Sample records for boric acid channel

  1. Chronic boric acid poisoning in infants.


    O`Sullivan, K.; Taylor, M.


    We report 7 infants suffering from seizures induced by chronic boric acid ingestion. The boric acid was given by dipping a soother in a proprietary borax and honey mixture. The babies have remained well since the mixture was withheld.

  2. Chronic boric acid poisoning in infants. (United States)

    O'Sullivan, K; Taylor, M


    We report 7 infants suffering from seizures induced by chronic boric acid ingestion. The boric acid was given by dipping a soother in a proprietary borax and honey mixture. The babies have remained well since the mixture was withheld.

  3. Boric Acid in Kjeldahl Analysis (United States)

    Cruz, Gregorio


    The use of boric acid in the Kjeldahl determination of nitrogen is a variant of the original method widely applied in many laboratories all over the world. Its use is recommended by control organizations such as ISO, IDF, and EPA because it yields reliable and accurate results. However, the chemical principles the method is based on are not…

  4. Nanoscale Properties of Boric Acid

    Institute of Scientific and Technical Information of China (English)


    Nanoscale properties of boric acid were studied by using atomic force microscopy (AFM) and nanome-chanical testing system. XPS was used to research on the transform behaviors of H3BO3 at different temperatures.The crystal structure, surface morphology, and mechanical properties of H3BO3 were described. The results showthat H3BO3 has layered structure, and can be transformed to boron oxide at high temperature. In addition there area lot of defects in H3BO3 crystal.

  5. OsNIP3;1, a rice boric acid channel, regulates boron distribution and is essential for growth under boron-deficient conditions. (United States)

    Hanaoka, Hideki; Uraguchi, Shimpei; Takano, Junpei; Tanaka, Mayuki; Fujiwara, Toru


    Boron is an essential micronutrient for higher plants. Boron deficiency is an important agricultural issue because it results in loss of yield quality and/or quantity in cereals and other crops. To understand boron transport mechanisms in cereals, we characterized OsNIP3;1, a member of the major intrinsic protein family in rice (Oryza sativa L.), because OsNIP3;1 is the most similar rice gene to the Arabidopsis thaliana boric acid channel genes AtNIP5;1 and AtNIP6;1. Yeast cells expressing OsNIP3;1 imported more boric acid than control cells. GFP-tagged OsNIP3;1 expressed in tobacco BY2 cells was localized to the plasma membrane. The accumulation of OsNIP3;1 transcript increased fivefold in roots within 6 h of the onset of boron starvation, but not in shoots. Promoter-GUS analysis suggested that OsNIP3;1 is expressed mainly in exodermal cells and steles in roots, as well as in cells around the vascular bundles in leaf sheaths and pericycle cells around the xylem in leaf blades. The growth of OsNIP3;1 RNAi plants was impaired under boron limitation. These results indicate that OsNIP3;1 functions as a boric acid channel, and is required for acclimation to boron limitation. Boron distribution among shoot tissues was altered in OsNIP3;1 knockdown plants, especially under boron-deficient conditions. This result demonstrates that OsNIP3;1 regulates boron distribution among shoot tissues, and that the correct boron distribution is crucial for plant growth.

  6. Boric acid and boronic acids inhibition of pigeonpea urease. (United States)

    Reddy, K Ravi Charan; Kayastha, Arvind M


    Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.

  7. Lubrication from mixture of boric acid with oils and greases (United States)

    Erdemir, Ali


    Lubricating compositions including crystalline boric acid and a base lubricant selected from oils, greases and the like. The lubricity of conventional oils and greases can also be improved by adding concentrates of boric acid.

  8. Boric acid ovicidal trap for the management of Aedes species

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    L Charlet Bhami


    Interpretation & conclusion: Boric acid is less toxic compared to different pesticides, and in low concentrations, it attracts the ovipositing female Aedes sp as well as fertile males. Dilute boric acid solution is an effective ovitrap since the eggs laid by mosquitoes either die or the larvae that hatch out from them do not survive in boric acid. Boric acid kills the males that come in contact with the solution, which are attracted to the trap by the females hovering around.

  9. Thermal properties of epoxy composites filled with boric acid (United States)

    Visakh, P. M.; Nazarenko, O. B.; Amelkovich, Yu A.; Melnikova, T. V.


    The thermal properties of epoxy composites filled with boric acid fine powder at different percentage were studied. Epoxy composites were prepared using epoxy resin ED-20, boric acid as flame-retardant filler, hexamethylenediamine as a curing agent. The prepared samples and starting materials were examined using methods of thermal analysis, scanning electron microscopy and infrared spectroscopy. It was found that the incorporation of boric acid fine powder enhances the thermal stability of epoxy composites.

  10. Thermal properties of epoxy composites filled with boric acid


    Visakh, P. M.; Nazarenko, Olga Bronislavovna; Amelkovich, Yuliya Alexandrovna; Melnikova, T. V.


    The thermal properties of epoxy composites filled with boric acid fine powder at different percentage were studied. Epoxy composites were prepared using epoxy resin ED-20, boric acid as flame-retardant filler, hexamethylenediamine as a curing agent. The prepared samples and starting materials were examined using methods of thermal analysis, scanning electron microscopy and infrared spectroscopy. It was found that the incorporation of boric acid fine powder enhances the thermal stability of ep...

  11. Chemical Reaction between Boric Acid and Phosphine Indicates Boric Acid as an Antidote for Aluminium Phosphide Poisoning

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    Motahareh Soltani


    Full Text Available Objectives: Aluminium phosphide (AlP is a fumigant pesticide which protects stored grains from insects and rodents. When it comes into contact with moisture, AlP releases phosphine (PH3, a highly toxic gas. No efficient antidote has been found for AlP poisoning so far and most people who are poisoned do not survive. Boric acid is a Lewis acid with an empty p orbital which accepts electrons. This study aimed to investigate the neutralisation of PH3 gas with boric acid. Methods: This study was carried out at the Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran, between December 2013 and February 2014. The volume of released gas, rate of gas evolution and changes in pH were measured during reactions of AlP tablets with water, acidified water, saturated boric acid solution, acidified saturated boric acid solution, activated charcoal and acidified activated charcoal. Infrared spectroscopy was used to study the resulting probable adduct between PH3 and boric acid. Results: Activated charcoal significantly reduced the volume of released gas (P <0.01. Although boric acid did not significantly reduce the volume of released gas, it significantly reduced the rate of gas evolution (P <0.01. A gaseous adduct was formed in the reaction between pure AlP and boric acid. Conclusion: These findings indicate that boric acid may be an efficient and non-toxic antidote for PH3 poisoning.

  12. Chemical Reaction between Boric Acid and Phosphine Indicates Boric Acid as an Antidote for Aluminium Phosphide Poisoning (United States)

    Soltani, Motahareh; Shetab-Boushehri, Seyed F.; Shetab-Boushehri, Seyed V.


    Objectives: Aluminium phosphide (AlP) is a fumigant pesticide which protects stored grains from insects and rodents. When it comes into contact with moisture, AlP releases phosphine (PH3), a highly toxic gas. No efficient antidote has been found for AlP poisoning so far and most people who are poisoned do not survive. Boric acid is a Lewis acid with an empty p orbital which accepts electrons. This study aimed to investigate the neutralisation of PH3 gas with boric acid. Methods: This study was carried out at the Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran, between December 2013 and February 2014. The volume of released gas, rate of gas evolution and changes in pH were measured during reactions of AlP tablets with water, acidified water, saturated boric acid solution, acidified saturated boric acid solution, activated charcoal and acidified activated charcoal. Infrared spectroscopy was used to study the resulting probable adduct between PH3 and boric acid. Results: Activated charcoal significantly reduced the volume of released gas (P <0.01). Although boric acid did not significantly reduce the volume of released gas, it significantly reduced the rate of gas evolution (P <0.01). A gaseous adduct was formed in the reaction between pure AlP and boric acid. Conclusion: These findings indicate that boric acid may be an efficient and non-toxic antidote for PH3 poisoning. PMID:27606109

  13. Influence of boric acid additive size on green lubricant performance. (United States)

    Lovell, Michael R; Kabir, M A; Menezes, Pradeep L; Higgs, C Fred


    As the industrial community moves towards green manufacturing processes, there is an increased demand for multi-functional, environmentally friendly lubricants with enhanced tribological performance. In the present investigation, green (environmentally benign) lubricant combinations were prepared by homogeneously mixing nano- (20 nm), sub-micrometre- (600 nm average size) and micrometre-scale (4 μm average size) boric acid powder additives with canola oil in a vortex generator. As a basis for comparison, lubricants of base canola oil and canola oil mixed with MoS(2) powder (ranging from 0.5 to 10 μm) were also prepared. Friction and wear experiments were carried out on the prepared lubricants using a pin-on-disc apparatus under ambient conditions. Based on the experiments, the nanoscale (20 nm) particle boric acid additive lubricants significantly outperformed all of the other lubricants with respect to frictional and wear performance. In fact, the nanoscale boric acid powder-based lubricants exhibited a wear rate more than an order of magnitude lower than the MoS(2) and larger sized boric acid additive-based lubricants. It was also discovered that the oil mixed with a combination of sub-micrometre- and micrometre-scale boric acid powder additives exhibited better friction and wear performance than the canola oil mixed with sub-micrometre- or micrometre-scale boric acid additives alone.

  14. The Acid-Base Titration of a Very Weak Acid: Boric Acid (United States)

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.


    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  15. Surface interactions of cesium and boric acid with stainless steel

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    Grossman-Canfield, N.


    In this report, the effects of cesium hydroxide and boric acid on oxidized stainless steel surfaces at high temperatures and near one atmosphere of pressure are investigated. This is the first experimental investigation of this chemical system. The experimental investigations were performed using a mass spectrometer and a mass electrobalance. Surfaces from the different experiments were examined using a scanning electron microscope to identify the presence of deposited species, and electron spectroscopy for chemical analysis to identify the species deposited on the surface. A better understanding of the equilibrium thermodynamics, the kinetics of the steam-accelerated volatilizations, and the release kinetics are gained by these experiments. The release rate is characterized by bulk vaporization/gas-phase mass transfer data. The analysis couples vaporization, deposition, and desorption of the compounds formed by cesium hydroxide and boric acid under conditions similar to what is expected during certain nuclear reactor accidents. This study shows that cesium deposits on an oxidized stainless steel surface at temperatures between 1000 and 1200 Kelvin. Cesium also deposits on stainless steel surfaces coated with boric oxide in the same temperature ranges. The mechanism for cesium deposition onto the oxide layer was found to involve the chemical reaction between cesium and chromate. Some revaporization in the cesium hydroxide-boric acid system was observed. It has been found that under the conditions given, boric acid will react with cesium hydroxide to form cesium metaborate. A model is proposed for this chemical reaction.

  16. 40 CFR 721.3032 - Boric acid (H3BO2), zinc salt. (United States)


    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN...

  17. Influence of boric acid on electrospray ionization efficiency. (United States)

    Rebane, Riin; Herodes, Koit


    Liquid chromatography electrospray ionization mass-spectrometry (LC-ESI-MS) was used to analyze 9-fluorenylmethylmethoxycarbonyl chloride (Fmoc-Cl) and diethyl ethoxymethylenemalonate (Deemm) derivatives of three amino acids and five other compounds. Influence of boric acid on their ionization was investigated and dramatic impact on the signal was observed. The strongest signal suppression (6% of signal remains) was observed for the Deemm derivative of beta-Alanine (with ammonium acetate in eluent). With only formic acid as the eluent pH modifier, signal enhancement was observed, being largest for Fmoc-Cl derivative of Phenylalanine, 267%. Investigation of the influence of boric acid shows that it is a possible signal enhancer for LC-ESI-MS analysis.

  18. Synthesis of Enriched 10B Boric Acid of Nuclear Grade

    Institute of Scientific and Technical Information of China (English)

    张雷; 张卫江; 徐姣; 任新


    An economic and effective method of preparing enriched 10B boric acid was established by chemical reac-tion of enriched 10BF3 and CaCO3. A process of boron trifluoride reacting with water was investigated under certain conditions. Calcium carbonate was selected to counteract hydrofluoric acid followed on. Some key operation factors were investigated, such as temperature, reaction time and the ratio of CaCO3 to 10BF3. The results showed that the yield of enriched 10B boric acid could reach 97. 2%and the purity was up to 94. 1%under the following conditions:the tem-perature was 50—60,℃, the reaction time was 28 h and the ratio of CaCO3 to 10BF3 was 4. In addition, after recrystal-lization and titration analysis, the purity of the product could reach over 99. 2%from 94.1%.

  19. Zinc-Nickel Codeposition in Sulfate Solution Combined Effect of Cadmium and Boric Acid

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    Y. Addi


    Full Text Available The combined effect of cadmium and boric acid on the electrodeposition of zinc-nickel from a sulfate has been investigated. The presence of cadmium ion decreases zinc in the deposit. In solution, cadmium inhibits the zinc ion deposition and suppresses it when deposition potential value is more negative than −1.2 V. Low concentration of CdSO4 reduces the anomalous nature of Zn-Ni deposit. Boric acid decreases current density and shifts potential discharge of nickel and hydrogen to more negative potential. The combination of boric acid and cadmium increases the percentage of nickel in the deposit. Boric acid and cadmium.

  20. Effect of boric acid supplementation of ostrich water on the expression of Foxn1 in thymus. (United States)

    Xiao, Ke; Ansari, Abdur Rahman; Rehman, Zia Ur; Khaliq, Haseeb; Song, Hui; Tang, Juan; Wang, Jing; Wang, Wei; Sun, Peng-Peng; Zhong, Juming; Peng, Ke-Mei


    Foxn1 is essential for thymus development. The relationship between boric acid and thymus development, optimal dose of boric acid in ostrich diets, and the effects of boric acid on the expression of Foxn1 were investigated in the present study. Thirty healthy ostriches were randomly divided into six groups: Group I, II, III, IV, V, VI, and supplemented with boric acid at the concentration of 0 mg/L, 40 mg/L, 80 mg/L, 160 mg/L, 320 mg/L, 640 mg/L, respectively. The histological changes in thymus were observed by HE staining, and the expression of Foxn1 analyzed by immunohistochemistry and western blot. TUNEL method was used to label the apoptotic cells. Ostrich Foxn1 was sequenced by Race method. The results were as following: Apoptosis in ostrich thymus was closely related with boric acid concentrations. Low boric acid concentration inhibited apoptosis in thymus, but high boric acid concentration promoted apoptosis. Foxn1-positive cells were mainly distributed in thymic medulla and rarely in cortex. Foxn1 is closely related to thymus growth and development. The nucleotide sequence and the encoded protein of Foxn1 were 2736 bases and 654 amino acids in length. It is highly conserved as compared with other species. These results demonstrated that the appropriate boric acid supplementation in water would produce positive effects on the growth development of ostrich thymus by promoting Foxn1 expression, especially at 80 mg/L, and the microstructure of the thymus of ostrich fed 80 mg/L boric acid was well developed. The supplementation of high dose boron (>320 mg/L) damaged the microstructure of thymus and inhibited the immune function by inhibiting Foxn1 expression, particularly at 640 mg/L. The optimal dose of boric acid supplementation in ostrich diets is 80 mg/L boric acid. The genomic full-length of African ostrich Foxn1 was cloned for the first time in the study.


    Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.Cherrington JW, Chernoff N.Department of Toxicology, North Carolina State University, Raleigh, NC 27695, USA. jana_cherrington@hotmail.comBoric acid (BA) has many uses as...

  2. Boric acid equilibria in near-critical and supercritical water

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    Wofford, W.T.; Gloyna, E.F.; Johnston, K.P. [Univ. of Texas, Austin, TX (United States)


    Greater knowledge of acid-base equilibria is crucial to understanding the chemistry of hydrothermal processes including oxidation of organics, corrosion, catalysis, hydrolysis reactions, crystal growth and formation, precipitation of metal complexes and steam power cycles. The pH values of aqueous solutions of boric acid and KOH were measured with the optical indicator 2-naphthol at temperatures from 300 to 380 C. The equilibrium constant K{sub b}{sup {minus}1} for the reaction B(OH){sub 3} + OH{sup {minus}} = B(OH){sub 4}{sup {minus}} was determined from the pH measurements and correlated with a modified Born model. The titration curve for the addition of HCl to sodium borate exhibits strong acid-strong base behavior even at 350 C and 24.1 MPa. At these conditions, aqueous solutions of sodium borate buffer the pH at 9.6 {+-} 0.25.

  3. Radiolysis of Boric Acid Solutions under Mixed Thermal and Fast Neutrons

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    Im, Heejung; Choi, Ke Chon; Yeon, Jeiwon; Song, Kyuseok; Jung Hoansung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    The thermal neutron irradiation of water samples containing neutron absorbers has not been published except for a paper reporting the experimental data obtained at high temperatures. However, irradiation or simulations of water and voluminous liquid samples with fast neutrons and gamma rays are frequently discussed in several published papers. Several water samples containing {sup 10}B-enriched boric acid, and natural and {sup 10}B-enriched mixed boric acids in the range of 0 to 2000 μg/mL for the function of {sup 10}B concentration, were irradiated to study the radiolysis of the cooling water containing boric acid. The concentration of natural boron in the primary coolant of pressurized water reactors (PWRs) is known to start at 1500 μg/mL, and boric acid is used for the purpose of nuclear reaction control.

  4. An efficient synthesis of 1,5-benzodiazepine derivatives catalyzed by boric acid

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Mei Yue Zhang; Shu Tao Gao; Jing Jun Ma; Chun Wang; Chao Liu


    1,5-Benzodiazepine derivatives have been synthesized by the condensation of o-phenylenediamines and ketones in the presence of boric acid as catalyst under mild conditions. This method is simple, environmentally benign and high yielding.

  5. Preparation and characterization of (10)B boric acid with high purity for nuclear industry. (United States)

    Zhang, Weijiang; Liu, Tianyu; Xu, Jiao


    Boric acid is often added into coolant as neutron capture agent for pressurized water reactor, whose amount is influenced by its abundance and purity. Therefore, the preparation of enriched (10)B boric acid with high purity is beneficial to nuclear industry. (10)B is also used in developing tumor-specific boronated drugs in boron neutron capture therapy. The boronated drug can be administered to patient intravenously, intratumorally, or deposited at tumor site in surgical excision. Thus, enriched (10)B boric acid is of practical significance in the field of medicine. Self-made boron trifluoride-methanol-complex solution was selected as one of the experimental reagents, and the preparation of (10)B acid was realized by one-step reaction for the complexes with water and calcium chloride. The determination of electrical conductivity in reaction process proves that the optimum reaction time was 16-20 h. Furthermore, the effect of reaction time, ratio of calcium chloride to complex as well as the amount of water on the purity and yield of boric acid was investigated. Finally, the optimum reaction time was 20 h, the optimal solid-liquid ratio (molar ratio) was 3:1, and the amount of water was 1 L of deionized water for each mol of the complex. H2O2 was added in the reaction process to remove Fe(2+). After recrystallization, IR spectra of (10)B boric acid was measured and compared with standard to verify the product of boric acid. The feasibility of the preparation method was determined by the detection of XRD of boric acid. To observe the morphology by polarizing microscope, crystal structure was obtained. The purity of the final product is 99.95 %, and the yield is 96.47 %. The ion concentration of boric acid accords with the national standard of high purity, which was determined by ICP.

  6. Rapid accurate isotopic measurements on boron in boric acid and boron carbide. (United States)

    Duchateau, N L; Verbruggen, A; Hendrickx, F; De Bièvre, P


    A procedure is described whereby rapid and accurate isotopic measurements can be performed on boron in boric acid and boron carbide after fusion of these compounds with calcium carbonate. It allows the determination of the isotopic composition of boron in boric acid and boron carbide and the direct assay of boron or the (10)B isotope in boron carbide by isotope-dilution mass spectrometry.

  7. Preparation and Characterization of High Purity Enriched10B Boric Acid via Anti-Solvent Recrystallization

    Institute of Scientific and Technical Information of China (English)

    张卫江; 刘天雨; 徐姣


    Self-made enriched10B boric acid as raw material was purified by recrystallization. The effects of final crystallization temperature, crystallization time, stirring speed, crystallization frequency and other factors on the purity were investigated. The appropriate operating condition was that the final crystallization temperature and time were 5,℃and 10 h respectively under a low-speed stirring for crystallizing twice, which would make the purity and yield of boric acid reach 99.94% and 95.36%, respectively. Taking this as foundation, recrystallization process was optimized with acetone as anti-solvent, whose amount was the most important index. The boric acid solution was added into acetone and recrystallized under the same condition, and the purity and yield of boric acid would reach 99.98% and 99.61%, respectively. The product detected by XRD was confirmed as boric acid crystal. Main ion concentration in the product was detected by ICP, which basically met the national standard of high purity. Crystal morphology of boric acid was observed by SEM.

  8. Removal of Aqueous Boron by Using Complexation of Boric Acid with Polyols: A Raman Spectroscopic Study

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    Eom, Ki Heon; Jeong, Hui Cheol; An, Hye Young; Lim, Jun-Heok; Lee, Jea-Keun; Won, Yong Sun [Pukyong National University, Busan (Korea, Republic of)


    Boron is difficult to be removed from seawater by simple RO (reverse osmosis) membrane process, because the size of boric acid (B(OH){sub 3}), the major form of aqueous boron, is as small as the nominal pore size of RO membrane. Thus, the complexation of boric acid with polyols was suggested as an alternative way to increase the size of aqueous boron compounds and the complexation behavior was investigated with Raman spectroscopy. As a reference, the Raman peak for symmetric B-O stretching vibrational mode both in boric acid and borate ion (B(OH){sub 4}{sup -}) was selected. A Raman peak shift (877 cm{sup -1} →730 cm{sup -1}) was observed to confirm that boric acid in water is converted to borate ion as the pH increases, which is also correctly predicted by frequency calculation. Meanwhile, the Raman peak of borate ion (730 cm{sup -1}) did not appear as the pH increased when polyols were applied into aqueous solution of boric acid, suggesting that the boric acid forms complexing compounds by combining with polyols.

  9. Boric acid as reference substance: pros, cons and standardization. (United States)

    Amorim, M J B; Natal-da-Luz, T; Sousa, J P; Loureiro, S; Becker, L; Römbke, J; Soares, A M V M


    Boric acid (BA) has been successfully used as reference substance in some standard test guidelines. Due to the fact that previously selected reference substances present a significant risk to human health and/or are banned for environmental reasons, BA is being discussed for broader adoption in OECD or ISO guidelines. To provide input on BA data and contribute to the discussion on its suitability as a reference substance, in the present study BA was tested with two standard soil organisms, Enchytraeus albidus and Folsomia candida, in terms of survival, reproduction and avoidance. Additionally, published data on other organisms was analysed to derive the most sensitive soil dwelling invertebrate (hazard concentration-HC5). Results showed that BA affected the tested organisms, being two times more toxic for collembolans (LC50 = 96; EC50 = 54 mg/kg) than for enchytraeids (LC50 = 325; EC50 = 104 mg/kg). No avoidance behaviour occurred despite the fact that BA affects earthworms. Actually, it is the recommended reference substance for the earthworm avoidance test. Clearly, the suitable performance of BA in one species should not be generalized to other species. Absolute toxicity is not an important criterion for the selection of a reference substance, but it has been proposed that effects should occur within a reasonable range, i.e. <1,000 mg/kg. We could confirm, compiling previous data that for most soil invertebrates, the EC50 is expected to be below 1,000 mg/kg. From these data it could be derived that the most sensitive soil dwelling invertebrate (HC5, 50%) is likely to be affected (EC10) at 28 (8-53) mg H(3)BO(3)/Kg, equivalent to 4.6 (1.4-8.7) mg boron/kg.

  10. Effect of Boric Acid on Properties of Calcined Flint Clay-Bauxite Castables

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei; DAI Wenyong


    In order to prolong the working time of calcined flint clay-bauxite castables during construction at high temperature,boric acid was added into the castables.The effect of boric acid on working time and curing cold crushing strength of the castables at 25 ℃ and 35 ℃were investigated.After 24 h curing in mould and another 24 h curing at 110 ℃ after demoulding,the specimens were heat treated at 1 000 ℃,1 300 ℃,and1 500 ℃ for 3 h,respectively.The permanent linear change,bulk density,modulus of rupture,and cold crushing strength were determined.The result shows that there is no need to add boric acid when calcined flint clay-bauxite ca.stables works at 25 ℃ ; when calcined flint clay-bauxite castables works at 35 ℃,boric acid can increase the working time of the castables,but decrease the curing cold crushing strength a little.Adding boric acid into calcined flint clay-bauxite castables doesn' t worsen performance of the castablcs.

  11. Chloride stress corrosion cracking of Alloy 600 in boric acid solutions

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    Berge, Ph. [Electricite de France, 92 - Paris la Defense (France); Noel, D.; Gras, J.M.; Prieux, B. [Electricite de France, 77 - Moret-sur-Loing (France). Direction des Etudes et Recherches


    The high nickel austenitic alloys are generally considered to have good resistance to chloride stress corrosion cracking. In the standard boiling magnesium chloride solution tests, alloys with more than 40% nickel are immune. Nevertheless, more recent data show that cracking can occur in both Alloys 600 and 690 if the solution is acidified. In other low pH media, such as boric acid solution at 100 deg C, transgranular and intergranular cracking are observed in Alloy 600 in the presence of minor concentrations of sodium chloride (2g/I). In concentrated boric acid at higher temperatures (250 and 290 deg C), intergranular cracking also occurs, either when the chloride concentration is high, or at low chloride contents and high oxygen levels. The role of pH and a possible specific action of boric acid are discussed, together with the influence of electrochemical potential. (author) 21 refs.

  12. CEC mechanism in electrochemical oxidation of nitrocatechol-boric acid complexes

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    Rafiee, Mohammad, E-mail: [Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan (Iran, Islamic Republic of); Nematollahi, Davood; Salehzadeh, Hamid [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of)


    Graphical abstract: Display Omitted Highlights: > Nitrochetechol and its anionic form undergo complex reaction with boric acid. > The electron transfer of complex is coupled with both proceeding and following chemical reactions. > Electrochemical behavior of complex is resolved by diagnostic criteria and digital simulation. - Abstract: The electrochemical behavior of nitrocatechols-boric acid complexes in aqueous solution has been studied using cyclic voltammetry. The results indicate that nitrocatechol-boric acid complex derivatives are involved in the CEC mechanism. In this work, the impact of empirical parameters on the shape of the voltammograms is examined based on a CEC mechanism. In addition, homogeneous rate constants of both the preceding and the following reactions were estimated by comparing the experimental cyclic voltammograms with the digitally simulated results. The calculated dissociation constants for the complexes (K{sub d}) and for ring cleavage of nitroquinone (k{sub f2}) were found to vary in the following order: 4-nitrocatechol > 3-methylnitrocatechol > 3-metoxynitrocatechol.

  13. Boric Acid Toxicity Trials on the Wood Borer Heterobostrychus aequalis Waterhouse (Coleoptera: Bostrychidae

    Directory of Open Access Journals (Sweden)

    Daljit K. Singh


    Full Text Available Problem statement: The Heterobostrychus aequalis Waterhouse was a serious pest lumber of timber heveawood. The H. aequalis infest and tunnel along the wood grain, depositing eggs, which concomitantly turn into larvae and reduces the wood starch to a soft powder. The objectives of the study were to establish a suitable method for preservative trials on the wood borer and access the toxicity levels of boric acid for controlling the H. aequalis infestation. Approach: The voracious H. aequalis was collected from infested heveawood, mated and cultured on cassava. The adult beetles were exposed to boric acid treated cassava blocks as pilot trials. The boric acid concentration used was 1-5% including a control. Each treatment consists of five replicates. The voracious of H. aequalis generation was cultured for obtaining its freshly new emerged adult by exposing a number of H. aequalis directly from infested heveawood into artificial diet block and cassava. The mortality, weight loss of the test blocks, frass discharge duration and numbers of holes caused by H. aequalis were observed. Results: The results showed that the H. aequalis infested tended to penetrate the film after wrapping the heveawood with a layer of transparent cling film for 24 h experiment. The H. aequalis larvae stock cultured collected from infested heveawood exhibited differences in colour, activeness and aggression among males and females. The suitable test block size used was (2.0×5.0×1.5 cm3. The freshly emerged voracious of H. aequalis adults was more suitable than the larvae for boric acid toxicity trials. The 2% concentration was sufficiently killed the 4% boric acid treated test blocks. There was no hole observed on 5% boric acid treated test block and hence these concentrations were not infested by H. aequalis due to absence of frass in exposed blocks. Conclusion/Recommendations: There are noticeable physical and behavioural differences between voracious

  14. Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay


    Gülsoy, Nagihan; Yavaş, Cüneyd; Mutlu, Özal


    The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and...

  15. Decay resistance of wood treated with boric acid and tall oil derivates. (United States)

    Temiz, Ali; Alfredsen, Gry; Eikenes, Morten; Terziev, Nasko


    In this study, the effect of two boric acid concentrations (1% and 2%) and four derivates of tall oil with varying chemical composition were tested separately and in combination. The tall oil derivates were chosen in a way that they consist of different amounts of free fatty, resin acids and neutral compounds. Decay tests using two brown rot fungi (Postia placenta and Coniophora puteana) were performed on both unleached and leached test samples. Boric acid showed a low weight loss in test samples when exposed to fungal decay before leaching, but no effect after leaching. The tall oil derivates gave better efficacy against decay fungi compared to control, but are not within the range of the efficacy needed for a wood preservative. Double impregnation with boric acid and tall oil derivates gave synergistic effects for several of the double treatments both in unleached and leached samples. In the unleached samples the double treatment gave a better efficacy against decay fungi than tall oil alone. In leached samples a better efficacy against brown rot fungi were achieved than in samples with boron alone and a nearly similar or better efficacy than for tall oil alone. Boric acid at 2% concentration combined with the tall oil derivate consisting of 90% free resin acids (TO-III) showed the best performance against the two decay fungi with a weight loss less than 3% after a modified pure culture test.

  16. Production of fired construction brick from high sulfate-containing fly ash with boric acid addition. (United States)

    Başpinar, M Serhat; Kahraman, Erhan; Görhan, Gökhan; Demir, Ismail


    The increase of power plant capacity has led to the production of an increasing amount of fly ash that causes high environmental impact in Turkey. Some of the fly ash is utilized within the fired brick industry but high sulfate-containing fly ash creates severe problems during sintering of the fired brick. This study attempted to investigate the potential for converting high sulfate-containing fly ash into useful material for the construction industry by the addition of boric acid. The chemical and mineralogical composition of fly ash and clay were investigated. Boric acid (H(3)BO(3)) was added to fly ash-clay mixtures with up to 5 wt.%. Six different series of test samples were produced by uniaxial pressing. The samples were fired at the industrial clay-brick firing temperatures of 800, 900 and 1000 degrees C. The microstructures of the fired samples were investigated by scanning electron microscopy and some physical and mechanical properties were measured. It was concluded that the firing at conventional brick firing temperature of high sulfate fly ash without any addition of boric acid resulted in very weak strength bricks. The addition of boric acid and clay simultaneously to the high sulfate- containing fly ash brick dramatically increased the compressive strength of the samples at a firing temperature of 1000 degrees C by modifying the sintering behaviour of high sulfate fly ash.

  17. 40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name). (United States)


    ... alkyl esters (generic name). 721.1875 Section 721.1875 Protection of Environment ENVIRONMENTAL... esters (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to...

  18. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Zahir Kzlay; Haydar Ali Erken; Nesibe Kahraman etin; Serdar Akta; Burin rem Abas; Ali Ylmaz


    hTe aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I) , and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI atfer injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA.In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were signiifcantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were signiifcantly greater in group BAI than in group I. Moreover, myelin injury was signiifcantly milder and the intensity of nuclear factor kappa B immunostaining was signiifcantly weaker in group BAI than in group I. hTe results of this study show that administration of boric acid at 100 mg/kg atfer sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions.

  19. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury (United States)

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali


    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions. PMID:27904499

  20. Proposing Boric Acid as an Antidote for Aluminium Phosphide Poisoning by Investigation of the Chemical Reaction Between Boric Acid and Phosphine

    Directory of Open Access Journals (Sweden)

    Motahareh Soltani


    Full Text Available Aluminium phosphide (AlP is a storage fumigant pesticide, which is used to protect stored grains especially from insects and rodents. It releases phosphine (PH3 gas, a highly toxic mitochondrial poison, in contact with moisture, particularly if acidic. Although the exact mechanism of action is unknown so far, the major mechanism of PH3 toxicity seems to be the inhibition of cytochrome-c oxidase and oxidative phosphorylation which eventually results in adenosine triphosphate (ATP depletion and cell death. Death due to AlP poisoning seems to be as a result of myocardial damage. No efficient antidote has been found for AlP poisoning so far, and unfortunately, most of the poisoned human cases die. PH3, like ammonia (NH3, is a Lewis base with a lone-pair electron. However, boric acid (B(OH3 is a Lewis acid with an empty p orbital. It is predicted that lone-pair electron from PH3 is shared with the empty p orbital from B(OH3 and a compound forms in which boron attains its octet. In other words, PH3 is trapped and neutralised by B(OH3. The resulting polar reaction product seems to be excretable by the body due to hydrogen bonding with water molecules. The present article proposes boric acid as a non-toxic and efficient trapping agent and an antidote for PH3 poisoning by investigating the chemical reaction between them.

  1. Evaluation on degradation of cable in nuclear power plant by boric acid

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Munhwan; Song, Geundong; Kim, Yeonku; Maeng, Wanyoung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    Exposures to these conditions for long periods of times can cause a degradation of cable. Borated water is used in the primary systems of PWR plants to control the reactivity during normal plant operation and refueling, and under potential accident conditions. If borated water leaks from primary and secondary systems, significant corrosion problems can develop. However, little research has been carried out on the effects of cable degradation by borated water. In this experiment, TGA, indenting test, and FT-IR were performed to evaluate the degradation of cable by borated water. An evaluation of cable degradation by borated water was carried out. A TGA analysis, the measurement of cable microhardness and an FT-IR analysis before and after spraying with boric acid (B:170,000ppm). It is considered that there is no significant degradation of cables due to spraying with boric acid. More studies on long-term experiments for severe conditions are now progressing.

  2. Effect of boric acid sintering aid on densification of barium ferrite

    Indian Academy of Sciences (India)

    S S Vidyawathi; R Amaresh; L N Satapathy


    Boric acid has been added in 0.1–0.6% range for studying the densification characteristics of solid state sintered barium hexaferrite. Sintering studies have been carried out at three different temperatures. Physical properties like density and porosity have been studied for all compositions. The phase identification and microstructural investigation on the fractured surface have been carried out to understand the effect of sintering aid on the densification characteristics.

  3. General corrosion of metallic materials in boric acid environments; La corrosion generalisee des materiaux metalliques en milieu acide borique

    Energy Technology Data Exchange (ETDEWEB)

    Gras, J.M.


    Certain low-alloy steel components in PWR primary circuit were corroded by leaking water containing boric acid. A number of studies have been performed by manufacturers in the USA and by EDF in France to determine the rate of general corrosion for low-alloy steels in media containing varying concentrations of boric acid. The first part of this paper summarizes the studies performed and indicates how far work has advanced to date in establishing the resistance of stainless steels to general corrosion in concentrated boric acid solutions. The second part of the paper discusses the mechanism of corrosion and proposes a model. Carbon steels and low-alloy steels - carbon steels and low-alloy steels in deaerated diluted boric acid solutions (pH > 4) corrode very slowly (<20{mu}m/year). The corrosion rate is approximately 1 {mu}m/year in the nominal primary water in static conditions; - in non-deaerated solutions, the corrosion rate is determined by the solubility of iron. Important factors are the pH, the temperature and the operating conditions, which determine the iron solubility in the medium: the rate of renewal of the medium or the S/V ratio of the metal surface exposed to the volume of solution. The steel composition is not a determinant factor. Stainless steels. General corrosion of stainless steels in concentrated boric acid solutions depends primarily on their chromium content. Steels containing less than 15% chromium offer excellent resistance to corrosion regardless of their structure or nickel content. The corrosion rate is less than 10 {mu}m/year at 250 deg C and approximately 40 {mu}m/year at 300 deg C. Steels containing 13% chromium corrode in hot concentrated media. The apparent activation energy of general corrosion is approximately 25 kJ.mol{sup -1}. (author). 31 refs., 12 figs., 13 tabs.

  4. Inhibition studies of soybean (Glycine max) urease with heavy metals, sodium salts of mineral acids, boric acid, and boronic acids. (United States)

    Kumar, Sandeep; Kayastha, Arvind M


    Various inhibitors were tested for their inhibitory effects on soybean urease. The K(i) values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20 +/- 0.05 mM, 0.22 +/- 0.04 mM, 1.50 +/- 0.10 mM, and 2.00 +/- 0.11 mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag(+), Hg(2+), and Cu(2+) showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC(50) = 2.3 x 10(-8) mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO(3), and Na(2)SO(4)) showed that only F(-) inhibited soybean urease significantly (IC(50) = 2.9 mM). Competitive type of inhibition was observed for this anion with a K(i) value of 1.30 mM.

  5. Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid (United States)

    Zhan, Honglei; Liang, Jun F.


    Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 drug delivery field.

  6. Evaluation of commercial boric acid containing vials for urine culture: Low risk of contamination and cost effectiveness considerations

    Directory of Open Access Journals (Sweden)

    Suma B Appannanavar


    Full Text Available Background: Urine culture is a gold standard in the diagnosis of urinary tract infection. Clean catch midstream urine collection and prompt transportation is essential for appropriate diagnosis. Improper collection and delay in transportation leads to diagnostic dilemma. In developing countries, higher ambient temperatures further complicate the scenario. Here, we have evaluated the role of boric acid as a preservative for urine samples prior to culture in female patients attending outpatient department at our center. Materials and Method: Consecutive 104 urine samples were cultured simultaneously in plain uricol (Control-C and boric acid containing tubes from Becton Dickinson urine culture kit (Boric acid group-BA. Results: In the real-time evaluation, we found that in almost 57% (59/104 of the urine samples tested, it was more effective in maintaining the number of the organisms as compared to samples in the container without any preservative. Our in vitro study of simulated urine cultures revealed that urine samples could be kept up to 12 h before culture in the preservative without any inhibitory effect of boric acid. Though the use of boric acid kit may marginally increase the initial cost but has indirect effects like preventing delays in treatment and avoidance of false prescription of antibiotics. If the man-hours spent on repeat investigations are also taken into consideration, then the economic cost borne by the laboratory would also decrease manifold with the use of these containers.

  7. Effect of Silica Sol on Boric-sulfuric Acid Anodic Oxidation of LY12CZ Aluminum Alloy

    Directory of Open Access Journals (Sweden)

    LIU Hui-cong


    Full Text Available Aluminum alloy anodizing coatings were prepared for LY12CZ in the boric-sulfuric acid solution (45g/L sulfuric acid,8g/L boric acid with the addition of 10%,20%,30% (volume fractionsilica sol,with the gradient voltage of 15V. The current and voltage transients of the anodizing process were collected by data collection instrument. The surface morphologies,microstructure and chemical composition of the anodic coatings were characterized by scanning electron microscopy (SEM. The corrosion resistance was examined by neutral salt spray,electrochemical impedance spectroscopy (EIS test and titrating test. The results show that the different concentration of silica sol addition can influence the forming and dissolution of anodizing coatings,improve the compactness smoothness and corrosion resistance during the anodizing process in the boric-sulfuric acid solution.

  8. Boric acid as a mobile phase additive for high performance liquid chromatography separation of ribose, arabinose and ribulose. (United States)

    De Muynck, Cassandra; Beauprez, Joeri; Soetaert, Wim; Vandamme, Erick J


    A new high performance liquid chromatographic (HPLC) method is described for the analysis of ribose, arabinose and ribulose mixtures obtained from (bio)chemical isomerization processes. These processes gain importance since the molecules can be used for the synthesis of antiviral therapeutics. The HPLC method uses boric acid as a mobile phase additive to enhance the separation on an Aminex HPX-87K column. By complexing with boric acid, the carbohydrates become negatively charged, thus elute faster from the column by means of ion exlusion and are separated because the complexation capacity with boric acid differs from one carbohydrate to another. Excellent separation between ribose, ribulose and arabinose was achieved with concentrations between 0.1 and 10 gL(-1) of discrete sugar.

  9. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results. (United States)

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian


    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

  10. 40 CFR 721.1730 - Poly(oxy-1,2-ethanediyl), α-butyl-ω-hydroxy, ester with boric acid (H3BO3). (United States)


    ...-hydroxy, ester with boric acid (H3BO3). 721.1730 Section 721.1730 Protection of Environment ENVIRONMENTAL..., ester with boric acid (H3BO3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly(oxy-1,2-ethanediyl), α-butyl-ω-hydroxy, ester with...

  11. 40 CFR 721.1731 - Poly(oxy-1,2-ethanediyl), α-methyl-ω-hydroxy, ester with boric acid (H3BO3). (United States)


    ...-hydroxy, ester with boric acid (H3BO3). 721.1731 Section 721.1731 Protection of Environment ENVIRONMENTAL..., ester with boric acid (H3BO3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly(oxy-1,2-ethanediyl), α-methyl-ω-hydroxy, ester with...

  12. Ecotoxicity of boric acid in standard laboratory tests with plants and soil organisms. (United States)

    Princz, Juliska; Becker, Leonie; Scheffczyk, Adam; Stephenson, Gladys; Scroggins, Rick; Moser, Thomas; Römbke, Jörg


    To verify the continuous sensitivity of ecotoxicological tests (mainly the test organisms), reference substances with known toxicity are regularly tested. Ideally, this substance(s) would lack specificity in its mode action, be bioavailable and readily attainable with cost-effective means of chemical characterization. Boric acid has satisfied these criteria, but has most recently been characterized as a substance of very high concern, due to reproductive effects in humans, thus limiting its recommendation as an ideal reference toxicant. However, there is probably no other chemical for which ecotoxicity in soil has been so intensively studied; an extensive literature review yielded lethal (including avoidance) and sublethal data for 38 taxa. The ecotoxicity data were evaluated using species sensitivity distributions, collectively across all taxa, and separately according to species type, endpoints, soil type and duration. The lack of specificity in the mode of action yielded broad toxicity among soil taxa and soil types, and provided a collective approach to assessing species sensitivity, while taking into consideration differences in test methodologies and exposure durations. Toxicity was species-specific with Folsomia candida and enchytraied species demonstrating the most sensitivity; among plants, the following trend occurred: dicotyledonous (more sensitive) ≫ monocotyledonous ≫ gymnosperm species. Sensitivity was also time and endpoint specific, with endpoints such as lethality and avoidance being less sensitive than reproduction effects. Furthermore, given the breadth of data and toxicity demonstrated by boric acid, lessons learned from its evaluation are discussed to recommend the properties required by an ideal reference substance for the soil compartment.

  13. Equilibrium studies of cellulase aggregates in presence of ascorbic and boric acid. (United States)

    Iram, Afshin; Amani, Samreen; Furkan, Mohammad; Naeem, Aabgeena


    The aggregate formation of cellulase was detected at 300 and 10 mM ascorbic and boric acid respectively. These aggregates showed reduced enzyme activity, loss in near-UV signal, decrease tryptophan and ANS fluorescence. They possess increase in non-native β-sheet structure as evident from far-UV CD and FTIR spectra, large hydrodynamic radii, increase thioflavin T fluorescence and shift in Congo red. Cellulase at 90 mM ascorbic acid exists as molten globule with retention of secondary structure, altered tryptophan environment, high ANS binding and loss in tertiary structure. Ascorbic acid acts as an antioxidant up to 90 mM and beyond this as a pro-oxidant.

  14. Nonclinical safety evaluation of boric acid and a novel borate-buffered contact lens multi-purpose solution, Biotrue™ multi-purpose solution. (United States)

    Lehmann, David M; Cavet, Megan E; Richardson, Mary E


    Multipurpose solutions (MPS) often contain low concentrations of boric acid as a buffering agent. Limited published literature has suggested that boric acid and borate-buffered MPS may alter the corneal epithelium; an effect attributed to cytotoxicity induced by boric acid. However, this claim has not been substantiated. We investigated the effect of treating cells with relevant concentrations of boric acid using two cytotoxicity assays, and also assessed the impact of boric acid on corneal epithelial barrier function by measuring TEER and immunostaining for tight junction protein ZO-1 in human corneal epithelial cells. Boric acid was also assessed in an in vivo ocular model when administered for 28 days. Additionally, we evaluated Biotrue multi-purpose solution, a novel borate-buffered MPS, alone and with contact lenses for ocular compatibility in vitro and in vivo. Boric acid passed both cytotoxicity assays and did not alter ZO-1 distribution or corneal TEER. Furthermore, boric acid was well-tolerated on-eye following repeated administration in a rabbit model. Finally, Biotrue multi-purpose solution demonstrated good ocular biocompatibility both in vitro and in vivo. This MPS was not cytotoxic and was compatible with the eye when administered alone and when evaluated with contact lenses. We demonstrate that boric acid and a borate-buffered MPS is compatible with the ocular environment. Our findings provide evidence that ocular effects reported for some borate-buffered MPS may be incorrectly attributed to boric acid and are more likely a function of the unique combination of ingredients in the MPS formulation tested.

  15. Molecular complexes of alprazolam with carboxylic acids, boric acid, boronic acids, and phenols. Evaluation of supramolecular heterosynthons mediated by a triazole ring. (United States)

    Varughese, Sunil; Azim, Yasser; Desiraju, Gautam R


    A series of molecular complexes, both co-crystals and salts, of a triazole drug-alprazolam-with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor with the acidic coformers. The hydrogen bond patterns exhibited with aromatic carboxylic acids were found to depend on the nature and position of the substituents. Being a strong acid, 2,6-dihydroxybenzoic acid forms a salt with alprazolam. With aliphatic dicarboxylic acids alprazolam forms hydrates and the water molecules play a central role in synthon formation and crystal packing. The triazole ring makes two distinct heterosynthons in the molecular complex with boric acid. Boronic acids and phenols form consistent hydrogen bond patterns, and these are seemingly independent of the substitutional effects. Boronic acids form noncentrosymmetric cyclic synthons, while phenols form O--H...N hydrogen bonds with the triazole ring.

  16. Boric Acid as an Accelerator of Cerium Surface Treatment on Aluminum

    Directory of Open Access Journals (Sweden)

    K. Cruz-Hernández


    Full Text Available Aluminum pieces are often used in various industrial processes like automotive and aerospace manufacturing, as well as in ornamental applications, so it is necessary to develop processes to protect these materials, processes that can be industrialized to protect the aluminum as well or better than chromate treatments. The purpose of this research is to evaluate boric acid as an accelerator by optimizing its concentration in cerium conversion coatings (CeCC with 10-minute immersion time with a concentration of 0.1 g L−1 over aluminum to protect it. The evaluation will be carried out by measuring anticorrosion properties with electrochemical techniques (polarization resistance, Rp, polarization curves, PC, and electrochemical impedance spectroscopy, EIS in NaCl 3.5% wt. aqueous solution and surface characterization with scanning electron microscopy (SEM.

  17. Synthesis of boron carbide nano particles using polyvinyl alcohol and boric acid

    Directory of Open Access Journals (Sweden)

    Amir Fathi


    Full Text Available In this study boron carbide nano particles were synthesized using polyvinyl alcohol and boric acid. First, initial samples with molar ratio of PVA : H3BO3 = 2.7:2.2 were prepared. Next, samples were pyrolyzed at 600, 700 and 800°C followed by heat treatment at 1400, 1500 and 1600°C. FTIR analysis was implemented before and after pyrolysis in order to study the reaction pathway. XRD technique was used to study the composition of produced specimens of boron carbide. Moreover, SEM and PSA analysis were also carried out to study the particle size and morphology of synthesized boron carbide. Finally, according to implemented tests and analyses, carbon-free boron carbide nano particles with an average size of 81 nm and mainly spherical morphology were successfully produced via this method.

  18. Evaluation of ultrasonic technique to characterize the concentration of boric acid in liquid medium; Avaliacao de tecnica ultrassonica para medida de concentracao de acido borico em meio liquido

    Energy Technology Data Exchange (ETDEWEB)

    Kohara, Richard Yuzo Ramida


    This dissertation is to analyze the viability of using ultrasonic technique to characterize the concentration of boric acid in liquid medium non-invasively, therefore, ultrasonic tests were performed relating different boric acid concentrations with the travel time of the ultrasonic wave, also were evaluated factors able to mask the characterization of these concentrations by ultrasonic technique. The results showed that the ultrasonic technique allows the characterization of boric acid concentrations in liquid medium in very simple terms by the ultrasonic wave travel time, requiring further studies in complex conditions. (author)

  19. One-pot Synthesis of Bis(dihydropyrimidinone-4-yl)benzene Using Boric Acid as a Catalyst

    Institute of Scientific and Technical Information of China (English)

    TU Shu-Jiang; ZHU Xiao-Tong; FANG Fang; ZHANG Xiao-Jing; ZHU Song-Lei; LI Tuan-Jie; SHI Da-Qing; WANG Xiang-Shan; JI Shun-Jun


    A simple effective synthesis of bis(dihydropyrimidinone-4-yl)benzene derivatives, using boric acid as catalyst,from isophthalic aldehyde or terephthalic aldehyde, 1,3-dicarbonyl compounds and urea or thiourea in glacial acetic acid was described. As the expansion of the classical Biginelli reaction, this method has the advantage of excellent yields 83%-94% and short reaction time 0.5-1.5 h.

  20. Boric acid as cost-effective and recyclable catalyst for trimethylsilyl protection and deprotection of alcohols and phenols

    Energy Technology Data Exchange (ETDEWEB)

    Rostami, Amin; Akradi, Jamal; Ahmad-Jangi, Firoz, E-mail: [University of Kurdistan, Sanandaj (Iran, Islamic Republic of). Faculty of Science. Dept. of Chemistry


    Boric acid has been used as a green, selective and recyclable catalyst for trimethysilylation of alcohols and phenols using hexamethyldisilazane in acetonitrile. Deprotection of trimethylsilyl ethers to their parent alcohols and phenols was also achieved using this catalyst in water at room temperature. The salient features of this methodology are cheap processing, mild acidity conditions, excellent yields of products and easy availability of the catalyst. (author)

  1. Experimental study on effects of boric acid on aerosol revaporization in wind project

    Energy Technology Data Exchange (ETDEWEB)

    Shibazaki, Hiroaki; Maruyama, Yu; Kudo, Tamotsu; Yuchi, Yoko; Chino, Eiichi; Nakamura, Hideo; Hidaka, Akihide; Hashimoto, Kazuichiro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment


    The revaporization of the once-deposited FPs onto surfaces of reactor coolant piping is being investigated in WIND (Wide Range Piping Integrity Demonstration) project at JAERI. The objectives of the present study are to characterize the aerosol revaporization from piping surfaces under various thermal-hydraulic conditions and to investigate the effects of boric acid on aerosol revaporization. Cesium iodide was introduced into the test section on which metaboric acid was/was not placed in advance. After quantifying the deposited mass of cesium and iodine, the test section was heated to realize the revaporization. The revaporized materials were deposited onto another test section with an axial temperature gradient located in downstream. In the cases that metaboric acid was placed on the test sections, it was found that the mole ratio of iodine to cesium deposited onto wall became gradually small as the wall temperature increased up to 500degC. Chemical analyses with XPS suggested that chemical reaction of deposited cesium iodide with metaboric acid would result in formation of borate, cesium oxide and molecular iodine. In the revaporization phase, the experiments showed that the once-deposited cesium and iodine compounds were mostly revaporized when the temperature exceeded 500degC. (author)

  2. Alternative method for thermal neutron flux measurements based on common boric acid as converter and Lr-15 detectors

    Energy Technology Data Exchange (ETDEWEB)

    Palacios, D.; Greaves, E. D.; Sajo B, L.; Barros, H. [Universidad Simon Bolivar, Laboratorio de Fisica Nuclear, Apdo. Postal 89000, Caracas (Venezuela, Bolivarian Republic of); Ingles, R. [Universidad Nacional de San Antonio Abad del Cusco, Av. de la Cultura No. 733, Cusco (Peru)


    A method to determine the flux and angular distribution of thermal neutrons with the use of Lr-115 detectors was developed. The use of the Lr-115 detector involves the exposure of a pressed boric acid sample (tablet) as a target, in tight contact with the track detector, to a flux of thermalized neutrons. The self-absorption effects in thin films or foil type thermal neutron detectors can be neglected by using the Lr-115 detector and boric acid tablet setup to operate via backside irradiation. The energy window and the critical angle-residual energy curve were determined by comparisons between the experimental and simulated track parameters. A computer program was developed to calculate the detector registration efficiency, so that the thermal neutron flux can be calculated from the track densities induced in the Lr-115 detector using the derived empirical formula. The proposed setup can serves as directional detector of thermal neutrons. (Author)

  3. Limitations when use chloramphenicol-bcyclodextrins complexes in ophtalmic solutions buffered with boric acid/borax system

    Directory of Open Access Journals (Sweden)

    Todoran Nicoleta


    Full Text Available Chloramphenicol eye drops are commonly prescribed in concentrations of 0.5-1% in the treatment of infectious conjunctivitis. In terms of ophthalmic solution preparation, the major disadvantage of chloramphenicol consists in its low solubility in water. The solubility is increased by substances that form chloramphenicol-complexes, for example: boric acid/borax or cyclodextrins. Objective: Experimental studies aimed to evaluate the potential advantages of enhancing the solubility and stability of chloramphenicol (API by molecular encapsulation in b-cyclodextrin (CD, in formulation of ophthalmic solutions buffered with boric acid/borax system. Methods and Results: We prepared four APIb- CD complexes, using two methods (kneading and co-precipitation and two molar ratio of API/b-cyclodextrin (1:1 and 1:2. The formation of complexes was proved by differential scanning calorimetry (DSC and the in vitro dissolution tests. Using these compounds, we prepared eight ophthalmic solutions, formulated in two variants of chloramphenicol concentrations (0.4% and 0.5%. Each solution was analyzed, by the official methods, at preparation and periodically during three months of storing in different temperature conditions (4°C, 20°C and 30°C. Conclusions: Inclusion of chloramphenicol in b-cyclodextrin only partially solves the difficulties due to the low solubility of chloramphenicol. The protection of chloramphenicol molecules is not completely ensured when the ophthalmic solutions are buffered with the boric acid/borax system.

  4. Potential of using boric acid as a boron drug for boron neutron capture therapy for osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, C.F.; Lin, S.Y. [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Peir, J.J. [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Liao, J.W. [Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan (China); Lin, Y.C. [Department of Veterinary Medicine, National Chung Hsing University, Taiwan (China); Chou, F.I., E-mail: [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China)] [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China)


    Osteosarcoma is a malignant tumor commonly found in human and animals. The ability of boric acid (BA) to accumulate in osteosarcoma due to the mechanism of the bone formation of cancer cells would make boron neutron capture therapy (BNCT) an alternative therapy for osteosarcoma. This study evaluated the feasibility of using BA as the boron drug for BNCT of bone cancer. The cytotoxicity of BA to L929 cells exceeded that of UMR-106 cells. With 25 {mu}g {sup 10}B/mL medium of BA treatment, the boron concentration in UMR-106 cells was higher than that in L929 cells. The biodistribution and pharmacokinetics of BA in Sprague-Dawley (SD) rats were studied by administrating 25 mg {sup 10}B/kg body weight to SD rats. Blood boron level decreased rapidly within one hour after BA injection. Boron concentration in the long bone was 4-6 time higher than that of blood. Results of this study suggest that BA may be a potential drug for BNCT for osteosarcoma.

  5. Experiments and Modeling of Boric Acid Permeation through Double-Skinned Forward Osmosis Membranes. (United States)

    Luo, Lin; Zhou, Zhengzhong; Chung, Tai-Shung; Weber, Martin; Staudt, Claudia; Maletzko, Christian


    Boron removal is one of the great challenges in modern wastewater treatment, owing to the unique small size and fast diffusion rate of neutral boric acid molecules. As forward osmosis (FO) membranes with a single selective layer are insufficient to reject boron, double-skinned FO membranes with boron rejection up to 83.9% were specially designed for boron permeation studies. The superior boron rejection properties of double-skinned FO membranes were demonstrated by theoretical calculations, and verified by experiments. The double-skinned FO membrane was fabricated using a sulfonated polyphenylenesulfone (sPPSU) polymer as the hydrophilic substrate and polyamide as the selective layer material via interfacial polymerization on top and bottom surfaces. A strong agreement between experimental data and modeling results validates the membrane design and confirms the success of model prediction. The effects of key parameters on boron rejection, such as boron permeability of both selective layers and structure parameter, were also investigated in-depth with the mathematical modeling. This study may provide insights not only for boron removal from wastewater, but also open up the design of next generation FO membranes to eliminate low-rejection molecules in wider applications.

  6. Hierarchical porous photoanode based on acid boric catalyzed sol for dye sensitized solar cells (United States)

    Maleki, Khatereh; Abdizadeh, Hossein; Golobostanfard, Mohammad Reza; Adelfar, Razieh


    The hierarchical porous photoanode of the dye sensitized solar cell (DSSC) is synthesized through non-aqueous sol-gel method based on H3BO3 as an acid catalyst and the efficiencies of the fabricated DSSC based on these photoanodes are compared. The sol parameters of 0.17 M, water mole ratio of 4.5, acid mole ratio of 0.45, and solvent type of ethanol are introduced as optimum parameters for photoanode formation without any detectable cracks. The optimized hierarchical photoanode mainly contains anatase phase with slight shift toward higher angles, confirming the doping of boron into titania structure. Moreover, the porous structure involves two ranges of average pore sizes of 20 and 635 nm. The diffuse reflectance spectroscopy (DRS) shows the proper scattering and blueshift in band gap. The paste parameters of solid:liquid, TiO2:ethyl cellulose, and terpineol:ethanol equal to 11:89, 3.5:7.5, and 25:64, respectively, are assigned as optimized parameters for this novel paste. The photovoltaic properties of short circuit current density, open circuit voltage, fill factor, and efficiency of 5.89 mA/cm2, 703 mV, 0.7, and 2.91% are obtained for the optimized sample, respectively. The relatively higher short circuit current of the main sample compared to other samples is mainly due to higher dye adsorption in this sample corresponding to its higher surface area and presumably higher charge transfer confirmed by low RS and Rct in electrochemical impedance spectroscopy data. Boric acid as a catalyst in titania sol not only forms hierarchical porous structure, but also dopes the titania lattice, which results in appreciated performance in this device.

  7. Reverse osmosis for the recovery of boric acid from the primary coolant at nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Bártová, Šárka, E-mail: [Research Centre Řež Ltd., Husinec-Řež 130, 250 68 Řež (Czech Republic); Kůs, Pavel [Research Centre Řež Ltd., Husinec-Řež 130, 250 68 Řež (Czech Republic); Skala, Martin [Research Centre Řež Ltd., Husinec-Řež 130, 250 68 Řež (Czech Republic); University of Chemical Technology, Prague, Department of Chemical Engineering, Technická 5, Prague 166 28 (Czech Republic); Vonková, Kateřina [Research Centre Řež Ltd., Husinec-Řež 130, 250 68 Řež (Czech Republic)


    Highlights: • RO membranes tested for boric acid recovery from primary coolant of nuclear power plants. • Scanning electron microscopy was used for the characterization of the membranes. • Lab scale experiments performed under various operation conditions. • We proposed configuration of and operation conditions for RO unit in nuclear power plant. - Abstract: At nuclear power plants (NPP), evaporators are used for the treatment of primary coolant and other liquid radioactive waste containing H{sub 3}BO{sub 3}. Because the operation of evaporators is expensive, a number of more cost-effective alternatives has been considered, one of which is reverse osmosis. We tested reverse osmosis modules from several manufactures on a batch laboratory apparatus. SEM images of the tested membranes were taken to distinguish the differences between the membranes. Water permeability through membranes was evaluated from the experiments with pure water. The experiments were performed with feed solutions containing various concentrations of H{sub 3}BO{sub 3} in a range commonly occurring in radioactive waste. The pH of the feed solutions ranged from 5.2 to 11.2. Our results confirmed that the pH of the feed solution plays the most important role in membrane separation efficiency of H{sub 3}BO{sub 3}. Certain modifications to the pH of the feed solution were needed to enable the tested membranes to concentrate the H{sub 3}BO{sub 3} in the retentate stream, separate from the pure water in the permeate stream. On this basis, we propose the configuration of and operational conditions for a reverse osmosis unit at NPP.

  8. Spatial self-phase modulation in the H2TPP(OH)4 doped in Boric Acid Glass

    CERN Document Server

    Allam, Srinivasa Rao; Venkatramaiah, N; Venkatesan, R; Sharan, Alok


    Self-diffraction rings or spatial self-phase modulation (SSPM) was observed in tetra-phenyl porphyrin derivative 5,10,15,20 - meso-tetrakis (4-hydroxyphenyl) porphyrin (H2TPP(OH)4) doped in boric acid glass (BAG) at 671 nm excitation wave-length lying within the absorption band of sample with TEM00 mode profile. Intensity modulated Z-scan was performed on these systems to study the thermal diffusion and to estimate the thermo-optic coefficients. The results obtained from self-diffraction rings experiment and modulated Z-scan are compared and analyzed for different concentration.

  9. Metal‐Free Dehydration of Glucose to 5‐(Hydroxymethyl)furfural in Ionic Liquids with Boric Acid as a Promoter

    DEFF Research Database (Denmark)

    Ståhlberg, Tim; Rodriguez, Sergio; Fristrup, Peter;


    The dehydration of glucose and other hexose carbohydrates to 5‐(hydroxymethyl)furfural (HMF) was investigated in imidazolium‐based ionic liquids with boric acid as a promoter. A yield of up to 42 % from glucose and as much as 66 % from sucrose was obtained. The yield of HMF decreased...... as the concentration of boric acid exceeded one equivalent, most likely as a consequence of stronger fructose–borate chelate complexes being formed. Computational modeling with DFT calculations confirmed that the formation of 1:1 glucose–borate complexes facilitated the conversion pathway from glucose to fructose....... Deuterium‐labeling studies elucidated that the isomerization proceeded via an ene–diol mechanism, which is different to that of the enzyme‐catalyzed isomerization of glucose to fructose. The introduced non‐metal system containing boric acid provides a new direction in the search for catalyst systems...

  10. Cover Picture: Metal‐Free Dehydration of Glucose to 5‐(Hydroxymethyl)furfural in Ionic Liquids with Boric Acid as a Promoter (Chem. Eur. J. 5/2011)

    DEFF Research Database (Denmark)

    Ståhlberg, Tim Johannes Bjarki; Rodriguez, Sergio; Fristrup, Peter;


    Boric acid promotes the dehydration of glucose to 5-(hydroxy)methylfurfural in ionic liquids. Computational analyses by DFT calculations show a significant decrease in energy for the isomerization of glucose to fructose when the sugars are bound to boric acid and isotopic labeling NMR studies con...

  11. 40 CFR 721.1729 - Boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol... (United States)


    ... polyethylene glycol mono-Bu ether and polyethylene glycol mono Me ether. 721.1729 Section 721.1729 Protection... acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol mono Me ether... identified as boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and......

  12. Reprint of The improvement of the energy resolution in epi-thermal neutron region of Bonner sphere using boric acid water solution moderator. (United States)

    Ueda, H; Tanaka, H; Sakurai, Y


    Bonner sphere is useful to evaluate the neutron spectrum in detail. We are improving the energy resolution in epi-thermal neutron region of Bonner sphere, using boric acid water solution as a moderator. Its response function peak is narrower than that for polyethylene moderator and the improvement of the resolution is expected. The resolutions between polyethylene moderator and boric acid water solution moderator were compared by simulation calculation. Also the influence in the uncertainty of Bonner sphere configuration to spectrum estimation was simulated.

  13. The improvement of the energy resolution in epi-thermal neutron region of Bonner sphere using boric acid water solution moderator. (United States)

    Ueda, H; Tanaka, H; Sakurai, Y


    Bonner sphere is useful to evaluate the neutron spectrum in detail. We are improving the energy resolution in epi-thermal neutron region of Bonner sphere, using boric acid water solution as a moderator. Its response function peak is narrower than that for polyethylene moderator and the improvement of the resolution is expected. The resolutions between polyethylene moderator and boric acid water solution moderator were compared by simulation calculation. Also the influence in the uncertainty of Bonner sphere configuration to spectrum estimation was simulated.

  14. Fabrication and study on tribological characteristics of cast copper-TiO{sub 2}-boric acid hybrid composites

    Energy Technology Data Exchange (ETDEWEB)

    Ramesh, C.S. [Department of Mechanical Engineering, PESIT, Bangalore (India); Noor Ahmed, R. [Department of Mechanical Engineering, Anjuman Engineering College, Bhatkal (India); Mujeebu, M.A. [Department of Mechanical Engineering, Anjuman Engineering College, Bhatkal (India); School of Mechanical Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia)], E-mail:; Abdullah, M.Z. [School of Mechanical Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia)


    Copper based composites having hard reinforcements such as silicon carbide, alumina and cerium oxide do possess higher strength, better wear resistance and higher coefficient of friction when compared to copper. However, they pose several challenges in machining such as higher tool wear and inferior surface finish. On the other hand, copper based composites having soft reinforcements such as graphite, molybdenum disulphide and calcium fluoride do possess lower coefficient of friction and better machinability characteristics. Against this background, an attempt is made to develop a new class of copper composite materials by dispersing both the hard and soft reinforcements in appropriate proportions to ensure optimization of mechanical properties and machinability characteristics. In this paper the development and testing of copper-TiO{sub 2}-boric acid composites by liquid metallurgy method is presented. Metallographic study, micro hardness, tensile strength, friction and wear tests on these hybrid composites have been carried out. The results show that copper-TiO{sub 2}-boric acid composites possess higher hardness, higher tensile strength, higher coefficient of friction and better wear resistance when compared with pure copper00.

  15. Simultaneous pollutant removal and electricity generation in denitrifying microbial fuel cell with boric acid-borate buffer solution. (United States)

    Chen, Gang; Zhang, Shaohui; Li, Meng; Wei, Yan


    A double-chamber denitrifying microbial fuel cell (MFC), using boric acid-borate buffer solution as an alternative to phosphate buffer solution, was set up to investigate the influence of buffer solution concentration, temperature and external resistance on electricity generation and pollutant removal efficiency. The result revealed that the denitrifying MFC with boric acid-borate buffer solution was successfully started up in 51 days, with a stable cell voltage of 205.1 ± 1.96 mV at an external resistance of 50 Ω. Higher concentration of buffer solution favored nitrogen removal and electricity generation. The maximum power density of 8.27 W/m(3) net cathodic chamber was obtained at a buffer solution concentration of 100 mmol/L. An increase in temperature benefitted electricity generation and nitrogen removal. A suitable temperature for this denitrifying MFC was suggested to be 25 °C. Decreasing the external resistance favored nitrogen removal and organic matter consumption by exoelectrogens.

  16. Boric acid as a mild and efficient catalyst for one-pot synthesis of 1-amidoalkyl-2-naphthols under solvent-free conditions

    Indian Academy of Sciences (India)

    Aziz Shahrisa; Somayeh Esmati; Mahdi Gholamhosseini Nazari


    An efficient green chemistry method has been developed for the synthesis of 1-amidoalkyl-2-naphthol derivatives via a one-pot three-component condensation of 2-naphthol, aldehydes and amide in the presence of boric acid as a mild catalyst.

  17. Some features of the effect the pH value and the physicochemical properties of boric acid have on mass transfer in a VVER reactor's core (United States)

    Gavrilov, A. V.; Kritskii, V. G.; Rodionov, Yu. A.; Berezina, I. G.


    Certain features of the effect of boric acid in the reactor coolant of nuclear power installations equipped with a VVER-440 reactor on mass transfer in the reactor core are considered. It is determined that formation of boric acid polyborate complexes begins under field conditions at a temperature of 300°C when the boric acid concentration is equal to around 0.065 mol/L (4 g/L). Operations for decontaminating the reactor coolant system entail a growth of corrosion product concentration in the coolant, which gives rise to formation of iron borates in the zones where subcooled boiling of coolant takes place and to the effect of axial offset anomalies. A model for simulating variation of pressure drop in a VVER-440 reactor's core that has invariable parameters during the entire fuel campaign is developed by additionally taking into account the concentrations of boric acid polyborate complexes and the quantity of corrosion products (Fe, Ni) represented by the ratio of their solubilities.

  18. The Simultaneous Determination of Silicic, Boric and Carbonic Acids in Natural Water via Ion-Exclusion Chromatography with a Charged Aerosol Detector

    Directory of Open Access Journals (Sweden)

    Yu Otsuka


    Full Text Available The simple and simultaneous determination of silicic, boric and carbonic acids was made using ion-exclusion chromatography (IEC and a Corona™ charged aerosol detector (C-CAD. Silicic and boric acids were separated by the column packed with a weakly acidic cation-exchange resin in H+-form and ultra-pure water eluent, and the detector responses were improved by the addition of acetonitrile to eluent. Under the optimized conditions, the simultaneous determination of weak inorganic acids, except for carbonic acid, was successfully performed. When the conversion column packed with a strong acidic cation-exchange resin in Na+- or K+-form was inserted between the separation column and the detector, weak inorganic acids including carbonic acid could be detected by the C-CAD. The calibration curves were linear in the range of 0.5–10 mg·L−1 as Si for silicic acid (r2 = 0.996, 10–100 mg·L−1 as B for boric acid (r2 = 0.998 and 1.3–21 mg·L−1 as C for carbonic acid (r2 = 0.993. The detection limits based on three times the standard deviation were 0.03 mg·L−1 as Si for silicic acid, 0.40 mg·L−1 as B for boric acid and 0.08 mg·L−1 as C for carbonic acid. This method was applicable to river, hot spring and drinking water.

  19. Cellular responses in the Malpighian tubules of Scaptotrigona postica (Latreille, 1807) exposed to low doses of fipronil and boric acid. (United States)

    Ferreira, Rafael Alexandre Costa; Silva Zacarin, Elaine Cristina Mathias; Malaspina, Osmar; Bueno, Odair Correa; Tomotake, Maria Eliza Miyoko; Pereira, Andrigo Monroe


    Studies of sub-lethal effects of pesticide residues on stingless bees are scarce and morphological analysis of organs would add information to toxicological analysis in order to clarify the continuous exposure of Scaptotrigona postica to insecticides. The aim of this study was to evaluate the morphology and histochemistry of the Malpighian tubules (excretory organ) of S. postica exposed to fipronil or boric acid to detect cellular responses that indicate toxicity or adaptative mechanisms to stress induced by exposure of worker bees to low doses of these chemical compounds. Newly emerged bees were submitted to toxicological bioassays and morphological analyses by optical microscopy and Transmission Electron Microscopy, as well as histochemical methods, were performed to detect proteins and glycoconjugates. Additionally, immunohistochemical detection of DNA fragmentation and HSP70 (70-kDa Heat shock protein) were performed to detect cell death and stress response, respectively. Statistical analysis, for the bioassays conducted with ingestion of contaminated diet with boric acid at 0.75% (w/w) or with fipronil at 0.1μg/kg of food, showed that the survival of bees that ingested the contaminated diets were significantly different to the survival rate presented by the control group (P<0.0001). Although some characteristics indicative of initiation of cell death were observed, the cells remained metabolically active in the processes of excretion and inactivation of chemical compounds. The data from this study reinforce the importance of research on sublethal effects of low doses of pesticides on bees in an attempt to assess a possible realistic dose and evaluate the risk assessment of stingless bee S. postica foraging in the vicinity of cultivated fields and/or in green urban areas.

  20. Influence of Polyethylene and Oxidized Polyethylene Wax Emulsions on Leaching Dynamics of Boric Acid from Impregnated Spruce Wood

    Directory of Open Access Journals (Sweden)

    Boštjan Lesar


    Full Text Available Boron biocides belong to the most frequently used ingredients of commercial wood preservatives. They are very effective fungicides and insecticides, but they do not react with wood and thus leach from it in wet applications. This fact signifi cantly limits use of boron compounds in the field of wood preservation. In order to reduce leaching of boric acid, the emulsion of polyethylene (WE1 and an emulsion of oxidized polyethylene (WE6 wax were combined with boric acid (cB = 0.1 % or 0.5 % of boron. Spruce wood specimens were vacuum impregnated and afterwards leached according to the prCEN/TS 15119-1, EN 1250-2 and EN 84 procedures. The results showed that the boron leaching is predominantly infl uenced by moisture content of wood during leaching, and furthermore by the concentration gradient (frequency of water replacement. The fact that the prCEN/TS 15119-1 leaching procedure is less severe than other two methods is also refl ected in the results. The results of the EN 84 and ENV 1250 test are comparable, while the results of the prCEN/TS 15119-1 testing are not in line with the other two methods. Considerable portions of boron are leached from wood in the first leaching cycles, already. WE6 wax emulsion (oxidized polyethylene wax emulsion in combination with heat treatment reduces boron leaching to a certain extent. On the other hand, impregnation of wood with WE1 (polyethylene wax emulsion does not reduce it and it even enhances it.

  1. Proposing Boric Acid as an Antidote for Aluminium Phosphide Poisoning by Investigation of the Chemical Reaction Between Boric Acid and Phosphine


    Motahareh Soltani; Seyed Farid Shetab-Boushehri; Hamidreza Mohammadi; Seyed Vahid Shetab-Boushehri


    Aluminium phosphide (AlP) is a storage fumigant pesticide, which is used to protect stored grains especially from insects and rodents. It releases phosphine (PH3) gas, a highly toxic mitochondrial poison, in contact with moisture, particularly if acidic. Although the exact mechanism of action is unknown so far, the major mechanism of PH3 toxicity seems to be the inhibition of cytochrome-c oxidase and oxidative phosphorylation which eventually results in adenosine triphosphate (ATP) depletion ...

  2. Equilibrium study on the reactions of boric acid with some cis-diaqua CrIII-complexes

    Indian Academy of Sciences (India)

    G N Mukherjee; Ansuman Das


    Substitution inert cis-diaqua CrIII complexes: cis-[(L-)CrIII(H2O)2](3-)+ derived from N-donor ligands (L-) viz., bipyridine and 1,10-phenanthroline ( = 0) and N,O-donor ligands viz., nitrilotriacetate and anthranilate N,N-diacetate ( = 3) titrate as diprotic acids in aqueous solution and enhance the acidity of otherwise weakly acidic boric acid (H3BO3) producing mononuclear and binuclear mixed ligand CrIII-borate complexes: [(L)Cr(H2BO4)]- and [(L)Cr(BO4)Cr(L)](1-2)+ respectively through coordination of the H2O and/or OH- ligands, cis-coordinated in the CrIII-complexes on the electron deficient BIII-atom in H3BO3 with release of protons. Deprotonation of the parent CrIII-complexes and their reactions with H3BO3 have been investigated by potentiometric method in aqueous solution, = 0.1 mol dm-3 (NaNO3) at 25 ± 0.1° C. The equilibrium constants have been evaluated by computerized methods and the tentative stoichiometry of the reactions have been worked out on the basis of the speciation curves.

  3. Effect of addition of tartaric acid on synthesis of boron carbide powder from condensed boric acid–glycerin product

    Energy Technology Data Exchange (ETDEWEB)

    Tahara, Naoki; Kakiage, Masaki, E-mail:; Yanase, Ikuo; Kobayashi, Hidehiko


    Highlights: •B{sub 4}C powder was synthesized from a condensed H{sub 3}BO{sub 3}-glycerin product with tartaric acid added. •A precursor consisting of B{sub 2}O{sub 3} and carbon was prepared by the thermal decomposition in air. •The precursors had a three-dimensional bicontinuous B{sub 2}O{sub 3}/carbon network structure. •The dispersion state became more homogeneous and finer with the addition of tartaric acid. •The complete formation of B{sub 4}C powder was achieved at 1250 °C within a shorter heat treatment time. -- Abstract: The effect of the addition of tartaric acid on the synthesis of boron carbide (B{sub 4}C) powder from a condensed boric acid (H{sub 3}BO{sub 3})–glycerin product was investigated in this study. The condensed product was prepared by dehydration condensation after directly mixing equimolar amounts of H{sub 3}BO{sub 3} and glycerin with the addition of 0–50 mol% tartaric acid (based on glycerin), which was followed by thermal decomposition in air to obtain a precursor powder from which excess carbon had been eliminated. The dispersion state of the boron oxide (B{sub 2}O{sub 3}) and carbon components in the precursor prepared from the condensed product with 25 mol% tartaric acid added was finer than that without tartaric acid added, in which both precursors had a three-dimensional bicontinuous B{sub 2}O{sub 3}/carbon network structure. The complete formation of crystalline B{sub 4}C powder was achieved at 1250 °C within a shorter heat treatment time for the precursor with a fine dispersion state. The synthesized B{sub 4}C powders became fine owing to the increased number of nucleation sites.

  4. Solubility study of nickel ferrite in boric acid using a flow-through autoclave system under high temperature and high pressure

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yong Joon; Choi, Ke Chon; Ha, Yeong Keong [Nuclear Chemistry Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    The solubility of nickel ferrite in an aqueous solution of boric acid was studied by varying the pH at the temperatures ranging from 25 .deg. C to 320 .deg. C. A flow-through autoclave system was specially designed and fabricated to measure the solubility of Fe in hydrothermal solutions under high temperature and pressure. The performance of this flow-through system was directly compared with the conventional static state technique using a batch-type autoclave system. The stability of fluid velocity for the flow-through autoclave system was verified prior to the solubility measurement. The influence of chemical additives, such as boric acid and H2, on the solubility of nickel ferrite was also evaluated.



    Arantes, Rafael Pereira; Faculdade Dr. Francisco Maeda; Cury, Tadeu Nascimento; Faculdade Dr. Francisco Maeda; Leão, Fabiana De Paula; Universidade Federal de Viçosa; Maciel Junior,Vinicius Antonio


    The experiment was conducted in the municipality of Ituverava, in the Estiva farm in the agricultural year of 07/08. The work used the soybean cultivar BRS Valiosa RR to evaluate the performace of the soybean with application of calcium chloride to 26% and boric acid to 17% in different stages of development of culture. The treatments consisted of applications in eight steps, as follows: pre-bloom, pre-bloom + flowering, pre-bloom + flowering + pod, pre - bloom + pod, bloomed, flowering ...

  6. 基于有机硼酸的糖传感器研究进展%Progress in Boric Acid-Based Saccharide Sensors

    Institute of Scientific and Technical Information of China (English)

    狄玲; 王苍; 吴健; 万灵书; 徐志康


    有机硼酸能与二羟基化合物高亲和性地可逆结合,是一类新型的糖传感器材料.根据检测手段的不同可将基于有机硼酸的糖传感器分为光谱传感器、pH指示型传感器、电化学传感器等几类.本文详细评述了各种传感器的检测原理、制备方法和应用,并系统总结了最新研究进展,展望了今后的研究方向.%Because of strong interaction with diol moieties, boric acid group often plays a critical role in the design of saccharide sensors. We presents an overview about the recent development of saccharide sensors based on various mechanisms, including spectroscopies, pH-indicators and electrochemistry. The chemistry involved in the binding between boric acid and saccharides are described also.Furthermore, potential directions of future research for these boric acid-based saccharide sensors arediscussed.

  7. The effects of temperature and aeration on the corrosion of A508III low alloy steel in boric acid solutions at 25-95 °C (United States)

    Xiao, Qian; Lu, Zhanpeng; Chen, Junjie; Yao, Meiyi; Chen, Zhen; Ejaz, Ahsan


    The effects of temperature, solution composition and dissolved oxygen on the corrosion rate and electrochemical behavior of an A508III low alloy steel in boric acid solution with lithium hydroxide at 25-95 °C are investigated. In aerated solutions, increasing the boric acid concentration increases the corrosion rate and the anodic current density. The corrosion rate in deaerated solutions increases with increasing temperature. A corrosion rate peak value is found at approximately 75 °C in aerated solutions. Increasing temperature increases the oxygen diffusion coefficient, decreases the dissolved oxygen concentration, accelerates the hydrogen evolution reaction, and accelerates both the active dissolution and the film forming reactions. Increasing dissolved oxygen concentration does not significantly affect the corrosion rate at 50 and 60 °C, increases the corrosion rate at 70 and 80 °C, and decreases the corrosion rate at 87.5 and 95 °C in a high concentration boric acid solution with lithium hydroxide.

  8. Electrochemical properties and stress corrosion cracking of alloys 600, 690, and 800 in solutions containing boric acid and chloride

    Energy Technology Data Exchange (ETDEWEB)

    Bae, J. H.; Won, C. H. [Chungnam Nation Univ., Taejon (Korea, Republic of); Lee, E. H.; Kim, H. P.; Kim, W. C. [KAERI, Taejon (Korea, Republic of)


    Electrochemical characteristics and stress corrosion cracking(SCC)of Alloy 600, Alloy 690 and Alloy 800 have been studied in boric acid solution with chloride. Electrochemical characteristics were measured in mixed solution of 3% H{sub 3}BO{sub 3} and 0.2g/l Cl{sup -} at 320 .deg. C. SCC resistance was predicted with Parameter(P{sub SCC}) including current density ratio obtained at two different scan rates. P{sub SCC} increased with a following sequence: Alloy 600MA, 600TT, 690TT and Alloy 800. SCC test was carried out with C-ring specimens and reverse U-bend(RUB) specimens at 320 .deg. C and 350 .deg. C. Test solutions were mixture of 3% H{sub 3}BO{sub 3} and 0.2g/l Cl{sup -} at 320 .deg. C and mixture of 27% H{sub 3}BO{sub 3} and 2g/l Cl{sup -} at 350 .deg. C. C-ring specimens test in the solution of 3% H{sub 3}BO{sub 3} and 0.2g/l Cl{sup -} at 320 .deg. C for 2400hrs did not show SCC. RUB specimen of Alloy600MA and 600TT showed SCC after 1920 hours exposure to the solution of 27% H{sub 3}BO{sub 3} and 0.2g/l Clat 350 .deg. C.

  9. Mixed ligand complex formation of FeIII with boric acid and typical N-donor multidentate ligands

    Indian Academy of Sciences (India)

    G N Mukherjee; Ansuman Das


    Equilibrium study of the mixed ligand complex formation of FeIII with boric acid in the absence and in the presence of 2,2'-bipyridine, 1,10-phenanthroline, diethylenetriamine and triethylenetetramine (L) in different molar ratios provides evidence of formation of Fe(OH)2+, Fe(OH)$^{+}_{2}$, Fe(L)3+, Fe(H2BO4), Fe(OH)(H2BO4)-, Fe(OH)2(H2BO4)2-, Fe(L)(H2BO4) and Fe2(L)2(BO4)+ complexes. Fe(L)$^{3+}_{2}$, Fe(L)2(H2BO4) and Fe2(L)4(BO4)+ complexes are also indicated with 2,2'-bipyridine and 1,10-phenanthroline. Complex formation equilibria and stability constants of the complexes at 25 ± 0 × 1° C in aqueous solution at a fixed ionic strength, = 0.1 mol -3 (NaNO3) have been determined by potentiometric method.

  10. Enhanced photoelectrochemical-response in highly ordered TiO{sub 2} nanotube-arrays anodized in boric acid containing electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, Chuanmin; Paulose, Maggie; Varghese, Oomman K.; Grimes, Craig A. [Department of Electrical Engineering, & amp; Department of Materials Science and Engineering, 217 Materials Research Laboratory, The Pennsylvania State University, University Park, PA 16802 (United States)


    We examine the photoelectrochemical properties of highly ordered titanium dioxide nanotube-array photoanodes, fabricated by anodization of titanium in a nitric acid/hydrofluoric acid electrolyte, with and without the addition of boric acid. Under UV-Vis illumination the photocurrent densities achieved with TiO{sub 2} nanotube-arrays fabricated in the H{sub 3}BO{sub 3}-HNO{sub 3}-HF electrolyte are a factor of seven greater than the TiO{sub 2} nanotube-array samples obtained in the commonly used HNO{sub 3}-HF electrolyte, indicating the ability to control the photoelectrochemical response of the highly ordered nanotube arrays by tailoring the electrolyte composition. For 560nm long boric-acid fabricated nanotube arrays, a photoconversion efficiency of 7.9% is achieved upon a 320-400nm illumination at an intensity of 98mW/cm{sup 2}, with hydrogen generated by water photoelectrolysis at the power-time normalized rate of 1708-{mu}mol/hW (42ml/hW). The resulting nanotube-arrays demonstrate excellent photocorrosion stability, with no detectable degradation in photoconversion properties over 6 months of testing. While the titania bandgap is not suitable for high visible spectrum efficiencies, the high photoconversion efficiency achieved under UV illumination indicates the suitability of the highly ordered nanotube-array architecture for hydrogen generation by water photoelectrolysis. (author)

  11. Study of Application of Boric Acid in High Temperature Coatings%硼酸应用在耐高温涂层中的研究

    Institute of Scientific and Technical Information of China (English)

    闫实; 刘朝辉; 成声月; 刘强; 阮峥; 邓智平


    选取硼酸高温脱水后的混合物作为填料,与高岭土、滑石粉、铝粉等填料制备了以有机硅树脂为基料,可以耐受800℃的耐高温防护涂层并测试了涂层的各项性能。为研究硼酸混合物在涂层高温灼烧过程中的作用机理,对涂层在经200℃固化、500℃高温灼烧和700℃高温灼烧后的表层形貌、元素和涂层物质变化情况进行分析。阐明了涂层中有机硅树脂上的有机基团会在500℃时大量分解。硼酸混合物在高温下,会以熔融态填充有机硅树脂分解挥发产生的空隙,并粘接其他颜填料,但是涂层表面会有硼酸混合物脱水造成的少量凹陷存在。%Using silicone resin as base stock, using dehydrated boric acid mixture,kaolin,talcum powder and aluminum powder as fillers, a high temperature coating which can resist 800 ℃ was prepared. And every performance of the coating was tested. In order to research the action mechanism of boric acid mixture in high temperature calcination process of the coating, changes of the surface morphology and composing elements of the coating during solidifying under 200 ℃ and calcining under 500 ℃ and 700 ℃ were analyzed. The results show that, lots of organic groups on the organosilicon resin can be decomposed at 500 ℃;under high temperature, boric acid mixture in the molten state can fill the voids of the organosilicon resin produced by decomposition of organic groups, but a small amount of pits on surface of the coat will be formed by dehydration of boric acid mixture.

  12. 多羟基化合物对硼酸络合效果的实验研究%Experimental Research on the Complexation Effect Between Polyol Compounds and Boric Acid

    Institute of Scientific and Technical Information of China (English)

    袁佳佳; 贾铭椿; 王晓伟


    通过将D-山梨醇、D-果糖、甘露醇、木糖醇与硼酸进行络合,在酸性和碱性条件下分别通过溶液电导率和pH值的变化情况来确定多羟基化合物与硼酸的最佳络合比,结果表明在酸性条件下,最佳络合比均为2∶1,当溶液呈碱性时,部分络合剂与硼酸反应会产生1∶1的化合物.只有当溶液中络合剂的物质的量过量达到硼酸的10倍以上的时候,硼酸才能够完全被络合成硼酸酯.%The boric acid is complexed with the D-sorbitol,D-fructose,mannitol and xylitol.Under the acidic and alkaline conditions it can fix on the best ratio of the polyol compounds and boric acid through the electrical conductivity and pH of the solution.The result indicates the best ratio is 2 ∶ 1 under the acidic condition.When in alkaline solution,some complexing agent and boric acid can generate the product that the ratio is 1 ∶ 1.Only when the amount of the complexing agent in the solution is excess of the 10 times of the boric acid,the boric acid can completely turn into boric acid ester.

  13. Separate vaporisation of boric acid and inorganic boron from tungsten sample cuvette-tungsten boat furnace followed by the detection of boron species by inductively coupled plasma mass spectrometry and atomic emission spectrometry (ICP-MS and ICP-AES). (United States)

    Kataoka, Hiroko; Okamoto, Yasuaki; Tsukahara, Satoshi; Fujiwara, Terufumi; Ito, Kazuaki


    Utilising extremely different vaporisation properties of boron compounds, the determination procedures of volatile boric acid and total boron using tungsten boat furnace (TBF) ICP-MS and TBF-ICP-AES have been investigated. For the determination of volatile boric acid by TBF-ICP-MS, tetramethylammonium hydroxide (TMAH, Me(4)NOH) was used as a chemical modifier to retain it during drying and ashing stages. As for the total boron, not only non-volatile inorganic boron such as boron nitride (BN), boron carbide (B(4)C), etc. but also boric acid (B(OH)(3)) was decomposed by a furnace-fusion digestion with NaOH to produce sodium salt of boron, a suitable species for the electrothermal vaporisation (ETV) procedure. The proposed method was applied to the analysis of various standard reference materials. The analytical results for various biological and steel samples are described.

  14. Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines

    Directory of Open Access Journals (Sweden)



    Full Text Available Objective: Many studies have been published on the antioxidative effects of boric acid (BA and sodium borates in in vitro studies. However, the boron (B concentrations tested in these in vitro studies have not been selected by taking into account the realistic blood B concentrations in humans due to the lack of comprehensive epidemiological studies. The recently published epidemiological studies on B exposure conducted in China and Turkey provided blood B concentrations for both humans in daily life and workers under extreme exposure conditions in occupational setting. The results of these studies have made it possible to test antioxidative effects of BA in in vitro studies within the concentration range relevant to humans. The aim of this study was to investigate the protective effects of BA against oxidative DNA damage in V79 (Chinese hamster lung fibroblast cells. The concentrations of BA tested for its protective effect was selected by taking the blood B concentrations into account reported in previously published epidemiological studies. Therefore, the concentrations of BA tested in this study represent the exposure levels for humans in both daily life and occupational settings. Materials and Methods: In this experimental study, comet assay and neutral red uptake (NRU assay methods were used to determinacy to toxicity and genotoxicity of BA and hydrogen peroxide (H2O2. Results: The results of the NRU assay showed that BA was not cytotoxic within the tested concentrations (3, 10, 30, 100 and 200 μM. These non-cytotoxic concentrations were used for comet assay. BA pre-treatment significantly reduced (P<0.05, one-way ANOVA the DNA damaging capacity of H2O2 at each tested BA concentrations in V79 cells. Conclusion: Consequently, pre-incubation of V79 cells with BA has significantly reduced the H2O2-induced oxidative DNA damage in V79 cells. The protective effect of BA against oxidative DNA damage in V79 cells at 5, 10, 50, 100 and 200 μM (54

  15. Quantity of non condensing gases (Such as hydrogen and oxygen) produced from the Irradiation of boric acid solutions in a research reactor

    Energy Technology Data Exchange (ETDEWEB)

    Im, Hee Jung; Choi, Ke Chon; Yeon, Jei Won; Kim, Hung Woo; Cho, Man Soon; Jang, Kyung Duk; Park, Ul Jae; Hong, Sung Tack; Han, Jae Sam; Park, Sang Jun; Jung, Hoan Sung; Song, Kyu Seok [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    Several pipeline rupture accidents as a result of the detonation of a hydrogen-oxygen mixture accumulated due to radiolysis have been reported. However, non-condensing gases (such as oxygen and hydrogen molecules) are usually not detected in cooling systems of pressurized water reactors (PWRs) under high temperature, or research reactors even under room temperature irradiation conditions. In the meantime, it was observed that the presence of certain amounts of boric acid, which is known as a water soluble thermal neutron absorber, produces an evolution of gases in significant quantity in the reactor at room temperature. Nuclear reactions of neutron absorbers such as B-10 or Li-6 in solid materials with thermal neutrons have been widely studied, and the applications are quite broad. Nevertheless, the irradiation of water samples containing neutron absorbers has not been published except for theoretical calculations using computer codes or a paper reporting experimental data obtained at high temperatures, written by B. Pas tina et al. To study the radiolysis of the cooling water and calculate the amount of gases that could have been produced in this manner, we irradiated several water samples containing natural, {sup 10}B-enriched, and mixed boric acid in the ranges of 0 to 2000 {mu}g/m L for the function of {sup 10}B concentration.

  16. Fabrication of Li{sub 2}TiO{sub 3} pebbles using PVA–boric acid reaction for solid breeding materials

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yi-Hyun, E-mail:; Cho, Seungyon; Ahn, Mu-Young


    Highlights: • Li{sub 2}TiO{sub 3} pebbles were successfully fabricated by the slurry droplet wetting method. • Boron was used as hardening agent of PVA and completely removed during sintering. • Microstructure of fabricated Li{sub 2}TiO{sub 3} pebble was exceptionally homogeneous. • Suitable process conditions for high-quality Li{sub 2}TiO{sub 3} pebble were summarized. - Abstract: Lithium metatitanate (Li{sub 2}TiO{sub 3}) is a candidate breeding material of the Helium Cooled Ceramic Reflector (HCCR) Test Blanket Module (TBM). The breeding material is used in pebble-bed form to reduce the uncertainty of the interface thermal conductance. In this study, Li{sub 2}TiO{sub 3} pebbles were successfully fabricated by the slurry droplet wetting method using the cross-linking reaction between polyvinyl alcohol (PVA) and boric acid. The effects of fabrication parameters on the shaping of Li{sub 2}TiO{sub 3} green body were investigated. In addition, the basic characteristics of the sintered pebble were also evaluated. The shape of Li{sub 2}TiO{sub 3} green bodies was affected by slurry viscosity, PVA content and boric acid content. The grain size and average crush load of sintered Li{sub 2}TiO{sub 3} pebble were controlled by the sintering time. The boron was completely removed during the final sintering process.

  17. Boric acid poisoning (United States)

    ... for any reason, 24 hours a day, 7 days a week. Take the container with you to the hospital, if possible. ... Transfer to a hospital that specializes in burn care Washing of the ... to a hospital for more treatment. Surgery may be needed if ...

  18. Determination of Iron in Layered Crystal Sodium Disilicate and Sodium Silicate by Flame Atomic Absorption Spectrometry with Boric Acid as a Matrix Modifier

    Institute of Scientific and Technical Information of China (English)

    Zhi Hua WANG; Min CAI; Shu Jun WANG


    The effects of matrix silicate and experimental conditions on the determination of iron in flame atomic absorption spectrometry (FAAS) were investigated. It was found that boric acid as a matrix modifier obviously eliminated silicate interference. Under the optimum operating conditions, the determination results of iron in layered crystal sodium disilicate and sodium silicate samples by FAAS were satisfactory. The linear range of calibration curve is 0-10.5 μg.mL-1, the relative standard deviation of method is 1.2%-2.2%, the recovery of added iron is 96.0%-101%, the of iron of the standard curve method, standard addition calibration and colorimetry method was the same, but the first has the merits of rapid sample preparation, reduced contamination risks and fast analysis.

  19. Effect of Addition of Boric Acid and Borax on Fire-Retardant and Mechanical Properties of Urea Formaldehyde Saw Dust Composites

    Directory of Open Access Journals (Sweden)

    Zenat A. Nagieb


    Full Text Available Properties of the flame retardant urea formaldehyde (UF board made from saw dust fibers were investigated. Flame retardant chemicals that were evaluated include boric acid (BA and borax (BX which were incorporated with saw dust fibers to manufacture experimental panels. Three concentration levels, (0.5, 1, and 5% of fire retardants and 10% urea formaldehyde resin based on oven dry fiber weight were used to manufacture experimental panels. Physical and mechanical properties including water absorption, modulus of rupture (MOR, and modulus of elasticity (MOE were determined. The results showed that water absorption and bending strength decreased as the flame retardant increased. The highest concentration of (BA + BX enhanced the fire retardant more than the lower ones. Scanning electron microscope and FTIR of composite panels were studied.

  20. The Efficacy of Boric Acid Used to Treat Experimental Osteomyelitis Caused by Methicillin-Resistant Staphylococcus aureus: an In Vivo Study. (United States)

    Güzel, Yunus; Golge, Umut H; Goksel, Ferdi; Vural, Ahmet; Akcay, Muruvvet; Elmas, Sait; Turkon, Hakan; Unver, Ahmet


    We explored the ability of local and systemic applications of boric acid (BA) to reduce the numbers of methicillin-resistant Staphylococcus aureus (MRSA) in a rat model of tibial osteomyelitis (OM), and compared boric acid with vancomycin (V). Implant-associated osteomyelitis was established in 35 rats. After 4 weeks, at which time OM was evident both radiologically and serologically in all animals, the rats were divided into five groups of equal number: group 1, control group (no local application of BA or other medication); group 2, V group; group 3, local BA + V group; group 4, local BA group; and group 5, local + systemic BA group. Serum total antioxidant status, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, were measured. Pathological changes attributable to bone OM were evaluated using a grading system. Bacterial colony-forming units (CFUs) per gram of bone were counted. The lowest bacterial numbers were evident in group 3, and the bacterial numbers were significantly lower than that of the control group in all four test groups (p < 0.001). Group 3 also had the least severe bone infection (OM score 1.7 ± 1.1, p < 0.05). Upon histological and microbiological evaluation, no significant difference was evident between groups 2 and 3. Total antioxidant levels were significantly different in all treatment groups compared to the control group. Microbiological and histopathological evaluation showed that systemic or local application of BA was effective to treat OM, although supplementary V increased the effectiveness of BA.

  1. Effect of boric acid composition on the properties of ZnO thin film nanotubes and the performance of dye-sensitized solar cell (DSSC)

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, M.Y.A., E-mail:; Roza, L.; Umar, A.A., E-mail:; Salleh, M.M.


    The effect of boric acid (H{sub 3}BO{sub 3}) composition at constant concentration of hexamethylenetetramine (HMT) and zinc nitrate (Zn(NO{sub 3}){sub 2}) on the morphology, thickness, elemental composition, optical absorption, structure, photoluminescence of ZnO nanotubes has been investigated. The performance of the DSSC utilizing the ZnO samples has also been studied. It was found that the structure, thickness, elemental composition, optical absorption and morphology of ZnO nanostructure are significantly affected by the concentration of H{sub 3}BO{sub 3}. The diameter and thickness of ZnO nanotubes decreases as the composition of H{sub 3}BO{sub 3} increases. The DSSC utilizing ZnO nanotubes synthesized at 2 wt. % H{sub 3}BO{sub 3} performs the highest J{sub SC} and η of 2.67 mA cm{sup −2} and 0.29%, respectively. The highest performance of the device is due to the highest optical absorption of ZnO nanotubes sample and lowest charge interfacial resistance. - Graphical abstract: Nyquist plots of the DSSCs utilizing ZnO nanotubes prepared at various boric acid compositions. - Highlights: • Boron was doped into ZnO films by adding H{sub 3}BO{sub 3} into the growth solution. • Diameter and thickness of ZnO nanotubes decreases with the composition of H{sub 3}BO{sub 3}. • The DSSC performs the highest J{sub SC} and η of 2.67 mA cm{sup −2} and 0.29%, respectively. • This is due to high specific surface area and low charge interfacial resistance.

  2. GEMAS: prediction of solid-solution phase partitioning coefficients (Kd) for oxoanions and boric acid in soils using mid-infrared diffuse reflectance spectroscopy. (United States)

    Janik, Leslie J; Forrester, Sean T; Soriano-Disla, José M; Kirby, Jason K; McLaughlin, Michael J; Reimann, Clemens


    The authors' aim was to develop rapid and inexpensive regression models for the prediction of partitioning coefficients (Kd), defined as the ratio of the total or surface-bound metal/metalloid concentration of the solid phase to the total concentration in the solution phase. Values of Kd were measured for boric acid (B[OH]3(0)) and selected added soluble oxoanions: molybdate (MoO4(2-)), antimonate (Sb[OH](6-)), selenate (SeO4(2-)), tellurate (TeO4(2-)) and vanadate (VO4(3-)). Models were developed using approximately 500 spectrally representative soils of the Geochemical Mapping of Agricultural Soils of Europe (GEMAS) program. These calibration soils represented the major properties of the entire 4813 soils of the GEMAS project. Multiple linear regression (MLR) from soil properties, partial least-squares regression (PLSR) using mid-infrared diffuse reflectance Fourier-transformed (DRIFT) spectra, and models using DRIFT spectra plus analytical pH values (DRIFT + pH), were compared with predicted log K(d + 1) values. Apart from selenate (R(2)  = 0.43), the DRIFT + pH calibrations resulted in marginally better models to predict log K(d + 1) values (R(2)  = 0.62-0.79), compared with those from PSLR-DRIFT (R(2)  = 0.61-0.72) and MLR (R(2)  = 0.54-0.79). The DRIFT + pH calibrations were applied to the prediction of log K(d + 1) values in the remaining 4313 soils. An example map of predicted log K(d + 1) values for added soluble MoO4(2-) in soils across Europe is presented. The DRIFT + pH PLSR models provided a rapid and inexpensive tool to assess the risk of mobility and potential availability of boric acid and selected oxoanions in European soils. For these models to be used in the prediction of log K(d + 1) values in soils globally, additional research will be needed to determine if soil variability is accounted on the calibration.

  3. Application study of boric acid glycerin polyester in electrolytic capacitors%硼酸丙三醇聚酯在铝电解电容器工作电解液中的应用研究

    Institute of Scientific and Technical Information of China (English)

    周攀登; 刘仁其; 龙立平


    采用正交实验法配制了一种耐高压电容器工作电解液配方,在该配方中添加自己合成的硼酸丙三醇聚酯.研究表明,随着硼酸丙三醇聚酯的添加,电解液的电导率较未加的高,而闪火电压没有明显的变化.即硼酸丙三醇聚酯能提高该工作电解液的电导率,而对闪火电压的影响较小.%Use the orthogonal experiment method to the preparation of a high voltage capacitor work electrolyte formula, Boric acid glycerin polyester have been added to this work electrolyte. The studies showed that the conductivity of the electrolyte had improved greatly, with the addition of boric acid glycerol polyester, while no significant change in the voltage of the flash fire. It means that, boric acid glycerol polyester can improve the conductivity of the electrolyte of the working, and less impact on the voltage of the flash fire.

  4. 非抑制离子色谱法测定膨化食品中硼砂(硼酸)%Determination of Borax( Boric Acid) in Puffing Foods by Non-suppressed Ion Chromatography

    Institute of Scientific and Technical Information of China (English)

    吴凌涛; 余欣达; 潘灿盛; 陈军; 钟新林


    A new method was developed for the determination of borax (boric acid) in puffing foods using non-suppressed ion chromatography. The samples were extracted with methanesulfonie acid by ultra-sound. The solution was made passed through OnGuard II RP, Ag column, Na column and filter membrane after centrifugation and filtration. The separation of boric acid was performed on an anion exchange column of Dionex Ionpac AG16(50 mm x4 mm) + AS16(250 mm x4 mm) with 5 mmol/L sodium hydroxide by isocratic elution at a column temperature of 30 °C. The optimum chromatography conditions were investigated. Under the optimal conditions, the calibration curve for boric acid showed a good linearity in the range of 0. 3 - 3. 0 mg/g with correlation coefficient of 0. 999 5. The spiked recoveries for boric acid were in the range of 78% - 105% with RSDs of 1. 5% -4. 6% . The detection limit was 0. 06 mg/g. This method was applicable for the determination of borax (boric acid) in puffing foods.%建立了非抑制离子色谱法测定膨化食品中硼砂(硼酸)的分析方法,优化了色谱分离条件.样品在甲基磺酸溶液中超声提取后,经离心、过滤,依次过RP固相萃取柱、银柱、钠柱、滤膜后,进样分析.采用5 mmol/L氢氧化钠作为淋洗液,硼酸根经Dionex Ionpac AG16(50 mm ×4 mm)+ AS16(250 mm×4 mm)阴离子交换柱等度分离,柱温30℃,电导检测器检测.在优化实验条件下,硼酸的线性范围为0.3~3.0 mg/g,相关系数(r)为0.999 5,回收率为78% ~ 105%,相对标准偏差为1.5% ~4.6%,检出限为0.06 mg/g.该方法适用于膨化食品中硼砂(硼酸)含量的测定.

  5. AN EFFICIENT SYNTHESIS OF 1,3-DIOXANE-4,6-DIONES CATALYZED BY BORIC ACID. Eine effiziente Synthese von 1,3-Dioxan-4 ,6-dione BY BORSÄURE katalysierten

    Directory of Open Access Journals (Sweden)

    Zhao hui XU*,Chun hua Lin ,Jian hui Xia


    Full Text Available Several kinds of 1,3-dioxane-4,6-diones have been synthesized from malonic acid and ketones using boric acid as catalyst, acetic anhydride as condensing regent at room temperature. The present method does not involve any hazardous organic solvents, it gives some notable advantages such as mild reaction conditions, short reaction time,less catalyst dosage and high yields.Further study showed that H3BO3 was reused for four times without any noticeable decrease in the catalytic activity.

  6. 复方硼酸含漱液的药理毒理学研究%Pharmacological and toxicological research of compound boric acid gargle

    Institute of Scientific and Technical Information of China (English)



    ObjectiveTo investigate pharmacology and toxicology of compound boric acid gargle. MethodsA total of 60 rats as study subjects were randomly divided into normal saline group, aspirin group, low, moderate and high compound borax solution groups, with 12 cases in each group. Another 12 rats were taken in acute toxicity test of compound borax solution. Anti-inflammatory, analgesic and bacteriostatic effects by compound borax solution were observed by hot plate test, writhing test and antibacterial experiment in vitro in xylene-induced rat auricle edema and carrageenin-induced rat toe inflammation models. Experimental findings were observed.Results Compound borax solution showed remarkable inhibiting effect on xylene-induced rat auricle edema, and its difference with the normal saline had statistical significance (P<0.05). The difference of improved pain threshold proportion in various compound borax solution dosage groups had statistical significance with the normal saline group (P<0.05). Compound borax solution showed good inhibiting and bactericidal effect on staphylococcus aureus and group A streptococcus, along with high safety and low toxicity.ConclusionCompound boric acid gargle provides remarkable anti-inflammatory, analgesic, and bactericidal effects. It can accelerate early rehabilitation in patients, with precise curative effect and low toxicity.%目的:探讨复方硼酸含漱液的药理毒理学。方法60只小鼠为实验对象,随机分为生理盐水组、阿司匹林组、复方硼酸含漱液低、中、高组,各12只。另选取12只大鼠进行复方硼酸含漱液急性毒性试验。采用二甲苯所致的小鼠耳廓肿胀和角叉菜胶所致大鼠足趾炎症模型、热板法、扭体法以及体外抑菌试验,观察复方硼酸含漱液的抗炎、镇痛以及抑菌作用。观察实验结果。结果复方硼酸含漱液对二甲苯所致的小鼠耳廓肿胀有显著的抑制作用,与生理盐水组比较

  7. Acid-Sensing Ion Channels and Pain

    Directory of Open Access Journals (Sweden)

    Qihai Gu


    Full Text Available Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management.

  8. Efficient boron abstraction using honeycomb-like porous magnetic hybrids: Assessment of techno-economic recovery of boric acid. (United States)

    Oladipo, Akeem Adeyemi; Gazi, Mustafa


    Porous magnetic hybrids were synthesized and functionalized with glycidol to produce boron-selective adsorbent. The magnetic hybrid (MH) comparatively out-performed the existing expensive adsorbents. MH had a saturation magnetisation of 63.48 emu/g and average pore diameter ranging from meso to macropores. The magnetic hybrids showed excellent selectivity towards boron and resulted in 79-93% boron removal even in the presence of competing metal ions (Na(+) and Cr(2+)). Experiments were performed in a column system, and breakthrough time was observed to increase with bed depths and decreased with flow rates. The batch experiments revealed that 60 min was enough to achieve equilibrium, and the level of boron sorption was 108.5 mg/g from a synthetic solution. Several adsorption-desorption cycles were performed using a simple acid-water treatment and evaluated using various kinetic models. The spent adsorbents could be separated easily from the mixture by an external magnetic field. The cost-benefit analysis was performed for the treatment of 72 m(3)/year boron effluent, including five years straight line depreciation charges of equipment. The net profit and standard percentage confirmed that the recovery process is economically feasible.

  9. Retention of ionisable compounds on high-performance liquid chromatography XVIII: pH variation in mobile phases containing formic acid, piperazine, tris, boric acid or carbonate as buffering systems and acetonitrile as organic modifier. (United States)

    Subirats, Xavier; Bosch, Elisabeth; Rosés, Martí


    In the present work dissociation constants of commonly used buffering species, formic acid, piperazine, tris(hydroxymethyl)-aminomethane, boric acid and carbonate, have been determined for several acetonitrile-water mixtures. From these pK(a) values a previous model has been successfully evaluated to estimate pH values in acetonitrile-aqueous buffer mobile phases from the aqueous pH and concentration of the above mentioned buffers up to 60% of acetonitrile, and aqueous buffer concentrations between 0.005 (0.001 mol L(-1) for formic acid-formate) and 0.1 mol L(-1). The relationships derived for the presently studied buffers, together with those established for previously considered buffering systems, allow a general prediction of the pH variation of the most commonly used HPLC buffers when the composition of the acetonitrile-water mobile phase changes during the chromatographic process, such as in gradient elution. Thus, they are an interesting tool that can be easily implemented in general retention models to predict retention of acid-base analytes and optimize chromatographic separations.

  10. Quantitative Analysis of Borax, Boric Acid and Total Boron in Zhengshiming Diyanye%珍视明滴眼液中硼砂、硼酸及总硼的含量测定

    Institute of Scientific and Technical Information of China (English)

    周平; 张倩; 赵翠; 王伯涛


    Objective;To establish the quantitative analysis method for borax, boric acid and total boron in Zhengshiming diyanye. Method; Borax, boric acid and total boron in Zhengshiming Diyanye were determined by micro-titration and constant titration. Result; The linear range of borax was from 8-16 mg, and the regression equation was Y = 504. 52X - 0. 14 ( r = 0. 998 8 ) with the average recovery rate 98. 29% ( n = 6, RSD 1. 37% ). The linear range of boric acid was from 50-70 mg, and the regression equation was Y = 141. 74.X+0. 07, r =0. 999 7 with the average recovery rate 97. 02% (n = 6, RSD 0. 78% ). The linear range of total boron was from 0. 8-1. 2 mmol, and the regression equation was Y = 9. 51 X -0. 05 , r =0. 999 7 with the average recovery rate 95. 29% (n = 6, RSD 0. 75 % ). Conclusion; This method is simple with high accuracy and easy to popularize, can provide foundation for the quality control of Zhengshiming diyanye.%目的:建立珍视明滴眼液中硼砂、硼酸及总硼的含量测定方法.方法:结合微量滴定法与常量滴定法测定珍视明滴眼液中硼砂、硼酸及总硼的含量.结果:硼砂的线性范围为8 ~16 mg,线性方程Y=504.52X -0.14(r=0.998 8),加样回收率为98.29% (n =6,RSD 1.37%).硼酸的线性范围为50 ~ 70 mg,线性方程y=141.74X +0.07,(r=0.999 7),加样回收率为97.02%(n=6,RSD 0.78%).总硼的线性范围在0.8 ~1.2 mmol,线性方程Y=9.51X -0.05 (r=0.999 7),加样回收率为95.29%(n =6,RSD 0.75%).结论:该方法简单、准确度高、易于推广,可用于珍视明滴眼液的质量评价.

  11. Research on the Antirust Performance of Eco-friendly Nitrogen Organic Boric Acid Ester%环境友好型含氮硼酸酯的防锈性能研究

    Institute of Scientific and Technical Information of China (English)

    张佳; 杨红刚; 陈琛; 曹居正; 毕玉岩


    Nitrogen organic boric acid ester was synthesized by hydroxymethylation BTA and oleic acid polyacrylamide boric acid ester two ethanol. The corrosion inhibition performance in the aqueous solution was evaluated by the weight-loss and antirust experiment. The lubricity was evaluated by four ball test machine test, and cleaning performance was e-valuated through ring method. Discuss the influence on the antirust performance such as volume, temperature and time. Results showed that all of the capabilities were good when the synthesis of product's additive quantity was 0. 25%, and antirust properties kept well under a little higher temperatures and longer working-time. The product could be used as anti-rust and lubricating additives for water-based cutting fluid.%合成出一种有机硼酸酯,含有羟甲基化苯并三氮唑和油酸二乙醇酰胺硼酸酯的特征基团.采用失重法、防锈试验方法测定了其防腐蚀及防锈性能.并采用四球摩擦磨损试验法、圆环法测定其润滑性与清洗性.在改变添加剂添加量、实验温度、实验时间的条件下探讨这些因素对切削液性能的影响.结果表明,在合成产物的质量分数添加量为0.25%时,各项性能测试情况良好,在较高温度及较长时间的连续工作情况下仍保持优良的防锈性能,可用作水基切削液中常用的防锈润滑添加剂.

  12. 柱前衍生-高效液相色谱法测定香精香料中硼酸和硼砂%HPLC Determination of Boric Acid and Borax in Essence and Perfume with Precolumn Derivatization

    Institute of Scientific and Technical Information of China (English)

    周示玉; 蒋健; 周国俊; 胡宝祥; 李祖光


    香精香料样品中的硼酸经姜黄素的乙酸溶液在室温下进行衍生化,所得硼的衍生物用高效液相色谱法分析。选用Hypersil ODS2色谱柱(4.6mm×250mm,5μm)为固定相,以甲醇与0.012m01.L^-1四丁基溴化铵(TBABr)溶液按体积比80比20混合所得溶液为流动相进行淋洗,于波长550nm处进行检测。根据硼砂在硫酸环境下定量转化成硼酸的原理间接测定硼砂。硼的色谱峰面积与其质量浓度在0.004-0.2mg·L叫范围内呈线性关系,检出限(3s)为4.0×10^-4mg·L^-1。在3个浓度水平下做加标回收试验,所得硼酸和硼砂的平均回收率分别在92.1%-106.6%和92.9%-107.1%之间。%Boric acid in samples of essence and perfume was derivatized with curcumin (dissolved in acetic acid) at room temperature. The derivatized product of boron was used for HPLC analysis, using Hypersil ODS2 chromatographic column (4.6 mm×250 mm, 5 μm) as stationary phase and mixtures of methanol and 0. 012 mol · L^-1 TBABr (802-20) as mobile phase. Based on the quantitative conversion of borax into boric acid in sulfuric acid medium, borax was determined by indirect determination of boric acid. I.inear relationship was found between values of peak area determined at wavelength of 550 ran and mass concentration of boron in the range of 0. 004-0. 2 mg· L^-1, with detection limit (3s) of 4. 0 × 10-4 mg· L^- 1. Tests for recovery were performed by standard addition method at 3 concentration levels; results of recovery of boric acid and borax found were in the ranges of 92. 1%- 106.6% and 92.9%-107. 1% respectively.

  13. 芳基硼酸聚合作用下高分子防火材料制备技术%Preparation Technology of Polymer Fire Retardant Materials Under Action of Aromatic Boric Acid Polymerization

    Institute of Scientific and Technical Information of China (English)



    The preparation of polymer materials with high polymer materials under the action of boric acid polymerization was proposed. First memory aryl boric acid polymer molecular characteristics analysis, polymer of fire resistance and flame retardant characteristics analysis, experiment, hafnium chloride (I. g, 4.0 mmol) and APTES (AR) AIDRICH- thiol acrylate (1.32 g, 8.0 mmol) was dissolved in DMF, aryl boric acid polymer nanometer TiO2 powder (30%) with Tween-208- crown 6 content increased with increasing. Under temperature programmed synthesized screw [4,4]-1,6- Ren dimethyl- 3- phenyl propylene, high pressure dense phase processing, in the hyperbaric chamber with 10 DEG C- min-1 speed heated from room temperature to 240 DEG C, join for thermionic coating and improve the fireproof material of thermal stability, chemical stability and mechanical stability in the expansion and contraction of the state, the completion of aryl boric acid polymerization under the action of macromolecule fire-proof material preparation. The experimental results show that the method has good thermal stability, high heat absorption peak and flame retardant layer with high thermal stability, high temperature resistance and fire resistance.%提出采用基硼酸聚合作用下高分子防火材料制备技术.首先根据芳基硼酸聚合物的分子特性分析,进行聚合物的防火性和阻燃性特征分析,实验中,将氯化铪(1.281 g,4.0 mmol)和APTES(AR AIDRICH)3-巯丙(1.32 g,8.0 mmol)溶于DMF中,芳基硼酸聚合物TiO2纳米粉体(30%))随着Tween-208-冠-6含量的增加而增加.在程序控温下,合成了螺[4,4]-1,6-壬二甲基-3-苯基丙烯,进行高压密相处理,在高压舱中以10℃·min-1的速度从室温加热到240℃,加入换热离子涂层,在热胀冷缩状态下提高防火材料的热稳定性、化学稳定性和力学稳定性,完成芳基硼酸聚合作用下高分子防火材料制备.实验结果表明,采用该方法制

  14. Acid-sensing ion channels and migraine

    Directory of Open Access Journals (Sweden)

    Yu-qi KANG


    Full Text Available Acid-sensing ion channels (ASICs are ligand-gated ion channels that are activated by extracellular protons (H+, which belong to epithelial sodium channels/degenerin (ENaC/DEG superfamily. ASICs are widely distributed in central nervous system, peripheral nervous system, digestive system and some tumor tissues. Different ASIC subunits play important roles in various pathophysiological processes such as touch, sour taste, learning and memory, including inflammation, ischemic stroke, pain, learning and memory decline, epilepsy, multiple sclerosis (MS, migraine, irritable bowel syndrome and tumor. Research over the last 2 decades has achieved substantial advances in migraine pathophysiology. It is now largely accepted that inflammatory pathways play a key role and three main events seem to take place: cortical spreading depression (CSD, activation of the trigeminovascular system (i.e. dural nociceptors, peripheral and central sensitization of this pain pathway. However, the exact mechanisms that link these three events to each other and to inflammation have so far remained to be studied. This article takes an overview of newly research advances in structure, distribution and the relationship with migraine of ASICs.  DOI: 10.3969/j.issn.1672-6731.2015.09.013

  15. 含氮硼酸酯在聚醚水溶液中的成膜性能%Film-forming Property of Polyether Aqueous Solutions with Nitrogenous Boric Acid Ester

    Institute of Scientific and Technical Information of China (English)

    耿明; 张朝辉; 刘思思; 孙跃涛; 明尔扬


    含氮硼酸酯和聚醚添加剂都是性能良好的水基润滑添加剂,两种添加剂的混合水基润滑液的成膜性能尚未研究.将月桂酸无规共聚醚(Lauric acid random copoly-ether,LPE)和硼酸三乙醇胺(Boric acid triethanolamine,BN)按质量比为1∶1混合后得到无色透明的水基润滑液,选取半浸泡的润滑方式,利用纳米级润滑膜厚度测量仪(NGY-6型)进行膜厚测量并做机理分析,分别从浓度、载荷和线速度三方面研究水基润滑液的成膜性能.结果表明该水基润滑液(浓度5%,载荷100N)膜厚度基本稳定在5.5 nm,承受0.86 GPa的载荷;水基润滑液的成膜性能受浓度、载荷和线速度综合影响,随着载荷的增大,线速度对成膜性能的影响越小.经分析该水基润滑液在试验中形成化学吸附膜.纳米级厚度润滑薄膜的成膜性能研究将在精密仪器领域有很大的应用.%Nitrogen contained boric acid ester and polyether additive are all well-performed water-based lubricant additives. The film forming properties of the two additives mixed water-based lubricating fluid is not studied. The transparent aqueous solution is the 1:1 (m/m) mixture of lauric acid random copoly-ether (LPE) and boric acid triethanolamine (BN). The effect of concentration, load and linear speed on the film-forming property of the mixed polyether aqueous solution are analyzed by the nanometer scale lubrication film thickness gauge (NGY-6). Results of the tests show that film thickness of the water-based lubricant (5%, v/v, load 100 N) is 5.5 nm, and it can bear the load of 0.86 GPa. The film-forming property of water-based lubricants is affected by the concentration, load and linear speed. With the increase in the load, the effect of linear speed on film-forming property decreases. Meanwhile, in the experiments, the chemical adsorption film is formed on the friction pair surfaces. The nanoscale film-forming properties of the lubricating film can be widely

  16. Development of Twelve Acid Diethanolamide Boric Acid Ester and Its Application in Semi-synthetic Cutting Fluid%十二酸二乙醇酰胺硼酸酯的制备及其在半合成切削液中的应用

    Institute of Scientific and Technical Information of China (English)

    袁博; 衣守志; 杜天源


    Twelve acid diethanolamide boric acid ester was prepared by using twelve acid and diethanolamine and boric acid as raw materials,and its structure was analyzed by using Fourier Transform Infrared Spectrometer. A semi⁃synthetic cutting fluid was prepared by adding a certain amount of boric acid ester into the base oil,the corrosion performance and anti⁃rust property were analyzed,and the extreme pressure and anti⁃wear properties were tested by four ball friction testing machine. The results show that the prepared borate ester has good extreme pressure and anti⁃wear properties in semi⁃syn⁃thetic cutting fluid,when the mass fraction of boric acid ester is 11�3%,the friction coefficient of 5% diluent of the cutting fluid reaches 0�056 and maximum non⁃seizure load reaches 392 N.The performance indicators of the semi synthetic cutting fluid with the borate ester as additive meet the national standard of GB/T 6144⁃2010.%采用十二酸、二乙醇胺和硼酸为原料制备十二酸二乙醇酰胺硼酸酯,采用傅里叶变换红外光谱仪分析其结构。将一定量的该硼酸酯加入基础油中制备一种半合成切削液,分析其腐蚀性能和防锈性能,并通过四球摩擦试验机测试其极压抗磨性能。结果表明;制备的硼酸酯在半合成切削液中具有良好的极压抗磨性能,当硼酸酯的质量分数为11�3%时,5%切削液稀释液的摩擦因数达到0�056,最大无卡咬负荷达到392 N。采用该硼酸酯制备的半合成切削液的各性能指标达到GB/T 6144⁃2010标准。



    Balderas, E; Arteaga-Tlecuitl, R; Rivera, M; Gomora, JC; Darszon, A.


    Voltage-dependent calcium channels are widely distributed in animal cells, including spermatozoa. Calcium is fundamental in many sperm functions such as: motility, capacitation and the acrosome reaction, all essential for fertilization. Pharmacological evidence has suggested T-type calcium channels participate in the acrosome reaction. Niflumic acid (NA), a non-steroidal anti-inflammatory drug commonly used as chloride channel blocker, blocks T-currents in mouse spermatogenic cells and Cl− ch...

  18. Activation of Slo2.1 channels by niflumic acid


    Dai, Li; Garg, Vivek; Sanguinetti, Michael C.


    Slo2.1 channels conduct an outwardly rectifying K+ current when activated by high [Na+]i. Here, we show that gating of these channels can also be activated by fenamates such as niflumic acid (NFA), even in the absence of intracellular Na+. In Xenopus oocytes injected with

  19. Enraizamento de estacas de Ginkgo biloba tratadas com ácido indolbutírico e ácido bórico Rooting of Ginkgo biloba cuttings treated with indolbutyric and boric acids

    Directory of Open Access Journals (Sweden)

    Janice Valmorbida


    Full Text Available Objetivou-se neste trabalho estudar o efeito do ácido indolbutírico (AIB e do ácido bórico (B no enraizamento de estacas de Ginkgo biloba. Em estacas com duas folhas, medindo 15 cm de comprimento foram provocadas duas lesões na base de aproximadamente 2 cm, expondo o câmbio e procedeu-se à imersão por 10 segundos no tratamento correspondente, AIB (0, 1000, 2000 e 3000 mg L-1 na ausência ou presença de B (0 e 150 mg L-1. Em seguida foram colocadas para enraizar em bandejas de polipropileno contendo areia lavada. O delineamento foi em blocos casualizados num fatorial 4X2, com seis repetições. Foram avaliadas porcentagem de estacas enraizadas, estacas não enraizadas e mortas, diâmetro e comprimento das raízes, aos 70 dias do tratamento. Os dados foram submetidos à análise de variância sendo previamente testados para normalidade pelo Teste de Shapiro-Wilk. As médias foram comparadas pelo Teste de Tukey. Os tratamentos com 2000 mg L-1 de AIB foram superiores à ausência de AIB (80,55% vs. 55,56%, respectivamente, não diferindo dos demais tratamentos. A utilização de B não afetou a taxa de enraizamento, de estacas não enraizadas e mortas, não havendo interação entre a concentração de AIB e a utilização ou não de B. O diâmetro e o comprimento das raízes não foram afetados pela utilização de AIB e B.The aim of the work was to study the effect of indolbutyric (IBA and boric (B acids to root Ginkgo biloba cuttings. At the base of cuttings, with two leaves and 15 cm of length, were made two lesions with 2 cm to expose the cambium. Cuttings were treated for a period of 10 seconds with four concentrations of IBA (0, 1000, 2000 and 3000 mg L-1 combined with two concentration of B (0 and 150 mg L-1. After that, cuttings were taken in polypropylene trays filled with washed sand. The experimental design was of randomized blocks in the factorial arrangement (4x2, with six replications. After 70 days, evaluations were done

  20. 不同浓度配比硼酸溶液比定压热容的实验测量%Experimental measurement of isobaric heat capacity of boric acid solution

    Institute of Scientific and Technical Information of China (English)

    宋星佑; 苏超; 刘向阳; 何茂刚


    采用高精度的流动型量热法测量了温度在303~396 K、压力在0.1~0.5 MPa时,质量摩尔浓度分别为0.648、3.700(无杂质)和3.700(含杂质)mol/kg 三种配比硼酸溶液的比定压热容。实验系统的温度、压力、比定压热容的测量不确定度分别小于0.05 K、18 kPa、0.28%。为了验证实验系统的测量精度和可靠性,测量了温度为296~396 K、压力为0.1~6.0 MPa内纯水的比定压热容,与 NIST 值相比的相对偏差绝对平均值为0.41%。%Isobaric heat capacities of boric acid solution at the concentrations of 0.648,3.700 (no impurities)and 3.700 mol/kg (containing impurities) were measured using high accuracy flow calorimeter at temperatures of 303-396 K and pressures of 0.1-0.5 MPa.The uncertainties of temperature,pressure,and isobaric haet capacity were less than ±0.05 K,±18 kPa and ±0.28 %, respectively.In order to evaluate the reliability of the experimental system,isobaric heat capacities of pure water at temperatures of 296-396 K and pressures from atmosphere to 6.0 MPa were measured, and the measured average relative deviation from the NIST literature values is within 0.41%.

  1. Insight toward epithelial Na+ channel mechanism revealed by the acid-sensing ion channel 1 structure. (United States)

    Stockand, James D; Staruschenko, Alexander; Pochynyuk, Oleh; Booth, Rachell E; Silverthorn, Dee U


    The epithelial Na(+) channel/degenerin (ENaC/DEG) protein family includes a diverse group of ion channels, including nonvoltage-gated Na(+) channels of epithelia and neurons, and the acid-sensing ion channel 1 (ASIC1). In mammalian epithelia, ENaC helps regulate Na(+) and associated water transport, making it a critical determinant of systemic blood pressure and pulmonary mucosal fluidity. In the nervous system, ENaC/DEG proteins are related to sensory transduction. While the importance and physiological function of these ion channels are established, less is known about their structure. One hallmark of the ENaC/DEG channel family is that each channel subunit has only two transmembrane domains connected by an exceedingly large extracellular loop. This subunit structure was recently confirmed when Jasti and colleagues determined the crystal structure of chicken ASIC1, a neuronal acid-sensing ENaC/DEG channel. By mapping ENaC to the structural coordinates of cASIC1, as we do here, we hope to provide insight toward ENaC structure. ENaC, like ASIC1, appears to be a trimeric channel containing 1alpha, 1beta, and 1gamma subunit. Heterotrimeric ENaC and monomeric ENaC subunits within the trimer possibly contain many of the major secondary, tertiary, and quaternary features identified in cASIC1 with a few subtle but critical differences. These differences are expected to have profound effects on channel behavior. In particular, they may contribute to ENaC insensitivity to acid and to its constitutive activity in the absence of time- and ligand-dependent inactivation. Experiments resulting from this comparison of cASIC1 and ENaC may help clarify unresolved issues related to ENaC architecture, and may help identify secondary structures and residues critical to ENaC function.

  2. Structural and functional diversity of acidic scorpion potassium channel toxins.

    Directory of Open Access Journals (Sweden)

    Zong-Yun Chen

    Full Text Available BACKGROUND: Although the basic scorpion K(+ channel toxins (KTxs are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K(+ channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. PRINCIPAL FINDINGS: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new α-KTx subfamilies (α-KTx28, α-KTx29, and α-KTx30, and two are new members of the known κ-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the α-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized α-helix-loop-β-sheet (CS-α/β fold motif that has no apparent α-helixs and β-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a K(d of 11.69 µM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized α-helix-loop-helix (CS-α/α fold scaffold motif, blocked both Kv1.3 and KCNQ1 channels. StKTx23 toxin, with a cystine-stabilized α-helix-loop-β-sheet (CS-α/β fold motif, could inhibit Kv1.3 channel, but not the KCNQ1 channel. CONCLUSIONS/SIGNIFICANCE: These findings characterize the structural and functional diversity of acidic KTxs, and could accelerate the development and clinical use of acidic KTxs as pharmacological tools and

  3. Acid-sensing ion channels in pain and disease. (United States)

    Wemmie, John A; Taugher, Rebecca J; Kreple, Collin J


    Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered.

  4. Niflumic acid blocks native and recombinant T-type channels. (United States)

    Balderas, Enrique; Ateaga-Tlecuitl, Rogelio; Rivera, Manuel; Gomora, Juan C; Darszon, Alberto


    Voltage-dependent calcium channels are widely distributed in animal cells, including spermatozoa. Calcium is fundamental in many sperm functions such as: motility, capacitation, and the acrosome reaction (AR), all essential for fertilization. Pharmacological evidence has suggested T-type calcium channels participate in the AR. Niflumic acid (NA), a non-steroidal anti-inflammatory drug commonly used as chloride channel blocker, blocks T-currents in mouse spermatogenic cells and Cl(-) channels in testicular sperm. Here we examine the mechanism of NA blockade and explore if it can be used to separate the contribution of different Ca(V)3 members previously detected in these cells. Electrophysiological patch-clamp recordings were performed in isolated mouse spermatogenic cells and in HEK cells heterologously expressing Ca(V)3 channels. NA blocks mouse spermatogenic cell T-type currents with an IC(50) of 73.5 µM, without major voltage-dependent effects. The NA blockade is more potent in the open and in the inactivated state than in the closed state of the T-type channels. Interestingly, we found that heterologously expressed Ca(V)3.1 and Ca(V)3.3 channels were more sensitive to NA than Ca(V)3.2 channels, and this drug substantially slowed the recovery from inactivation of the three isoforms. Molecular docking modeling of drug-channel binding predicts that NA binds preferentially to the extracellular face of Ca(V)3.1 channels. The biophysical characteristics of mouse spermatogenic cell T-type currents more closely resemble those from heterologously expressed Ca(V)3.1 channels, including their sensitivity to NA. As Ca(V)3.1 null mice maintain their spermatogenic cell T-currents, it is likely that a novel Ca(V)3.2 isoform is responsible for them.

  5. 硼酸及硼酸酯类过氧化氢荧光探针的最新研究进展%Recent advances in the boric acid/boronate-based fluorescent probes for detection of hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    李震宇; 李静; 杜吕佩; 李敏勇; 沈月毛


    生物新陈代谢过程中产生的过氧化氢(H2O2)是生命活动所必需的,但是过量过氧化氢的存在可以引发多种疾病,因此对体内过氧化氢的检测具有重要意义.采用荧光探针法,借助激光共聚焦成像技术能够实现对活细胞和组织内的过氧化氢“实时、可见、定量”的检测,为深入阐明过氧化氢在生理和病理过程中所起的作用提供了一个重要手段.本文按荧光探针的结构分类,对近几年来以硼酸及硼酸酯基团作为荧光开关的具有高选择性和灵敏度的过氧化氢荧光探针进行了综述,主要探讨其设计思想、作用机制及应用,为过氧化氢探针的设计提供了新思路.%The physiological level of hydrogen peroxide (H2O2) is believed to be indispensable in regulating diverse cellular processes. However, excessive hydrogen peroxide generation is involved in the pathogenesis of many diseases, including cardiovascular disease, cancer, and neurological disorders. Thus, it is of significance to detect hydrogen peroxide in vivo. Fluorescent probe method, combined with confocal laser scanning microscopy (CLSM) can be used in real-time, visible and quantitative detection of hydrogen peroxide in living cells and tissues, which provides powerful tools for the understanding of hydrogen peroxide in physiological and pathological processes. This critical review highlights recent advances of design, mechanisms and applications of boric acid/boronate-based fluorescent probes employed to monitor hydrogen peroxide.

  6. Controlling fungus on channel catfish eggs with peracetic acid (United States)

    There is much interest in the use of peracetic acid (PAA) to treat pathogens in aquaculture. It is a relatively new compound and is approved for use in Europe, but not in the United States. This study determined the effectiveness of PAA for fungus control on channel catfish Ictalurus punctatus egg...

  7. 硼酸木材防虫剂预防建筑物白蚁药效研究%Efficacy of boric acid wood preservative against termite in buildings

    Institute of Scientific and Technical Information of China (English)

    尹红; 隋晓斐


    Objective To measure the efficacy of boric acid wood preservatives in the prevention of Coptotermes formosanus (Shiraki) and Reticulitermes speratus (Kolbe) in buildings. Methods A cohort of C. formosanus or R. speratus were subject to timbers or wood blocks treated with 5% or 10% borate preservative by painting or dipping to determine the respective toxicity and residual effect. Results Borate treated wood demonstrated a good resistance effect against C. formosanus and R. speratus, which were dead at both concentrations with either wood treatment approach. C. formosanus were more susceptible to the agent as the subjects demonstrated shorter survival duration. All subjects of C. formosanus died in ( 12.6 ± 2.4) days and all R. speratus in (16.8 ± 1.7)days as exposed to wood without ageing, both shorter than the time for death of the groups exposed to wood after ageing, (19.1 ±2.7) days for C. formosanus and (21.8±5.0) days for R. speratus, respectively. The death rate of the control group was lower than 0.1%. C. formosanus was more susceptible to boric acid in view of the resistance effect, as the intactness index of each piece of borate treated wood in that group was higher than 90. The intactness index of wood treated in 5% by painting or 10% agent by either painting or dipping, with or without ageing, remained above 90. In contrast, wood in the control group was seriously damaged with the intactness index as low as 60 and 40, respectively. It was suggested that borate treated wood had satisfyingly stable and long-last toxicity against termites, which was not compromised by ageing. Conclusion Borate wood preservative can be used for wood treatment for effective termite prevention in buildings.%目的 研究硼酸木材防护剂对危害建筑物的台湾乳白蚁和栖北散白蚁的预防效果.方法 用涂刷法和浸泡法处理木材,然后采用群体法测定5%和10%浓度的药液对台湾乳白蚁和栖北散白蚁的毒效

  8. Acid-sensing ion channels contribute to neurotoxicity. (United States)

    Chu, Xiang-Ping; Grasing, Kenneth A; Wang, John Q


    Acidosis that occurs under pathological conditions not only affects intracellular signaling molecules, but also directly activates a unique family of ligand-gated ion channels: acid-sensing ion channels (ASICs). ASICs are widely expressed throughout the central and peripheral nervous systems and play roles in pain sensation, learning and memory, and fear conditioning. Overactivation of ASICs contributes to neurodegenerative diseases such as ischemic brain/spinal cord injury, multiple sclerosis, Parkinson's disease, and Huntington's disease. Thus, targeting ASICs might be a potential therapeutic strategy for these conditions. This mini-review focuses on the electrophysiology and pharmacology of ASICs and roles of ASICs in neuronal toxicity.

  9. Functional modifications of acid-sensing ion channels by ligand-gated chloride channels.

    Directory of Open Access Journals (Sweden)

    Xuanmao Chen

    Full Text Available Together, acid-sensing ion channels (ASICs and epithelial sodium channels (ENaC constitute the majority of voltage-independent sodium channels in mammals. ENaC is regulated by a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR. Here we show that ASICs were reversibly inhibited by activation of GABA(A receptors in murine hippocampal neurons. This inhibition of ASICs required opening of the chloride channels but occurred with both outward and inward GABA(A receptor-mediated currents. Moreover, activation of the GABA(A receptors modified the pharmacological features and kinetic properties of the ASIC currents, including the time course of activation, desensitization and deactivation. Modification of ASICs by open GABA(A receptors was also observed in both nucleated patches and outside-out patches excised from hippocampal neurons. Interestingly, ASICs and GABA(A receptors interacted to regulate synaptic plasticity in CA1 hippocampal slices. The activation of glycine receptors, which are similar to GABA(A receptors, also modified ASICs in spinal neurons. We conclude that GABA(A receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels.

  10. Activation of Slo2.1 channels by niflumic acid. (United States)

    Dai, Li; Garg, Vivek; Sanguinetti, Michael C


    Slo2.1 channels conduct an outwardly rectifying K(+) current when activated by high [Na(+)](i). Here, we show that gating of these channels can also be activated by fenamates such as niflumic acid (NFA), even in the absence of intracellular Na(+). In Xenopus oocytes injected with <10 ng cRNA, heterologously expressed human Slo2.1 current was negligible, but rapidly activated by extracellular application of NFA (EC(50) = 2.1 mM) or flufenamic acid (EC(50) = 1.4 mM). Slo2.1 channels activated by 1 mM NFA exhibited weak voltage dependence. In high [K(+)](e), the conductance-voltage (G-V) relationship had a V(1/2) of +95 mV and an effective valence, z, of 0.48 e. Higher concentrations of NFA shifted V(1/2) to more negative potentials (EC(50) = 2.1 mM) and increased the minimum value of G/G(max) (EC(50) = 2.4 mM); at 6 mM NFA, Slo2.1 channel activation was voltage independent. In contrast, V(1/2) of the G-V relationship was shifted to more positive potentials when [K(+)](e) was elevated from 1 to 300 mM (EC(50) = 21.2 mM). The slope conductance measured at the reversal potential exhibited the same [K(+)](e) dependency (EC(50) = 23.5 mM). Conductance was also [Na(+)](e) dependent. Outward currents were reduced when Na(+) was replaced with choline or mannitol, but unaffected by substitution with Rb(+) or Li(+). Neutralization of charged residues in the S1-S4 domains did not appreciably alter the voltage dependence of Slo2.1 activation. Thus, the weak voltage dependence of Slo2.1 channel activation is independent of charged residues in the S1-S4 segments. In contrast, mutation of R190 located in the adjacent S4-S5 linker to a neutral (Ala or Gln) or acidic (Glu) residue induced constitutive channel activity that was reduced by high [K(+)](e). Collectively, these findings indicate that Slo2.1 channel gating is modulated by [K(+)](e) and [Na(+)](e), and that NFA uncouples channel activation from its modulation by transmembrane voltage and intracellular Na(+).

  11. 铈盐对铝合金硼酸-硫酸阳极氧化膜的封闭效应%Sealing effect of cerium salt on boric-sulfuric acid anodic film of aluminum alloy

    Institute of Scientific and Technical Information of China (English)

    王帅星; 赵晴; 杜楠; 邵志松; 舒伟发; 陈庆龙


    The boric-sulfuric acid anodic (BSAA) film on aluminum alloy was sealed by cerium salt conversion solution. The effects of sealing parameters on the corrosion resistance of BSAA film were researched through electrochemical impedance spectroscopy (EIS), while the corrosion resistance of anodic films sealed by different methods was studied. It is found that the resistance of porous layer increases significantly, the corrosion resistance is improved greatly and the corrosion current density is reduced by about 1 order of magnitude when the BSAA film was immersed in the cerium conversion solution (5 g/L Ce(NO3)3+0.5% H2O2) at 30 ℃ for 30 min. Besides, the corrosion resistance of BSAA film sealed by this method is much better than that by boiling water sealing, and also slightly superior to that of the dilute CrO3 solution sealing. Combined with EDS analysis results, it is indicated that a intact, compact cerium conversion film forms on the outside surface of BSAA film, and the porous layer is also filled with sealing products when the BSAA film is sealed by cerium salt conversion solution. The synergism of the two actions almost completely sealed the pores of BSAA film, thereby effectively improving the corrosion resistance of anodic film.%将铝合金硼酸-硫酸阳极氧化膜浸入铈盐转化液中进行封闭.采用交流阻抗谱技术研究各封闭参数对氧化膜耐蚀性的影响,比较了不同方法封闭的氧化膜的耐蚀性差异.结果表明:将硼酸-硫酸阳极氧化试样浸入30℃的铈盐转化液(5 g/L Ce(NO3)3+0.5% H2O2)中处理30min后,多孔层电阻Rp大幅增加,且腐蚀电流密度降低1个数量级,耐蚀性明显优于沸水封闭氧化膜的,也稍优于稀铬酸封闭氧化膜的耐蚀性.结合EDS分析表明:铈盐转化封闭后硼酸-硫酸阳极氧化膜的外表面形成了一层完整致密的铈盐转化膜,多孔层内也充满了铈的封闭产物,二者的协同作用几乎完全封住了硼酸-硫酸阳极氧

  12. Amino acid-sensing ion channels in plants

    Energy Technology Data Exchange (ETDEWEB)

    Spalding, Edgar P. [Univ. of Wisconsin, Madison, WI (United States)


    The title of our project is “Amino acid-sensing ion channels in plants”. Its goals are two-fold: to determine the molecular functions of glutamate receptor-like (GLR) proteins, and to elucidate their biological roles (physiological or developmental) in plants. Here is our final technical report. We were highly successful in two of the three aims, modestly successful in the third.

  13. Regulation of Connexin-Based Channels by Fatty Acids. (United States)

    Puebla, Carlos; Retamal, Mauricio A; Acuña, Rodrigo; Sáez, Juan C


    In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood.

  14. Regulation of Connexin-Based Channels by Fatty Acids (United States)

    Puebla, Carlos; Retamal, Mauricio A.; Acuña, Rodrigo; Sáez, Juan C.


    In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood. PMID:28174541

  15. Epithelial Sodium and Acid-Sensing Ion Channels (United States)

    Kellenberger, Stephan

    The epithelial Na+ channel (ENaC) and acid-sensing ion channels (ASICs) are non-voltage-gated Na+ channels that form their own subfamilies within the ENaC/degenerin ion channel family. ASICs are sensors of extracellular pH, and ENaC, whose main function is trans-epithelial Na+ transport, can sense extra- and intra-cellular Na+. In aldosterone-responsive epithelial cells of the kidney, ENaC plays a critical role in the control of sodium balance, blood volume and blood pressure. In airway epithelia, ENaC has a distinct role in controlling fluid reabsorption at the air-liquid interface, thereby determining the rate of mucociliary transport. In taste receptor cells of the tongue, ENaC is involved in salt taste sensation. ASICs have emerged as key sensors for extracellular protons in central and peripheral neurons. Although not all of their physiological and pathological functions are firmly established yet, there is good evidence for a role of ASICs in the brain in learning, expression of fear, and in neurodegeneration after ischaemic stroke. In sensory neurons, ASICs are involved in nociception and mechanosensation. ENaC and ASIC subunits share substantial sequence homology and the conservation of several functional domains. This chapter summarises our current understanding of the physiological functions and of the mechanisms of ion permeation, gating and regulation of ENaC and ASICs.

  16. 星点设计-效应面法优化硼酸乳膏基质配方及质量控制%Optimization of the Base Formula of Boric Acid Cream by Central Composite Design-response Surface Methodology and Its Quality Control

    Institute of Scientific and Technical Information of China (English)

    侯晓军; 唐菱; 周芃; 张小琼


    Objective:To optimize the base formula of boric acid cream,and investigate its quality. Methods:Using central composite design-response surface methodology,with the viscosity of cream as the index,the amounts of Cremophor A6,Cremophor A25,cetyl alcohol,stearyl alcohol,isooctadecyl isooctadecanoate,jojoba oil and light liquid paraffin were optimized. The appearance characteristics,particle size,viscosity and stability of the preparation and the content of boric acid were studied. Results:The optimal conditions were as follows:50 g Cremophor A6-Cremophor A25(3 ∶2),65 g cetyl alcohol-stearyl alcohol(3∶7),and 125 g isooctadecyl isooctadecanoate-jojoba oil- light liquid paraffin(5 ∶3 ∶2). According to the optimal formula,the cream showed the property of semi-fluid cream,the content of boric acid was 98. 5% of the labeling amount,and the viscosity was about 1. 64 × 104 mPa·s. The predicted value was equivalent to the measured one,and the stability of the preparation was promising. Conclusion:The central composite design-response surface methodology used in the base optimization of boric acid cream is simple with high precision and good predictability,and the quality of the preparation is stable and controllable.%目的:优化硼酸乳膏基质配方,考察制剂成品质量。方法:采用星点设计效应面法,以乳膏黏度为评价指标,优化脂肪醇醚-6(和)硬脂醇、鲸蜡硬脂醇聚醚-25、十六醇、十八醇、异硬脂醇异硬脂酸酯、霍霍巴油、轻质液状石蜡的用量;考察优化后制剂的外观性状、粒度、黏度、稳定性及硼酸的含量。结果:配方中含脂肪醇醚-6-鲸蜡硬脂醇聚醚-25(3∶2)50 g、十六醇-十八醇(3∶7)65 g、异硬脂醇异硬脂酸酯-霍霍巴油-轻质液状石蜡(5∶3∶2)125 g 时,制得的成品为白色半流体乳膏,硼酸含量为标示量的98.50%,粘度为1.64×104 mPa·s,预测值与实测值相当,制剂稳定性较好

  17. 氦氖激光照射联合硼酸湿敷治疗老年患者压疮的效果%Effect of helium neon laser irradiation combined with boric acid wet packing on elder patients with pressure ulcers

    Institute of Scientific and Technical Information of China (English)

    黄萍; 王怡; 张宇; 周翠柳; 潘切; 丁桂凤


    Objective To investigate the clinical effect of helium neon laser irradiation combined with boric acid wet packing on elder patients with pressure ulcers.Methods 52 cases of elderly patients with pressure ulcer were randomly divided into treatment group and control group.The control group was treated with boric acid wet packing after the wound debridement.The treatment group was treated with the helium neon laser irradiation on the pressure ulcer surface 20 minutes after the wound debridement and then boric acid wet packing once a day.Both groups received comprehensive treatment and nursing measures of pressure ulcers.Pressure ulcer healing was observed for 30 days.Results The effective rate of the treatment group was 96.2% and that of the control group was 69.2%.Clinical effect of the treatment group was better than that of the control group,and the difference was statistically significant( x2 =4.837,P <0.05 ).The effect initiating time of the treatment group was lower than the control group [ ( 12.19 ± 6.40) d vs ( 19.36 ± 9.30) d],and the difference was statistically significant ( t =- 2.425,P < 0.05 ).Conclusions Helium neon laser irradiation combined with boric acid wet packing can promote wound healing of pressure ulcers in elder patients,shorten course of disease.%目的 探讨氦氖激光照射联合硼酸湿敷治疗老年患者压疮的效果.方法 将52例住院带有压疮的老年患者随机分成对照组和治疗组,对照组常规清洁疮面后用硼酸纱布湿敷;治疗组同样清创后给予氦氖激光照射压疮表面20 min,再用硼酸纱布湿敷,每天1次.两组患者治疗期间均采用压疮综合治疗护理措施.观察30 d压疮愈合情况.结果 治疗组有效率为96.2%,对照组有效率为69.2%.两组比较差异有统计学意义(x2=4.837,P<0.05);治疗组显效时间也明显较对照组缩短[(12.19 ±6.40)d比(19.36±9.30)d],差异有统计学意义(t=-2.425,P<0.05).结论 氦氖激光照射联合

  18. Receptor for protons: First observations on Acid Sensing Ion Channels. (United States)

    Krishtal, Oleg


    The history of ASICs began in 1980 with unexpected observation. The concept of highly selective Na(+) current gated by specific receptors for protons was not easily accepted. It took 16 years to get these receptor/channels cloned and start a new stage in their investigation. "The receptor for protons" became ASIC comprising under this name a family of receptor/channels ubiquitous for mammalian nervous system, both peripheral and central. The role of ASICs as putative nociceptors was suggested almost immediately after their discovery. This role subsequently was proven in many forms of pain-related phenomena. Many other functions of ASICs have been also found or primed for speculations both in physiology and in disease. Despite the width of field and strength of efforts, numerous basic questions are to be answered before we understand how the local changes in pH in the nervous tissue transform into electric and messenger signaling via ASICs as transducers. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.

  19. Acid-sensing ion channels: trafficking and synaptic function

    Directory of Open Access Journals (Sweden)

    Zha Xiang-ming


    Full Text Available Abstract Extracellular acidification occurs in the brain with elevated neural activity, increased metabolism, and neuronal injury. This reduction in pH can have profound effects on brain function because pH regulates essentially every single biochemical reaction. Therefore, it is not surprising to see that Nature evolves a family of proteins, the acid-sensing ion channels (ASICs, to sense extracellular pH reduction. ASICs are proton-gated cation channels that are mainly expressed in the nervous system. In recent years, a growing body of literature has shown that acidosis, through activating ASICs, contributes to multiple diseases, including ischemia, multiple sclerosis, and seizures. In addition, ASICs play a key role in fear and anxiety related psychiatric disorders. Several recent reviews have summarized the importance and therapeutic potential of ASICs in neurological diseases, as well as the structure-function relationship of ASICs. However, there is little focused coverage on either the basic biology of ASICs or their contribution to neural plasticity. This review will center on these topics, with an emphasis on the synaptic role of ASICs and molecular mechanisms regulating the spatial distribution and function of these ion channels.

  20. Anion-Channel Blockers Inhibit S-Type Anion Channels and Abscisic Acid Responses in Guard Cells. (United States)

    Schwartz, A.; Ilan, N.; Schwarz, M.; Scheaffer, J.; Assmann, S. M.; Schroeder, J. I.


    The effects of anion-channel blockers on light-mediated stomatal opening, on the potassium dependence of stomatal opening, on stomatal responses to abscisic acid (ABA), and on current through slow anion channels in the plasma membrane of guard cells were investigated. The anion-channel blockers anthracene-9-carboxylic acid (9-AC) and niflumic acid blocked current through slow anion channels of Vicia faba L. guard cells. Both 9-AC and niflumic acid reversed ABA inhibition of stomatal opening in V. faba L. and Commelina communis L. The anion-channel blocker probenecid also abolished ABA inhibition of stomatal opening in both species. Additional tests of 9-AC effects on stomatal aperture in Commelina revealed that application of this anion-channel blocker allowed wide stomatal opening under low (1 mM) KCI conditions and increased the rate of stomatal opening under both low and high (100 mM) KCI conditions. These results indicate that anion channels can function as a negative regulator of stomatal opening, presumably by allowing anion efflux and depolarization, which prohibits ion up-take in guard cells. Furthermore, 9-AC prevented ABA induction of stomatal closure. A model in which ABA activation of anion channels contributes a rate-limiting mechanism during ABA-induced stomatal closure and inhibition of stomatal opening is discussed.

  1. The antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors? (United States)

    Cheng, Jen-Kun; Chen, Chien-Chuan; Yang, Jia-Rung; Chiou, Lih-Chu


    Gabapentin is a novel analgesic whose mechanism of action is not known. We investigated in a postoperative pain model whether adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channels, N-methyl-d-aspartic acid (NMDA) receptors, and Ca2+ channels are involved in the antiallodynic effect of intrathecal gabapentin. Mechanical allodynia was induced by a paw incision in isoflurane-anesthetized rats. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before and after incision and after intrathecal drug administration. The antiallodynic effect of gabapentin (100 mug) was not affected by intrathecal pretreatment with antagonists of K(ATP) channels, NMDA receptors or gamma-aminobutyric acid (GABA)(A) receptors. K(ATP) channel openers and GABA(A) receptor agonist, per se, had little effect on the postincision allodynic response. The Ca2+ channel blocker of N-type (omega-conotoxin GVIA, 0.1-3 microg), but not of P/Q-type (omega-agatoxin IVA), L-type (verapamil, diltiazem or nimodipine), or T-type (mibefradil), attenuated the incision-induced allodynia, as did gabapentin. Both the antiallodynic effects of gabapentin and omega-conotoxin GVIA were attenuated by Bay K 8644, an L-type Ca2+ channel activator. These results provide correlative evidence to support the contention that N-type Ca2+ channels, but not K(ATP) channels or NMDA or GABA(A) receptors, might be involved in the antiallodynic effect of intrathecal gabapentin.

  2. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons


    Sutherland, Stephani P.; Christopher J. Benson; Adelman, John P.; McCleskey, Edwin W.


    Cardiac afferents are sensory neurons that mediate angina, pain that occurs when the heart receives insufficient blood supply for its metabolic demand (ischemia). These neurons display enormous acid-evoked depolarizing currents, and they fire action potentials in response to extracellular acidification that accompanies myocardial ischemia. Here we show that acid-sensing ion channel 3 (ASIC3), but no other known acid-sensing ion channel, reproduces the functional featur...

  3. Niflumic acid differentially modulates two types of skeletal ryanodine-sensitive Ca(2+)-release channels. (United States)

    Oba, T


    The effects of niflumic acid on ryanodine receptors (RyRs) of frog skeletal muscle were studied by incorporating sarcoplasmic reticulum (SR) vesicles into planar lipid bilayers. Frog muscle had two distinct types of RyRs in the SR: one showed a bell-shaped channel activation curve against cytoplasmic Ca2+ or niflumic acid, and its mean open probability (Po) was increased by perchlorate at 20-30 mM (termed "alpha-like" RyR); the other showed a sigmoidal activation curve against Ca2+ or niflumic acid, with no effect on perchlorate (termed "beta-like" RyR). The unitary conductance and reversal potential of both channel types were unaffected after exposure to niflumic acid when clamped at 0 mV. When clamped at more positive potentials, the beta-like RyR channel rectified this, increasing the unitary current. Treatment with niflumic acid did not inhibit the response of both channels to Ca2+ release channel modulators such as caffeine, ryanodine, and ruthenium red. The different effects of niflumic acid on Po and the unitary current amplitude in both types of channels may be attributable to the lack or the presence of inactivation sites and/or distinct responses to agonists.

  4. Direct block of the cystic fibrosis transmembrane conductance regulator Cl(-) channel by niflumic acid. (United States)

    Scott-Ward, T S; Li, H; Schmidt, A; Cai, Z; Sheppard, D N


    Niflumic acid is widely used to inhibit Ca(2+) -activated Cl(-) channels. However, the chemical structure of niflumic acid resembles that of diphenylamine-2-carboxylate, a drug that inhibits the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. To investigate how niflumic acid inhibits CFTR Cl(-) channel, we studied recombinant wild-type human CFTR in excised inside-out membrane patches. When added to the intracellular solution, niflumic acid caused a concentration- and voltage-dependent decrease of CFTR Cl(-) current with half-maximal inhibitory concentration (K(i)) of 253 microM and Hill co-efficient of approximately 1, at -50 mV. Niflumic acid inhibition of single CFTR Cl(-) channels was characterized by a very fast, flickery block that decreased dramatically current amplitude without altering open-probability. Consistent with these data, spectral analysis of CFTR Cl(-) currents suggested that channel block by niflumic acid was described by the closed open blocked kinetic scheme with blocker on rate (k(on)) = 13.9 x 10(6) M(-1)s(-1), off rate (k(off))=3348 s(-1) and dissociation constant (K(d)) = 241 microM, at -50 mV. Based on these data, we tested the effects of niflumic acid on transepithelial Cl(-) secretion and cyst growth using type I MDCK epithelial cells. Niflumic acid (200 microM) inhibited cAMP-stimulated, bumetanide-sensitive short-circuit current by 55%. Moreover, the drug potently retarded cyst growth. We conclude that niflumic acid is an open-channel blocker of CFTR that inhibits Cl(-) permeation by plugging the channel pore. It or related agents might be of value in the development of new therapies for autosomal dominant polycystic kidney disease.

  5. Acidity and Acid-Sensing Ion Channels in the Normal and Alzheimer's Disease Brain. (United States)

    Gonzales, Eric B; Sumien, Nathalie


    Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain. We will also cover the pathophysiological associations between ASICs and modulators of ASICs. Finally, this review will sum up how the studies of protons, ASICs and their modulators may generate new therapeutic molecules for Alzheimer's disease and other neurodegenerative diseases.

  6. The fifth solvatomorph of gallic acid with a supramolecular channel structure: Structural complexity and phase transitions (United States)

    Thomas, Sajesh P.; Kaur, Ramanpreet; Kaur, Jassjot; Sankolli, Ravish; Nayak, Susanta K.; Guru Row, Tayur N.


    A new solvatomorph of gallic acid was generated using chiral additive technique and characterized by single crystal and powder X-ray diffraction, C-13 NMR, IR spectroscopic techniques and thermal analysis. The supramolecular channels formed by hexameric motifs of gallic acid and solvent molecules contain highly disordered solvent molecules with fractional occupancies.

  7. Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel. (United States)

    Blondeau, Nicolas; Pétrault, Olivier; Manta, Stella; Giordanengo, Valérie; Gounon, Pierre; Bordet, Régis; Lazdunski, Michel; Heurteaux, Catherine


    Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially alpha-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly alpha-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. alpha-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.

  8. Differences between main-channel and off-channel food webs in the upper Mississippi River revealed by fatty acid profiles of consumers (United States)

    Larson, James H.; Bartsch, Michelle; Gutreuter, Steve; Knights, Brent C.; Bartsch, Lynn; Richardson, William B.; Vallazza, Jonathan M.; Arts, Michael T.


    Large river systems are often thought to contain a mosaic of patches with different habitat characteristics driven by differences in flow and mixing environments. Off-channel habitats (e.g., backwater areas, secondary channels) can become semi-isolated from main-channel water inputs, leading to the development of distinct biogeochemical environments. Observations of adult bluegill (Lepomis macrochirus) in the main channel of the Mississippi River led to speculation that the main channel offered superior food resources relative to off-channel areas. One important aspect of food quality is the quantity and composition of polyunsaturated fatty acids (PUFA). We sampled consumers from main-channel and backwater habitats to determine whether they differed in PUFA content. Main-channel individuals for relatively immobile species (young-of-year bluegill, zebra mussels [Dreissena polymorpha], and plain pocketbook mussels [Lampsilis cardium]) had significantly greater PUFA content than off-channel individuals. No difference in PUFA was observed for the more mobile gizzard shad (Dorsoma cepedianum), which may move between main-channel and off-channel habitats even at early life-history stages. As off-channel habitats become isolated from main-channel waters, flow and water column nitrogen decrease, potentially improving conditions for nitrogen-fixing cyanobacteria and vascular plants that, in turn, have low PUFA content. We conclude that main-channel food webs of the upper Mississippi River provide higher quality food resources for some riverine consumers as compared to food webs in off-channel habitats.

  9. Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels. (United States)

    Elinder, Fredrik; Liin, Sara I


    Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general. Common features for the fatty acids to act on the ion channels are at least two double bonds in cis geometry and a charged carboxyl group. In total we identify and label five different sites for the PUFAs. PUFA site 1: The intracellular cavity. Binding of PUFA reduces the current, sometimes as a time-dependent block, inducing an apparent inactivation. PUFA site 2: The extracellular entrance to the pore. Binding leads to a block of the channel. PUFA site 3: The intracellular gate. Binding to this site can bend the gate open and increase the current. PUFA site 4: The interface between the extracellular leaflet of the lipid bilayer and the voltage-sensor domain. Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. PUFA site 5: The interface between the extracellular leaflet of the lipid bilayer and the pore domain. Binding to this site affects slow inactivation. This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels.

  10. Solid Phase Extraction by Boric Acid-Functionalized Silica for Determination of Dopamine with High Performance Liquid Chromatography%基于新型硼酸固相萃取柱的多巴胺色谱分析方法

    Institute of Scientific and Technical Information of China (English)

    段语晖; 卫引茂


    用“点击化学”方法,将炔基化3-氨基苯硼酸与叠氮化硅胶反应,制备了新型硼酸固相萃取吸附剂.采用固相萃取(SPE)对样品进行前处理,反相高效液相色谱分离,紫外检测,建立了一种快速、高效、灵敏的多巴胺分析方法.固相萃取的最优条件为:对200 mg吸附剂装填的萃取柱,用甲醇活化,磷酸盐缓冲溶液(pH 8.0)平衡,再分别用1mL水和2 mL 20%甲醇淋洗,3 mL 1 mol/L醋酸甲醇溶液洗脱.采用C18反相色谱柱,50 mmol/L磷酸二氢钠-乙腈-甲醇流动相(7∶2∶1,V/V)和检测波长280nm的色谱条件,对洗脱液进行色谱分析.结果表明,该吸附剂对顺式邻羟基化合物有良好的识别能力.在最优萃取条件下,多巴胺的回收率达90%以上.多巴胺分析的线性范围为0.1 ~ 100 mg/L,检出限为0.0001 mg/L,相对标准偏差(RSD)<10.6%.在实际样品分析中,大鼠空白血加标液的回收率均高于97%,相对标准偏差为4.30%.%A new boronic acid-functionalized solid phase extraction ( SPE) sorbent was prepared by the reaction of 3-aminophenyl boronic acid with azide-functionalized silica through "click chemistry". A SPE-HPLC-UV method was developed for the determination of dopamine. The solid-phase extraction conditions were optimized as following: the extraction column packed with 200 mg of sorbent was activated by methanol and equilibrated with phosphate buffer (pH 8.0), and then the loaded sample was washed with 1.0 mL of water followed by 2. 0 mL of 20% methanol aqueous solution to remove interferences and finally the dopamine was eluted with 3 mL of 1. 0 mol/L acetic acid in methanol solution. Using C18 reversed phase chromatographic column, dihydrogen phosphate buffer (50 mmol/L; sodium salt)-acetonitrile-methanol (7:2:1, V/V) as the mobile phase, the eluent was analyzed by HPLC at wavelength of 280 nm. The results showed that the sorbent had excellent recognition ability toward cis-diols compounds. Under the

  11. Structure of the Cyanuric Acid Hydrolase TrzD Reveals Product Exit Channel

    Energy Technology Data Exchange (ETDEWEB)

    Bera, Asim K.; Aukema, Kelly G.; Elias, Mikael; Wackett, Lawrence P.


    Cyanuric acid hydrolases are of industrial importance because of their use in aquatic recreational facilities to remove cyanuric acid, a stabilizer for the chlorine. Degradation of excess cyanuric acid is necessary to maintain chlorine disinfection in the waters. Cyanuric acid hydrolase opens the cyanuric acid ring hydrolytically and subsequent decarboxylation produces carbon dioxide and biuret. In the present study, we report the X-ray structure of TrzD, a cyanuric acid hydrolase from Acidovorax citrulli. The crystal structure at 2.19 Å resolution shows a large displacement of the catalytic lysine (Lys163) in domain 2 away from the active site core, whereas the two other active site lysines from the two other domains are not able to move. The lysine displacement is proposed here to open up a channel for product release. Consistent with that, the structure also showed two molecules of the co-product, carbon dioxide, one in the active site and another trapped in the proposed exit channel. Previous data indicated that the domain 2 lysine residue plays a role in activating an adjacent serine residue carrying out nucleophilic attack, opening the cyanuric acid ring, and the mobile lysine guides products through the exit channel.

  12. JZTX-IV, a unique acidic sodium channel toxin isolated from the spider Chilobrachys jingzhao. (United States)

    Wang, Meichi; Diao, Jianbo; Li, Jiang; Tang, Jianzhou; Lin, Yin; Hu, Weijun; Zhang, Yongqun; Xiao, Yucheng; Liang, Songping


    Neurotoxins are important tools to explore the structure and function relationship of different ion channels. From the venom of Chinese spider Chilobrachys jingzhao, a novel toxin, Jingzhaotoxin-IV (JZTX-IV), is isolated and characterized. It consists of 34 amino acid residues including six acidic residues clustered with negative charge (pI=4.29). The full-length cDNA of JZTX-IV encodes an 86-amino acid precursor containing a signal peptide of 21 residues, a mature peptide of 34 residues and an intervening sequence of 29 residues with terminal Lys-Gly as the signal of amidation. Under whole-cell patch clamp conditions, JZTX-IV inhibits current and slows the inactivation of sodium channels by shifting the voltage dependence of activation to more depolarized potentials on DRG neurons, therefore, differs from the classic site 4 toxins that shift voltage dependence of activation in the opposite direction. In addition, JZTX-IV shows a slowing inactivation of sodium channel with a hyperpolarizing shift of the steady-state inactivation on acutely isolated rat cardiac cell and DRG neurons, differs from the classic site 3 toxins that do not affect the steady-state of inactivation. At high concentration, JZTX-IV has no significant effect on tetrodotoxin-resistant (TTX-R) sodium channels on rat DRG neurons and tetrodotoxin-sensitive (TTX-S) sodium channels on hippocampal neurons. Our data establish that, contrary to known toxins, JZTX-IV neither binds to the previously characterized classic site 4, nor site 3 by modifying channel gating, thus making it a novel probe of channel gating in sodium channels with potential to shed new light on this process.

  13. The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel.

    Directory of Open Access Journals (Sweden)

    Samira Yazdi


    Full Text Available Voltage-gated potassium (KV channels are membrane proteins that respond to changes in membrane potential by enabling K+ ion flux across the membrane. Polyunsaturated fatty acids (PUFAs induce channel opening by modulating the voltage-sensitivity, which can provide effective treatment against refractory epilepsy by means of a ketogenic diet. While PUFAs have been reported to influence the gating mechanism by electrostatic interactions to the voltage-sensor domain (VSD, the exact PUFA-protein interactions are still elusive. In this study, we report on the interactions between the Shaker KV channel in open and closed states and a PUFA-enriched lipid bilayer using microsecond molecular dynamics simulations. We determined a putative PUFA binding site in the open state of the channel located at the protein-lipid interface in the vicinity of the extracellular halves of the S3 and S4 helices of the VSD. In particular, the lipophilic PUFA tail covered a wide range of non-specific hydrophobic interactions in the hydrophobic central core of the protein-lipid interface, while the carboxylic head group displayed more specific interactions to polar/charged residues at the extracellular regions of the S3 and S4 helices, encompassing the S3-S4 linker. Moreover, by studying the interactions between saturated fatty acids (SFA and the Shaker KV channel, our study confirmed an increased conformational flexibility in the polyunsaturated carbon tails compared to saturated carbon chains, which may explain the specificity of PUFA action on channel proteins.

  14. Acute toxicity and histopathology of channel catfish fry exposed to peracetic acid (United States)

    Channel catfish Ictalurus punctatus yolk-sac fry and swim-up fry were exposed to peracetic acid (PAA) for 48h in static toxicity bioassays at 23C. The test water was 217 and 126 mg/L (as CaCO3) total alkalinity and total hardness, respectively. Probit LC50 values were estimated with the trimmed Sp...

  15. The formate channel FocA exports the products of mixed-acid fermentation. (United States)

    Lü, Wei; Du, Juan; Schwarzer, Nikola J; Gerbig-Smentek, Elke; Einsle, Oliver; Andrade, Susana L A


    Formate is a major metabolite in the anaerobic fermentation of glucose by many enterobacteria. It is translocated across cellular membranes by the pentameric ion channel/transporter FocA that, together with the nitrite channel NirC, forms the formate/nitrite transporter (FNT) family of membrane transport proteins. Here we have carried out an electrophysiological analysis of FocA from Salmonella typhimurium to characterize the channel properties and assess its specificity toward formate and other possible permeating ions. Single-channel currents for formate, hypophosphite and nitrite revealed two mechanistically distinct modes of gating that reflect different types of structural rearrangements in the transport channel of each FocA protomer. Moreover, FocA did not conduct cations or divalent anions, but the chloride anion was identified as further transported species, along with acetate, lactate and pyruvate. Formate, acetate and lactate are major end products of anaerobic mixed-acid fermentation, the pathway where FocA is predominantly required, so that this channel is ideally adapted to act as a multifunctional export protein to prevent their intracellular accumulation. Because of the high degree of conservation in the residues forming the transport channel among FNT family members, the flexibility in conducting multiple molecules is most likely a general feature of these proteins.

  16. TRP channels, omega-3 fatty acids, and oxidative stress in neurodegeneration: from the cell membrane to intracellular cross-links

    Directory of Open Access Journals (Sweden)

    M. Leonelli


    Full Text Available The transient receptor potential channels family (TRP channels is a relatively new group of cation channels that modulate a large range of physiological mechanisms. In the nervous system, the functions of TRP channels have been associated with thermosensation, pain transduction, neurotransmitter release, and redox signaling, among others. However, they have also been extensively correlated with the pathogenesis of several innate and acquired diseases. On the other hand, the omega-3 polyunsaturated fatty acids (n-3 fatty acids have also been associated with several processes that seem to counterbalance or to contribute to the function of several TRPs. In this short review, we discuss some of the remarkable new findings in this field. We also review the possible roles played by n-3 fatty acids in cell signaling that can both control or be controlled by TRP channels in neurodegenerative processes, as well as both the direct and indirect actions of n-3 fatty acids on TRP channels.

  17. Effects of n-3 polyunsaturated fatty acids on cardiac ion channels

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    Cristina eMoreno


    Full Text Available Dietary n-3 polyunsaturated fatty acids (PUFAs have been reported to exhibit antiarrhythmic properties, attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on cardiac sodium channel (Nav1.5 and two potassium channels (Kv (Kv1.5 and Kv11.1. n-3 marine (docohexaenoic and eicohexapentaenoic acid and plant origin (alpha-linolenic acid PUFAs block Kv1.5 and Kv11.1 channels at physiological concentrations. Also, DHA and EPA decreased Nav1.5 and calcium channels. These effects on Na and Ca channels theoretically should shorten the cardiac APD, whereas the blocking actions of n-3 PUFAs of Kv channels should lengthen the cardiac action potential. Experiments performed in female rabbits fed with a diet rich in n-3 PUFAs show a longer cardiac action potential and effective refractory period. This study was performed to analyze if their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability and dispersion of the cardiac action potential (TRIaD as a measure of proarrhythmic effects. Dietary n-3 PUFAs supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced torsades de pointes (TdP. Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of dietary supplements of n-3 PUFAs against dofetilide induced proarrhythmia observed in this animal model. The cardiac effects of n-3 PUFAs resemble those of amiodarone: both block sodium, calcium and potassium channels, have anti-adrenergic properties, can prolong the cardiac action potential, reverse TRIaD and suppress TdP. The main difference is that sodium channel block by n-3 PUFAs has a much faster onset and offset kinetics. Therefore, the electrophysiological profile of n-3 PUFAs appears more desirable: the duration of reduced sodium current (facilitates re-entry is much shorter. The n-3 PUFAs appear as a safer alternative to other antiarrhythmic

  18. Acid activation mechanism of the influenza A M2 proton channel. (United States)

    Liang, Ruibin; Swanson, Jessica M J; Madsen, Jesper J; Hong, Mei; DeGrado, William F; Voth, Gregory A


    The homotetrameric influenza A M2 channel (AM2) is an acid-activated proton channel responsible for the acidification of the influenza virus interior, an important step in the viral lifecycle. Four histidine residues (His37) in the center of the channel act as a pH sensor and proton selectivity filter. Despite intense study, the pH-dependent activation mechanism of the AM2 channel has to date not been completely understood at a molecular level. Herein we have used multiscale computer simulations to characterize (with explicit proton transport free energy profiles and their associated calculated conductances) the activation mechanism of AM2. All proton transfer steps involved in proton diffusion through the channel, including the protonation/deprotonation of His37, are explicitly considered using classical, quantum, and reactive molecular dynamics methods. The asymmetry of the proton transport free energy profile under high-pH conditions qualitatively explains the rectification behavior of AM2 (i.e., why the inward proton flux is allowed when the pH is low in viral exterior and high in viral interior, but outward proton flux is prohibited when the pH gradient is reversed). Also, in agreement with electrophysiological results, our simulations indicate that the C-terminal amphipathic helix does not significantly change the proton conduction mechanism in the AM2 transmembrane domain; the four transmembrane helices flanking the channel lumen alone seem to determine the proton conduction mechanism.

  19. [Kv3.4 channel is involved in rat pulmonary vasoconstriction induced by 15-hydroxyeicosatetraenoic acid]. (United States)

    Li, Qian; Bi, Hai-Rong; Zhang, Rong; Zhu, Da-Ling


    We have reported that hypoxia increases the activation of 15-lipoxygenase (15-LO), which converts arachidonic acid (AA) into 15-hydroxyeicosatetraenoic acid (15-HETE) in small pulmonary arteries (PAs). Through inhibition of Kv channels, 15-HETE causes more robust concentration-dependent contraction of PA rings from the hypoxic compared to the normoxic controls. However, the subtypes of Kv channels inhibited by 15-HETE are incompletely understood. The aim of the present study was to identify the contribution of Kv3.4 channel in the process of pulmonary vasoconstriction induced by 15-HETE using the tension studies of PA rings from rat with Kv3.4 channel blocker in tissue bath; to explore the role of vascular endothelium in15-HETE-induced pulmonary vasoconstriction through denuded endothelia of PA rings; and to define the downregulation of 15-HETE on the expression of Kv3.4 channel in cultured pulmonary artery smooth muscle cells (PASMCs) with RT-PCR and Western blot. In the present study, healthy Wistar rats were divided randomly into two groups: Group A with normal oxygen supply and group B with hypoxia. Six days later, the rats were killed. Pulmonary artery rings were prepared for organ bath experiments. Firstly, different concentrations of 15-HETE (10~1 000 nmol/L) were added to the Krebs solution. The isometric tension was recorded using a four-channel force-displacement transducer. Then Kv3.4 channel blocker, 100 nmol/L BDS-I, was added, followed by adding 1 mumol/L 15-HETE, and the isometric tension was recorded. Furthermore, RT-PCR and Western blot were employed to identify the influence of 15-HETE on the expression of Kv3.4 channel in cultured rat PASMCs.The results showed the PA tension was significantly increased both in groups A and B by 15-HETE in a concentration-dependent manner (PKv3.4 channel blocker, BDS-I, significantly decreased the PA ring constriction induced by 15-HETE (PKv3.4 mRNA and protein in rat PASMCs were significantly downregulated by 15

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

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    Juan Francisco Rodríguez-Landa


    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.

  1. Niflumic acid, a TRPV1 channel modulator, ameliorates stavudine-induced neuropathic pain. (United States)

    Marwaha, Lovish; Bansal, Yashika; Singh, Raghunath; Saroj, Priyanka; Sodhi, Rupinder Kaur; Kuhad, Anurag


    TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain. Various behavioral tests were performed to access neuropathic pain (hyperalgesia and allodynia) on 7th, 14th, 21st, and 28th days. Electrophysiology (motor nerve conduction velocity; MNCV) and biochemical estimations were conducted after 28th day. Niflumic acid (10, 15, and 20 mg/kg) was administered intraperitoneally and evaluated against behavioral, electrophysiological (MNCV), and biochemical alterations in stavudine-treated rats. Pregabalin (30 mg/kg) was taken as reference standard and administered intraperitoneally. Four weeks after stavudine injection, rats developed behavioral, electrophysiological (MNCV), and biochemical (oxidative, nitrosative stress, and inflammatory cytokines, TRPV1) alterations. Niflumic acid restored core and associated symptoms of peripheral neuropathy by suppressing oxidative-nitrosative stress, inflammatory cytokines (TNF-α, IL-1β) and TRPV1 level in stavudine-induced neuropathic pain in rats. Pharmacological efficacy of niflumic acid (20 mg/kg) was equivalent to pregabalin (30 mg/kg). In conclusion, niflumic acid attenuates STV-induced behavioral, electrophysiological and biochemical alterations by manipulating TRP channel activity in two manners: (1) direct antagonistic action against TRPV1 channels and (2) indirect inhibition of TRP channels by blocking oxidative and inflammatory surge. Therefore, NA can be developed as a potential pharmacotherapeutic

  2. Structural Basis for Ether-a-go-go-Related Gene K+ Channel Subtype-Dependent Activation by Niflumic Acid[S


    Fernandez, David; Sargent, John; Frank B Sachse; Sanguinetti, Michael C.


    Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridin-ecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K+ channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel ...

  3. Cl- channel blockers NPPB and niflumic acid blunt Ca(2+)-induced erythrocyte 'apoptosis'. (United States)

    Myssina, Svetlana; Lang, Philipp A; Kempe, Daniela S; Kaiser, Stefanie; Huber, Stephan M; Wieder, Thomas; Lang, Florian


    Exposure to Ca2+ ionophore ionomycin, osmotic shock, oxidative stress and glucose depletion trigger cell shrinkage and scramblase-mediated phosphatidylserine exposure at the outer leaflet of the erythrocyte cell membrane. The effects are partially due to activation of GARDOS channels and subsequent cellular K+ loss leading not only to cell shrinkage but also participating in the triggering of erythrocyte scramblase. As conductive loss of K+ would depend on the parallel loss of anions we hypothesised that activation of scramblase is similarly dependent on the activity of Cl- channels. To test this hypothesis, we used Cl- channel blockers NPPB and niflumic acid. It is shown here that treatment of erythrocytes with 1 microM ionomycin leads to cellular K+ loss, decrease of hematocrit and decrease of forward scatter in FACS analysis reflecting cell shrinkage as well as increase of annexin positive cells reflecting phosphatidylserine exposure. Those events were significantly blunted in the presence of 100 microM NPPB by 34% (K+ loss), 45% (hematocrit), 32% (forward scatter) and 69% (annexin binding), or in the presence of 100 microM niflumic acid by 15% (forward scatter) and 45% (annexin binding), respectively. Moreover, oxidative stress triggered annexin binding which was again significantly inhibited (by 51%) in the presence of 100 microM NPPB. In conclusion, Cl- channels presumably participate in the regulation of erythrocyte 'apoptosis'.

  4. Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating mechanism.

    Directory of Open Access Journals (Sweden)

    Huaiyu Yang


    Full Text Available The acid-sensing ion channel 1 (ASIC1 is a key receptor for extracellular protons. Although numerous structural and functional studies have been performed on this channel, the structural dynamics underlying the gating mechanism remains unknown. We used normal mode analysis, mutagenesis, and electrophysiological methods to explore the relationship between the inherent dynamics of ASIC1 and its gating mechanism. Here we show that a series of collective motions among the domains and subdomains of ASIC1 correlate with its acid-sensing function. The normal mode analysis result reveals that the intrinsic rotation of the extracellular domain and the collective motions between the thumb and finger induced by proton binding drive the receptor to experience a deformation from the extracellular domain to the transmembrane domain, triggering the channel pore to undergo "twist-to-open" motions. The movements in the transmembrane domain indicate that the likely position of the channel gate is around Leu440. These motion modes are compatible with a wide body of our complementary mutations and electrophysiological data. This study provides the dynamic fundamentals of ASIC1 gating.

  5. Flufenamic acid decreases neuronal excitability through modulation of voltage-gated sodium channel gating. (United States)

    Yau, Hau-Jie; Baranauskas, Gytis; Martina, Marco


    The electrophysiological phenotype of individual neurons critically depends on the biophysical properties of the voltage-gated channels they express. Differences in sodium channel gating are instrumental in determining the different firing phenotypes of pyramidal cells and interneurons; moreover, sodium channel modulation represents an important mechanism of action for many widely used CNS drugs. Flufenamic acid (FFA) is a non-steroidal anti-inflammatory drug that has been long used as a blocker of calcium-dependent cationic conductances. Here we show that FFA inhibits voltage-gated sodium currents in hippocampal pyramidal neurons; this effect is dose-dependent with IC(50) = 189 μm. We used whole-cell and nucleated patch recordings to investigate the mechanisms of FFA modulation of TTX-sensitive voltage-gated sodium current. Our data show that flufenamic acid slows down the inactivation process of the sodium current, while shifting the inactivation curve ~10 mV toward more hyperpolarized potentials. The recovery from inactivation is also affected in a voltage-dependent way, resulting in slower recovery at hyperpolarized potentials. Recordings from acute slices demonstrate that FFA reduces repetitive- and abolishes burst-firing in CA1 pyramidal neurons. A computational model based on our data was employed to better understand the mechanisms of FFA action. Simulation data support the idea that FFA acts via a novel mechanism by reducing the voltage dependence of the sodium channel fast inactivation rates. These effects of FFA suggest that it may be an effective anti-epileptic drug.

  6. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss


    Ramadoss, Jayanth; Lunde, Emilie R.; Ouyang, Nengtai; Chen, Wei-Jung A.; Cudd, Timothy A.


    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury...

  7. Photoaffinity Probe Candidates for Gamma-aminobutyric Acid (GABAA)-Gated Chloride Channel

    Institute of Scientific and Technical Information of China (English)

    Shang Zhong LIU; Qing Xiao LI


    New photoaffinity ligand candidates were synthesized based on 5-t-butyl-2-(4- (substituted-ethynyl)phenyl)-1, 3-dithiane for the noncompetitive blocker site on the gamma- aminobutyric acid -gated chloride channel. Their half-maximal inhibition concentrations ranged from 4 to 32 nmol/L as measured by 4'-ethynyl-4-n-[2,3-3H2]-propylbicycloorthobenzoate (3H EBOB) assay.

  8. Modulation of Ionotropic Glutamate Receptors and Acid-Sensing Ion Channels by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    John Q Wang


    Full Text Available Ionotropic glutamate receptors (iGluR are ligand-gated ion channels and are densely expressed in broad areas of mammalian brains. Like iGluRs, acid-sensing ion channels (ASIC are ligand (H+-gated channels and are enriched in brain cells and peripheral sensory neurons. Both ion channels are enriched at excitatory synaptic sites, functionally coupled to each other, and subject to the modulation by a variety of signaling molecules. Central among them is a gasotransmitter, nitric oxide (NO. Available data show that NO activity-dependently modulates iGluRs and ASICs via either a direct or an indirect pathway. The former involves a NO-based and cGMP-independent posttranslational modification (S-nitrosylation of extracellular cysteine residues in channel subunits or channel-interacting proteins. The latter is achieved by NO activation of soluble guanylyl cyclase, which in turn triggers an intracellular cGMP-sensitive cascade to indirectly modulate iGluRs and ASICs. The NO modification is usually dynamic and reversible. Modified channels undergo significant, interrelated changes in biochemistry and electrophysiology. Since NO synthesis is enhanced in various neurological disorders, the NO modulation of iGluRs and ASICs is believed to be directly linked to the pathogenesis of these disorders. This review summarizes the direct and indirect modifications of iGluRs and ASICs by NO and analyzes the role of the NO-iGluR and NO-ASIC coupling in cell signaling and in the pathogenesis of certain related neurological diseases.


    Institute of Scientific and Technical Information of China (English)

    王长罡; 董俊华; 柯伟; 陈楠


    The strategy for disposal of high-level radioactive waste in china is to enclose the spent nuclear fuel in sealed metal canisters which are embedded in bentonite clay hundreds meters deep in the bed-rock. The choice of container material depends largely on the redox conditions and the aqueous environment of the repository. One of the choices for the fabrication of waste canisters is copper, for it is thermodynamically stable under the saline, anoxic conditions over the large majority of the container lifetime. For this advantage, some other countries (Canada, Sweden) have selected copper as the material of nuclear waste container. However, in the early aerobic phase of the geological disposal the corrosion of copper could take place, and the corrosion behavior of copper would be influenced by the complex chemical conditions of groundwater markedly. Regularly, in atmosphere environment the semiconductor passive film which is constructed by Cu2O would generate on the surface of copper. On the one hand, the Cu2O film could protect copper from corrosion. On the other hand, the formation of Cu2O film is necessary to maintain the propagation of crack during the stress corrosion cracking. Therefore, the study of the effect of water chemistry conditions on the stability of Cu2O passive film makes great sense for the general corrosion and stress corrosion cracking of copper. For copper and copper alloy, Cl- is a highly aggressive ion. Lots of cases of failure and corrosion behavior of copper and copper alloy in Cl- environment have been studied. The immersion of Cl- would affect the semiconductor properties of Cu2O, therefore, we focused on the effect of pH and Cl- concentration on the corrosion behavior and semiconductor properties of Cu2O in this paper. The polarization behavior of Cu electrodes and the stability of passive film Cu2O in boric acid buffer solution have been investigated respectively by potentiodynamic polarization, electrochemical impedance spectroscopy

  10. Efeito da época de estaquia, fitorreguladores e ácido bórico no enraizamento de estacas de porta-enxertos de videira Effect of pruning time, growth regulators and boric acid on rooting of grape rootstock cuttings

    Directory of Open Access Journals (Sweden)

    S. Leonel


    Full Text Available Estudaram-se as interações entre os ácidos indol-butírico, alfa-naftaleno-acético e bórico no desenvolvimento de raízes em estacas de porta-enxertos de videira (Vitis vinifera L.. As estacas tinham aproximadamente 25 cm de comprimento e, necessariamente, 2 gemas, sendo obtidas em três épocas distintas (janeiro, abril e julho e colocadas para enraizar em bandejas de isopor, tendo vermiculita como substrato, e mantidas sob nebulização. O tratamento constou da imersão de 2,5 cm da base das estacas em soluções, por um tempo de imersão de 1 minuto. Os tratamentos utilizados corresponderam a: 1 .000; 2.000 e 5.000 ppm de IBA; 1.500 e 3.000 ppm de NAA; 150 microgramas/ml de H3BO3; IBA 1.000; 2.000 e 5.000 + H3BO3 150 microgramas/ml e H2O. Avaliaram-se a porcentagem de enraizamento, o número médio de raízes formadas por estaca e o comprimento médio das raízes (mm aos 90 dias após a instalação, no mês de julho. O IBA 2.000 ppm propiciou o enraizamento em 88,87% das estacas, contudo não diferiu estatisticamente da testemunha (H2O-61,10%. A melhor época de coleta de estaca para o enraizamento foi o mês de julho (inverno.The effects of indolebutyric, naphtalen acetic and boric acids were studied on rooting of grape rootstock cuttings. The cuttings were 25 cm long with two buds and were taken in three different times (January, April and July. Rooting was carried out in styrofoam trays with vermiculite as substratum and under intermittent mist. Cuttings were imersed up to 2.5 cm from the base in solutions for one minute. The treatments were: 1,000; 2,000 and 5,000 ppm of IBA; 1,500 and 3,000 ppm of NAA; 150 micrograms/ml H3BO3; IBA 1,000; 2,000 and 5,000 ppm plus H3BO(3150 niicrograins/ml and H2O. Rooting percentage, average number of roots per cutting and average length of roots (mm were evaluated 90 days after planting, in July. IBA at 2,000 ppm was the best treatment with 88.8% of rooted cuttings. The best time for rooting was

  11. Mechanism of interaction of niflumic acid with heterologously expressed kidney CLC-K chloride channels. (United States)

    Picollo, Alessandra; Liantonio, Antonella; Babini, Elena; Camerino, Diana Conte; Pusch, Michael


    CLC-K Cl(-) channels belong to the CLC protein family. In kidney and inner ear, they are involved in transepithelial salt transport. Mutations in ClC-Kb lead to Bartter's syndrome, and mutations in the associated subunit barttin produce Bartter's syndrome and deafness. We have previously found that 3-phenyl-CPP blocks hClC-Ka and rClC-K1 from the extracellular side in the pore entrance. Recently, we have shown that niflumic acid (NFA), a nonsteroidal anti-inflammatory fenamate, produces biphasic behavior on human CLC-K channels that suggests the presence of two functionally different binding sites: an activating site and a blocking site. Here, we investigate in more detail the interaction of NFA on CLC-K channels. Mutants that altered block by 3-phenyl-2-(p-chlorophenoxy)propionic acid (CPP) had no effect on NFA block, indicating that the inhibition binding site of NFA is different from that of 3-phenyl-CPP and flufenamic acid. Moreover, NFA does not compete with extracellular Cl(-) ions, suggesting that the binding sites of NFA are not located deep in the pore. Differently from ClC-Ka, on the rat homologue ClC-K1, NFA has only an inhibitory effect. We developed a quantitative model to describe the complex action of NFA on ClC-Ka. The model predicts that ClC-Ka possesses two NFA binding sites: when only one site is occupied, NFA increases ClC-Ka currents, whereas the occupation of both binding sites leads to channel block.

  12. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    Directory of Open Access Journals (Sweden)

    Kummer Wolfgang


    Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

  13. An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels. (United States)

    Nolting, Andreas; Ferraro, Teresa; D'hoedt, Dieter; Stocker, Martin


    Small conductance calcium-activated potassium channels (SK, K(Ca)) are a family of voltage-independent K+ channels with a distinct physiology and pharmacology. The bee venom toxin apamin inhibits exclusively the three cloned SK channel subtypes (SK1, SK2, and SK3) with different affinity, highest for SK2, lowest for SK1, and intermediate for SK3 channels. The high selectivity of apamin made it a valuable tool to study the molecular makeup and function of native SK channels. Three amino acids located in the outer vestibule of the pore are of particular importance for the different apamin sensitivities of SK channels. Chimeric SK1 channels, enabling the homomeric expression of the rat SK1 (rSK1) subunit and containing the core domain (S1-S6) of rSK1, are apamin-insensitive. By contrast, channels formed by the human orthologue human SK1 (hSK1) are sensitive to apamin. This finding hinted at the involvement of regions beyond the pore as determinants of apamin sensitivity, because hSK1 and rSK1 have an identical amino acid sequence in the pore region. Here we investigated which parts of the channels outside the pore region are important for apamin sensitivity by constructing chimeras between apamin-insensitive and -sensitive SK channel subunits and by introducing point mutations. We demonstrate that a single amino acid situated in the extracellular loop between the transmembrane segments S3 and S4 has a major impact on apamin sensitivity. Our findings enabled us to convert the hSK1 channel into a channel that was as sensitive for apamin as SK2, the SK channel with the highest sensitivity.

  14. Potassium channel currents in intact stomatal guard cells: rapid enhancement by abscisic acid. (United States)

    Blatt, M R


    Evidence of a role for abscisic acid (ABA) in signalling conditions of water stress and promoting stomatal closure is convincing, but past studies have left few clues as to its molecular mechanism(s) of action; arguments centred on changes in H(+)-pump activity and membrane potential, especially, remain ambiguous without the fundamental support of a rigorous electrophysiological analysis. The present study explores the response to ABA of K(+) channels at the membrane of intact guard cells of Vicia faba L. Membrane potentials were recorded before and during exposures to ABA, and whole-cell currents were measured at intervals throughout to quantitate the steady-state and time-dependent characteristics of the K(+) channels. On adding 10 μM ABA in the presence of 0.1, 3 or 10 mM extracellular K(+), the free-running membrane potential (V m) shifted negative-going (-)4-7 mV in the first 5 min of exposure, with no consistent effect thereafter. Voltage-clamp measurements, however, revealed that the K(+)-channel current rose to between 1.84- and 3.41-fold of the controls in the steady-state with a mean halftime of 1.1 ± 0.1 min. Comparable changes in current return via the leak were also evident and accounted for the minimal response in V m. Calculated at V m, the K(+) currents translated to an average 2.65-fold rise in K(+) efflux with ABA. Abscisic acid was not observed to alter either K(+)-current activation or deactivation.These results are consistent with an ABA-evoked mobilization of K(+) channels or channel conductance, rather than a direct effect of the phytohormone on K(+)-channel gating. The data discount notions that large swings in membrane voltage are a prerequisite to controlling guard-cell K(+) flux. Instead, thev highlight a rise in membrane capacity for K(+) flux, dependent on concerted modulations of K(+)-channel and leak currents, and sufficiently rapid to account generally for the onset of K(+) loss from guard cells and stomatal closure in ABA.

  15. Optical control of trimeric P2X receptors and acid-sensing ion channels. (United States)

    Browne, Liam E; Nunes, João P M; Sim, Joan A; Chudasama, Vijay; Bragg, Laricia; Caddick, Stephen; North, R Alan


    P2X receptors are trimeric membrane proteins that function as ion channels gated by extracellular ATP. We have engineered a P2X2 receptor that opens within milliseconds by irradiation at 440 nm, and rapidly closes at 360 nm. This requires bridging receptor subunits via covalent attachment of 4,4'-bis(maleimido)azobenzene to a cysteine residue (P329C) introduced into each second transmembrane domain. The cis-trans isomerization of the azobenzene pushes apart the outer ends of the transmembrane helices and opens the channel in a light-dependent manner. Light-activated channels exhibited similar unitary currents, rectification, calcium permeability, and dye uptake as P2X2 receptors activated by ATP. P2X3 receptors with an equivalent mutation (P320C) were also light sensitive after chemical modification. They showed typical rapid desensitization, and they could coassemble with native P2X2 subunits in pheochromocytoma cells to form light-activated heteromeric P2X2/3 receptors. A similar approach was used to open and close human acid-sensing ion channels (ASICs), which are also trimers but are unrelated in sequence to P2X receptors. The experiments indicate that the opening of the permeation pathway requires similar and substantial movements of the transmembrane helices in both P2X receptors and ASICs, and the method will allow precise optical control of P2X receptors or ASICs in intact tissues.

  16. Channel-mediated lactic acid transport: a novel function for aquaglyceroporins in bacteria. (United States)

    Bienert, Gerd P; Desguin, Benoît; Chaumont, François; Hols, Pascal


    MIPs (major intrinsic proteins), also known as aquaporins, are membrane proteins that channel water and/or uncharged solutes across membranes in all kingdoms of life. Considering the enormous number of different bacteria on earth, functional information on bacterial MIPs is scarce. In the present study, six MIPs [glpF1 (glycerol facilitator 1)-glpF6] were identified in the genome of the Gram-positive lactic acid bacterium Lactobacillus plantarum. Heterologous expression in Xenopus laevis oocytes revealed that GlpF2, GlpF3 and GlpF4 each facilitated the transmembrane diffusion of water, dihydroxyacetone and glycerol. As several lactic acid bacteria have GlpFs in their lactate racemization operon (GlpF1/F4 phylogenetic group), their ability to transport this organic acid was tested. Both GlpF1 and GlpF4 facilitated the diffusion of D/L-lactic acid. Deletion of glpF1 and/or glpF4 in Lb. plantarum showed that both genes were involved in the racemization of lactic acid and, in addition, the double glpF1 glpF4 mutant showed a growth delay under conditions of mild lactic acid stress. This provides further evidence that GlpFs contribute to lactic acid metabolism in this species. This lactic acid transport capacity was shown to be conserved in the GlpF1/F4 group of Lactobacillales. In conclusion, we have functionally analysed the largest set of bacterial MIPs and demonstrated that the lactic acid membrane permeability of bacteria can be regulated by aquaglyceroporins.

  17. Effects of Glutamic Acid on C-type Inactivation of Kvl.4△N Channel

    Institute of Scientific and Technical Information of China (English)

    Cheng Ye; Xiaoyan Li; Zhouwu Shu; Xuejun Jiang


    Objectives Acidosis has an inhibitory effect on the inactivation of Kvl.4 AN channel through the position H508.So in order to show the effects of glutamic acid on the mutant Kv 1.4 channel that lacks N-type inactivation(Kvl.4A2-146),we studied in the expression system of the Xenopus oocytes.Methods The two-electrode voltage-clamp technique(TEV)was used to record the currents.Results Acidosis increased fKvl.4 △2-146 C-type inactivation.After application of glutamic acid(1 mmol/L) to Kvl.4 △2-146 increased C-type inactivation further,changed inactivation time constants from (2.02±0.39s)to(1.71±0.23 s)(P<0.05)at +50my,and shifted the steadystate inactivation curves of Kvl.4 △N to positive potential,which was from(-44.30±0.59 mV) to(-39.88±0.29 mV)(P<0.05 ).and slowed the rate of recovery from inactivation,which was from(1.64±0.19s) to (1.91±0.23 s)(P<0.05).Conclusions Together,these results suggest that 1 mmol/L glutamic acid accelerates the Ctype inactivation of Kvl.4 AN in pH 6.8.

  18. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss. (United States)

    Ramadoss, Jayanth; Lunde, Emilie R; Ouyang, Nengtai; Chen, Wei-Jung A; Cudd, Timothy A


    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258+/-10 mg/dl peak blood ethanol concentration) or saline in a "3 days/wk binge" pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

  19. Structural Basis for Ether-a-go-go-Related Gene K+ Channel Subtype-Dependent Activation by Niflumic Acid[S (United States)

    Fernandez, David; Sargent, John; Sachse, Frank B.; Sanguinetti, Michael C.


    Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridin-ecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K+ channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel currents independent of channel state. At 1 mM, NFA shifted the half-point for activation by −6, −18, and −11 mV for ERG1, ERG2, and ERG3 channels, respectively. The half-point for channel inactivation was shifted by +5 to +9 mV by NFA. The structural basis for the ERG subtype-specific response to NFA was explored with chimeric channels and site-directed mutagenesis. The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker. PMID:18218980

  20. Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid. (United States)

    Fernandez, David; Sargent, John; Sachse, Frank B; Sanguinetti, Michael C


    Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel currents independent of channel state. At 1 mM, NFA shifted the half-point for activation by -6, -18, and -11 mV for ERG1, ERG2, and ERG3 channels, respectively. The half-point for channel inactivation was shifted by +5 to +9 mV by NFA. The structural basis for the ERG subtype-specific response to NFA was explored with chimeric channels and site-directed mutagenesis. The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker.

  1. The bile acid-sensitive ion channel (BASIC), the ignored cousin of ASICs and ENaC. (United States)

    Wiemuth, Dominik; Assmann, Marc; Gründer, Stefan


    The DEG/ENaC gene family of ion channels is characterized by a high degree of structural similarity and an equally high degree of diversity concerning the physiological function. In humans and rodents, the DEG/ENaC family comprises 2 main subgroups: the subunits of the epithelial Na(+) channel (ENaC) and the subunits of the acid sensing ion channels (ASICs). The bile acid-sensitive channel (BASIC), previously known as BLINaC or INaC, represents a third subgroup within the DEG/ENaC family. Although BASIC was identified more than a decade ago, very little is known about its physiological function. Recent progress in the characterization of this neglected member of the DEG/ENaC family, which is summarized in this focused review, includes the discovery of surprising species differences, its pharmacological characterization, and the identification of bile acids as putative natural activators.

  2. Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons. (United States)

    Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung


    The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K(+) and Ca(2+) channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K(+) currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K(+) currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs(+) (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca(2+) channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.

  3. Hydrogen bonding: a channel for protons to transfer through acid-base pairs. (United States)

    Wu, Liang; Huang, Chuanhui; Woo, Jung-Je; Wu, Dan; Yun, Sung-Hyun; Seo, Seok-Jun; Xu, Tongwen; Moon, Seung-Hyeon


    Different from H(3)O(+) transport as in the vehicle mechanism, protons find another channel to transfer through the poorly hydrophilic interlayers in a hydrated multiphase membrane. This membrane was prepared from poly(phthalazinone ether sulfone kentone) (SPPESK) and H(+)-form perfluorosulfonic resin (FSP), and poorly hydrophilic electrostatically interacted acid-base pairs constitute the interlayer between two hydrophilic phases (FSP and SPPESK). By hydrogen bonds forming and breaking between acid-base pairs and water molecules, protons transport directly through these poorly hydrophilic zones. The multiphase membrane, due to this unique transfer mechanism, exhibits better electrochemical performances during fuel cell tests than those of pure FSP and Nafion-112 membranes: 0.09-0.12 S cm(-1) of proton conductivity at 25 degrees C and 990 mW cm(-2) of the maximum power density at a current density of 2600 mA cm(-2) and a cell voltage of 0.38 V.

  4. Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases. (United States)

    Radu, Beatrice Mihaela; Banciu, Adela; Banciu, Daniel Dumitru; Radu, Mihai


    Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed.

  5. Acid-sensing ion channels (ASICs: therapeutic targets for neurological diseases and their regulation

    Directory of Open Access Journals (Sweden)

    Hae-Jin Kweon


    Full Text Available Extracellular acidification occurs not only in pathologicalconditions such as inflammation and brain ischemia, but alsoin normal physiological conditions such as synaptic transmission.Acid-sensing ion channels (ASICs can detect a broadrange of physiological pH changes during pathological andsynaptic cellular activities. ASICs are voltage-independent,proton-gated cation channels widely expressed throughout thecentral and peripheral nervous system. Activation of ASICs isinvolved in pain perception, synaptic plasticity, learning andmemory, fear, ischemic neuronal injury, seizure termination,neuronal degeneration, and mechanosensation. Therefore,ASICs emerge as potential therapeutic targets for manipulatingpain and neurological diseases. The activity of these channelscan be regulated by many factors such as lactate, Zn2+, andPhe-Met-Arg-Phe amide (FMRFamide-like neuropeptides byinteracting with the channel’s large extracellular loop. ASICsare also modulated by G protein-coupled receptors such asCB1 cannabinoid receptors and 5-HT2. This review focuses onthe physiological roles of ASICs and the molecularmechanisms by which these channels are regulated. [BMBReports 2013; 46(6: 295-304

  6. Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration. (United States)

    Behan, A T; Breen, B; Hogg, M; Woods, I; Coughlan, K; Mitchem, M; Prehn, J H M


    Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1(G93A) ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS.

  7. Photocatalytic Degradation of Dicofol and Pyrethrum with Boric and Cerous Co-doped TiO2 under Light Irradiation

    Institute of Scientific and Technical Information of China (English)

    GONG Lifen; ZOU Jing; ZENG Jinbin; CHEN Wenfeng; CHEN Xi; WANG Xiaoru


    Boric and cerous co-doped nano titanium dioxide (B/Ce co-doped TiO2) was synthesized using a sol-gel tech-nique, which involved the hydrolyzation of tetrabutyl titanate with the addition of boric acid and cerous nitrate. The B/Ce co-doped TiO2 was employed for the photocatalytic degradation of dicofol, cyfluthrin and fenvalerate under light irradiation. XRD, TEM, Fr-IR and UV-Vis DRS methods were used to characterize the crystalline structure. Experimental results showed that only the anatase signal phase was found for B/Ce co-doped TiO2, but multiplicate phases, including anatase, rutile and less brookite phases, were identified both in the pure TiO2 nanoparticles and Ce-doped TiO2 nanoparticles. The band gap value of B/Ce co-doped nano TiO2 was narrower than that of undoped nano TiO2. Compared to undoped TiO2, a stronger absorption in the range of 420 to 850 nm was found for B/Ce co-doped nano TiO2, which presented a higher photocatalytic activity in the degradation of dicofol, cyfluthrin and fenvalerate than both Ce doped nano TiO2 and pure nano TiO2 under the same light irradiation.

  8. Elevated Expression of Acid-Sensing Ion Channel 3 Inhibits Epilepsy via Activation of Interneurons. (United States)

    Cao, Qingqing; Wang, Wei; Gu, Juan; Jiang, Guohui; Bian, Xiling; Wang, Kewei; Xu, Zucai; Li, Jie; Chen, Guojun; Wang, Xuefeng


    Recent studies have indicated that acid-sensing ion channels may play a significant role in the termination of epilepsy. In particular, acid-sensing ion channel 3 (ASIC3) is expressed in the central nervous system and is most sensitive to extracellular pH. However, whether ASIC3 plays a role in epilepsy is unknown. In this study, qRT-PCR, Western blot, immunohistochemistry, double immunofluorescence labeling, and slice recordings were used. We first detected elevated ASIC3 expression patterns in the brains of temporal lobe epilepsy patients and epileptic rats. ASIC3 was expressed in neurons and glia in both humans and in an experimental model of epilepsy, and ASIC3 was colocalized with inhibitory GABAergic interneurons. By blocking ASIC3 with its antagonist APETx2, we observed that injected APETx2 shortened the latency to seizure and increased the incidence of generalized tonic clonic seizure compared to the control group in models of both pilocarpine- and pentylenetetrazole (PTZ)-induced seizures. Additionally, blocking ASIC3 significantly decreased the frequency of action potential (AP) firing in interneurons. Moreover, APETx2 significantly reduced the amplitudes and frequencies of miniature inhibitory postsynaptic currents (mIPSCs) while showed no differences with the APETx2 + bicuculline group and the bicuculline group. These findings suggest that elevated levels of ASIC3 may serve as an anti-epileptic mechanism via postsynaptic mechanisms in interneurons. It could represent a novel therapeutic strategy for epilepsy treatment.

  9. Dampening of hyperexcitability in CA1 pyramidal neurons by polyunsaturated fatty acids acting on voltage-gated ion channels.

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    Jenny Tigerholm

    Full Text Available A ketogenic diet is an alternative treatment of epilepsy in infants. The diet, rich in fat and low in carbohydrates, elevates the level of polyunsaturated fatty acids (PUFAs in plasma. These substances have therefore been suggested to contribute to the anticonvulsive effect of the diet. PUFAs modulate the properties of a range of ion channels, including K and Na channels, and it has been hypothesized that these changes may be part of a mechanistic explanation of the ketogenic diet. Using computational modelling, we here study how experimentally observed PUFA-induced changes of ion channel activity affect neuronal excitability in CA1, in particular responses to synaptic input of high synchronicity. The PUFA effects were studied in two pathological models of cellular hyperexcitability associated with epileptogenesis. We found that experimentally derived PUFA modulation of the A-type K (K(A channel, but not the delayed-rectifier K channel, restored healthy excitability by selectively reducing the response to inputs of high synchronicity. We also found that PUFA modulation of the transient Na channel was effective in this respect if the channel's steady-state inactivation was selectively affected. Furthermore, PUFA-induced hyperpolarization of the resting membrane potential was an effective approach to prevent hyperexcitability. When the combined effect of PUFA on the K(A channel, the Na channel, and the resting membrane potential, was simulated, a lower concentration of PUFA was needed to restore healthy excitability. We therefore propose that one explanation of the beneficial effect of PUFAs lies in its simultaneous action on a range of ion-channel targets. Furthermore, this work suggests that a pharmacological cocktail acting on the voltage dependence of the Na-channel inactivation, the voltage dependences of K(A channels, and the resting potential can be an effective treatment of epilepsy.

  10. Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid. (United States)

    Comoglio, Yannick; Levitz, Joshua; Kienzler, Michael A; Lesage, Florian; Isacoff, Ehud Y; Sandoz, Guillaume


    Membrane lipids serve as second messengers and docking sites for proteins and play central roles in cell signaling. A major question about lipid signaling is whether diffusible lipids can selectively target specific proteins. One family of lipid-regulated membrane proteins is the TWIK-related K channel (TREK) subfamily of K2P channels: TREK1, TREK2, and TWIK-related arachdonic acid stimulated K(+) channel (TRAAK). We investigated the regulation of TREK channels by phosphatidic acid (PA), which is generated by phospholipase D (PLD) via hydrolysis of phosphatidylcholine. Even though all three of the channels are sensitive to PA, we found that only TREK1 and TREK2 are potentiated by PLD2 and that none of these channels is modulated by PLD1, indicating surprising selectivity. We found that PLD2, but not PLD1, directly binds to the C terminus of TREK1 and TREK2, but not to TRAAK. The results have led to a model for selective lipid regulation by localization of phospholipid enzymes to specific effector proteins. Finally, we show that regulation of TREK channels by PLD2 occurs natively in hippocampal neurons.

  11. Differential modulation of TWIK-related K(+) channel (TREK) and TWIK-related acid-sensitive K(+) channel 2 (TASK2) activity by pyrazole compounds. (United States)

    Kim, Hyun Jong; Woo, Joohan; Nam, Yuran; Nam, Joo Hyun; Kim, Woo Kyung


    Pyrazole derivatives were originally suggested as selective blockers of the transient receptor potential cation 3 (TRPC3) and channel. In particular, pyr3 and 10 selectively inhibit TRPC3, whereas pyr2 (BTP2) and 6 inhibit ORAI1. However, their effects on background K(+) channel activity have not been elucidated. In this study, the effects of BTP2, pyr3, pyr6, and pyr10 were studied on cloned human TWIK-related K(+) channels (TREKs) and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) channels, which modulate Ca(2+) signaling by controlling membrane potential, in HEK293T-overexpressing cells by using a whole-cell patch clamp technique. Pyr3 potently inhibited TREK-1 (ITREK1), TREK-2 (ITREK2), and TASK2 current (ITASK-2) with half-maximal inhibitory concentrations (IC50) of 0.89±0.27, 1.95±1.44, and 2.42±0.39µM, respectively. BTP2 slightly inhibited ITASK-2 (80.3±2.5% at 100μM). In contrast, pyr6 at 100µM potentiated ITREK1 and ITREK2 by approximately 2.6- and 3.6-fold compared to the control and inhibited ITASK2 (38.7±9.2%). Pyr10 showed a subtype-specific inhibition of ITREK1 but not ITREK2. It also inhibited ITASK2 (70.9±3.1% at 100μM). To the best of our knowledge, this study is the first to describe the differential modulation of TREKs and TASK2 channels by pyrazole derivatives, previously used as inhibitors of TRPC3 and ORAI1. Therefore, studies using these drugs should consider their modulation of other channels such as TREK and TASK-2.

  12. Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

    Institute of Scientific and Technical Information of China (English)

    Jie Wang; Yinghui Xu; Zhigang Lian; Jian Zhang; Tingzhun Zhu; Mengkao Li; Yi Wei; Bin Dong


    Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2+-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2+-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups: adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/l expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2+ influx, inhibit calcium overload, and diminish Ca2+ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.

  13. Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

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    Chen Chien-Ju


    Full Text Available Abstract Background Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3 in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of ASIC3 knockout (ASIC3-/- or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation. Results Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in ASIC3-/- mice induced by complete Freund's adjuvant (CFA or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the ASIC3+/+ controls, ASIC3-/- mice showed normal thermal and mechanical hyperalgesia with acute (4-h intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an ASIC3-dependent Nav1.9 up-regulation and increase of tetrodotoxin (TTX-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in ASIC3-/- or ASIC3+/+ mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in ASIC3-/- mice, as previously described. However, ASIC3-/- mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with ASIC3+/+ mice. Conclusion We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.

  14. Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function (United States)

    Antollini, Silvia S.; Barrantes, Francisco J.


    Free fatty acids (FFA) are essential components of the cell, where they play a key role in lipid and carbohydrate metabolism, and most particularly in cell membranes, where they are central actors in shaping the physicochemical properties of the lipid bilayer and the cellular adaptation to the environment. FFA are continuously being produced and degraded, and a feedback regulatory function has been attributed to their turnover. The massive increase observed under some pathological conditions, especially in brain, has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature and in other cases inhibitory. Here we discuss the correlation between the structure of FFA and their ability to modulate protein function, evaluating the influence of saturation/unsaturation, number of double bonds, and cis vs. trans isomerism. We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, contrasting the still conflicting evidence on direct vs. indirect mechanisms of action. PMID:27965583

  15. Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function. (United States)

    Antollini, Silvia S; Barrantes, Francisco J


    Free fatty acids (FFA) are essential components of the cell, where they play a key role in lipid and carbohydrate metabolism, and most particularly in cell membranes, where they are central actors in shaping the physicochemical properties of the lipid bilayer and the cellular adaptation to the environment. FFA are continuously being produced and degraded, and a feedback regulatory function has been attributed to their turnover. The massive increase observed under some pathological conditions, especially in brain, has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature and in other cases inhibitory. Here we discuss the correlation between the structure of FFA and their ability to modulate protein function, evaluating the influence of saturation/unsaturation, number of double bonds, and cis vs. trans isomerism. We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, contrasting the still conflicting evidence on direct vs. indirect mechanisms of action.

  16. Localization of the nucleic acid channel regulatory subunit, cytosolic malate dehydrogenase. (United States)

    Hanss, Basil; Leal-Pinto, Edgar; Teixeira, Avelino; Tran, Baohuong; Lee, Chun-Hui; Henderson, Scott C; Klotman, Paul E


    NACh is a nucleic acid-conducting channel found in apical membrane of rat kidney proximal tubules. It is a heteromultimeric complex consisting of at least two proteins: a 45-kDa pore-forming subunit and a 36-kDa regulatory subunit. The regulatory subunit confers ion selectivity and influences gating kinetics. The regulatory subunit has been identified as cytosolic malate dehydrogenase (cMDH). cMDH is described in the literature as a soluble protein that is not associated with plasma membrane. Yet a role for cMDH as the regulatory subunit of NACh requires that it be present at the plasma membrane. To resolve this conflict, studies were initiated to determine whether cMDH could be found at the plasma membrane. Before performing localization studies, a suitable model system that expressed NACh was identified. A channel was identified in LLC-PK(1) cells, a line derived from pig proximal tubule, that is selective for nucleic acid and has a conductance of approximately 10 pS. It exhibits dose-dependent blockade by heparan sulfate or L-malate. These characteristics are similar to what has been reported for NACh from rat kidney and indicate that NACh is present in LLC-PK(1) cells. LLC-PK(1) cells were therefore used as a model system for immunolocalization of cMDH. Both immunofluorescence and immunoelectron microscopy demonstrated cMDH at the plasma membrane of LLC-PK(1) cells. This finding supports prior functional data that describe a role for cMDH as the regulatory subunit of NACh.

  17. Cannabinoids inhibit acid-sensing ion channel currents in rat dorsal root ganglion neurons.

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    Yu-Qiang Liu

    Full Text Available Local acidosis has been found in various pain-generating conditions such as inflammation and tissue injury. Cannabinoids exert a powerful inhibitory control over pain initiation via peripheral cognate receptors. However, the peripheral molecular targets responsible for the antinociceptive effects of cannabinoids are still poorly understood. Here, we have found that WIN55,212-2, a cannabinoid receptor agonist, inhibits the activity of native acid-sensing ion channels (ASICs in rat dorsal root ganglion (DRG neurons. WIN55,212-2 dose-dependently inhibited proton-gated currents mediated by ASICs. WIN55,212-2 shifted the proton concentration-response curve downwards, with an decrease of 48.6±3.7% in the maximum current response but with no significant change in the EC(50 value. The inhibition of proton-gated current induced by WIN55,212-2 was almost completely blocked by the selective CB1 receptor antagonist AM 281, but not by the CB2 receptor antagonist AM630. Pretreatment of forskolin, an AC activator, and the addition of cAMP also reversed the inhibition of WIN55,212-2. Moreover, WIN55,212-2 altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. Finally, WIN55,212-2 attenuated nociceptive responses to injection of acetic acid in rats. These results suggest that WIN55,212-2 inhibits the activity of ASICs via CB1 receptor and cAMP dependent pathway in rat primary sensory neurons. Thus, cannabinoids can exert their analgesic action by interaction with ASICs in the primary afferent neurons, which was novel analgesic mechanism of cannabinoids.

  18. Phenolic acids isolated from the fungus Schizophyllum commune exert analgesic activity by inhibiting voltage-gated sodium channels. (United States)

    Yao, Hui-Min; Wang, Gan; Liu, Ya-Ping; Rong, Ming-Qiang; Shen, Chuan-Bin; Yan, Xiu-Wen; Luo, Xiao-Dong; Lai, Ren


    The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3-hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant (TTX-r) and tetrodotoxin-sensitive (TTX-s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia.

  19. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons

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    Fierro Leonardo


    Full Text Available Abstract Background ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1 ASIC3 might trigger ischemic pain in heart and muscle; 2 it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. Results Less than half (40% of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small ( Conclusion Our data indicates that: 1 ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2 co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen.

  20. K-channels inhibited by hydrogen peroxide mediate abscisic acid signaling in Vicia guard cells

    Institute of Scientific and Technical Information of China (English)


    A number of studies show that environmental stress conditions increase abscisic acid (ABA) and hydrogen peroxide (H2O2) levels in plant cells. Despite this central role of ABA in altering stomatal aperture by regulating guard cell ion transport, little is known concerning the relationship between ABA and H2O2 in signal transduction leading to stomatal movement. Epidermal strip bioassay illustrated that ABA-inhibited stomatal opening and ABA-induced stomatal closure were abolished partly by externally added catalase (CAT) or diphenylene iodonium (DPI), which are a H2O2 scavenger and a NADPH oxidase inhibitor respectively. In contrast, internally added CAT or DPI nearly completely or partly reversed ABA-induced closure in half-stoma. Consistent with these results, whole-cell patch-clamp analysis showed that intracellular application of CAT or DPI partly abolished ABA-inhibited inward K+ current across the plasma membrane of guard cells. H2O2 mimicked ABA to inhibit inward K+ current, an effect which was reversed by the addition of ascorbic acid (Vc) in patch clamping micropipettes. These results suggested that H2O2 mediated ABA-induced stomatal movement by targeting inward K+ channels at plasma membrane.

  1. Prolactin potentiates the activity of acid-sensing ion channels in female rat primary sensory neurons. (United States)

    Liu, Ting-Ting; Qu, Zu-Wei; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Hu, Wang-Ping


    Prolactin (PRL) is a polypeptide hormone produced and released from the pituitary and extrapituitary tissues. It regulates activity of nociceptors and causes hyperalgesia in pain conditions, but little is known the molecular mechanism. We report here that PRL can exert a potentiating effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRL dose-dependently increased the amplitude of ASIC currents with an EC50 of (5.89 ± 0.28) × 10(-8) M. PRL potentiation of ASIC currents was also pH dependent. Second, PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRL receptor antagonist, and removed by intracellular dialysis of either protein kinase C inhibitor GF109203X, protein interacting with C-kinase 1(PICK1) inhibitor FSC-231, or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Four, PRL exacerbated nociceptive responses to injection of acetic acid in female rats. Finally, PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behavior in intact female rats than OVX female and male rats and thus modulation of PRL may be gender-dependent. These results suggest that PRL up-regulates the activity of ASICs and enhances ASIC mediated nociceptive responses in female rats, which reveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia.

  2. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate. (United States)

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias


    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  3. 20-Hydroxyeicosatetraenoic acid (20-HETE Modulates Canonical Transient Receptor Potential-6 (TRPC6 Channels in Podocytes

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    Hila Roshanravan


    Full Text Available The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF. This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La3+, and which are attenuated after siRNA knockdown of TRPC6 subunits. Similar currents are evoked by a membrane-permeable analog of diacylgycerol (OAG, but OAG does not occlude responses to maximally-activating concentrations of 20-HETE (20 μM. Exposure to 20-HETE also increased steady-state surface abundance of TRPC6 subunits in podocytes as assessed by cell-surface biotinylation assays, and increased cytosolic concentrations of reactive oxygen species (ROS. TRPC6 activation by 20-HETE was eliminated in cells pretreated with TEMPOL, a membrane-permeable superoxide dismutase mimic. Activation of TRPC6 by 20-HETE was also blocked when whole-cell recording pipettes contained GDP-βS, indicating a role for either small or heterotrimeric G proteins in the transduction cascade. Responses to 20-HETE were eliminated by siRNA knockdown of podocin, a protein that organizes NADPH oxidase complexes with TRPC6 subunits in this cell type. In summary, modulation of ionic channels in podocytes may contribute to glomerular actions of 20-HETE.

  4. Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures. (United States)

    Wu, Hao; Wang, Chao; Liu, Bei; Li, Huanfa; Zhang, Yu; Dong, Shan; Gao, Guodong; Zhang, Hua


    The piriform cortex (PC) is highly susceptible to chemical and electrical seizure induction. Epileptiform activity is associated with an acid shift in extracellular pH, suggesting that acid-sensing ion channels (ASICs) expressed by PC neurons may contribute to this enhanced epileptogenic potential. In epileptic rats and surgical samples from patients with medial temporal lobe epilepsy (TLE), PC layer II ASIC1a-immunopositive neurons appeared swollen with dendritic elongation, and there was loss of ASIC1a-positive neurons in layer III, consistent with enhanced vulnerability to TLE-induced plasticity and cell death. In rats, pilocarpine-induced seizures led to transient downregulation of ASIC1a and concomitant upregulation of ASIC2a in the first few days post-seizure. These changes in expression may be due to seizure-induced oxidative stress as a similar reciprocal change in ASIC1a, and ASIC2a expression was observed in PC12 cells following H2O2 application. The proportion of ASIC1a/ASIC2a heteromers was reduced in the acute phase following status epilepticus (SE) but increased during the latent phase when rats developed spontaneous seizures. Knockdown of ASIC2a by RNAi reduced dendritic length and spine density in primary neurons, suggesting that seizure-induced upregulation of ASIC2a contributes to dendritic lengthening in PC layer II in rats. Administration of the ASIC inhibitor amiloride before pilocarpine reduced the proportion of rats reaching Racine level IV seizures, protected layer II and III neurons, and prolonged survival in the acute phase following SE. Our findings suggest that ASICs may enhance susceptibility to epileptogenesis in the PC. Inhibition of ASICs, particularly ASIC2a, may suppress seizures originating in the PC.

  5. Acid sensing ion channel 1 in lateral hypothalamus contributes to breathing control.

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    Nana Song

    Full Text Available Acid-sensing ion channels (ASICs are present in neurons and may contribute to chemoreception. Among six subunits of ASICs, ASIC1 is mainly expressed in the central nervous system. Recently, multiple sites in the brain including the lateral hypothalamus (LH have been found to be sensitive to extracellular acidification. Since LH contains orexin neurons and innervates the medulla respiratory center, we hypothesize that ASIC1 is expressed on the orexin neuron and contributes to acid-induced increase in respiratory drive. To test this hypothesis, we used double immunofluorescence to determine whether ASIC1 is expressed on orexin neurons in the LH, and assessed integrated phrenic nerve discharge (iPND in intact rats in response to acidification of the LH. We found that ASIC1 was co-localized with orexinA in the LH. Microinjection of acidified artificial cerebrospinal fluid increased the amplitude of iPND by 70% (pH 7.4 v.s. pH 6.5:1.05±0.12 v.s. 1.70±0.10, n = 6, P<0.001 and increased the respiratory drive (peak amplitude of iPND/inspiratory time, PA/Ti by 40% (1.10±0.23 v.s. 1.50±0.38, P<0.05. This stimulatory effect was abolished by blocking ASIC1 with a nonselective inhibitor (amiloride 10 mM, a selective inhibitor (PcTX1, 10 nM or by damaging orexin neurons in the LH. Current results support our hypothesis that the orexin neuron in the LH can exert an excitation on respiration via ASIC1 during local acidosis. Since central acidification is involved in breathing dysfunction in a variety of pulmonary diseases, understanding its underlying mechanism may improve patient management.

  6. Dynamics of Ca2+-dependent Cl- channel modulation by niflumic acid in rabbit coronary arterial myocytes. (United States)

    Ledoux, Jonathan; Greenwood, Iain A; Leblanc, Normand


    Calcium-activated chloride channels (Cl(Ca)) are crucial regulators of vascular tone by promoting a depolarizing influence on the resting membrane potential of vascular smooth muscle cells. Niflumic acid (NFA), a potent blocker of Cl(Ca) in vascular myocytes, was shown recently to cause inhibition and paradoxical stimulation of sustained calcium-activated chloride currents [I(Cl(Ca))] in rabbit pulmonary artery myocytes. The aims of the present study were to investigate whether NFA produced a similar dual effect in coronary artery smooth muscle cells and to determine the concentration-dependence and dynamics of such a phenomenon. Sustained I(Cl(Ca)) evoked by intracellular Ca(2+) clamped at 500 nM were dose-dependently inhibited by NFA (IC(50) = 159 microM) and transiently augmented in a concentration-independent manner (10 microM to 1 mM) approximately 2-fold after NFA removal. However, the time to peak and duration of NFA-enhanced I(Cl(Ca)) increased in a concentration-dependent fashion. Moreover, the rate of recovery was reduced by membrane depolarization, suggesting the involvement of a voltage-dependent step in the interaction of NFA, leading to stimulation of I(Cl(Ca)). Computer simulations derived from a kinetic model involving low (K(i) = 1.25 mM) and high (K(i) < 30 microM) affinity sites could reproduce the properties of the NFA-modulated I(Cl(Ca)) fairly well.

  7. Direct ab initio molecular dynamics study of the two photodissociation channels of formic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Yuzuru; Yokoyama, Keiichi; Teranishi, Yoshiaki


    A total of {approx}1200 trajectories have been integrated for the two photodissociation channels of formic acid, HCOOH {yields} H{sub 2}O + CO (1) and HCOOH {yields} CO{sub 2} + H{sub 2} (2), which occur with 248 and 193 nm photons, using the direct ab initio molecular dynamics method at the RMP2(full)/cc-pVDZ level of theory. It was found that the percentage of the energy distributed to a relative translational mode in reaction is much larger than that in reaction . This is mainly due to the difference in the geometry of transition state (TS); the H{sub 2}O geometry in the TS of reaction was predicted to significantly deviate from the equilibrium one, whereas the CO{sub 2} and H{sub 2} geometries in the TS of reaction were found to be more similar to their equilibrium ones. It was also found that the product diatomic molecules, CO and H{sub 2}, are both vibrationally and rotationally excited. The calculated relative population of the vibrationally excited CO for the 248 nm photodissociation was consistent with experiment.

  8. Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery. (United States)

    Guo, Lei; Qiu, Zhaoping; Zhang, Lei; Chen, Shuo; Zhu, Daling


    We have previously reported that hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Hypoxia suppresses Kv2.1 channel expression. Although the Kv channel inhibition by hypoxia is likely to be mediated through 15-HETE, direct evidence is still lacking. To explore whether 15-LOX/15-HETE pathway contributes to the hypoxia-induced down-regulation of Kv2.1 channel, we performed studies using 15-LOX blockers, semi-quantitative PCR and western blot analysis. We found that Kv2.1 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary artery (PA) after blockade of endogenous 15-HETE under hypoxic condition. 15-HETE further decreased Kv2.1 channel expression in comparison with 12-HETE and 5-HETE in cultured PASMCs and PA under normoxic conditions. These data indicate that hypoxia suppresses Kv2.1 channel expression through endogenous 15-HETE in PA.

  9. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    Institute of Scientific and Technical Information of China (English)

    Wang-sheng Duanmu; Liu Cao; Jing-yu Chen; Hong-fei Ge; Rong Hu; Hua Feng


    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treat-ment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These ifndings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippo-campus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury.

  10. Peracetic acid is effective for controlling fungus on channel catfish eggs. (United States)

    Straus, D L; Meinelt, T; Farmer, B D; Mitchell, A J


    Peracetic acid (PAA) is a relatively new compound suggested for use to treat pathogens in aquaculture. It is approved for use in Europe, but not in the United States. This study determined the effectiveness of PAA for fungus control on channel catfish, Ictalurus punctatus (Rafinesque), eggs. The study consisted of five PAA concentrations (2.5, 5, 10, 15 and 20mgL(-1) ) and an untreated control in a flow-through system. A single spawn was used for each replication (N =4). Eggs were treated twice daily until the embryos developed eyes. When hatching was complete for all viable eggs, fry were counted to determine the percent survival in each treatment. Fungal growth was severe in the untreated controls resulting in 11% survival. Treatments of 2.5, 5 and 10mgL(-1) PAA were significantly different from the controls (P<0.05). The highest percent survival of hatched fry was with 5mgL(-1) PAA administered twice daily; the 2.5mgL(-1) PAA treatment had slightly less survival, but gives a higher margin of safety in case of treatment error. Very little fungus was present in treatments receiving 2.5mgL(-1) PAA or higher, and concentrations of 15 and 20mgL(-1) PAA were toxic to the eggs. The mean survivals in the 0, 2.5, 5, 10, 15 and 20mgL(-1) PAA treatments were 11%, 60%, 63%, 62%, 32% and 0%, respectively. Therefore, PAA may be a compound that merits further investigations regarding its use in U.S. aquaculture.

  11. Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel

    DEFF Research Database (Denmark)

    Liin, Sara I.; Silverå Ejneby, Malin; Barro-Soria, Rene;


    charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act...

  12. Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells.

    Directory of Open Access Journals (Sweden)

    Xi Chu

    Full Text Available Tannic acid presents in varying concentrations in plant foods, and in relatively high concentrations in green teas and red wines. Human ether-à-go-go-related gene (hERG channels expressed in multiple tissues (e.g. heart, neurons, smooth muscle and cancer cells, and play important roles in modulating cardiac action potential repolarization and tumor cell biology. The present study investigated the effects of tannic acid, green teas and red wines on hERG currents. The effects of tannic acid, teas and red wines on hERG currents stably transfected in HEK293 cells were studied with a perforated patch clamp technique. In this study, we demonstrated that tannic acid inhibited hERG currents with an IC50 of 3.4 μM and ~100% inhibition at higher concentrations, and significantly shifted the voltage dependent activation to more positive potentials (Δ23.2 mV. Remarkably, a 100-fold dilution of multiple types of tea (green tea, oolong tea and black tea or red wine inhibited hERG currents by ~90%, and significantly shifted the voltage dependent activation to more positive potentials (Δ30.8 mV and Δ26.0 mV, respectively. Green tea Lung Ching and red wine inhibited hERG currents, with IC50 of 0.04% and 0.19%, respectively. The effects of tannic acid, teas and red wine on hERG currents were irreversible. These results suggest tannic acid is a novel hERG channel blocker and consequently provide a new mechanistic evidence for understanding the effects of tannic acid. They also revealed the potential pharmacological basis of tea- and red wine-induced biology activities.

  13. Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells. (United States)

    Chu, Xi; Guo, Yusong; Xu, Bingyuan; Li, Wenya; Lin, Yue; Sun, Xiaorun; Ding, Chunhua; Zhang, Xuan


    Tannic acid presents in varying concentrations in plant foods, and in relatively high concentrations in green teas and red wines. Human ether-à-go-go-related gene (hERG) channels expressed in multiple tissues (e.g. heart, neurons, smooth muscle and cancer cells), and play important roles in modulating cardiac action potential repolarization and tumor cell biology. The present study investigated the effects of tannic acid, green teas and red wines on hERG currents. The effects of tannic acid, teas and red wines on hERG currents stably transfected in HEK293 cells were studied with a perforated patch clamp technique. In this study, we demonstrated that tannic acid inhibited hERG currents with an IC50 of 3.4 μM and ~100% inhibition at higher concentrations, and significantly shifted the voltage dependent activation to more positive potentials (Δ23.2 mV). Remarkably, a 100-fold dilution of multiple types of tea (green tea, oolong tea and black tea) or red wine inhibited hERG currents by ~90%, and significantly shifted the voltage dependent activation to more positive potentials (Δ30.8 mV and Δ26.0 mV, respectively). Green tea Lung Ching and red wine inhibited hERG currents, with IC50 of 0.04% and 0.19%, respectively. The effects of tannic acid, teas and red wine on hERG currents were irreversible. These results suggest tannic acid is a novel hERG channel blocker and consequently provide a new mechanistic evidence for understanding the effects of tannic acid. They also revealed the potential pharmacological basis of tea- and red wine-induced biology activities.

  14. Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels. (United States)

    Guo, Kai; Wang, Xianming; Gao, Guofeng; Huang, Congxin; Elmslie, Keith S; Peterson, Blaise Z


    We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149-1159, 2010). The short 17 amino acid extracellular NH(2)-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate Ca(V)1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with Ca(V)1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on Ca(V)1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca(2+) dynamics in the heart.

  15. Stochastic pumping of ions based on colored noise in bacterial channels under acidic stress (United States)

    López, M. Lidón; Queralt-Martín, María; Alcaraz, Antonio


    Fluctuation-driven ion transport can be obtained in bacterial channels with the aid of different types of colored noise including the biologically relevant Lorentzian one. Using the electrochemical rectification of the channel current as a ratchet mechanism we observe transport of ions up to their concentration gradient under conditions similar to that met in vivo, namely moderate pH gradients and asymmetrically charged lipid membranes. We find that depending on the direction of the concentration gradient the channel can pump either cations or anions from the diluted side to the concentrated one. We discuss the possible relevance of this phenomenon for the pH homeostasis of bacterial cells.Fluctuation-driven ion transport can be obtained in bacterial channels with the aid of different types of colored noise including the biologically relevant Lorentzian one. Using the electrochemical rectification of the channel current as a ratchet mechanism we observe transport of ions up to their concentration gradient under conditions similar to that met in vivo, namely moderate pH gradients and asymmetrically charged lipid membranes. We find that depending on the direction of the concentration gradient the channel can pump either cations or anions from the diluted side to the concentrated one. We discuss the possible relevance of this phenomenon for the pH homeostasis of bacterial cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02638a

  16. The Cl− channel blocker niflumic acid releases Ca2+ from an intracellular store in rat pulmonary artery smooth muscle cells (United States)

    Cruickshank, Stuart F; Baxter, Lynne M; Drummond, Robert M


    The effect of the Cl− channel blockers niflumic acid (NFA), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), and anthracene-9-carboxylic acid (A-9-C), on Ca2+ signalling in rat pulmonary artery smooth muscle cells was examined. Intracellular Ca2+ concentration ([Ca2+]i) was monitored with either fura-2 or fluo-4, and caffeine was used to activate the ryanodine receptor, thereby releasing Ca2+ from the sarcoplasmic reticulum (SR). NFA and NPPB significantly increased basal [Ca2+]i and attenuated the caffeine-induced increase in [Ca2+]i. These Cl− channel blockers also increased the half-time (t1/2) to peak for the caffeine-induced [Ca2+]i transient, and slowed the removal of Ca2+ from the cytosol following application of caffeine. Since DIDS and A-9-C were found to adversely affect fura-2 fluorescence, fluo-4 was used to monitor intracellular Ca2+ in studies involving these Cl− channel blockers. Both DIDS and A-9-C increased basal fluo-4 fluorescence, indicating an increase in intracellular Ca2+, and while DIDS had no significant effect on the t1/2 to peak for the caffeine-induced Ca2+ transient, it was significantly increased by A-9-C. In the absence of extracellular Ca2+, NFA significantly increased basal [Ca2+]i, suggesting that the release of Ca2+ from an intracellular store was responsible for the observed effect. Depleting the SR with the combination of caffeine and cyclopiazonic acid prevented the increase in basal [Ca2+]i induced by NFA. Additionally, incubating the cells with ryanodine also prevented the increase in basal [Ca2+]i induced by NFA. These data show that Cl− channel blockers have marked effects on Ca2+ signalling in pulmonary artery smooth muscle cells. Furthermore, examination of the NFA-induced increase in [Ca2+]i indicates that it is likely due to Ca2+ release from an intracellular store, most probably the SR. PMID:14623766

  17. The Cl(-) channel blocker niflumic acid releases Ca(2+) from an intracellular store in rat pulmonary artery smooth muscle cells. (United States)

    Cruickshank, Stuart F; Baxter, Lynne M; Drummond, Robert M


    The effect of the Cl- channel blockers niflumic acid (NFA), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and anthracene-9-carboxylic acid (A-9-C), on Ca2+ signalling in rat pulmonary artery smooth muscle cells was examined. Intracellular Ca2+ concentration ([Ca2+]i) was monitored with either fura-2 or fluo-4, and caffeine was used to activate the ryanodine receptor, thereby releasing Ca2+ from the sarcoplasmic reticulum (SR). NFA and NPPB significantly increased basal [Ca2+]i and attenuated the caffeine-induced increase in [Ca2+]i. These Cl- channel blockers also increased the half-time (t1/2) to peak for the caffeine-induced [Ca2+]i transient, and slowed the removal of Ca2+ from the cytosol following application of caffeine. Since DIDS and A-9-C were found to adversely affect fura-2 fluorescence, fluo-4 was used to monitor intracellular Ca2+ in studies involving these Cl- channel blockers. Both DIDS and A-9-C increased basal fluo-4 fluorescence, indicating an increase in intracellular Ca2+, and while DIDS had no significant effect on the t1/2 to peak for the caffeine-induced Ca2+ transient, it was significantly increased by A-9-C. In the absence of extracellular Ca2+, NFA significantly increased basal [Ca2+]i, suggesting that the release of Ca2+ from an intracellular store was responsible for the observed effect. Depleting the SR with the combination of caffeine and cyclopiazonic acid prevented the increase in basal [Ca2+]i induced by NFA. Additionally, incubating the cells with ryanodine also prevented the increase in basal [Ca2+]i induced by NFA. These data show that Cl- channel blockers have marked effects on Ca2+ signalling in pulmonary artery smooth muscle cells. Furthermore, examination of the NFA-induced increase in [Ca2+]i indicates that it is likely due to Ca2+ release from an intracellular store, most probably the SR.

  18. Aspartic Acid Residue D3 Critically Determines Cx50 Gap Junction Channel Transjunctional Voltage-Dependent Gating and Unitary Conductance (United States)

    Xin, Li; Nakagawa, So; Tsukihara, Tomitake; Bai, Donglin


    Previous studies have suggested that the aspartic acid residue (D) at the third position is critical in determining the voltage polarity of fast Vj-gating of Cx50 channels. To test whether another negatively charged residue (a glutamic acid residue, E) could fulfill the role of the D3 residue, we generated the mutant Cx50D3E. Vj-dependent gating properties of this mutant channel were characterized by double-patch-clamp recordings in N2A cells. Macroscopically, the D3E substitution reduced the residual conductance (Gmin) to near zero and outwardly shifted the half-inactivation voltage (V0), which is a result of both a reduced aggregate gating charge (z) and a reduced free-energy difference between the open and closed states. Single Cx50D3E gap junction channels showed reduced unitary conductance (γj) of the main open state, reduced open dwell time at ±40 mV, and absence of a long-lived substate. In contrast, a G8E substitution tested to compare the effects of the E residue at the third and eighth positions did not modify the Vj-dependent gating profile or γj. In summary, this study is the first that we know of to suggest that the D3 residue plays an essential role, in addition to serving as a negative-charge provider, as a critical determinant of the Vj-dependent gating sensitivity, open-closed stability, and unitary conductance of Cx50 gap junction channels. PMID:22404924

  19. Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Elstone, Fisal D; Niciforovic, Ana P


    Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain...... largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1.......4). The results show that the highly conserved aromatic side chain constituting the S2 HC makes distinct functional contributions in each of the four NaV domains. No obvious cation-pi interaction exists with nearby S4 charges in any domain, and natural and unnatural mutations at these aromatic sites produce...

  20. Alternative splicing modulates inactivation of type 1 voltage-gated sodium channels by toggling an amino acid in the first S3-S4 linker. (United States)

    Fletcher, Emily V; Kullmann, Dimitri M; Schorge, Stephanie


    Voltage-gated sodium channels underlie the upstroke of action potentials and are fundamental to neuronal excitability. Small changes in the behavior of these channels are sufficient to change neuronal firing and trigger seizures. These channels are subject to highly conserved alternative splicing, affecting the short linker between the third transmembrane segment (S3) and the voltage sensor (S4) in their first domain. The biophysical consequences of this alternative splicing are incompletely understood. Here we focus on type 1 sodium channels (Nav1.1) that are implicated in human epilepsy. We show that the functional consequences of alternative splicing are highly sensitive to recording conditions, including the identity of the major intracellular anion and the recording temperature. In particular, the inactivation kinetics of channels containing the alternate exon 5N are more sensitive to intracellular fluoride ions and to changing temperature than channels containing exon 5A. Moreover, Nav1.1 channels containing exon 5N recover from inactivation more rapidly at physiological temperatures. Three amino acids differ between exons 5A and 5N. However, the changes in sensitivity and stability of inactivation were reproduced by a single conserved change from aspartate to asparagine in channels containing exon 5A, which was sufficient to make them behave like channels containing the complete exon 5N sequence. These data suggest that splicing at this site can modify the inactivation of sodium channels and reveal a possible interaction between splicing and anti-epileptic drugs that stabilize sodium channel inactivation.

  1. Bile acids stimulate chloride secretion through CFTR and calcium-activated Cl- channels in Calu-3 airway epithelial cells. (United States)

    Hendrick, Siobhán M; Mroz, Magdalena S; Greene, Catherine M; Keely, Stephen J; Harvey, Brian J


    Bile acids resulting from the aspiration of gastroesophageal refluxate are often present in the lower airways of people with cystic fibrosis and other respiratory distress diseases. Surprisingly, there is little or no information on the modulation of airway epithelial ion transport by bile acids. The secretory effect of a variety of conjugated and unconjugated secondary bile acids was investigated in Calu-3 airway epithelial cells grown under an air-liquid interface and mounted in Ussing chambers. Electrogenic transepithelial ion transport was measured as short-circuit current (Isc). The taurine-conjugated secondary bile acid, taurodeoxycholic acid (TDCA), was found to be the most potent modulator of basal ion transport. Acute treatment (5 min) of Calu-3 cells with TDCA (25 μM) on the basolateral side caused a stimulation of Isc, and removal of extracellular Cl(-) abolished this response. TDCA produced an increase in the cystic fibrosis transmembrane conductance regulator (CFTR)-dependent current that was abolished by pretreatment with the CFTR inhibitor CFTRinh172. TDCA treatment also increased Cl(-) secretion through calcium-activated chloride (CaCC) channels and increased the Na(+)/K(+) pump current. Acute treatment with TDCA resulted in a rapid cellular influx of Ca(2+) and increased cAMP levels in Calu-3 cells. Bile acid receptor-selective activation with INT-777 revealed TGR5 localized at the basolateral membrane as the receptor involved in TDCA-induced Cl(-) secretion. In summary, we demonstrate for the first time that low concentrations of bile acids can modulate Cl(-) secretion in airway epithelial cells, and this effect is dependent on both the duration and sidedness of exposure to the bile acid.

  2. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1. (United States)

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina


    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  3. Novel Metal-organic Framework Compound Pb(C5H4NCOO)2 Showing One-dimensional Channel Defined as Four Leads and Four Nicotinic Acids

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-yu; ZHOU Rui-sha; SONG Jiang-feng; XU Ji-qing


    the zigzag chain by edge-sharing mode along(001) direction. Pb atom is connected by six nicotinic acid molecules, leading neutral 3D metal-organic framework with a channel defined by four Pb atoms and four nicotinic acid molecules.

  4. Sulphonic acid derivatives as probes of pore properties of volume-regulated anion channels in endothelial cells. (United States)

    Droogmans, G; Maertens, C; Prenen, J; Nilius, B


    1. We have used the whole-cell patch-clamp technique to study the effects of 4-sulphonic-calixarenes and some other poly-sulphonic acid agents, such as suramin and basilen blue, on volume-regulated anion channel (VRAC) currents in cultured endothelial cells (CPAE cells). 2. The 4-sulphonic-calixarenes induced a fast inhibition at positive potentials but were ineffective at negative potentials. At small positive potentials, 4-sulphonic-calix[4]arene was a more effective inhibitor than 4-sulphonic-calix[6]arene and -calix[8]arene, which became more effective at more positive potentials. 3. Also suramin and basilen blue induced a voltage dependent current inhibition, reaching a maximum around +40 mV and declining at more positive potentials. 4. The voltage dependence of inhibition was modelled by assuming that these negatively charged molecules bind to a site inside VRAC that senses a fraction delta of the applied electrical field, ranging beween 0.16 to 0.32. 4-Sulphonic-calix[4]arene, suramin and basilen blue bind and occlude VRAC at moderate potentials, but permeate the channel at more positive potentials. 4-Sulphonic-calix[6]arene and -calix[8]arene however do not permeate the channel. From the structural information of the calixarenes, we estimate a lower and upper limit of 11*12 and 17*12 A2 respectively for the cross-sectional area of the pore.

  5. The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention

    Institute of Scientific and Technical Information of China (English)

    Tian-dong LENG; Zhi-gang XIONG


    In the nervous system,a decrease in extracellular pH is a common feature of various physiological and pathological processes,including synaptic transmission,cerebral ischemia,epilepsy,brain trauma,and tissue inflammation.Acid-sensing ion channels (ASICs) are proton-gated cation channels that are distributed throughout the central and peripheral nervous systems.Following the recent identification of ASICs as critical acid-sensing extracellular proton receptors,growing evidence has suggested that the activation of ASICs plays important roles in physiological processes such as nociception,mechanosensation,synaptic plasticity,learning and memory.However,the over-activation of ASICs is also linked to adverse outcomes for certain pathological processes,such as brain ischemia and multiple sclerosis.Based on the well-demonstrated role of ASlC1a activation in acidosis-mediated brain injury,small molecule inhibitors of ASIC1a may represent novel therapeutic agents for the treatment of neurological disorders,such as stroke.

  6. Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Terry Yin

    Full Text Available Traumatic brain injury (TBI is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 (- after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs, we also studied ASIC1a(-/- mice and found reduced neurodegeneration after FPI. Both HCO3 (- administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

  7. In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Taufiq, E-mail:; Smith, Ewan St. John


    Highlights: • We have made a reasonable model of rat ASIC3 using published structure of chicken ASIC1. • We have docked sea anemone toxin APETx2 on the model. • We have identified two putative sites for toxin binding. • We have argued for plausibility one site over the other. • We have identified the residues that are likely to be critical for APETx2–ASIC3 interaction. - Abstract: Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed throughout the nervous system and have been implicated in mediating sensory perception of noxious stimuli. Amongst the six ASIC isoforms, ASIC1a, 1b, 2a and 3 form proton-gated homomers, which differ in their activation and inactivation kinetics, expression profiles and pharmacological modulation; protons do not gate ASIC2b and ASIC4. As with many other ion channels, structure-function studies of ASICs have been greatly aided by the discovery of some toxins that act in isoform-specific ways. ASIC3 is predominantly expressed by sensory neurons of the peripheral nervous system where it acts to detect acid as a noxious stimulus and thus plays an important role in nociception. ASIC3 is the only ASIC subunit that is inhibited by the sea anemone (Anthopleura elegantissima)-derived toxin APETx2. However, the molecular mechanism by which APETx2 interacts with ASIC3 remains largely unknown. In this study, we made a homology model of ASIC3 and used extensive protein–protein docking to predict for the first time, the probable sites of APETx2 interaction on ASIC3. Additionally, using computational alanine scanning, we also suggest the ‘hot-spots’ that are likely to be critical for ASIC3–APETx2 interaction.

  8. Niflumic acid affects store-operated Ca(2+)-permeable (SOC) and Ca (2+)-dependent K (+) and Cl (-) ion channels and induces apoptosis in K562 cells. (United States)

    Kucherenko, Yuliya V; Lang, Florian


    Non-steroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a variety of cancer cells. However, the precise mechanisms by which NSAIDs facilitate apoptosis in tumor cells are not clear. In the present study, we show that niflumic acid (NA), a member of the fenamates group of NSAIDs and Cl(-) and Ca(2+)-activated Cl(-) (CAC) channels blocker, induced apoptosis (by ~8 %, 24 h treatment) and potentiated (by 8-10 %) apoptotic effect of endoplasmic reticulum Ca(2+) mobilizer thapsigargin (Tg) in human erythroleukemic K562 cell line. The whole-cell patch clamp and Fluo-3 flow cytometric experiments confirmed an inhibitory effect of NA (100 and 300 µM) on store-operated (SOC) channels. We also found that NA-blocked CAC channels were activated by acute application of Tg (2 µM) in K562 cells. NA blockage of CAC channels was accompanied by activation of Ca(2+)-activated K(+) (SK4) channels. The observed effects of NA were not connected with COX-2 inhibition since 100-nM NA (IC50 for COX-2 inhibition) did not induce either apoptosis or affect the channels activity. We conclude that inhibition of SOC channels plays a major role in NA-induced apoptosis. Increased apoptotic levels in Tg-treated K562 cells in the presence of NA may be due to the blockage of CAC and stimulation of SK4 channels in addition to SOC channels inhibition.

  9. Mouse sperm patch-clamp recordings reveal single Cl- channels sensitive to niflumic acid, a blocker of the sperm acrosome reaction. (United States)

    Espinosa, F; de la Vega-Beltrán, J L; López-González, I; Delgado, R; Labarca, P; Darszon, A


    Ion channels lie at the heart of gamete signaling. Understanding their regulation will improve our knowledge of sperm physiology, and may lead to novel contraceptive strategies. Sperm are tiny (approximately 3 microm diameter) and, until now, direct evidence of ion channel activity in these cells was lacking. Using patch-clamp recording we document here, for the first time, the presence of cationic and anionic channels in mouse sperm. Anion selective channels were blocked by niflumic acid (NA) (IC50 = 11 microM). The blocker was effective also in inhibiting the acrosome reaction induced by the zona pellucida, GABA or progesterone. These observations suggest that Cl- channels participate in the sperm acrosome reaction in mammals.

  10. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK Channel Antagonist Mycotoxin Penitrem A

    Directory of Open Access Journals (Sweden)

    Amira A. Goda


    Full Text Available Penitrem A (PA is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs, inducing neuroprotective effects. Docosahexaenoic acid (DHA is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU, aspartate (ASP, and gamma amino butyric acid (GABA, with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA, serotonin (5-HT, and norepinephrine (NE levels were abnormal, Nitric Oxide (NO and Malondialdehyde (MDA levels were significantly increased, and total antioxidant capacity (TAC level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST

  11. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A (United States)

    Goda, Amira A.; Naguib, Khayria M.; Mohamed, Magdy M.; Amra, Hassan A.; Nada, Somaia A.; Abdel-Ghaffar, Abdel-Rahman B.; Gissendanner, Chris R.; El Sayed, Khalid A.


    Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST

  12. Acid-sensing ion channels expression, identity and role in the excitability of the cochlear afferent neurons

    Directory of Open Access Journals (Sweden)

    Antonia eGonzález-Garrido


    Full Text Available Acid-sensing ion channels (ASICs are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4 that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs. These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations and N,N,N’,N’–tetrakis-(2-piridilmetil-etilendiamina (TPEN increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2 and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs.

  13. Acid-Sensing Ion Channels Expression, Identity and Role in the Excitability of the Cochlear Afferent Neurons (United States)

    González-Garrido, Antonia; Vega, Rosario; Mercado, Francisco; López, Iván A.; Soto, Enrique


    Acid-sensing ion channels (ASICs) are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4) that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs). These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations) and N,N,N’,N’–tetrakis-(2-piridilmetil)-ethylenediamine increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2, and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b, and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs. PMID:26733809

  14. Corynebacterium jeikeium jk0268 constitutes for the 40 amino acid long PorACj, which forms a homooligomeric and anion-selective cell wall channel.

    Directory of Open Access Journals (Sweden)

    Narges Abdali

    Full Text Available Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.

  15. Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel. (United States)

    Lishko, Polina V; Botchkina, Inna L; Fedorenko, Andriy; Kirichok, Yuriy


    Human spermatozoa are quiescent in the male reproductive system and must undergo activation once introduced into the female reproductive tract. This process is known to require alkalinization of sperm cytoplasm, but the mechanism responsible for transmembrane proton extrusion has remained unknown because of the inability to measure membrane conductance in human sperm. Here, by successfully patch clamping human spermatozoa, we show that proton channel Hv1 is their dominant proton conductance. Hv1 is confined to the principal piece of the sperm flagellum, where it is expressed at unusually high density. Robust flagellar Hv1-dependent proton conductance is activated by membrane depolarization, an alkaline extracellular environment, endocannabinoid anandamide, and removal of extracellular zinc, a potent Hv1 blocker. Hv1 allows only outward transport of protons and is therefore dedicated to inducing intracellular alkalinization and activating spermatozoa. The importance of Hv1 for sperm activation makes it an attractive target for controlling male fertility.

  16. Effect of acid-sensing ion channel 1a on the process of liver fibrosis under hyperglycemia. (United States)

    Wang, Huan; Wang, Ying-hong; Yang, Feng; Li, Xiao-feng; Tian, Yuan-yao; Ni, Ming-ming; Zuo, Long-quan; Meng, Xiao-Ming; Huang, Yan


    Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetes complication liver fibrosis.

  17. Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

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    Delin Wu


    Full Text Available Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA. However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (IK, the rapidly activating (IKr and slowly activating (IKs components of IK, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record IK (IKr, IKs and the HERG K+ current. Results. GA (1, 5, and 10 μM inhibited IK (IKr, IKs and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of IK (IKr, IKs and HERG K+ channel.

  18. Niflumic acid hyperpolarizes smooth muscle cells via calcium-activated potassium channel in spiral modiolar artery of guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Li LI; Ke-tao MA; Lei ZHAO; Jun-qiang SI; Zhong-shuang ZHANG; He ZHU; Jing LI


    Aim: The influence of niflumic acid (NFA), a C1- channel antagonist, on the mem-brane potentials in smooth muscle cells (SMC) of the cochlear spiral modiolar artery (SMA) in guinea pigs was examined. Methods: The intracellular recording and whole-cell recording technique were used to record the NFA-induced re-sponse on the acutely-isolated SMA preparation. Results: The SMC had 2 stable but mutually convertible levels of resting potentials (RP), that is, one was near-45 mV and the other was approximately -75 mV, termed as low and high RP, respectively. The bath application of NFA could cause a hyperpolarization in all the low RP cells, but had little effect on high RP cells. The induced responses were concentration-dependent. Large concentrations of NFA (≥100 μmol/L) often in-duced a shift of a low RP to high RP in cells with an initial RP at low level, and NFA (up to 100 μmol/L) had little effect on the membrane potentials of the high RP cells. However, when the high RP cells were depolarized to a level beyond -45 mV by barium and ouabain, NFA hyperpolarized these cells with the similar effect on those cells initially being the low RP. The NFA-induced response was almost completely blocked by charybdotoxin, iberiotoxin, tetraethylammonium, 1,2-bis(2-aminophenoxy) ethane-N,N,N,N,N,-tetraacetic acid tetrakis acetoxymethyl ester, but not by 4-aminopyridine, barium, glipizide, apamin, ouabain, and CdC12. Conclusion: NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2+-activated potassium channels.

  19. Relaxation of endothelin-1-induced pulmonary arterial constriction by niflumic acid and NPPB: mechanism(s) independent of chloride channel block. (United States)

    Kato, K; Evans, A M; Kozlowski, R Z


    We investigated the effects of the Cl- channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on endothelin-1 (ET-1)-induced constriction of rat small pulmonary arteries (diameter 100-400 microm) in vitro, following endothelium removal. ET-1 (30 nM) induced a sustained constriction of rat pulmonary arteries in physiological salt solution. Arteries preconstricted with ET-1 were relaxed by niflumic acid (IC50: 35.8 microM) and NPPB (IC50: 21.1 microM) in a reversible and concentration-dependent manner. However, at concentrations known to block Ca++-activated Cl- channels, DIDS (channel blockers. When L-type Ca++ channels were blocked by nifedipine (10 microM), the ET-1-induced (30 nM) constriction was inhibited by only 5.8%. However, niflumic acid (30 microM) and NPPB (30 microM) inhibited the ET-1-induced constriction by approximately 53% and approximately 60%, respectively, both in the continued presence of nifedipine and in Ca++-free physiological salt solution. The Ca++ ionophore A23187 (10 microM) also evoked a sustained constriction of pulmonary arteries. Surprisingly, the A23187-induced constriction was also inhibited in a reversible and concentration-dependent manner by niflumic acid (IC50: 18.0 microM) and NPPB (IC50: 8.8 microM), but not by DIDS (acid and NPPB inhibit pulmonary artery constriction is independent of Cl- channel blockade. One possibility is that these compounds may block the Ca++-dependent contractile processes.

  20. Determination of organic acids evolution during apple cider fermentation using an improved HPLC analysis method

    NARCIS (Netherlands)

    Zhang, H.; Zhou, F.; Ji, B.; Nout, M.J.R.; Fang, Q.; Zhang, Z.


    An efficient method for analyzing ten organic acids in food, namely citric, pyruvic, malic, lactic, succinic, formic, acetic, adipic, propionic and butyric acids, using HPLC was developed. Boric acid was added into the mobile phase to separate lactic and succinic acids, and a post-column buffer solu

  1. The deletion of several amino acid stretches of Escherichia coli alpha-hemolysin (HlyA suggests that the channel-forming domain contains beta-strands.

    Directory of Open Access Journals (Sweden)

    Roland Benz

    Full Text Available Escherichia coli α-hemolysin (HlyA is a pore-forming protein of 110 kDa belonging to the family of RTX toxins. A hydrophobic region between the amino acid residues 238 and 410 in the N-terminal half of HlyA has previously been suggested to form hydrophobic and/or amphipathic α-helices and has been shown to be important for hemolytic activity and pore formation in biological and artificial membranes. The structure of the HlyA transmembrane channel is, however, largely unknown. For further investigation of the channel structure, we deleted in HlyA different stretches of amino acids that could form amphipathic β-strands according to secondary structure predictions (residues 71-110, 158-167, 180-203, and 264-286. These deletions resulted in HlyA mutants with strongly reduced hemolytic activity. Lipid bilayer measurements demonstrated that HlyAΔ71-110 and HlyAΔ264-286 formed channels with much smaller single-channel conductance than wildtype HlyA, whereas their channel-forming activity was virtually as high as that of the wildtype toxin. HlyAΔ158-167 and HlyAΔ180-203 were unable to form defined channels in lipid bilayers. Calculations based on the single-channel data indicated that the channels generated by HlyAΔ71-110 and HlyAΔ264-286 had a smaller size (diameter about 1.4 to 1.8 nm than wildtype HlyA channels (diameter about 2.0 to 2.6 nm, suggesting that in these mutants part of the channel-forming domain was removed. Osmotic protection experiments with erythrocytes confirmed that HlyA, HlyAΔ71-110, and HlyAΔ264-286 form defined transmembrane pores and suggested channel diameters that largely agreed with those estimated from the single-channel data. Taken together, these results suggest that the channel-forming domain of HlyA might contain β-strands, possibly in addition to α-helical structures.

  2. The volume-regulated anion channel (LRRC8) in nodose neurons is sensitive to acidic pH. (United States)

    Wang, Runping; Lu, Yongjun; Gunasekar, Susheel; Zhang, Yanhui; Benson, Christopher J; Chapleau, Mark W; Sah, Rajan; Abboud, François M


    The leucine rich repeat containing protein 8A (LRRC8A), or SWELL1, is an essential component of the volume-regulated anion channel (VRAC) that is activated by cell swelling and ionic strength. We report here for the first time to our knowledge its expression in a primary cell culture of nodose ganglia neurons and its localization in the soma, neurites, and neuronal membrane. We show that this neuronal VRAC/SWELL1 senses low external pH (pHo) in addition to hypoosmolarity. A robust sustained chloride current is seen in 77% of isolated nodose neurons following brief exposures to extracellular acid pH. Its activation involves proton efflux, intracellular alkalinity, and an increase in NOX-derived H2O2. The molecular identity of both the hypoosmolarity-induced and acid pHo-conditioned VRAC as LRRC8A (SWELL1) was confirmed by Cre-flox-mediated KO, shRNA-mediated knockdown, and CRISPR/Cas9-mediated LRRC8A deletion in HEK cells and in primary nodose neuronal cultures. Activation of VRAC by low pHo reduces neuronal injury during simulated ischemia and N-methyl-D-aspartate-induced (NMDA-induced) apoptosis. These results identify the VRAC (LRRC8A) as a dual sensor of hypoosmolarity and low pHo in vagal afferent neurons and define the mechanisms of its activation and its neuroprotective potential.

  3. The volume-regulated anion channel (LRRC8) in nodose neurons is sensitive to acidic pH (United States)

    Wang, Runping; Lu, Yongjun; Gunasekar, Susheel; Zhang, Yanhui; Benson, Christopher J.; Chapleau, Mark W.; Sah, Rajan; Abboud, François M.


    The leucine rich repeat containing protein 8A (LRRC8A), or SWELL1, is an essential component of the volume-regulated anion channel (VRAC) that is activated by cell swelling and ionic strength. We report here for the first time to our knowledge its expression in a primary cell culture of nodose ganglia neurons and its localization in the soma, neurites, and neuronal membrane. We show that this neuronal VRAC/SWELL1 senses low external pH (pHo) in addition to hypoosmolarity. A robust sustained chloride current is seen in 77% of isolated nodose neurons following brief exposures to extracellular acid pH. Its activation involves proton efflux, intracellular alkalinity, and an increase in NOX-derived H2O2. The molecular identity of both the hypoosmolarity-induced and acid pHo–conditioned VRAC as LRRC8A (SWELL1) was confirmed by Cre-flox–mediated KO, shRNA-mediated knockdown, and CRISPR/Cas9-mediated LRRC8A deletion in HEK cells and in primary nodose neuronal cultures. Activation of VRAC by low pHo reduces neuronal injury during simulated ischemia and N-methyl-D-aspartate–induced (NMDA-induced) apoptosis. These results identify the VRAC (LRRC8A) as a dual sensor of hypoosmolarity and low pHo in vagal afferent neurons and define the mechanisms of its activation and its neuroprotective potential. PMID:28289711

  4. Role in fast inactivation of conserved amino acids in the IV/S4-S5 loop of the human muscle Na+ channel. (United States)

    Mitrovic, N; Lerche, H; Heine, R; Fleischhauer, R; Pika-Hartlaub, U; Hartlaub, U; George, A L; Lehmann-Horn, F


    Since it has been shown that point mutations in the S4-S5 loop of the Shaker K+ channel may disrupt fast inactivation, we investigated the role of three conserved amino acids in IV/S4-S5 of the adult human muscle Na+ channel (L1471, S1478, L1482). In contrast to the K+ channel mutations, the analogous substitutions in the Na+ channel (S1478A/C, L1482A) did not substantially affect fast inactivation. Nevertheless, the mutations S1478A/C/Q shifted the voltage dependence of steady-state inactivation; L1471Q and S1478C slowed recovery from inactivation. In contrast, a novel non-conserved IV/S4-S5 mutation causing paramyotonia congenita (F1473S) slowed fast inactivation 2-fold and accelerated recovery from inactivation 5-fold. The results indicate involvement of the IV/ S4-S5 loop of the human muscle Na+ channel in fast inactivation, but different roles for conserved amino acids among Na+ and K+ channels.

  5. Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome

    DEFF Research Database (Denmark)

    Jons, Christian; Moss, Arthur J; Lopes, Coeli M


    BACKGROUND: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac even...

  6. Niflumic acid alters gating of HCN2 pacemaker channels by interaction with the outer region of S4 voltage sensing domains. (United States)

    Cheng, Lan; Sanguinetti, Michael C


    Niflumic acid, 2-[[3-(trifluoromethyl)phenyl]amino]pyridine-3-carboxylic acid (NFA), is a nonsteroidal anti-inflammatory drug that also blocks or modifies the gating of many ion channels. Here, we investigated the effects of NFA on hyperpolarization-activated cyclic nucleotide-gated cation (HCN) pacemaker channels expressed in X. laevis oocytes using site-directed mutagenesis and the two-electrode voltage-clamp technique. Extracellular NFA acted rapidly and caused a slowing of activation and deactivation and a hyperpolarizing shift in the voltage dependence of HCN2 channel activation (-24.5 +/- 1.2 mV at 1 mM). Slowed channel gating and reduction of current magnitude was marked in oocytes treated with NFA, while clamped at 0 mV but minimal in oocytes clamped at -100 mV, indicating the drug preferentially interacts with channels in the closed state. NFA at 0.1 to 3 mM shifted the half-point for channel activation in a concentration-dependent manner, with an EC(50) of 0.54 +/- 0.068 mM and a predicted maximum shift of -38 mV. NFA at 1 mM also reduced maximum HCN2 conductance by approximately 20%, presumably by direct block of the pore. The rapid onset and state-dependence of NFA-induced changes in channel gating suggests an interaction with the extracellular region of the S4 transmembrane helix, the primary voltage-sensing domain of HCN2. Neutralization (by mutation to Gln) of any three of the outer four basic charged residues in S4, but not single mutations, abrogated the NFA-induced shift in channel activation. We conclude that NFA alters HCN2 gating by interacting with the extracellular end of the S4 voltage sensor domains.

  7. Knockdown of acid-sensing ion channel 1a (ASIC1a) suppresses disease phenotype in SCA1 mouse model. (United States)

    Vig, Parminder J S; Hearst, Scoty M; Shao, Qingmei; Lopez, Maripar E


    The mutated ataxin-1 protein in spinocerebellar ataxia 1 (SCA1) targets Purkinje cells (PCs) of the cerebellum and causes progressive ataxia due to loss of PCs and neurons of the brainstem. The exact mechanism of this cellular loss is still not clear. Currently, there are no treatments for SCA1; however, understanding of the mechanisms that regulate SCA1 pathology is essential for devising new therapies for SCA1 patients. We previously established a connection between the loss of intracellular calcium-buffering and calcium-signalling proteins with initiation of neurodegeneration in SCA1 transgenic (Tg) mice. Recently, acid-sensing ion channel 1a (ASIC1a) have been implicated in calcium-mediated toxicity in many brain disorders. Here, we report generating SCA1 Tg mice in the ASIC1a knockout (KO) background and demonstrate that the deletion of ASIC1a gene expression causes suppression of the SCA1 disease phenotype. Loss of the ASIC1a channel in SCA1/ASIC1a KO mice resulted in the improvement of motor deficit and decreased PC degeneration. Interestingly, the expression of the ASIC1 variant, ASIC1b, was upregulated in the cerebellum of both SCA1/ASIC1a KO and ASIC1a KO animals as compared to the wild-type (WT) and SCA1 Tg mice. Further, these SCA1/ASIC1a KO mice exhibited translocation of PC calcium-binding protein calbindin-D28k from the nucleus to the cytosol in young animals, which otherwise have both cytosolic and nuclear localization. Furthermore, in addition to higher expression of calcium-buffering protein parvalbumin, PCs of the older SCA1/ASIC1a KO mice showed a decrease in morphologic abnormalities as compared to the age-matched SCA1 animals. Our data suggest that ASIC1a may be a mediator of SCA1 pathogenesis and targeting ASIC1a could be a novel approach to treat SCA1.

  8. Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains. (United States)

    Liu, Dan; Zhang, Zheng; Liman, Emily R


    TRPM5, a member of the superfamily of transient receptor potential ion channels, is essential for the detection of bitter, sweet, and amino acid tastes. In heterologous cell types it forms a nonselective cation channel that is activated by intracellular Ca(2+). TRPM5 is likely to be part of the taste transduction cascade, and regulators of TRPM5 are likely to affect taste sensation. In this report we show that TRPM5, but not the related channel TRPM4b, is potently blocked by extracellular acidification. External acidification has two effects, a fast reversible block of the current (IC(50) pH = 6.2) and a slower irreversible enhancement of current inactivation. Mutation of a single Glu residue in the S3-S4 linker and a His residue in the pore region each reduced sensitivity of TRPM5 currents to fast acid block (IC(50) pH = 5.8 for both), and the double mutant was nearly insensitive to acidic pH (IC(50) pH = 5.0). Prolonged exposure to acidic pH enhanced inactivation of TRPM5 currents, and mutant channels that were less sensitive to acid block were also less sensitive to acid-enhanced inactivation, suggesting an intimate association between the two processes. These processes are, however, distinct because the pore mutant H896N, which has normal sensitivity to acid block, shows significant recovery from acid-enhanced inactivation. These data show that extracellular acidification acts through specific residues on TRPM5 to block conduction through two distinct but related mechanisms and suggest a possible interaction between extracellular pH and activation and adaptation of bitter, sweet, and amino acid taste transduction.

  9. Biochemical engineering of the N-acyl side chain of sialic acids alters the kinetics of a glycosylated potassium channel Kv3.1. (United States)

    Hall, M Kristen; Reutter, Werner; Lindhorst, Thisbe; Schwalbe, Ruth A


    The sialic acid of complex N-glycans can be biochemically engineered by substituting the physiological precursor N-acetylmannosamine with non-natural N-acylmannosamines. The Kv3.1 glycoprotein, a neuronal voltage-gated potassium channel, contains sialic acid. Western blots of the Kv3.1 glycoprotein isolated from transfected B35 neuroblastoma cells incubated with N-acylmannosamines verified sialylated N-glycans attached to the Kv3.1 glycoprotein. Outward ionic currents of Kv3.1 transfected B35 cells treated with N-pentanoylmannosamine or N-propanoylmannosamine had slower activation and inactivation rates than those of untreated cells. Therefore, the N-acyl side chain of sialic acid is intimately connected with the activation and inactivation rates of this glycosylated potassium channel.

  10. Preparation of MoO3-V2O5 Nanowires with Controllable Mo/V Ratios inside SBA-15 Channels Using a Chemical Approach with Heteropoly Acid

    Institute of Scientific and Technical Information of China (English)

    岳斌; 谭德军; 闫世润; 周琰; 朱卡克; 潘建烽; 庄继华; 贺鹤勇


    A new approach was developed to fabricate nanowires of mixed oxides MoO3-V2O5 inside the channels of mesoporous silica SBA-15. The method involves functionalization of the channel surface of SBA-15 with aminosilane groups, immobilization of Keggin-type molybdovanadophosphoric acids through an acid-base interaction, and heat treatment. The immobilization of the heteropolyacid containing mixed addenda makes the molar ratio of the loaded components controllable. The formation of the MoO3-V2O5 nanowires inside the channels was monitored by variable temperature in situ XRD. The materials obtained by heat treatment at 400℃ for 5 h were characterized by TEM, N2-sorption measurements, laser Raman spectra and UV-Vis diffuse reflectance spectra. Further heat treatment of the MoO3-V2O5 nanowires inside the SBA-15 channels at higher temperature (700℃) destroys the framework integrity of SBA-15 by complete sublimation of MoO3 through the SBA-15 channel walls.

  11. The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors

    Directory of Open Access Journals (Sweden)

    J.F. Cunha


    Full Text Available We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC50 values of 18 µM and Emax of 100% (N = 10 or 20 µM and Emax of 92% (N = 10, respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP. The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 ± 7.0, 43 ± 3.9 and 78 ± 5.6% in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively. Tetraethylammonium (100 µM, a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 µM, a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 ± 12%. Glibenclamide (1 or 3 µM, at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K+ channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 µM, a selective blocker of the large-conductance Ca2+-activated K+ channels, caused rightward shifts (6- and 7-fold of the gentisic acid concentration-relaxation curve. L-N G-nitroarginine (100 µM, a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 µM, while methylene blue (10 or 30 µM or ODQ (1 µM, the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-P-Cl-Phe6,Leu17[VIP] (0.1 µM, a VIP receptor antagonist

  12. Cementation of wastes with boric acid; Cimentacao de rejeitos contendo acido borico

    Energy Technology Data Exchange (ETDEWEB)

    Tello, Cledola C.O.; Haucz, Maria Judite A. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil); Alves, Lilian J.L.; Oliveira, Arno H. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear


    In nuclear power plants (PWR) are generated wastes, such as concentrate, which comes from the evaporation of liquid radioactive wastes, and spent resins. Both have boron in their composition. The cementation process is one of the options to solidify these wastes, but the boron has a negative effect on the setting of the cement mixture. In this paper are presented the experiments that are being carried out in order to overcome this problem and also to improve the efficiency of the process. Simulated wastes were cemented using additives (clays, admixtures etc.). In the process and product is being evaluated the effect of the amount, type and addition order of the materials. The mixtures were selected in accordance with their workability and incorporated waste. The solidified products are monolithic without free water with a good mechanical resistance. (author)

  13. Low-temperature sintering of silica-boric acid-doped willemite and microwave dielectric properties (United States)

    Ando, Minato; Ohsato, Hitoshi; Igimi, Daisuke; Higashida, Yutaka; Kan, Akinori; Suzuki, Sadahiko; Yasufuku, Yoshitoyo; Kagomiya, Isao


    Millimeter-wave wireless communications in a high-level information society have been expanding in terms of high-density data transfer and radar for pre-crash safety systems. For these communications, millimeter-wave dielectrics have been expected for the development of substrates with high quality factor (Qf), low dielectric constant (ɛr), and near-zero temperature coefficient of resonance frequency (TCf). We have been studying several silicates such as forsterite, willemite, diopside, wollastonite, and cordierite/indialite glass ceramics. In this study, the synthesis of willemite and low-temperature-sintered willemite for low temperature co-fired ceramics (LTCC) is examined. The raw materials used for preparing slurries in doctor blade tape casting are also analyzed.


    Institute of Scientific and Technical Information of China (English)


    IntroductionIt is known that bastnasite is one of the mainsources of cerium. Bac it is still a problem forhydrometallurgy of bastnasite because of large amountof fluorine in the ore. Fltiorine in the bastnasiteleaching liquor forms precipitation with trivalent rareearths and leads to emulsion. So several roastingprocesses of bastnasite with alkali have been putforward and chelants have been added tO eliminate theinfluence of fluorinell-4]. The general chelant is boricacid. One new process with Cyanex 923151...

  15. Role of boric acid in nickel nanotube electrodeposition: a surface-directed growth mechanism. (United States)

    Graham, Lauren M; Cho, Seungil; Kim, Sung Kyoung; Noked, Malachi; Lee, Sang Bok


    Nickel nanotubes have been synthesized by the popular and versatile method of template-assisted electrodeposition, and a surface-directed growth mechanism based on the adsorption of the nickel-borate complex has been proposed.

  16. Boric acid permeation in forward osmosis membrane processes: modeling, experiments, and implications. (United States)

    Jin, Xue; Tang, Chuyang Y; Gu, Yangshuo; She, Qianhong; Qi, Saren


    Forward osmosis (FO) is attracting increasing interest for its potential applications in desalination. In FO, permeation of contaminants from feed solution into draw solution through the semipermeable membrane can take place simultaneously with water diffusion. Understanding the contaminants transport through and rejection by FO membrane has significant technical implications in the way to separate clean water from the diluted draw solution. In this study, a model was developed to predict boron flux in FO operation. A strong agreement between modeling results and experimental data indicates that the model developed in this study can accurately predict the boron transport through FO membranes. Furthermore, the model can guide the fabrication of improved FO membranes with decreased boron permeability and structural parameter to minimize boron flux. Both theoretical model and experimental results demonstrated that when membrane active layer was facing draw solution, boron flux was substantially greater compared to the other membrane orientation due to more severe internal concentration polarization. In this investigation, for the first time, rejection of contaminants was defined in FO processes. This is critical to compare the membrane performance between different membranes and experimental conditions.

  17. Research strategies for pain in lumbar radiculopathy focusing on acid-sensing ion channels and their toxins. (United States)

    Lin, Jiann-Her; Chiang, Yung-Hsiao; Chen, Chih-Cheng


    In lumbar radiculopathy, the dorsal root or dorsal root ganglia (DRG) are compressed or affected by herniated discs or degenerative spinal canal stenosis. The disease is multi-factorial and involves almost all types of pain, such as ischemic, inflammatory, mechanical, and neuropathic pain. Acid-sensing ion channels (ASICs) activated by extracellular acidosis play an important role in pain generation, and the effects of ASICs are widespread in lumbar radiculopathy. ASICs may be involved in the disc degeneration process, which results in disc herniation and, therefore, the compression of the dorsal roots or DRG. ASIC3 is involved in inflammatory pain and ischemic pain, and, likely, mechanical pain. ASIC1a and ASIC3 may have an important effect on control of the vascular tone of the radicular artery. In the central nervous system, ASIC1a modulates the central sensitization of the spinal dorsal horn. Thus, toxins targeting ASICs, because of their specificity, may help elucidate the roles of ASICs in lumbar radiculopathy and could be developed as novel analgesic agents.

  18. Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

    Directory of Open Access Journals (Sweden)

    Chen Wei-Hsin


    Full Text Available Abstract Background Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3 in both carrageenan- and complete Freund's adjuvant (CFA-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation. Methods Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG neurons. Results In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation. Conclusions In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.

  19. Alterations of N-3 polyunsaturated fatty acid-activated K2P channels in hypoxia-induced pulmonary hypertension

    DEFF Research Database (Denmark)

    Nielsen, Gorm; Wandall-Frostholm, Christine; Sadda, Veeranjaneyulu


    in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch...... clamp (PC) and myography. K2P -gene expression was examined in chronic hypoxic mice. qRT-PCR showed that the K2P 2.1 and K2P 6.1 were the predominantly expressed K2P in the murine lung. IHC revealed protein expression of K2P 2.1 and K2P 6.1 in the endothelium of pulmonary arteries and of K2P 6.......1 in bronchial epithelium. PC showed pimozide-sensitive K2P -like K(+) -current activated by docosahexaenoic acid (DHA) in freshly isolated endothelial cells as well as DHA-induced membrane hyperpolarization. Myography on pulmonary arteries showed that DHA induced concentration-dependent instantaneous...

  20. Subacute hypoxia suppresses Kv3.4 channel expression and whole-cell K+ currents through endogenous 15-hydroxyeicosatetraenoic acid in pulmonary arterial smooth muscle cells. (United States)

    Guo, Lei; Tang, Xiaobo; Tian, Hua; Liu, Ye; Wang, Zhigang; Wu, Hong; Wang, Jing; Guo, Sholi; Zhu, Daling


    We have previously reported that subacute hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Subacute hypoxia suppresses Kv3.4 channel expression and results in an inhibition of whole-cell K(+) currents (I(K)). Although the Kv channel inhibition is likely to be mediated through 15-HETE, direct evidence is still lacking. To reveal the role of the 15-LOX/15-HETE pathway in the hypoxia-induced down-regulation of Kv3.4 channel expression and inhibition of I(K), we performed studies using 15-LOX blockers, whole-cell patch-clamp, semi-quantitative PCR, ELISA and Western blot analysis. We found that Kv3.4 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells after blockade of 15-LOX by CDC or NDGA. The 15-LOX blockade also partially restored I(K). In comparison, 15-HETE had a stronger effect than 12-HETE on the expression of Kv3.4 channels. 5-HETE had no noticeable effect on Kv3.4 channel expression. These data indicate that the 15-LOX pathway via its metabolite, 15-HETE, seems to play a role in the down-regulation of Kv3.4 expression and I(K) inhibition after subacute hypoxia.

  1. Excitotoxic death induced by released glutamate in depolarized primary cultures of mouse cerebellar granule cells is dependent on GABAA receptors and niflumic acid-sensitive chloride channels. (United States)

    Babot, Zoila; Cristòfol, Rosa; Suñol, Cristina


    Excitotoxic neuronal death has been linked to neurological and neurodegenerative diseases. Several studies have sought to clarify the involvement of Cl(-) channels in neuronal excitotoxicity using either N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainic acid agonists. In this work we induced excitotoxic death in primary cultures of cerebellar granule cells by means of endogenously released glutamate. Excitotoxicity was provoked by exposure to high extracellular K(+) concentrations ([K(+)](o)) for 5 min. Under these conditions, a Ca(2+)-dependent release of glutamate was evoked. When extracellular glutamate concentration rose to between 2 and 4 microM, cell viability was significantly reduced by 30-40%. The NMDA receptor antagonists (MK-801 and D-2-amino-5-phosphonopentanoic acid) prevented cell death. Exposure to high [K(+)](o) produced a (36)Cl(-) influx which was significantly reduced by picrotoxinin. In addition, the GABA(A) receptor antagonists (bicuculline, picrotoxinin and SR 95531) protected cells from high [K(+)](o)-triggered excitotoxicity and reduced extracellular glutamate concentration. The Cl(-) channel blockers niflumic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid also exerted a neuroprotective effect and reduced extracellular glutamate concentration, even though they did not reduce high [K(+)](o)-induced (36)Cl(-) influx. Primary cultures of cerebellar granule cells also contain a population of GABAergic neurons that released GABA in response to high [K(+)](o). Chronic treatment of primary cultures with kainic acid abolished GABA release and rendered granule cells insensitive to high [K(+)](o) exposure, even though NMDA receptors were functional. Altogether, these results demonstrate that, under conditions of membrane depolarization, low micromolar concentrations of extracellular glutamate might induce an excitotoxic process through both NMDA and GABA(A) receptors and niflumic acid-sensitive Cl

  2. Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase. (United States)

    Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang


    γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca(2+)-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca(2+) increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca(2+)-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca(2+)-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes.

  3. Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition. (United States)

    Mourier, Gilles; Salinas, Miguel; Kessler, Pascal; Stura, Enrico A; Leblanc, Mathieu; Tepshi, Livia; Besson, Thomas; Diochot, Sylvie; Baron, Anne; Douguet, Dominique; Lingueglia, Eric; Servent, Denis


    Mambalgins are peptides isolated from mamba venom that specifically inhibit a set of acid-sensing ion channels (ASICs) to relieve pain. We show here the first full stepwise solid phase peptide synthesis of mambalgin-1 and confirm the biological activity of the synthetic toxin both in vitro and in vivo. We also report the determination of its three-dimensional crystal structure showing differences with previously described NMR structures. Finally, the functional domain by which the toxin inhibits ASIC1a channels was identified in its loop II and more precisely in the face containing Phe-27, Leu-32, and Leu-34 residues. Moreover, proximity between Leu-32 in mambalgin-1 and Phe-350 in rASIC1a was proposed from double mutant cycle analysis. These data provide information on the structure and on the pharmacophore for ASIC channel inhibition by mambalgins that could have therapeutic value against pain and probably other neurological disorders.

  4. Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce sensory-specific analgesic effects.

    Directory of Open Access Journals (Sweden)

    He Liu

    Full Text Available BACKGROUND: Previous studies have demonstrated that QX-314, an intracellular sodium channel blocker, can enter into nociceptors through capsaicin-activated TRPV1 or permeation of the membrane by chemical enhancers to produce a sensory-selective blockade. However, the obvious side effects of these combinations limit the application of QX-314. A new strategy for targeting delivery of QX-314 into nociceptors needs further investigation. The aim of this study is to test whether acidic QX-314, when dissolves in acidic solution directly, can enter into nociceptors through acid-activated TRPV1 and block sodium channels from the intracellular side to produce a sensory-specific analgesic effect. METHODOLOGY/PRINCIPAL FINDINGS: Acidic solution or noradrenaline was injected intraplantarly to induce acute pain behavior in mice. A chronic constrictive injury model was performed to induce chronic neuropathic pain. A sciatic nerve blockade model was used to evaluate the sensory-specific analgesic effects of acidic QX-314. Thermal and mechanical hyperalgesia were measured by using radiant heat and electronic von Frey filaments test. Spinal Fos protein expression was determined by immunohistochemistry. The expression of p-ERK was detected by western blot assay. Whole cell clamp recording was performed to measure action potentials and total sodium current in rats DRG neurons. We found that pH 5.0 PBS solution induced behavioral hyperalgesia accompanied with the increased expression of spinal Fos protein and p-ERK. Pretreatment with pH 5.0 QX-314, and not pH 7.4 QX-314, alleviated pain behavior, inhibited the increased spinal Fos protein and p-ERK expression induced by pH 5.0 PBS or norepinephrine, blocked sodium currents and abolished the production of action potentials evoked by current injection. The above effects were prevented by TRPV1 channel inhibitor SB366791, but not by ASIC channel inhibitor amiloride. Furthermore, acidic QX-314 employed adjacent to the

  5. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate


    Ivanov, Vadim; Ivanova, Svetlana; KALINOVSKY, TATIANA; NIEDZWIECKI, ALEKSANDRA; Rath, Matthias


    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition...

  6. Protective role of acidic pH-activated chloride channel in severe acidosis-induced contraction from the aorta of spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Zhiyong Ma

    Full Text Available Severe acidic pH-activated chloride channel (ICl,acid has been found in various mammalian cells. In the present study, we investigate whether this channel participates in reactions of the thoracic aorta to severe acidosis and whether it plays a role in hypertension. We measured isometric contraction in thoracic aorta rings from spontaneously hypertensive rats (SHRs and normotensive Wistar rats. Severe acidosis induced contractions of both endothelium-intact and -denuded thoracic aorta rings. In Wistar rats, contractions did not differ at pH 6.4, 5.4 and 4.4. However, in SHRs, contractions were higher at pH 5.4 or 4.4 than pH 6.4, with no difference between contractions at pH 5.4 and 4.4. Nifedipine, ICl,acid blockers 5-nitro-2-(3-phenylpropylamino benzoic acid (NPPB and 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS inhibited severe acidosis-induced contraction of aortas at different pH levels. When blocking ICl,acid, the remnant contraction was greater at pH 4.4 than pH 5.4 and 6.4 for both SHRs and Wistar rats. With nifedipine, the remnant contraction was greatly reduced at pH 4.4 as compared with at pH 6.4 and 5.4. With NPPB or DIDS, the ratio of remnant contractions at pH 4.4 and 5.4 (R4.4/5.4 was lower for SHRs than Wistar rats (all 1. Furthermore, patch clamp recordings of ICl,acid and intracellular Ca(2+ measurements in smooth muscle cells confirmed these findings. ICl,acid may protect arteries against excess vasoconstriction under extremely acidic extracellular conditions. This protective effect may be decreased in hypertension.

  7. Effect of Diaminopropionic acid (Dap) on the Biophysical Properties of a Modified Synthetic Channel-Forming Peptide


    Bukovnik, Urska; Sala-Rabanal, Monica; Francis, Simonne; Frazier, Shawnalea J.; Schultz, Bruce D.; Nichols, Colin G.; John M Tomich


    Channel replacement therapy, based on synthetic channel-forming peptides (CFPs) with the ability to supersede defective endogenous ion channels, is a novel treatment modality that may augment existing interventions against multiple diseases. Previously, we derived CFPs from the second transmembrane segment of the α-subunit of the glycine receptor, M2GlyR, which forms chloride-selective channels in its native form. The best candidate, NK4-M2GlyR T19R, S22W (p22-T19R, S22W), was water-soluble, ...

  8. Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain. (United States)

    Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li


    Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain.

  9. The aminoglycosides modulate the acid-sensing ionic channel currents in dorsal root ganglion neurons from the rat. (United States)

    Garza, Aníbal; López-Ramírez, Omar; Vega, Rosario; Soto, Enrique


    Acid-sensing ionic channels (ASICs) have been shown to have a significant role in a growing number of physiological and pathological processes, such as nociception, synaptic transmission and plasticity, mechanosensation, and acidosis-induced neuronal injury. The discovery of pharmacological agents targeting ASICs has significant therapeutic potential and use as a research tool. In our work, we studied the action of transient perfusion (5-15 s) of aminoglycosides (AGs) (streptomycin and neomycin) on the proton-gated ionic currents in dorsal root ganglion (DRG) neurons of the rat and in human embryonic kidney (HEK)-293 cells. In DRG neurons, streptomycin and neomycin (30 microM) produced a significant, concentration-dependent, and reversible reduction in the amplitude of the proton-gated current, and a slowing of the desensitization rate of the ASIC current. Gentamycin (30 microM) also showed a significant reversible action on the ASIC currents. The curves of the pH effect for streptomycin and neomycin indicated that their effect was not significantly affected by pH. In HEK-293 cells, streptomycin (30 microM) produced a significant reduction in the amplitude of the proton-gated current. Neomycin and gentamycin had no significant action. Reduction of extracellular Ca(2+) concentration produced a significant increase in the action of streptomycin and neomycin on the desensitization time course of ASIC currents. These results indicate that ASICs are molecular targets for AGs, which may contribute to the understanding of their actions on excitable cells. Moreover, AGs may constitute a source to develop novel molecules with a greater affinity, specificity, and selectivity for the different ASIC subunits.

  10. Molecular physiology of the insect K-activated amino acid transporter 1 (KAAT1) and cation-anion activated amino acid transporter/channel 1 (CAATCH1) in the light of the structure of the homologous protein LeuT. (United States)

    Castagna, M; Bossi, E; Sacchi, V F


    K-activated amino acid transporter 1 (KAAT1) and cation-anion-activated amino acid transporter/channel 1 (CAATCH1) are amino acid cotransporters, belonging to the Na/Cl-dependent neurotransmitter transporter family (also called SLC6/NSS), that have been cloned from Manduca sexta midgut. They have been thoroughly studied by expression in Xenopus laevis oocytes, and structure/function analyses have made it possible to identify the structural determinants of their cation and amino acid selectivity. About 40 mutants of these proteins have been studied by measuring amino acid uptake and current/voltage relationships. The results obtained since the cloning of KAAT1 and CAATCH1 are here discussed in the light of the 3D model of the first crystallized member of the family, the leucine transporter LeuT.

  11. Inhibition of Intermediate-Conductance Calcium-Activated K Channel (KCa3.1) and Fibroblast Mitogenesis by α-Linolenic Acid and Alterations of Channel Expression in the Lysosomal Storage Disorders, Fabry Disease, and Niemann Pick C (United States)

    Oliván-Viguera, Aida; Lozano-Gerona, Javier; López de Frutos, Laura; Cebolla, Jorge J.; Irún, Pilar; Abarca-Lachen, Edgar; García-Malinis, Ana J.; García-Otín, Ángel Luis; Gilaberte, Yolanda; Giraldo, Pilar; Köhler, Ralf


    The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K+-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation. In the second, we study whether KCa3.1 is altered in the LSDs, FD, and Niemann-Pick disease type C (NPC). Our patch-clamp and mRNA-expression studies on murine and human fibroblasts show functional expression of KCa3.1. KCa currents display the typical pharmacological fingerprint of KCa3.1: Ca2+-activation, potentiation by the positive-gating modulators, SKA-31 and SKA-121, and inhibition by TRAM-34, Senicapoc (ICA-17043), and the negative-gating modulator, 13b. Considering modulation by omega-3 fatty acids we found that α-linolenic acid (α-LA) and docosahexanenoic acid (DHA) inhibit KCa3.1 currents and strongly reduce fibroblast growth. The α-LA-rich linseed oil and γ-LA-rich borage oil at 0.5% produce channel inhibition while α-LA/γ-LA-low oils has no anti-proliferative effect. Concerning KCa3.1 in LSD, mRNA expression studies, and patch-clamp on primary fibroblasts from FD and NPC patients reveal lower KCa3.1-gene expression and membrane expression than in control fibroblasts. In conclusion, the omega-3 fatty acid, α-LA, and α-LA/γ-LA-rich plant oils, inhibit fibroblast KCa3.1 channels and mitogenesis. Reduced fibroblast KCa3.1 functions are a feature and possible biomarker of cell dysfunction in FD and NPC and supports the concept that biased lipid metabolism is capable of negatively modulating KCa3.1 expression. PMID:28197106

  12. Performance of an open limestone channel for treating a stream affected by acid rock drainage (León, Spain). (United States)

    Santofimia, Esther; López-Pamo, Enrique


    The generation of acid rock drainage (ARD) was observed after the oxidation dissolution of pyrite-rich black shales, which were excavated during the construction of a highway in León (Spain). ARDs are characterized by the presence of high concentrations of sulfate and metals (Al, Fe, Mn, Zn, Cu, Co, Ni, Th, and U) that affect the La Silva stream. Dissolved element concentrations showed values between one and four orders of magnitude higher than those of natural waters of this area. A passive treatment system was constructed; the aim of which was to improve the quality of the water of the stream. This work provides a hydrochemical characterization of the La Silva stream after its transit through the different elements that constitute the passive treatment system (open limestone channel (OLC), small ponds, and a wetland), during its first year of operation. The passive treatment system has two sections separated by a tunnel 230 m long. The first section, which stretches between the highway and the tunnel entrance, is an OLC 350 m long with a slope of 16 %. The second section, which stretches from the tunnel exit to the end wetland, has a length of 700 m and a slope of 6 %; it is in this section where six small ponds are located. In the first section of this passive treatment system, the OLC was effectively increasing the pH from 3 to 4-4.5 and eliminating all of the dissolved Fe and the partially dissolved Al. These elements, after hydrolysis at a pH 3-3.5 and 4-4.5, respectively, had precipitated as schwertmannite and hydrobasaluminite, while other dissolved metals were removed totally or partially for adsorption by the precipitates and/or by coprecipitation. The second section receives different inputs of water such as ARDs and natural waters. After exiting the treatment system, the stream is buffered by Al at a pH of 4-4.3, showing high Al concentrations (19-101 mg/L) but with a complete removal of dissolved Fe. Unfortunately, the outflow shows similar or

  13. Covalent modification of mutant rat P2X2 receptors with a thiol-reactive fluorophore allows channel activation by zinc or acidic pH without ATP.

    Directory of Open Access Journals (Sweden)

    Shlomo S Dellal

    Full Text Available Rat P2X2 receptors open at an undetectably low rate in the absence of ATP. Furthermore, two allosteric modulators, zinc and acidic pH, cannot by themselves open these channels. We describe here the properties of a mutant receptor, K69C, before and after treatment with the thiol-reactive fluorophore Alexa Fluor 546 C(5-maleimide (AM546. Xenopus oocytes expressing unmodified K69C were not activated under basal conditions nor by 1,000 µM ATP. AM546 treatment caused a small increase in the inward holding current which persisted on washout and control experiments demonstrated this current was due to ATP independent opening of the channels. Following AM546 treatment, zinc (100 µM or acidic external solution (pH 6.5 elicited inward currents when applied without any exogenous ATP. In the double mutant K69C/H319K, zinc elicited much larger inward currents, while acidic pH generated outward currents. Suramin, which is an antagonist of wild type receptors, behaved as an agonist at AM546-treated K69C receptors. Several other cysteine-reactive fluorophores tested on K69C did not cause these changes. These modified receptors show promise as a tool for studying the mechanisms of P2X receptor activation.

  14. Activation of SUR2B/Kir6.1-type KATP channels protects glomerular endothelial, mesangial and tubular epithelial cells against oleic acid renal damage

    Institute of Scientific and Technical Information of China (English)

    Ying ZHAO; Hai WANG


    Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure.Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (KATP) in the endothelium.It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium,glomerular mesangium,and the endothelium and the smooth muscle of blood vessels.Herein,we hypothesized that activating renal KATP channels with iptakalim might have directly neroprotective effects.In this study,glomerular endothelial,mesangial and tubular epithelial cells which are the main cell types to form nephron were exposed to oleic acid (OA) at various concentrations for 24 h.0.25 μl/ml OA could cause cellular damage of glomerular endothelium and mesangium,while 1.25μl/ml OA could lead to the injury of three types of renal cells.It was observed that pretreatment with iptakalim at concentrations of 0.1,1,10 or 100 μmol/L prevented cellular damage of glomerular endothelium and tubular epithelium,whereas iptakalim from 1 to 100 μmol/L prevented the injury of mesangial cells.Our data showed iptakalim significantly increased survived cell rates in a concentration-dependent manner,significantly antagonized by glibenclamide,a KATP blocker.Iptakalim played a protective role in the main cell types of kidney,which was consistent with natakalim,a highly selective SUR2B/Kir6.1 channel opener.Iptakalim exerted protective effects through activating SUR2B/Kir6.1 channels,suggesting a new strategy for renal injury by its endothelial and renal cell protection.

  15. Improvement of Vegetative and Reproductive Growth of ‘Camarosa’ Strawberry: Role of Humic Acid, Zn, and B

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    Somaye Rafeii


    Full Text Available This experiment was conducted with the aim to improve vegetative and reproductive growth of strawberry (Fragaria × ananassa Duch. cv. ‘Camarosa’ using humic acid, zinc sulfate (ZnSO4, and boric acid. We evaluated applications of humic acid at 0, 20 and 40 mg·L-1, ZnSO4 at 0, 50 and 100 mg·L-1, and boric acid at 0, 50 and 100 mg·L-1 at 30 days after planting and blooming stage on growth of strawberry cv. ‘Camarosa’. Results indicated that humic acid, ZnSo4, and boric acid application improved reproductive and vegetative characteristics compared to control treatment. The results showed, that plants treated with humic acid, ZnSO4, and boric acid at higher their concentrations exhibited generally higher dry weight of roots and shoots, number of flowers and inflorescences, leaf area, length of roots and shoots, length of flowering period, yield, weight of primary and secondary fruits and number of their achenes. Total yield was significantly increased by all treatments compared to control treatment at both stages of application, especially at blooming stage. Moreover, conclusion showed that the mentioned materials could have impact on vegetative and reproductive growth of strawberry generally. In this study humic acid at 40 mg L-1 at blooming stage resulted in best effects on development of strawberry cv. ‘Camarosa’.

  16. 1D Ladder-like Chain and 1D Channeled 3D Supramolecular Architectures Based on Benzophenone-2,4'-dicarboxylic Acid

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-Gang; LI Dong-Sheng; FU Feng; WU Ya-Pan; WANG Ji-Jiang; WANG Yao-Yu


    The hydrothermal reactions of AgNO3, 2,2'-bipyridyl, and benzophenone-2,4'-dicarboxylic acid gave rise to two benzophenone-2,4'-dicarboxylic acid). The two compounds are extended by hydrogen bonds in two different apbonding between H2L ligands and water molecules, then extended to a 3D supramolecular architecture. Compound 2 possesses 3D supramolecular architecture containing 1D open channels, which are driven due to the strong H-bonding interactions occurring between the HL anions and water molecules; interestingly, [Ag(bpy)2]+ cations vestigated, the emission maxima for 2 exhibits red-shift compared with that of free ligand and 1 due to chelating effect of the 2,2'-bipyridine ligand to the silver ion and the presence of aromatic π-packing.

  17. Microchip CE analysis of amino acids on a titanium dioxide nanoparticles-coated PDMS microfluidic device with in-channel indirect amperometric detection. (United States)

    Qiu, Jian-Ding; Wang, Li; Liang, Ru-Ping; Wang, Jing-Wu


    In this paper, titanium dioxide nanoparticles (TiO(2) NPs) were employed to construct a functional film on PDMS microfluidic channel surface, which was formed by sequentially immobilizing poly(diallyldimethylammonium chloride) and TiO(2) NPs on PDMS surface by layer-by-layer assembly technique. The modified PDMS microchip exhibited a decreased and stable EOF, which was favorable for the separation of biomolecules with similar migration times. Arginine, phenylalanine, serine and threonine were used as model analytes to evaluate the performance of the modified microchip. The four amino acids were efficiently separated within 100 s in a 3.7 cm long separation channel and successfully detected on the carbon fiber electrode in conjunction with in-channel indirect amperometry. Resolutions and theoretical plate numbers of the analytes were considerably enhanced in the presence of TiO(2) NPs. The modified microchip demonstrated excellent stability and reproducibility with improved RSDs of migration times and peak currents for run-to-run, day-to-day and chip-to-chip analyses, respectively. Variables influencing the separation efficiency and amperometric response, including injection and separation voltage, the working electrode position and buffer concentration, were optimized in detail.

  18. A functional assay to measure postsynaptic gamma-aminobutyric acidB responses in cultured spinal cord neurons: Heterologous regulation of the same K+ channel

    Energy Technology Data Exchange (ETDEWEB)

    Kamatchi, G.L.; Ticku, M.K. (Univ. of Texas Health Science Center, San Antonio (USA))


    The stimulation of postsynaptic gamma-aminobutyric acid (GABA)B receptors leads to slow inhibitory postsynaptic potentials due to the influx of K(+)-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABAB receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen. Apart from the GABAB receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT1 alpha agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABAB, adenosine1 and 5-HT1 alpha receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K(+)-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K(+)-channel through the Gi/Go proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABAB synaptic pharmacology in vitro, using spinal cord neurons.

  19. Non-charged amino acids from three different domains contribute to link agonist binding to channel gating in alpha7 nicotinic acetylcholine receptors. (United States)

    Aldea, Marcos; Mulet, José; Sala, Salvador; Sala, Francisco; Criado, Manuel


    Binding of agonists to nicotinic acetylcholine receptors results in channel opening. Previously, we have shown that several charged residues at three different domains of the alpha7 nicotinic receptor are involved in coupling binding and gating, probably through a network of electrostatic interactions. This network, however, could also be integrated by other residues. To test this hypothesis, non-charged amino acids were mutated and expression levels and electrophysiological responses of mutant receptors were determined. Mutants at positions Asn47 and Gln48 (loop 2), Ile130, Trp134, and Gln140 (loop 7), and Thr264 (M2-M3 linker) showed poor or null functional responses, despite significant membrane expression. By contrast, mutants F137A and S265A exhibited a gain of function effect. In all cases, changes in dose-response relationships were small, EC(50) values being between threefold smaller and fivefold larger, arguing against large modifications of agonist binding. Peak currents decayed at the same rate in all receptors except two, excluding large effects on desensitization. Thus, the observed changes could be mostly caused by alterations of the gating characteristics. Moreover, analysis of double mutants showed an interconnection between some residues in these domains, especially Gln48 with Ile130, suggesting a potential coupling between agonist binding and channel gating through these amino acids.

  20. Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.

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    Nicole K McKinnon

    Full Text Available 5-HT3A receptors are pentameric neurotransmitter-gated ion channels in the Cys-loop receptor family. Each subunit contains an extracellular domain, four transmembrane segments (M1, M2, M3, M4 and a 115 residue intracellular loop between M3 and M4. In contrast, the M3M4 loop in prokaryotic homologues is <15 residues. To investigate the limits of M3M4 loop length and composition on channel function we replaced the 5-HT3A M3M4 loop with two to seven alanine residues (5-HT3A-A(n = 2-7. Mutants were expressed in Xenopus laevis oocytes and characterized using two electrode voltage clamp recording. All mutants were functional. The 5-HT EC(50's were at most 5-fold greater than wild-type (WT. The desensitization rate differed significantly among the mutants. Desensitization rates for 5-HT3A-A(2, 5-HT3A-A(4, 5-HT3A-A(6, and 5-HT3A-A(7 were similar to WT. In contrast, 5-HT3A-A(3 and 5-HT3A-A(5 had desensitization rates at least an order of magnitude faster than WT. The one Ala loop construct, 5-HT3A-A(1, entered a non-functional state from which it did not recover after the first 5-HT application. These results suggest that the large M3M4 loop of eukaryotic Cys-loop channels is not required for receptor assembly or function. However, loop length and amino acid composition can effect channel expression and desensitization. We infer that the cytoplasmic ends of the M3 and M4 segments may undergo conformational changes during channel gating and desensitization and/or the loop may influence the position and mobility of these segments as they undergo gating-induced conformational changes. Altering structure or conformational mobility of the cytoplasmic ends of M3 and M4 may be the basis by which phosphorylation or protein binding to the cytoplasmic loop alters channel function.

  1. Identification of Amino Acid Residues in Fibroblast Growth Factor 14 (FGF14) Required for Structure-Function Interactions with Voltage-gated Sodium Channel Nav1.6. (United States)

    Ali, Syed R; Singh, Aditya K; Laezza, Fernanda


    The voltage-gated Na(+) (Nav) channel provides the basis for electrical excitability in the brain. This channel is regulated by a number of accessory proteins including fibroblast growth factor 14 (FGF14), a member of the intracellular FGF family. In addition to forming homodimers, FGF14 binds directly to the Nav1.6 channel C-tail, regulating channel gating and expression, properties that are required for intrinsic excitability in neurons. Seeking amino acid residues with unique roles at the protein-protein interaction interface (PPI) of FGF14·Nav1.6, we engineered model-guided mutations of FGF14 and validated their impact on the FGF14·Nav1.6 complex and the FGF14:FGF14 dimer formation using a luciferase assay. Divergence was found in the β-9 sheet of FGF14 where an alanine (Ala) mutation of Val-160 impaired binding to Nav1.6 but had no effect on FGF14:FGF14 dimer formation. Additional analysis revealed also a key role of residues Lys-74/Ile-76 at the N-terminal of FGF14 in the FGF14·Nav1.6 complex and FGF14:FGF14 dimer formation. Using whole-cell patch clamp electrophysiology, we demonstrated that either the FGF14(V160A) or the FGF14(K74A/I76A) mutation was sufficient to abolish the FGF14-dependent regulation of peak transient Na(+) currents and the voltage-dependent activation and steady-state inactivation of Nav1.6; but only V160A with a concomitant alanine mutation at Tyr-158 could impede FGF14-dependent modulation of the channel fast inactivation. Intrinsic fluorescence spectroscopy of purified proteins confirmed a stronger binding reduction of FGF14(V160A) to the Nav1.6 C-tail compared with FGF14(K74A/I76A) Altogether these studies indicate that the β-9 sheet and the N terminus of FGF14 are well positioned targets for drug development of PPI-based allosteric modulators of Nav channels.

  2. 酸敏感离子通道参与伤害性感受的研究%Advance in nociception mediated by acid sensing ion channels

    Institute of Scientific and Technical Information of China (English)

    刘鹤; 曹君利


    背景 组织酸化是炎症、缺血/缺氧、骨质破坏等多种疼痛条件下的共同病理特征.酸敏感离子通道(acid-sensingion channels,ASICs)是一类兴奋性阳离子通道,表达在神经系统,可直接被细胞外质子激活,介导组织酸化所致的伤害性感受. 目的 以ASICs为疼痛治疗靶标,将为疼痛治疗提供一条新途径. 内容 综述ASICs参与组织酸化所致伤害性感受的相关研究. 趋向 近年来,研究发现ASICs在介导组织酸化所致伤害性感受过程中发挥重要作用,以ASICs为靶点,将为开发新型镇痛药物和疼痛治疗提供新思路.%Background Tissue acidosis is a common pathological feature of many painful conditions including inflammation,ischemia and bone destruction.Acid sensing ion channels (ASICs) are excitatory cation channels directly activated by extracellular protons that are expressed in the nervous system,and mediate nociception indcued by tissue acidosis.Objective It will provide a new approach to take ASICs for pain treatment targets.Content The studies of ASICs in mediating nociception associated with tissue acidosis is reviewed.Trend Recent studies show that ASICs play a key role in mediating nociception associated with tissue acidosis,and it will provide a novel approach for development new analgesic drugs and pain treatment targeted ASICs.

  3. Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus. (United States)

    Mango, D; Braksator, E; Battaglia, G; Marcelli, S; Mercuri, N B; Feligioni, M; Nicoletti, F; Bashir, Z I; Nisticò, R


    Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na(+) channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca(2+) and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

  4. Hepatic ATGL mediates PPAR-α signaling and fatty acid channeling through an L-FABP independent mechanism. (United States)

    Ong, Kuok Teong; Mashek, Mara T; Davidson, Nicholas O; Mashek, Douglas G


    Adipose TG lipase (ATGL) catalyzes the rate-limiting step in TG hydrolysis in most tissues. We have shown that hepatic ATGL preferentially channels hydrolyzed FAs to β-oxidation and induces PPAR-α signaling. Previous studies have suggested that liver FA binding protein (L-FABP) transports FAs from lipid droplets to the nucleus for ligand delivery and to the mitochondria for β-oxidation. To determine if L-FABP is involved in ATGL-mediated FA channeling, we used adenovirus-mediated suppression or overexpression of hepatic ATGL in either WT or L-FABP KO mice. Hepatic ATGL knockdown increased liver weight and TG content of overnight fasted mice regardless of genotype. L-FABP deletion did not impair the effects of ATGL overexpression on the oxidation of hydrolyzed FAs in primary hepatocyte cultures or on serum β-hydroxybutyrate concentrations in vivo. Moreover, L-FABP deletion did not influence the effects of ATGL knockdown or overexpression on PPAR-α target gene expression. Taken together, we conclude that L-FABP is not required to channel ATGL-hydrolyzed FAs to mitochondria for β-oxidation or the nucleus for PPAR-α regulation.

  5. Mechanism of block of single protopores of the Torpedo chloride channel ClC-0 by 2-(p-chlorophenoxy)butyric acid (CPB). (United States)

    Pusch, M; Accardi, A; Liantonio, A; Ferrera, L; De Luca, A; Camerino, D C; Conti, F


    We investigated in detail the mechanism of inhibition by the S(-) enantiomer of 2-(p-chlorophenoxy)butyric acid (CPB) of the Torpedo Cl(-)channel, ClC-0. The substance has been previously shown to inhibit the homologous skeletal muscle channel, CLC-1. ClC-0 is a homodimer with probably two independently gated protopores that are conductive only if an additional common gate is open. As a simplification, we used a mutant of ClC-0 (C212S) that has the common gate "locked open" (Lin, Y.W., C.W. Lin, and T.Y. Chen. 1999. J. Gen. Physiol. 114:1-12). CPB inhibits C212S currents only when applied to the cytoplasmic side, and single-channel recordings at voltages (V) between -120 and -80 mV demonstrate that it acts independently on individual protopores by introducing a long-lived nonconductive state with no effect on the conductance and little effect on the lifetime of the open state. Steady-state macroscopic currents at -140 mV are half-inhibited by approximately 0.5 mM CPB, but the inhibition decreases with V and vanishes for V > or = 40 mV. Relaxations of CPB inhibition after voltage steps are seen in the current responses as an additional exponential component that is much slower than the gating of drug-free protopores. For V = 60 mV) with an IC50 of approximately 30-40 mM. Altogether, these findings support a model for the mechanism of CPB inhibition in which the drug competes with Cl(-) for binding to a site of the pore where it blocks permeation. CPB binds preferentially to closed channels, and thereby also strongly alters the gating of the single protopore. Since the affinity of CPB for open WT pores is extremely low, we cannot decide in this case if it acts also as an open pore blocker. However, the experiments with the mutant K519E strongly support this interpretation. CPB block may become a useful tool to study the pore of ClC channels. As a first application, our results provide additional evidence for a double-barreled structure of ClC-0 and ClC-1.

  6. Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion.

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    Meghali P Nighot

    Full Text Available The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05 and 53% (P<0.001 respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025 lower by 9.4 fold (89% in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84-95%, P<0.005 in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.

  7. Effects of deletion and insertion of amino acids on the activity of HelaTx1, a scorpion toxin on potassium channels. (United States)

    Peigneur, Steve; Esaki, Nao; Yamaguchi, Yoko; Tytgat, Jan; Sato, Kazuki


    Four analogs of HelaTx1, a 25-mer peptide from scorpion venom, were synthesized by deleting its C-terminal hexapeptide fragment and N-terminal Ser residue and by inserting an amino acid in the middle part of the molecule. CD spectrum of HelaTx1(1-19) was almost superimposable to that of native HelaTx1. Functional characterization showed that HelaTx1(1-19) retained its inhibitory activity on Kv1.1 channel although 3 times less potent than HelaTx1, indicating that C-terminal part of HelaTx1 was not essential for its conformation and activity. Further deletion of N-terminal Ser residue and insertion of Ala in the middle part of the molecule affected the CD spectra and resulted in the decrease of activity.

  8. Control of the Position of Oxygen Delivery in Soybean Lipoxygenase-1 by Amino Acid Side Chains within a Gas Migration Channel. (United States)

    Collazo, Lara; Klinman, Judith P


    Understanding gas migration pathways is critical to unraveling structure-function relationships in enzymes that process gaseous substrates such as O2, H2, and N2 This work investigates the role of a defined pathway for O2 in regulating the peroxidation of linoleic acid by soybean lipoxygenase 1. Computational and mutagenesis studies provide strong support for a dominant delivery channel that shuttles molecular oxygen to a specific region of the active site, thereby ensuring the regio- and stereospecificity of product. Analysis of reaction kinetics and product distribution in channel mutants also reveals a plasticity to the gas migration pathway. The findings show that a single site mutation (I553W) limits oxygen accessibility to the active site, greatly increasing the fraction of substrate that reacts with oxygen free in solution. They also show how a neighboring site mutation (L496W) can result in a redirection of oxygen toward an alternate position of the substrate, changing the regio- and stereospecificity of peroxidation. The present data indicate that modest changes in a protein scaffold may modulate the access of small gaseous molecules to enzyme-bound substrates.

  9. Cyclisation Increases the Stability of the Sea Anemone Peptide APETx2 but Decreases Its Activity at Acid-Sensing Ion Channel 3

    Directory of Open Access Journals (Sweden)

    Lachlan D. Rash


    Full Text Available APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3 and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory pain. As a peptide it faces many challenges in the drug development process, including the potential lack of stability often associated with therapeutic peptides. In this study we determined the susceptibility of wild-type APETx2 to trypsin and pepsin and tested the applicability of backbone cyclisation as a strategy to improve its resistance to enzymatic degradation. Cyclisation with either a six-, seven- or eight-residue linker vastly improved the protease resistance of APETx2 but substantially decreased its potency against ASIC3. This suggests that either the N- or C-terminus of APETx2 is involved in its interaction with the channel, which we confirmed by making N- and C-terminal truncations. Truncation of either terminus, but especially the N-terminus, has detrimental effects on the ability of APETx2 to inhibit ASIC3. The current work indicates that cyclisation is unlikely to be a suitable strategy for stabilising APETx2, unless linkers can be engineered that do not interfere with binding to ASIC3.

  10. Distinct abscisic acid signaling pathways for modulation of guard cell versus mesophyll cell potassium channels revealed by expression studies in Xenopus laevis oocytes (United States)

    Sutton, F.; Paul, S. S.; Wang, X. Q.; Assmann, S. M.; Evans, M. L. (Principal Investigator)


    Regulation of guard cell ion transport by abscisic acid (ABA) and in particular ABA inhibition of a guard cell inward K(+) current (I(Kin)) is well documented. However, little is known concerning ABA effects on ion transport in other plant cell types. Here we applied patch clamp techniques to mesophyll cell protoplasts of fava bean (Vicia faba cv Long Pod) plants and demonstrated ABA inhibition of an outward K(+) current (I(Kout)). When mesophyll cell protoplast mRNA (mesophyll mRNA) was expressed in Xenopus laevis oocytes, I(Kout) was generated that displayed similar properties to I(Kout) observed from direct analysis of mesophyll cell protoplasts. I(Kout) expressed by mesophyll mRNA-injected oocytes was inhibited by ABA, indicating that the ABA signal transduction pathway observed in mesophyll cells was preserved in the frog oocytes. Co-injection of oocytes with guard cell protoplast mRNA and cRNA for KAT1, an inward K(+) channel expressed in guard cells, resulted in I(Kin) that was similarly inhibited by ABA. However, oocytes co-injected with mesophyll mRNA and KAT1 cRNA produced I(Kin) that was not inhibited by ABA. These results demonstrate that the mesophyll-encoded signaling mechanism could not substitute for the guard cell pathway. These findings indicate that mesophyll cells and guard cells use distinct and different receptor types and/or signal transduction pathways in ABA regulation of K(+) channels.

  11. Niflumic acid hyperpolarizes the smooth muscle cells by opening BK(Ca) channels through ryanodine-sensitive Ca(2+) release in spiral modiolar artery. (United States)

    Li, Li; Ma, Ke-Tao; Zhao, Lei; Si, Jun-Qiang


    The mechanism by which niflumic acid (NFA), a Cl(-) channel antagonist, hyperpolarizes the smooth muscle cells (SMCs) of cochlear spiral modiolar artery (SMA) was explored. Guinea pigs were used as subjects and perforated patch clamp and intracellular recording technique were used to observe NFA-induced response of SMC in the acutely isolated SMA preparation. The results showed that bath application of NFA, indanyloxyacetic acid 94 (IAA-94) and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) caused hyperpolarization and evoked outward currents in all cells at low resting potential (RP), but had no effects in cells at high RP. In the low RP SMCs, the average RP was about (-42.47+/-1.38) mV (n=24). Application of NFA (100 mumol/L), IAA-94 (10 mumol/L) and DIDS (200 mumol/L) shifted the RP to (13.7+/-4.3) mV (n=9, P<0.01), (11.4+/-4.2) mV (n=7, P<0.01) and (12.3+/-3.7) mV (n=8, P<0.01), respectively. These drug-induced responses were in a concentration-dependent manner. NFA-induced hyperpolarization and outward current were almost blocked by charybdotoxin (100 nmol/L), iberiotoxin (100 nmol/L), tetraethylammonium (10 mmol/L), BAPTA-AM (50 mumol/L), ryanodine (10 mumol/L) and caffeine (0.1-10 mmol/L), respectively, but not by nifedipine (100 mumol/L), CdCl2 (100 mumol/L) and Ca(2+)-free medium. It is concluded that NFA induces a release of intracellular calcium from the Ca(2+) stores and the released intracellular calcium in turn causes concentration-dependent and reversible hyperpolarization and evokes outward currents in the SMCs of the cochlear SMA via activation of the Ca(2+)-activated potassium channels.

  12. Inhibition of inward K+ channels and stomatal response by abscisic acid: an intracellular locus of phytohormone action.


    Schwartz, A; Wu, W. H.; Tucker, E B; Assmann, S M


    Abscisic acid (ABA), a plant hormone whose production is stimulated by water stress, reduces the apertures of stomatal pores in the leaf surface, thereby lessening transpirational water loss. It has been thought that inhibition of stomatal opening and promotion of stomatal closure by ABA are initiated by the binding of extracellular ABA to a receptor located in the guard-cell plasma membrane. However, in the present research, we employ three distinct experimental approaches to demonstrate tha...

  13. Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy. (United States)

    Qiao, Xin; Werkman, Taco R; Gorter, Jan A; Wadman, Wytse J; van Vliet, Erwin A


    Voltage-gated Na(+) channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na(+) channel α subunits: NaV1.1, NaV1.2 and NaV1.6 during epileptogenesis (induced by kainic acid) using time points that cover the period from induction to the chronic phase of epilepsy. NaV1.1 immunoreactivity was persistently reduced at 1 day, 3 weeks and 2 months after SE in CA1 and CA3. About 50% of the NaV1.1-positive interneurons was lost at one day after SE in all regions investigated. In the hilus a similar reduction in NeuN-positive neurons was found, while in the CA1 and CA3 region the loss in NeuN-positive neurons only reached 15% in the chronic phase of epilepsy. This implies a stronger shift in the balance between excitation and inhibition toward excitation in the CA1 and CA3 region than in the hilus. NaV1.2 immunoreactivity in the inner molecular layer of the dentate gyrus was lower than control at 1 day after SE. It increased at 3 weeks and 2 months after SE in the inner molecular layer and overlapped with sprouted mossy fibers. NaV1.6 immunoreactivity in the dendritic region of CA1 and CA3 was persistently reduced at all time-points during epileptogenesis. Some astrocytes expressed NaV1.1 and NaV1.6 at 3 weeks after SE. Expression data alone are not sufficient to explain changes in network stability, or infer causality in epileptogenesis. These results demonstrate that hippocampal sub-regional expression of NaV1.1, NaV1.2 and NaV1.6 Na(+) channel α subunits is altered during epileptogenesis in a time and location specific way. This implies that understanding epileptogenesis has to take into account several distinct and type-specific changes in sodium channel expression.

  14. Dual-channel optical sensing platform for detection of diminazene aceturate based on thioglycolic acid-wrapped cadmium telluride/cadmium sulfide quantum dots. (United States)

    Hao, Chenxia; Zhou, Tao; Liu, Shaopu; Wang, Linlin; Huang, Bowen; Kuang, Nianxi; He, Youqiu


    A dual-channel optical sensing platform which combines the advantages of dual-wavelength overlapping resonance Rayleigh scattering (DWO-RRS) and fluorescence has been designed for the detection of diminazene aceturate (DA). It is based on the use of thioglycolic acid-wrapped CdTe/CdS quantum dots (Q-dots). In the absence of DA, the thioglycolic acid-wrapped CdTe/CdS Q-dots exhibit the high fluorescence spectrum and low RRS spectrum, so are selected to develop an easy-to-get system. In the presence of DA, the thioglycolic acid-wrapped CdTe/CdS Q-dots and DA form a complex through electrostatic interaction, which result in the RRS intensity getting enhanced significantly with new RRS peaks appearing at 317 and 397 nm; the fluorescence is powerfully quenched. Under optimum conditions, the scattering intensities of the two peaks are proportional to the concentration of DA in the range of 0.0061-3.0 μg mL(-1). The detection limits for the two single peaks are 4.1 ng mL(-1) and 3.3 ng mL(-1), while that of the DWO-RRS method is 1.8 ng mL(-1), indicating that the DWO-RRS method has high sensitivity. Besides, the fluorescence also exhibits good linear range from 0.0354 to 10.0 μg mL(-1) with a detection limit of 10.6 ng mL(-1). In addition, the system has been applied to the detection of DA in milk samples with satisfactory results.

  15. Novel self-assembled phosphonic acids monolayers applied in N-channel perylene diimide (PDI) organic field effect transistors (United States)

    Cheng, Heng; Huai, Jinyue; Cao, Li; Li, Zhefeng


    Phosphoric acid (PA) self-assembled monolayers (SAMs) have been developed for applications in organic field-effect transistors (OFETs). This efficient interface modification is helpful for semiconductor layer to form crystal thin film during vapor deposition. Results show that the PDI-i8C based OFETs with PA SAMs exhibit field-effect mobilities up to 0.014 cm2 V-1 s-1 (with ODPA as SAMs), which is over 500 times higher than the device without SAMs. Also, transistors with Naph6PA as SAMs show up to 1.5 × 10-3 cm2 V-1 s-1. By studying the morphology of semiconductor layer and SAMs surface, it is found that ODPA bilayer structure plays a key role in inducing PDI-i8C to form orderly crystal thin film.

  16. Inhibition of inward K+ channels and stomatal response by abscisic acid: an intracellular locus of phytohormone action. (United States)

    Schwartz, A; Wu, W H; Tucker, E B; Assmann, S M


    Abscisic acid (ABA), a plant hormone whose production is stimulated by water stress, reduces the apertures of stomatal pores in the leaf surface, thereby lessening transpirational water loss. It has been thought that inhibition of stomatal opening and promotion of stomatal closure by ABA are initiated by the binding of extracellular ABA to a receptor located in the guard-cell plasma membrane. However, in the present research, we employ three distinct experimental approaches to demonstrate that ABA can act from within guard cells to regulate stomatal apertures. (i) The extent to which ABA inhibits stomatal opening and promotes stomatal closure in Commelina communis L. is proportional to the extent of ABA uptake, as assayed with [3H]ABA. (ii) Direct microinjection of ABA into the cytoplasm of Commelina guard cells precipitates stomatal closure. (iii) Application of ABA to the cytosol of Vicia faba L. guard-cell protoplasts via patch-clamp techniques inhibits inward K+ currents, an effect sufficient to inhibit stomatal opening. These results demonstrate an intracellular locus of phytohormone action and imply that the search for hormone receptor proteins should be extended to include intracellular compartments.

  17. Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B

    Directory of Open Access Journals (Sweden)

    Thomas Olivier P


    Full Text Available Abstract Background Acid-sensing ion channels (ASICs have a significant role in the sensation of pain and constitute an important target for the search of new antinociceptive drugs. In this work we studied the antinociceptive properties of the BM-21 extract, obtained from the sea grass Thalassia testudinum, in chemical and thermal models of nociception in mice. The action of the BM-21 extract and the major phenolic component isolated from this extract, a sulphated flavone glycoside named thalassiolin B, was studied in the chemical nociception test and in the ASIC currents of the dorsal root ganglion (DRG neurons obtained from Wistar rats. Results Behavioral antinociceptive experiments were made on male OF-1 mice. Single oral administration of BM-21 produced a significant inhibition of chemical nociception caused by acetic acid and formalin (specifically during its second phase, and increased the reaction time in the hot plate test. Thalassiolin B reduced the licking behavior during both the phasic and tonic phases in the formalin test. It was also found that BM-21 and thalassiolin B selectively inhibited the fast desensitizing (τ Conclusions To our knowledge, this is the first report of an ASIC-current inhibitor derived of a marine-plant extract, and in a phenolic compound. The antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs. That the active components of the extract are able to cross the blood-brain barrier gives them an additional advantage for future uses as tools to study pain mechanisms with a potential therapeutic application.

  18. In vivo and ex vivo evaluation of L-type calcium channel blockers on acid beta-glucosidase in Gaucher disease mouse models.

    Directory of Open Access Journals (Sweden)

    Ying Sun

    Full Text Available Gaucher disease is a lysosomal storage disease caused by mutations in acid beta-glucosidase (GCase leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC blockers-verapamil and diltiazem-have been reported to modulate endoplasmic reticulum (ER folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT, V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50-200 mg/kg/d intraperitoneally had minor effects on increasing GCase activity in brain and liver (1.2-fold. Diltiazem treatment (10 mg/kg/d had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses.

  19. Complexion of Boric Acid with 2-Deoxy-D-glucose (DG) as a novel boron carrier for BNCT


    Akan, Zafer; Demiroglu, Hasan; Avcibasi, Ugur; Oto, Gokhan; Ozdemir, Hulya; Deniz, Sabahattin; Basak, Ali Sadi


    Objective: Boron neutron capture therapy (BNCT) is an intensive research area for cancer researchers. Especially the side effects and inabilities of conventional therapies in some cases, directs researchers to find out a new cancer therapy methods such as BNCT. One of three important problem of BNCT is targeting of boron to tumor tissue. Borono Phenyl Alanine (BPA) and Borono Sodium Borocaptate (BSH) are already using in clinical studies as boron carriers. New boron carriers are searching fo...

  20. Enhanced Control of PWR Primary Coolant Water Chemistry Using Selective Separation Systems for Recovery and Recycle of Enriched Boric Acid

    Energy Technology Data Exchange (ETDEWEB)

    Ken Czerwinski; Charels Yeamans; Don Olander; Kenneth Raymond; Norman Schroeder; Thomas Robison; Bryan Carlson; Barbara Smit; Pat Robinson


    The objective of this project is to develop systems that will allow for increased nuclear energy production through the use of enriched fuels. The developed systems will allow for the efficient and selective recover of selected isotopes that are additives to power water reactors' primary coolant chemistry for suppression of corrosion attack on reactor materials.


    Brdicka, R


    1. The rate of the saponification of iodoacetic acid in sodium hydroxide and alkaline buffer solutions yielding glycollic acid was measured by means of Heyrovský's polarographic method. 2. From the bimolecular velocity constants, increasing with the ionic strength of the solution, the Brönsted factor, F, which characterizes the primary salt effect, was calculated. 3. In the borate buffer solutions the monomolecular constants of the saponification were determined which, at values above the pH of neutralization of boric acid, show a proportionality to the concentration of hydroxyl anions. Below the pH of neutralization of boric acid, they are proportional to the concentration of borate anions.

  2. 酸敏感离子通道在类风湿关节炎中作用的研究进展%Research progress on role of acid-sensing ion channels in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    周仁鹏; 陈飞虎


    Acid-sensing ion channels ( ASICs) are cation chan-nels activated by extracellular H+, which belong to the amilo-ride-sensitive epithelial Na+ channels/degenerin ( ENaC/DEG ) superfamily. These channels are widely expressed in the central and peripheral nervous systems and have crucial biological func-tions. Recent studies have demonstrated that ASICs play an im- portant role in the pathogenesis of rheumatoid arthritis. This re-view concerns the cell biological characteristics of ASICs as well as its role in inflammation, pain, cartilage destruction and other aspects in rheumatoid arthritis.%酸敏感离子通道( acid-sensing ion channels, ASICs)是一类胞外H+激活的阳离子通道,属于阿米洛利敏感的上皮钠通道/退变素( epithelial Na+ channels/ degenerin, ENaC/DEG)超家族中的一员,该通道广泛分布在周围和中枢神经系统中,并且具有重要的生物学功能。近来研究表明,ASICs在类风湿关节炎发病过程中发挥着重要作用。该文对ASICs的细胞生物学特点以及ASICs在类风湿关节炎中对炎症、疼痛和软骨损伤等方面的作用进行综述。

  3. Chemistry in Microfluidic Channels (United States)

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.


    General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

  4. Growth inhibition of fungus Phycomyces blakesleeanus by anion channel inhibitors anthracene-9-carboxylic and niflumic acid attained through decrease in cellular respiration and energy metabolites. (United States)

    Stanić, Marina; Križak, Strahinja; Jovanović, Mirna; Pajić, Tanja; Ćirić, Ana; Žižić, Milan; Zakrzewska, Joanna; Cvetić Antić, Tijana; Todorović, Nataša; Živić, Miroslav


    Increasing resistance of fungal strains to known fungicides has prompted identification of new candidates for fungicides among substances previously used for other purposes. We have tested the effects of known anion channel inhibitors anthracene-9-carboxylic (A9C) and niflumic acid (NFA) on growth, energy metabolism and anionic current of mycelium of fungus Phycomyces blakesleeanus. Both inhibitors significantly decreased growth and respiration of mycelium, but complete inhibition was only achieved by 100 or 500 µM NFA, for growth and respiration, respectively. A9C had no effect on respiration of human NCI-H460 cell line, and very little effect on cucumber root sprout clippings, which nominates this inhibitor for further investigation as a potential new fungicide. Effects of A9C and NFA on respiration of isolated mitochondria of P. blakesleeanus were significantly smaller, which indicates that their inhibitory effect on respiration of mycelium is indirect. NMR spectroscopy showed that both A9C and NFA decrease the levels of ATP and polyphosphates in the mycelium of P. blakesleanus, but only A9C caused intracellular acidification. Outwardly rectifying, fast inactivating instantaneous anionic current (ORIC) was also reduced to 33±5% and 21±3% of its pre-treatment size by A9C and NFA, respectively, but only in the absence of ATP. It can be assumed from our results that the regulation of ORIC is tightly linked to cellular energy metabolism in P. blakesleeanus, and the decrease in ATP and polyphosphate levels could be a direct cause of growth inhibition.

  5. Local anesthetic interaction with human ether-a-go-go-related gene (HERG) channels: role of aromatic amino acids Y652 and F656

    DEFF Research Database (Denmark)

    Siebrands, Cornelia C; Schmitt, Nicole; Friederich, Patrick


    : wild-type IC50 = 22 +/- 2 microm, n = 38; Y652A IC50 = 95 +/- 5 microm, n = 31). The mutations resulted in a change of the stereoselectivity of HERG channel block by ropivacaine. The potency of the local anesthetics to inhibit wild-type and mutant channels correlated with the lipophilicity of the drug...

  6. Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy

    NARCIS (Netherlands)

    Qiao, X.; Werkman, T.R.; Gorter, J.A.; Wadman, W.J.; van Vliet, E.A.


    Voltage-gated Na(+) channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na(+) channel α subunits: NaV1.1, NaV1.2 and NaV1.6 during epileptogenesis

  7. 乳酸提取鮰鱼皮胶原蛋白工艺优化%Optimization of Conditions for Collagen Extraction with Lactic Acid from Channel Catfish (Ictalurus punctatus) Skin

    Institute of Scientific and Technical Information of China (English)

    宫子慧; 林琳; 孟昌伟; 叶应旺; 姜绍通; 陆剑锋


    This study was undertaken to optimize the acidic extraction of collagen from channel catfish (lctalurus punctatus) skin. Lactic acid was found to be a better solvent for extracting collagen from channel catfish skin than formic acid, acetic acid, citric acid and hydrochloric acid. Further, three process conditions affecting the extraction rate of collagen with lactic acid, such as pH value, solid-to-liquid ratio and extraction time, were optimized by one-factor-at-a-time method and Box-Benhnken experimental design combined with response surface methodology. The results indicated that the optimal conditions for collagen extraction were pH 2.3, solid-to-liquid ratio 1:60 (g/mL) and extraction time 46 h, under which, an extraction rate of 46.28% was obtained.%以斑点叉尾鮰鱼皮为实验材料,选用乳酸从中提取胶原蛋白。通过单因素试验分别考察pH值、料液比和时间3个参数对胶原蛋白提取率的影响,在此基础上,利用Box—Benhnken中心组合试验设计和响应面分析法对乳酸提取阚鱼皮胶原蛋白条件进行优化。结果表明,乳酸提取鮰鱼皮胶原蛋白的优化工艺为pH2.3、料液比1:60(g/mL)、时间46h,在此条件下鮰鱼皮胶原蛋白的提取率达到46.28%。

  8. Chloride channels in stroke

    Institute of Scientific and Technical Information of China (English)

    Ya-ping ZHANG; Hao ZHANG; Dayue Darrel DUAN


    Vascular remodeling of cerebral arterioles,including proliferation,migration,and apoptosis of vascular smooth muscle cells (VSMCs),is the major cause of changes in the cross-sectional area and diameter of the arteries and sudden interruption of blood flow or hemorrhage in the brain,ie,stroke.Accumulating evidence strongly supports an important role for chloride (Clˉ) channels in vascular remodeling and stroke.At least three Clˉ channel genes are expressed in VSMCs:1) the TMEM16A (or Ano1),which may encode the calcium-activated Clˉ channels (CACCs); 2) the CLC-3 Clˉ channel and Clˉ/H+ antiporter,which is closely related to the volume-regulated Clˉ channels (VRCCs); and 3) the cystic fibrosis transmembrane conductance regulator (CFTR),which encodes the PKA-and PKC-activated Clˉ channels.Activation of the CACCs by agonist-induced increase in intracellular Ca2+ causes membrane depolarization,vasoconstriction,and inhibition of VSMC proliferation.Activation of VRCCs by cell volume increase or membrane stretch promotes the production of reactive oxygen species,induces proliferation and inhibits apoptosis of VSMCs.Activation of CFTR inhibits oxidative stress and may prevent the development of hypertension.In addition,Clˉ current mediated by gammaaminobutyric acid (GABA) receptor has also been implicated a role in ischemic neuron death.This review focuses on the functional roles of Clˉ channels in the development of stroke and provides a perspective on the future directions for research and the potential to develop Clˉ channels as new targets for the prevention and treatment of stroke.

  9. Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide. (United States)

    Park, Ki Duk; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Ripsch, Matthew S; White, Fletcher A; Khanna, Rajesh; Kohn, Harold


    The functionalized amino acid, lacosamide ((R)-2), and the α-aminoamide, safinamide ((S)-3), are neurological agents that have been extensively investigated and have displayed potent anticonvulsant activities in seizure models. Both compounds have been reported to modulate voltage-gated sodium channel activity. We have prepared a series of chimeric compounds, (R)-7-(R)-10, by merging key structural units in these two clinical agents, and then compared their activities with (R)-2 and (S)-3. Compounds were assessed for their ability to alter sodium channel kinetics for inactivation, frequency (use)-dependence, and steady-state activation and fast inactivation. We report that chimeric compounds (R)-7-(R)-10 in catecholamine A-differentiated (CAD) cells and embryonic rat cortical neurons robustly enhanced sodium channel inactivation at concentrations far lower than those required for (R)-2 and (S)-3, and that (R)-9 and (R)-10, unlike (R)-2 and (S)-3, produce sodium channel frequency (use)-dependence at low micromolar concentrations. We further show that (R)-7-(R)-10 displayed excellent anticonvulsant activities and pain-attenuating properties in the animal formalin model. Of these compounds, only (R)-7 reversed mechanical hypersensitivity in the tibial-nerve injury model for neuropathic pain in rats.

  10. Direct solid surface fluorescence spectroscopy of standard chemicals and humic acid in ternary system (United States)

    Mounier, S.; Nicolodelli, G.; Redon, R.; Milori, D. M. B. P.


    The front face fluorescence spectroscopy is often used to quantify chemicals in well-known matrices as it is a rapid and powerful technique, with no sample preparation. However it was not used to investigate extracted organic matter like humic substances. This work aims to fully investigate for the first time front face fluorescence spectroscopy response of a ternary system including boric acid, tryptophan and humic substances, and two binaries system containing quinine sulfate or humic substance in boric acid. Pure chemicals, boric acid, tryptophan, quinine sulfate and humic acid were mixed together in solid pellet at different contents from 0 to 100% in mass. The measurement of excitation emission matrix of fluorescence (3D fluorescence) and laser induced fluorescence were then done in the front face mode. Fluorescence matrices were decomposed using the CP/PARAFAC tools after scattering treatments. Results show that for 3D fluorescence there is no specific component for tryptophan and quinine sulfate, and that humic substances lead to a strong extinction effect for mixture containing quinine sulfate. Laser induced fluorescence gives a very good but non-specific related response for both quinine sulfate and tryptophan. No humic substances fluorescence response was found, but extinction effect is observed as for 3D fluorescence. This effect is stronger for quinine sulfate than for tryptophan. These responses were modeled using a simple absorbance versus emission model.

  11. Direct solid surface fluorescence spectroscopy of standard chemicals and humic acid in ternary system. (United States)

    Mounier, S; Nicolodelli, G; Redon, R; Milori, D M B P


    The front face fluorescence spectroscopy is often used to quantify chemicals in well-known matrices as it is a rapid and powerful technique, with no sample preparation. However it was not used to investigate extracted organic matter like humic substances. This work aims to fully investigate for the first time front face fluorescence spectroscopy response of a ternary system including boric acid, tryptophan and humic substances, and two binaries system containing quinine sulfate or humic substance in boric acid. Pure chemicals, boric acid, tryptophan, quinine sulfate and humic acid were mixed together in solid pellet at different contents from 0 to 100% in mass. The measurement of excitation emission matrix of fluorescence (3D fluorescence) and laser induced fluorescence were then done in the front face mode. Fluorescence matrices were decomposed using the CP/PARAFAC tools after scattering treatments. Results show that for 3D fluorescence there is no specific component for tryptophan and quinine sulfate, and that humic substances lead to a strong extinction effect for mixture containing quinine sulfate. Laser induced fluorescence gives a very good but non-specific related response for both quinine sulfate and tryptophan. No humic substances fluorescence response was found, but extinction effect is observed as for 3D fluorescence. This effect is stronger for quinine sulfate than for tryptophan. These responses were modeled using a simple absorbance versus emission model.

  12. Mechanosensitive Channels (United States)

    Martinac, Boris

    Living cells are exposed to a variety of mechanical stimuli acting throughout the biosphere. The range of the stimuli extends from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. Cellular membranes present a major target for these stimuli. To detect mechanical forces acting upon them cell membranes are equipped with mechanosensitive (MS) ion channels. Functioning as molecular mechanoelectrical transducers of mechanical forces into electrical and/or chemical intracellular signals these channels play a critical role in the physiology of mechanotransduction. Studies of prokaryotic MS channels and recent work on MS channels of eukaryotes have significantly increased our understanding of their gating mechanism, physiological functions, and evolutionary origins as well as their role in the pathology of disease.

  13. Structural and functional changes in a synthetic S5 segment of KvLQT1 channel as a result of a conserved amino acid substitution that occurs in LQT1 syndrome of human. (United States)

    Verma, Richa; Ghosh, Jimut Kanti


    Mutations in various voltage gated cardiac ion channels are the cause of different forms of long QT syndrome (LQTS), which is an inherited arrhythmic disorder marked as a prolonged QT interval on electrocardiogram. Of these LQTS1 is associated with mutations in the gene encoding KCNQ1 (KvLQT1) channel. One responsible mutation, G269S, in the S5 segment of KvLQT1, that affects the proper expression and function of channel protein leads to LQTS1. Our objective was to study how G269S mutation interferes with the structure and function of a synthetic S5 segment of KvLQT1 channel. One wild type 22-residue peptide and another mutant peptide of the same length with G269S mutation, derived from the S5 segment were synthesized and labeled with fluorescent probes. The mutant peptide exhibited lower affinity towards phospholipid vesicles as compared to the wild type peptide and showed impaired assembly and localization onto the lipid vesicles as evidenced by membrane-binding, energy transfer and proteolytic cleavage experiments. Loss in the helical content of S5 mutant peptide in membrane-mimetic environments was observed. Furthermore, it was observed that G269S mutation significantly inhibited the ability of S5 peptide to permeabilize the lipid vesicles. The present studies show the basis of change in function of the selected S5 segment as a result of G269S mutation which is associated with LQT1 syndrome. We speculate that the structural and functional changes related to the glycine to serine amino acid substitution in the S5 segment may also influence the activity of the whole KvLQT1 channel.

  14. Brands & Channels

    Institute of Scientific and Technical Information of China (English)

    Alice Yang


    @@ "Brands" and "Channels" are the two most important things in Ku-Hai Chen's eyes when doing business with Main-land China. Ku-Hai Chen, Executive Director of the International Trade Institute of Taiwan External Trade Development Council (TAITRA), flies frequently between Chinese Taipei and Mainland China, and was in Beijing earlier this month for his seminar.

  15. Positron Channeling

    CERN Document Server

    Badikyan, Karen


    The possibility of channeling the low-energy relativistic positrons around separate crystallographic axes with coaxial symmetry of negative ions in some types of crystals is shown. The process of annihilation of positrons with electrons of medium was studied in detail.

  16. Stimulation of large-conductance calcium-activated potassium channels inhibits neurogenic contraction of human bladder from patients with urinary symptoms and reverses acetic acid-induced bladder hyperactivity in rats. (United States)

    La Fuente, José M; Fernández, Argentina; Cuevas, Pedro; González-Corrochano, Rocío; Chen, Mao Xiang; Angulo, Javier


    We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats. Bladder specimens were obtained from organ donors and from men with benign prostatic hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS) and carbachol (CCh) were evaluated in isolated bladder strips. in vivo cystometric recordings were obtained in anesthetized rats under control and acetic acid-induced hyperactive conditions. Neurogenic contractions of human bladder were potentiated by blockade of BK and small-conductance calcium-activated potassium channels (SK) but were unaffected by the blockade of intermediate calcium-activated potassium channels (IK). EFS-induced contractions were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with NS309 (3µM). CCh-induced contractions were not modified by blockade or stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3µM) inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions of bladders from BPH patients were less sensitive to BK inhibition and more sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5mg/kg; i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or heart rate. BK stimulation specifically inhibits neurogenic contractions in patients with urinary symptoms and relieves bladder hyperactivity in vivo without compromising bladder contractile capacity or cardiovascular safety, supporting its potential therapeutic use for relieving bladder overactivity.

  17. 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))


    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.

  18. Anticonvulsant effects of N-arachidonoyl-serotonin, a dual fatty acid amide hydrolase enzyme and transient receptor potential vanilloid type-1 (TRPV1) channel blocker, on experimental seizures: the roles of cannabinoid CB1 receptors and TRPV1 channels. (United States)

    Vilela, Luciano R; Medeiros, Daniel C; de Oliveira, Antonio Carlos P; Moraes, Marcio F; Moreira, Fabricio A


    Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH enzyme, has anticonvulsant effects, which are mediated by CB1 receptors. Anandamide, however, also activates TRPV1 channels, generally with an opposite outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV1 blockade with N-arachidonoyl-serotonin (AA-5-HT) would be efficacious in inhibiting pentylenetetrazole (PTZ)-induced seizures in mice. We also investigated the contribution of CB1 activation and TRPV1 blockade to the overt effect of AA-5-HT. In the first experiment, injection of AA-5-HT (0.3-3.0 mg/kg) delayed the onset and reduced the duration of PTZ (60 mg)-induced seizures in mice. These effects were reversed by pre-treatment with the CB1 antagonist, AM251 (1.0-3.0 mg/kg). Finally, we observed that administration of the selective TRPV1 antagonist, SB366791 (0.1-1 mg/kg), did not entirely mimic AA-5-HT effects. In conclusion, AA-5-HT alleviates seizures in mice, an effect inhibited by CB1 antagonism, but not completely mimicked by TRPV1 blockage, indicating that the overall effect of AA-5-HT seems to depend mainly on CB1 receptors. This may represent a new strategy for the development of drugs against seizures, epilepsies and related syndromes.

  19. Ion channels in inflammation. (United States)

    Eisenhut, Michael; Wallace, Helen


    Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

  20. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

    M.G. Dekimpe (Marnik); B. Skiera (Bernd)


    textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key compon

  1. Sea Anemone Toxins Affecting Potassium Channels (United States)

    Diochot, Sylvie; Lazdunski, Michel

    The great diversity of K+ channels and their wide distribution in many tissues are associated with important functions in cardiac and neuronal excitability that are now better understood thanks to the discovery of animal toxins. During the past few decades, sea anemones have provided a variety of toxins acting on voltage-sensitive sodium and, more recently, potassium channels. Currently there are three major structural groups of sea anemone K+ channel (SAK) toxins that have been characterized. Radioligand binding and electrophysiological experiments revealed that each group contains peptides displaying selective activities for different subfamilies of K+ channels. Short (35-37 amino acids) peptides in the group I display pore blocking effects on Kv1 channels. Molecular interactions of SAK-I toxins, important for activity and binding on Kv1 channels, implicate a spot of three conserved amino acid residues (Ser, Lys, Tyr) surrounded by other less conserved residues. Long (58-59 amino acids) SAK-II peptides display both enzymatic and K+ channel inhibitory activities. Medium size (42-43 amino acid) SAK-III peptides are gating modifiers which interact either with cardiac HERG or Kv3 channels by altering their voltage-dependent properties. SAK-III toxins bind to the S3C region in the outer vestibule of Kv channels. Sea anemones have proven to be a rich source of pharmacological tools, and some of the SAK toxins are now useful drugs for the diagnosis and treatment of autoimmune diseases.

  2. Nonlinear channelizer (United States)

    In, Visarath; Longhini, Patrick; Kho, Andy; Neff, Joseph D.; Leung, Daniel; Liu, Norman; Meadows, Brian K.; Gordon, Frank; Bulsara, Adi R.; Palacios, Antonio


    The nonlinear channelizer is an integrated circuit made up of large parallel arrays of analog nonlinear oscillators, which, collectively, serve as a broad-spectrum analyzer with the ability to receive complex signals containing multiple frequencies and instantaneously lock-on or respond to a received signal in a few oscillation cycles. The concept is based on the generation of internal oscillations in coupled nonlinear systems that do not normally oscillate in the absence of coupling. In particular, the system consists of unidirectionally coupled bistable nonlinear elements, where the frequency and other dynamical characteristics of the emergent oscillations depend on the system's internal parameters and the received signal. These properties and characteristics are being employed to develop a system capable of locking onto any arbitrary input radio frequency signal. The system is efficient by eliminating the need for high-speed, high-accuracy analog-to-digital converters, and compact by making use of nonlinear coupled systems to act as a channelizer (frequency binning and channeling), a low noise amplifier, and a frequency down-converter in a single step which, in turn, will reduce the size, weight, power, and cost of the entire communication system. This paper covers the theory, numerical simulations, and some engineering details that validate the concept at the frequency band of 1-4 GHz.

  3. Circulating insulin stimulates fatty acid retention in white adipose tissue via KATP channel activation in the central nervous System only in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Geerling, J.J.; Guigas, B.; Hoek, A.M. van den; Parlevliet, E.T.; Ouwens, D.M.; Pijl, H.; Voshol, P.J.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.


    Insulin signaling in the central nervous system (CNS) is required for the inhibitory effect of insulin on glucose production. Our aim was to determine whether the CNS is also involved in the stimulatory effect of circulating insulin on the tissue-specific retention of fatty acid (FA) from plasma. In

  4. Poly(ADP-Ribose)Polymerase 1 (PARP-1) Activation and Ca(2+) Permeable α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) Channels in Post-Ischemic Brain Damage: New Therapeutic Opportunities? (United States)

    Gerace, Elisabetta; Pellegrini-Giampietro, Domenico E; Moroni, Flavio; Mannaioni, Guido


    A significant number of laboratories observed that poly (ADP-ribose) polymerase (PARP) inhibitors, administered a few hours after ischemic or traumatic brain injury, may drastically reduce the subsequent neurological damage. It has also been shown that PARP inhibitors, administered for 24 hours to rats with permanent middle cerebral artery occlusion (MCAO), may reduce the number of dying neurons for a long period after surgery, thus suggesting that these agents could reduce the delayed brain damage and the neurological and cognitive impairment (dementia) frequently observed a few months after a stroke. In organotypic hippocampal slices exposed to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG), an alkylating agent able to activate PARP, a selective and delayed degeneration of the CA1 pyramidal cells which was anatomically similar to that observed after a short period of oxygen and glucose deprivation (OGD) has been described. Biochemical and electrophysiological approaches showed that MNNG exposure caused an increased expression and function of the calcium permeable α-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) channels in the CA1 but not in the CA3 hippocampal region. PARP inhibitors prevented this increase and reduced CA1 cell death. The AMPA receptor antagonist 2,3-dihydroxy-6- nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione or the selective Ca(2+) permeable AMPA channel blocker 1-Naphthyl acetyl spermine (NASPM), also reduced the MNNG-induced CA1 pyramidal cell death. Since activation of PARP-1 facilitate the expression of Ca(2+) permeable channels and the subsequent delayed cell death, PARP inhibitors administered a few hours after a stroke may not only reduce the early post-ischemic brain damage but also the late neuronal death frequently occurring after severe stroke.

  5. Cavity residue leucine 95 and channel residues glutamine 204, aspartic acid 211, and phenylalanine 269 of toluene o-xylene monooxygenase influence catalysis. (United States)

    Kurt, Cansu; Sönmez, Burcu; Vardar, Nurcan; Yanık-Yıldırım, K Cansu; Vardar-Schara, Gönül


    Structural analysis of toluene-o-xylene monooxygenase (ToMO) hydroxylase revealed the presence of three hydrophobic cavities, a channel, and a pore leading from the protein surface to the active site. Here, saturation mutagenesis was used to investigate the catalytic roles of alpha-subunit (TouA) second cavity residue L95 and TouA channel residues Q204, D211, and F269. By testing the substrates toluene, phenol, nitrobenzene, and/or naphthalene, these positions were found to influence the catalytic activity of ToMO. Several regiospecific variants were identified from TouA positions Q204, F269, and L95. For example, TouA variant Q204H had the regiospecificity of nitrobenzene changed significantly from 30 to 61 % p-nitrophenol. Interestingly, a combination of mutations at Q204H and A106V altered the regiospecificity of nitrobenzene back to 27 % p-nitrophenol. TouA variants F269Y, F269P, Q204E, and L95D improved the meta-hydroxylating capability of nitrobenzene by producing 87, 85, 82, and 77 % m-nitrophenol, respectively. For naphthalene oxidation, TouA variants F269V, Q204A, Q204S/S222N, and F269T had the regiospecificity changed from 16 to 9, 10, 23, and 25 % 2-naphthol, respectively. Here, two additional TouA residues, S222 and A106, were also identified that may have important roles in catalysis. Most of the isolated variants from D211 remained active, whereas having a hydrophobic residue at this position appeared to diminish the catalytic activity toward naphthalene. The mutational effects on the ToMO regiospecificity described here suggest that it is possible to further fine tune and engineer the reactivity of multicomponent diiron monooxygenases toward different substrates at positions that are relatively distant from the active site.

  6. Microwave-assisted reaction of peptide formation by amino acid with phosphate: Exploration of the most possible channels for the origin of life

    Institute of Scientific and Technical Information of China (English)

    HU Rong; TIAN Jinping; YIN Yingwu


    Microwave-assisted reaction of peptide formation by amino acids with phosphate was studied. The results showed that the products were a mixture of peptides containing dipeptide, octapeptides and cyclic peptides, which could be obtained in a short time. Polyphosphate was also produced synchronously by the intermolecular condensation of phosphate. The polymerization degree reached 99% (pyrophosphate 64%, trimetaphosphate 35%) after 2 h at 200℃ under microwave irradiation. The intermediates of the mixed anhydrides formed by the intermolecular condensation of phosphates and glycin were determined by ESI-MS. Peptides were also produced by the reaction of amino acids with trimetaphosphate in aqueous solution. The conversion degree of valine reached 46.5% even at room temperature. The cyclic process of peptide formation and phosphate polymerization, regeneration and utilization in amino acids-phosphate system under microwave irradiation was detected and proved. Peptides could be continually formed only by inputting energy into this system. The above recycle may be the most possible process for primitive peptide formation in the origin of life.

  7. Responsiveness of voltage-gated calcium channels in SH-SY5Y human neuroblastoma cells on quasi-three-dimensional micropatterns formed with poly (l-lactic acid

    Directory of Open Access Journals (Sweden)

    Kisaalita WS


    Full Text Available Ze-Zhi Wu,1 Zheng-Wei Wang,1 Li-Guang Zhang,1 Zhi-Xing An,1 Dong-Huo Zhong,1 Qi-Ping Huang,1 Mei-Rong Luo,1 Yan-Jian Liao,1 Liang Jin,1 Chen-Zhong Li,2 William S Kisaalita31Key Laboratory of Biorheological Science and Technology of the State Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China; 2Nanobioengineering/Bioelectronics Laboratory, Department of Biomedical Engineering, Florida International University, Miami, Florida, 3Cellular Bioengineering Laboratory, College of Engineering, University of Georgia, Athens, Georgia, USAIntroduction: In this study, quasi-three-dimensional (3D microwell patterns were fabricated with poly (l-lactic acid for the development of cell-based assays, targeting voltage-gated calcium channels (VGCCs.Methods and materials: SH-SY5Y human neuroblastoma cells were interfaced with the microwell patterns and found to grow as two dimensional (2D, 3D, and near two dimensional (N2D, categorized on the basis of the cells’ location in the pattern. The capability of the microwell patterns to support 3D cell growth was evaluated in terms of the percentage of the cells in each growth category. Cell spreading was analyzed in terms of projection areas under light microscopy. SH-SY5Y cells’ VGCC responsiveness was evaluated with confocal microscopy and a calcium fluorescent indicator, Calcium GreenTM-1. The expression of L-type calcium channels was evaluated using immunofluorescence staining with DM-BODIPY.Results: It was found that cells within the microwells, either N2D or 3D, showed more rounded shapes and less projection areas than 2D cells on flat poly (l-lactic acid substrates. Also, cells in microwells showed a significantly lower VGCC responsiveness than cells on flat substrates, in terms of both response magnitudes and percentages of responsive cells, upon depolarization with 50 mM K+. This lower VGCC responsiveness could not be explained by the difference in

  8. The selectivity of conantokin-G for ion channel inhibition of NR2B subunit-containing NMDA receptors is regulated by amino acid residues in the S2 region of NR2B. (United States)

    Sheng, Zhenyu; Liang, Zhong; Geiger, James H; Prorok, Mary; Castellino, Francis J


    The conantokins are short, naturally occurring peptides that inhibit ion flow through N-methyl-d-aspartate receptor (NMDAR) channels. One member of this peptide family, conantokin-G (con-G), shows high selectivity for antagonism of NR2B-containing NMDAR channels, whereas other known conantokins are less selective inhibitors with regard to the nature of the NR2 subunit of the NMDAR complex. In order to define the molecular determinants of NR2B that govern con-G selectivity, we evaluated the ability of con-G to inhibit NMDAR ion channels expressed in human embryonic kidney (HEK)293 cells transfected with NR1, in combination with various NR2A/2B chimeras and point mutants, by electrophysiology using cells voltage-clamped in the whole-cell configuration. We found that a variant of the con-G-insensitive subunit, NR2A, in which the 158 residues comprising the S2 peptide segment (E(657)-I(814)) were replaced by the corresponding S2 region of NR2B (E(658)-I(815)), results in receptors that are highly sensitive to inhibition by con-G. Of the 22 amino acids that are different between the NR2A-S2 and the NR2B-S2 regions, exchange of one of these, M(739) of NR2B for the equivalent K(738) of NR2A, was sufficient to completely import the inhibitory activity of con-G into NR1b/NR2A-containing NMDARs. Some reinforcement of this effect was found by substitution of a second amino acid, K(755) of NR2B for Y(754) of NR2A. The discovery of the molecular determinants of NR2B selectivity with con-G has implications for the design of subunit-selective neurobiological probes and drug therapies, in addition to advancing our understanding of NR2B- versus NR2A-mediated neurological processes.

  9. Development and Production of Boric-Magnesium-Zinc Nitro-Compound Fertilizer with 100 kt/a Compound Fertilizer Production Unit%采用100 kt/a 复合肥生产装置开发生产硼镁锌硝基复合肥

    Institute of Scientific and Technical Information of China (English)



    Using phosphoric acid, ammonium nitrate solution, gaseous ammonia, sulfuric acid, solid potassium sulfate, borax, magnesium sulfate and zinc sulfate as raw materials, the new type of functional boric-magnesium-zinc nitro-compound fertilizer is produced with revamped 100 kt /a compound fertilizer production unit.The production conditions and technical features of the new functional compound fertilizer are introduced, and matters needing attention in production are summarized.%采用磷酸、硝酸铵溶液、气氨、硫酸、固体硫酸钾、硼砂、硫酸镁、硫酸锌为原料,在100 kt/a 复合肥生产装置上改造生产新型功能型硼镁锌硝基复合肥。介绍了该新型功能型复合肥料的生产情况、技术特点,并对生产中应注意的问题进行总结。

  10. 柠檬酸对腐蚀铝箔高压阳极氧化膜微观结构与电化学性能的影响%Effect of citric acid on microstructure and electrochemical characteristics of high voltage anodized alumina film formed on etched Al Foils

    Institute of Scientific and Technical Information of China (English)

    班朝磊; 何业东; 邵鑫


    将高压铝电解电容器用腐蚀铝箔与沸水反应,然后再在硼酸溶液或硼酸-柠檬酸混合酸溶液中进行530 V高压阳极氧化制得耐压薄膜,应用透射电镜(TEM)、X射线衍射(XRD)研究不同电解液所形成的高压阳极氧化膜的微观结构与结晶程度,利用电化学交流阻抗(EIS)、LCR数字电桥与小电流充电测试阳极氧化膜的电化学性能.结果表明:高压阳极氧化膜具有明显层状结构,内层结晶程度较高、外层结晶程度较低;与单纯硼酸溶液所形成的氧化膜相比,混合酸液所形成的阳极氧化膜的外层结晶程度与晶粒平均尺寸较大,抗电场强度与比电容均比较高,但相变使得氧化膜外层微观缺陷密度增多,氧化膜比电阻与耐电压值有所降低.%Aluminum capacitor foils with a tunnel etch structure were reacted with boiling water and then anodized at 530 V in boric acid solution or boric acid+citric acid mixed solution. The microstructure and crystallinity of the resulting anodized film were examined by TEM and XRD. The special capacitance, resistance and withstanding voltage of the film were explored with electrochemical impedance spectroscopy (EIS), LCR meter and small-current charging. The results show that the high voltage anodized oxide film consists of an inner layer with high crystallinity and an outer layer with low crystallinity. However, the crystallinity of the film formed in boric acid+citric acid mixed solution is higher than that of the film formed in only boric acid solution, leading to an increase in film's field strength and special capacitance. Meanwhile, there are more defects from phase transformation in the out layer of the film formed in boric acid+citric acid mixed solution than in that of film formed in only boric acid solution, leading to a decrease in film's resistance and withstanding voltage.

  11. Effects of arachidonic acid on L-type calcium channel and its mechanism of antiarrhythmia%花生四烯酸对L-型钙通道的作用及其抗心律失常机制

    Institute of Scientific and Technical Information of China (English)

    刘承云; 陈桂青; 耿小晶; 陈心; 万晶晶


    目的 研究花生四烯酸(arachidonic acid,AA)对家兔单个心室肌细胞L-广型钙通道的作用及其抗心律失常作用的机制.方法 采用酶解法分离得到家兔单个心室肌细胞,全细胞膜片钳技术记录单个心室肌细胞L-型钙电流(L-type calcium current,Ica-L),用累积给药的方法在灌流液中加入不同浓度的AA,观察给药前后L-型钙电流的变化,统计学方法采用单因素方差分析.结果 不同浓度的从均能明显抑制心室肌细胞,Ica-L.3 μmol/L,μmol/L,20,μmol/L的AA使Ica-L峰电流密度从(10.79±0.93)pA/pF分别减少剑(8.99 ±0.43)pA/pF、(7.60 ±0.35)pA/pF和(5.60±0.30)pA/pF(n=7,P<0.05),经冲洗后Ica-L可部分恢复,并且AA可使Ica-L的I-V关系曲线上移,其形状和峰值电压保持不变;20 μmol/L的AA使Ica-L失活曲线左移,失活后恢复时间明显延长,但对激活曲线无明显影响.结论 花生四烯酸可通过加快L-型钙通道失活,延长其失活后的恢复过程而减少细胞外钙离子的内流,延长有效不应期,从而发挥抗心律失常作用.%Objective To study the influence of arachidonic acid (AA) on L-type calcium channel in rabbits sin-gle cardiomyocyte and its mechanism of antiarrhythmia. Method The single ventricular cardiomyocyte was isolat-ed by using enzyme dispersion method and whole-cell clamp-patch technique was used to record L-type calcium current.All data were analyzed using ANOVA. Results AA inhibited Ica-L in a concentration-dependent manner. The application of 3 μmol/L, 10 μmol/L and 20 μmol/L arachidonic acid reduced the density of peak Ica-L from (10.79±0.93)pA/pF to (8.99±0.43)pA/pF to (7.60±0.35)pA/pF and to (5.60±0.30)pA/pF, respctive-ly (n=7, P<0. O1 ). The Ica-Lpartially resumed after washout. The AA up-shifted the I-V curves of Ica-L without changes of their shape,peak and reverse potentials. The AA also markedly shifted the inactivation curve to left, and prolonged the recorvery time from inactivation

  12. Pharmacokinetics, metabolism and excretion of [(14)C]-lanicemine (AZD6765), a novel low-trapping N-methyl-d-aspartic acid receptor channel blocker, in healthy subjects. (United States)

    Guo, Jian; Zhou, Diansong; Grimm, Scott W; Bui, Khanh H


    1.(1S)-1-phenyl-2-(pyridin-2-yl)ethanamine (lanicemine; AZD6765) is a low-trapping N-methyl-d-aspartate (NMDA) channel blocker that has been studied as an adjunctive treatment in major depressive disorder. The metabolism and disposition of lanicemine was determined in six healthy male subjects after a single intravenous infusion dose of 150 mg [(14)C]-lanicemine. 2.Blood, urine and feces were collected from all subjects. The ratios of Cmax and AUC(0-∞) of lanicemine to plasma total radioactivity were 84 and 66%, respectively, indicating that lanicemine was the major circulating component with T1/2 at 16 h. The plasma clearance of lanicemine was 8.3 L/h, revealing that lanicemine is a low-clearance compound. The mean recovery of radioactivity from urine was 93.8% of radioactive dose. 3.In urine samples, 10 metabolites of lanicemine were identified. Among which, an O-glucuronide conjugate (M1) was the most abundant metabolite (∼11% of the dose in excreta). In plasma, the circulatory metabolites were identified as a para-hydroxylated metabolite (M1), an O-glucuronide (M2), an N-carbamoyl glucuronide (M3) and an N-acetylated metabolite (M6). The average amount of each of metabolite was less than 4% of total radioactivity detected in plasma or urine. 4.In conclusion, lanicemine is a low-clearance compound. The unchanged drug and metabolites are predominantly eliminated via urinary excretion.

  13. Lubiprostone: a chloride channel activator. (United States)

    Lacy, Brian E; Levy, L Campbell


    In January 2006 the Food and Drug Administration approved lubiprostone for the treatment of chronic constipation in men and women aged 18 and over. Lubiprostone is categorized as a prostone, a bicyclic fatty acid metabolite of prostaglandin E1. Lubiprostone activates a specific chloride channel (ClC-2) in the gastrointestinal (GI) tract to enhance intestinal fluid secretion, which increases GI transit and improves symptoms of constipation. This article reviews the role of chloride channels in the GI tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses clinically important data on this new medication.

  14. Marine Toxins Targeting Ion Channels

    Directory of Open Access Journals (Sweden)

    Hugo R. Arias


    Full Text Available Abstract: This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs, as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs, are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV, Ca2+ (CaV, and K+ (KV channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR, and the ATP-activated (P2XnR receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+, whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−. In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers of ion channel functions to treat or to alleviate a specific

  15. The Origins of Transmembrane Ion Channels (United States)

    Pohorille, Andrew; Wilson, Michael A.


    Even though membrane proteins that mediate transport of ions and small molecules across cell walls are among the largest and least understood biopolymers in contemporary cells, it is still possible to shed light on their origins and early evolution. The central observation is that transmembrane portions of most ion channels are simply bundles of -helices. By combining results of experimental and computer simulation studies on synthetic models and natural channels, mostly of non-genomic origin, we show that the emergence of -helical channels was protobiologically plausible, and did not require highly specific amino acid sequences. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. Specifically, we explain how the antiamoebin channels, which are made of identical helices, 16 amino acids in length, achieve efficiency comparable to that of highly evolved channels. We further show that antiamoebin channels are extremely flexible, compared to modern, genetically coded channels. On the basis of our results, we propose that channels evolved further towards high structural complexity because they needed to acquire stable rigid structures and mechanisms for precise regulation rather than improve efficiency. In general, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

  16. A unique iridium(III) complex-based chemosensor for multi-signal detection and multi-channel imaging of hypochlorous acid in liver injury. (United States)

    Zhang, Feiyue; Liang, Xiaowen; Zhang, Wenzhu; Wang, Yong-Lei; Wang, Haolu; Mohammed, Yousuf H; Song, Bo; Zhang, Run; Yuan, Jingli


    Although hypochlorous acid (HOCl) has long been associated with a number of inflammatory diseases in mammalian bodies, the functions of HOCl in specific organs at abnormal conditions, such as liver injury, remain unclear due to its high reactivity and the lack of effective methods for its detection. Herein, a unique Ir(III) complex-based chemosensor, Ir-Fc, was developed for highly sensitive and selective detection of HOCl. Ir-Fc was designed by incorporating a ferrocene (Fc) quencher to a Ir(III) complex through a HOCl-responsive linker. In the presence of HOCl, the fast cleavage of Fc moiety in less than 1s led to the enhancement of photoluminescence (PL) and electrochemical luminescence (ECL), by which the concentration of HOCl was determined by both PL and ECL analysis. Taking advantages of excellent properties of Ir(III) complexes, optical and electrochemical analyses of the response of Ir-Fc towards HOCl were fully investigated. Followed by the measurements of low cytotoxicity of Ir-Fc by MTT analysis, one-photon (OP), two-photon (TP) and lifetime imaging experiments were conducted to visualise the generation of HOCl in live microphage and HepG2 cells, and in zebrafish and mouse, respectively. Furthermore, the generation and distribution of HOCl in liver cells and liver injury of zebrafish and mouse were investigated. The results demonstrated the applicability of Ir-Fc as an effective chemosensor for imaging of HOCl generation in mitochondria of cells and liver injury in vivo, implying the potential of Ir-Fc for biomedical diagnosis and monitoring applications.

  17. Ion channel stability and hydrogen bonding. Molecular modelling of channels formed by synthetic alamethicin analogues. (United States)

    Breed, J; Kerr, I D; Molle, G; Duclohier, H; Sansom, M S


    Several analogues of the channel-forming peptaibol alamethicin have been demonstrated to exhibit faster switching between channel substates than does unmodified alamethicin. Molecular modelling studies are used to explore the possible molecular basis of these differences. Models of channels formed by alamethicin analogues were generated by restrained molecular dynamics in vacuo and refined by short molecular dynamics simulations with water molecules within and at either mouth of the channel. A decrease in backbone solvation was found to correlate with a decrease in open channel stability between alamethicin and an analogue in which all alpha-amino-isobutyric acid residues of alamethicin were replaced by leucine. A decrease in the extent of hydrogen-bonding at residue 7 correlates with lower open channel stabilities of analogues in which the glutamine at position 7 was replaced by smaller polar sidechains. These two observations indicate the importance of alamethicin/water H-bonds in stabilizing the open channel.

  18. Utilization of Negative Ion ESI-MS and Tandem Mass Spectrometry to Detect and Confirm the NADH-Boric Acid Complex (United States)

    Kim, Danny H.; Eckhert, Curtis D.; Faull, Kym F.


    Mass spectrometry (MS) is a powerful analytical technique that is now widely used in the chemical, physical, engineering, and life sciences, with rapidly growing applications in many areas including clinical, forensic, pharmaceutical, and environmental fields. The increase in use of MS in both academic and industrial settings for research and…

  19. 硼酸双甘油酯硬脂酸酯的合成研究%Synthetic Study of Boric Diglyceride Stearic Acid Ester Surfactant

    Institute of Scientific and Technical Information of China (English)

    洪哲; 黄凤远; 姜云鹏



  20. 硼酸二甘油酯脂肪酸酯的合成研究%Study of synthesis of boric diglyceride fatty acid ester surfactant

    Institute of Scientific and Technical Information of China (English)

    杜春霖; 刘波; 洪哲


    以硼酸、甘油为原料,在氮气保护下合成硼酸二甘油酯,然后在强酸性阳离子交换树脂催化下分别与月桂酸、肉豆蔻酸、硬脂酸反应合成出3种具有半极性键的有机硼酸酯表面活性剂.用红外光谱确定了产物的结构.研究了硼酸二甘油酯月桂酸酯的合成工艺,得到了优化的工艺条件,结果表明:硼酸与甘油的摩尔比为1∶2.0,反应温度为180 ℃,反应时间为4 h时,硼酸二甘油酯的收率为96.0%;硼酸二甘油酯与月桂酸的摩尔比为1∶0.9,反应温度为200 ℃,反应时间为3.5 h,催化剂用量(相对于月桂酸的质量)为2.0%时,月桂酸转化率为97.5%.硼酸二甘油酯肉豆蔻酸酯和硼酸二甘油酯硬脂酸酯在相同的工艺条件下合成时酸转化率分别为97.0%和96.4%.该工艺具有酸转化率高,后处理工艺简单的优点.

  1. Effect of time period after boric acid injection on {sup 10}B absorption in different regions of adult male rat's brain

    Energy Technology Data Exchange (ETDEWEB)

    Baghban Khojasteh, Nasrin, E-mail: [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of); Pazirandeh, Ali [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of); Jameie, Behnam [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of); Laboratory of Basic Science and Neuroscience, Basic Science Dept, Faculty of Allied Medicine, Cellular and Molecular Research Center, Tehran University of Medical Science, Pardis-e-Hemmat,Tehran (Iran, Islamic Republic of); Goodarzi, Samereh [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of)


    Distribution of {sup 10}B in different regions of rat normal brain was studied. Two groups were chosen as control and trial. Trial group received 2 ml of neutral boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections of forebrain, midbrain and hindbrain were sandwiched between two pieces of polycarbonate. Autoradiography plots of {sup 10}B distribution showed significant differences in three regions with the highest {sup 10}B concentration in the forebrain during 4 h after injection. - Highlights: Black-Right-Pointing-Pointer Normal tissue tolerance is very important in BNCT. Black-Right-Pointing-Pointer This study has been done to determine {sup 10}B distribution in three anatomical regions of rat normal brain. Black-Right-Pointing-Pointer These specific regions of brain have not been studied in previous BNCT projects. Black-Right-Pointing-Pointer We found significant differences in {sup 10}B distribution between these three regions. Black-Right-Pointing-Pointer In different time periods after neutral boron compound injection, there has been a significant difference in boron absorption.

  2. Mobile radio channels

    CERN Document Server

    Pätzold, Matthias


    Providing a comprehensive overview of the modelling, analysis and simulation of mobile radio channels, this book gives a detailed understanding of fundamental issues and examines state-of-the-art techniques in mobile radio channel modelling. It analyses several mobile fading channels, including terrestrial and satellite flat-fading channels, various types of wideband channels and advanced MIMO channels, providing a fundamental understanding of the issues currently being investigated in the field. Important classes of narrowband, wideband, and space-time wireless channels are explored in deta

  3. Channel nut tool

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Marvin


    A method, system, and apparatus for installing channel nuts includes a shank, a handle formed on a first end of a shank, and an end piece with a threaded shaft configured to receive a channel nut formed on the second end of the shaft. The tool can be used to insert or remove a channel nut in a channel framing system and then removed from the channel nut.

  4. Interaction of hydrogen sulfide with ion channels. (United States)

    Tang, Guanghua; Wu, Lingyun; Wang, Rui


    1. Hydrogen sulfide (H(2)S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H(2)S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H(2)S is the first identified endogenous gaseous opener of ATP-sensitive K(+) channels in vascular smooth muscle cells. Through the activation of ATP-sensitive K(+) channels, H(2)S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic beta cells, and exerts anti-inflammatory, anti-nociceptive and anti-apoptotic effects. 3. H(2)S inhibited L-type Ca(2+) channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca(2+) levels. H(2)S activated small and medium conductance K(Ca) channels but its effect on BK(Ca) channels has not been consistent. 4. H(2)S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca(2+) channels and TRPV(1) channels. The activation of TRPV(1) and TRPA(1) by H(2)S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl(-) secretion. 5. The activation of Cl(-) channel by H(2)S has been shown as a protective mechanism for neurons from oxytosis. H(2)S also potentiates N-methyl-d-aspartic acid receptor-mediated currents that are involved in regulating synaptic plasticity for learning and memory. 6. Given the important modulatory effects of H(2)S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated.

  5. Multi-Channel Retailing

    Directory of Open Access Journals (Sweden)

    Dirk Morschett, Dr.,


    Full Text Available Multi-channel retailing entails the parallel use by retailing enterprises of several sales channels. The results of an online buyer survey which has been conducted to investigate the impact of multi-channel retailing (i.e. the use of several retail channels by one retail company on consumer behaviour show that the frequently expressed concern that the application of multi-channel systems in retailing would be associated with cannibalization effects, has proven unfounded. Indeed, the appropriate degree of similarity, consistency, integration and agreement achieves the exact opposite. Different channels create different advantages for consumers. Therefore the total benefit an enterprise which has a multi-channel system can offer to its consumers is larger, the greater the number of available channels. The use of multi-channel systems is associated with additional purchases in the different channels. Such systems are thus superior to those offering only one sales channel to their customers. Furthermore, multi-channel systems with integrated channels are superior to those in which the channels are essentially autonomous and independent of one another. In integrated systems, consumers can achieve synergy effects in the use of sales-channel systems. Accordingly, when appropriately formulated, multi-channel systems in retailing impact positively on consumers. They use the channels more frequently, buy more from them and there is a positive customer-loyalty impact. Multi-channel systems are strategic options for achieving customer loyalty, exploiting customer potential and for winning new customers. They are thus well suited for approaching differing and varied target groups.

  6. Spectrophotometric determination of channel black in small arms propellants. (United States)

    Galan, M; Norwitz, G


    A spectrophotometric method is proposed for the determination of Channel Black in small arms propellants. The Channel Black is separated from the nitrocellulose and other organic compounds by dissolution of the propellant in morpholine and filtration through a sintered porcelain crucible containing an asbestos mat. The Channel Black is then dissolved by treating the mat and crucible with boiling nitric acid for 3 hr, the solution is filtered, and the yellow colour is measured. The colour is due to polycarboxylic acids with cyclic nuclei. The range of the method is from 0 to 0.5% of Channel Black.

  7. Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK : The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a

    NARCIS (Netherlands)

    Deplazes, Evelyne; Davies, Josephine; Bonvin, Alexandre M J J; King, Glenn F; Mark, Alan Edward


    Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived f

  8. USACE Navigation Channels 2012 (United States)

    California Department of Resources — This dataset represents both San Francisco and Los Angeles District navigation channel lines. All San Francisco District channel lines were digitized from CAD files...

  9. KV7 potassium channels

    DEFF Research Database (Denmark)

    Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A


    Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

  10. Quantum Multiple Access Channel

    Institute of Scientific and Technical Information of China (English)

    侯广; 黄民信; 张永德


    We consider the transmission of classical information over a quantum channel by many senders, which is a generalization of the two-sender case. The channel capacity region is shown to be a convex hull bound by the yon Neumann entropy and the conditional yon Neumann entropies. The result allows a reasonable distribution of channel capacity over the senders.

  11. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter


    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...

  12. Boron (United States)

    ... an eye wash. Boron was used as a food preservative between 1870 and 1920, and during World Wars ... chemical symbol), B (symbole chimique), Borate, Borate de Sodium, Borates, Bore, Boric Acid, Boric Anhydride, Boric Tartrate, ...

  13. Protocol channels as a new design alternative of covert channels

    CERN Document Server

    Wendzel, Steffen


    Covert channel techniques are used by attackers to transfer hidden data. There are two main categories of covert channels: timing channels and storage channels. This paper introduces a third category called protocol channels. A protocol channel switches one of at least two protocols to send a bit combination to a destination while sent packets include no hidden information themselves.

  14. Surface vacancy channels through ion channeling

    Energy Technology Data Exchange (ETDEWEB)

    Redinger, Alex; Standop, Sebastian; Michely, Thomas [II. Physikalisches Institut, Universitaet Koeln, Zuelpicher Strasse 77, 50937 Koeln (Germany); Rosandi, Yudi; Urbassek, Herbert M. [Fachbereich Physik, Technische Universitaet Kaiserslautern, Erwin-Schroedinger-Strasse, D-67663 Kaiserslautern (Germany)


    Damage patterns of single ion impacts on Pt(111) have been studied by scanning tunneling microscopy (STM) and molecular dynamics simulations (MD). Low temperature experiments, where surface diffusion is absent, have been performed for argon and xenon ions with energies between 1 keV and 15 keV at an angle of incidence of 86 {sup circle} measured with respect to the surface normal. Ions hitting preexisting illuminated step edges penetrate into the crystal and are guided in open crystallographic directions, one or more layers underneath the surface (subsurface channeling). In the case of argon channeling the resulting surface damage consists of adatom and vacancy pairs aligned in ion beam direction. After xenon channeling thin surface vacancy trenches along the ion trajectories - surface vacancy channels - are observed. They result from very efficient sputtering and adatom production along the ion trajectory. This phenomena is well reproduced in molecular dynamics simulations of single ion impacts at 0 K. The damage patterns of Argon and Xenon impacts can be traced back to the different energy losses of the particles in the channel. Channeling distances exceeding 1000 A for 15 keV xenon impacts are observed.

  15. Subcellular localization of the voltage-gated potassium channels Kv3.1b and Kv3.3 in the cerebellar dentate nucleus of glutamic acid decarboxylase 67-green fluorescent protein transgenic mice. (United States)

    Alonso-Espinaco, V; Elezgarai, I; Díez-García, J; Puente, N; Knöpfel, T; Grandes, P


    Deep cerebellar dentate nuclei are in a key position to control motor planning as a result of an integration of cerebropontine inputs and hemispheric Purkinje neurons signals, and their influence through synaptic outputs onto extracerebellar hubs. GABAergic dentate neurons exhibit broader action potentials and slower afterhyperpolarization than non-GABAergic (presumably glutamatergic) neurons. Specific potassium channels may be involved in these distinct firing profiles, particularly, Kv3.1 and Kv3.3 subunits which rapidly activate at relatively positive potentials to support the generation of fast action potentials. To investigate the subcellular localization of Kv3.1b and Kv3.3 in GAD- and GAD+ dentate neurons of glutamic acid decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mice a preembedding immunocytochemical method for electron microscopy was used. Kv3.1b and Kv3.3 were in membranes of cell somata, dendrites, axons and synaptic terminals of both GAD- and GAD+ dentate neurons. The vast majority of GAD- somatodendritic membrane segments domains labeled for Kv3.1b and Kv3.3 (96.1% and 84.7%, respectively) whereas 56.2% and 69.8% of GAD- axonal membrane segments were immunopositive for these subunits. Furthermore, density of Kv3.1b immunoparticles was much higher in GAD- somatodendritic than axonal domains. As to GAD+ neurons, only 70.6% and 50% of somatodendritic membrane segments, and 53.3% and 59.5% of axonal membranes exhibited Kv3.1b and Kv3.3 labeling, respectively. In contrast to GAD- cells, GAD+ cells exhibited a higher density labeling for both Kv3 subunits at their axonal than at their somatodendritic membranes. Taken together, Kv3.1b and Kv3.3 potassium subunits are expressed in both GAD- and GAD+ cells, albeit at different densities and distribution. They likely contribute to the distinct biophysical properties of both GAD- and GAD+ neurons in the dentate nucleus.

  16. Ion Channel Formation by Tau Protein: Implications for Alzheimer's Disease and Tauopathies


    Patel, N; S. Ramachandran; Azimov, R; Kagan, BL; Lal, R


    © 2015 American Chemical Society. Tau is a microtubule associated protein implicated in the pathogenesis of several neurodegenerative diseases. Because of the channel forming properties of other amyloid peptides, we employed planar lipid bilayers and atomic force microscopy to test tau for its ability to form ion permeable channels. Our results demonstrate that tau can form such channels, but only under acidic conditions. The channels formed are remarkably similar to amyloid peptide channels ...

  17. A Single Amino Acid Deletion (ΔF1502 in the S6 Segment of CaV2.1 Domain III Associated with Congenital Ataxia Increases Channel Activity and Promotes Ca2+ Influx.

    Directory of Open Access Journals (Sweden)

    Maria Isabel Bahamonde

    Full Text Available Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type channel α1A subunit, result in heterogeneous human neurological disorders, including familial and sporadic hemiplegic migraine along with episodic and progressive forms of ataxia. Hemiplegic Migraine (HM mutations induce gain-of-channel function, mainly by shifting channel activation to lower voltages, whereas ataxia mutations mostly produce loss-of-channel function. However, some HM-linked gain-of-function mutations are also associated to congenital ataxia and/or cerebellar atrophy, including the deletion of a highly conserved phenylalanine located at the S6 pore region of α1A domain III (ΔF1502. Functional studies of ΔF1502 CaV2.1 channels, expressed in Xenopus oocytes, using the non-physiological Ba2+ as the charge carrier have only revealed discrete alterations in channel function of unclear pathophysiological relevance. Here, we report a second case of congenital ataxia linked to the ΔF1502 α1A mutation, detected by whole-exome sequencing, and analyze its functional consequences on CaV2.1 human channels heterologously expressed in mammalian tsA-201 HEK cells, using the physiological permeant ion Ca2+. ΔF1502 strongly decreases the voltage threshold for channel activation (by ~ 21 mV, allowing significantly higher Ca2+ current densities in a range of depolarized voltages with physiological relevance in neurons, even though maximal Ca2+ current density through ΔF1502 CaV2.1 channels is 60% lower than through wild-type channels. ΔF1502 accelerates activation kinetics and slows deactivation kinetics of CaV2.1 within a wide range of voltage depolarization. ΔF1502 also slowed CaV2.1 inactivation kinetic and shifted the inactivation curve to hyperpolarized potentials (by ~ 28 mV. ΔF1502 effects on CaV2.1 activation and deactivation properties seem to be of high physiological relevance. Thus, ΔF1502 strongly promotes Ca2+ influx in response to either single or

  18. Transient Receptor Potential Mucolipin 1 (TRPML1) and Two-pore Channels Are Functionally Independent Organellar Ion Channels*



    NAADP is a potent second messenger that mobilizes Ca2+ from acidic organelles such as endosomes and lysosomes. The molecular basis for Ca2+ release by NAADP, however, is uncertain. TRP mucolipins (TRPMLs) and two-pore channels (TPCs) are Ca2+-permeable ion channels present within the endolysosomal system. Both have been proposed as targets for NAADP. In the present study, we probed possible physical and functional association of these ion channels. Exogenously expressed TRPML1 showed near com...

  19. Functional diversity and evolutionary dynamics of thermoTRP channels. (United States)

    Saito, Shigeru; Tominaga, Makoto


    Animals have evolved sophisticated physiological systems for sensing ambient temperature since changes in environmental temperatures affect various biological processes. Thermosensitive transient receptor potential (thermoTRP) channels serve as thermal sensors in diverse animal species. They are multimodal receptors that are activated by temperature as well as other physical and chemical stimuli. Since thermoTRP channels are calcium permeable non-selective cation channels, their activation leads to an influx of calcium and sodium ions into the cell and triggers downstream signal transduction. ThermoTRP channels have been characterized in diverse animal species over the past several years, illuminating the diversification of thermoTRP channels in the course of evolution. The gene repertoires of thermoTRP channels differ among animal species. Additionally, in some cases, the temperature and chemical sensitivities among orthologous thermoTRP channels vary among species. The evolutionary flexibility of thermoTRP channels enabled them to contribute to unique physiological systems such as infrared sensation in snakes and bats and seasonal adaptation in silk moth. On the other hand, the functional differences of thermoTRP channels among species have been utilized for understanding the molecular basis for their activation (or inhibition) mechanisms, and amino acid residues (or domains) responsible for the respective channel properties have been identified in various thermoTRP channels. Here we summarize the current understanding of the functional diversity and evolutionary dynamics of thermoTRP channels.

  20. 水杨酸二甘酯的合成及工艺优化%The Synthesize and Craftsmanship Optimization of Salicylic Acid Diglyceride

    Institute of Scientific and Technical Information of China (English)



    Salicylic acid diglyceride, as an important chemical raw material, is an organic solvent and synthetic perfume. The article researches the compound of salieylic acid diglyeefide from salicylic acid and diglyceride and finds a better result of the eatalyst of a mixture of boric acid, paratoluenesulfonic acid, sulphurie acid and oxalic acid.%水杨酸二甘酯是一种重要的化工原料,也是很好的有机溶荆和合成香料.文章研究由水杨酸和二甘醇合成水杨酸二甘酯,发现硼酸、对甲苯磺酸、硫酸及草酸的混合酸作催化荆效果较好.

  1. Quantum broadcast channels

    CERN Document Server

    Yard, J; Devetak, I; Yard, Jon; Hayden, Patrick; Devetak, Igor


    We analyze quantum broadcast channels, which are quantum channels with a single sender and many receivers. Focusing on channels with two receivers for simplicity, we generalize a number of results from the network Shannon theory literature which give the rates at which two senders can receive a common message, while a personalized one is sent to one of them. Our first collection of results applies to channels with a classical input and quantum outputs. The second class of theorems we prove concern sending a common classical message over a quantum broadcast channel, while sending quantum information to one of the receivers. The third group of results we obtain concern communication over an isometry, giving the rates at quantum information can be sent to one receiver, while common quantum information is sent to both, in the sense that tripartite GHZ entanglement is established. For each scenario, we provide an additivity proof for an appropriate class of channels, yielding single-letter characterizations of the...

  2. Quantum feedback channels

    CERN Document Server

    Bowen, G


    In classical information theory the capacity of a noisy communication channel cannot be increased by the use of feedback. In quantum information theory the no-cloning theorem means that noiseless copying and feedback of quantum information cannot be achieved. In this paper, quantum feedback is defined as the unlimited use of a noiseless quantum channel from receiver to sender. Given such quantum feedback, it is shown to provide no increase in the entanglement-assisted capacities of a noisy quantum channel, in direct analogy to the classical case. It is also shown that in various cases of non-assisted capacities, feedback can increase the capacity of many quantum channels.

  3. Ion channels in asthma. (United States)

    Valverde, Miguel A; Cantero-Recasens, Gerard; Garcia-Elias, Anna; Jung, Carole; Carreras-Sureda, Amado; Vicente, Rubén


    Ion channels are specialized transmembrane proteins that permit the passive flow of ions following their electrochemical gradients. In the airways, ion channels participate in the production of epithelium-based hydroelectrolytic secretions and in the control of intracellular Ca(2+) levels that will ultimately activate almost all lung cells, either resident or circulating. Thus, ion channels have been the center of many studies aiming to understand asthma pathophysiological mechanisms or to identify therapeutic targets for better control of the disease. In this minireview, we focus on molecular, genetic, and animal model studies associating ion channels with asthma.

  4. TRP channels in schistosomes

    Directory of Open Access Journals (Sweden)

    Swarna Bais


    Full Text Available Praziquantel (PZQ is effectively the only drug currently available for treatment and control of schistosomiasis, a disease affecting hundreds of millions of people worldwide. Many anthelmintics, likely including PZQ, target ion channels, membrane protein complexes essential for normal functioning of the neuromusculature and other tissues. Despite this fact, only a few classes of parasitic helminth ion channels have been assessed for their pharmacological properties or for their roles in parasite physiology. One such overlooked group of ion channels is the transient receptor potential (TRP channel superfamily. TRP channels share a common core structure, but are widely diverse in their activation mechanisms and ion selectivity. They are critical to transducing sensory signals, responding to a wide range of external stimuli. They are also involved in other functions, such as regulating intracellular calcium and organellar ion homeostasis and trafficking. Here, we review current literature on parasitic helminth TRP channels, focusing on those in schistosomes. We discuss the likely roles of these channels in sensory and locomotor activity, including the possible significance of a class of TRP channels (TRPV that is absent in schistosomes. We also focus on evidence indicating that at least one schistosome TRP channel (SmTRPA has atypical, TRPV1-like pharmacological sensitivities that could potentially be exploited for future therapeutic targeting.

  5. A linearization of quantum channels (United States)

    Crowder, Tanner


    Because the quantum channels form a compact, convex set, we can express any quantum channel as a convex combination of extremal channels. We give a Euclidean representation for the channels whose inverses are also valid channels; these are a subset of the extreme points. They form a compact, connected Lie group, and we calculate its Lie algebra. Lastly, we calculate a maximal torus for the group and provide a constructive approach to decomposing any invertible channel into a product of elementary channels.

  6. Ion channels in toxicology. (United States)

    Restrepo-Angulo, Iván; De Vizcaya-Ruiz, Andrea; Camacho, Javier


    Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases.

  7. Heterodimerization within the TREK channel subfamily produces a diverse family of highly regulated potassium channels. (United States)

    Levitz, Joshua; Royal, Perrine; Comoglio, Yannick; Wdziekonski, Brigitte; Schaub, Sébastien; Clemens, Daniel M; Isacoff, Ehud Y; Sandoz, Guillaume


    Twik-related K(+) channel 1 (TREK1), TREK2, and Twik-related arachidonic-acid stimulated K(+) channel (TRAAK) form the TREK subfamily of two-pore-domain K(+) (K2P) channels. Despite sharing up to 78% sequence homology and overlapping expression profiles in the nervous system, these channels show major differences in their regulation by physiological stimuli. For instance, TREK1 is inhibited by external acidification, whereas TREK2 is activated. Here, we investigated the ability of the members of the TREK subfamily to assemble to form functional heteromeric channels with novel properties. Using single-molecule pull-down (SiMPull) from HEK cell lysate and subunit counting in the plasma membrane of living cells, we show that TREK1, TREK2, and TRAAK readily coassemble. TREK1 and TREK2 can each heterodimerize with TRAAK, but do so less efficiently than with each other. We functionally characterized the heterodimers and found that all combinations form outwardly rectifying potassium-selective channels but with variable voltage sensitivity and pH regulation. TREK1-TREK2 heterodimers show low levels of activity at physiological external pH but, unlike their corresponding homodimers, are activated by both acidic and alkaline conditions. Modeling based on recent crystal structures, along with mutational analysis, suggests that each subunit within a TREK1-TREK2 channel is regulated independently via titratable His. Finally, TREK1/TRAAK heterodimers differ in function from TRAAK homodimers in two critical ways: they are activated by both intracellular acidification and alkalinization and are regulated by the enzyme phospholipase D2. Thus, heterodimerization provides a means for diversifying functionality through an expansion of the channel types within the K2P channels.

  8. Athermalized channeled spectropolarimeter enhancement.

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Julia Craven; Way, Brandyn Michael; Mercier, Jeffrey Alan; Hunt, Jeffery P.


    Channeled spectropolarimetry can measure the complete polarization state of light as a function of wavelength. Typically, a channeled spectropolarimeter uses high order retarders made of uniaxial crystal to amplitude modulate the measured spectrum with the spectrally-dependent Stokes polarization information. A primary limitation of conventional channeled spectropolarimeters is related to the thermal variability of the retarders. Thermal variation often forces frequent system recalibration, particularly for field deployed systems. However, implementing thermally stable retarders, made of biaxial crystal, results in an athermal channeled spectropolarimeter that relieves the need for frequent recalibration. This report presents experimental results for an anthermalized channeled spectropolarimeter prototype produced using potassium titanyl phosphate. The results of this prototype are compared to the current thermal stabilization state of the art. Finally, the application of the technique to the thermal infrared is studied, and the athermalization concept is applied to an infrared imaging spectropolarimeter design.

  9. 5,6-EET potently inhibits T-type calcium channels

    DEFF Research Database (Denmark)

    Cazade, M.; Bidaud, I.; Hansen, Pernille B. Lærkegaard;


    T-type calcium channels (T-channels) are important actors in neuronal pacemaking, in heart rhythm, and in the control of the vascular tone. T-channels are regulated by several endogenous lipids including the primary eicosanoid arachidonic acid (AA), which display an important role in vasodilation...

  10. Channel Access in Erlang

    Energy Technology Data Exchange (ETDEWEB)

    Nicklaus, Dennis J. [Fermilab


    We have developed an Erlang language implementation of the Channel Access protocol. Included are low-level functions for encoding and decoding Channel Access protocol network packets as well as higher level functions for monitoring or setting EPICS process variables. This provides access to EPICS process variables for the Fermilab Acnet control system via our Erlang-based front-end architecture without having to interface to C/C++ programs and libraries. Erlang is a functional programming language originally developed for real-time telecommunications applications. Its network programming features and list management functions make it particularly well-suited for the task of managing multiple Channel Access circuits and PV monitors.

  11. An Insight to Covert Channels


    Salwan, Nitish; Singh, Sandeep; Arora, Suket; Singh, Amarpreet


    This paper presents an overview of different concepts regarding covert channels. It discusses the various classifications and the detailing of various fields used to manipulate for the covert channel execution.Different evaluation criterias are presented for measuring the strength of covert channels. The defenses and prevention schemes for this covert channel will also be discussed. This paper also discuss about an advanced timing channel i.e.Temperature Based Covert Channel.

  12. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille


    The channel choice branch of e-government studies citizens’ and businesses’ choice of channels for interacting with government, and how government organizations can integrate channels and migrate users towards the most cost-efficient channels. In spite of the valuable contributions offered no sys...... no systematic overview exist of channel choice. We present a literature review of channel choice studies in government to citizen context identifying authors, countries, methods, concepts, units of analysis, and theories, and offer suggestionsfor future studies....

  13. The Earliest Ion Channels in Protocellular Membranes (United States)

    Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu


    Cellular membranes with their hydrophobic interior are virtually impermeable to ions. Bulk of ion transport through them is enabled through ion channels. Ion channels of contemporary cells are complex protein molecules which span the membrane creating a cylindrical pore filled with water. Protocells, which are widely regarded as precursors to modern cells, had similarly impermeable membranes, but the set of proteins in their disposal was much simpler and more limited. We have been, therefore, exploring an idea that the first ion channels in protocellular membranes were formed by much smaller peptide molecules that could spontaneously selfassemble into short-lived cylindrical bundles in a membrane. Earlier studies have shown that a group of peptides known as peptaibols is capable of forming ion channels in lipid bilayers when they are exposed to an electric field. Peptaibols are small, non-genetically encoded peptides produced by some fungi as a part of their system of defense against bacteria. They are usually only 14-20 residues long, which is just enough to span the membrane. Their sequence is characterized by the presence of non-standard amino acids which, interestingly, are also expected to have existed on the early earth. In particular, the presence of 2-aminoisobutyric acid (AIB) gives peptaibols strong helix forming propensities. Association of the helices inside membranes leads to the formation of cylindrical bundles, typically containing 4 to 10 monomers. Although peptaibols are excellent candidates for models of the earliest ion channels their structures, which are stabilized only by van der Waals forces and occasional hydrogen bonds between neighboring helices, are not very stable. Although it might properly reflect protobiological reality, it is also a major obstacle in studying channel behavior. For this reason we focused on two members of the peptaibol family, trichotoxin and antiamoebin, which are characterized by a single conductance level. This

  14. Cooperative gating between ion channels. (United States)

    Choi, Kee-Hyun


    Cooperative gating between ion channels, i.e. the gating of one channel directly coupled to the gating of neighboring channels, has been observed in diverse channel types at the single-channel level. Positively coupled gating could enhance channel-mediated signaling while negative coupling may effectively reduce channel gating noise. Indeed, the physiological significance of cooperative channel gating in signal transduction has been recognized in several in vivo studies. Moreover, coupled gating of ion channels was reported to be associated with some human disease states. In this review, physiological roles for channel cooperativity and channel clustering observed in vitro and in vivo are introduced, and stimulation-induced channel clustering and direct channel cross linking are suggested as the physical mechanisms of channel assembly. Along with physical clustering, several molecular mechanisms proposed as the molecular basis for functional coupling of neighboring channels are covered: permeant ions as a channel coupling mediator, concerted channel activation through the membrane, and allosteric mechanisms. Also, single-channel analysis methods for cooperative gating such as the binomial analysis, the variance analysis, the conditional dwell time density analysis, and the maximum likelihood fitting analysis are reviewed and discussed.

  15. Purinergic regulation of CFTR and Ca2+ -activated Cl- channels and K+ channels in human pancreatic duct epithelium

    DEFF Research Database (Denmark)

    Wang, Jing; Haanes, Kristian A; Novak, Ivana


    dependent on intracellular Ca(2+). Apically applied ATP/UTP stimulated CF transmembrane conductance regulator (CFTR) and Ca(2+)-activated Cl(-) (CaCC) channels, which were inhibited by CFTRinh-172 and niflumic acid, respectively. The basolaterally applied ATP stimulated CFTR. In CFPAC-1 cells, which have...... mutated CFTR, basolateral ATP and UTP had negligible effects. In addition to Cl(-) transport in Capan-1 cells, the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DC-EBIO) and clotrimazole indicated functional expression of the intermediate conductance K(+) channels (IK, KCa3...... receptors both Cl(-) channels (TMEM16A/ANO1 and CFTR) and K(+) channels (IK). The K(+) channels provide the driving force for Cl(-)-channel-dependent secretion, and luminal ATP provided locally or secreted from acini may potentiate secretory processes. Future strategies in augmenting pancreatic duct...

  16. Sensing with Ion Channels

    CERN Document Server

    Martinac, Boris


    All living cells are able to detect and translate environmental stimuli into biologically meaningful signals. Sensations of touch, hearing, sight, taste, smell or pain are essential to the survival of all living organisms. The importance of sensory input for the existence of life thus justifies the effort made to understand its molecular origins. Sensing with Ion Channels focuses on ion channels as key molecules enabling biological systems to sense and process the physical and chemical stimuli that act upon cells in their living environment. Its aim is to serve as a reference to ion channel specialists and as a source of new information to non specialists who want to learn about the structural and functional diversity of ion channels and their role in sensory physiology.

  17. Covert Channels within IRC (United States)


    Communications ....................................... 2 1.3 Steganography and Covert Channels .......................................................... 3...Internet Relay Chat ..................................................................................... 7 2.2 Steganography ...13 2.2.2 Encrypted Steganographic Systems .............................................. 15 2.2.3 Text-Based Steganography

  18. Channelized Streams in Iowa (United States)

    Iowa State University GIS Support and Research Facility — This draft dataset consists of all ditches or channelized pieces of stream that could be identified using three input datasets; namely the1:24,000 National...

  19. Authentication over Noisy Channels

    CERN Document Server

    Lai, Lifeng; Poor, H Vincent


    In this work, message authentication over noisy channels is studied. The model developed in this paper is the authentication theory counterpart of Wyner's wiretap channel model. Two types of opponent attacks, namely impersonation attacks and substitution attacks, are investigated for both single message and multiple message authentication scenarios. For each scenario, information theoretic lower and upper bounds on the opponent's success probability are derived. Remarkably, in both scenarios, lower and upper bounds are shown to match, and hence the fundamental limit of message authentication over noisy channels is fully characterized. The opponent's success probability is further shown to be smaller than that derived in the classic authentication model in which the channel is assumed to be noiseless. These results rely on a proposed novel authentication scheme in which key information is used to provide simultaneous protection again both types of attacks.

  20. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida


    , and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also......(-) channels or as regulators of other apoptotic Cl(-) channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated...... by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling....

  1. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  2. The Epithelial Calcium Channel TRPV5 Is Regulated Differentially by Klotho and Sialidase.

    NARCIS (Netherlands)

    Leunissen, E.H.P.; Nair, A.V.; Büll, C.; Lefeber, D.J.; Delft, F.L. van; Bindels, R.J.M.; Hoenderop, J.G.J.


    The transient receptor potential vanilloid type 5 (TRPV5) Ca(2+) channel facilitates transcellular Ca(2+) transport in the distal convoluted tubule (DCT) of the kidney. The channel is glycosylated with a complex type N-glycan and it has been postulated that hydrolysis of the terminal sialic acid(s)

  3. Fracture channel waves (United States)

    Nihei, Kurt T.; Yi, Weidong; Myer, Larry R.; Cook, Neville G. W.; Schoenberg, Michael


    The properties of guided waves which propagate between two parallel fractures are examined. Plane wave analysis is used to obtain a dispersion equation for the velocities of fracture channel waves. Analysis of this equation demonstrates that parallel fractures form an elastic waveguide that supports two symmetric and two antisymmetric dispersive Rayleigh channel waves, each with particle motions and velocities that are sensitive to the normal and tangential stiffnesses of the fractures. These fracture channel waves degenerate to shear waves when the fracture stiffnesses are large, to Rayleigh waves and Rayleigh-Lamb plate waves when the fracture stiffnesses are low, and to fracture interface waves when the fractures are either very closely spaced or widely separated. For intermediate fracture stiffnesses typical of fractured rock masses, fracture channel waves are dispersive and exhibit moderate to strong localization of guided wave energy between the fractures. The existence of these waves is examined using laboratory acoustic measurements on a fractured marble plate. This experiment confirms the distinct particle motion of the fundamental antisymmetric fracture channel wave (A0 mode) and demonstrates the ease with which a fracture channel wave can be generated and detected.

  4. Course on Ionic Channels

    CERN Document Server


    This book is based on a series of lectures for a course on ionic channels held in Santiago, Chile, on November 17-20, 1984. It is intended as a tutorial guide on the properties, function, modulation, and reconstitution of ionic channels, and it should be accessible to graduate students taking their first steps in this field. In the presentation there has been a deliberate emphasis on the spe­ cific methodologies used toward the understanding of the workings and function of channels. Thus, in the first section, we learn to "read" single­ channel records: how to interpret them in the theoretical frame of kinetic models, which information can be extracted from gating currents in re­ lation to the closing and opening processes, and how ion transport through an open channel can be explained in terms of fluctuating energy barriers. The importance of assessing unequivocally the origin and purity of mem­ brane preparations and the use of membrane vesicles and optical tech­ niques in the stUGY of ionic channels a...

  5. Aspartic acid (United States)

    Aspartic acid is a nonessential amino acids . Amino acids are building blocks of proteins. "Nonessential" means that our ... this amino acid from the food we eat. Aspartic acid is also called asparaginic acid. Aspartic acid helps ...

  6. Kinetics and Product Channels in Combustion Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Hershberger, John F. [North Dakota State Univ., Fargo, ND (United States)


    We report study of the chemical kinetics and/or photochemistry of several chemical reactions of potential interest in understanding the gas phase combustion chemistry of nitrogen-containing molecules. Studies completed during the final grant period include determination of quantum yields of the photolysis of HCNO, fulminic acid, a kinetics and product channel study of the reaction of CN radicals with methyl bromide, and study of the products of the reaction of hydroxymethyl radical with nitric oxide.

  7. Molecular modeling of mechanosensory ion channel structural and functional features. (United States)

    Gessmann, Renate; Kourtis, Nikos; Petratos, Kyriacos; Tavernarakis, Nektarios


    The DEG/ENaC (Degenerin/Epithelial Sodium Channel) protein family comprises related ion channel subunits from all metazoans, including humans. Members of this protein family play roles in several important biological processes such as transduction of mechanical stimuli, sodium re-absorption and blood pressure regulation. Several blocks of amino acid sequence are conserved in DEG/ENaC proteins, but structure/function relations in this channel class are poorly understood. Given the considerable experimental limitations associated with the crystallization of integral membrane proteins, knowledge-based modeling is often the only route towards obtaining reliable structural information. To gain insight into the structural characteristics of DEG/ENaC ion channels, we derived three-dimensional models of MEC-4 and UNC-8, based on the available crystal structures of ASIC1 (Acid Sensing Ion Channel 1). MEC-4 and UNC-8 are two DEG/ENaC family members involved in mechanosensation and proprioception respectively, in the nematode Caenorhabditis elegans. We used these models to examine the structural effects of specific mutations that alter channel function in vivo. The trimeric MEC-4 model provides insight into the mechanism by which gain-of-function mutations cause structural alterations that result in increased channel permeability, which trigger cell degeneration. Our analysis provides an introductory framework to further investigate the multimeric organization of the DEG/ENaC ion channel complex.

  8. Molecular modeling of mechanosensory ion channel structural and functional features.

    Directory of Open Access Journals (Sweden)

    Renate Gessmann

    Full Text Available The DEG/ENaC (Degenerin/Epithelial Sodium Channel protein family comprises related ion channel subunits from all metazoans, including humans. Members of this protein family play roles in several important biological processes such as transduction of mechanical stimuli, sodium re-absorption and blood pressure regulation. Several blocks of amino acid sequence are conserved in DEG/ENaC proteins, but structure/function relations in this channel class are poorly understood. Given the considerable experimental limitations associated with the crystallization of integral membrane proteins, knowledge-based modeling is often the only route towards obtaining reliable structural information. To gain insight into the structural characteristics of DEG/ENaC ion channels, we derived three-dimensional models of MEC-4 and UNC-8, based on the available crystal structures of ASIC1 (Acid Sensing Ion Channel 1. MEC-4 and UNC-8 are two DEG/ENaC family members involved in mechanosensation and proprioception respectively, in the nematode Caenorhabditis elegans. We used these models to examine the structural effects of specific mutations that alter channel function in vivo. The trimeric MEC-4 model provides insight into the mechanism by which gain-of-function mutations cause structural alterations that result in increased channel permeability, which trigger cell degeneration. Our analysis provides an introductory framework to further investigate the multimeric organization of the DEG/ENaC ion channel complex.

  9. 斑点叉尾触内脏粗鱼油的精制及其理化指标和脂肪酸组成的分析%Refinement, physicochemical and fatty acid composition analysis of crude fish oil from the viscera of channel catfish

    Institute of Scientific and Technical Information of China (English)

    陆剑锋; 张伟伟; 林琳; 叶应旺; 姜绍通


    The crude fish oil from channel catfish was refined by degumming, neutralizing, bleach- ing and deodorizing. The refined fish oil was yellowish and transparent with very light fishiness. The physi- coehemical indices of refined fish oil were determined, which reached to the fist - grade criterion of refined fish oil of aquatic industry (SC/T 3502 -2000) except the iodine value. The compositions and contents of fatty acid in the refined fish oil were analyzed by gas chromatography - mass spectrometry. The results showed that there were mainly 19 types of fatty acid including C14 - C22 in refined fish oil, including 6 types of saturated fatty acids, 5 types of single unsaturated fatty acids, and 8 types of polyunsaturated fatty acids. The contents of saturated fatty acids, single unsaturated fatty acids and polyunsaturated fatty acids were 20.37% , 65.20% , and 13.66% , respectively. The ratio of ∑n-3 to ∑n-6 was reasonable, indicating that the fatty acids composition of the refined oil was good for human health.%斑点叉尾鲴内脏粗鱼油通过脱胶、脱酸、脱色、脱臭工艺精制后,外观澄清透明,略显淡黄色,并有淡淡的鱼腥味,除碘价低于我国水产行业精制鱼油的一级标准(SC/T3502—2000),其它各类指标均符合精制鱼油的一级标准。对脂肪酸的组成和含量进行分析,斑点叉尾蛔内脏精制油含有19种脂肪酸,主要是由C14-C22组成,其中饱和脂肪酸6种,单不饱和脂肪酸5种,多不饱和脂肪酸8种,其含量分别为20.37%、65.20%和13.66%。∑n-3/∑n-6的比值也较为合理,表明斑点叉尾钿内脏精制油的脂肪酸组成有利于人体健康。

  10. Chloride channels of platelets%血小板氯通道

    Institute of Scientific and Technical Information of China (English)

    陈晓琳; 尹松梅


    Chloride channels distribute widely in the body, and participate in many physiological actions and regulatory processes. Based on their physiological roles and molecular structures, six kinds of chloride channels have been identified: (1) The chloride channels family; (2) Cystic fibrosis transmembrane conductance regulator; (3) Swelling-activated chloride channels; (4) Calcium-activated chloride channels; (5) The p64 (CLIC) gene family; (6) γ-aminobutyric acid and glycine receptors. The chloride channels do exist in platelets, and their appearances are dependent on the presence of intracellular calcium. Blocking agents of chloride channels inhibit the thrombin-activated platelet aggregation and the elevation of the intracellular calcium concentration in a dose-dependent manner. It is suggested that chloride channels play a role in the activation of platelets. In addition, chloride channels act on both the cell volume regulation and the intracellular pH regulation in platelets.

  11. Analysis of Glutamic Acid in Cerebrospinal Fluid by Capillary Electrophoresis with High Frequency Conductivity Detection

    Institute of Scientific and Technical Information of China (English)

    Hai Yun ZHAI; Jun Mei WANG; Xiao Li YAO; Xue Cai TAN; Pei Xiang CAI; Zuan Guang CHEN


    A rapid method to determine glutamic acid (Glu) in cerebrospinal fluid (CSF) by capillary electrophoresis with high frequency conductivity detection (contactless conductivity detection) was described. The CSF sample was pretreated with silver cation resin to remove high concentration of Cl- ions in CSF. The separation was achieved in the buffer solution of 10 mmol/L Tris and 8 mmol/L boric acid at the separation voltage of 20.0 kV. Glu showed linear response in the range of 5.0×10-6 to 6.0×10-3 mol/L, the limit of detection was 1.0×10-6 mol/L. The method was used for analysis Glu in CSF satisfactorily with a recovery of 97.8-98.8%.

  12. Separation of glycols from dilute aqueous solutions via complexation with boronic acids

    Energy Technology Data Exchange (ETDEWEB)

    Randel, L.A.; King, C.J.


    This work examines methods of separating low molecular weight glycols from dilute aqueous solution. Extraction into conventional solvents is generally not economical, since, in the literature reviewed, distribution ratios for the two- to four-carbon glycols are all less than one. Distribution ratios can be increased, however, by incorporating into the organic phase an extracting agent that will complex with the solute of interest. The extracting agent investigated in this work is 3-nitrophenylboronic acid (NPBA). NPBA, a boric acid derivative, reversibly complexes with many glycols. The literature on complexation of borate and related compounds with glycols, including mechanistic data, measurement techniques, and applications to separation processes, provides information valuable for designing experiments with NPBA and is reviewed herein. 88 refs., 15 figs., 24 tabs.

  13. Electrodeposition of nickel powder from nickel sulphate solution in presence of glycerol and sulphuric acid

    Directory of Open Access Journals (Sweden)

    S.G. Viswanath


    Full Text Available Nickel powder was obtained by electrodeposition of nickel from boric acid, glycerol and sulphuric acid. The morphology and particle size of these powders were studied. Spongy, irregular, flaky, fibrous and aggregate particles were obtained. Size of more than 85% particles was smaller than 384µm. From XRD graphs, it was found that the smaller particles are in the range of 106 and 373 nm. The apparent density of nickel powder decreased with increase in concentration of glycerol. The stability of the powder and current efficiency were also studied. In absence of nickel sulphate there was some nickel deposition on the cathode. The effect was discussed in present work. New definition for electrodeposition was suggested.

  14. MEMS in microfluidic channels.

    Energy Technology Data Exchange (ETDEWEB)

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.


    Microelectromechanical systems (MEMS) comprise a new class of devices that include various forms of sensors and actuators. Recent studies have shown that microscale cantilever structures are able to detect a wide range of chemicals, biomolecules or even single bacterial cells. In this approach, cantilever deflection replaces optical fluorescence detection thereby eliminating complex chemical tagging steps that are difficult to achieve with chip-based architectures. A key challenge to utilizing this new detection scheme is the incorporation of functionalized MEMS structures within complex microfluidic channel architectures. The ability to accomplish this integration is currently limited by the processing approaches used to seal lids on pre-etched microfluidic channels. This report describes Sandia's first construction of MEMS instrumented microfluidic chips, which were fabricated by combining our leading capabilities in MEMS processing with our low-temperature photolithographic method for fabricating microfluidic channels. We have explored in-situ cantilevers and other similar passive MEMS devices as a new approach to directly sense fluid transport, and have successfully monitored local flow rates and viscosities within microfluidic channels. Actuated MEMS structures have also been incorporated into microfluidic channels, and the electrical requirements for actuation in liquids have been quantified with an elegant theory. Electrostatic actuation in water has been accomplished, and a novel technique for monitoring local electrical conductivities has been invented.

  15. Drosophila KCNQ channel displays evolutionarily conserved electrophysiology and pharmacology with mammalian KCNQ channels.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

    Full Text Available Of the five human KCNQ (Kv7 channels, KCNQ1 with auxiliary subunit KCNE1 mediates the native cardiac I(Ks current with mutations causing short and long QT cardiac arrhythmias. KCNQ4 mutations cause deafness. KCNQ2/3 channels form the native M-current controlling excitability of most neurons, with mutations causing benign neonatal febrile convulsions. Drosophila contains a single KCNQ (dKCNQ that appears to serve alone the functions of all the duplicated mammalian neuronal and cardiac KCNQ channels sharing roughly 50-60% amino acid identity therefore offering a route to investigate these channels. Current information about the functional properties of dKCNQ is lacking therefore we have investigated these properties here. Using whole cell patch clamp electrophysiology we compare the biophysical and pharmacological properties of dKCNQ with the mammalian neuronal and cardiac KCNQ channels expressed in HEK cells. We show that Drosophila KCNQ (dKCNQ is a slowly activating and slowly-deactivating K(+ current open at sub-threshold potentials that has similar properties to neuronal KCNQ2/3 with some features of the cardiac KCNQ1/KCNE1 accompanied by conserved sensitivity to a number of clinically relevant KCNQ blockers (chromanol 293B, XE991, linopirdine and opener (zinc pyrithione. We also investigate the molecular basis of the differential selectivity of KCNQ channels to the opener retigabine and show a single amino acid substitution (M217W can confer sensitivity to dKCNQ. We show dKCNQ has similar electrophysiological and pharmacological properties as the mammalian KCNQ channels, allowing future study of physiological and pathological roles of KCNQ in Drosophila and whole organism screening for new modulators of KCNQ channelopathies.

  16. TRP channels and pain. (United States)

    Julius, David


    Nociception is the process whereby primary afferent nerve fibers of the somatosensory system detect noxious stimuli. Pungent irritants from pepper, mint, and mustard plants have served as powerful pharmacological tools for identifying molecules and mechanisms underlying this initial step of pain sensation. These natural products have revealed three members of the transient receptor potential (TRP) ion channel family--TRPV1, TRPM8, and TRPA1--as molecular detectors of thermal and chemical stimuli that activate sensory neurons to produce acute or persistent pain. Analysis of TRP channel function and expression has validated the existence of nociceptors as a specialized group of somatosensory neurons devoted to the detection of noxious stimuli. These studies are also providing insight into the coding logic of nociception and how specification of nociceptor subtypes underlies behavioral discrimination of noxious thermal, chemical, and mechanical stimuli. Biophysical and pharmacological characterization of these channels has provided the intellectual and technical foundation for developing new classes of analgesic drugs.

  17. Dequantization Via Quantum Channels (United States)

    Andersson, Andreas


    For a unital completely positive map {Φ} ("quantum channel") governing the time propagation of a quantum system, the Stinespring representation gives an enlarged system evolving unitarily. We argue that the Stinespring representations of each power {Φ^m} of the single map together encode the structure of the original quantum channel and provide an interaction-dependent model for the bath. The same bath model gives a "classical limit" at infinite time {mto∞} in the form of a noncommutative "manifold" determined by the channel. In this way, a simplified analysis of the system can be performed by making the large- m approximation. These constructions are based on a noncommutative generalization of Berezin quantization. The latter is shown to involve very fundamental aspects of quantum-information theory, which are thereby put in a completely new light.

  18. Chaos in quantum channels

    CERN Document Server

    Hosur, Pavan; Roberts, Daniel A; Yoshida, Beni


    We study chaos and scrambling in unitary channels by considering their entanglement properties as states. Using out-of-time-order correlation functions to diagnose chaos, we characterize the ability of a channel to process quantum information. We show that the generic decay of such correlators implies that any input subsystem must have near vanishing mutual information with almost all partitions of the output. Additionally, we propose the negativity of the tripartite information of the channel as a general diagnostic of scrambling. This measures the delocalization of information and is closely related to the decay of out-of-time-order correlators. We back up our results with numerics in two non-integrable models and analytic results in a perfect tensor network model of chaotic time evolution. These results show that the butterfly effect in quantum systems implies the information-theoretic definition of scrambling.


    Institute of Scientific and Technical Information of China (English)

    Zhao Zheng; Jia Ying; Yin Qinye


    Delay diversity is an effective transmit diversity technique to combat adverse ef-fects of fading. Thus far, previous work in delay diversity assumed that perfect estimates ofcurrent channel fading conditions are available at the receiver and training symbols are requiredto estimate the channel from the transmitter to the receiver. However, increasing the number ofthe antennas increases the required training interval and reduces the available time within whichdata may be transmitted. Learning the channel coefficients becomes increasingly difficult for thefrequency selective channels. In this paper, with the subspace method and the delay character ofdelay diversity, a channel estimation method is proposed, which does not use training symbols. Itaddresses the transmit diversity for a frequency selective channel from a single carrier perspectivein the form of a simple equivalent fiat fading model. Monte Carlo simulations give the perfor-mance of channel estimation and the performance comparison of our channel-estimation-baseddetector with decision feedback equalization, which uses the perfect channel information.

  20. K(v)7 channels: function, pharmacology and channel modulators. (United States)

    Dalby-Brown, William; Hansen, Henrik H; Korsgaard, Mads P G; Mirza, Naheed; Olesen, Søren-P


    K(v)7 channels are unique among K(+) channels, since four out of the five channel subtypes have well-documented roles in the development of human diseases. They have distinct physiological functions in the heart and in the nervous system, which can be ascribed to their voltage-gating properties. The K(v)7 channels also lend themselves to pharmacological modulation, and synthetic openers as well as blockers of the channels, regulating neuronal excitability, have existed even before the K(v)7 channels were identified by cloning. In the present review we give an account on the focused efforts to develop selective modulators, openers as well as blockers, of the K(v)7 channel subtypes, which have been undertaken during recent years, along with a discussion of the K(v)7 ion channel physiology and therapeutic indications for modulators of the neuronal K(v)7 channels.

  1. Ionic Channels in Thunderclouds (United States)

    Losseva, T. V.; Fomenko, A. S.; Nemtchinov, I. V.


    We proceed to study the formation and propagation of ionic channels in thunderclouds in the framework of the model of the corona discharge wave propagation (Fomenko A.S., Losseva T.V., Nemtchinov I.V. The corona discharge waves in thunderclouds and formation of ionic channels // 2004 Fall Meeting. EOS Trans. AGU. 2004. V. 85. ¹ 47. Suppl. Abstract AE23A-0835.). In this model we proposed a hypothesis that the structure of a thundercloud becomes nonuniform due to corona discharge on the drops and ice particles and formation of ionic channels with higher conductivity than the surrounding air. When the onset strength of corona discharge becomes smaller than the electric field strength the corona discharge increases concentrations of ions in a small part of the cloud (a hot spot). An additional charge at opposite ends of the hot spot forms due to polarization process. The increased electric field initiates corona discharge in other parts of the cloud on ice particles and water drops with smaller sizes. The corona discharge front moves as a wave with the velocity of the order of ion drift and formes a highly conductive channel. We model this non-stationary problem with Poisson equation which is solved simultaneously with a simplified set of kinetic equations for ions, small charged particles and electrons (at high electric fields), including ionization due to electronic impact, attachment and formation of positive ions. By applying 3D numerical simulations we obtain the parameters of formed ionic channels with respect to onset electric fields both from large particles (in hot spot) and from small particles (surrounding hot spot), microscopic currents from particles with different sizes and the external electric field in the cloud. The interaction of ionic channels is also investigated. This work was supported by Russian Foundation of Basic Research (Project No 07-05-00998-à).

  2. Communicating Under Channel Uncertainty

    CERN Document Server

    Warsi, Naqueeb; Shah, Tapan


    For a single transmit and receive antenna system, a new constellation design is proposed to combat errors in the phase estimate of the channel coefficient. The proposed constellation is a combination of PSK and PAM constellations, where PSK is used to provide protection against phase errors, while PAM is used to increase the transmission rate using the knowledge of the magnitude of the channel coefficient. The performance of the proposed constellation is shown to be significantly better than the widely used QAM in terms of probability of error. The proposed strategy can also be extended to systems using multiple transmit and receive antennas.

  3. Characterization of two-pore channel 2 (TPCN2)-mediated Ca2+ currents in isolated lysosomes. (United States)

    Schieder, Michael; Rötzer, Katrin; Brüggemann, Andrea; Biel, Martin; Wahl-Schott, Christian A


    Two-pore channels (TPCNs) have been proposed to form lysosomal Ca(2+) release channels that are activated by nicotinic acid adenine dinucleotide phosphate. Here, we employ a glass chip-based method to record for the first time nicotinic acid adenine dinucleotide phosphate -dependent currents through a two-pore channel (TPCN2) from intact lysosomes. We show that TPCN2 is a highly selective Ca(2+) channel that is regulated by intralysosomal pH. Using site-directed mutagenesis, we identify an amino acid residue in the putative pore region that is crucial for conferring high Ca(2+) selectivity. Our glass chip-based method will provide electrophysiological access not only to lysosomal TPCN channels but also to a broad range of other intracellular ion channels.

  4. Characterization of Two-pore Channel 2 (TPCN2)-mediated Ca2+ Currents in Isolated Lysosomes* (United States)

    Schieder, Michael; Rötzer, Katrin; Brüggemann, Andrea; Biel, Martin; Wahl-Schott, Christian A.


    Two-pore channels (TPCNs) have been proposed to form lysosomal Ca2+ release channels that are activated by nicotinic acid adenine dinucleotide phosphate. Here, we employ a glass chip-based method to record for the first time nicotinic acid adenine dinucleotide phosphate -dependent currents through a two-pore channel (TPCN2) from intact lysosomes. We show that TPCN2 is a highly selective Ca2+ channel that is regulated by intralysosomal pH. Using site-directed mutagenesis, we identify an amino acid residue in the putative pore region that is crucial for conferring high Ca2+ selectivity. Our glass chip-based method will provide electrophysiological access not only to lysosomal TPCN channels but also to a broad range of other intracellular ion channels. PMID:20495006

  5. Designer proton-channel transgenic algae for photobiological hydrogen production (United States)

    Lee, James Weifu


    A designer proton-channel transgenic alga for photobiological hydrogen production that is specifically designed for production of molecular hydrogen (H.sub.2) through photosynthetic water splitting. The designer transgenic alga includes proton-conductive channels that are expressed to produce such uncoupler proteins in an amount sufficient to increase the algal H.sub.2 productivity. In one embodiment the designer proton-channel transgene is a nucleic acid construct (300) including a PCR forward primer (302), an externally inducible promoter (304), a transit targeting sequence (306), a designer proton-channel encoding sequence (308), a transcription and translation terminator (310), and a PCR reverse primer (312). In various embodiments, the designer proton-channel transgenic algae are used with a gas-separation system (500) and a gas-products-separation and utilization system (600) for photobiological H.sub.2 production.

  6. Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels. (United States)

    Zhao, Qiancheng; Wu, Kun; Geng, Jie; Chi, Shaopeng; Wang, Yanfeng; Zhi, Peng; Zhang, Mingmin; Xiao, Bailong


    Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively.

  7. The phosphoric acid leak from the wreck of the MV Ece in the English Channel in 2006: Assessment with a ship of opportunity, an operational ecosystem model and historical data. (United States)

    Kelly-Gerreyn, Boris A; Hydes, David J; Hartman, Mark C; Siddorn, John; Hyder, Patrick; Holt, Martin W


    This study evaluates the ship of opportunity (Ferrybox) concept for both sustained monitoring of UK shelf sea waters and numerical model validation. Release of phosphate from the wreck of a chemical tanker (MV Ece) in the western English Channel (49.73 degrees N, 3.25 degrees W) in March 2006 is used to demonstrate the importance of sustained observations in decision support systems and policy development. The Ferrybox system continuously collects sea surface (5m) data from a suite of autonomous electronic sensors installed on a passenger ferry operating year-round between Portsmouth (UK) and Bilbao (Spain). The detection of anomalously high concentrations of phosphate (1.54mmolm(-3), four times the usual level) and onset of phytoplankton growth close to the wreck site in March 2006 was placed in the context of multiple years of measurements (phosphate, nitrate, silicate and chlorophyll) collected from the Ferrybox system (2003-2006) and the long-term time series station E1 (50.03 degrees N, 4.65 degrees W, 1930-1987) in the English Channel. With regard to decision support, release of phosphate from the tanker is unlikely to pose a threat as phytoplankton growth at the end of winter is not unusual in this region and dissolved inorganic nitrogen rather than phosphate (DIN:DIP=10-18) is likely to ultimately limit algal growth in spring 2006. With regard to policy development, the Oslo and Paris (OSPAR) commissions recommendation of sampling every three years in "non-problem areas" is likely to provide statistically inadequate data, given the interannual and decadal variability identified in the Ferrybox and E1 data: the Ferrybox data show that oceanic winter nutrient concentrations varied by 35-50% between 2003/2004 and 2005/2006 due to deeper mixing of water off-shelf in early 2005/2006 and comparisons between the Ferrybox and E1 years show that the western English Channel is currently experiencing a low in phosphate concentrations similar to those in the 1960s. The

  8. Conductance of Ion Channels - Theory vs. Experiment (United States)

    Pohorille, Andrew; Wilson, Michael; Mijajlovic, Milan


    Transmembrane ion channels mediate a number of essential physiological processes in a cell ranging from regulating osmotic pressure to transmission of neural signals. Kinetics and selectivity of ion transport is of critical importance to a cell and, not surprisingly, it is a subject of numerous experimental and theoretical studies. In this presentation we will analyze in detail computer simulations of two simple channels from fungi - antiamoebin and trichotoxin. Each of these channels is made of an alpha-helical bundle of small, nongenomically synthesized peptides containing a number of rare amino acids and exhibits strong antimicrobial activity. We will focus on calculating ionic conductance defined as the ratio of ionic current through the channel to applied voltage. From molecular dynamics simulations, conductance can be calculated in at least two ways, each involving different approximations. Specifically, the current, given as the number of charges transferred through the channel per unit of time, can be obtained from the number of events in which ions cross the channel during the simulation. This method works well for large currents (high conductance values and/or applied voltages). If the number of crossing events is small, reliable estimates of current are difficult to achieve. Alternatively, conductance can be estimated assuming that ion transport can be well approximated as diffusion in the external potential given by the free energy profile. Then, the current can be calculated by solving the one-dimensional diffusion equation in this external potential and applied voltage (the generalized Nernst-Planck equation). To do so three ingredients are needed: the free energy profile, the position-dependent diffusion coefficient and the diffusive flux of ions into the channel. All these quantities can be obtained from molecular dynamics simulations. An important advantage of this method is that it can be used equally well to estimating large and small currents

  9. Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function. (United States)

    Baycin-Hizal, Deniz; Gottschalk, Allan; Jacobson, Elena; Mai, Sunny; Wolozny, Daniel; Zhang, Hui; Krag, Sharon S; Betenbaugh, Michael J


    Voltage-gated ion channels are transmembrane proteins that regulate electrical excitability in cells and are essential components of the electrically active tissues of nerves, muscle and the heart. Potassium channels are one of the largest subfamilies of voltage sensitive channels and are among the most-studied of the voltage-gated ion channels. Voltage-gated channels can be glycosylated and changes in the glycosylation pattern can affect ion channel function, leading to neurological and neuromuscular disorders and congenital disorders of glycosylation (CDG). Alterations in glycosylation can also be acquired and appear to play a role in development and aging. Recent studies have focused on the impact of glycosylation and sialylation on ion channels, particularly for voltage-gated potassium and sodium channels. The terminal step of sialylation often affects channel activation and inactivation kinetics. The presence of sialic acids on O or N-glycans can alter the gating mechanism and cause conformational changes in the voltage-sensing domains due to sialic acid's negative charges. This manuscript will provide an overview of sialic acids, potassium and sodium channel function, and the impact of sialylation on channel activation and deactivation.

  10. All channels open

    NARCIS (Netherlands)

    Frank Huysmans; Jos de Haan


    Original title: Alle kanalen staan open. The rapid changes taking place in the media landscape in the Netherlands - characterised by digitisation and convergence of media technologies - raise the question of how the Dutch are dealing with the many new opportunities that have opened up. All channels


    Directory of Open Access Journals (Sweden)

    Enrique eBalderas


    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.

  12. Ion Channels in Leukocytes (United States)


    muscle k142), heart muscle (80), bo- are released. In recent years much has been learned vine pulmonar arter endothelial cells (251), and rat about analysbib of Lt. Potassium permeability in HeLa cancer BioL Chem. 265: 142416-141263, 1990. cells. evidence for a calcium-a’tivated potassium

  13. Intermittency and exotic channels

    CERN Document Server

    Bialas, A


    It is pointed out that accurate measurements of short-range two-particle correlations in like-charge K\\pi and in \\pi^ 0\\pi^ 0 channels should be very helpful in determining the origin of the \\lq\\lq intermittency\\rq\\rq\\ phenomenon observed recently for the like-charge pion pairs.

  14. TRP channels: an overview

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd


    to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs....

  15. Chip-based sequencing nucleic acids (United States)

    Beer, Neil Reginald


    A system for fast DNA sequencing by amplification of genetic material within microreactors, denaturing, demulsifying, and then sequencing the material, while retaining it in a PCR/sequencing zone by a magnetic field. One embodiment includes sequencing nucleic acids on a microchip that includes a microchannel flow channel in the microchip. The nucleic acids are isolated and hybridized to magnetic nanoparticles or to magnetic polystyrene-coated beads. Microreactor droplets are formed in the microchannel flow channel. The microreactor droplets containing the nucleic acids and the magnetic nanoparticles are retained in a magnetic trap in the microchannel flow channel and sequenced.

  16. Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions. (United States)

    Feijóo-Bandín, Sandra; García-Vence, María; García-Rúa, Vanessa; Roselló-Lletí, Esther; Portolés, Manuel; Rivera, Miguel; González-Juanatey, José Ramón; Lago, Francisca


    Two-pore channels (TPC1-3) comprise a subfamily of the eukaryotic voltage-gated ion channels (VGICs) superfamily that are mainly expressed in acidic stores in plants and animals. TPCS are widespread across the animal kingdom, with primates, mice and rats lacking TPC3, and mainly act as Ca(+) and Na(+) channels, although it was also suggested that they could be permeable to other ions. Nowadays, TPCs have been related to the development of different diseases, including Parkinson´s disease, obesity or myocardial ischemia. Due to this, their study has raised the interest of the scientific community to try to understand their mechanism of action in order to be able to develop an efficient drug that could regulate TPCs activity. In this review, we will provide an updated view regarding TPCs structure, function and activation, as well as their role in different pathophysiological processes.

  17. K sup + channel openers activate brain sulfonylurea-sensitive K sup + channels and block neurosecretion

    Energy Technology Data Exchange (ETDEWEB)

    Schmid-Antomarchi, H.; Amoroso, S.; Fosset, M.; Lazdunski, M. (Centre National de la Recherche Scientifique, Valbonne (France))


    Vascular K{sup +} channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate {sup 86}Rb{sup +} efflux from slices of substantia nigra. This {sup 86}Rb{sup +} efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K{sup +} channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K{sub 0.5}, the half-maximal effect of the enantiomer ({minus})-cromakalim, is as low as 10 nM, whereas K{sub 0.5} for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K{sup +} channels lead to inhibition of {gamma}-aminobutyric acid release. There is an excellent relationship between potency to activate {sup 86}Rb{sup +} efflux and potency to inhibit neurotransmitter release.

  18. Characterization of Two-pore Channel 2 (TPCN2)-mediated Ca2+ Currents in Isolated Lysosomes*


    Schieder, Michael; Rötzer, Katrin; Brüggemann, Andrea; Biel, Martin; Wahl-Schott, Christian A.


    Two-pore channels (TPCNs) have been proposed to form lysosomal Ca2+ release channels that are activated by nicotinic acid adenine dinucleotide phosphate. Here, we employ a glass chip-based method to record for the first time nicotinic acid adenine dinucleotide phosphate -dependent currents through a two-pore channel (TPCN2) from intact lysosomes. We show that TPCN2 is a highly selective Ca2+ channel that is regulated by intralysosomal pH. Using site-directed mutagenesis, we identify an amino ...

  19. Mathematical Modeling on Open Limestone Channel

    CERN Document Server

    Bandstra, Joel; Wu, Naiyi


    Acid mine drainage (AMD) is the outflow of acidic water from metal mines or coal mines. When exposed to air and water, metal sulfides from the deposits of the mines are oxidized and produce acid, metal ions and sulfate, which lower the pH value of the water. An open limestone channel (OLC) is a passive and low cost way to neutralize AMD. The dissolution of calcium into the water increases the pH value of the solution. A differential equation model is numerically solved to predict the variation of concentration of each species in the OLC solution. The diffusion of Calcium due to iron precipitates is modeled by a linear equation. The results give the variation of pH value and the concentration of Calcium.

  20. A New Covert Channel over Cellular Voice Channel in Smartphones


    Aloraini, Bushra; Johnson, Daryl; Stackpole, Bill; Mishra, Sumita


    Investigating network covert channels in smartphones has become increasingly important as smartphones have recently replaced the role of traditional computers. Smartphones are subject to traditional computer network covert channel techniques. Smartphones also introduce new sets of covert channel techniques as they add more capabilities and multiple network connections. This work presents a new network covert channel in smartphones. The research studies the ability to leak information from the...

  1. An Optical Test Strip for the Detection of Benzoic Acid in Food

    Directory of Open Access Journals (Sweden)

    Fatimah Abu Bakar


    Full Text Available Fabrication of a test strip for detection of benzoic acid was successfully implemented by immobilizing tyrosinase, phenol and 3-methyl-2-benzothiazolinone hydrazone (MBTH onto filter paper using polystyrene as polymeric support. The sensing scheme was based on the decreasing intensity of the maroon colour of the test strip when introduced into benzoic acid solution. The test strip was characterized using optical fiber reflectance and has maximum reflectance at 375 nm. It has shown a highly reproducible measurement of benzoic acid with a calculated RSD of 0.47% (n = 10. The detection was optimized at pH 7. A linear response of the biosensor was obtained in 100 to 700 ppm of benzoic acid with a detection limit (LOD of 73.6 ppm. At 1:1 ratio of benzoic acid to interfering substances, the main interfering substance is boric acid. The kinetic analyses show that, the inhibition of benzoic is competitive inhibitor and the inhibition constant (Ki is 52.9 ppm. The activity of immobilized tyrosinase, phenol, and MBTH in the test strip was fairly sustained during 20 days when stored at 3 °C. The developed test strip was used for detection of benzoic acid in food samples and was observed to have comparable results to the HPLC method, hence the developed test strip can be used as an alternative to HPLC in detecting benzoic acid in food products.

  2. 丹酚酸B和延胡索乙素对大鼠心室肌细胞L-型钙通道的影响%Effect of Salvianolic Acid B and Tetrahydropalmatine on the L-type Calcium Channel of Rat Ventricular Myocytes

    Institute of Scientific and Technical Information of China (English)

    孟红旭; 王宝; 刘建勋


    目的 观察单独及联合使用丹酚酸B和延胡索乙素对大鼠心室肌细胞L-型钙通道的影响.方法 采用急性酶解分离法获得大鼠的单个心肌细胞,使用全细胞膜片钳技术记录钙通道电流.观察给药前后钙通道电流峰值(钙电流活化后峰值点与完全失活后电流轨迹的垂直距离)的变化.结果 单独使用丹酚酸B(1,10,100 μmol/L)对钙电流峰值的抑制率分别为:(25.3±16.4)%(n=4),(44.6±24.0)%(n=6),(86.0±20.4)%(n=4).单独使用延胡索乙素(10,30,100 μmol/L)对钙电流峰值的抑制率分别为:(22.2±6.4)%(n=5),(27.4±1.6)%(n=3),(51.0±23.0)%(n=9);联合使用丹酚酸B(1μmoL/L)和延胡索乙素(10 μmol/L)对钙通道电流峰值的抑制作用强于单独使用丹酚酸B(1 μmol/L)或延胡索乙素(10μmoL/L),差异有统计学意义(P<0.05);盐酸阿托品(14 mmoL/L)能够逆转延胡索乙素对L-型钙通道的抑制作用,而加强丹酚酸B的抑制作用.结论 丹酚酸B和延胡索乙素对大鼠心室肌细胞L-型钙通道均有抑制作用,两者之间能够产生协同效应,并且这两种有效成分调控L-型钙通道的作用机制不同.%Objective To observe the effects of the separate and joint use of salvianolic acid B (SalB) and tetrahydropalmatine (THP) on the L-type calcium channel of rat ventricular myocytes. Methods Single isolated ventricular myocytes of rats were obtained using acute enzymolysis separation. The current of the L-type calcium channel was recorded using whole-cell patch clamp technique. Changes of the current peak value of the calcium channel (the vertical distance between the peak value point after activation of the calcium electric current and the electric current track after complete inactivation) were observed before and after medication. Results The inhibition rate of using SalB (at the dose of 1, 10, and 100 μmol/L) alone on the current peak value of the calcium channel was respectively (25. 3 ±16. 4)% (n=4

  3. Radar channel balancing with commutation

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter


    When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

  4. Geysering in boiling channels

    Energy Technology Data Exchange (ETDEWEB)

    Aritomi, Masanori; Takemoto, Takatoshi [Tokyo Institute of Technology, Tokyo (Japan); Chiang, Jing-Hsien [Japan NUS Corp. Ltd., Toyko (Japan)] [and others


    A concept of natural circulation BWRs such as the SBWR has been proposed and seems to be promising in that the primary cooling system can be simplified. The authors have been investigating thermo-hydraulic instabilities which may appear during the start-up in natural circulation BWRs. In our previous works, geysering was investigated in parallel boiling channels for both natural and forced circulations, and its driving mechanism and the effect of system pressure on geysering occurrence were made clear. In this paper, geysering is investigated in a vertical column and a U-shaped vertical column heated in the lower parts. It is clarified from the results that the occurrence mechanism of geysering and the dependence of system pressure on geysering occurrence coincide between parallel boiling channels in circulation systems and vertical columns in non-circulation systems.

  5. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas


    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  6. ``Just Another Distribution Channel?'' (United States)

    Lemstra, Wolter; de Leeuw, Gerd-Jan; van de Kar, Els; Brand, Paul

    The telecommunications-centric business model of mobile operators is under attack due to technological convergence in the communication and content industries. This has resulted in a plethora of academic contributions on the design of new business models and service platform architectures. However, a discussion of the challenges that operators are facing in adopting these models is lacking. We assess these challenges by considering the mobile network as part of the value system of the content industry. We will argue that from the perspective of a content provider the mobile network is ‘just another’ distribution channel. Strategic options available for the mobile communication operators are to deliver an excellent distribution channel for content delivery or to move upwards in the value chain by becoming a content aggregator. To become a mobile content aggregator operators will have to develop or acquire complementary resources and capabilities. Whether this strategic option is sustainable remains open.

  7. DMT of weighted Parallel Channels: Application to Broadcast Channel

    CERN Document Server

    Mroueh, Lina; Othman, Ghaya Rekaya-Ben; Belfiore, Jean-Claude


    In a broadcast channel with random packet arrival and transmission queues, the stability of the system is achieved by maximizing a weighted sum rate capacity with suitable weights that depend on the queue size. The weighted sum rate capacity using Dirty Paper Coding (DPC) and Zero Forcing (ZF) is asymptotically equivalent to the weighted sum capacity over parallel single-channels. In this paper, we study the Diversity Multiplexing Tradeoff (DMT) of the fading broadcast channel under a fixed weighted sum rate capacity constraint. The DMT of both identical and different parallel weighted MISO channels is first derived. Finally, we deduce the DMT of a broadcast channel using DPC and ZF precoders.

  8. On partially entanglement breaking channels

    CERN Document Server

    Chruscinski, D; Chruscinski, Dariusz; Kossakowski, Andrzej


    Using well known duality between quantum maps and states of composite systems we introduce the notion of Schmidt number of a quantum channel. It enables one to define classes of quantum channels which partially break quantum entanglement. These classes generalize the well known class of entanglement breaking channels.

  9. Ion channels: molecular targets of neuroactive insecticides. (United States)

    Raymond-Delpech, Valérie; Matsuda, Kazuhiko; Sattelle, Benedict M; Rauh, James J; Sattelle, David B


    Many of the insecticides in current use act on molecular targets in the insect nervous system. Recently, our understanding of these targets has improved as a result of the complete sequencing of an insect genome, i.e., Drosophila melanogaster. Here we examine the recent work, drawing on genetics, genomics and physiology, which has provided evidence that specific receptors and ion channels are targeted by distinct chemical classes of insect control agents. The examples discussed include, sodium channels (pyrethroids, p,p'-dichlorodiphenyl-trichloroethane (DDT), dihydropyrazoles and oxadiazines); nicotinic acetylcholine receptors (cartap, spinosad, imidacloprid and related nitromethylenes/nitroguanidines); gamma-aminobutyric acid (GABA) receptors (cyclodienes, gamma-BHC and fipronil) and L-glutamate receptors (avermectins). Finally, we have examined the molecular basis of resistance to these molecules, which in some cases involves mutations in the molecular target, and we also consider the future impact of molecular genetic technologies in our understanding of the actions of neuroactive insecticides.

  10. Ion channeling revisited

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, Barney Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Corona, Aldo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nguyen, Anh [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    A MS Excel program has been written that calculates accidental, or unintentional, ion channeling in cubic bcc, fcc and diamond lattice crystals or polycrystalline materials. This becomes an important issue when simulating the creation by energetic neutrons of point displacement damage and extended defects using beams of ions. All of the tables and graphs in the three Ion Beam Analysis Handbooks that previously had to be manually looked up and read from were programed into Excel in handy lookup tables, or parameterized, for the case of the graphs, using rather simple exponential functions with different powers of the argument. The program then offers an extremely convenient way to calculate axial and planar half-angles and minimum yield or dechanneling probabilities, effects on half-angles of amorphous overlayers, accidental channeling probabilities for randomly oriented crystals or crystallites, and finally a way to automatically generate stereographic projections of axial and planar channeling half-angles. The program can generate these projections and calculate these probabilities for axes and [hkl] planes up to (555).

  11. Cloning and expression of a FMRFamide-gated Na+ channel from Helisoma trivolvis and comparison with the native neuronal channel (United States)

    Jeziorski, Michael C; Green, Kevin A; Sommerville, John; Cottrell, Glen A


    We have cloned a cDNA encoding a Phe-Met-Arg-Phe-NH2 (FMRFamide)-gated Na+ channel from nervous tissue of the pond snail Helisoma trivolvis (HtFaNaC) and expressed the channel in Xenopus oocytes. The deduced amino acid sequence of the protein expressed by HtFaNaC is 65 % identical to that of the FMRFamide-gated channel cloned from Helix aspersa (HaFaNaC). HtFaNaC expressed in oocytes was less sensitive to FMRFamide (EC50 = 70 μM) than HaFaNaC (EC50 = 2 μM). The two had a similar selectivity for Na+. The amplitude of the FMRFamide response of HtFaNaC was increased by reducing the extracellular concentration of divalent cations. The conductance of the two channels was similar, but the mean open time of unitary events was shorter for expressed HtFaNaC compared to expressed HaFaNaC. Each channel was susceptible to peptide block by high agonist concentrations. In marked contrast to HaFaNaC and other amiloride-sensitive Na+ channels, amiloride, and the related drugs benzamil and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), enhanced the FMRFamide response in oocytes expressing HtFaNaC cRNA. The potentiating effects of EIPA and benzamil were greater than those of amiloride. Unitary current analysis showed that with such drugs, there was channel blockade as well as an increased probability of channel opening. The similar permeability of the oocyte-expressed HtFaNaC and the Helisoma neuronal channel, and the susceptibility of both to agonist blockade and blockade by divalent cations, suggest that the channels are the same. However, neuronal channels were less susceptible to enhancement by amiloride analogues and in some patches were more sensitive to FMRFamide than expressed HtFaNaC. PMID:10878095

  12. Ultrasonic Strengthening Low Grade Boric Magnesium Ore Acidolysis Reaction%超声强化低品位硼镁矿石酸解反应过程研究

    Institute of Scientific and Technical Information of China (English)

    王国胜; 杨鹤南; 齐广


    以辽宁花园沟低品位硼镁矿为原料,在搅拌和硫酸酸解过程基础上,引入超声辅助强化酸解过程,考察了超声功率与温度的影响,对比搅拌与超声辅助酸解过程得到,超声辅助可以降低反应温度,缩短反应时间,其产品收率增加,质量提高,硼酸晶体颗粒均匀且晶粒大。%Used low grade boric magnesium ore from Liaoning garden ditch as raw material, based on the condition of stirring, introduction of ultrasonic auxiliary have strengthened acidolysis process, the effect of ultrasonic power and temperature were investigated, and compared to stir and ultrasonic assisted acidolysis process, ultrasound assisted can reduce the reaction temperature, reaction time, the product yield increased, quality improved, borate crystals was uniform grain and grain size was big.

  13. Ion selectivity strategies of sodium channel selectivity filters. (United States)

    Dudev, Todor; Lim, Carmay


    CONSPECTUS: Sodium ion channels selectively transport Na(+) cations across the cell membrane. These integral parts of the cell machinery are implicated in regulating the cardiac, skeletal and smooth muscle contraction, nerve impulses, salt and water homeostasis, as well as pain and taste perception. Their malfunction often results in various channelopathies of the heart, brain, skeletal muscles, and lung; thus, sodium channels are key drug targets for various disorders including cardiac arrhythmias, heart attack, stroke, migraine, epilepsy, pain, cancer, and autoimmune disorders. The ability of sodium channels to discriminate the native Na(+) among other competing ions in the surrounding fluids is crucial for proper cellular functions. The selectivity filter (SF), the narrowest part of the channel's open pore, lined with amino acid residues that specifically interact with the permeating ion, plays a major role in determining Na(+) selectivity. Different sodium channels have different SFs, which vary in the symmetry, number, charge, arrangement, and chemical type of the metal-ligating groups and pore size: epithelial/degenerin/acid-sensing ion channels have generally trimeric SFs lined with three conserved neutral serines and/or backbone carbonyls; eukaryotic sodium channels have EKEE, EEKE, DKEA, and DEKA SFs with an invariant positively charged lysine from the second or third domain; and bacterial voltage-gated sodium (Nav) channels exhibit symmetrical EEEE SFs, reminiscent of eukaryotic voltage-gated calcium channels. How do these different sodium channel SFs achieve high selectivity for Na(+) over its key rivals, K(+) and Ca(2+)? What factors govern the metal competition in these SFs and which of these factors are exploited to achieve Na(+) selectivity in the different sodium channel SFs? The free energies for replacing K(+) or Ca(2+) bound inside different model SFs with Na(+), evaluated by a combination of density functional theory and continuum dielectric

  14. Pharmacodynamics of potassium channel openers in cultured neuronal networks. (United States)

    Wu, Calvin; V Gopal, Kamakshi; Lukas, Thomas J; Gross, Guenter W; Moore, Ernest J


    A novel class of drugs - potassium (K(+)) channel openers or activators - has recently been shown to cause anticonvulsive and neuroprotective effects by activating hyperpolarizing K(+) currents, and therefore, may show efficacy for treating tinnitus. This study presents measurements of the modulatory effects of four K(+) channel openers on the spontaneous activity and action potential waveforms of neuronal networks. The networks were derived from mouse embryonic auditory cortices and grown on microelectrode arrays. Pentylenetetrazol was used to create hyperactivity states in the neuronal networks as a first approximation for mimicking tinnitus or tinnitus-like activity. We then compared the pharmacodynamics of the four channel activators, retigabine and flupirtine (voltage-gated K(+) channel KV7 activators), NS1619 and isopimaric acid ("big potassium" BK channel activators). The EC50 of retigabine, flupirtine, NS1619, and isopimaric acid were 8.0, 4.0, 5.8, and 7.8µM, respectively. The reduction of hyperactivity compared to the reference activity was significant. The present results highlight the notion of re-purposing the K(+) channel activators for reducing hyperactivity of spontaneously active auditory networks, serving as a platform for these drugs to show efficacy toward target identification, prevention, as well as treatment of tinnitus.

  15. Ion Channels in Neurological Disorders. (United States)

    Kumar, Pravir; Kumar, Dhiraj; Jha, Saurabh Kumar; Jha, Niraj Kumar; Ambasta, Rashmi K


    The convergent endeavors of the neuroscientist to establish a link between clinical neurology, genetics, loss of function of an important protein, and channelopathies behind neurological disorders are quite intriguing. Growing evidence reveals the impact of ion channels dysfunctioning in neurodegenerative disorders (NDDs). Many neurological/neuromuscular disorders, viz, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and age-related disorders are caused due to altered function or mutation in ion channels. To maintain cell homeostasis, ion channels are playing a crucial role which is a large transmembrane protein. Further, these channels are important as it determines the membrane potential and playing critically in the secretion of neurotransmitter. Behind NDDs, losses of pathological proteins and defective ion channels have been reported and are found to aggravate the disease symptoms. Moreover, ion channel dysfunctions are eliciting a range of symptoms, including memory loss, movement disabilities, neuromuscular sprains, and strokes. Since the possible mechanistic role played by aberrant ion channels, their receptor and associated factors in neurodegeneration remained elusive; therefore, it is a challenging task for the neuroscientist to implement the therapeutics for targeting NDDs. This chapter reviews the potential role of the ion channels in membrane physiology and brain homeostasis, where ion channels and their associated factors have been characterized with their functional consequences in neurological diseases. Moreover, mechanistic role of perturbed ion channels has been identified in various NDDs, and finally, ion channel modulators have been investigated for their therapeutic intervention in treating common NDDs.

  16. HCN Channels and Heart Rate

    Directory of Open Access Journals (Sweden)

    Ilaria Dentamaro


    Full Text Available Hyperpolarization and Cyclic Nucleotide (HCN -gated channels represent the molecular correlates of the “funny” pacemaker current (If, a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

  17. Effects of calcium channel on 3-morpholinosydnonimine-induced rat hippocampal neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Quanzhong Chang; Shuling Zhang; Yuanyin Zheng; Lijuan Xu; Jinbao Yin; Shining Cai


    Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus.The present study investigated the effects of the broad-spectrum calcium channel blocker CdC12 on survival rate, percentage of apoptosis, and morphological changes in hippocampal neurons cultured in vitro, as well as the effects of calcium channels on neuronal apoptosis.The chloride channel blockers 4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulfonic acid (SITS) or 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) increased the survival rate of 3-morpholinosydnonimine (SIN-1)-treated neurons and suppressed SIN-1-induced neuronal apoptosis.The calcium channel blocker CdC12 did not increase the survival rate of neurons and did not affect SIN-1-induced apoptosis or SITS- or DIDS-suppressed neuronal apoptosis.Results demonstrated that calcium channels did not significantly affect neuronal apoptosis.

  18. Nanometer-scale water- and proton-diffusion heterogeneities across water channels in polymer electrolyte membranes. (United States)

    Song, Jinsuk; Han, Oc Hee; Han, Songi


    Nafion, the most widely used polymer for electrolyte membranes (PEMs) in fuel cells, consists of a fluorocarbon backbone and acidic groups that, upon hydration, swell to form percolated channels through which water and ions diffuse. Although the effects of the channel structures and the acidic groups on water/ion transport have been studied before, the surface chemistry or the spatially heterogeneous diffusivity across water channels has never been shown to directly influence water/ion transport. By the use of molecular spin probes that are selectively partitioned into heterogeneous regions of the PEM and Overhauser dynamic nuclear polarization relaxometry, this study reveals that both water and proton diffusivity are significantly faster near the fluorocarbon and the acidic groups lining the water channels than within the water channels. The concept that surface chemistry at the (sub)nanometer scale dictates water and proton diffusivity invokes a new design principle for PEMs.

  19. Identification of cyclic nucleotide gated channels using regular expressions

    KAUST Repository

    Zelman, Alice K.


    Cyclic nucleotide-gated channels (CNGCs) are nonselective cation channels found in plants, animals, and some bacteria. They have a six-transmembrane/one- pore structure, a cytosolic cyclic nucleotide-binding domain, and a cytosolic calmodulin-binding domain. Despite their functional similarities, the plant CNGC family members appear to have different conserved amino acid motifs within corresponding functional domains than animal and bacterial CNGCs do. Here we describe the development and application of methods employing plant CNGC-specific sequence motifs as diagnostic tools to identify novel candidate channels in different plants. These methods are used to evaluate the validity of annotations of putative orthologs of CNGCs from plant genomes. The methods detail how to employ regular expressions of conserved amino acids in functional domains of annotated CNGCs and together with Web tools such as PHI-BLAST and ScanProsite to identify novel candidate CNGCs in species including Physcomitrella patens. © Springer Science+Business Media New York 2013.

  20. VGIchan: Prediction and Classification of Voltage-Gated Ion Channels

    Institute of Scientific and Technical Information of China (English)

    Sudipto Saha; Jyoti Zack; Balvinder Singh; G.P.S. Raghava


    This study describes methods for predicting and classifying voltage-gated ion channels. Firstly, a standard support vector machine (SVM) method was developed for predicting ion channels by using amino acid composition and dipeptide composition, with an accuracy of 82.89% and 85.56%, respectively. The accuracy of this SVM method was improved from 85.56% to 89.11% when combined with PSIBLAST similarity search. Then we developed an SVM method for classifying ion channels (potassium, sodium, calcium, and chloride) by using dipeptide composition and achieved an overall accuracy of 96.89%. We further achieved a classification accuracy of 97.78% by using a hybrid method that combines dipeptidebased SVM and hidden Markov model methods. A web server VGIchan has been developed for predicting and classifying voltage-gated ion channels using the above approaches. VGIchan is freely available at

  1. The Structural Basis and Functional Consequences of Interactions Between Tetrodotoxin and Voltage-Gated Sodium Channels

    Directory of Open Access Journals (Sweden)

    C. Ruben


    Full Text Available Abstract: Tetrodotoxin (TTX is a highly specific blocker of voltage-gated sodium channels. The dissociation constant of block varies with different channel isoforms. Until recently, channel resistance was thought to be primarily imparted by amino acid substitutions at a single position in domain I. Recent work reveals a novel site for tetrodotoxin resistance in the P-region of domain IV.

  2. Study on stabilities and electrochemical behavior of V(V) electrolyte with acid additives for vanadium redox flow battery

    Institute of Scientific and Technical Information of China (English)

    Gang; Wang; Jinwei; Chen; Xueqin; Wang; Jing; Tian; Hong; Kang; Xuejing; Zhu; Yu; Zhang; Xiaojiang; Liu; Ruilin; Wang


    Several acid compounds have been employed as additives of the V(V) electrolyte for vanadium redox flow battery(VRB) to improve its stability and electrochemical activity. Stability of the V(V) electrolyte with and without additives was investigated with ex-situ heating/cooling treatment at a wide temperature range of-5 ?C to 60 ?C. It was observed that methanesulfonic acid, boric acid, hydrochloric acid, trifluoroacetic acid,polyacrylic acid, oxalic acid, methacrylic acid and phosphotungstic acid could improve the stability of the V(V) electrolyte at a certain range of temperature. Their electrochemical behaviors in the V(V) electrolyte were further studied by cyclic voltammetry(CV), steady state polarization and electrochemical impedance spectroscopy(EIS). The results showed that the electrochemical activity, including the reversibility of electrode reaction, the diffusivity of V(V) species, the polarization resistance and the flexibility of charge transfer for the V(V) electrolyte with these additives were all improved compared with the pristine solution.

  3. Carbon monoxide: an emerging regulator of ion channels. (United States)

    Wilkinson, William J; Kemp, Paul J


    Carbon monoxide is rapidly emerging as an important cellular messenger, regulating a wide range of physiological processes. Crucial to its role in both physiology and disease is its ability differentially to regulate several classes of ion channels, including examples from calcium-activated K(+) (BK(Ca)), voltage-activated K(+) (K(v)) and Ca(2+) channel (L-type) families, ligand-gated P2X receptors (P2X2 and P2X4), tandem P domain K(+) channels (TREK1) and the epithelial Na(+) channel (ENaC). The mechanisms by which CO regulates these ion channels are still unclear and remain somewhat controversial. However, available structure-function studies suggest that a limited range of amino acid residues confer CO sensitivity, either directly or indirectly, to particular ion channels and that cellular redox state appears to be important to the final integrated response. Whatever the molecular mechanism by which CO regulates ion channels, endogenous production of this gasotransmitter has physiologically important roles and is currently being explored as a potential therapeutic.

  4. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan


    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  5. Channel Wall Landslides (United States)


    [figure removed for brevity, see original site] The multiple landslides in this VIS image occur along a steep channel wall. Note the large impact crater in the context image. The formation of the crater may have initially weakened that area of the surface prior to channel formation. Image information: VIS instrument. Latitude -2.7, Longitude 324.8 East (35.2 West). 19 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  6. Multiuser MIMO Channel Estimation

    Directory of Open Access Journals (Sweden)



    Full Text Available In this paper, three beamforming design are considered for multi user MIMO system. First, transmit beamformers are fixed and the receive (RX beamformers are calculated. Transmit beamformer (TX-BFis projectedas a null space of appropriate channels. It reduces the interference for each user. Then the receiver beamformer is determined which maximize the SNR. This beamforming design provides less computation time. The second case is joint TX and RX beamformer for SNR maximization. In this transmitter and receiver beamformer are calculated using extended alternating optimization (EAO algorithm. The third one is joint transmitter and receiver beamforming for SNR and SINR maximization using EAO algorithm. This algorithm provides better error performance and sum rate performance. All the design cases are simulated by using standard multipath channel model. Our simulation results illustrate that compared to the least square design and zero forcing design, the joint TX and RX beamforming design using EAO algorithm provides faster beamforming and improved error performance and sum rate.

  7. A Micromechanical RF Channelizer (United States)

    Akgul, Mehmet

    The power consumption of a radio generally goes as the number and strength of the RF signals it must process. In particular, a radio receiver would consume much less power if the signal presented to its electronics contained only the desired signal in a tiny percent bandwidth frequency channel, rather than the typical mix of signals containing unwanted energy outside the desired channel. Unfortunately, a lack of filters capable of selecting single channel bandwidths at RF forces the front-ends of contemporary receivers to accept unwanted signals, and thus, to operate with sub-optimal efficiency. This dissertation focuses on the degree to which capacitive-gap transduced micromechanical resonators can achieve the aforementioned RF channel-selecting filters. It aims to first show theoretically that with appropriate scaling capacitive-gap transducers are strong enough to meet the needed coupling requirements; and second, to fully detail an architecture and design procedure needed to realize said filters. Finally, this dissertation provides an actual experimentally demonstrated RF channel-select filter designed using the developed procedures and confirming theoretical predictions. Specifically, this dissertation introduces four methods that make possible the design and fabrication of RF channel-select filters. The first of these introduces a small-signal equivalent circuit for parallel-plate capacitive-gap transduced micromechanical resonators that employs negative capacitance to model the dependence of resonance frequency on electrical stiffness in a way that facilitates the analysis of micromechanical circuits loaded with arbitrary electrical impedances. The new circuit model not only correctly predicts the dependence of electrical stiffness on the impedances loading the input and output electrodes of parallel-plate capacitive-gap transduced micromechanical device, but does so in a visually intuitive way that identifies current drive as most appropriate for

  8. Determination of Protocatechuic Acid in CORTEX ACANTHOPANACIS Using High Proficiency Liquid Chromatography Coupled with Four-channel UV-visible Detector%高效液相色谱-四通道紫外可见检测法测定五加皮中原儿茶酸含量

    Institute of Scientific and Technical Information of China (English)

    陈芳; 冯丽娟


    [目的]建立五加皮中原儿茶酸的含量测定方法.[方法]采用高效液相色谱-四通道紫外可见检测法,以ODSC18(柱长250mm,内径4.6mm,涂布厚度5μm)为色谱柱,流动相为甲醇∶磷酸二氢钠缓冲溶液(浓度0.1 mol/L)=15:85,pH =2.5,测定五加皮中原儿荼酸的含量.四通道紫外检测的定性检测波长分别为245、260、275、290 nm;定量检测波长为260nm.[结果]原儿茶酸在0.5 ~6.0 mg/L范围内线性关系良好(r =0.999 9),平均回收率为99.87%,RSD为2.11%.[结论]该方法测定结果可靠,稳定易行,重复性好,可用于五加皮中原儿茶酸的含量测定.%[Objective]To established a quantitative method of determination of protocatechuic acid in cortex acanthopanacis radicis. [Method] High proficiency liquid chromatography ( HPLC ) coupled with four-channel UV-visible detector was used, C,, chromatographic column, mobile phase was the buffer solution of methanol and sodium dihydrogen phosphate (0.1 mol/L) ,the volume ratio of methanol and sodium dihydrogen phosphate was 15=85 ,pH = 2.5. Qualitative evaluation was done by retention time and four-channel UV spectrum at the same time,and the detec tion wavelength were 245 nm,260 nm,275 nm,290 nm. Selected the best sensitive wave of 260 nm to make quantitative evaluation. Result:The linearity of protocatechuic acid was in the range of 0. 5 -6.0 ml/L (r =0.999 9) ,the average recovery was 99.87% ,the RSD was 2.11%. [Con clusion] The method is reliable,and can be used for quality control of cortex acanthopanacis radicis.

  9. In vivo evaluation of [{sup 11}C]-3-[2-[(3-methoxyphenylamino)carbonyl]ethenyl]-4,6-dichloroindole- 2-carboxylic acid ([{sup 11}C]3MPICA) as a PET radiotracer for the glycine site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail:; Sultana, Abida; Laruelle, M


    Alterations in normal NMDA receptor composition, densities and function have been implicated in the pathophysiology of certain neurological and neuropsychiatric disorders such as Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. In our first effort to provide PET ligands for the NMDA/glycine site, we reported the synthesis of a novel high affinity glycine site ligand, 3-[2-[(3-methoxyphenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2 -carboxylic acid ((3MPICA), Ki=4.8{+-}0.9 nM) and the corresponding carbon-11 labeled PET ligand, [{sup 11}C]3MPICA. We report here the in vivo evaluation of [{sup 11}C]3MPICA in rats. Biodistribution analysis revealed that [{sup 11}C]3MPICA exhibited low degree of brain penetration and high blood concentration. The average uptake at two minutes was highest in the cerebellum (0.19{+-}0.04 %ID/g) and thalamus (0.18{+-}0.05 %ID/g) and lower in the hippocampus (0.13{+-}0.03) and frontal cortex (0.11{+-}0.04 %ID/g). The radioactivity cleared quickly from all brain regions examined. Administration of unlabeled 3MPICA (1 mg/kg, i.v.) revealed at 60 minutes a small general reduction in regional brain radioactivity concentrations in treated animals versus controls, however, the blood radioactivity concentration was also lowered, confounding the assessment of the degree of saturable binding. Warfarin co-administration (100 mg/kg, i.v.) significantly lowered blood activity at 5 minutes post-injection (-27%, P<0.01) but failed to significantly increase the brain uptake of the radiotracer. In view of these results, and especially considering the low brain penetration of this tracer, [{sup 11}C]3MPICA does not appear to be a promising PET radiotracer for in vivo use.

  10. Ion channels-related diseases. (United States)

    Dworakowska, B; Dołowy, K


    There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia may result from dysfunction of voltage-gated sodium, potassium and calcium channels, or acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's syndrome, policystic kidney disease and Dent's disease, secretion disorders, e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision disorders, e.g., congenital stationary night blindness and total colour-blindness may also be linked to mutations in ion channels.

  11. Unifying Theories of Mobile Channels

    Directory of Open Access Journals (Sweden)

    Gerard Ekembe Ngondi


    Full Text Available In this paper we present the denotational semantics for channel mobility in the Unifying Theories of Programming (UTP semantics framework. The basis for the model is the UTP theory of reactive processes (precisely, the UTP semantics for Communicating Sequential Processes (CSP, which is slightly extended to allow the mobility of channels: the set of actions in which a process is authorised to participate, originally static or constant (set during the process's definition, is now made dynamic or variable: it can change during the process's execution. A channel is thus moved around by communicating it via other channels and then allowing the receiving process to extend its alphabet with the received channel. New healthiness conditions are stated to ensure an appropriate use of mobile channels.

  12. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma


    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  13. Single-channel kinetics of BK (Slo1 channels

    Directory of Open Access Journals (Sweden)

    Yanyan eGeng


    Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

  14. Geometric pumping in autophoretic channels

    CERN Document Server

    Michelin, Sebastien; De Canio, Gabriele; Lobato-Dauzier, Nicolas; Lauga, Eric


    Many microfluidic devices use macroscopic pressure differentials to overcome viscous friction and generate flows in microchannels. In this work, we investigate how the chemical and geometric properties of the channel walls can drive a net flow by exploiting the autophoretic slip flows induced along active walls by local concentration gradients of a solute species. We show that chemical patterning of the wall is not required to generate and control a net flux within the channel, rather channel geometry alone is sufficient. Using numerical simulations, we determine how geometric characteristics of the wall influence channel flow rate, and confirm our results analytically in the asymptotic limit of lubrication theory.

  15. Genetic Control of Potassium Channels. (United States)

    Amin, Ahmad S; Wilde, Arthur A M


    Approximately 80 genes in the human genome code for pore-forming subunits of potassium (K(+)) channels. Rare variants (mutations) in K(+) channel-encoding genes may cause heritable arrhythmia syndromes. Not all rare variants in K(+) channel-encoding genes are necessarily disease-causing mutations. Common variants in K(+) channel-encoding genes are increasingly recognized as modifiers of phenotype in heritable arrhythmia syndromes and in the general population. Although difficult, distinguishing pathogenic variants from benign variants is of utmost importance to avoid false designations of genetic variants as disease-causing mutations.

  16. TRP channels and psychiatric disorders. (United States)

    Chahl, Loris A


    Depression and schizophrenia are major psychiatric disorders that cause much human suffering. Current treatments have major limitations and new drug targets are eagerly sought. Study of transient receptor potential (TRP) channels in these disorders is at an early stage and the potential of agents that activate or inhibit these channels remains speculative. The findings that TRPC6 channels promote dendritic growth and are selectively activated by hyperforin, the key constitutent of St John's wort, suggest that TRPC6 channels might prove to be a new target for antidepressant drug development. There is now considerable evidence that TRPV1 antagonists have anxiolytic activity but there is no direct evidence that they have antidepressant activity. There is also no direct evidence that TRP channels play a role in schizophrenia. However, the findings that TRPC channels are involved in neuronal development and fundamental synaptic mechanisms, and that TRPV1 channels play a role in central dopaminergic and cannabinoid mechanisms is suggestive of potential roles of these channels in schizophrenia. Investigation of TRP channels in psychiatric disorders holds the promise of yielding further understanding of the aetiology of psychiatric disorders and the development of new drug treatments.

  17. Capacities of quantum amplifier channels (United States)

    Qi, Haoyu; Wilde, Mark M.


    Quantum amplifier channels are at the core of several physical processes. Not only do they model the optical process of spontaneous parametric down-conversion, but the transformation corresponding to an amplifier channel also describes the physics of the dynamical Casimir effect in superconducting circuits, the Unruh effect, and Hawking radiation. Here we study the communication capabilities of quantum amplifier channels. Invoking a recently established minimum output-entropy theorem for single-mode phase-insensitive Gaussian channels, we determine capacities of quantum-limited amplifier channels in three different scenarios. First, we establish the capacities of quantum-limited amplifier channels for one of the most general communication tasks, characterized by the trade-off between classical communication, quantum communication, and entanglement generation or consumption. Second, we establish capacities of quantum-limited amplifier channels for the trade-off between public classical communication, private classical communication, and secret key generation. Third, we determine the capacity region for a broadcast channel induced by the quantum-limited amplifier channel, and we also show that a fully quantum strategy outperforms those achieved by classical coherent-detection strategies. In all three scenarios, we find that the capacities significantly outperform communication rates achieved with a naive time-sharing strategy.

  18. Demystifying Mechanosensitive Piezo Ion Channels. (United States)

    Xu, X Z Shawn


    Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

  19. Beyond the Manual Channel

    DEFF Research Database (Denmark)

    , the main focus there is on spoken languages in their written and spoken forms. This series of workshops, however, offers a forum for researchers focussing on sign languages. For the fourth time, the workshop had sign language corpora as its main topic. This time, the focus was on any aspect beyond......This collection of papers stems from the Sixth Workshop on the Representation and Processing of Sign Languages, held in May 2014 as a satellite to the Language Resources and Evaluation Conference in Reykjavik. While there has been occasional attention for sign languages at the main LREC conference...... the manual channel. Not surprisingly, most papers deal with non-manuals on the face. Once again, the papers at this workshop clearly identify the potentials of even closer cooperation between sign linguists and sign language engineers, and we think it is events like this that contribute a lot to a better...

  20. Channel Floor Yardangs (United States)


    [figure removed for brevity, see original site] Released 19 July 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth. Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms. The yardangs in this image are forming in channel floor deposits. The channel itself is funneling the wind to cause the erosion. Image information: VIS instrument. Latitude 4.5, Longitude 229.7 East (133.3 West). 19 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from

  1. Negative particle planar and axial channeling and channeling collimation

    Energy Technology Data Exchange (ETDEWEB)

    Carrigan, Richard A., Jr.; /Fermilab


    While information exists on high energy negative particle channeling there has been little study of the challenges of negative particle bending and channeling collimation. Partly this is because negative dechanneling lengths are relatively much shorter. Electrons are not particularly useful for investigating negative particle channeling effects because their material interactions are dominated by channeling radiation. Another important factor is that the current central challenge in channeling collimation is the proton-proton Large Hadron Collider (LHC) where both beams are positive. On the other hand in the future the collimation question might reemerge for electon-positron or muon colliders. Dechanneling lengths increase at higher energies so that part of the negative particle experimental challenge diminishes. In the article different approaches to determining negative dechanneling lengths are reviewed. The more complicated case for axial channeling is also discussed. Muon channeling as a tool to investigate dechanneling is also discussed. While it is now possible to study muon channeling it will probably not illuminate the study of negative dechanneling.

  2. Preservation of meandering river channels in uniformly aggrading channel belts

    NARCIS (Netherlands)

    van de Lageweg, W.I.; Schuurman, F.; Cohen, K.M.; van Dijk, W. M.; Shimizu, Y.; Kleinhans, M.G.


    Channel belt deposits from meandering river systems commonly display an internal architecture of stacked depositional features with scoured basal contacts due to channel and bedform migration across a range of scales. Recognition and correct interpretation of these bounding surfaces is essential to

  3. A conserved residue cluster that governs kinetics of ATP-dependent gating of Kir6.2 potassium channels

    DEFF Research Database (Denmark)

    Zhang, Roger S; Wright, Jordan; Pless, Stephan Alexander;


    that these residues play a role in lowering the transition state energy barrier between open and closed channel states. Using unnatural amino acid incorporation, we demonstrate the requirement for a planar amino acid at Kir6.2 position 68 for normal channel gating, potentially necessary to localize the ε-amine of Lys......ATP-sensitive potassium (KATP) channels are heteromultimeric complexes of an inwardly-rectifying Kir channel (Kir6.x) and sulfonylurea receptors (SUR). Their regulation by intracellular ATP and ADP generates electrical signals in response to changes in cellular metabolism. We investigated channel...... elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of approximately 60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly...

  4. Atom-by-atom engineering of voltage-gated ion channels: Magnified insights into function and pharmacology

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Kim, Robin Y; Ahern, Christopher A


    Unnatural amino acid incorporation into ion channels has proven to be a valuable approach to interrogate detailed hypotheses arising from atomic resolution structures. In this short review, we provide a brief overview of some of the basic principles and methods for incorporation of unnatural amin...... acids into proteins. We also review insights into the function and pharmacology of voltage-gated ion channels that have emerged from unnatural amino acid mutagenesis approaches....


    Institute of Scientific and Technical Information of China (English)

    K. H. Sayhood; Wu Lenan


    A method of coherent detection and channel estimation for punctured convolutional coded binary Quadrature Amplitude Modulation (QAM) signals transmitted over a frequency-flat Rayleigh fading channels used for a digital radio broadcasting transmission is presented. Some known symbols are inserted in the encoded data stream to enhance the channel estimation process.The pilot symbols are used to replace the existing parity symbols so no bandwidth expansion is required. An iterative algorithm that uses decoding information as well as the information contained in the known symbols is used to improve the channel parameter estimate. The scheme complexity grows exponentially with the channel estimation filter length. The performance of the system is compared for a normalized fading rate with both perfect coherent detection (corresponding to a perfect knowledge of the fading process and noise variance) and differential detection of Differential Amplitude Phase Shift Keying (DAPSK). The tradeoff between simplicity of implementation and bit-error-rate performance of different techniques is also compared.

  6. Mirrored serpentine flow channels for fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Rock, Jeffrey Allan (Rochester, NY)


    A PEM fuel cell having serpentine flow field channels wherein the input/inlet legs of each channel border the input/inlet legs of the next adjacent channels in the same flow field, and the output/exit legs of each channel border the output/exit legs of the next adjacent channels in the same flow field. The serpentine fuel flow channels may be longer, and may contain more medial legs, than the serpentine oxidant flow channels.

  7. Littoral steering of deltaic channels (United States)

    Nienhuis, Jaap H.; Ashton, Andrew D.; Giosan, Liviu


    The typically single-threaded channels on wave-influenced deltas show striking differences in their orientations, with some channels oriented into the incoming waves (e.g., Ombrone, Krishna), and others oriented away from the waves (e.g., Godavari, Sao Francisco). Understanding the controls on channel orientation is important as the channel location greatly influences deltaic morphology and sedimentology, both subaerially and subaqueously. Here, we explore channel orientation and consequent feedbacks with local shoreline dynamics using a plan-form numerical model of delta evolution. The model treats fluvial sediment delivery to a wave-dominated coast in two ways: 1) channels are assumed to prograde in a direction perpendicular to the local shoreline orientation and 2) a controlled fraction of littoral sediment transport can bypass the river mouth. Model results suggest that channels migrate downdrift when there is a significant net littoral transport and alongshore transport bypassing of the river mouth is limited. In contrast, river channels tend to orient themselves into the waves when fluvial sediment flux is relatively large, causing the shoreline of the downdrift delta flank to attain the orientation of maximum potential sediment transport for the incoming wave climate. Using model results, we develop a framework to estimate channel orientations for wave-influenced deltas that shows good agreement with natural examples. An increase in fluvial sediment input can cause a channel to reorient itself into incoming waves, behavior observed, for example, in the Ombrone delta in Italy. Our results can inform paleoclimate studies by linking channel orientation to fluvial sediment flux and wave energy. In particular, our approach provides a means to quantify past wave directions, which are notoriously difficult to constrain.

  8. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo


    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  9. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Directory of Open Access Journals (Sweden)

    Francisco Andrés Peralta


    Full Text Available Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

  10. Hydraulic jumps in a channel

    DEFF Research Database (Denmark)

    Bonn, D.; Andersen, Anders Peter; Bohr, Tomas


    We present a study of hydraulic jumps with flow predominantly in one direction, created either by confining the flow to a narrow channel with parallel walls or by providing an inflow in the form of a narrow sheet. In the channel flow, we find a linear height profile upstream of the jump as expected...

  11. An improved channel assessment scheme

    KAUST Repository

    Bader, Ahmed


    A source node in a multihop network determines whether to transmit in a channel based on whether the channel is occupied by a packet transmission with a large number of relays; whether the source node is in the data tones back-off zone; and the source node is in the busy tone back-off zone.

  12. Channel's Concurrence and Quantum Teleportation

    Institute of Scientific and Technical Information of China (English)

    LING Yin-Sheng


    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

  13. Quantum channel capacities - multiparty communication

    CERN Document Server

    Demianowicz, M; Demianowicz, Maciej; Horodecki, Pawel


    We analyze different aspects of multiparty communication over quantum memoryless channels and generalize some of key results known from bipartite channels to that of multiparty scenario. In particular, we introduce multiparty versions of minimal subspace transmission fidelity and entanglement transmission fidelity. We also provide alternative, local, versions of fidelities and show their equivalence to the global ones in context of capacity regions defined. The equivalence of two different capacity notions with respect to two types of the fidelities is proven. In analogy to bipartite case it is shown, via sufficiency of isometric encoding theorem, that additional classical forward side channel does not increase capacity region of any quantum channel with $k$ senders and $m$ receivers which represents a compact unit of general quantum networks theory. The result proves that recently provided capacity region of multiple access channel ([M. Horodecki et al, Nature {\\bf 436} 673 (2005)], [J.Yard et al, quant-ph/0...

  14. Channelling, a new immunization strategy. (United States)

    Gacharna Romero, M G; Silva Pizano, E; Avendano Lamo, J


    In 1981, with PAHO/WHO technical assistance, the Ministry of Health, Colombia, designed what is known as the channelling strategy, aimed at improving immunization coverage. This name was given because the strategy is designed to establish communication channels through direct action aimed at promoting health. Health workers and community leaders or guides conduct household visits to identify unvaccinated children or those with incomplete vaccination schedules and "channel" them to health centers or health posts. The channelling strategy developed in Colombia was briefly mentioned in the case study on the Colombian Vaccination Crusade of 1984. It is now being employed for ORT and other PHC components in the Colombian Child Survival and Development Plan, 1985-1987. In the meantime, other countries have adopted the channelling strategy, which is described in this article.

  15. A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus (United States)

    Scott, L. L.; Brecht, E. J.; Philpo, A.; Iyer, S.; Wu, N. S.; Mihic, S. J.; Aldrich, R. W.; Pierce, J.; Walton, J. P.


    Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins. LS3 suppresses locomotor activity via a BK channel-specific mechanism in wild-type or BK channel-humanized Caenorhabditis elegans. Topical application on the dural surface of the auditory midbrain in mouse suppresses sound evoked neural activity, similar to a well-characterized pore blocker of the BK channel. Moreover, this novel ion channel-targeted peptide rapidly crosses the BBB after systemic delivery to modulate auditory processing. Thus, a potent BK channel peptide modulator is open to neurological applications, such as preventing audiogenic seizures that originate in the auditory midbrain. PMID:28195225

  16. Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes

    Directory of Open Access Journals (Sweden)

    Ravshan Z. Sabirov


    Full Text Available Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR chloride channel of intermediate conductance. A VSOR inhibitor, phloretin, significantly suppressed both macroscopic VSOR-type conductance and single-channel activity of intermediate amplitude. The maxi-anion channel activity was largely suppressed by Gd3+ ions but not by phloretin. Surprisingly, [(dihydroindenyloxy] alkanoic acid (DIOA, a known antagonist of K-Cl cotransporter, was found to significantly suppress the activity of the VSOR-type single-channel events with no effect on the maxi-anion channels at 10 μM. The regulatory volume decrease (RVD phase of cellular response to hypotonicity was mildly suppressed by Gd3+ ions and was completely abolished by phloretin suggesting a major impact of the VSOR chloride channel and modulatory role of the maxi-anion channel. The inhibitory effect of DIOA was also strong, and, most likely, it occurred via blocking the VSOR Cl− channels.

  17. Microfluidic channel-assisted screening of hematopoietic malignancies. (United States)

    Mughal, Farah; Baldock, Sara J; Karimiani, Ehsan Ghayoor; Telford, Nick; Goddard, Nicholas J; Day, Philip J R


    A simple microfluidic fluorescence in situ hybridization (FISH) device allowing accurate analysis of interphase nuclei in 1 hr in narrow channels is presented. Photolithography and fluorosilicic acid etching were used to fabricate microfluidic channels (referred to as FISHing lines) that allowed analysis of 10 samples on a glass microscope slide 0.2 µl of sample volume was used to fill a micro-channel, which resembled a 250-fold reduction compared to conventional FISH. FISH signals were comparable to conventional FISH, with 50-fold less probe consumption and 10-fold less time. Cells were immobilized in single file in channels just exceeding the diameter of the cells, and were used for minimal residual disease (MRD) analysis. To test the micro-channels for application in FISH, MRD was simulated by mixing K562 cells (an established chronic myeloid leukemia cell line) carrying the BCR/ABL fusion gene across 1:1 to 1:1,000 Jurkat cells (an established acute lymphoblastic leukemia cell line). The limit of detection was seen to be 1:100 cells and 1:1,000 cells for FISHing lines and conventional FISH, respectively; however, the conventional method seemed to over-score the presence of K562 cells. This may in part be attributed to FISHing lines practically eliminating the chance of duplicate screening of cells and hastened the time of screening, enhancing scoring of all cells within the channels. This was compared to 1 in 500 cells on the slide being analyzed with the conventional FISH.

  18. The Wiretap Channel with Feedback: Encryption over the Channel

    CERN Document Server

    Lai, Lifeng; Poor, H Vincent


    In this work, the critical role of noisy feedback in enhancing the secrecy capacity of the wiretap channel is established. Unlike previous works, where a noiseless public discussion channel is used for feedback, the feed-forward and feedback signals share the same noisy channel in the present model. Quite interestingly, this noisy feedback model is shown to be more advantageous in the current setting. More specifically, the discrete memoryless modulo-additive channel with a full-duplex destination node is considered first, and it is shown that the judicious use of feedback increases the perfect secrecy capacity to the capacity of the source-destination channel in the absence of the wiretapper. In the achievability scheme, the feedback signal corresponds to a private key, known only to the destination. In the half-duplex scheme, a novel feedback technique that always achieves a positive perfect secrecy rate (even when the source-wiretapper channel is less noisy than the source-destination channel) is proposed....

  19. Experiment on the Application of Ionic Liquid as Green Medium for Extraction of Boric Acid from Salt Lake Brine%离子液体作为绿色介质从盐湖卤水中萃取硼酸

    Institute of Scientific and Technical Information of China (English)

    宋贤菊; 李在均


    Ionic liquid is a green solvent for extraction of boron from salt lake beine as extraction medium, 1-octyl-3-methylimidazolium hexafluorophosphate ionic liquid was prepared and the ionic liquid, isooctyl alcohol and kerosene were used as extraction medium, synergic reagent and diluent respectively. The influence of ionic liquid dosage and extraction conditions on the boron extraction were investigated. The optimal experimental parameters were obtained as follows: ionic liquid dosage 10% ,the extractant 50% ,the ratio of organic phase to brine 1:1, the extraction time 10 min, and pH 2.4. The concentration of Mg2+ 4.268 mollL. Under optimal conditions, the boron can be fully extracted to the organic phase with three step extractions and a recovey of 99.54% was obtained.%制备了1-辛烷基-3-甲基咪唑六氟磷酸盐离子液体,再以离子液体(IL)为萃取介质、异辛醇为萃取剂及煤油为稀释剂建立盐湖卤水硼萃取研究模型,考察了离子液体用量和萃取条件对硼萃取的影响.异辛醇从卤水中萃取提硼的最佳实验条件:离子液体体积分数为10%,萃取剂体积分数为50%,相比(O/A)为1:1,萃取时间10 min,pH 2.4,Mg2+浓度为4.268 mol/L.在此条件下,当萃取级数为3级时,萃取率为99.54%,卤水中的硼可被完全萃取到有机相中.

  20. Un nuevo Método para Mejorar el Proceso de Producción de Acido Bórico A New Method to Improve the Production Process of Boric Acid


    Orlando J Domínguez; Emilio M Serrano; Jorge E Flores; Raquel L Michel


    En este trabajo se propone una modificación al proceso tradicional para obtener ácido bórico, con el agregado fraccionado del ácido lixiviante, para lograr un producto altamente soluble, como el pentaborato de sodio. Con esto se consigue la disolución del mineral en frío con menor cantidad de reactivo lixiviante, ahorrando así energía. Al líquido clarificado se le disminuye el pH logrando así la precipitación del ácido bórico. La ganga se agota con diferentes etapas de precipitación y filtrac...

  1. 硼酸对顺铂致体外人胚肾细胞毒性保护作用%Preventive effects of boric acid on cisplatin-induced nephrotoxicity in 293 cells

    Institute of Scientific and Technical Information of China (English)

    曹军; 姜丽平; 耿成燕; 姚晓峰; 薛向欣; 仲来福


    目的 体外研究硼酸对顺铂所致肾毒性的保护作用,并探讨其可能机制.方法 体外培养人胚肾293(HEK293)细胞,四甲基偶氮噻唑蓝(MTT)法观察硼酸对顺铂细胞毒性的保护作用,硫代巴比妥酸反应产物测定法观察硼酸对顺铂引起的脂质过氧化的影响,荧光比色法观察硼酸对顺铂诱导的谷胱甘肽耗竭的影响.结果 硼酸能明显抑制顺铂对HEK293细胞的细胞毒性作用,24h半数抑制浓度(IC50)值由(0.38±0.04)mmol.L升高为(0.87±0.10)mmol.L,2者之间差异有统计学意义(P<0.05);硼酸能明显抑制顺铂所致脂质过氧化产物的形成.并能提升顺铂引起的还原型谷胱苷肽(GSH)含量的下降.结论 硼酸能抑制顺铂所致HEK293细胞的细胞毒性,其机制可能与其抗氧化作用和清除自由基活性有密切关系.

  2. 用硼酸作为显色剂光度法测定阿昔洛韦%Spectrophotometric determination of acyclovir with boric acid as a chromogenic agent

    Institute of Scientific and Technical Information of China (English)

    李晶; 汪瑾; 魏献军; 李全民


    在pH 12.00的缓冲溶液中,阿昔洛韦(ACV)与H_3BO_3形成组成比为1∶1的反应产物,其最大吸收波长λ_max=289 nm,ACV的质量浓度在0.48~57.6 mg/L范围内与吸光度成良好关系,线性回归方程A=-0.01796+0.01624ρ,相关系数r=0.9990,表观摩尔吸光系数ε=3.7×10~3 L·mol~(-1)·cm~(-1),回收率为99.9%~101.6%. 据此建立了测定ACV的新方法,能够直接用于药物样品中ACV的测定.

  3. Based on Channel Characteristics

    Directory of Open Access Journals (Sweden)

    Zhuo Hao


    Full Text Available A number of key agreement schemes based on wireless channel characteristics have been proposed recently. However, previous key agreement schemes require that two nodes which need to agree on a key are within the communication range of each other. Hence, they are not suitable for multihop wireless networks, in which nodes do not always have direct connections with each other. In this paper, we first propose a basic multihop key agreement scheme for wireless ad hoc networks. The proposed basic scheme is resistant to external eavesdroppers. Nevertheless, this basic scheme is not secure when there exist internal eavesdroppers or Man-in-the-Middle (MITM adversaries. In order to cope with these adversaries, we propose an improved multihop key agreement scheme. We show that the improved scheme is secure against internal eavesdroppers and MITM adversaries in a single path. Both performance analysis and simulation results demonstrate that the improved scheme is efficient. Consequently, the improved key agreement scheme is suitable for multihop wireless ad hoc networks.

  4. Opening Channels of Communication

    Directory of Open Access Journals (Sweden)

    Clarice Moura Costa


    Full Text Available Psychosis, as described through a psychodynamic perspective, is conceptualized as an attempt to deny the enveloping reality to avoid contact with the other. Music therapy is a way to break this barrier of non-communication raised by the patients. The music therapy process is configured as a trinomial – action (making music/ relationship (action with the other/communication (musical or verbal voluntary expression of feelings and conflicts, which, although intrinsically connected, is perceived in a sequential process. Aulagnier asserts that psychic activity represents the conjunction of three modes of functioning: the original process, the primary process and the secondary process. The perception of sound passes through three phases, corresponding to each manner of functioning of the psychic system – the pleasure of hearing, the desire to listen (to the other and the imperative of meaning. The music therapy process offers a significant similarity with the theory proposed by Aulagnier. We propose the hypothesis that in music therapy, there is an opportunity to (reexperience very archaic phases in the constitution of the ego, but in a new manner, so helping to open communication channels. This theoretical hypothesis is illustrated by real examples of patients.

  5. Ergodic channel capacity of the spatial correlated rayleigh MIMO channel

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-ping; WU Ping; LIU Ai-jun


    The theoretical capacity of the spatial correlated Rayleigh multiple input multiple output (MIMO) channel is an important issue in MIMO technology. In this article, an ergodic channel capacity formula of the spatial correlated rayleigh MIMO channel is provided, which is deduced when two antennas exist at either the transmitter or the receiver. The multi-dimensional least-squares fit algorithm is employed to narrow the difference between the theoretical formula capacity and the practical capacity. Simulation results show that the theoretical capacity approaches the practical one closely.

  6. A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC channels, an arachidonate-regulated store-independent Orai channel. (United States)

    Thompson, Jill L; Shuttleworth, Trevor J


    The Orai family of calcium channels includes the store-operated CRAC channels and store-independent, arachidonic acid (AA)-regulated ARC channels. Both depend on STIM1 for their activation but, whereas CRAC channel activation involves sensing the depletion of intracellular calcium stores via a luminal N terminal EF-hand of STIM1 in the endoplasmic reticulum (ER) membrane, ARC channels are exclusively activated by the pool of STIM1 that constitutively resides in the plasma membrane (PM). Here, the EF-hand is extracellular and unlikely to ever lose its bound calcium, suggesting that STIM1-dependent activation of ARC channels is very different from that of CRAC channels. We now show that attachment of the cytosolic portion of STIM1 to the inner face of the PM via an N terminal Lck-domain sequence is sufficient to enable normal AA-dependent activation of ARC channels, while failing to allow activation of store-operated CRAC channels. Introduction of a point mutation within the Lck-domain resulted in the loss of both PM localization and ARC channel activation. Reversing the orientation of the PM-anchored STIM1 C terminus via a C-terminal CAAX-box fails to support either CRAC or ARC channel activation. Finally, the Lck-anchored STIM1 C-terminal domain also enabled the exclusive activation of the ARC channels following physiological agonist addition. These data demonstrate that simple tethering of the cytosolic C-terminal domain of STIM1 to the inner face of the PM is sufficient to allow the full, normal and exclusive activation of ARC channels, and that the N-terminal regions of STIM1 (including the EF-hand domain) play no significant role in this activation.

  7. Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating. (United States)

    Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G


    We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating.

  8. Folic acid (United States)

    ... taking folic acid by itself, or with L-carnitine a compound similar to an amino acid from ... levels. It is not clear if folic acid supplementation reduces hearing loss in people with normal folate ...

  9. Voltage-dependent gating of hERG potassium channels

    Directory of Open Access Journals (Sweden)

    Yen May eCheng


    Full Text Available The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4-S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-a-go-go related gene, hERG, which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure-function relationships underlying voltage-dependent gating in Shaker and hERG channels, with a focus on the roles of the voltage sensing domain and the S4-S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter charge interactions. More recent data suggest that key amino acid differences in the hERG voltage sensing unit and S4-S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor.

  10. Channel Coding in Random Access Communication over Compound Channels

    CERN Document Server

    Wang, Zheng


    Due to the short and bursty incoming messages, channel access activities in a wireless random access system are often fractional. The lack of frequent data support consequently makes it difficult for the receiver to estimate and track the time varying channel states with high precision. This paper investigates random multiple access communication over a compound wireless channel where channel realization is known neither at the transmitters nor at the receiver. An achievable rate and error probability tradeoff bound is derived under the non-asymptotic assumption of a finite codeword length. The results are then extended to the random multiple access system where the receiver is only interested in decoding messages from a user subset.

  11. Channel estimation in TDD mode

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi; GU Jian; YANG Da-cheng


    An efficient solution is proposed in this article for the channel estimation in time division duplex (TDD) mode wireless communication systems. In the proposed solution, the characteristics of fading channels in TDD mode systems are fully exploited to estimate the path delay of the fading channel.The corresponding amplitude is estimated using the minimum mean square error (MMSE) criterion. As a result, it is shown that the proposed novel solution is more accurate and efficient than the traditional solution, and the improvement is beneficial to the performance of Joint Detection.

  12. Ion channels in neuronal survival

    Institute of Scientific and Technical Information of China (English)


    The study of ion channels represents one of the most active fields in neuroscience research in China.In the last 10 years,active research in various Chinese neuroscience institutions has sought to understand the mechanisms responsible for sensory processing,neural development and neurogenesis,neural plasticity,as well as pathogenesis.In addition,extensive studies have been directed to measure ion channel activity,structure-function relationships,as well as many other biophysical and biochemical properties.This review focuses on the progress achieved in the investigation of ion channels in neuronal survival during the past 10 years in China.

  13. Skeletal Muscle Na+ Channel Disorders

    Directory of Open Access Journals (Sweden)

    Dina eSimkin


    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.

  14. Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor. (United States)

    Sugawara, M; Hirano, A; Rehák, M; Nakanishi, J; Kawai, K; Sato, H; Umezawa, Y


    A new method for evaluating chemical selectivity of agonists towards receptor ion channel proteins is proposed by using glutamate receptor (GluR) ion channel proteins and their agonists N-methyl-D-aspartic acid (NMDA), L-glutamate, and (2S, 3R, 4S) isomer of 2-(carboxycyclopropyl)glycine (L-CCG-IV). Integrated multi-channel currents, corresponding to the sum of total amount of ions passed through the multiple open channels, were used as a measure of agonists' selectivity to recognize ion channel proteins and induce channel currents. GluRs isolated from rat synaptic plasma membranes were incorporated into planar bilayer lipid membranes (BLMs) formed by the folding method. The empirical factors that affect the selectivity were demonstrated: (i) the number of GluRs incorporated into BLMs varied from one membrane to another; (ii) each BLM contained different subtypes of GluRs (NMDA and/or non-NMDA subtypes); and (iii) the magnitude of multi-channel responses induced by L-glutamate at negative applied potentials was larger than at positive potentials, while those by NMDA and L-CCG-IV were linearly related to applied potentials. The chemical selectivity among NMDA, L-glutamate and L-CCG-IV for NMDA subtype of GluRs was determined with each single BLM in which only NMDA subtype of GluRs was designed to be active by inhibiting the non-NMDA subtypes using a specific antagonist DNQX. The order of selectivity among the relevant agonists for the NMDA receptor subtype was found to be L-CCG-IV > L-glutamate > NMDA, which is consistent with the order of binding affinity of these agonists towards the same NMDA subtypes. The potential use of this approach for evaluating chemical selectivity towards non-NMDA receptor subtypes of GluRs and other receptor ion channel proteins is discussed.

  15. Infinitely many kinds of quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Matthew B [Los Alamos National Laboratory


    We define the ability of a quantum channel to simulate another by means of suitable encoding and decoding operations. While classical channels have only two equivalence classes under simulation (channels with non-vanishing capacity and those with vanishing capacity), we show that there are an uncountable infinity of different equivalence classes of quantum channels using the example of the quantum erasure channel. Our results also imply a kind of 'Matthew principle' for error correction on certain channels.

  16. A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1

    NARCIS (Netherlands)

    Bánfi, B; Maturana, A; Jaconi, S; Arnaudeau, S; Laforge, T; Sinha, B; Ligeti, E; Demaurex, N; Krause, K H


    Voltage-gated proton (H+) channels are found in many human and animal tissues and play an important role in cellular defense against acidic stress. However, a molecular identification of these unique ion conductances has so far not been achieved. A 191-amino acid protein is described that, upon hete

  17. Message Authentication over Noisy Channels

    Directory of Open Access Journals (Sweden)

    Fanfan Zheng


    Full Text Available The essence of authentication is the transmission of unique and irreproducible information. In this paper, the authentication becomes a problem of the secure transmission of the secret key over noisy channels. A general analysis and design framework for message authentication is presented based on the results of Wyner’s wiretap channel. Impersonation and substitution attacks are primarily investigated. Information-theoretic lower and upper bounds on the opponent’s success probability are derived, and the lower bound and the upper bound are shown to match. In general, the fundamental limits on message authentication over noisy channels are fully characterized. Analysis results demonstrate that introducing noisy channels is a reliable way to enhance the security of authentication.