CFS/ME group, of which 35 were in mAChM3. The remaining SNPs were identified in nAChR delta (n = 12), nAChR alpha 9 (n = 5), TRPV2 (n = 7), TRPM3 (n = 4), TRPM4 (n = 1) mAChRM3 2 (n = 2), and mAChRM5 (n = 3) genes. Nine genotypes were identified from SNPs in TRPM3 (n = 1), TRPC6 (n = 1), mAChRM3 (n = 2), nAChR alpha 4 (n = 1), and nAChR beta 1 (n = 4) genes, and were located in introns and 3' untranslated regions. Odds ratios for these specific genotypes ranged between 7.11 and 26.67 for CFS/ME compared with the non-fatigued control group. Conclusion This preliminary investigation identified a number of SNPs and genotypes in genes encoding TRP ion channels and AChRs from B cells in patients with CFS/ME. These may be involved in B cell functional changes, and suggest a role for Ca 2+ dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.

40 CFR 61.64 - Emission standard for polyvinyl chloride plants.

Science.gov (United States)

2010-07-01

... chloride plants. 61.64 Section 61.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Standard for Vinyl Chloride § 61.64 Emission standard for polyvinyl chloride plants. An owner or operator of a polyvinyl chloride plant shall comply with the requirements of this section and § 61.65. (a...

G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer

International Nuclear Information System (INIS)

Takanami, Iwao; Inoue, Yoshimasa; Gika, Masatoshi

2004-01-01

G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis. In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I). These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs

Removal of iron contaminant from zirconium chloride solution

International Nuclear Information System (INIS)

Voit, D.O.

1992-01-01

This patent describes a process for eliminating iron contaminant from an aqueous zirconium chloride solution that has been contaminated with FeCl 3 in a plant in which zirconium and hafnium chloride solutions are separated by a main MINK solvent extraction system and the FeCl 3 is normally removed from the zirconium chloride solution by a secondary MINK solvent extraction system

Genetics Home Reference: Gitelman syndrome

Science.gov (United States)

... MJ, Lifton RP, Simon DB; Yale Gitelman's and Bartter's Syndrome Collaborative Study Group. Gitelman's syndrome revisited: an evaluation ... chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype. Pediatr Res. 2000 ... NV, Levtchenko EN. Gitelman syndrome. Orphanet J Rare Dis. 2008 Jul 30;3: ...

Expression, purification and functional reconstitution of slack sodium-activated potassium channels.

Science.gov (United States)

Yan, Yangyang; Yang, Youshan; Bian, Shumin; Sigworth, Fred J

2012-11-01

The slack (slo2.2) gene codes for a potassium-channel α-subunit of the 6TM voltage-gated channel family. Expression of slack results in Na(+)-activated potassium channel activity in various cell types. We describe the purification and reconstitution of Slack protein and show that the Slack α-subunit alone is sufficient for potassium channel activity activated by sodium ions as assayed in planar bilayer membranes and in membrane vesicles.

NuLYTELY (PEG 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution).

Science.gov (United States)

Swartz, M L

1992-02-01

NuLYTELY (PEG 3350, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride for Oral Solution), a product from Braintree Laboratories, Inc. is a modification of GoLYTELY (PEG 3350 and Electrolytes for Oral Solution) that has been found to have the same therapeutic advantages in terms of safety, efficacy, speed and patient acceptance. This product was developed to improve upon the taste of GoLYTELY. NuLYTELY represents an effective alternative for bowel cleansing prior to colonoscopy that may be more acceptable to some patients.

[Determination of Chloride Salt Solution by NIR Spectroscopy].

Science.gov (United States)

Zhang, Bin; Chen, Jian-hong; Jiao, Ming-xing

2015-07-01

Determination of chloride salt solution by near infrared spectrum plays a very important role in Biomedicine. The near infrared spectrum analysis of Sodium chloride, potassium chloride, calcium chloride aqueous solution shows that the concentration change of chloride salt can affect hydrogen bond, resulting in the variation of near infrared spectrum of water. The temperature influence on NIR spectrum has been decreased by choosing reasonable wavelength range and the wavelength where the temperature effects are zero (isosbestic point). Chlorine salt prediction model was established based on partial least squares method and used for predicting the concentration of the chlorine ion. The impact on near infrared spectrum of the cation ionic radius, the number of ionic charge, the complex effect of ionic in water has also discussed in this article and the reason of every factor are analysed. Experimental results show that the temperature and concentration will affect the near-infrared spectrum of the solution, It is found that the effect of temperature plays the dominant role at low concentrations of chlorine salt; rather, the ionic dominates at high concentration. Chloride complexes are formed in aqueous solution, It has an effect on hydrogen bond of water combining with the cations in chlorine salt solution, Comparing different chloride solutions at the same concentration, the destruction effects of chloride complexes and catnions on the hydrogen bond of water increases in the sequences: CaCl2 >NaCl>KC. The modeling result shows that the determination coefficients (R2) = 99.97%, the root mean square error of cross validation (RM- SECV) = 4.51, and the residual prediction deviation (RPD) = 62.7, it meets the daily requirements of biochemical detection accuracy.

Neurotoxic Effects of Linalool and β-Pinene on Tribolium castaneum Herbst

Directory of Open Access Journals (Sweden)

Nerlis Pajaro-Castro

2017-11-01

Full Text Available Effective, ethical pest control requires the use of chemicals that are highly specific, safe, and ecofriendly. Linalool and β-pinene occur naturally as major constituents of the essential oils of many plant species distributed throughout the world, and thus meet these requirements. These monoterpenes were tested as repellents against Tribolium castaneum, using the area preference method, after four hours of exposure and the effect transcriptional of genes associated with neurotransmission. Changes in gene expression of acetylcholinesterase (Ace1, GABA-gated anion channel splice variant 3a6a (Rdl, GABA-gated ion channel (Grd, glutamate-gated chloride channel (Glucl, and histamine-gated chloride channel 2 (Hiscl2 were assessed and the interaction with proteins important for the insect using in silico methods was also studied. For linalool and β-pinene, the repellent concentration 50 (RC50 values were 0.11 µL/cm2 and 0.03 µL/cm2, respectively. Both compounds induced overexpression of Hiscl2 gen in adult insects, and β-pinene also promoted the overexpression of Grd and the Ace1 gene. However, β-pinene and linalool had little potential to dock on computer-generated models for GABA-gated ion channel LCCH3, nicotinic acetylcholine receptor subunits alpha1 and alpha2, and putative octopamine/tyramine receptor proteins from T. castaneum as their respective binding affinities were marginal, and therefore the repellent action probably involved mechanisms other than direct interaction with these targets. Results indicated that β-pinene was more potent than linalool in inducing insect repellency, and also had a greater capacity to generate changes in the expression of genes involved in neuronal transmission.

Detection of colloidal silver chloride near solubility limit

Science.gov (United States)

Putri, K. Y.; Adawiah, R.

2018-03-01

Detection of nanoparticles in solution has been made possible by several means; one of them is laser-induced breakdown detection (LIBD). LIBD is able to distinguish colloids of various sizes and concentrations. This technique has been used in several solubility studies. In this study, the formation of colloids in a mixed system of silver nitrate and sodium chloride was observed by acoustic LIBD. Silver chloride has low solubility limit, therefore LIBD measurement is appropriate. Silver and chloride solutions with equal concentrations, set at below and above the solubility of silver chloride as the expected solid product, were mixed and the resulting colloids were observed. The result of LIBD measurement showed that larger particles were present as more silver and chloride introduced. However, once the concentrations exceeded the solubility limit of silver chloride, the detected particle size seemed to be decreasing, hence suggested the occurrence of coprecipitation process. This phenomenon indicated that the ability of LIBD to detect even small changes in colloid amounts might be a useful tool in study on formation and stability of colloids, i.e. to confirm whether nanoparticles synthesis has been successfully performed and whether the system is stable or not.

Low Doses of Cadmium Chloride and Methallothionein-1-Bound Cadmium Display Different Accumulation Kinetics and Induce Different Genes in Cells of the Human Nephron

Directory of Open Access Journals (Sweden)

Dana Cucu

2011-08-01

Full Text Available Background/Aims: The present study was conducted to investigate the renal tubular handling of inorganic cadmium (Cd2+ by exposing primary human tubular cell cultures to physiologically relevant doses of cadmium chloride (CdCl2. Furthermore, the cellular accumulation of Cd2+ was compared to that of metallothionein-1-bound Cd (Cd7MT-1. Finally, this study aimed to investigate the effect of the accumulation of Cd (both Cd2+ and Cd7MT-1 in renal cells on the expression of genes relevant to nephrotoxic processes. Methods: Cd concentration was measured using atomic absorption spectrometry. mRNA expression was evaluated by quantitative real-time RT-PCR. Results: Cd2+ accumulated into human tubular cells in a concentration- and time-dependent way. Furthermore, cellular accumulation of Cd2+ was different from the cellular accumulation of Cd7MT-1, indicative for different uptake routes. Finally, mRNA expression of the genes encoding the anti-oxidative proteins metallothionein-1 (MT-1 and heme-oxygenase-1 (HO-1 as well as the pro-apoptotic Bcl-2-associated X protein (Bax were upregulated by CdCl2 and not by Cd7MT1. Conclusion: In the presence of physiologically relevant Cd concentrations, tubular accumulation of the element in its inorganic form is different from that of Cd7MT-1. Furthermore, the tubular accumulation of inorganic Cd induces mRNA expression of genes of which the protein products may play a role in Cd-associated renal toxicity.

Effects of platinic chloride on Tetrahymena pyrifromis GL

DEFF Research Database (Denmark)

Nilsson, Jytte R.

1992-01-01

Cellebiologi, platinum(IV)chloride, endocytosis, detoxification, cell proliferation, fine structure, cisplatin......Cellebiologi, platinum(IV)chloride, endocytosis, detoxification, cell proliferation, fine structure, cisplatin...

Surface Chloride Levels in Colorado Structural Concrete

Science.gov (United States)

2018-01-01

This project focused on the chloride-induced corrosion of reinforcing steel in structural concrete. The primary goal of this project is to analyze the surface chloride concentration level of the concrete bridge decks throughout Colorado. The study in...

Simple chloride sensors for continuous groundwater monitoring

DEFF Research Database (Denmark)

Thorn, Paul; Mortensen, John

2012-01-01

The development of chloride sensors which can be used for continuous, on-line monitoring of groundwater could be very valuable in the management of our coastal water resources. However, sensor stability, drift, and durability all need to be addressed in order for the sensors to be used in continu......The development of chloride sensors which can be used for continuous, on-line monitoring of groundwater could be very valuable in the management of our coastal water resources. However, sensor stability, drift, and durability all need to be addressed in order for the sensors to be used...... in continuous application. This study looks at the development of a simple, inexpensive chloride electrode, and evaluates its performance under continuous use, both in the laboratory and in a field test in a monitoring well. The results from the study showed a consistent response to changing chloride...... concentrations over longer periods. The signal was seen to be stable, with regular drift in both laboratory and field test. In the field application, the sensor signal was corrected for drift, and errors were observed to be under 7% of that of conductivity measurements. The study also found that the chloride...

New insights about antibiotic production by Pseudomonas aeruginosa: a gene expression analysis

Science.gov (United States)

Gionco, Bárbara; Tavares, Eliandro R.; de Oliveira, Admilton G.; Yamada-Ogatta, Sueli F.; do Carmo, Anderson O.; Pereira, Ulisses de Pádua; Chideroli, Roberta T.; Simionato, Ane S.; Navarro, Miguel O. P.; Chryssafidis, Andreas L.; Andrade, Galdino

2017-09-01

The bacterial resistance for antibiotics is one of the most important problems in public health and only a small number of new products are in development. Antagonistic microorganisms from soil are a promising source of new candidate molecules. Products of secondary metabolism confer adaptive advantages for their producer, in the competition for nutrients in the microbial community. The biosynthesis process of compounds with antibiotic activity is the key to optimize their production and the transcriptomic study of microorganisms is of great benefit for the discovery of these metabolic pathways. Pseudomonas aeruginosa LV strain growing in the presence of copper chloride produces a bioactive organometallic compound, which has a potent antimicrobial activity against various microorganisms. The objective of this study was to verify overexpressed genes and evaluate their relation to the organometallic biosynthesis in this microorganism. P. aeruginosa LV strain was cultured in presence and absence of copper chloride. Two methods were used for transcriptomic analysis, genome reference-guided assembly and de novo assembly. The genome referenced analysis identified nine upregulated genes when bacteria were exposed to copper chloride, while the De Novo Assembly identified twelve upregulated genes. Nineteen genes can be related to an increased microbial metabolism for the extrusion process of exceeding intracellular copper. Two important genes are related to the biosynthesis of phenazine and tetrapyrroles compounds, which can be involved in the bioremediation of intracellular copper and biosynthesis of the organometallic compound. Additional studies are being carried out to further prove the function of the described genes and relate them to the biosynthetic pathway of the organometallic compound.

Interpretation of postmortem vitreous concentrations of sodium and chloride.

Science.gov (United States)

Zilg, B; Alkass, K; Berg, S; Druid, H

2016-06-01

Vitreous fluid can be used to analyze sodium and chloride levels in deceased persons, but it remains unclear to what extent such results can be used to diagnose antemortem sodium or chloride imbalances. In this study we present vitreous sodium and chloride levels from more than 3000 cases. We show that vitreous sodium and chloride levels both decrease with approximately 2.2mmol/L per day after death. Since potassium is a well-established marker for postmortem interval (PMI) and easily can be analyzed along with sodium and chloride, we have correlated sodium and chloride levels with the potassium levels and present postmortem reference ranges relative the potassium levels. We found that virtually all cases outside the reference range show signs of antemortem hypo- or hypernatremia. Vitreous sodium or chloride levels can be the only means to diagnose cases of water or salt intoxication, beer potomania or dehydration. We further show that postmortem vitreous sodium and chloride strongly correlate and in practice can be used interchangeably if analysis of one of the ions fails. It has been suggested that vitreous sodium and chloride levels can be used to diagnose drowning or to distinguish saltwater from freshwater drowning. Our results show that in cases of freshwater drowning, vitreous sodium levels are decreased, but that this mainly is an effect of postmortem diffusion between the eye and surrounding water rather than due to the drowning process, since the decrease in sodium levels correlates with immersion time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antibodies to the CFTR modulate the turgor pressure of guard cell protoplasts via slow anion channels.

Science.gov (United States)

Leonhardt, N; Bazin, I; Richaud, P; Marin, E; Vavasseur, A; Forestier, C

2001-04-06

The plasma membrane guard cell slow anion channel is a key element at the basis of water loss control in plants allowing prolonged osmolite efflux necessary for stomatal closure. This channel has been extensively studied by electrophysiological approaches but its molecular identification is still lacking. Recently, we described that this channel was sharing some similarities with the mammalian ATP-binding cassette protein, cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel [Leonhardt, N. et al. (1999) Plant Cell 11, 1141-1151]. Here, using the patch-clamp technique and a bioassay, consisting in the observation of the change in guard cell protoplasts volume, we demonstrated that a functional antibody raised against the mammalian CFTR prevented ABA-induced guard cell protoplasts shrinking and partially inhibited the slow anion current. Moreover, this antibody immunoprecipitated a polypeptide from guard cell protein extracts and immunolabeled stomata in Vicia faba leaf sections. These results indicate that the guard cell slow anion channel is, or is closely controlled by a polypeptide, exhibiting one epitope shared with the mammalian CFTR.

Hydrolysis of ferric chloride in solution

International Nuclear Information System (INIS)

Lussiez, G.; Beckstead, L.

1996-11-01

The Detox trademark process uses concentrated ferric chloride and small amounts of catalysts to oxidize organic compounds. It is under consideration for oxidizing transuranic organic wastes. Although the solution is reused extensively, at some point it will reach the acceptable limit of radioactivity or maximum solubility of the radioisotopes. This solution could be cemented, but the volume would be increased substantially because of the poor compatibility of chlorides and cement. A process has been developed that recovers the chloride ions as HCl and either minimizes the volume of radioactive waste or permits recycling of the radioactive chlorides. The process involves a two-step hydrolysis at atmospheric pressure, or preferably under a slight vacuum, and relatively low temperature, about 200 degrees C. During the first step of the process, hydrolysis occurs according to the reaction below: FeCl 3 liquid + H 2 O → FeOCl solid + 2 HCl gas During the second step, the hot, solid, iron oxychloride is sprayed with water or placed in contact with steam, and hydrolysis proceeds to the iron oxide according to the following reaction: 2 FeOCl solid + H 2 O → Fe 2 O 3 solid + 2 HCl gas . The iron oxide, which contains radioisotopes, can then be disposed of by cementation or encapsulation. Alternately, these chlorides can be washed off of the solids and can then either be recycled or disposed of in some other way

Transport and fate of chloride from road salt within a mixed urban and agricultural watershed in Illinois (USA): assessing the influence of chloride application rates

Science.gov (United States)

Ludwikowski, Jessica J.; Peterson, Eric W.

2018-01-01

In a typical winter season, approximately 471,000 tons of road salt are deposited along roadways in Illinois, USA. An estimated 45% of the deposited road salt will infiltrate through the soils and into shallow aquifers. Transported through shallow aquifers, chloride associated with the road salts has the potential to reside within groundwater for years based on the pathway, the geologic material, and the recharge rate of the aquifer system. Utilizing MODFLOW and MT3D, simulations employing various road-salt application rates were conducted to assess the net accumulation of chloride and the residence times of chloride in an agriculture-dominated watershed that originates in an urban area. A positive-linear relationship was observed between the application rate of chloride and both the maximum chloride concentration and total mass accumulated within the watershed. Simulated annual recharge rates along impacted surfaces ranged from 1,000 to 10,000 mg/L. After 60 years of application, simulated chloride concentrations in groundwater ranged from 197 to 1,900 mg/L. For all application rates, chloride concentrations within the groundwater rose at an annual rate of >3 mg/L. While concentrations increase throughout the system, the majority of chloride accumulation occurs near the roads and the urban areas. Model simulations reveal a positive relationship between application rate and residence time of chloride (1,123-1,288 days based on application rate). The models indicate that continued accumulation of chloride in shallow aquifers can be expected, and methods that apply less chloride effectively need to be examined.

Arrhythmogenic KCNE gene variants: current knowledge and future challenges

Directory of Open Access Journals (Sweden)

Shawn M Crump

2014-01-01

Full Text Available There are twenty-five known inherited cardiac arrhythmia susceptibility genes, all of which encode either ion channel pore-forming subunits or proteins that regulate aspects of ion channel biology such as function, trafficking and localization. The human KCNE gene family comprises five potassium channel regulatory subunits, sequence variants in each of which are associated with cardiac arrhythmias. KCNE gene products exhibit promiscuous partnering and in some cases ubiquitous expression, hampering efforts to unequivocally correlate each gene to specific native potassium currents. Likewise, deducing the molecular etiology of cardiac arrhythmias in individuals harboring rare KCNE gene variants, or more common KCNE polymorphisms, can be challenging. In this review we provide an update on putative arrhythmia-causing KCNE gene variants, and discuss current thinking and future challenges in the study of molecular mechanisms of KCNE-associated cardiac rhythm disturbances.

Extractive process for preparing high purity magnesium chloride hexahydrate

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Fezei Radouanne

2012-01-01

Full Text Available This paper refers a method for the preparation of magnesium chloride hexahydrate (bischofite from Sebkha el Melah of Zarzis Tunisian natural brine. It is a five-stage process essentially based on crystallization by isothermal evaporation and chemical precipitation. The two first steps were dedicated to the crystallization of sodium chloride and potassiummagnesium double salts, respectively. Then, the resulting liquor was desulfated using calcium chloride solution. After that another isothermal evaporation stage was implemented in order to eliminate potassium ions in the form of carnallite, KCl.MgCl2.6H2O. At the end of this step, the recovered solution primarily composed of magnesium and chloride ions was treated by dioxan in order to precipitate magnesium chloride as MgCl2.6H2O.C4H8O2. This compound dried at constant temperature of 100°C gave good quality magnesium chloride hexahydrate. Besides this salt, the various by-products obtained from the different treatment stages are also useful.

Solid-phase extraction of cobalt(II) from lithium chloride solutions using a poly(vinyl chloride)-based polymer inclusion membrane with Aliquat 336 as the carrier.

Science.gov (United States)

Kagaya, Shigehiro; Cattrall, Robert W; Kolev, Spas D

2011-01-01

The extraction of cobalt(II) from solutions containing various concentrations of lithium chloride, hydrochloric acid, and mixtures of lithium chloride plus hydrochloric acid is reported using a poly(vinyl chloride) (PVC)-based polymer inclusion membrane (PIM) containing 40% (w/w) Aliquat 336 as a carrier. The extraction from lithium chloride solutions and mixtures with hydrochloric acid is shown to be more effective than extraction from hydrochloric acid solutions alone. The solution concentrations giving the highest amounts of extraction are 7 mol L(-1) for lithium chloride and 8 mol L(-1) lithium chloride plus 1 mol L(-1) hydrochloric acid for mixed solutions. Cobalt(II) is easily stripped from the membrane using deionized water. The cobalt(II) species extracted into the membrane are CoCl(4)(2-) for lithium chloride solutions and HCoCl(4)(-) for mixed solutions; these form ion-pairs with Aliquat 336. It is also shown that both lithium chloride and hydrochloric acid are extracted by the PIM and suppress the extraction of cobalt(II) by forming ion-pairs in the membrane (i.e. R(3)MeN(+)·HCl(2)(-) for hydrochloric acid and R(3)MeN(+)·LiCl(2)(-) for lithium chloride). 2011 © The Japan Society for Analytical Chemistry

Desulfonatronovibrio halophilus sp. nov., a novel moderately halophilic sulfate-reducing bacterium from hypersaline chloride-sulfate lakes in Central Asia

NARCIS (Netherlands)

Sorokin, D.Y.; Tourova, T.P.; Abbas, B.; Suhacheva, M.V.; Muyzer, G.

2012-01-01

Four strains of lithotrophic sulfate-reducing bacteria (SRB) have been enriched and isolated from anoxic sediments of hypersaline chloride-sulfate lakes in the Kulunda Steppe (Altai, Russia) at 2 M NaCl and pH 7.5. According to the 16S rRNA gene sequence analysis, the isolates were closely related

40 CFR 721.6167 - Piperdinium, 1,1-dimethyl-, chloride.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Piperdinium, 1,1-dimethyl-, chloride... Substances § 721.6167 Piperdinium, 1,1-dimethyl-, chloride. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as piperdinium, 1,1-dimethyl-, chloride. (PMN...

Synthesis of 14C-dehydrocorydaline chloride

International Nuclear Information System (INIS)

Zhang Rui; Wang Ding

1988-01-01

A method for synthesis of 14 C-dehydrocorydaline chloride is described. In the presence of sodium hydroxide, acetonylpalmatine is reacted with 14 C-methyl iodide in sealed glass ampoule to give 14 C-13-methylpalmatine iodide which is then converted to chloride. The radiochemical purity of 14 C-dehydrocorydaline determined by TLC is over 98% and the labelling efficiency is 54%

Chloride ingress in cement paste and mortar

DEFF Research Database (Denmark)

Jensen, Ole Mejlhede; Hansen, Per Freiesleben; Coats, Alison M.

1999-01-01

In this paper chloride ingress in cement paste and mortar is followed by electron probe microanalysis. The influence of several paste and exposure parameters on chloride ingress are examined (e.g., water-cement ratio, silica fume addition, exposure time, and temperature), The measurements...

Chronopotentiometric chloride sensing using transition time measurement

NARCIS (Netherlands)

Abbas, Yawar; de Graaf, D.B.; Olthuis, Wouter; van den Berg, Albert

2013-01-01

Detection of chloride ions is crucial to accurately access the concrete structure durability[1]. The existing electrochemical method of chloride ions detection in concrete, potentiometry[1], is not suitable for in-situ measurement due to the long term stability issue of conventional reference

Method for synthesizing pollucite from chabazite and cesium chloride

International Nuclear Information System (INIS)

Pereira, C.

1999-01-01

A method is described for immobilizing waste chlorides salts containing radionuclides and hazardous nuclear material for permanent disposal, and in particular, a method is described for immobilizing waste chloride salts containing cesium, in a synthetic form of pollucite. The method for synthesizing pollucite from chabazite and cesium chloride includes mixing dry, non-aqueous cesium chloride with chabazite and heating the mixture to a temperature greater than the melting temperature of the cesium chloride, or above about 700 C. The method further comprises significantly improving the rate of retention of cesium in ceramic products comprised of a salt-loaded zeolite by adding about 10% chabazite by weight to the salt-loaded zeolite prior to conversion at elevated temperatures and pressures to the ceramic composite. 3 figs

On solubility of rare earth chlorides in water at different temperatures

International Nuclear Information System (INIS)

Nikolaev, A.V.; Sorokina, A.A.; Sokolova, N.P.; Kotlyar-Shapirov, G.S.; Bagryantseva, L.I.

1978-01-01

Solubility of rare earth chlorides at -5, -10 and -15 deg C is studied. Rare earth chloride solubility dependences on the temperature in the interval from -15 to 50 deg C are presented. Decrease of solubility temperature coefficient to a zero is observed at temperature drop almost for all rare earth chlorides. Solubility temperature coefficient at the same temperature but for different rare earth chlorides reduces appreciably with the growth of rare earth chloride serial number. This testifies to the corresponding decrease of integral solution heat of rare earth chloride crystallohydrates

Resistance of Alkali-Activated Slag Concrete to Chloride-Induced Corrosion

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Joon Woo Park

2015-01-01

Full Text Available The corrosion resistance of steel in alkali-activated slag (AAS mortar was evaluated by a monitoring of the galvanic current and half-cell potential with time against a chloride-contaminated environment. For chloride transport, rapid chloride penetration test was performed, and chloride binding capacity of AAS was evaluated at a given chloride. The mortar/paste specimens were manufactured with ground granulated blast-furnace slag, instead of Portland cement, and alkali activators were added in mixing water, including Ca(OH2, KOH and NaOH, to activate hydration process. As a result, it was found that the corrosion behavior was strongly dependent on the type of alkali activator: the AAS containing the Ca(OH2 activator was the most passive in monitoring of the galvanic corrosion and half-cell potential, while KOH, and NaOH activators indicated a similar level of corrosion to Portland cement mortar (control. Despite a lower binding of chloride ions in the paste, the AAS had quite a higher resistance to chloride transport in rapid chloride penetration, presumably due to the lower level of capillary pores, which was ensured by the pore distribution of AAS mortar in mercury intrusion porosimetry.

The gene for the alpha 1 subunit of the skeletal muscle dihydropyridine-sensitive calcium channel (Cchl1a3) maps to mouse chromosome 1.

Science.gov (United States)

Chin, H; Krall, M; Kim, H L; Kozak, C A; Mock, B

1992-12-01

Cchl1a3 encodes the dihydropyridine-sensitive calcium channel alpha 1 subunit isoform predominantly expressed in skeletal muscle. mdg (muscular dysgenesis) has previously been implicated as a mutant allele of this gene. Hybridization of a rat brain cDNA probe for Cchl1a3 to Southern blots of DNAs from a panel of Chinese hamster x mouse somatic cell hybrids suggested that this gene maps to mouse Chromosome 1. Analysis of the progeny of an inbred strain cross-positioned Cchl1a3 1.3 cM proximal to the Pep-3 locus on Chr 1.

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels.

Science.gov (United States)

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-03-01

1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The effects of n-alkanols like octanol on CFTR activity were measured by iodide ((125)I) efflux and patch-clamp techniques on three distinct cellular models: (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3 epithelial cells and (3). human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents induced by octanol were blocked by glibenclamide but insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-) current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanoloctanoloctanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF.

Subminimal Inhibitory Concentrations of the Disinfectant Benzalkonium Chloride Select for a Tolerant Subpopulation of Escherichia coli with Inheritable Characteristics

Directory of Open Access Journals (Sweden)

Solveig Langsrud

2012-03-01

Full Text Available Exposure of Escherichia coli to a subminimal inhibitory concentration (25% below MIC of benzalkonium chloride (BC, an antimicrobial membrane-active agent commonly used in medical and food-processing environments, resulted in cell death and changes in cell morphology (filamentation. A small subpopulation (1–5% of the initial population survived and regained similar morphology and growth rate as non-exposed cells. This subpopulation maintained tolerance to BC after serial transfers in medium without BC. To withstand BC during regrowth the cells up regulated a drug efflux associated gene (the acrB gene, member of the AcrAB-TolC efflux system and changed expression of outer membrane porin genes (ompFW and several genes involved in protecting the cell from the osmotic- and oxidative stress. Cells pre-exposed to osmotic- and oxidative stress (sodium chloride, salicylic acid and methyl viologen showed higher tolerance to BC. A control and two selected isolates showing increased BC-tolerance after regrowth in BC was genome sequenced. No common point mutations were found in the BC- isolates but one point mutation in gene rpsA (Ribosomal protein S1 was observed in one of the isolates. The observed tolerance can therefore not solely be explained by the observed point mutation. The results indicate that there are several different mechanisms responsible for the regrowth of a tolerant subpopulation in BC, both BC-specific and general stress responses, and that sub-MIC of BC may select for phenotypic variants in a sensitive E. coli culture.

Chloride binding site of neurotransmitter sodium symporters

DEFF Research Database (Denmark)

Kantcheva, Adriana Krassimirova; Quick, Matthias; Shi, Lei

2013-01-01

Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs...

Catalytic Conversion of Cellulose to Levulinic Acid by Metal Chlorides

Directory of Open Access Journals (Sweden)

Beixiao Zhang

2010-08-01

Full Text Available The catalytic performance of various metal chlorides in the conversion of cellulose to levulinic acid in liquid water at high temperatures was investigated. The effects of reaction parameters on the yield of levulinic acid were also explored. The results showed that alkali and alkaline earth metal chlorides were not effective in conversion of cellulose, while transition metal chlorides, especially CrCl3, FeCl3 and CuCl2 and a group IIIA metal chloride (AlCl3, exhibited high catalytic activity. The catalytic performance was correlated with the acidity of the reaction system due to the addition of the metal chlorides, but more dependent on the type of metal chloride. Among those metal chlorides, chromium chloride was found to be exceptionally effective for the conversion of cellulose to levulinic acid, affording an optimum yield of 67 mol % after a reaction time of 180 min, at 200 °C, with a catalyst dosage of 0.02 M and substrate concentration of 50 wt %. Chromium metal, most of which was present in its oxide form in the solid sample and only a small part in solution as Cr3+ ion, can be easily separated from the resulting product mixture and recycled. Finally, a plausible reaction scheme for the chromium chloride catalyzed conversion of cellulose in water was proposed.

On barium oxide solubility in barium-containing chloride melts

International Nuclear Information System (INIS)

Nikolaeva, Elena V.; Zakiryanova, Irina D.; Bovet, Andrey L.; Korzun, Iraida V.

2016-01-01

Oxide solubility in chloride melts depends on temperature and composition of molten solvent. The solubility of barium oxide in the solvents with barium chloride content is essentially higher than that in molten alkali chlorides. Spectral data demonstrate the existence of oxychloride ionic groupings in such melts. This work presents the results of the BaO solubility in two molten BaCl 2 -NaCl systems with different barium chloride content. The received data together with earlier published results revealed the main regularities of BaO solubility in molten BaO-BaCl 2 -MCl systems.

Effects of Cations on Corrosion of Inconel 625 in Molten Chloride Salts

Science.gov (United States)

Zhu, Ming; Ma, Hongfang; Wang, Mingjing; Wang, Zhihua; Sharif, Adel

2016-04-01

Hot corrosion of Inconel 625 in sodium chloride, potassium chloride, magnesium chloride, calcium chloride and their mixtures with different compositions is conducted at 900°C to investigate the effects of cations in chloride salts on corrosion behavior of the alloy. XRD, SEM/EDS were used to analyze the compositions, phases, and morphologies of the corrosion products. The results showed that Inconel 625 suffers more severe corrosion in alkaline earth metal chloride molten salts than alkaline metal chloride molten salts. For corrosion in mixture salts, the corrosion rate increased with increasing alkaline earth metal chloride salt content in the mixture. Cations in the chloride molten salts mainly affect the thermal and chemical properties of the salts such as vapor pressure and hydroscopicities, which can affect the basicity of the molten salt. Corrosion of Inconel 625 in alkaline earth metal chloride salts is accelerated with increasing basicity.

Bone marrow scintigraphy with 111In-chloride

International Nuclear Information System (INIS)

Aburano, Tamio; Ueno, Kyoichi; Sugihara, Masami; Tada, Akira; Tonami, Norihisa

1977-01-01

It is assumed that 111 In-chloride is bound to serum transferrin and then transported into reticulocyte in erythropoietic marrow. However, several biochemical differences between radioiron and 111 In have been reported since these years. In present study, clinical usefulness of 111 In-chloride bone marrow scintigraphy was examined especially by comparing 111 In-chloride image with sup(99m)Tc-colloid. Obtained results are as follows: 1) In most cases, both 111 In-chloride and sup(99m)Tc-colloid images showed similar bone marrow distributions. 2) In three out of 7 cases with hypoplastic anemia and two patients with bone marrow irradiation (700-1,000 rad), the central marrow or irradiated marrow showed marked decreased uptake of 111 In, and showed normal uptake of sup(99m)Tc. 3) In two out of 3 cases with chronic myelogenous leucemia, central marrow showed normal uptake of 111 In, and showed decreased uptake of sup(99m)Tc. From the present study, the same dissociation findings as those between radioiron and radiocolloid could be obtained in hypoplastic anemia and bone marrow irradiation. 111 In-chloride would appear to be a useful erythropoietic imaging agent, although further study of exact comparison with radioiron should be necessary. (auth.)

Electrodeposition behavior of nickel and nickel-zinc alloys from the zinc chloride-1-ethyl-3-methylimidazolium chloride low temperature molten salt

International Nuclear Information System (INIS)

Gou Shiping; Sun, I.-W.

2008-01-01

The electrodeposition of nickel and nickel-zinc alloys was investigated at polycrystalline tungsten electrode in the zinc chloride-1-ethyl-3-methylimidazolium chloride molten salt. Although nickel(II) chloride dissolved easily into the pure chloride-rich 1-ethyl-3-methylimidazolium chloride ionic melt, metallic nickel could not be obtained by electrochemical reduction of this solution. The addition of zinc chloride to this solution shifted the reduction of nickel(II) to more positive potential making the electrodeposition of nickel possible. The electrodeposition of nickel, however, requires an overpotential driven nucleation process. Dense and compact nickel deposits with good adherence could be prepared by controlling the deposition potential. X-ray powder diffraction measurements indicated the presence of crystalline nickel deposits. Non-anomalous electrodeposition of nickel-zinc alloys was achieved through the underpotential deposition of zinc on the deposited nickel at a potential more negative than that of the deposition of nickel. X-ray powder diffraction and energy-dispersive spectrometry measurements of the electrodeposits indicated that the composition and the phase types of the nickel-zinc alloys are dependent on the deposition potential. For the Ni-Zn alloy deposits prepared by underpotential deposition of Zn on Ni, the Zn content in the Ni-Zn was always less than 50 atom%

Calcium Channel Genes Associated with Bipolar Disorder Modulate Lithium's Amplification of Circadian Rhythms

Science.gov (United States)

McCarthy, Michael J.; LeRoux, Melissa; Wei, Heather; Beesley, Stephen; Kelsoe, John R.; Welsh, David K.

2015-01-01

Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2∷luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 hr in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms. PMID:26476274

Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

Science.gov (United States)

Wu, Wei; Sanguinetti, Michael C

2016-06-01

Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Endocochlear potential depends on Cl− channels: mechanism underlying deafness in Bartter syndrome IV

Science.gov (United States)

Rickheit, Gesa; Maier, Hannes; Strenzke, Nicola; Andreescu, Corina E; De Zeeuw, Chris I; Muenscher, Adrian; Zdebik, Anselm A; Jentsch, Thomas J

2008-01-01

Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a β-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K+-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd−/− mice thus demonstrate a novel function of Cl− channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV. PMID:18833191

Effect of ultrasound on electrochemical chloride extraction from mortar

Science.gov (United States)

Chen, Yiqun; Yao, Wu; Zuo, Junqing

2018-03-01

In this paper, the effect of auxiliary ultrasound on electrochemical chloride extraction (ECE) was studied. The chloride removal efficiency was investigated by examining the chloride content with ultrasound-assisted ECE and changing the introducing time of ultrasound. The experimental results showed that removal of chloride ions was noted to be more effective in ECE treatment assisted with ultrasound treatment (UT). In addition, the lower w/c ratio led to more distinct effect of ultrasonic cavitation on chloride removal. Electrochemical behaviors measured with different treatment revealed that UT treatment was effective on moderating the corrosion condition. Microstructural analyses revealed a significant alteration in composition and morphology of cementitious phases with UT treatment. Pull-out tests indicated that ultrasound had a certain negative impact on the bond strength. Although the effect of introducing ultrasound in the first 2 weeks or the last 2 weeks on the extraction efficiency was not obvious, intermittent ultrasound could not only ensure the chloride extraction efficiency, but also reduce the adverse effect of ultrasound on the bond strength.

The signaling role for chloride in the bidirectional communication between neurons and astrocytes.

Science.gov (United States)

Wilson, Corinne S; Mongin, Alexander A

2018-01-09

It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl - ) fluxes via the inhibitory GABA A 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. The existing literature suggests that neurons can alter astrocytic Cl - levels in a number of ways; via (a) the release of neurotransmitters and activation of glial transporters that have intrinsic Cl - conductance, (b) the metabotropic receptor-driven changes in activity of the electroneutral cation-Cl - cotransporter NKCC1, and (c) the transient, activity-dependent changes in glial cell volume which open the volume-regulated Cl - /anion channel VRAC. Reciprocally, astrocytes are thought to alter neuronal [Cl - ] i through either (a) VRAC-mediated release of the inhibitory gliotransmitters, GABA and taurine, which open neuronal GABA A and glycine receptor/Cl - channels, or (b) the gliotransmitter-driven stimulation of NKCC1. The most important recent developments in this area are the identification of the molecular composition and functional heterogeneity of brain VRAC channels, and the discovery of a new cytosolic [Cl - ] sensor - the Wnk family protein kinases. With new work in the field, our understanding of the role of Cl - in information processing within the CNS is expected to be significantly updated. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiac Delayed Rectifier Potassium Channels in Health and Disease

Science.gov (United States)

Chen, Lei; Sampson, Kevin J.; Kass, Robert S.

2016-01-01

Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this chapter, we will review the molecular identities and biophysical properties of these channels. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the possibility and prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. PMID:27261823

Contribution of Ca2+-Dependent Cl- Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing

Czech Academy of Sciences Publication Activity Database

Líšková, Silvia; Petrová, M.; Karen, Petr; Behuliak, Michal; Zicha, Josef

2014-01-01

Roč. 2014, č. 2014 (2014), s. 289361 ISSN 2314-6133 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : calcium-dependent chloride channels * endothelium-derived contracting factor * ageing Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.579, year: 2014

New Insights about Antibiotic Production by Pseudomonas aeruginosa: A Gene Expression Analysis

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Bárbara Gionco

2017-09-01

Full Text Available The bacterial resistance for antibiotics is one of the most important problems in public health and only a small number of new products are in development. Antagonistic microorganisms from soil are a promising source of new candidate molecules. Products of secondary metabolism confer adaptive advantages for their producer, in the competition for nutrients in the microbial community. The biosynthesis process of compounds with antibiotic activity is the key to optimize their production and the transcriptomic study of microorganisms is of great benefit for the discovery of these metabolic pathways. Pseudomonas aeruginosa LV strain growing in the presence of copper chloride produces a bioactive organometallic compound, which has a potent antimicrobial activity against various microorganisms. The objective of this study was to verify overexpressed genes and evaluate their relation to the organometallic biosynthesis in this microorganism. P. aeruginosa LV strain was cultured in presence and absence of copper chloride. Two methods were used for transcriptomic analysis, genome reference-guided assembly and de novo assembly. The genome referenced analysis identified nine upregulated genes when bacteria were exposed to copper chloride, while the De Novo Assembly identified 12 upregulated genes. Nineteen genes can be related to an increased microbial metabolism for the extrusion process of exceeding intracellular copper. Two important genes are related to the biosynthesis of phenazine and tetrapyrroles compounds, which can be involved in the bioremediation of intracellular copper and we suggesting that may involve in the biosynthesis of the organometallic compound. Additional studies are being carried out to further prove the function of the described genes and relate them to the biosynthetic pathway of the organometallic compound.

VOLATILE CHLORIDE PROCESS FOR THE RECOVERY OF METAL VALUES

Science.gov (United States)

Hanley, W.R.

1959-01-01

A process is presented for recovering uranium, iron, and aluminum from centain shale type ores which contain uranium in minute quantities. The ore is heated wiih a chlorinating agent. such as chlorine, to form a volatilized stream of metal chlorides. The chloride stream is then passed through granular alumina which preferentially absorbs the volatile uranium chloride and from which the uranium may later be recovered. The remaining volatilized chlorides, chiefly those of iron and aluminum, are further treated to recover chlorine gas for recycle, and to recover ferric oxide and aluminum oxide as valuable by-products.

Molecular Characterization of LRB7 Gene and a Water Channel Protein TIP2 in Chorispora bungeana

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Ming Li

2016-01-01

Full Text Available Background. Water channel proteins, also called aquaporins, are integral membrane proteins from major intrinsic protein (MIP family and involved in several pathways including not only water transport but also cell signaling, reproduction, and photosynthesis. The full cDNA and protein sequences of aquaporin in Chorispora bungeana Fisch. & C.A. Mey (C. bungeana are still unknown. Results. In this study, PCR and rapid amplification of cDNA ends approaches were used to clone the full cDNA of LRB7 (GenBank accession number: EU636988 of C. bungeana. Sequence analysis indicated that it was 1235 bp, which had two introns and encoded a protein of 250 amino acids. Structure analysis revealed that the protein had two conserved NPA motifs, one of which is MIP signature sequence (SGxHxNPAVT, six membrane helix regions, and additional membrane-embedded domains. Phylogenetic analysis suggested that the protein was from TIP2 subgroup. Surprisingly, semiquantitative RT-PCR experiment and western blot analysis showed that LRB7 and TIP2 were only detectable in roots, unlike Arabidopsis and Raphanus. Connecting with our previous studies, LRB7 was supported to associate with chilling-tolerance in C. bungeana. Conclusion. This is the first time to characterize the full sequences of LRB7 gene and water channel protein in C. bungeana. Our findings contribute to understanding the water transports in plants under low temperatures.

Hydrocracking mechanisms in molten zinc chloride. Isotope scrambling and pyrolysis studies

International Nuclear Information System (INIS)

Larsen, J.W.; Earnest, S.

1979-01-01

Bruceton coal was hydrocracked in molten zinc chloride using H 2 -D 2 mixtures. No H-D was observed. The pyrolysis of Bruceton coal and a lignite in molten zinc chloride and an inert salt was carried out and the tetrahydrofuran and pyridine extractability of the products determined. In the absence of H 2 , zinc chloride is not an effective cracking catalyst. It is tentatively concluded that the catalytically active species is formed from zinc chloride and something in the coal and H 2 . The interactions between zinc chloride and the lignite appear to be significantly different than the interactions between zinc chloride and the bituminous coal. (Auth.)

Repassivation Potential of Alloy 22 in Sodium and Calcium Chloride Brines

International Nuclear Information System (INIS)

Rebak, R B; Ilevbare, G O; Carranza, R M

2007-01-01

A comprehensive matrix of 60 tests was designed to explore the effect of calcium chloride vs. sodium chloride and the ratio R of nitrate concentration over chloride concentration on the repassivation potential of Alloy 22. Tests were conducted using the cyclic potentiodynamic polarization (CPP) technique at 75 C and at 90 C. Results show that at a ratio R of 0.18 and higher nitrate was able to inhibit the crevice corrosion in Alloy 22 induced by chloride. Current results fail to show in a consistent way a different effect on the repassivation potential of Alloy 22 for calcium chloride solutions than for sodium chloride solutions

Two-electron oxidation of cobalt phthalocyanines by thionyl chloride: Implications for lithium/thionyl chloride batteries. Technical report

Energy Technology Data Exchange (ETDEWEB)

Bernstein, P.A.; Lever, A.B.

1989-10-20

Cyclic voltammetry, DPV and electronic spectroscopy are used to study the reaction between thionyl chloride and cobalt phthalocyanine. SOCl2 reacts with (Co(I)Tn Pc(2-)) and Co(II)Tn Pc(2-) to give two-electron oxidized species. Implications for Li/SOCl2 batteries are discussed. Thionyl chloride also forms a mono SOCl2 adduct with Co(II)TnPc(2-). Driving forces (Delta E values) were calculated for CoTnPc comproportionation and CoTnPc + SOCl2 reactions. Rest potential measurements of a Li/SOCl2 cells show that addition of AlCl3 stabilizes the LiCl product as LiAlCl4. A catalytic two-electron mechanism is indicated for the reduction of thionyl chloride in a Li/SOCl2/(CoTnPc,C) battery.

Novel Compound Heterozygous CLCNKB Gene Mutations (c.1755A>G/ c.848_850delTCT) Cause Classic Bartter Syndrome.

Science.gov (United States)

Wang, Chunli; Chen, Ying; Zheng, Bixia; Zhu, Mengshu; Fan, Jia; Wang, Juejin; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

2018-02-14

Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT/c.1755A>G). Compound heterozygosity was confirmed by amplifying and sequencing the patient's genomic DNA. The synonymous mutation c.1755A>G (Thr585Thr) was located at +2bp from the 5' splice donor site in exon 15, further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother. Furthermore, we investigated the expression and protein trafficking change of c.848_850delTCT (TCT) and exon 15 deletion（E15）mutation in vitro. The E15 mutation markedly decreased the expression of ClC-Kb and resulted in a low-molecular-weight band (~55kD) trapping in the endoplasmic reticulum, while the TCT mutant only decreased the total and plasma membrane ClC-Kb protein expression but did not affect the subcellular localization. Finally, we studied the physiological functions of mutations by using whole-cell patch clamp and found that E15 or TCT mutation decreased the current of ClC-Kb/barttin channel. These results suggested that the compound defective mutations of CLCNKB gene are the molecular mechanism of the two cBS siblings.

Phosphatidylinositol 4,5-bisphosphate, cholesterol, and fatty acids modulate the calcium-activated chloride channel TMEM16A (ANO1).

Science.gov (United States)

De Jesús-Pérez, José J; Cruz-Rangel, Silvia; Espino-Saldaña, Ángeles E; Martínez-Torres, Ataúlfo; Qu, Zhiqiang; Hartzell, H Criss; Corral-Fernandez, Nancy E; Pérez-Cornejo, Patricia; Arreola, Jorge

2018-03-01

The TMEM16A-mediated Ca 2+ -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 Ca 2+ . On the other hand, supplying PI(4,5)P2 to inside-out patches attenuated channel rundown and/or partially rescued activity after channel rundown. Also, depletion (with methyl-β-cyclodextrin M-βCD) or restoration (with M-βCD+cholesterol) of membrane cholesterol slows down the current decay observed after reduction of PI(4,5)P2. Neither depletion nor restoration of cholesterol change PI(4,5)P2 content. However, M-βCD alone transiently increases TMEM16A activity and dampens rundown whereas M-βCD+cholesterol increases channel rundown. Thus, PI(4,5)P2 is required for TMEM16A function while cholesterol directly and indirectly via a PI(4,5)P2-independent mechanism regulate channel function. Stearic, arachidonic, oleic, docosahexaenoic, and eicosapentaenoic fatty acids as well as methyl stearate inhibit TMEM16A in a dose- and voltage-dependent manner. Phosphatidylserine, a phospholipid whose hydrocarbon tails contain stearic and oleic acids also inhibits TMEM16A. Finally, we show that TMEM16A remains in the plasma membrane after treatment with M-βCD, M-βCD+cholesterol, oleic, or docosahexaenoic acids. Thus, we propose that lipids and fatty acids regulate TMEM16A channels through a membrane-delimited protein-lipid interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced intermediate temperature sodium copper chloride battery

Science.gov (United States)

Yang, Li-Ping; Liu, Xiao-Min; Zhang, Yi-Wei; Yang, Hui; Shen, Xiao-Dong

2014-12-01

Sodium metal chloride batteries, also called as ZEBRA batteries, possess many merits such as low cost, high energy density and high safety, but their high operation temperature (270-350 °C) may cause several issues and limit their applications. Therefore, decreasing the operation temperature is of great importance in order to broaden their usage. Using a room temperature ionic liquid (RTIL) catholyte composed of sodium chloride buffered 1-ethyl-3-methylimidazolium chloride-aluminum chloride and a dense β″-aluminates solid electrolyte film with 500 micron thickness, we report an intermediate temperature sodium copper chloride battery which can be operated at only 150 °C, therefore alleviating the corrosion issues, improving the material compatibilities and reducing the operating complexities associated with the conventional ZEBRA batteries. The RTIL presents a high ionic conductivity (0.247 S cm-1) at 150 °C and a wide electrochemical window (-2.6 to 2.18 vs. Al3+/Al). With the discharge plateau at 2.64 V toward sodium and the specific capacity of 285 mAh g-1, this intermediate temperature battery exhibits an energy density (750 mWh g-1) comparable to the conventional ZEBRA batteries (728-785 mWh g-1) and superior to commercialized Li-ion batteries (550-680 mWh g-1), making it very attractive for renewable energy integration and other grid related applications.

Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels.

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Yan Xu

Full Text Available Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to 10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

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Stylianos Michalakis

2018-03-01

Full Text Available The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP or cyclic adenosine monophosphate (cAMP. Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN channels and voltage-gated potassium channels (KCN. In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

Radiation fixation of vinyl chloride in an insecticide aerosol container

International Nuclear Information System (INIS)

Kagiya, V.T.; Takemoto, K.

1975-01-01

Recently, a large quantity of vinyl chloride has been used as spraying additive for insecticide aerosols. Since January 1974 when the Food and Drug Administration of the United States of America announced that vinyl chloride causes liver cancer, it has been forbidden in Japan and the United States of America to market insecticide aerosol containers containing vinyl chloride. In Japan, following a government order, about 20 million insecticide aerosol containers have been collected and put into storage. A report is given on the radiation fixation of vinyl chloride as polyvinylchloride powder by gamma-ray-induced polymerization in the aerosol container. Insecticide aerosol containers containing vinyl chloride were irradiated by gamma rays from 60 Co at room temperature. Vinyl chloride polymerized to form powdered polymer in the container. Polymerization conversion increased with the irradiation dose, and after 10 Mrad irradiation, vinyl chloride was not found in the sprayed gas. This establishes that vinyl chloride can be fixed by gamma-ray irradiation in the aerosol container. To accelerate the reaction rate, the effect of various additives on the reaction was investigated. It was found that halogenated hydrocarbons, such as chloroform and carbon tetrachloride, accelerated the initiation of the polymerization, and that a vinyl monomer such as vinyl acetate accelerated the reaction rate due to the promotion of the initiation and the high reactivity of the polyvinylacetate radical to vinyl chloride. Consequently, the required irradiation dose for the fixation of vinyl chloride was decreased to less than 5 Mrad by the addition of various kinds of additives. Following the request of the Ministry of Public Welfare, various technical problems for large-scale treatment are being studied with the co-operation of the Federation of Insecticide Aerosols. (author)

Viscosity and density tables of sodium chloride solutions

Energy Technology Data Exchange (ETDEWEB)

Fair, J.A.; Ozbek, H. (comps.)

1977-04-01

A file is presented containing tabulated data extracted from the scientific literature on the density and viscosity of aqueous sodium chloride solutions. Also included is a bibliography of the properties of aqueous sodium chloride solutions. (MHR)

Determination of chloride in water. A comparison of three methods

International Nuclear Information System (INIS)

Steele, P.J.

1978-09-01

The presence of chloride in the water circuits of nuclear reactors, power stations and experimental rigs is undesirable because of the possibility of corrosion. Three methods are considered for the determination of chloride in water in the 0 to 10 μg ml -1 range. The potentiometric method, using a silver-silver chloride electrode, is capable of determining chloride above the 0.1μg ml -1 level, with a standard deviation of 0.03 to 0.12 μg ml -1 in the range 0.1 to 6.0 μg ml -1 chloride. Bromide, iodide and strong reducing agents interfere but none of the cations likely to be present has an effect. The method is very susceptible to variations in temperature. The turbidimetric method involves the production of suspended silver chloride by the addition of silver nitride solution to the sample. The method is somewhat unreliable and is more useful as a rapid, routine limit-testing technique. In the third method, chloride in the sample is pre-concentrated by co-precipitation on lead phosphate, redissolved in acidified ferric nitrate solution and determined colorimetrically by the addition of mercuric thiocyanate solution. It is suitable for determining chloride in the range 0 to 50 μg, using a sample volume of 100 to 500 ml. None of the chemical species likely to be present interferes. In all three methods, chloride contamination can occur at any point in the determination. Analyses should be carried out in conditions where airborne contamination is minimised and a high degree of cleanliness must be maintained. (author)

Corrosion Risk of Reinforced Concrete Structure Arising from Internal and External Chloride

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M. J. Kim

2018-01-01

Full Text Available The corrosion risk of internal chloride and external chloride from three different exposure conditions was evaluated. The initiation of corrosion was detected by monitoring the galvanic current between cathode metal and embedded steel. The chloride threshold was determined by measuring the corrosion rate of steel by the polarization technique for internal chloride and the chloride profiling test for external chloride. As the result, the initiation of corrosion was accelerated with a cyclic wet/dry condition, compared to the totally wet condition. In addition, it was found that an increase of the drying ratio in the exposure condition resulted in an increase of corrosion rate after initiation. The threshold level of external chloride ranged from 0.2 to 0.3% weight by cement and internal chloride shows higher range, equated to 1.59–3.10%. Based on these data, the chloride penetration with exposure condition was predicted to determine the service life of reinforced concrete structure.

Accelerated testing for chloride threshold of reinforcing steel in concrete

NARCIS (Netherlands)

Polder, R.B.; Put, M. van; Peelen, W.H.A.

2017-01-01

Testing for the chloride threshold (also called critical chloride content) for corrosion initiation of steel in concrete has been found difficult and, at best, time consuming. Nevertheless, the chloride threshold is an important parameter in service life design of new structures and for evaluation

High lumenal chloride in the lysosome is critical for lysosome function.

Science.gov (United States)

Chakraborty, Kasturi; Leung, KaHo; Krishnan, Yamuna

2017-07-25

Lysosomes are organelles responsible for the breakdown and recycling of cellular machinery. Dysfunctional lysosomes give rise to lysosomal storage disorders as well as common neurodegenerative diseases. Here, we use a DNA-based, fluorescent chloride reporter to measure lysosomal chloride in Caenorhabditis elegans as well as murine and human cell culture models of lysosomal diseases. We find that the lysosome is highly enriched in chloride, and that chloride reduction correlates directly with a loss in the degradative function of the lysosome. In nematodes and mammalian cell culture models of diverse lysosomal disorders, where previously only lysosomal pH dysregulation has been described, massive reduction of lumenal chloride is observed that is ~10 3 fold greater than the accompanying pH change. Reducing chloride within the lysosome impacts Ca 2+ release from the lysosome and impedes the activity of specific lysosomal enzymes indicating a broader role for chloride in lysosomal function.

Absorption media for irreversibly gettering thionyl chloride

Science.gov (United States)

Buffleben, George; Goods, Steven H.; Shepodd, Timothy; Wheeler, David R.; Whinnery, Jr., LeRoy

2002-01-01

Thionyl chloride is a hazardous and reactive chemical used as the liquid cathode in commercial primary batteries. Contrary to previous thinking, ASZM-TEDA.RTM. carbon (Calgon Corporation) reversibly absorbs thionyl chloride. Thus, several candidate materials were examined as irreversible getters for thionyl chloride. The capacity, rate and effect of temperature were also explored. A wide variety of likely materials were investigated through screening experiments focusing on the degree of heat generated by the reaction as well as the material absorption capacity and irreversibility, in order to help narrow the group of possible getter choices. More thorough, quantitative measurements were performed on promising materials. The best performing getter was a mixture of ZnO and ASZM-TEDA.RTM. carbon. In this example, the ZnO reacts with thionyl chloride to form ZnCl.sub.2 and SO.sub.2. The SO.sub.2 is then irreversibly gettered by ASZM-TEDA.RTM. carbon. This combination of ZnO and carbon has a high capacity, is irreversible and functions effectively above -20.degree. C.

Amperometric Sensor for Detection of Chloride Ions†

Science.gov (United States)

Trnkova, Libuse; Adam, Vojtech; Hubalek, Jaromir; Babula, Petr; Kizek, Rene

2008-01-01

Chloride ion sensing is important in many fields such as clinical diagnosis, environmental monitoring and industrial applications. We have measured chloride ions at a carbon paste electrode (CPE) and at a CPE modified with solid AgNO3, a solution of AgNO3 and/or solid silver particles. Detection limits (3 S/N) for chloride ions were 100 μM, 100 μM and 10 μM for solid AgNO3, solution of AgNO3 and/or solid silver particles, respectively. The CPE modified with silver particles is the most sensitive to the presence chloride ions. After that we approached to the miniaturization of the whole electrochemical instrument. Measurements were carried out on miniaturized instrument consisting of a potentiostat with dimensions 35 × 166 × 125 mm, screen printed electrodes, a peristaltic pump and a PC with control software. Under the most suitable experimental conditions (Britton-Robinson buffer, pH 1.8 and working electrode potential 550 mV) we estimated the limit of detection (3 S/N) as 500 nM. PMID:27873832

Amperometric Sensor for Detection of Chloride Ions.

Science.gov (United States)

Trnkova, Libuse; Adam, Vojtech; Hubalek, Jaromir; Babula, Petr; Kizek, Rene

2008-09-15

Chloride ion sensing is important in many fields such as clinical diagnosis, environmental monitoring and industrial applications. We have measured chloride ions at a carbon paste electrode (CPE) and at a CPE modified with solid AgNO₃, a solution of AgNO₃ and/or solid silver particles. Detection limits (3 S/N) for chloride ions were 100 μM, 100 μM and 10 μM for solid AgNO₃, solution of AgNO₃ and/or solid silver particles, respectively. The CPE modified with silver particles is the most sensitive to the presence chloride ions. After that we approached to the miniaturization of the whole electrochemical instrument. Measurements were carried out on miniaturized instrument consisting of a potentiostat with dimensions 35 × 166 × 125 mm, screen printed electrodes, a peristaltic pump and a PC with control software. Under the most suitable experimental conditions (Britton-Robinson buffer, pH 1.8 and working electrode potential 550 mV) we estimated the limit of detection (3 S/N) as 500 nM.

21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pantothenate, calcium chloride double salt... FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.330 Calcium pantothenate, calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may...

Mutagenicity of vinyl chloride after metabolic activation

Energy Technology Data Exchange (ETDEWEB)

Rannug, U; Johansson, A; Ramel, C; Wachtmeister, C A

1974-01-01

Vinyl chloride has recently been shown to cause a malignant liver tumor disease in man after occupational exposure in PVC plants. This actualizes the problem of whether such hazards could be avoided or at least diminished in the future by a screening for mutagenicity of chemicals used in industries. The basis for such a screening procedure is the close correlation between carcinogenic and mutagenic effects of chemicals. Experiments with Salmonella bacteria showed that the carcinogenic hazard of vinyl chloride could have been traced by means of mutagenicity tests. The data indicate that vinyl chloride is not mutagenic per se but becomes mutagenic after a metabolic activation in the liver. 24 references, 1 figure, 4 tables.

Chloride Ingress in Concrete Cracks under Cyclic Loading

DEFF Research Database (Denmark)

Küter, André; Geiker, Mette Rica; Olesen, John Forbes

2005-01-01

was similar for both sets and the maximum crack width was kept constant throughout the exposure period by means of precracking and an external prestressed reinforcement. Chloride profiles after 40 days revealed a considerable increase in ingress towards the crack tip in contrast to data from the literature....... Preliminary investigations have been undertaken to quantify the effect of dynamic load application on the chloride ingress into concrete cracks. Specimens were designed allowing ingress of a chloride solution into a single crack of a saturated unreinforced mortar beam. One set of specimens was subjected...... to a load frequency of ten applications per minute and a second set to one application per hour simulating static cracks, however limiting the ingress hampering effects of autogenous healing and a possible dense precipitation on the crack faces. The averaged chloride exposure interval of the crack faces...

Denitrification of fertilizer wastewater at high chloride concentration

DEFF Research Database (Denmark)

Ucisik, Ahmed Süheyl; Henze, Mogens

Wastewater from fertilizer industry is characterized by high contents of chloride concentration, which normally vary between 60 and 76 g/l. Experiments with bilogical denitrification were performed in lab-scale "fill and draw" reactors with synthetic wastewater with chloride concentrations up to 77.......4 g/l. The results of the experiments showed that biological denitrification was feasible at the extreme environmental conditions prevailing in fertilizer wastewater. Stable continuous biological denitrfication of the synthetic high chloride wastewater was performed up to 77.4 g Cl/l at 37 degree C...

Lithium-thionyl chloride batteries - past, present and future

Energy Technology Data Exchange (ETDEWEB)

McCartney, J.F.; Lund, T.J.; Sturgeon, W.J.

1980-02-01

Lithium based batteries have the highest theoretical energy density of known battery types. Of the lithium batteries, the lithium-thionyl chloride electrochemistry has the highest energy density of those which have been reduced to practice. The characteristics, development status, and performance of lithium-thionyl chloride batteries are treated in this paper. Safety aspects of lithium-thionyl chloride batteries are discussed along with impressive results of hazard/safety tests of these batteries. An orderly development plan of a minimum family of standard cells to avoid a proliferation of battery sizes and discharge rates is presented.

Formation of mixed hydroxides in the thorium chloride-iron chloride-sodium hydroxide system

International Nuclear Information System (INIS)

Krivokhatskij, A.S.; Prokudina, A.F.; Sapozhnikova, T.V.

1976-01-01

The process of formation of mixed hydroxides in the system thorium chloride-iron chloride-NaOH was studied at commensurate concentrations of Th and Fe in solution (1:1 and 1:10 mole fractions, respectively) with ionic strength 0.3, 2.1, and 4.1, created with the electrolyte NaCl, at room temperature 22+-1degC. By the methods of chemical, potentiometric, thermographic, and IR-spectrometric analyses, it was shown that all the synthesized precipitates are mechanical mixtures of two phases - thorium hydroxide and iron hydroxide - and not a new hydrated compound. The formal solubility of the precipitates of mixed hydroxides was determined. It was shown that the numerical value of the formal solubility depends on the conditions of formation and age of the precipitates

Genomic characterization, phylogenetic comparison and differential expression of the cyclic nucleotide-gated channels gene family in pear (Pyrus bretchneideri Rehd.).

Science.gov (United States)

Chen, Jianqing; Yin, Hao; Gu, Jinping; Li, Leiting; Liu, Zhe; Jiang, Xueting; Zhou, Hongsheng; Wei, Shuwei; Zhang, Shaoling; Wu, Juyou

2015-01-01

The cyclic nucleotide-gated channel (CNGC) family is involved in the uptake of various cations, such as Ca(2+), to regulate plant growth and respond to biotic and abiotic stresses. However, there is far less information about this family in woody plants such as pear. Here, we provided a genome-wide identification and analysis of the CNGC gene family in pear. Phylogenetic analysis showed that the 21 pear CNGC genes could be divided into five groups (I, II, III, IVA and IVB). The majority of gene duplications in pear appeared to have been caused by segmental duplication and occurred 32.94-39.14 million years ago. Evolutionary analysis showed that positive selection had driven the evolution of pear CNGCs. Motif analyses showed that Group I CNGCs generally contained 26 motifs, which was the greatest number of motifs in all CNGC groups. Among these, eight motifs were shared by each group, suggesting that these domains play a conservative role in CNGC activity. Tissue-specific expression analysis indicated that functional diversification of the duplicated CNGC genes was a major feature of long-term evolution. Our results also suggested that the P-S6 and PBC & hinge domains had co-evolved during the evolution. These results provide valuable information to increase our understanding of the function, evolution and expression analyses of the CNGC gene family in higher plants. Copyright © 2014 Elsevier Inc. All rights reserved.

Preparation and characterization of poly-(methacrylatoethyl trimethylammonium chloride-co-vinylbenzyl chloride-co-ethylene dimethacrylate monolith

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Eko Malis

2015-05-01

Full Text Available A polymer monolithic column, poly-(methacrylatoethyltrimethylammonium chloride-co-vinylbenzyl chloride-co-ethylene dimethacrylate or poly-(MATE-co-VBC-co-EDMA was successfully prepared in the current study by one-step thermally initiated in situ polymerization, confined in a steel tubing of 0.5 mm i.d. and 1/16” o.d. The monoliths were prepared from methacrylatoethyltrimethylammonium chloride (MATE and vinylbenzyl chloride (VBC as monomer and ethylene dimethacrylate (EDMA as crosslinker using a binary porogen system of 1-propanol and 1,4-butanediol. The inner wall of steel tubing was pretreated with 3-methacryloxypropyl-trimethoxysilane (MAPS. In order to obtain monolith with adequate column efficiency and low flow resistance, some parameters such as total monomer concentration (%T and crosslinker concentration (%C were optimized. The morphology of this monolith was assessed by scanning electron microscopy (SEM. The properties of the monolithic column, such as permeability, binding capacity, and pore size distribution were also characterized in detail. From the results of the characterization of all monolith variation, monolith with %T 30 %C 50 and %T 35 %C 50 give the best characteristic. These monoliths have high permeability, adequate molecular recognition sites (represented with binding capacity value of over 20 mg/mL, and have over 80% flow through pores in their pore structure contribute to low flow resistance. The resulted monolithic columns have promising potential for dual mode liquid chromatography. MATE may contribute for anion-exchange while VBC may responsible for reversed-phase liquid chromatography.

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer.

Science.gov (United States)

Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

2016-12-01

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

VOCl as a Cathode for Rechargeable Chloride Ion Batteries.

Science.gov (United States)

Gao, Ping; Reddy, M Anji; Mu, Xiaoke; Diemant, Thomas; Zhang, Le; Zhao-Karger, Zhirong; Chakravadhanula, Venkata Sai Kiran; Clemens, Oliver; Behm, R Jürgen; Fichtner, Maximilian

2016-03-18

A novel room temperature rechargeable battery with VOCl cathode, lithium anode, and chloride ion transporting liquid electrolyte is described. The cell is based on the reversible transfer of chloride ions between the two electrodes. The VOCl cathode delivered an initial discharge capacity of 189 mAh g(-1) . A reversible capacity of 113 mAh g(-1) was retained even after 100 cycles when cycled at a high current density of 522 mA g(-1) . Such high cycling stability was achieved in chloride ion batteries for the first time, demonstrating the practicality of the system beyond a proof of concept model. The electrochemical reaction mechanism of the VOCl electrode in the chloride ion cell was investigated in detail by ex situ X-ray diffraction (XRD), infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The results confirm reversible deintercalation-intercalation of chloride ions in the VOCl electrode. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Local impermeant anions establish the neuronal chloride concentration

DEFF Research Database (Denmark)

Glykys, J; Dzhala, V; Egawa, K

2014-01-01

Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of γ-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulat...

Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells.

Science.gov (United States)

Canella, Rita; Benedusi, Mascia; Martini, Marta; Cervellati, Franco; Cavicchio, Carlotta; Valacchi, Giuseppe

2018-08-01

The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O 3 exposure alters the Cl - current-voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O 3 byproducts (4hydroxynonenal (HNE) and/or H 2 O 2 ) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30' before electrophysiological analysis) did not reproduce O 3 effect, H 2 O 2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O 3 response. This result was confirmed treating the cell with catalase (CAT) before O 3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl - current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre-treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl - current. These data bring new insights into the mechanisms involved in OS-induced lung tissue damage, pointing out the role of H 2 O 2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect. © 2017 Wiley Periodicals, Inc.

AlN powder synthesis via nitriding reaction of aluminum sub-chloride

Energy Technology Data Exchange (ETDEWEB)

Ohashi, T.; Nishida, T.; Sugiura, M. (Waseda Univ., Tokyo (Japan). Graduate School); Fuwa, A. (Waseda Univ., Tokyo (Japan))

1993-06-01

In order to obtain the pertinent properties of aluminium nitride in its sintered form, it is desirable to have powders of finer sizes with narrower size distribution and higher purity, thereby making the sintering processing easier and the final body denser. Instead of using sublimated aluminum tri-chloride vapor (AlCl3) as an aluminum source in the vapor phase nitriding reaction, the mixed aluminum chloride vapor consisted of aluminum tri-chloride, bi-chloride and mono-chloride are used in the reaction with ammonia at temperatures of 1000 and 1200K. The mixed chloride vapors are produced by reacting chlorine with molten aluminum at 1000 or 1200K under atmospheric pressure. The reaction of this mixed chloride vapor with ammonia is then experimentally investigated to study the aluminum nitride powder morphology. The aluminum nitride powders synthesized under various ammonia concentrations are characterized for size distribution, mean particle size and particle morphology. 24 refs., 8 figs., 2 tabs.

High lumenal chloride in the lysosome is critical for lysosome function

Science.gov (United States)

Chakraborty, Kasturi; Leung, KaHo; Krishnan, Yamuna

2017-01-01

Lysosomes are organelles responsible for the breakdown and recycling of cellular machinery. Dysfunctional lysosomes give rise to lysosomal storage disorders as well as common neurodegenerative diseases. Here, we use a DNA-based, fluorescent chloride reporter to measure lysosomal chloride in Caenorhabditis elegans as well as murine and human cell culture models of lysosomal diseases. We find that the lysosome is highly enriched in chloride, and that chloride reduction correlates directly with a loss in the degradative function of the lysosome. In nematodes and mammalian cell culture models of diverse lysosomal disorders, where previously only lysosomal pH dysregulation has been described, massive reduction of lumenal chloride is observed that is ~103 fold greater than the accompanying pH change. Reducing chloride within the lysosome impacts Ca2+ release from the lysosome and impedes the activity of specific lysosomal enzymes indicating a broader role for chloride in lysosomal function. DOI: http://dx.doi.org/10.7554/eLife.28862.001 PMID:28742019

Chloride Sources and Losses in Two Tile-Drained Agricultural Watersheds.

Science.gov (United States)

David, Mark B; Mitchell, Corey A; Gentry, Lowell E; Salemme, Ronald K

2016-01-01

Chloride is a relatively unreactive plant nutrient that has long been used as a biogeochemical tracer but also can be a pollutant causing aquatic biology impacts when concentrations are high, typically from rock salt applications used for deicing roads. Chloride inputs to watersheds are most often from atmospheric deposition, road salt, or agricultural fertilizer, although studies on agricultural watersheds with large fertilizer inputs are few. We used long-term (21 and 17 yr) chloride water quality data in two rivers of east-central Illinois to better understand chloride biogeochemistry in two agricultural watersheds (Embarras and Kaskaskia), the former with a larger urban land use and both with extensive tile drainage. During our sampling period, the average chloride concentration was 23.7 and 20.9 mg L in the Embarras and Kaskaskia Rivers, respectively. Annual fluxes of chloride were 72.5 and 61.2 kg ha yr in the Embarras and Kaskaskia watersheds, respectively. In both watersheds, fertilizer chloride was the dominant input (∼49 kg ha yr), with road salt likely the other major source (23.2 and 7.2 kg ha yr for the Embarras and Kaskaskia watersheds, respectively). Combining our monitoring data with earlier published data on the Embarras River showed an increase in chloride concentrations as potash use increased in Illinois during the 1960s and 1970s with a lag of about 2 to 6 yr to changes in potash inputs based on a multiple-regression model. In these agricultural watersheds, riverine chloride responds relatively quickly to potash fertilization as a result of tile-drainage. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Thermodynamic properties of molten mixtures of lithium, rubidium, cesium and beryllium chlorides

International Nuclear Information System (INIS)

Zarubitskij, O.G.; Podafa, B.P.; Dubovoj, P.G.

1982-01-01

e. m. f. in binary systems of beryllium chloride with rubidium and cesium chlorides were measured. Concentration dependences of thermodynamic functions (mixing entropy Gibbs free energy) of beryllium chloride in the systems as well as with the participation of lithium chloride were analysed

MITOCHONDRIAL BKCa CHANNEL

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Enrique eBalderas

2015-03-01

Full Text Available Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS, voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.

Potentiometric Determination of Free Chloride in Cement Paste – an ...

African Journals Online (AJOL)

... cement paste.16 The accuracy and reliability of this analytical technique has been checked against a certified reference material, Merck sodium chloride solution. Confidence levels (CL0.95), of 0.03 and relative standard deviations of 0.2 % for chloride were determined for ordinary Portland cement (OPC) chloride binding ...

Impact of chloride on denitrification potential in roadside wetlands

International Nuclear Information System (INIS)

Lancaster, Nakita A.; Bushey, Joseph T.; Tobias, Craig R.; Song, Bongkeun; Vadas, Timothy M.

2016-01-01

Developed landscapes are exposed to changes in hydrology and water chemistry that limit their ability to mitigate detrimental impacts to coastal water bodies, particularly those that result from stormwater runoff. The elevated level of impervious cover increases not only runoff but also contaminant loading of nutrients, metals, and road salt used for deicing to water bodies. Here we investigate the impact that road salt has on denitrification in roadside environments. Sediments were collected from a series of forested and roadside wetlands and acclimated with a range of Cl − concentrations from 0 to 5000 mg L −1 for 96 h. Denitrification rates were measured by the isotope pairing technique using 15 N–NO 3 − , while denitrifying community structures were compared using terminal restriction fragment length polymorphism (T-RFLP) of nitrous oxide reductase genes (nosZ). Chloride significantly (p < 0.05) inhibited denitrification in forested wetlands at a Cl − dosage of 2500 or 5000 mg L −1 , but the decrease in denitrification rates was less and not significant for the roadside wetlands historically exposed to elevated concentrations of Cl − . The difference could not be attributed to other significant changes in conditions, such as DOC concentrations, N species concentrations, or pH levels. Denitrifying communities, as measured by T-RFs of the nosZ gene, in the roadside wetlands with elevated concentration of Cl − were distinctly different and more diverse compared to forested wetlands, and also different in roadside wetlands after 96 h exposures to Cl − . The shifts in denitrifying communities seem to minimize the decrease in denitrification rates in the wetlands previously exposed to Cl. As development results in more Cl − use and exposure to a broad range of natural or manmade wetland structures, an understanding of the seasonal effect of Cl on denitrification processes in these systems would aid in design or mitigation of the effects on

New Potentiometric Wireless Chloride Sensors Provide High Resolution Information on Chemical Transport Processes in Streams

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Keith Smettem

2017-07-01

Full Text Available Quantifying the travel times, pathways, and dispersion of solutes moving through stream environments is critical for understanding the biogeochemical cycling processes that control ecosystem functioning. Validation of stream solute transport and exchange process models requires data obtained from in-stream measurement of chemical concentration changes through time. This can be expensive and time consuming, leading to a need for cheap distributed sensor arrays that respond instantly and record chemical transport at points of interest on timescales of seconds. To meet this need we apply new, low-cost (in the order of a euro per sensor potentiometric chloride sensors used in a distributed array to obtain data with high spatial and temporal resolution. The application here is to monitoring in-stream hydrodynamic transport and dispersive mixing of an injected chemical, in this case NaCl. We present data obtained from the distributed sensor array under baseflow conditions for stream reaches in Luxembourg and Western Australia. The reaches were selected to provide a range of increasingly complex in-channel flow patterns. Mid-channel sensor results are comparable to data obtained from more expensive electrical conductivity meters, but simultaneous acquisition of tracer data at several positions across the channel allows far greater spatial resolution of hydrodynamic mixing processes and identification of chemical ‘dead zones’ in the study reaches.

Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome.

Science.gov (United States)

Matsunoshita, Natsuki; Nozu, Kandai; Yoshikane, Masahide; Kawaguchi, Azusa; Fujita, Naoya; Morisada, Naoya; Ishimori, Shingo; Yamamura, Tomohiko; Minamikawa, Shogo; Horinouchi, Tomoko; Nakanishi, Keita; Fujimura, Junya; Ninchoji, Takeshi; Morioka, Ichiro; Nagase, Hiroaki; Taniguchi-Ikeda, Mariko; Kaito, Hiroshi; Iijima, Kazumoto

2018-05-30

Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.

Chloride transport in mortar at low moisture concentration

NARCIS (Netherlands)

Taher, A.; Zanden, van der A.J.J.; Brouwers, H.J.H.

2014-01-01

Chloride penetration into cementitious structures with a steel reinforcement results in corrosion of the steel. Concrete columns of bridges, which are in frequent contact with sea water, are an example of these structures. Understanding the chloride transport in cementitious materials can lead to

Role of chloride ions in the promotion of auxin-induced growth of maize coleoptile segments.

Science.gov (United States)

Burdach, Zbigniew; Kurtyka, Renata; Siemieniuk, Agnieszka; Karcz, Waldemar

2014-10-01

The mechanism of auxin action on ion transport in growing cells has not been determined in detail. In particular, little is known about the role of chloride in the auxin-induced growth of coleoptile cells. Moreover, the data that do exist in the literature are controversial. This study describes experiments that were carried out with maize (Zea mays) coleoptile segments, this being a classical model system for studies of plant cell elongation growth. Growth kinetics or growth and pH changes were recorded in maize coleoptiles using two independent measuring systems. The growth rate of the segments was measured simultaneously with medium pH changes. Membrane potential changes in parenchymal cells of the segments were also determined for chosen variants. The question of whether anion transport is involved in auxin-induced growth of maize coleoptile segments was primarily studied using anion channel blockers [anthracene-9-carboxylic acid (A-9-C) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS)]. In addition, experiments in which KCl was replaced by KNO3 were also performed. Both anion channel blockers, added at 0·1 mm, diminished indole-3-acetic acid (IAA)-induced elongation growth by ~30 %. Medium pH changes measured simultaneously with growth indicated that while DIDS stopped IAA-induced proton extrusion, A-9-C diminished it by only 50 %. Addition of A-9-C to medium containing 1 mm KCl did not affect the characteristic kinetics of IAA-induced membrane potential changes, while in the presence of 10 mm KCl the channel blocker stopped IAA-induced membrane hyperpolarization. Replacement of KCl with KNO3 significantly decreased IAA-induced growth and inhibited proton extrusion. In contrast to the KCl concentration, the concentration of KNO3 did not affect the growth-stimulatory effect of IAA. For comparison, the effects of the cation channel blocker tetraethylammonium chloride (TEA-Cl) on IAA-induced growth and proton extrusion were also determined. TEA

The use of dansyl-calmodulin to study interactions with channels and other proteins.

Science.gov (United States)

Alaimo, Alessandro; Malo, Covadonga; Areso, Pilar; Aloria, Kerman; Millet, Oscar; Villarroel, Alvaro

2013-01-01

Steady-state fluorescence spectroscopy is a biophysical technique widely employed to characterize -interactions between proteins in vitro. Only a few proteins naturally fluoresce in cells, but by covalently attaching fluorophores virtually all proteins can be monitored. One of the first extrinsic fluorescent probes to be developed, and that is still in use, is dansyl chloride. We have used this method to monitor the interaction of a variety of proteins, including ion channels, with the Ca(2+)-dependent regulatory protein calmodulin. Here we describe the preparation and use of dansyl-calmodulin (D-CaM).

Surface adsorption in strontium chloride ammines

DEFF Research Database (Denmark)

Ammitzbøll, Andreas L.; Lysgaard, Steen; Klukowska, Agata

2013-01-01

An adsorbed state and its implications on the ab- and desorption kinetics of ammonia in strontium chloride ammine is identified using a combination of ammonia absorption measurements, thermogravimetric analysis, and density functional theory calculations. During thermogravimetric analysis, ammonia...... desorption originating from the adsorbed state is directly observed below the bulk desorption temperature, as confirmed by density functional theory calculations. The desorption enthalpy of the adsorbed state of strontium chloride octa-ammine is determined with both techniques to be around 37-39 k...

Free and bound chloride contents in cementitious materials

NARCIS (Netherlands)

Marinescu, M.V.A.; Brouwers, H.J.H.; Fischer, G.; Geiker, M.; Hededal, O.; Ottoson, L.; Stang, H.

2010-01-01

Chloride attack is the main cause of structural damage in reinforced concrete buildings exposed to marine environments. When a certain threshold concentration of chlorides is reached at the concrete-reinforcement interface, the corrosion of the steel rebars is initiated. A part of the intruding

Effect of multipurpose solutions against Acinetobacter carrying QAC genes.

Science.gov (United States)

Boost, Maureen V; Chan, Jessica; Shi, Guang-sen; Cho, Pauline

2014-03-01

Acinetobacter has low virulence but causes infections in subjects with reduced immunity. It has been reported in ocular infections including those of patients using contact lenses. Treatment is difficult because Acinetobacter is frequently multidrug resistant. Antibiotic-resistant strains frequently also harbor genes for antiseptic resistance (quaternary ammonium compound [QAC]) genes. Because Acinetobacter is part of the normal flora, it may contaminate contact lens and accessories. This study aims to investigate carriage rates of QAC genes in household and clinical isolates of Acinetobacter and to determine the effectiveness of two multipurpose solutions (MPSs) for soft lenses against organisms carrying QAC genes. DNA was extracted from 11 bathroom isolates and 15 clinical isolates and amplified by polymerase chain reaction to determine the presence of qacEΔ1. Gene-positive and gene-negative control strains were used to challenge the two MPSs, and minimum inhibitory concentrations (MICs) of these organisms to benzalkonium chloride and chlorhexidine gluconate were determined. More than 90% of isolates carried qacEΔ1. The MICs of clinical isolates were higher than those of isolates of bathrooms. Both MPSs were able to produce a 3-log reduction in the numbers of all isolates. Although most isolates carried qacEΔ1 and elevated MICs to benzalkonium chloride and chlorhexidine gluconate were observed, all were susceptible to both MPSs tested. However, if there were to be poor compliance with care procedures, it is probable that such organisms could survive in the presence of diluted or expired solutions.

Chloride ion erosion experiment research in cracked concrete

Science.gov (United States)

Ting, Shu; Yang, Li

2017-08-01

For the study of chloride ion erosion in cracked concrete, this essay tries to take advantages of relevant trails to build up concrete chloride ion diffusion model based on the Fick’s second law. The parameter of this model is easy to be set, and many factors such as the effect of cracks are taken into consideration in this experiment. The concept of “chloride ion diffusion coefficient of equivalent apparent” is introduced to simplify the calculation. It can help simplify the calculation process, and get a more accurate test result, as well as facilitating the practical application of this parameter.

separation of strontium and cesium from ternary and quaternary lithium chloride-potassium chloride salts via melt crystallization

Directory of Open Access Journals (Sweden)

Ammon N. Williams

2015-12-01

Full Text Available Separation of cesium chloride (CsCl and strontium chloride (SrCl2 from the lithium chloride-potassium chloride (LiCl-KCl salt was studied using a melt crystallization process similar to the reverse vertical Bridgeman growth technique. A ternary SrCl2-LiCl-KCl salt was explored at similar growth rates (1.8–5 mm/h and compared with CsCl ternary results to identify similarities. Quaternary experiments were also conducted and compared with the ternary cases to identify trends and possible limitations to the separations process. In the ternary case, as much as 68% of the total salt could be recycled per batch process. In the quaternary experiments, separation of Cs and Sr was nearly identical at the slower rates; however, as the growth rate increased, SrCl2 separated more easily than CsCl. The quaternary results show less separation and rate dependence than in both ternary cases. As an estimated result, only 51% of the total salt could be recycled per batch. Furthermore, two models have been explored to further understand the growth process and separation. A comparison of the experimental and modeling results reveals that the nonmixed model fits reasonably well with the ternary and quaternary data sets. A dimensional analysis was performed and a correlation was identified to semipredict the segregation coefficient.

Separation of strontium and cesium from ternary and quaternary lithium chloride-potassium chloride salts via melt crystallization

Energy Technology Data Exchange (ETDEWEB)

Williams, Ammon n.; Pack, Michael [Dept. of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond (United States); Phongikaroon, Spathorn [Dept. of Chemical and Materials Engineering and Nuclear Engineering Program, University of Idaho, Idaho Falls (United States)

2015-12-15

Separation of cesium chloride (CsCl) and strontium chloride (SrCl{sub 2}) from the lithium chloride-potassium chloride (LiCl-KCl) salt was studied using a melt crystallization process similar to the reverse vertical Bridgeman growth technique. A ternary SrCl2-LiCl-KCl salt was explored at similar growth rates (1.8-5 mm/h) and compared with CsCl ternary results to identify similarities. Quaternary experiments were also conducted and compared with the ternary cases to identify trends and possible limitations to the separations process. In the ternary case, as much as 68% of the total salt could be recycled per batch process. In the quaternary experiments, separation of Cs and Sr was nearly identical at the slower rates; however, as the growth rate increased, SrCl{sub 2} separated more easily than CsCl. The quaternary results show less separation and rate dependence than in both ternary cases. As an estimated result, only 51% of the total salt could be recycled per batch. Furthermore, two models have been explored to further understand the growth process and separation. A comparison of the experimental and modeling results reveals that the nonmixed model fits reasonably well with the ternary and quaternary data sets. A dimensional analysis was performed and a correlation was identified to semipredict the segregation coefficient.

Gene expression profile of sodium channel subunits in the anterior cingulate cortex during experimental paclitaxel-induced neuropathic pain in mice

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Willias Masocha

2016-11-01

Full Text Available Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Nav subunits by real time polymerase chain reaction (PCR in the anterior cingulate cortex (ACC at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia. The ACC was chosen because increased activity in the ACC has been observed during neuropathic pain. In the ACC of vehicle-treated animals the threshold cycle (Ct values for Nav1.4, Nav1.5, Nav1.7, Nav1.8 and Nav1.9 were above 30 and/or not detectable in some samples. Thus, comparison in mRNA expression between untreated control, vehicle-treated and paclitaxel treated animals was done for Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nax as well as Navβ1–Navβ4. There were no differences in the transcript levels of Nav1.1–Nav1.3, Nav1.6, Nax, Navβ1–Navβ3 between untreated and vehicle-treated mice, however, vehicle treatment increased Navβ4 expression. Paclitaxel treatment significantly increased the mRNA expression of Nav1.1, Nav1.2, Nav1.6 and Nax, but not Nav1.3, sodium channel alpha subunits compared to vehicle-treated animals. Treatment with paclitaxel significantly increased the expression of Navβ1 and Navβ3, but not Navβ2 and Navβ4, sodium channel beta subunits compared to vehicle-treated animals. These findings suggest that during paclitaxel-induced neuropathic pain (PINP there is differential upregulation of sodium channels in the ACC, which might contribute to the increased neuronal activity observed in the area during neuropathic pain.

Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

Science.gov (United States)

Facer, Paul; Punjabi, Prakash P; Abrari, Andleeb; Kaba, Riyaz A; Severs, Nicholas J; Chambers, John; Kooner, Jaspal S; Anand, Praveen

2011-01-01

We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

Chloride ingress profiles measured by electron probe micro analysis

DEFF Research Database (Denmark)

Jensen, Ole mejlhede; Coats, Alison M.; Glasser, Fred P.

1996-01-01

Traditional techniques for measuring chloride ingress profiles do not apply well to high performance cement paste systems; the geometric resolution of the traditional measuring techniques is too low. In this paper measurements by Electron Probe Micro Analysis (EPMA) are presented. EPMA is demonst......Traditional techniques for measuring chloride ingress profiles do not apply well to high performance cement paste systems; the geometric resolution of the traditional measuring techniques is too low. In this paper measurements by Electron Probe Micro Analysis (EPMA) are presented. EPMA...... is demonstated to determine chloride ingress in cement paste on a micrometer scale. Potential chloride ingress routes such as cracks or the paste-aggregate interface may also be characterized by EPMA. Copyright (C) 1996 Elsevier Science Ltd...

A study on dehydration of rare earth chloride hydrate

International Nuclear Information System (INIS)

Cho, Yong Zun; Eun, Hee Chul; Son, Sung Mo; Lee, Tae Kyo; Hwang, Taek Sung

2012-01-01

The dehydration schemes of rare earth (La, Ce, Nd, Pr, Sm. Eu, Gd, Y) chloride hydrates was investigated by using a dehydration apparatus. To prevent the formation of the rare earth oxychlorides, the operation temperature was changed step by step (80→150→230 degree C) based on the TGA (thermo-gravimetric analysis) results of the rare earth chloride hydrates. A vacuum pump and preheated Ar gas were used to effectively remove the evaporated moisture and maintain an inert condition in the dehydration apparatus. The dehydration temperature of the rare earth chloride hydrate was increased when the atomic number of the rare earth nuclide was increased. The content of the moisture in the rare earth chloride hydrate was decreased below 10% in the dehydration apparatus.

Amperometric Sensor for Detection of Chloride Ions

Directory of Open Access Journals (Sweden)

Rene Kizek

2008-09-01

Full Text Available Chloride ion sensing is important in many fields such as clinical diagnosis, environmental monitoring and industrial applications. We have measured chloride ions at a carbon paste electrode (CPE and at a CPE modified with solid AgNO3, a solution of AgNO3 and/or solid silver particles. Detection limits (3 S/N for chloride ions were 100 μM, 100 μM and 10 μM for solid AgNO3, solution of AgNO3 and/or solid silver particles, respectively. The CPE modified with silver particles is the most sensitive to the presence chloride ions. After that we approached to the miniaturization of the whole electrochemical instrument. Measurements were carried out on miniaturized instrument consisting of a potentiostat with dimensions 35 × 166 × 125 mm, screen printed electrodes, a peristaltic pump and a PC with control software. Under the most suitable experimental conditions (Britton-Robinson buffer, pH 1.8 and working electrode potential 550 mV we estimated the limit of detection (3 S/N as 500 nM.

Diffusion Decay Coefficient for Chloride Ions of Concrete Containing Mineral Admixtures

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Jae-Im Park

2016-01-01

Full Text Available The diffusion coefficient for chloride ions and the diffusion decay coefficient for chloride ions are essential variables for a service life evaluation of concrete structures. They are influenced by water-binder ratio, exposure condition, curing temperature, cement type, and the type and use of mineral admixture. Mineral admixtures such as ground granulated blast furnace slag, fly ash, and silica fume have been increasingly used to improve resistance against chloride ions penetration in concrete structures built in an offshore environment. However, there is not enough measured data to identify the statistical properties of diffusion decay coefficient for chloride ions in concrete using mineral admixtures. This paper is aimed at evaluating the diffusion decay coefficient for chloride ions of concrete using ordinary Portland cement or blended cement. NT BUILD 492 method, an electrophoresis experiment, was used to measure the diffusion coefficient for chloride ions with ages. It was revealed from the test results that the diffusion decay coefficient for chloride ions was significantly influenced by W/B and the replacement ratio of mineral admixtures.

Calcium homeostasis modulator (CALHM) ion channels.

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Ma, Zhongming; Tanis, Jessica E; Taruno, Akiyuki; Foskett, J Kevin

2016-03-01

Calcium homeostasis modulator 1 (CALHM1), formerly known as FAM26C, was recently identified as a physiologically important plasma membrane ion channel. CALHM1 and its Caenorhabditis elegans homolog, CLHM-1, are regulated by membrane voltage and extracellular Ca(2+) concentration ([Ca(2+)]o). In the presence of physiological [Ca(2+)]o (∼1.5 mM), CALHM1 and CLHM-1 are closed at resting membrane potentials but can be opened by strong depolarizations. Reducing [Ca(2+)]o increases channel open probability, enabling channel activation at negative membrane potentials. Together, voltage and Ca(2+) o allosterically regulate CALHM channel gating. Through convergent evolution, CALHM has structural features that are reminiscent of connexins and pannexins/innexins/LRRC8 (volume-regulated anion channel (VRAC)) gene families, including four transmembrane helices with cytoplasmic amino and carboxyl termini. A CALHM1 channel is a hexamer of CALHM1 monomers with a functional pore diameter of ∼14 Å. CALHM channels discriminate poorly among cations and anions, with signaling molecules including Ca(2+) and ATP able to permeate through its pore. CALHM1 is expressed in the brain where it plays an important role in cortical neuron excitability induced by low [Ca(2+)]o and in type II taste bud cells in the tongue that sense sweet, bitter, and umami tastes where it functions as an essential ATP release channel to mediate nonsynaptic neurotransmitter release. CLHM-1 is expressed in C. elegans sensory neurons and body wall muscles, and its genetic deletion causes locomotion defects. Thus, CALHM is a voltage- and Ca(2+) o-gated ion channel, permeable to large cations and anions, that plays important roles in physiology.

Improved electrolyte for lithium-thionyl chloride battery. [Patent application

Energy Technology Data Exchange (ETDEWEB)

Shipman, W.H.; McCartney, J.F.

1980-12-17

A lithium, thionyl chloride battery is provided with an electrolyte which makes it safe under a reverse voltage condition. The electrolyte is niobium pentachloride which is dissolved in the thionyl chloride.

Tissue distribution of 1,2-14C-vinyl chloride in rats

International Nuclear Information System (INIS)

Buchter, A.; Bolt, H.M.; Kappus, H.; Bolt, W.

1977-01-01

Rats have been pretreatet with 6-nitro-1.2.3-benzothiadiazole which completely blocks the metabolism of vinyl chloride. If the animals are exposed to atmospheric vinyl chloride, the formation of an equilibrium between the compound in the gas phase and in the animal's organism is observed. Unmetabolized vinyl chloride is accumulated in the adipose tissue. The distribution pattern of vinyl in different organs of the rat is constant over the concentration range of 25-10,000 ppm of vinyl chloride in the exposure atmosphere. The distribution of metabolites of vinyl chloride contrasts to that of the original compound; metabolites primarily are concentrated in liver and in kidneys. (orig.) [de

Computer Simulation Studies of Ion Channels at High Temperatures

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Song, Hyun Deok

The gramicidin channel is the smallest known biological ion channel, and it exhibits cation selectivity. Recently, Dr. John Cuppoletti's group at the University of Cincinnati showed that the gramicidin channel can function at high temperatures (360 ˜ 380K) with significant currents. This finding may have significant implications for fuel cell technology. In this thesis, we have examined the gramicidin channel at 300K, 330K, and 360K by computer simulation. We have investigated how the temperature affects the current and differences in magnitude of free energy between the two gramicidin forms, the helical dimer (HD) and the double helix (DH). A slight decrease of the free energy barrier inside the gramicidin channel and increased diffusion at high temperatures result in an increase of current. An applied external field of 0.2V/nm along the membrane normal results in directly observable ion transport across the channels at high temperatures for both HD and DH forms. We found that higher temperatures also affect the probability distribution of hydrogen bonds, the bending angle, the distance between dimers, and the size of the pore radius for the helical dimer structure. These findings may be related to the gating of the gramicidin channel. Methanococcus jannaschii (MJ) is a methane-producing thermophile, which was discovered at a depth of 2600m in a Pacific Ocean vent in 1983. It has the ability to thrive at high temperatures and high pressures, which are unfavorable for most life forms. There have been some experiments to study its stability under extreme conditions, but still the origin of the stability of MJ is not exactly known. MJ0305 is the chloride channel protein from the thermophile MJ. After generating a structure of MJ0305 by homology modeling based on the Ecoli ClC templates, we examined the thermal stability, and the network stability from the change of network entropy calculated from the adjacency matrices of the protein. High temperatures increase the

Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

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Sheila G Crewther

Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

Modelling of chloride penetration in concrete under wet/dry cycle

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Hong Sung-In

2017-01-01

Full Text Available This present study concerns modelling of chloride penetration in partially saturated concrete. To mimic the intermittent exposure of sea water to concrete, varying environmental conditions for relative humidity and chloride concentration were considered. As for the moisture distribution in concrete, statistical permeability model based on pore size distribution was used to represent influence of material properties on moisture transport. Then, a combined chloride diffusion and convection was modelled in variation of moisture level in concrete. As a result, smaller relative wet duration induces higher rate of chloride penetration due to enhanced moisture permeability from the surface, and also higher concentration gradient near the surface of concrete due to repeated wet/dry cycle. This implies that only diffusion analysis on chloride induced corrosion in concrete structure may underestimate the serviceability in given material performance.

Genome-wide gene expression profiling of acute metal exposures in male zebrafish

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Christine E. Baer

2014-12-01

Full Text Available To capture global responses to metal poisoning and mechanistic insights into metal toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate at concentrations corresponding to their respective 96 h LC20, LC40 and LC60 (i.e. 96 h concentrations at which 20%, 40% and 60% lethality is expected, respectively. Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal exposure. Here we describe in detail the contents and quality controls for the gene expression and other data associated with the study published by Hussainzada and colleagues in BMC Pharmacology and Toxicology (Hussainzada et al., 2014 with the data uploaded to Gene Expression Omnibus (accession number GSE50648.

The Arabidopsis vacuolar malate channel is a member of the ALMT family.

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Kovermann, Peter; Meyer, Stefan; Hörtensteiner, Stefan; Picco, Cristiana; Scholz-Starke, Joachim; Ravera, Silvia; Lee, Youngsook; Martinoia, Enrico

2007-12-01

In plants, malate is a central metabolite and fulfills a large number of functions. Vacuolar malate may reach very high concentrations and fluctuate rapidly, whereas cytosolic malate is kept at a constant level allowing optimal metabolism. Recently, a vacuolar malate transporter (Arabidopsis thaliana tonoplast dicarboxylate transporter, AttDT) was identified that did not correspond to the well-characterized vacuolar malate channel. We therefore hypothesized that a member of the aluminum-activated malate transporter (ALMT) gene family could code for a vacuolar malate channel. Using GFP fusion constructs, we could show that AtALMT9 (A. thaliana ALMT9) is targeted to the vacuole. Promoter-GUS fusion constructs demonstrated that this gene is expressed in all organs, but is cell-type specific as GUS activity in leaves was detected nearly exclusively in mesophyll cells. Patch-clamp analysis of an Atalmt9 T-DNA insertion mutant exhibited strongly reduced vacuolar malate channel activity. In order to functionally characterize AtALMT9 as a malate channel, we heterologously expressed this gene in tobacco and in oocytes. Overexpression of AtALMT9-GFP in Nicotiana benthamiana leaves strongly enhanced the malate current densities across the mesophyll tonoplasts. Functional expression of AtALMT9 in Xenopus oocytes induced anion currents, which were clearly distinguishable from endogenous oocyte currents. Our results demonstrate that AtALMT9 is a vacuolar malate channel. Deletion mutants for AtALMT9 exhibit only slightly reduced malate content in mesophyll protoplasts and no visible phenotype, indicating that AttDT and the residual malate channel activity are sufficient to sustain the transport activity necessary to regulate the cytosolic malate homeostasis.

Chloride migration in concrete with superabsorbent polymers

DEFF Research Database (Denmark)

Hasholt, Marianne Tange; Jensen, Ole Mejlhede

2015-01-01

Superabsorbent polymers (SAP) can be used as a means for internal curing of concrete. In the present study, the development of transport properties of concrete with SAP is investigated. The chloride migration coefficient according to NT BUILD 492 is used as a measure of this. Twenty concrete...... contribute to increase the degree of hydration. No matter if SAP is added with or without extra water, it appears that the so-called gel space ratio can be used as a key parameter to link age and mixture proportions (water-to-cement ratio and SAP dosage) to the resulting chloride migration coefficient......; the higher the volume of gel solid relative to the space available for it, the lower the chloride migration coefficient, because the pore system becomes more tortuous and the porosity becomes less....

Optimization of the lithium/thionyl chloride battery

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