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Sample records for calcium-dependent chloride channel

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    waves sweeping through the cytoplasm when the sarcoplasmic reticulum (SR) is stimulated to release calcium. A rise in cGMP leads to the experimentally observed transition from waves to whole cell calcium oscillations. At the same time, membrane potential starts to oscillate and the frequency...... approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes a uniform opening of L-type calcium...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  3. Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine.

    Science.gov (United States)

    Schreiber, Rainer; Faria, Diana; Skryabin, Boris V; Wanitchakool, Podchanart; Rock, Jason R; Kunzelmann, Karl

    2015-06-01

    Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca(2+) and opening of apical Cl(-) channels. In infants and young animals, but not in adults, Ca(2+)-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) channels, analysis of the role of Ca(2+)-dependent Cl(-) channels became possible through identification of the anoctamin (TMEM16) family of proteins. We demonstrate expression of several anoctamin paralogues in mouse small and large intestines. Using intestinal-specific mouse knockout models for anoctamin 1 (Ano1) and anoctamin 10 (Ano10) and a conventional knockout model for anoctamin 6 (Ano6), we demonstrate the role of anoctamins for Ca(2+)-dependent Cl(-) secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca(2+)-activated Cl(-) secretion. In contrast, Ano10 is essential for Ca(2+)-dependent Cl(-) secretion in jejunum, where expression of Ano1 was not detected. Although broadly expressed, Ano6 has no role in intestinal cholinergic Cl(-) secretion. Ano1 is located in a basolateral compartment/membrane rather than in the apical membrane, where it supports CCH-induced Ca(2+) increase, while the essential and possibly only apical Cl(-) channel is CFTR. These results define a new role of Ano1 for intestinal Ca(2+)-dependent Cl(-) secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.

  4. JNK mitogen-activated protein kinase limits calcium-dependent chloride secretion across colonic epithelial cells.

    LENUS (Irish Health Repository)

    Donnellan, Fergal

    2010-01-01

    Neuroimmune agonists induce epithelial Cl(-) secretion through elevations in intracellular Ca2+ or cAMP. Previously, we demonstrated that epidermal growth factor receptor (EGFR) transactivation and subsequent ERK MAPK activation limits secretory responses to Ca2+-dependent, but not cAMP-dependent, agonists. Although JNK MAPKs are also expressed in epithelial cells, their role in regulating transport function is unknown. Here, we investigated the potential role for JNK in regulating Cl(-) secretion in T(84) colonic epithelial cells. Western blot analysis revealed that a prototypical Ca2+-dependent secretagogue, carbachol (CCh; 100 microM), induced phosphorylation of both the 46-kDa and 54-kDa isoforms of JNK. This effect was mimicked by thapsigargin (TG), which specifically elevates intracellular Ca2+, but not by forskolin (FSK; 10 microM), which elevates cAMP. CCh-induced JNK phosphorylation was attenuated by the EGFR inhibitor, tyrphostin-AG1478 (1 microM). Pretreatment of voltage-clamped T(84) cells with SP600125 (2 microM), a specific JNK inhibitor, potentiated secretory responses to both CCh and TG but not to FSK. The effects of SP600125 on CCh-induced secretion were not additive with those of the ERK inhibitor, PD98059. Finally, in apically permeabilized T(84) cell monolayers, SP600125 potentiated CCh-induced K+ conductances but not Na+\\/K+ATPase activity. These data demonstrate a novel role for JNK MAPK in regulating Ca2+ but not cAMP-dependent epithelial Cl(-) secretion. JNK activation is mediated by EGFR transactivation and exerts its antisecretory effects through inhibition of basolateral K+ channels. These data further our understanding of mechanisms regulating epithelial secretion and underscore the potential for exploitation of MAPK-dependent signaling in treatment of intestinal transport disorders.

  5. Chloride channels in stroke

    Institute of Scientific and Technical Information of China (English)

    Ya-ping ZHANG; Hao ZHANG; Dayue Darrel DUAN

    2013-01-01

    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.

  6. Anion channels in Chara corallina tonoplast membrane: Calcium dependence and rectification

    NARCIS (Netherlands)

    Berecki, G.; Varga, Z.; Iren, F. van; Duijn, B. van

    1999-01-01

    Tonoplast K+ channels of Chara corallina are well characterized but only a few reports mention anion channels, which are likely to play an important role in the tonoplast action potential and osmoregulation of this plant. For experiments internodal cells were isolated. Cytoplasmic droplets were form

  7. A Calcium-Dependent Protein Kinase Interactswith and Activates A Calcium Channel toRequlate Pollen Tube Growth

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    ABSTRACT Calcium, as a ubiquitous second messenger, plays essential roles in tip-growing cells, such as animal neu-rons, plant pollen tubes, and root hairs. However, little is known concerning the regulatory mechanisms that code anddecode Ca2+ signals in plants. The evidence presented here indicates that a calcium-dependent protein kinase, CPK32,controls polar growth of pollen tubes. Overexpression of CPK32 disrupted the polar growth along with excessive Ca2+accumulation in the tip. A search of downstream effector molecules for CPK32 led to identification of a cyclic nucleotide-gated channel, CNGC18, as an interacting partner for CPK32. Co-expression of CPK32 and CNGC18 resulted in activationof CNGC18 in Xenopus oocytes where expression of CNGC18 alone did not exhibit significant calcium channel activity.Overexpression of CNGC18 produced a growth arrest phenotype coupled with accumulation of calcium in the tip, simi-lar to that induced by CPK32 overexpression. Co-expression of CPK32 and CNGC18 had a synergistic effect leading tomore severe depolarization of pollen tube growth. These results provide a potential feed-forward mechanism in whichcalcium-activated CPK32 activates CNGC18, further promoting calcium entry during the elevation phase of Ca2+ oscilla-tions in the polar growth of pollen tubes.

  8. The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels

    OpenAIRE

    Barrett, Curtis F.; Tsien, Richard W.

    2008-01-01

    Calcium entry into excitable cells is an important physiological signal, supported by and highly sensitive to the activity of voltage-gated Ca2+ channels. After membrane depolarization, Ca2+ channels first open but then undergo various forms of negative feedback regulation including voltage- and calcium-dependent inactivation (VDI and CDI, respectively). Inactivation of Ca2+ channel activity is perturbed in a rare yet devastating disorder known as Timothy syndrome (TS), whose features include...

  9. Stimulation of beta-adrenoceptors inhibits calcium-dependent potassium-channels in mouse macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Rosati, C.; Hannaert, P.; Dausse, J.P.; Braquet, P.; Garay, R.

    1986-12-01

    K/sup +/ efflux in mouse macrophages exhibited a rate constant (k/sub k/) of 0.67 +/- 0.04 (h)/sup -1/. This was strongly stimulated by increasing concentrations of the Ca/sup 2 +/ ionophore A23187 up to a maximal value of 4.01 +/- 0.25 (h)/sup -1/ with an IC/sub 50/ of 7.6 +/- 1.9 ..mu..M. Similar results were obtained with the Ca/sup 2 +/ ionophore ionomycin. Binding experiments with /sup 3/H-dihydroalprenolol revealed a high density of beta-adrenergic receptors with apparent dissociation constant of 2.03 +/- 0.06 nM. Isoproterenol at a concentration of 10/sup -6/ -10/sup -5/ M induced a two- to threefold stimulation of endogenous levels of cyclic AMP (cAMP). A23187-stimulated K/sup +/ efflux was partially inhibited by (i) stimulation of adenylate cyclase with isoproterenol, forskolin or, PGE/sub 1/; (ii) exogenous cAMP; and (iii) inhibition of phosphodiesterase with MIX (1-methyl-3-isobutylxanthine). Maximal inhibition of K/sup +/ efflux was obtained by simultaneous addition of isoproterenol and MIX. In dose-response curves, the isoproterenol-sensitive K/sup +/ efflux was half-maximally inhibited (IC/sub 50/) with 2-5 x 10/sup -10/ M of isoproterenol concentration. Propranolol was able to completely block the effect of isoproterenol, with an IC/sub 50/ of about 1-2 x 10/sup -7/ M. Isoproterenol and MIX did not inhibit A23187-stimulated K/sup +/ efflux in an incubation medium where NaCl was replaced by sucrose (or choline), suggesting the involvement of an Na/sup +/:Ca/sup 2 +/ exchange mechanism. The results show that stimulation of beta-adrenoceptors in mouse macrophages counter balances the opening of K/sup +/ channels induced by the calcium ionophore A23187. This likely reflects a decrease in cytoslic free calcium content via a cAMP-mediated stimulation of Na/sup +/:Ca/sup 2 +/ exchange.

  10. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.

    Directory of Open Access Journals (Sweden)

    Weiping Zhang

    Full Text Available Calcium-activated chloride channels of the anoctamin (alias TMEM16 protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.

  11. A cell model study of calcium influx mechanism regulated by calcium-dependent potassium channels in Purkinje cell dendrites.

    Science.gov (United States)

    Chono, Koji; Takagi, Hiroshi; Koyama, Shozo; Suzuki, Hideo; Ito, Etsuro

    2003-10-30

    The present study was designed to elucidate the roles of dendritic voltage-gated K+ channels in Ca2+ influx mechanism of a rat Purkinje cell using a computer simulation program. First, we improved the channel descriptions and the maximum conductance in the Purkinje cell model to mimic both the kinetics of ion channels and the Ca2+ spikes, which had failed in previous studies. Our cell model is, therefore, much more authentic than those in previous studies. Second, synaptic inputs that mimic stimulation of parallel fibers and induce sub-threshold excitability were simultaneously applied to the spiny dendrites. As a result, transient Ca2+ responses were observed in the stimulation points and they decreased with the faster decay rate in the cell model including high-threshold Ca2+-dependent K+ channels than in those excluding these channels. Third, when a single synaptic input was applied into a spiny dendrite, Ca2+-dependent K+ channels suppressed Ca2+ increases at stimulation and recording points. Finally, Ca2+-dependent K+ channels were also found to suppress the time to peak Ca2+ values in the recording points. These results suggest that the opening of Ca2+-dependent K+ channels by Ca2+ influx through voltage-gated Ca2+ channels hyperpolarizes the membrane potentials and deactivates these Ca2+ channels in a negative feedback manner, resulting in local, weak Ca2+ responses in spiny dendrites of Purkinje cells.

  12. Calcium-dependent expression of transient receptor potential canonical type 3 channels in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Liu, Ying; Krueger, Katharina; Hovsepian, Anahit;

    2011-01-01

    It is unknown whether extracellular calcium may regulate the expression of transient receptor potential canonical type 3 (TRPC3) channels in patients with chronic kidney disease. Using quantitative in-cell Western assay we compared the expression of TRPC3 channel protein in monocytes from 20...... patients with chronic kidney disease and 19 age- and sex-matched healthy control subjects. TRPC3 channels were identified by immunoblotting using specific antibodies and TRPC3 protein was further confirmed by mass spectrometry. We observed a significant increase of TRPC3 channel protein expression...... in patients with chronic kidney disease compared to healthy control subjects (normalized expression, 0.42±0.06 vs. 0.19±0.03; p...

  13. Regulated trafficking of the CFTR chloride channel

    NARCIS (Netherlands)

    Braakman, L.J.; Kleizen, B.; Jonge, H.R. de

    2000-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR), the ABC transporter encoded by the cystic fibrosis gene, is localized in the apical membrane of epithelial cells where it functions as a cyclic AMP-regulated chloride channel and as a regulator of other ion channels and transporters. Wh

  14. Effects of manipulating slowpoke calcium-dependent potassium channel expression on rhythmic locomotor activity in Drosophila larvae

    Directory of Open Access Journals (Sweden)

    Erin C. McKiernan

    2013-03-01

    Full Text Available Rhythmic motor behaviors are generated by networks of neurons. The sequence and timing of muscle contractions depends on both synaptic connections between neurons and the neurons’ intrinsic properties. In particular, motor neuron ion currents may contribute significantly to motor output. Large conductance Ca2+-dependent K+ (BK currents play a role in action potential repolarization, interspike interval, repetitive and burst firing, burst termination and interburst interval in neurons. Mutations in slowpoke (slo genes encoding BK channels result in motor disturbances. This study examined the effects of manipulating slo channel expression on rhythmic motor activity using Drosophila larva as a model system. Dual intracellular recordings from adjacent body wall muscles were made during spontaneous crawling-related activity in larvae expressing a slo mutation or a slo RNA interference construct. The incidence and duration of rhythmic activity in slo mutants were similar to wild-type control animals, while the timing of the motor pattern was altered. slo mutants showed decreased burst durations, cycle durations, and quiescence intervals, and increased duty cycles, relative to wild-type. Expressing slo RNAi in identified motor neurons phenocopied many of the effects observed in the mutant, including decreases in quiescence interval and cycle duration. Overall, these results show that altering slo expression in the whole larva, and specifically in motor neurons, changes the frequency of crawling activity. These results suggest an important role for motor neuron intrinsic properties in shaping the timing of motor output.

  15. Cyclic 3'-5'-adenosine monophosphate binds to annexin I and regulates calcium-dependent membrane aggregation and ion channel activity.

    Science.gov (United States)

    Cohen, B E; Lee, G; Arispe, N; Pollard, H B

    1995-12-27

    The annexin (Anx) gene family comprises a set of calcium-dependent membrane binding proteins, which have been implicated in a wide variety of cellular processes including membrane fusion and calcium channel activity. We report here that cAMP activates Ca(2+)-dependent aggregation of both phosphatidylserine (PS) liposomes and bovine chromaffin granules driven by [des 1-12]annexin I (lipocortin I, Anx1). The mechanism of cAMP action involves an increase in AnxI-dependent cooperativity on the rate of such a reaction without affecting the corresponding k1/2 values. Cyclic AMP causes the values of the Hill coefficient (nH) for AnxI to change from 3 to 6 in both PS liposomes and chromaffin granules. By contrast, ATP inhibits the rate of aggregation activity without affecting the cooperativity or the extent of aggregation process. We were also able to photolabel Anx1 specifically with an 8-azido analogue of cAMP by a calcium-independent process. Such a process is saturable, yielding a Kd = 0.8 microM by Scatchard analysis. Specific displacement occurs in the presence of cAMP and ATP. Finally, we found that cAMP alters the conductance of calcium channels formed by AnxI in planar lipid bilayers. We interpret these data to indicate that AnxI binds both calcium and cAMP independently, and that both actions have functional consequences. This is the first report of a nucleotide binding function for a member of the annexin gene family.

  16. Phosphatase inhibitors activate normal and defective CFTR chloride channels.

    OpenAIRE

    Becq, F; Jensen, T J; Chang, X B; Savoia, A.; Rommens, J M; Tsui, L C; Buchwald, M; Riordan, J R; Hanrahan, J W

    1994-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is regulated by phosphorylation and dephosphorylation at multiple sites. Although activation by protein kinases has been studied in some detail, the dephosphorylation step has received little attention. This report examines the mechanisms responsible for the dephosphorylation and spontaneous deactivation ("rundown") of CFTR chloride channels excised from transfected Chinese hamster ovary (CHO) and human airway epi...

  17. Purification and reconstitution of chloride channels from kidney and trachea

    International Nuclear Information System (INIS)

    Chloride channels mediate absorption and secretion of fluid in epithelia, and the regulation of these channels is now known to be defective in cystic fibrosis. Indanyl-oxyacetic acid 94 (IAA-94) is a high-affinity ligand for the chloride channel, and an affinity resin based on that structure was developed. Solubilized proteins from kidney and trachea membranes were applied to the affinity matrix, and four proteins with apparent molecular masses of 97, 64, 40, and 27 kilodaltons were eluted from the column by excess IAA-94. A potential-dependent 36Cl- uptake was observed after reconstituting these proteins into liposomes. Three types of chloride channels with single-channel conductances of 26, 100, and 400 picosiemens were observed after fusion of these liposomes with planar lipid bilayers. Similar types of chloride channels have been observed in epithelia

  18. Silent S-Type Anion Channel Subunit SLAH1 Gates SLAH3 Open for Chloride Root-to-Shoot Translocation.

    Science.gov (United States)

    Cubero-Font, Paloma; Maierhofer, Tobias; Jaslan, Justyna; Rosales, Miguel A; Espartero, Joaquín; Díaz-Rueda, Pablo; Müller, Heike M; Hürter, Anna-Lena; Al-Rasheid, Khaled A S; Marten, Irene; Hedrich, Rainer; Colmenero-Flores, José M; Geiger, Dietmar

    2016-08-22

    Higher plants take up nutrients via the roots and load them into xylem vessels for translocation to the shoot. After uptake, anions have to be channeled toward the root xylem vessels. Thereby, xylem parenchyma and pericycle cells control the anion composition of the root-shoot xylem sap [1-6]. The fact that salt-tolerant genotypes possess lower xylem-sap Cl(-) contents compared to salt-sensitive genotypes [7-10] indicates that membrane transport proteins at the sites of xylem loading contribute to plant salinity tolerance via selective chloride exclusion. However, the molecular mechanism of xylem loading that lies behind the balance between NO3(-) and Cl(-) loading remains largely unknown. Here we identify two root anion channels in Arabidopsis, SLAH1 and SLAH3, that control the shoot NO3(-)/Cl(-) ratio. The AtSLAH1 gene is expressed in the root xylem-pole pericycle, where it co-localizes with AtSLAH3. Under high soil salinity, AtSLAH1 expression markedly declined and the chloride content of the xylem sap in AtSLAH1 loss-of-function mutants was half of the wild-type level only. SLAH3 anion channels are not active per se but require extracellular nitrate and phosphorylation by calcium-dependent kinases (CPKs) [11-13]. When co-expressed in Xenopus oocytes, however, the electrically silent SLAH1 subunit gates SLAH3 open even in the absence of nitrate- and calcium-dependent kinases. Apparently, SLAH1/SLAH3 heteromerization facilitates SLAH3-mediated chloride efflux from pericycle cells into the root xylem vessels. Our results indicate that under salt stress, plants adjust the distribution of NO3(-) and Cl(-) between root and shoot via differential expression and assembly of SLAH1/SLAH3 anion channel subunits. PMID:27397895

  19. Chloride dependence of hyperpolarization-activated chloride channel gates.

    Science.gov (United States)

    Pusch, M; Jordt, S E; Stein, V; Jentsch, T J

    1999-03-01

    1. ClC proteins are a class of voltage-dependent Cl- channels with several members mutated in human diseases. The prototype ClC-0 Torpedo channel is a dimeric protein; each subunit forms a pore that can gate independently from the other one. A common slower gating mechanism acts on both pores simultaneously; slow gating activates ClC-0 at hyperpolarized voltages. The ClC-2 Cl- channel is also activated by hyperpolarization, as are some ClC-1 mutants (e.g. D136G) and wild-type (WT) ClC-1 at certain pH values. 2. We studied the dependence on internal Cl- ([Cl-]i) of the hyperpolarization-activated gates of several ClC channels (WT ClC-0, ClC-0 mutant P522G, ClC-1 mutant D136G and an N-terminal deletion mutant of ClC-2), by patch clamping channels expressed in Xenopus oocytes. 3. With all these channels, reducing [Cl-]i shifted activation to more negative voltages and reduced the maximal activation at most negative voltages. 4. We also investigated the external halide dependence of WT ClC-2 using two-electrode voltage-clamp recording. Reducing external Cl- ([Cl-]o) activated ClC-2 currents. Replacing [Cl-]o by the less permeant Br- reduced channel activity and accelerated deactivation. 5. Gating of the ClC-2 mutant K566Q in normal [Cl-]o resembled that of WT ClC-2 in low [Cl-]o, i.e. channels had a considerable open probability (Po) at resting membrane potential. Substituting external Cl- by Br- or I- led to a decrease in Po. 6. The [Cl-]i dependence of the hyperpolarization-activated gates of various ClC channels suggests a similar gating mechanism, and raises the possibility that the gating charge for the hyperpolarization-activated gate is provided by Cl-. 7. The external halide dependence of hyperpolarization-activated gating of ClC-2 suggests that it is mediated or modulated by anions as in other ClC channels. In contrast to the depolarization-activated fast gates of ClC-0 and ClC-1, the absence of Cl- favours channel opening. Lysine 556 may be important for the

  20. Chloride Channels: Often enigmatic, rarely predictable

    Science.gov (United States)

    Duran, Charity; Thompson, Christopher H.; Xiao, Qinghuan; Hartzell, Criss

    2010-01-01

    Until recently, anion (Cl−) channels have received considerably less attention than cation channels. One reason for this may be that many Cl− channels perform functions that might be considered cell biological, like fluid secretion and cell volume regulation, whereas cation channels have historically been associated with cellular excitability that typically happens more rapidly. In this review, we discuss the recent explosion of interest in Cl− channels with special emphasis on new and often surprising developments over the last 5 years. This is exemplified by the findings that more than half of the ClC family members are antiporters, and not channels as was previously thought, and that bestrophins, previously prime candidates for Ca2+-activated Cl− channels, have been supplanted by the newly discovered anoctamins and now hold a tenuous position in the Cl− channel world. PMID:19827947

  1. Calcium-dependent modulation and plasma membrane targeting of the AKT2 potassium channel by the CBL4/ CIPK6 calcium sensor/protein kinase complex

    Institute of Scientific and Technical Information of China (English)

    Katrin Held; Jean-Baptiste Thibaud; J(o)rg Kudla; Francois Pascaud; Christian Eckert; Pawel Gajdanowicz; Kenji Hashimoto; Claire Corratgé-Faillie; Jan Niklas Offenborn; Beno(i)t Lacombe; Ingo Dreyer

    2011-01-01

    Potassium (K+) channel function is fundamental to many physiological processes. However, components and mechanisms regulating the activity of plant K+ channels remain poorly understood. Here, we show that the calcium (Ca2+)sensor CBL4 together with the interacting protein kinase CIPK6 modulates the activity and plasma membrane (PM)targeting of the K+ channel AKT2 from Arabidopsis thaliana by mediating translocation of AKT2 to the PM in plant cells and enhancing AKT2 activity in oocytes. Accordingly, akt2, cbl4 and cipk6 mutants share similar developmental and delayed flowering pheuotypes. Moreover, the isolated regulatory C-terminal domain of CIPK6 is sufficient for mediating CBL4- and Ca2+-dependent channel translocation from the endoplasmic reticulum membrane to the PM by a novel targeting pathway that is dependent on dual lipid modifications of CBL4 by myristoylation and palmitoylation. Thus, we describe a critical mechanism of ion-channel regulation where a Ca2+ sensor modulates K+ channel activity by promoting a kinase interaction-dependent but phosphorylation-independent translocation of the channel to the PM.

  2. Inhibition of nitrite-induced toxicity in channel catfish by calcium chloride and sodium chloride

    Science.gov (United States)

    Tommasso J.R., Wright; Simco, B.A.; Davis, K.B.

    1980-01-01

    Environmental chloride has been shown to inhibit methemoglobin formation in fish, thereby offering a protective effect against nitrite toxicity. Channel catfish (Ictalurus punctatus) were simultaneously exposed to various environmental nitrite and chloride levels (as either CaCl2 or NaCl) in dechlorinated tap water (40 mg/L total hardness, 47 mg/L alkalinity, 4 mg/L chloride, pH = 6.9-7.1, and temperature 21-24°C). Methemoglobin levels in fish simultaneously exposed to 2.5 mg/L nitrite and up to 30 mg/L chloride as either CaCl2 or NaCl were similar but significantly lower than in unprotected fish. Exposure to 10 mg/L nitrite and 60 mg/L chloride resulted in methemoglobin levels similar to those of the controls; most unprotected fish died. Fish exposed to 10 mg/L nitrite had significantly lower methemoglobin levels when protected with 15.0 mg/L chloride as CaCl2 than with NaCl. Fish exposed to nitrite in the presence of 60 mg/L chloride (as either CaCl2 or NaCl) had similar 24-h LC50 values that were significantly elevated above those obtained in the absence of chloride. Calcium had little effect on tolerance to nitrite toxicity in channel catfish in contrast to its large effect reported in steelhead trout (Salmo gairdneri).

  3. 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

    2004-01-01

    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.

  4. Chloride channels and the reactions of cells to topography

    Directory of Open Access Journals (Sweden)

    Tobasnick G.

    2001-12-01

    Full Text Available The reactions of rat epitenon cells to substratum topography on the micrometric and nanometric scale such as groove-ridge structures include cell extension, elongation and orientation reactions. In this paper we report that stretch-sensitive chloride channels may be involved in the earliest stages of these reactions in epitenon fibroblast-like cells. We report that rat epitenon-cells can develop appreciable lateral mechanical tension that could stretch both the force generating cells themselves and those nearby. We show that cells in medium in which more than 80% of the chloride has been replaced by nitrate show little reaction to topography. Spreading of the cells takes place but is much reduced along the direction of the groove-ridge topography but enhanced across the topography. The chloride channel inhibitors NPPB (5-Nitro-2- (3phenylpropylamino benzoicacid 4,4'-disothiocyanostilbene-2, 2' sulphonic acid (DIDS and Chlorotoxin produce similar results which are further accentuated when these inhibitors are presented in low chloride medium. An antibody against ClC3, which has close homology to ClC5/6 also, blocked reaction to topography. These treatments have no significant effect on cell spreading on planar surfaces nor do they lead to changes in internal pH in the cells. There is a slight inhibition of rates of cell movement . Experiments using antisense oligoribonucleotides to ClC-5 or ClC-6 channel m-RNA also inhibit topographic reactions, which provides further confirmation of the hypothesis. Since the ClC-3,4 and 5 share considerable sequence similarities in the genes and in their proteins it has not been possible to make an unambigous determination of which precise chloride channel(s is (are involved.

  5. ClC-3 chloride channel in hippocampal neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Lijuan Xu; Shuling Zhang; Hongling Fan; Zhichao Zhong; Xi Li; Xiaoxiao Jin; Quanzhong Chang

    2013-01-01

    Over-production of nitric oxide is pathogenic for neuronal apoptosis around the ischemic area fol-lowing ischemic brain injury. In this study, an apoptotic model in rat hippocampal neurons was tablished by 0.5 mmol/L 3-morpholinosyndnomine (SIN-1), a nitric oxide donor. The models were then cultured with 0.1 mmol/L of 4,4’-di sothiocyanostilbene-2,2’-disulfonic acid (DIDS;the chloride channel blocker) for 18 hours. Neuronal survival was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was assayed by Hoechst 33342-labeled neuronal DNA fluorescence staining. Western blot analysis and immunoche-nescence staining were applied to determine the changes of activated caspase-3 and CIC-3 channel proteins. Real-time PCR was used to detect the mRNA expression of CIC-3. The results showed that SIN-1 reduced the neuronal survival rate, induced neuronal apoptosis, and promoted ClC-3 chloride channel protein and mRNA expression in the apoptotic neurons. DIDS reversed the effect of SIN-1. Our findings indicate that the increased activities of the ClC-3 chloride channel may be involved in hippocampal neuronal apoptosis induced by nitric oxide.

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

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina;

    2004-01-01

    Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone form...

  7. Expression and cellular localisation of chloride intracellular channel 3 in human placenta and fetal membranes

    NARCIS (Netherlands)

    Money, T. T.; King, R. G.; Wong, M.H.; Stevenson, J. L.; Kalionis, B.; Erwich, J. J. H. M.; Huisman, Marcel; Timmer, A.; Hiden, U.; Desoye, G.; Gude, N. M.

    2007-01-01

    Chloride channels regulate the movement of a major cellular anion and are involved in fundamental processes that are critical for cell viability. Regulation of intracellular chloride is achieved by multiple classes of channel proteins. One class of putative channels are the chloride intracellular ch

  8. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  9. [Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel].

    Science.gov (United States)

    Cao, Huan-Huan; Fang, Fang; Yu, Bo; Luan, Jian; Jiang, Yu; Yang, Hong

    2015-04-25

    Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed additive effect with FSK and 3-Isobutyl-1-methylx (IBMX) in the activation of CFTR, while had no additive effect with genistein (GEN). In ex vivo studies, HMF and HTF could stimulate transepithelial Cl(-) secretion in rat colonic mucosa and enhance fluid secretion in mouse trachea submucosal glands. These results suggest that HMF and HTF may potentiate CFTR Cl(-) channel activities through both elevation of cAMP level and binding to CFTR protein pathways. The results provide new clues in elucidating structure and activity relationship of flavonoid CFTR activators. HMF might be developed as a new drug in the therapy of CFTR-related diseases such as bronchiectasis and habitual constipation. PMID:25896054

  10. Multiple P2Y receptors couple to calcium-dependent, chloride channels in smooth muscle cells of the rat pulmonary artery

    Directory of Open Access Journals (Sweden)

    Gurney Alison M

    2005-10-01

    Full Text Available Abstract Background Uridine 5'-triphosphate (UTP and uridine 5'-diphosphate (UDP act via P2Y receptors to evoke contraction of rat pulmonary arteries, whilst adenosine 5'-triphosphate (ATP acts via P2X and P2Y receptors. Pharmacological characterisation of these receptors in intact arteries is complicated by release and extracellular metabolism of nucleotides, so the aim of this study was to characterise the P2Y receptors under conditions that minimise these problems. Methods The perforated-patch clamp technique was used to record the Ca2+-dependent, Cl- current (ICl,Ca activated by P2Y receptor agonists in acutely dissociated smooth muscle cells of rat small (SPA and large (LPA intrapulmonary arteries, held at -50 mV. Contractions to ATP were measured in isolated muscle rings. Data were compared by Student's t test or one way ANOVA. Results ATP, UTP and UDP (10-4M evoked oscillating, inward currents (peak = 13–727 pA in 71–93% of cells. The first current was usually the largest and in the SPA the response to ATP was significantly greater than those to UTP or UDP (P -1 and changed little during agonist application. The non-selective P2 receptor antagonist suramin (10-4M abolished currents evoked by ATP in SPA (n = 4 and LPA (n = 4, but pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS (10-4M, also a non-selective P2 antagonist, had no effect (n = 4, 5 respectively. Currents elicited by UTP (n = 37 or UDP (n = 14 were unaffected by either antagonist. Contractions of SPA evoked by ATP were partially inhibited by PPADS (n = 4 and abolished by suramin (n = 5. Both antagonists abolished the contractions in LPA. Conclusion At least two P2Y subtypes couple to ICl,Ca in smooth muscle cells of rat SPA and LPA, with no apparent regional variation in their distribution. The suramin-sensitive, PPADS-resistant site activated by ATP most resembles the P2Y11 receptor. However, the suramin- and PPADS-insensitive receptor activated by UTP and UDP does not correspond to any of the known P2Y subtypes. These receptors likely play a significant role in nucleotide-induced vasoconstriction.

  11. 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.

  12. The CIC-3 chloride channels in cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    Dayue Darrel DUAN

    2011-01-01

    CIC-3 is a member of the CIC voltage-gated chloride(Cl-) channel superfamily. Recent studies have demonstrated the abundant expression and pleiotropy of CIC-3 in cardiac atrial and ventricular myocytes, vascular smooth muscle cells, and endothelial cells.CIC-3 Cl- channels can be activated by increase in cell volume, direct stretch of β1-integrin through focal adhesion kinase and many active molecules or growth factors including angiotensin Ⅱ and endothelin-1-mediated signaling pathways, Ca2+/calmodulin-dependent protein kinase Ⅱ and reactive oxygen species. CIC-3 may function as a key component of the volume-regulated Cl- channels, a superoxide anion transport and/or NADPH oxidase interaction partner, and a regulator of many other transporters. CIC-3 has been implicated in the regulation of electrical activity, cell volume, proliferation, differentiation, migration, apoptosis and intracellular pH. This review will highlight the major findings and recent advances in the study of CIC-3 Cl- channels in the cardiovascular system and discuss their important roles in cardiac and vascular remodeling during hypertension, myocardial hypertrophy, ischemia/reperfusion, and heart failure.

  13. Effects of antigliomatin from the scorpion venom of Buthus martensii Karsch on chloride channels on C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Zan Wang; Mingxian Li; Hongmei Meng; Min Huang; Weihong Lin; Li Cui; Shao Wang

    2011-01-01

    Using whole-cell patch-clamp recordings, the effects of antigliomatin were observed on chloride channels on C6 glioma cells cultured in vitro. Antigliomatin was extracted from the venom of the scorpion Buthus martensii Karsch. Chloride channels are closed under normal osmotic pressure. When osmotic pressure was reduced to 120, 110 and 100 mV, the cell volume enlarged, chloride channels opened, and the chloride channel current increased. Three minutes after antigliomatin treatment, the chloride channel current decreased in a dose-dependent manner. These results show that antigliomatin extracted from the venom of the scorpion Buthus martensii Karsch diminishes chloride channel currents on C6 glioma cells.

  14. Cystic fibrosis transmembrane conductance regulator and the outwardly rectifying chloride channel: a relationship between two chloride channels expressed in epithelial cells.

    Science.gov (United States)

    Hryciw, D H; Guggino, W B

    2000-11-01

    1. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) result in the primary defect observed in patients with cystic fibrosis. 2. The CFTR is a member of the ATPase-binding cassette (ABC) transporter family but, unlike other members of this group, CFTR conducts a chloride current that is activated by cAMP. 3. In epithelial cells, the cAMP-stimulated chloride current is conducted by both CFTR and the outwardly rectifying chloride channel (ORCC). 4. The present review summarizes the current knowledge of the properties of the two channels, as well as their relationship. Because the gene encoding the ORCC has not been identified, a discussion as to possible candidates for this chloride channel is included. PMID:11071305

  15. Cystic Fibrosis Gene Encodes a cAMP-Dependent Chloride Channel in Heart

    Science.gov (United States)

    Hart, Padraig; Warth, John D.; Levesque, Paul C.; Collier, Mei Lin; Geary, Yvonne; Horowitz, Burton; Hume, Joseph R.

    1996-06-01

    cAMP-dependent chloride channels in heart contribute to autonomic regulation of action potential duration and membrane potential and have been inferred to be due to cardiac expression of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In this report, a cDNA from rabbit ventricle was isolated and sequenced, which encodes an exon 5 splice variant (exon 5-) of CFTR, with >90% identity to human CFTR cDNA present in epithelial cells. Expression of this cDNA in Xenopus oocytes gave rise to robust cAMP-activated chloride currents that were absent in control water-injected oocytes. Antisense oligodeoxynucleotides directed against CFTR significnatly reduced the density of cAMP-dependent chloride currents in acutely cultured myocytes, thereby establishing a direct functional link between cardiac expression of CFTR protein and an endogenous chloride channel in native cardiac myocytes.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    -cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150...

  17. Function of chloride intracellular channel 1 in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Peng-Fei Ma; Jun-Qiang Chen; Zhen Wang; Jin-Lu Liu; Bo-Pei Li

    2012-01-01

    AIM:To investigate the effect of chloride intracellular channel 1 (CLIC1) on the cell proliferation,apoptosis,migration and invasion of gastric cancer cells.METHODS:CLIC1 expression was evaluated in human gastric cancer cell lines SGC-7901 and MGC-803 by real time polymerase chain reaction (RT-PCR).Four segments of small interference RNA (siRNA) targeting CLIC1 mRNA and a no-sense control segment were designed by bioinformatics technology.CLIC1 siRNA was selected using Lipofectamine 2000 and transfected transiently into human gastric cancer SGC-7901 and MGC-803 cells.The transfected efficiency was observed under fluorescence microscope.After transfection,mRNA expression of CLIC1 was detected with RT-PCR and Western blotting was used to detect the protein expression.Proliferation was examined by methyl thiazolyl tetrazolium and apoptosis was detected with flow cytometry.Polycarbonate membrane transwell chamber and Matrigel were used for the detection of the changes of invasion and migration of the two cell lines.RESULTS:In gastric cancer cell lines SGC-7901 and MGC-803,CLIC1 was obviously expressed and CLIC1 siRNA could effectively suppress the expression of CLIC1 protein and mRNA.Proliferation of cells transfected with CLIC1 siRNA3 was enhanced notably,and the highest proliferation rate was 23.3% (P =0.002) in SGC-7901 and 35.55% (P =0.001) in MGC-803 cells at 48 h.The G2/M phase proportion increased,while G0/G1 and S phase proportions decreased.The apoptotic rate of the CLIC1 siRNA3 group obviously decreased in both SGC-7901 cells (62.24%,P =0.000) and MGC-803 cells (52.67%,P =0.004).Down-regulation of CLIC1 led to the inhibition of invasion and migration by 54.31% (P =0.000) and 33.62% (P =0.001) in SGC-7901 and 40.74% (P =0.000) and 29.26% (P =0.002) in MGC-803.However,there was no significant difference between the mock group cells and the negative control group cells.CONCLUSION:High CLIC1 expression can efficiently inhibit proliferation and

  18. Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Long, Yan; Lin, Zuoxian [Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China); Xia, Menghang; Zheng, Wei [National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Zhiyuan, E-mail: li_zhiyuan@gibh.ac.cn [Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China)

    2013-03-01

    Tetra-n-octylammonium bromide and benzethonium chloride are synthetic quaternary ammonium salts that are widely used in hospitals and industries for the disinfection and surface treatment and as the preservative agent. Recently, the activities of HERG channel inhibition by these compounds have been found to have potential risks to induce the long QT syndrome and cardiac arrhythmia, although the mechanism of action is still elusive. This study was conducted to investigate the mechanism of HERG channel inhibition by these compounds by using whole-cell patch clamp experiments in a CHO cell line stably expressing HERG channels. Tetra-n-octylammonium bromide and benzethonium chloride exhibited concentration-dependent inhibitions of HERG channel currents with IC{sub 50} values of 4 nM and 17 nM, respectively, which were also voltage-dependent and use-dependent. Both compounds shifted the channel activation I–V curves in a hyperpolarized direction for 10–15 mV and accelerated channel activation and inactivation processes by 2-fold. In addition, tetra-n-octylammonium bromide shifted the inactivation I–V curve in a hyperpolarized direction for 24.4 mV and slowed the rate of channel deactivation by 2-fold, whereas benzethonium chloride did not. The results indicate that tetra-n-octylammonium bromide and benzethonium chloride are open-channel blockers that inhibit HERG channels in the voltage-dependent, use-dependent and state-dependent manners. - Highlights: ► Tetra-n-octylammonium and benzethonium are potent HERG channel inhibitors. ► Channel activation and inactivation processes are accelerated by the two compounds. ► Both compounds are the open-channel blockers to HERG channels. ► HERG channel inhibition by both compounds is use-, voltage- and state dependent. ► The in vivo risk of QT prolongation needs to be studied for the two compounds.

  19. Identification of Herbal Compound lmperatorin with Adverse Effects on ANO1 and CFTR Chloride Channels

    Institute of Scientific and Technical Information of China (English)

    HAO Feng; YI Fei; ZHANG Di; NING Yan; SU Wei-heng; FENG Xue-chao; YANG Hong; MA Tong-hui

    2011-01-01

    Calcium-activated chloride channels(CaCCs) are the crucial regulators of transepithelial fluid secretion,smooth muscle contraction and sensory transduction. Recently, compelling evidence has indicated that TMEM 16A(ANO 1 or anoctamin-i ) is a bona fide calcium-acvtivated chloride channel. A few small molecule CaCCs regulators are available for functional and therapeutic studies. We screened 126 natural compounds from Chinese herbs. Screening was performed with an iodide influx assay in Fischer rat thyroid epithelial cells to coexpress ANOI and an iodide-sensitive fluorescent indicator(EYFP-HI48Q/I152L). lmperatorin, a coumarin compound, was identifled to inhibit ANOl-mediated chloride transport activated by multiple calcium-elevating agonists. The inhibitory effect is dose-dependent with IC50 ~14.63 μmol/L. Interestingly, imperatorin activated CFTR chloride channel with EC50 ~35.52 μmol/L. The adverse effects of imperatorin on CaCC and CFTR chloride channels will make it useful in pharmacological dissection of chloride transport in airway and intestinal epithelium. Further studies are required to evaluate the therapeutic effects of imperatorin on hypertension, asthma and certain tumors.

  20. Effect of trimethyllead chloride on slowly activating (SV) channels in red beet (Beta vulgaris L.) taproots.

    Science.gov (United States)

    Trela, Zenon; Burdach, Zbigniew; Przestalski, Stanisław; Karcz, Waldemar

    2012-12-01

    The patch-clamp technique was used to examine the effect of trimethyllead chloride (Met(3)PbCl) on SV channel activity in red beet (Beta vulgaris L.) taproot vacuoles. It was found that in the control bath the macroscopic currents showed the typical slow activation and a strong outward rectification of the steady-state currents. An addition of Met(3)PbCl to the bath solution blocked, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant τ increased several times in the presence of 100 μM trimethyllead chloride at all voltages tested. When single channel properties were analyzed, only little channel activity could be recorded in the presence of 100 μM Met(3)PbCl. Trimethyllead chloride decreased significantly (by about one order of magnitude) the open probability of single channels. The recordings of single channel activity obtained in the presence and absence of Met(3)PbCl showed that organolead only slightly (by ca. 10%) decreased the unitary conductance of single channels. It was also found that Met(3)PbCl diminished significantly the number of SV channel openings, whereas it did not change the opening times of the channels. Taken together, these results suggest that Met(3)PbCl binding site is located outside the channel selectivity filter. PMID:23312295

  1. Myotonia Congenita Mutation Enhances the Degradation of Human CLC-1 Chloride Channels

    OpenAIRE

    Lee, Ting-Ting; Zhang, Xiao-Dong; Chuang, Chao-Chin; Chen, Jing-Jer; Chen, Yi-An; Chen, Shu-Ching; Chen, Tsung-Yu; Tang, Chih-Yung

    2013-01-01

    Myotonia congenita is a hereditary muscle disorder caused by mutations in the human voltage-gated chloride (Cl−) channel CLC-1. Myotonia congenita can be inherited in an autosomal recessive (Becker type) or dominant (Thomsen type) fashion. One hypothesis for myotonia congenita is that the inheritance pattern of the disease is determined by the functional consequence of the mutation on the gating of CLC-1 channels. Several disease-related mutations, however, have been shown to yield functional...

  2. Novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids as calcium activated chloride channel inhibitors

    OpenAIRE

    Kumar, Satish; Namkung, Wan; A S Verkman; Sharma, Pawan K

    2012-01-01

    Transmembrane protein 16A (TMEM16A) channels are recently discovered membrane proteins that functions as a calcium activated chloride channel (CaCC). CaCCs are major regulators of various physiological processes, such as sensory transduction, epithelial secretion, smooth muscle contraction and oocyte fertilization. Thirty novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids (B01–B30) were synthesized and evaluated for their TMEM16A inhibitory activity by using short circuit curre...

  3. The Validation of Nematode-Specific Acetylcholine-Gated Chloride Channels as Potential Anthelmintic Drug Targets

    Science.gov (United States)

    Wever, Claudia M.; Farrington, Danielle; Dent, Joseph A.

    2015-01-01

    New compounds are needed to treat parasitic nematode infections in humans, livestock and plants. Small molecule anthelmintics are the primary means of nematode parasite control in animals; however, widespread resistance to the currently available drug classes means control will be impossible without the introduction of new compounds. Adverse environmental effects associated with nematocides used to control plant parasitic species are also motivating the search for safer, more effective compounds. Discovery of new anthelmintic drugs in particular has been a serious challenge due to the difficulty of obtaining and culturing target parasites for high-throughput screens and the lack of functional genomic techniques to validate potential drug targets in these pathogens. We present here a novel strategy for target validation that employs the free-living nematode Caenorhabditis elegans to demonstrate the value of new ligand-gated ion channels as targets for anthelmintic discovery. Many successful anthelmintics, including ivermectin, levamisole and monepantel, are agonists of pentameric ligand-gated ion channels, suggesting that the unexploited pentameric ion channels encoded in parasite genomes may be suitable drug targets. We validated five members of the nematode-specific family of acetylcholine-gated chloride channels as targets of agonists with anthelmintic properties by ectopically expressing an ivermectin-gated chloride channel, AVR-15, in tissues that endogenously express the acetylcholine-gated chloride channels and using the effects of ivermectin to predict the effects of an acetylcholine-gated chloride channel agonist. In principle, our strategy can be applied to validate any ion channel as a putative anti-parasitic drug target. PMID:26393923

  4. Physiology and Pathophysiology of CLC-1: Mechanisms of a Chloride Channel Disease, Myotonia

    Directory of Open Access Journals (Sweden)

    Chih-Yung Tang

    2011-01-01

    Full Text Available The CLC-1 chloride channel, a member of the CLC-channel/transporter family, plays important roles for the physiological functions of skeletal muscles. The opening of this chloride channel is voltage dependent and is also regulated by protons and chloride ions. Mutations of the gene encoding CLC-1 result in a genetic disease, myotonia congenita, which can be inherited as an autosmal dominant (Thomsen type or an autosomal recessive (Becker type pattern. These mutations are scattered throughout the entire protein sequence, and no clear relationship exists between the inheritance pattern of the mutation and the location of the mutation in the channel protein. The inheritance pattern of some but not all myotonia mutants can be explained by a working hypothesis that these mutations may exert a “dominant negative” effect on the gating function of the channel. However, other mutations may be due to different pathophysiological mechanisms, such as the defect of protein trafficking to membranes. Thus, the underlying mechanisms of myotonia are likely to be quite diverse, and elucidating the pathophysiology of myotonia mutations will require the understanding of multiple molecular/cellular mechanisms of CLC-1 channels in skeletal muscles, including molecular operation, protein synthesis, and membrane trafficking mechanisms.

  5. An improved ivermectin-activated chloride channel receptor for inhibiting electrical activity in defined neuronal populations

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Lynch, Joseph W

    2010-01-01

    for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain...

  6. Mitochondria-Rich Cells as Experimental Model in Studies of Epithelial Chloride Channels

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Amstrup, Jan; Møbjerg, Nadja;

    2002-01-01

    The mitochondria-rich (mr) cell of amphibian skin epithelium is differentiated as a highly specialised pathway for passive transepithelial transport of chloride. The apical membrane of mr cells expresses several types of Cl- channels, of which the function of only two types has been studied...

  7. Chloride channels in the small intestinal cell line IEC-18.

    Science.gov (United States)

    Basavappa, Srisaila; Vulapalli, Sreesatya Raju; Zhang, Hui; Yule, David; Coon, Steven; Sundaram, Uma

    2005-01-01

    Small intestinal crypt cells play a critical role in modulating Cl- secretion during digestion. The types of Cl- channels mediating Cl- secretion in the small intestine was investigated using the intestinal epithelial cell line, IEC-18, which was derived from rat small intestine crypt cells. In initial radioisotope efflux studies, exposure to forskolin, ionomycin or a decrease in extracellular osmolarity significantly increased 36Cl efflux as compared to control cells. Whole cell patch clamp techniques were subsequently used to examine in more detail the swelling-, Ca2+-, and cAMP-activated Cl- conductance. Decreasing the extracellular osmolarity from 290 to 200 mOsm activated a large outwardly rectifying Cl- current that was voltage-independent and had an anion selectivity of I- > Cl-. Increasing cytosolic Ca2+ by ionomycin activated whole cell Cl- currents, which were also outwardly rectifying but were voltage-dependent. The increase in intracellular Ca2+ levels with ionomycin was confirmed with fura-2 loaded IEC-18 cells. A third type of whole cell Cl- current was observed after increases in intracellular cAMP induced by forskolin. These cAMP-activated Cl- currents have properties consistent with cystic fibrosis transmembrane regulator (CFTR) Cl- channels, as the currents were blocked by glibenclamide or NPPB but insensitive to DIDS. In addition, the current-voltage relationship was linear and had an anion selectivity of Cl- > I-. Confocal immunofluorescence studies and Western blots with two different anti-CFTR antibodies confirmed the expression of CFTR. These results suggest that small intestinal crypt cells express multiple types of Cl- channels, which may all contribute to net Cl- secretion. PMID:15389550

  8. Simultaneous optical recording in multiple cells by digital holographic microscopy of chloride current associated to activation of the ligand-gated chloride channel GABA(A receptor.

    Directory of Open Access Journals (Sweden)

    Pascal Jourdain

    Full Text Available Chloride channels represent a group of targets for major clinical indications. However, molecular screening for chloride channel modulators has proven to be difficult and time-consuming as approaches essentially rely on the use of fluorescent dyes or invasive patch-clamp techniques which do not lend themselves to the screening of large sets of compounds. To address this problem, we have developed a non-invasive optical method, based on digital holographic microcopy (DHM, allowing monitoring of ion channel activity without using any electrode or fluorescent dye. To illustrate this approach, GABA(A mediated chloride currents have been monitored with DHM. Practically, we show that DHM can non-invasively provide the quantitative determination of transmembrane chloride fluxes mediated by the activation of chloride channels associated with GABA(A receptors. Indeed through an original algorithm, chloride currents elicited by application of appropriate agonists of the GABA(A receptor can be derived from the quantitative phase signal recorded with DHM. Finally, chloride currents can be determined and pharmacologically characterized non-invasively simultaneously on a large cellular sampling by DHM.

  9. The ABC protein turned chloride channel whose failure causes cystic fibrosis

    Science.gov (United States)

    Gadsby, David C.; Vergani, Paola; Csanády, László

    2006-03-01

    CFTR chloride channels are encoded by the gene mutated in patients with cystic fibrosis. These channels belong to the superfamily of ABC transporter ATPases. ATP-driven conformational changes, which in other ABC proteins fuel uphill substrate transport across cellular membranes, in CFTR open and close a gate to allow transmembrane flow of anions down their electrochemical gradient. New structural and biochemical information from prokaryotic ABC proteins and functional information from CFTR channels has led to a unifying mechanism explaining those ATP-driven conformational changes.

  10. Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea.

    Science.gov (United States)

    Jiang, Yu; Yu, Bo; Yang, Hong; Ma, Tonghui

    2016-01-01

    Secretory diarrhea remains a global health burden and causes major mortality in children. There have been some focuses on antidiarrheal therapies that may reduce fluid losses and intestinal motility in diarrheal diseases. In the present study, we identified shikonin as an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. The IC50 value of shikonin was 6.5 μM. Short-circuit current measurements demonstrated that shikonin inhibited Eact-induced Cl(-) current in a dose-dependent manner, with IC50 value of 1.5 μM. Short-circuit current measurement showed that shikonin exhibited inhibitory effect against CCh-induced Cl(-) currents in mouse colonic epithelia but did not affect cytoplasmic Ca(2+) concentration as well as the other major enterocyte chloride channel conductance regulator. Characterization study found that shikonin inhibited basolateral K(+) channel activity without affecting Na(+)/K(+)-ATPase activities. In vivo studies revealed that shikonin significantly delayed intestinal motility in mice and reduced stool water content in a neonatal mice model of rotaviral diarrhea without affecting the viral infection process in vivo. Taken together, the results suggested that shikonin inhibited enterocyte calcium-activated chloride channels, the inhibitory effect was partially through inhbition of basolateral K(+) channel activity, and shikonin could be a lead compound in the treatment of rotaviral secretory diarrhea. PMID:27601995

  11. Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance

    Institute of Scientific and Technical Information of China (English)

    Paul; Linsdell

    2014-01-01

    Dysfunction of the cystic fibrosis transmembrane con-ductance regulator(CFTR) chloride channel causes cys-tic fibrosis, while inappropriate activity of this channeloccurs in secretory diarrhea and polycystic kidney dis-ease. Drugs that interact directly with CFTR are there-fore of interest in the treatment of a number of diseasestates. This review focuses on one class of small mol-ecules that interacts directly with CFTR, namely inhibi-tors that act by directly blocking chloride movementthrough the open channel pore. In theory such com-pounds could be of use in the treatment of diarrheaand polycystic kidney disease, however in practice allknown substances acting by this mechanism to inhibitCFTR function lack either the potency or specificity forin vivo use. Nevertheless, this theoretical pharmaco-logical usefulness set the scene for the developmentof more potent, specific CFTR inhibitors. Biophysically,open channel blockers have proven most useful as ex-perimental probes of the structure and function of theCFTR chloride channel pore. Most importantly, the useof these blockers has been fundamental in developing afunctional model of the pore that includes a wide innervestibule that uses positively charged amino acid sidechains to attract both permeant and blocking anionsfrom the cell cytoplasm. CFTR channels are also subjectto this kind of blocking action by endogenous anionspresent in the cell cytoplasm, and recently this blocking effect has been suggested to play a role in the physio-logical control of CFTR channel function, in particular as a novel mechanism linking CFTR function dynamically to the composition of epithelial cell secretions. It has also been suggested that future drugs could target this same pathway as a way of pharmacologically increasing CFTR activity in cystic fibrosis. Studying open channel blockers and their mechanisms of action has resulted in significant advances in our understanding of CFTR as a pharmacological target in disease states, of

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

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1996-01-01

    or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate...... arterioles with the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was equally enhanced by omission of extracellular calcium and by addition of 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. The stimulatory effects of low calcium [with...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-18

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-09-01

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

  16. Design and Synthesis of Photoaffinity Probe Candidates for the GABA-gated Chloride Channel

    Institute of Scientific and Technical Information of China (English)

    LIU Shang-Zhong; LI Qing-X.

    2006-01-01

    In order to characterize binding sites of insecticidal compounds on GABA gated chloride channel, new photoaffinity probe candidates based on 5e-t-butyl-2e-[4-(substituted-propynyl)phenyl]-1,3-dithiane for the noncompetitive blocker (NCB) site of the γ-aminobutyric acid (GABA)-gated chloride channel were designed and synthesized, and their potency as an inhibitor on NCB was measured by 4'-ethynyl-4-n-[2,3-3H2]-propylbicycloorthobenzoate (3H EBOB) assay. The synthesized compounds showed high inhibition activities with half maximum inhibition concentrations (IC50) of lower than 35 nmol/L and were very stable in binding conditions as well photoreacted quickly at 300 nm light. These new compounds are expected to be good photoaffinity labeling probes if radioisotope iodine is incorporated.

  17. Ligand-gated chloride channels are receptors for biogenic amines in C. elegans

    OpenAIRE

    Ringstad, Niels; Abe, Namiko; Horvitz, H. Robert

    2009-01-01

    Biogenic amines such as serotonin and dopamine are intercellular signaling molecules that function widely as neurotransmitters and neuromodulators. We have identified in the nematode Caenorhabditis elegans three ligand-gated chloride channels that are receptors for biogenic amines: LGC-53 is a high-affinity dopamine receptor, LGC-55 is a high-affinity tyramine receptor, and LGC-40 is a low-affinity serotonin receptor that is also gated by choline and acetylcholine. lgc-55 mutants are defectiv...

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

    OpenAIRE

    Hou, Yuning; Guan, Xiaoqing; Yang, Zhe; Li, Chunying

    2016-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially...

  19. Stable ATP binding mediated by a partial NBD dimer of the CFTR chloride channel

    OpenAIRE

    Tsai, Ming-Feng; Li, Min; Hwang, Tzyh-Chang

    2010-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a member of the adenosine triphosphate (ATP) binding cassette (ABC) superfamily, is an ATP-gated chloride channel. Like other ABC proteins, CFTR encompasses two nucleotide binding domains (NBDs), NBD1 and NBD2, each accommodating an ATP binding site. It is generally accepted that CFTR’s opening–closing cycles, each completed within 1 s, are driven by rapid ATP binding and hydrolysis events in NBD2. Here, by recording CFTR currents in...

  20. Activation Effect of Cathartic Natural Compound Rhein to CFTR Chloride Channel

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed in intestinal exocrine glands, which plays a key role in intestinal fluid secretion. A natural anthraquinone activator of CFTR Cl- channel, rhein, was identified by screening 217 single compounds from Chinese herbs via a cellbased halide-sensitive fluorescent assay. Rhein activates CFTR Cl- transportation in a dose-dependent manner in the presence of cAMP with a physiological concentration. This study provides a novel molecular pharmacological mechanism for the laxative drugs in Traditional Chinese Medicine such as aloe, cascara and senna.

  1. Cys-loop ligand-gated chloride channels in dorsal unpaired median neurons of Locusta migratoria.

    Science.gov (United States)

    Janssen, Daniel; Derst, Christian; Rigo, Jean-Michel; Van Kerkhove, Emmy

    2010-05-01

    In insects, inhibitory neurotransmission is generally associated with members of the cys-loop ligand-gated anion channels, such as the glutamate-gated chloride channel (GluCl), the GABA-gated chloride channels (GABACl), and the histamine-gated chloride channels (HisCl). These ionotropic receptors are considered established target sites for the development of insecticides, and therefore it is necessary to obtain a better insight in their distribution, structure, and functional properties. Here, by combining electrophysiology and molecular biology techniques, we identified and characterized GluCl, GABACl, and HisCl in dorsal unpaired median (DUM) neurons of Locust migratoria. In whole cell patch-clamp recordings, application of glutamate, GABA, or histamine induced rapidly activating ionic currents. GluCls were sensitive to ibotenic acid and blocked by picrotoxin and fipronil. The pharmacological profile of the L. migratoria GABACl fitted neither the vertebrate GABA(A) nor GABA(C) receptor and was similar to the properties of the cloned Drosophila melanogaster GABA receptor subunit (Rdl). The expression of Rdl-like subunit-containing GABA receptors was shown at the molecular level using RT-PCR. Sequencing analysis indicated that the orthologous GABACl of D. melanogaster CG10357-A is expressed in DUM neurons of L. migratoria. Histamine-induced currents exhibited a fast onset and desensitized completely on continuous application of histamine. In conclusion, within the DUM neurons of L. migratoria, we identified three different cys-loop ligand-gated anion channels that use GABA, glutamate, or histamine as their neurotransmitter. PMID:20200125

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

    Institute of Scientific and Technical Information of China (English)

    Hong YANG; Li-na XU; Cheng-yan HE; Xin LIU; Rou-yu FANG; Tong-hui MA

    2011-01-01

    Aim: To clarify whether CFTR is a molecular target of intestinal fluid secretion caused by the anthraquinone compounds from laxative herbal plants.Methods: A cell-based fluorescent assay to measure I- influx through CFTR chloride channel. A short-circuit current assay to measure transcellular Cl- current across single layer FRT cells and freshly isolated colon mucosa. A closed loop experiment to measure colon fluid secretion in vivo.Results: Anthraquinone compounds rhein, aloe-emodin and 1,8-dihydroxyanthraquinone (DHAN) stimulated l- influx through CFTR chloride channel in a dose-dependent manner in the presence of physiological concentration of cAMP. In the short-circuit current assay,the three compound enhanced Cl- currents in epithelia formed by CFTR-expressing FRT cells with EC5o values of 73±1.4, 56±1.7, and 50±0.5 μmol/L, respectively, and Rhein also enhanced Cl- current in freshly isolated rat colonic mucosa with a similar potency. These effects were completely reversed by the CFTR selective blocker CFTRinh-172. In in vivo closed loop experiments, rhein 2 mmol/L stimu-lated colonic fluid accumulation that was largely blocked by CFTRinh-172. The anthraquinone compounds did not elevate cAMP level in cultured FRT cells and rat colonic mucosa, suggesting a direct effect on CFTR activity.Conclusion: Natural anthraquinone compounds in vegetable laxative drugs are CFTR potsntiators that stimulated colonic chloride and fluid secretion. Thus CFTR chloride channel is a molecular target of vegetable laxative drugs.

  3. Enhancement of an outwardly rectifying chloride channel in hippocampal pyramidal neurons after cerebral ischemia.

    Science.gov (United States)

    Li, Jianguo; Chang, Quanzhong; Li, Xiaoming; Li, Xiawen; Qiao, Jiantian; Gao, Tianming

    2016-08-01

    Cerebral ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms remain unclear, but it is known that apoptosis is involved in this process. Chloride efflux has been implicated in the progression of apoptosis in various cell types. Using both the inside-out and whole-cell configurations of the patch-clamp technique, the present study characterized an outwardly rectifying chloride channel (ORCC) in acutely dissociated pyramid neurons in the hippocampus of adult rats. The channel had a nonlinear current-voltage relationship with a conductance of 42.26±1.2pS in the positive voltage range and 18.23±0.96pS in the negative voltage range, indicating an outward rectification pattern. The channel is Cl(-) selective, and the open probability is voltage-dependent. It can be blocked by the classical Cl(-) channel blockers DIDS, SITS, NPPB and glibenclamide. We examined the different changes in ORCC activity in CA1 and CA3 pyramidal neurons at 6, 24 and 48h after transient forebrain ischemia. In the vulnerable CA1 neurons, ORCC activity was persistently enhanced after ischemic insult, whereas in the invulnerable CA3 neurons, no significant changes occurred. Further analysis of channel kinetics suggested that multiple openings are a major contributor to the increase in channel activity after ischemia. Pharmacological blockade of the ORCC partly attenuated cell death in the hippocampal neurons. We propose that the enhanced activity of ORCC might contribute to selective neuronal damage in the CA1 region after cerebral ischemia, and that ORCC may be a therapeutic target against ischemia-induced cell death. PMID:27181516

  4. Glutamate-activated chloride channels: Unique fipronil targets present in insects but not in mammals

    OpenAIRE

    NARAHASHI, Toshio; Zhao, Xilong; Ikeda, Tomoko; Salgado, Vincent L.; Yeh, Jay Z.

    2010-01-01

    Selectivity to insects over mammals is one of the important characteristics for a chemical to become a useful insecticide. Fipronil was found to block cockroach GABA receptors more potently than rat GABAA receptors. Furthermore, glutamate-activated chloride channels (GluCls), which are present in cockroaches but not in mammals, were very sensitive to the blocking action of fipronil. The IC50s of fipronil block were 30 nM in cockroach GABA receptors and 1600 nM in rat GABAA receptors. Moreover...

  5. Chloride channel-dependent copper acquisition of laccase in the basidiomycetous fungus Cryptococcus neoformans

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The CLC chloride channel gene CLC-A of the pathogen yeast Cryptococcus neoformans was previously reported to be critical for multicopper laccase activity and growth at an elevated pH.This study reports that copper homeostasis was impaired in the clc-a mutant.This was demonstrated by the substantial decrease of the intracellular quantity of copper under copper-limited growth as determined by flame atomic absorption spectrometry.CLC-A is a critical factor in copper homeostasis which is required for copper acquisition of laccase in C.neoformans.

  6. The Granular Chloride Channel ClC-3 Is Permissive For Insulin Secretion

    OpenAIRE

    Deriy, Ludmila V.; Gomez, Erwin A.; Jacobson, David A.; Wang, Xueqing; Hopson, Jessika A.; Liu, Xiang Y.; Zhang, Guangping; Bindokas, Vytautas P.; Philipson, Louis H.; Nelson, Deborah J.

    2009-01-01

    Insulin secretion from pancreatic β–cells is dependent on maturation and acidification of the secretory granule necessary for prohormone convertase cleavage of proinsulin. Previous studies in isolated β–cells revealed that acidification may be dependent on the granule membrane chloride channel ClC-3, in a step permissive for a regulated secretory response. In this study, immuno-electron microscopy of β–cells revealed colocalization of ClC-3 and insulin on secretory granules. Clc-3−/− mice as ...

  7. Synthesis and Characterization of A Small Molecule CFTR Chloride Channel Inhibitor

    Institute of Scientific and Technical Information of China (English)

    HE Cheng-yan; ZHANG Heng-jun; SU Zhong-min; ZHOU Jin-song; YANG Hong; MA Tong-hui

    2004-01-01

    A thiazolidinone CFTR inhibitor(CFTRinh-172) was synthesized by a three-step procedure with trifluromethylaniline as the starting material. The synthesized CFTR inhibitor was characterized structurally by means of 1H NMR and functionally in a CFTR-expressing cell line FRT/hCFTR/EYFP-H148Q by both fluorescent and electrophysiological methods. A large amount(100 g) of high-quality small molecule thiazolidinone CFTR chloride channel inhibitor, CFTRinh-172, can be produced with this simple three-step synthetic procedure. The structure of the final product 2-thioxo-3-(3-trifluromethylphenyl)-5-[4-carboxyphenyl-methylene]-4-thiazolidinone was confirmed by 1H NMR. The overall yield was 58% with a purity over 99% as analyzed by HPLC. The synthesized CFTRinh-172 specifically inhibited CFTR chloride channel function in a cell-based fluorescence assay(Kd≈1.5 μmol/L) and in a Ussing chamber-based short-circuit current assay(Kd≈0.2 μmol/L), indicating better quality than that of the commercial combinatorial compound. The synthesized inhibitor is nontoxic to cultured cells at a high concentration and to mouse at a high dose. The synthetic procedure developed here can be used to produce a large amount of the high-quality CFTRinh-172 suitable for antidiarrheal studies and for creation of cystic fibrosis models in large animals. The procedure can be used to synthesize radiolabled CFTRinh-172 for in vivo pharmacokinetics studies.

  8. Chloride channel protein 2 prevents glutamate-induced apoptosis in retinal ganglion cells

    Science.gov (United States)

    Bi, Miao-Miao; Hong, Sen; Ma, Ling-Jun; Zhou, Hong-Yan; Lu, Jia; Zhao, Jing; Zheng, Ya-Juan

    2016-01-01

    Objective(s): The purpose of this study was to investigate the role of chloride channel protein 2 (ClC-2) in glutamate-induced apoptosis in the retinal ganglion cell line (RGC-5). Materials and Methods: RGC-5 cells were treated with 1 mM glutamate for 24 hr. The expression of ClC-2, Bax, and Bcl-2 was detected by western blot analysis. Cell survival and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Caspase-3 and -9 activities were determined by a colorimetric assay. The roles of ClC-2 in glutamate-induced apoptosis were examined by using ClC-2 complementary deoxyribonucleic acid (cDNA) and small inference ribonucleic acid (RNA) transfection technology. Results: Overexpression of ClC-2 in RGC-5 cells significantly decreased glutamate-induced apoptosis and increased cell viability, whereas silencing of ClC-2 with short hairpin (sh) RNA produced opposite effects. ClC-2 overexpression increased the expression of Bcl-2, decreased the expression of Bax, and decreased caspase-3 and -9 activation in RGC-5 cells treated with glutamate, but silencing of ClC-2 produced opposite effects. Conclusion: Our data suggest that ClC-2 chloride channels might play a protective role in glutamate-induced apoptosis in retinal ganglion cells via the mitochondria-dependent apoptosis pathway. PMID:27635193

  9. Huntington disease skeletal muscle is hyperexcitable owing to chloride and potassium channel dysfunction.

    Science.gov (United States)

    Waters, Christopher W; Varuzhanyan, Grigor; Talmadge, Robert J; Voss, Andrew A

    2013-05-28

    Huntington disease is a progressive and fatal genetic disorder with debilitating motor and cognitive defects. Chorea, rigidity, dystonia, and muscle weakness are characteristic motor defects of the disease that are commonly attributed to central neurodegeneration. However, no previous study has examined the membrane properties that control contraction in Huntington disease muscle. We show primary defects in ex vivo adult skeletal muscle from the R6/2 transgenic mouse model of Huntington disease. Action potentials in diseased fibers are more easily triggered and prolonged than in fibers from WT littermates. Furthermore, some action potentials in the diseased fibers self-trigger. These defects occur because of decreases in the resting chloride and potassium conductances. Consistent with this, the expression of the muscle chloride channel, ClC-1, in Huntington disease muscle was compromised by improper splicing and a corresponding reduction in total Clcn1 (gene for ClC-1) mRNA. Additionally, the total Kcnj2 (gene for the Kir2.1 potassium channel) mRNA was reduced in disease muscle. The resulting muscle hyperexcitability causes involuntary and prolonged contractions that may contribute to the chorea, rigidity, and dystonia that characterize Huntington disease.

  10. A High-affinity Activator of G551D-CFTR Chloride Channel Identified By High Throughput Screening

    Institute of Scientific and Technical Information of China (English)

    ZHAO Lu; HE Cheng-yan; LIU Yan-li; ZHOU Hong-lan; ZHOU Jin-song; SHANG De-jing; YANG Hong

    2004-01-01

    A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(Kd=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.

  11. Effect of Trimethyltin Chloride on Slow Vacuolar (SV Channels in Vacuoles from Red Beet (Beta vulgaris L. Taproots.

    Directory of Open Access Journals (Sweden)

    Zenon Trela

    Full Text Available In the present study, patch-clamp techniques have been used to investigate the effect of trimethyltin chloride (Met3SnCl on the slow vacuolar (SV channels in vacuoles from red beet (Beta vulgaris L. taproots. Activity of SV channels has been measured in whole-vacuole and cytosolic side-out patch configurations. It was found that addition of trimethyltin chloride to the bath solution suppressed, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant, τ, increased significantly in the presence of the organotin. When single channel activity was analyzed, only little channel activity could be recorded at 100 μM Met3SnCl. Trimethyltin chloride added to the bath medium significantly decreased (by ca. threefold at 100 μM Met3SnCl and at 100 mV voltage, as compared to the control medium the open probability of single channels. Single channel recordings obtained in the presence and absence of trimethyltin chloride showed that the organotin only slightly (by <10% decreased the unitary conductance of single channels. It was also found that Met3SnCl significantly diminished the number of SV channel openings, whereas it did not change the opening times of the channels. Taking into account the above and the fact that under the here applied experimental conditions (pH = 7.5 Met3SnCl is a non-dissociated (more lipophilic compound, we suggest that the suppression of SV currents observed in the presence of the organotin results probably from its hydrophobic properties allowing this compound to translocate near the selectivity filter of the channel.

  12. Effect of Trimethyltin Chloride on Slow Vacuolar (SV) Channels in Vacuoles from Red Beet (Beta vulgaris L.) Taproots.

    Science.gov (United States)

    Trela, Zenon; Burdach, Zbigniew; Siemieniuk, Agnieszka; Przestalski, Stanisław; Karcz, Waldemar

    2015-01-01

    In the present study, patch-clamp techniques have been used to investigate the effect of trimethyltin chloride (Met3SnCl) on the slow vacuolar (SV) channels in vacuoles from red beet (Beta vulgaris L.) taproots. Activity of SV channels has been measured in whole-vacuole and cytosolic side-out patch configurations. It was found that addition of trimethyltin chloride to the bath solution suppressed, in a concentration-dependent manner, SV currents in red beet vacuoles. The time constant, τ, increased significantly in the presence of the organotin. When single channel activity was analyzed, only little channel activity could be recorded at 100 μM Met3SnCl. Trimethyltin chloride added to the bath medium significantly decreased (by ca. threefold at 100 μM Met3SnCl and at 100 mV voltage, as compared to the control medium) the open probability of single channels. Single channel recordings obtained in the presence and absence of trimethyltin chloride showed that the organotin only slightly (by <10%) decreased the unitary conductance of single channels. It was also found that Met3SnCl significantly diminished the number of SV channel openings, whereas it did not change the opening times of the channels. Taking into account the above and the fact that under the here applied experimental conditions (pH = 7.5) Met3SnCl is a non-dissociated (more lipophilic) compound, we suggest that the suppression of SV currents observed in the presence of the organotin results probably from its hydrophobic properties allowing this compound to translocate near the selectivity filter of the channel. PMID:26317868

  13. TRPC1 regulates calcium-activated chloride channels in salivary gland cells.

    Science.gov (United States)

    Sun, Yuyang; Birnbaumer, Lutz; Singh, Brij B

    2015-11-01

    Calcium-activated chloride channel (CaCC) plays an important role in modulating epithelial secretion. It has been suggested that in salivary tissues, sustained fluid secretion is dependent on Ca(2+) influx that activates ion channels such as CaCC to initiate Cl(-) efflux. However direct evidence as well as the molecular identity of the Ca(2+) channel responsible for activating CaCC in salivary tissues is not yet identified. Here we provide evidence that in human salivary cells, an outward rectifying Cl(-) current was activated by increasing [Ca(2+)]i, which was inhibited by the addition of pharmacological agents niflumic acid (NFA), an antagonist of CaCC, or T16Ainh-A01, a specific TMEM16a inhibitor. Addition of thapsigargin (Tg), that induces store-depletion and activates TRPC1-mediated Ca(2+) entry, potentiated the Cl(-) current, which was inhibited by the addition of a non-specific TRPC channel blocker SKF96365 or removal of external Ca(2+). Stimulation with Tg also increased plasma membrane expression of TMEM16a protein, which was also dependent on Ca(2+) entry. Importantly, in salivary cells, TRPC1 silencing, but not that of TRPC3, inhibited CaCC especially upon store depletion. Moreover, primary acinar cells isolated from submandibular gland also showed outward rectifying Cl(-) currents upon increasing [Ca(2+)]i. These Cl(-) currents were again potentiated with the addition of Tg, but inhibited in the presence of T16Ainh-A01. Finally, acinar cells isolated from the submandibular glands of TRPC1 knockout mice showed significant inhibition of the outward Cl(-) currents without decreasing TMEM16a expression. Together the data suggests that Ca(2+) entry via the TRPC1 channels is essential for the activation of CaCC.

  14. Novel chloride channel gene mutations in two unrelated Chinese families with myotonia congenita

    Directory of Open Access Journals (Sweden)

    Gao Feng

    2010-12-01

    Full Text Available Myotonia congenita (MC is a genetic disease characterized by mutations in the muscle chloride channel gene (CLCN1. To date, approximately 130 different mutations on the CLCN1 gene have been identified. However, most of the studies have focused on Caucasians, and reports on CLCN1 mutations in Chinese population are rare. This study investigated the mutation of CLCN1 in two Chinese families with MC. Direct sequencing of the CLCN1 gene revealed a heterozygous mutation (892G>A, resulting in A298T in one family and a compound heterozygous mutations (782A>G, resulting in Y261C; 1679T>C, resulting in M560T in the other family, None of the 100 normal controls had these mutations. Our findings add more to the available information on the CLCN1 mutation spectrum, and provide a valuable reference for studying the mutation types and inheritance pattern of CLCN1 in the Chinese population.

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

    Science.gov (United States)

    Hou, Yuning; Guan, Xiaoqing; Yang, Zhe; Li, Chunying

    2016-03-15

    Cystic fibrosis transmembrane conductance regulator (CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers. PMID:26989463

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

    Directory of Open Access Journals (Sweden)

    Juan Francisco Rodríguez-Landa

    2013-01-01

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

  17. Inhibitors of swelling-activated chloride channels increase infarct size and apoptosis in rabbit myocardium.

    Science.gov (United States)

    Souktani, Rachid; Ghaleh, Bijan; Tissier, Renaud; d'Anglemont de Tassigny, Alexandra; Aouam, Karim; Bedossa, Pierre; Charlemagne, Danièle; Samuel, Janelyse; Henry, Patrick; Berdeaux, Alain

    2003-10-01

    Apoptosis is a significant contributor to myocardial cell death during ischemia-reperfusion and swelling-activated chloride channels (I(Cl,swell)) contribute to apoptosis. However, the relationship between I(Cl,swell) ischemia-reperfusion and apoptosis remains unknown. To further investigate this, New Zealand rabbits underwent a 20-min coronary artery occlusion (CAO) followed by 72 h of coronary artery reperfusion (CAR). Two I(Cl,swell) blockers, 5-nitro-2-[3-phenylpropylamino]benzoic acid (NPPB) and indanyloxyacetic acid 94 (IAA-94) (both 1 mg/kg), were administered prior to CAO and throughout the 72 h CAR. Infarct size (IS) was increased with NPPB and IAA-94 compared with control (vehicle) rabbits (51 +/- 2% and 48 +/- 3% and vs. 35 +/- 2%, respectively, P < 0.05). Similar results were found when NPPB was administered only during the reperfusion period. The percentage of TUNEL-positive nuclei in the border zone of the infarct was increased with NPPB compared with control (37 +/- 2% vs. 25 +/- 31%, P < 0.05) as well as the number of cytoplasmic histone-associated DNA fragments (0.45 +/- 0.06 vs. 0.33 +/- 0.04 absorbance units, P < 0.05). These findings support the concept that I(Cl,swell) channels play an important role in the determination of myocardial infarct size and apoptosis during ischemia-reperfusion. PMID:14703716

  18. Molecular dissection of gating in the ClC-2 chloride channel.

    Science.gov (United States)

    Jordt, S E; Jentsch, T J

    1997-04-01

    The ClC-2 chloride channel is probably involved in the regulation of cell volume and of neuronal excitability. Site-directed mutagenesis was used to understand ClC-2 activation in response to cell swelling, hyperpolarization and acidic extracellular pH. Similar to equivalent mutations in ClC-0, neutralizing Lys566 at the end of the transmembrane domains results in outward rectification and a shift in voltage dependence, but leaves the basic gating mechanism, including swelling activation, intact. In contrast, mutations in the cytoplasmic loop between transmembrane domains D7 and D8 abolish all three modes of activation by constitutively opening the channel without changing its pore properties. These effects resemble those observed with deletions of an amino-terminal inactivation domain, and suggest that it may act as its receptor. Such a 'ball-and-chain' type mechanism may act as a final pathway in the activation of ClC-2 elicited by several stimuli. PMID:9130703

  19. Interaction of Human Chloride Intracellular Channel Protein 1 (CLIC1) with Lipid Bilayers: A Fluorescence Study.

    Science.gov (United States)

    Hare, Joanna E; Goodchild, Sophia C; Breit, Samuel N; Curmi, Paul M G; Brown, Louise J

    2016-07-12

    Chloride intracellular channel protein 1 (CLIC1) is very unusual as it adopts a soluble glutathione S-transferase-like canonical fold but can also autoinsert into lipid bilayers to form an ion channel. The conversion between these forms involves a large, but reversible, structural rearrangement of the CLIC1 module. The only identified environmental triggers controlling the metamorphic transition of CLIC1 are pH and oxidation. Until now, there have been no high-resolution structural data available for the CLIC1 integral membrane state, and consequently, a limited understanding of how CLIC1 unfolds and refolds across the bilayer to form a membrane protein with ion channel activity exists. Here we show that fluorescence spectroscopy can be used to establish the interaction and position of CLIC1 in a lipid bilayer. Our method employs a fluorescence energy transfer (FRET) approach between CLIC1 and a dansyl-labeled lipid analogue to probe the CLIC1-lipid interface. Under oxidizing conditions, a strong FRET signal between the single tryptophan residue of CLIC1 (Trp35) and the dansyl-lipid analogue was detected. When considering the proportion of CLIC1 interacting with the lipid bilayer, as estimated by fluorescence quenching experiments, the FRET distance between Trp35 and the dansyl moiety on the membrane surface was determined to be ∼15 Å. This FRET-detected interaction provides direct structural evidence that CLIC1 associates with membranes. The results presented support the current model of an oxidation-driven interaction of CLIC1 with lipid bilayers and also propose a membrane anchoring role for Trp35. PMID:27299171

  20. Expression pattern and function of alternative splice variants of glutamate-gated chloride channel in the housefly Musca domestica.

    Science.gov (United States)

    Kita, Tomo; Ozoe, Fumiyo; Ozoe, Yoshihisa

    2014-02-01

    Glutamate-gated chloride channels (GluCls) mediate fast inhibitory neurotransmission in invertebrate nervous systems. cDNAs encoding two alternative splice variants (MdGluClB and C) of the GluCl subunit were cloned from the housefly Musca domestica. The expression patterns of three variants, including the previously reported MdGluClA, differed among the body parts (head, thorax, abdomen, and leg) of the adult housefly and among developmental stages (embryo, larva, pupa, and adult). The MdGluClA and B transcripts were abundant in the central nervous system of the adult, whereas the MdGluClC transcript was expressed in the central nervous system and as the predominant variant in the peripheral tissues. The sensitivities to the agonist glutamate and the allosteric activator ivermectin B1a did not differ between channels containing MdGluCl variants when they were singly or co-expressed in Xenopus oocytes. By contrast, MdGluClA and B channels were more sensitive to the channel blockers fipronil and picrotoxinin than was MdGluClC channels. Heteromeric channels containing different subunit variants were more sensitive to picrotoxinin than were homomeric channels. Heteromeric channels were more sensitive to fipronil than were homomeric MdGluClC channels but not than homomeric MdGluClA and B channels. These results suggest that functionally indistinguishable but pharmacologically distinct GluCls are expressed in a spatially and temporally distinct manner in the housefly.

  1. Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β

    Science.gov (United States)

    Peng, Yi-Jheng; Huang, Jing-Jia; Wu, Hao-Han; Hsieh, Hsin-Ying; Wu, Chia-Ying; Chen, Shu-Ching; Chen, Tsung-Yu; Tang, Chih-Yung

    2016-01-01

    Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation. PMID:27580824

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

    Directory of Open Access Journals (Sweden)

    Wei Cheng

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

  3. Myotonia Congenita-Associated Mutations in Chloride Channel-1 Affect Zebrafish Body Wave Swimming Kinematics

    Science.gov (United States)

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

    2014-01-01

    Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1). Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in human patients suffering from myotonia congenita. We developed video analytic tools that are able to provide precise quantitative measurements of movement abnormalities in order to analyse the effect of these CLCN1 mutations on adult transgenic zebrafish swimming. Two new parameters for body-wave kinematics of swimming reveal changes in body curvature and tail offset in transgenic zebrafish expressing the disease-associated CLCN1 mutants, presumably due to their effect on muscle function. The capability of the developed video analytic tool to distinguish wild-type from transgenic zebrafish could provide a useful asset to screen for compounds that reverse the disease phenotype, and may be applicable to other movement disorders besides myotonia congenita. PMID:25083883

  4. Calcium-dependent activation of Pyk2 by hypoxia.

    Science.gov (United States)

    Beitner-Johnson, Dana; Ferguson, Tsuneo; Rust, Randy T; Kobayashi, Shuichi; Millhorn, David E

    2002-02-01

    The Pyk2 tyrosine kinase can be activated by both calcium-dependent and calcium-independent mechanisms. Exposure to moderate hypoxia (5% O(2)) induced a rapid and persistent tyrosine phosphorylation of Pyk2 in pheochromocytoma (PC12) cells. Hypoxia and KCl-depolarization increased the phosphotyrosine content of Pyk2 by twofold and fourfold, respectively. Both of these effects were abolished in the absence of extracellular calcium. There was a modest activation of MAPK in parallel with the onset of Pyk2 phosphorylation. However, there was no detectable activation of either JNK or c-src, two other known downstream targets of Pyk2. Thus, exposure to hypoxia may selectively target specific subsets of Pyk2 signalling pathways. PMID:11781137

  5. Mapping convulsants’ binding to the GABA-A receptor chloride ionophore: a proposed model for channel binding sites

    OpenAIRE

    Kalueff, A.V.

    2006-01-01

    Gamma aminobutyric acid (GABA) type A receptors play a key role in brain inhibitory neurotransmission, and are ligand-activated chloride channels blocked by numerous convulsant ligands. Here we summarize data on binding of picrotoxin, tetrazoles, β-lactams, bicyclophosphates, butyrolactones and neurotoxic pesticides to GABA-A ionophore, and discuss functional and structural overlapping of their binding sites. The paper reviews data on convulsants’ binding sensitivity to different point mutati...

  6. Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.

    OpenAIRE

    Meyer-Kleine, C; Steinmeyer, K; Ricker, K; Jentsch, T J; Koch, M C

    1995-01-01

    Autosomal dominant myotonia congenita and autosomal recessive generalized myotonia (GM) are genetic disorders characterized by the symptom of myotonia, which is based on an electrical instability of the muscle fiber membrane. Recently, these two phenotypes have been associated with mutations in the major muscle chloride channel gene CLCN1 on human chromosome 7q35. We have systematically screened the open reading frame of the CLCN1 gene for mutations by SSC analysis (SSCA) in a panel of 24 fam...

  7. Revealing the activation pathway for TMEM16A chloride channels from macroscopic currents and kinetic models.

    Science.gov (United States)

    Contreras-Vite, Juan A; Cruz-Rangel, Silvia; De Jesús-Pérez, José J; Figueroa, Iván A Aréchiga; Rodríguez-Menchaca, Aldo A; Pérez-Cornejo, Patricia; Hartzell, H Criss; Arreola, Jorge

    2016-07-01

    TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca(2+)]i), membrane depolarization, extracellular Cl(-) or permeant anions and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations. (a) TMEM16A is activated by voltage in the absence of intracellular Ca(2+). (b) The Cl(-) conductance is decreased after reducing extracellular Cl(-) concentration ([Cl(-)]o). (c) ICl is regulated by physiological concentrations of [Cl(-)]o. (d) In cells dialyzed with 0.2 μM [Ca(2+)]i, Cl(-) has a bimodal effect: at [Cl(-)]o kinetics. To explain the contribution of Vm, Ca(2+) and Cl(-) to gating, we developed a 12-state Markov chain model. This model explains TMEM16A activation as a sequential, direct, and Vm-dependent binding of two Ca(2+) ions coupled to a Vm-dependent binding of an external Cl(-) ion, with Vm-dependent transitions between states. Our model predicts that extracellular Cl(-) does not alter the apparent Ca(2+) affinity of TMEM16A, which we corroborated experimentally. Rather, extracellular Cl(-) acts by stabilizing the open configuration induced by Ca(2+) and by contributing to the Vm dependence of activation. PMID:27138167

  8. Fluid shear stress enhances the cell volume decrease of osteoblast cells by increasing the expression of the ClC-3 chloride channel

    OpenAIRE

    Liu, Li; Cai, Siyi; Qiu, Guixing; Lin, Jin

    2016-01-01

    ClC-3 is a volume-sensitive chloride channel that is responsible for cell volume adjustment and regulatory cell volume decrease (RVD). In order to evaluate the effects of fluid shear stress (FSS) stimulation on the osteoblast ClC-3 chloride channel, MC3T3-E1 cells were stimulated by FSS in the experimental group. Fluorescence quantitative polymerase chain reaction was used to detect changes in ClC-3 mRNA expression, the chloride ion fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolin...

  9. The chloride-channel blocker 9-anthracenecarboxylic acid reduces the nonlinear capacitance of prestin-associated charge movement.

    Science.gov (United States)

    Harasztosi, Csaba; Gummer, Anthony W

    2016-04-01

    The basis of the extraordinary sensitivity and frequency selectivity of the cochlea is a chloride-sensitive protein called prestin which can produce an electromechanical response and which resides in the basolateral plasma membrane of outer hair cells (OHCs). The compound 9-anthracenecarboxylic acid (9-AC), an inhibitor of chloride channels, has been found to reduce the electromechanical response of the cochlea and the OHC mechanical impedance. To elucidate these 9-AC effects, the functional electromechanical status of prestin was assayed by measuring the nonlinear capacitance of OHCs from the guinea-pig cochlea and of prestin-transfected human embryonic kidney 293 (HEK 293) cells. Extracellular application of 9-AC caused reversible, dose-dependent and chloride-sensitive reduction in OHC nonlinear charge transfer, Qmax . Prestin-transfected cells also showed reversible reduction in Qmax . For OHCs, intracellular 9-AC application as well as reduced intracellular pH had no detectable effect on the reduction in Qmax by extracellularly applied 9-AC. In the prestin-transfected cells, cytosolic application of 9-AC approximately halved the blocking efficacy of extracellularly applied 9-AC. OHC inside-out patches presented the whole-cell blocking characteristics. Disruption of the cytoskeleton by preventing actin polymerization with latrunculin A or by decoupling of spectrin from actin with diamide did not affect the 9-AC-evoked reduction in Qmax . We conclude that 9-AC acts on the electromechanical transducer principally by interaction with prestin rather than acting via the cytoskeleton, chloride channels or pH. The 9-AC block presents characteristics in common with salicylate, but is almost an order of magnitude faster. 9-AC provides a new tool for elucidating the molecular dynamics of prestin function. PMID:26869218

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

    DEFF Research Database (Denmark)

    Asmild, Margit; Willumsen, Niels J.

    2000-01-01

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

  11. Benzopyrimido-pyrrolo-oxazine-dione (R)-BPO-27 Inhibits CFTR Chloride Channel Gating by Competition with ATP.

    Science.gov (United States)

    Kim, Yonjung; Anderson, Marc O; Park, Jinhong; Lee, Min Goo; Namkung, Wan; Verkman, A S

    2015-10-01

    We previously reported that benzopyrimido-pyrrolo-oxazinedione BPO-27 [6-(5-bromofuran-2-yl)-7,9-dimethyl-8,10-dioxo-11-phenyl-7,8,9,10-tetrahydro-6H-benzo[b]pyrimido [4',5':3,4]pyrrolo [1,2-d][1,4]oxazine-2-carboxylic acid] inhibits the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel with low nanomolar potency and reduces cystogenesis in a model of polycystic kidney disease. We used computational chemistry and patch-clamp to show that enantiomerically pure (R)-BPO-27 inhibits CFTR by competition with ATP, whereas (S)-BPO-27 is inactive. Docking computations using a homology model of CFTR structure suggested that (R)-BPO-27 binds near the canonical ATP binding site, and these findings were supported by molecular dynamics simulations showing a lower binding energy for the (R) versus (S) stereoisomers. Three additional lower-potency BPO-27 analogs were modeled in a similar fashion, with the binding energies predicted in the correct order. Whole-cell patch-clamp studies showed linear CFTR currents with a voltage-independent (R)-BPO-27 block mechanism. Single-channel recordings in inside-out patches showed reduced CFTR channel open probability and increased channel closed time by (R)-BPO-27 without altered unitary channel conductance. At a concentration of (R)-BPO-27 that inhibited CFTR chloride current by ∼50%, the EC50 for ATP activation of CFTR increased from 0.27 to 1.77 mM but was not changed by CFTRinh-172 [4-[[4-oxo-2-thioxo-3-[3-trifluoromethyl)phenyl]-5-thiazolidinylidene]methyl]benzoic acid], a thiazolidinone CFTR inhibitor that acts at a site distinct from the ATP binding site. Our results suggest that (R)-BPO-27 inhibition of CFTR involves competition with ATP.

  12. High glucose inhibits ClC-2 chloride channels and attenuates cell migration of rat keratinocytes

    Directory of Open Access Journals (Sweden)

    Pan F

    2015-08-01

    Full Text Available Fuqiang Pan, Rui Guo, Wenguang Cheng, Linlin Chai, Wenping Wang, Chuan Cao, Shirong LiDepartment of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing, People’s Republic of China Background: Accumulating evidence has demonstrated that migration of keratinocytes is critical to wound epithelialization, and defects of this function result in chronic delayed-healing wounds in diabetes mellitus patients, and the migration has been proved to be associated with volume-activated chloride channels. The aim of the study is to investigate the effects of high glucose (HG, 25 mM on ClC-2 chloride channels and cell migration of keratinocytes.Methods: Newborn Sprague Dawley rats were used to isolate and culture the keratinocyte in this study. Immunofluorescence assay, real-time polymerase chain reaction, and Western blot assay were used to examine the expression of ClC-2 protein or mRNA. Scratch wound assay was used to measure the migratory ability of keratinocytes. Transwell cell migration assay was used to measure the invasion and migration of keratinocytes. Recombinant lentivirus vectors were established and transducted to keratinocytes. Whole-cell patch clamp was used to perform the electrophysiological studies.Results: We found that the expression of ClC-2 was significantly inhibited when keratinocytes were exposed to a HG (25 mM medium, accompanied by the decline of volume-activated Cl- current (ICl,vol, migration potential, and phosphorylated PI3K as compared to control group. When knockdown of ClC-2 by RNAi or pretreatment with wortmannin, similar results were observed, including ICl,vol and migration keratinocytes were inhibited.Conclusion: Our study proved that HG inhibited ClC-2 chloride channels and attenuated cell migration of rat keratinocytes via inhibiting PI3K signaling.Keywords: high glucose, keratinocytes, ClC-2, cell migration, PI3K

  13. Characterization of the putative chloride channel xClC-5 expressed in Xenopus laevis oocytes and comparison with endogenous chloride currents.

    Science.gov (United States)

    Schmieder, S; Lindenthal, S; Banderali, U; Ehrenfeld, J

    1998-09-01

    1. We recently cloned a putative chloride channel (xClC-5) from the renal cell line A6, which induced the appearance of a Cl- conductance not found in control oocytes after homologous expression in Xenopus oocytes. With the aim of increasing the Xenopus oocyte xClC-5 expression, we constructed a new plasmid in which the native 5' and 3' non-coding regions of xClC-5 were replaced by the non-coding regions of the Xenopus beta-globin sequence and in which a Kozak consensus site was introduced before the initiator ATG. 2. We then compared the induced currents Inative (induced by injection of cRNA presenting the native non-coding regions of xClC-5) and Ibeta-globin (induced by injection of cRNA presenting the non-coding regions of the Xenopus beta-globin sequence) investigating anion selectivity and anion blocker sensitivity. Several differences were found: (1) expression yield and oocyte surviving rate were largely increased by injecting (beta) xClC-5 cRNA, (2) the Ibeta-globin outward rectification score was 2.6 times that of Inative, (3) the anion conductivity sequence was nitrate > bromide > chloride > iodide > gluconate for Ibeta-globin and iodide > bromide > nitrate > chloride > gluconate for Inative, (4) 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), anthracene-9-carboxylic acid (9-AC), DIDS, lanthanum ions, cAMP and ionomycin-induced [Ca2+]i increase inhibited Inative but had no effect on Ibeta-globin, and (5) Inative showed considerable similarity to the previously reported endogenous current appearing after ClC-6 or pICln cRNA injection. 3. Comparison of Inative with the endogenous chloride current ICl,swell which develops under hyposmotic conditions demonstrated several similarities in their electrophysiological and pharmacological characteristics but were nevertheless distinguishable. 4. In vitro translation assays demonstrated that protein synthesis was much greater using the (beta) xClC-5 construct than that of xClC-5. Furthermore, immunoreactivity

  14. Regulation of the membrane insertion and conductance activity of the metamorphic chloride intracellular channel protein CLIC1 by cholesterol.

    Directory of Open Access Journals (Sweden)

    Stella M Valenzuela

    Full Text Available The Chloride Intracellular ion channel protein CLIC1 has the ability to spontaneously insert into lipid membranes from a soluble, globular state. The precise mechanism of how this occurs and what regulates this insertion is still largely unknown, although factors such as pH and redox environment are known contributors. In the current study, we demonstrate that the presence and concentration of cholesterol in the membrane regulates the spontaneous insertion of CLIC1 into the membrane as well as its ion channel activity. The study employed pressure versus area change measurements of Langmuir lipid monolayer films; and impedance spectroscopy measurements using tethered bilayer membranes to monitor membrane conductance during and following the addition of CLIC1 protein. The observed cholesterol dependent behaviour of CLIC1 is highly reminiscent of the cholesterol-dependent-cytolysin family of bacterial pore-forming proteins, suggesting common regulatory mechanisms for spontaneous protein insertion into the membrane bilayer.

  15. Neuroprotective effects of ClC-3 chloride channel in glutamate-induced retinal ganglion cell RGC-5 apoptosis

    Institute of Scientific and Technical Information of China (English)

    Li Yu; Ning Han; Ligang Jiang; Yajuan Zheng; Lifeng Liu

    2011-01-01

    Transforming growth factor β plays a role in regulation of apoptosis in ClC-3 and the Smads signaling pathway, although the underlying mechanisms remain unclear. The present study determined possible signal transduction mechanisms based on CIC-3 expression, which accordingly affected apoptosis of retinal ganglion cells in a glutamate-induced retinal ganglion cell RGC-5 apoptosis model. Results revealed significantly increased cell survival rate and significantly decreased apoptosis rate following apoptosis of ClC-3 cDNA-transfected glutamate-induced retinal ganglion cells. Following inhibition of the ClC-3 chloride channel using RNAi technology, cell survival and apoptosis rates were reversed. In addition, expression of transforming growth factor β2, Smads2, Smads3, Smads4, and Smads7 increased to varying degrees. These results suggest that ClC-3 chloride channel plays a protective role in glutamate-induced apoptosis of retinal ganglion cells, and transforming growth factor β/Smads signal transduction pathways are involved in this process.

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

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Hoffmann, Else Kay

    1994-01-01

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

  17. Control of sensory neuron excitability by serotonin involves 5HT2C receptors and Ca(2+)-activated chloride channels.

    Science.gov (United States)

    Salzer, Isabella; Gantumur, Enkhbileg; Yousuf, Arsalan; Boehm, Stefan

    2016-11-01

    Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron. Unlike other algogenic mediators, such as PGE2 and bradykinin, 5HT did not affect currents through TTX-resistant Na(+) channels or Kv7 K(+) channels. In all neurons investigated, 5HT potentiated capsaicin-evoked currents through TRPV1 channels, an effect that was attenuated by antagonists at 5HT2A (4 F 4 PP), 5HT2B (SB 204741), as well as 5HT2C (RS 102221) receptors. 5HT triggered slowly arising inward Cl(-) currents in 53% of the neurons. This effect was antagonized by the 5HT2C receptor blocker only, and the current was prevented by an inhibitor of Ca(2+)-activated chloride channels (CaCC). The 5HT-induced increase in action potential firing was also abolished by this CaCC blocker and by the TRPV1 inhibitor capsazepine. Amongst the subtype selective 5HT2 antagonists, only RS 102221 (5HT2C-selectively) counteracted the rise in action potential firing elicited by 5HT. These results show that 5HT excites DRG neurons mainly via 5HT2C receptors which concomitantly mediate a sensitization of TRPV1 channels and an opening of CaCCs.

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

    Directory of Open Access Journals (Sweden)

    Oscar Sacchi

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

  19. A family of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans.

    Science.gov (United States)

    Putrenko, Igor; Zakikhani, Mahvash; Dent, Joseph A

    2005-02-25

    The genome of the nematode Caenorhabditis elegans encodes a surprisingly large and diverse superfamily of genes encoding Cys loop ligand-gated ion channels. Here we report the first cloning, expression, and pharmacological characterization of members of a family of anion-selective acetylcholine receptor subunits. Two subunits, ACC-1 and ACC-2, form homomeric channels for which acetylcholine and arecoline, but not nicotine, are efficient agonists. These channels are blocked by d-tubocurarine but not by alpha-bungarotoxin. We provide evidence that two additional subunits, ACC-3 and ACC-4, interact with ACC-1 and ACC-2. The acetylcholine-binding domain of these channels appears to have diverged substantially from the acetylcholine-binding domain of nicotinic receptors. PMID:15579462

  20. Isolated-patch recording from liposomes containing functionally reconstituted chloride channels from Torpedo electroplax.

    OpenAIRE

    Tank, D W; Miller, C.; Webb, W W

    1982-01-01

    Small unilamellar vesicles formed from purified phospholids by detergent/dialysis methods may be enlarged to 30-microns diameter by freezing and thawing. Very-high-resistance seals were formed by applying a glass micropipette to the surface of these large liposomes, and single bilayer "patches" of membrane were isolated from the liposome surface while remaining sealed to the micropipette. The exogenous channel-forming peptides gramicidin and alamethicin induced characteristic single-channel f...

  1. Novel residues lining the CFTR chloride channel pore identified by functional modification of introduced cysteines.

    Science.gov (United States)

    Fatehi, Mohammad; Linsdell, Paul

    2009-04-01

    Substituted cysteine accessibility mutagenesis (SCAM) has been used widely to identify pore-lining amino acid side chains in ion channel proteins. However, functional effects on permeation and gating can be difficult to separate, leading to uncertainty concerning the location of reactive cysteine side chains. We have combined SCAM with investigation of the charge-dependent effects of methanethiosulfonate (MTS) reagents on the functional permeation properties of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. We find that cysteines substituted for seven out of 21 continuous amino acids in the eleventh and twelfth transmembrane (TM) regions can be modified by external application of positively charged [2-(trimethylammonium)ethyl] MTS bromide (MTSET) and negatively charged sodium [2-sulfonatoethyl] MTS (MTSES). Modification of these cysteines leads to changes in the open channel current-voltage relationship at both the macroscopic and single-channel current levels that reflect specific, charge-dependent effects on the rate of Cl(-) permeation through the channel from the external solution. This approach therefore identifies amino acid side chains that lie within the permeation pathway. Cysteine mutagenesis of pore-lining residues also affects intrapore anion binding and anion selectivity, giving more information regarding the roles of these residues. Our results demonstrate a straightforward method of screening for pore-lining amino acids in ion channels. We suggest that TM11 contributes to the CFTR pore and that the extracellular loop between TMs 11 and 12 lies close to the outer mouth of the pore. PMID:19381710

  2. Molecular pharmacology of kidney and inner ear CLC-K chloride channels

    Directory of Open Access Journals (Sweden)

    Antonella eGradogna

    2010-10-01

    Full Text Available CLC-K channels belong to the CLC gene family, which comprises both Cl- channels and Cl-/H+ antiporters. They form homodimers which additionally co-assemble with the small protein barttin. In the kidney, they are involved in NaCl reabsorption ; in the inner ear they are important for endolymph production. Mutations in CLC-Kb lead to renal salt loss (Bartter’s syndrome; mutations in barttin lead additionally to deafness. CLC-K channels are interesting potential drug targets. CLC-K channel blockers have potential as alternative diuretics, whereas CLC-K activators could be used for the treatment of patients with Bartter’s syndrome. Several small organic acids inhibit CLC-K channels from the outside by binding to a site in the external vestibule of the ion conducting pore. Benzofuran derivatives with affinities better than 10 µM have been discovered. Niflumic acid (NFA exhibits a complex interaction with CLC-K channels. Below ~ 1 mM, NFA activates CLC-Ka, whereas at higher concentrations NFA inhibits channel activity. The co-planarity of the rings of the NFA molecule is essential for its activating action. Mutagenesis has led to the identification of potential regions of the channel that interact with NFA. CLC-K channels are also modulated by pH and [Ca2+]ext. The inhibition at low pH has been shown to be mediated by a His-residue at the beginning of helix Q, the penultimate transmembrane helix. Two acidic residues from opposite subunits form two symmetrically related intersubunit Ca2+ binding sites, whose occupation increases channel activity.The relatively high affinity CLC-K blockers may already serve as leads for the development of useful drugs. On the other hand, the CLC-K potentiator NFA has a quite low affinity, and, being a non-steroidal anti-inflammatory drug, can be expected to exert significant side effects. More specific and more potent activators will be needed and it will be important to understand the molecular mechanisms that

  3. Voltage- and calcium-dependent motility of saccular hair bundles

    Science.gov (United States)

    Quiñones, Patricia M.; Meenderink, Sebastiaan W. F.; Bozovic, Dolores

    2015-12-01

    Active bundle motility, which is hypothesized to supply feedback for mechanical amplification of signals, is thought to enhance sensitivity and sharpen tuning in vestibular and auditory organs. To study active hair bundle motility, we combined high-speed camera recordings of bullfrog sacculi, which were mounted in a two-compartment chamber, and voltage-clamp of the hair cell membrane potential. Using this paradigm, we measured three types of bundle motions: 1) spontaneous oscillations which can be analyzed to measure the physiological operating range of the transduction channel; 2) a sustained quasi-static movement of the bundle that depends on membrane potential; and 3) a fast, transient and asymmetric movement that resets the bundle position and depends on changes in the membrane potential. These data support a role for both calcium and voltage in the transduction-channel function.

  4. Calcium dependence of Eugenol tolerance and toxicity in Saccharomyces cerevisiae

    OpenAIRE

    Roberts, Stephen K.; Martin McAinsh; Hanna Cantopher; Sean Sandison

    2014-01-01

    Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. ...

  5. Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

    Science.gov (United States)

    Harasztosi, Csaba; Gummer, Anthony W.

    2011-11-01

    The voltage-dependent chloride-channel blocker anthracene-9-carboxylic acid (9AC) has been found to reduce the imaginary but not the real part of the mechanical impedance of the organ of Corti, suggesting that the effective stiffness of outer hair cells (OHCs) is reduced by 9AC. To examine whether 9AC interacts directly with the motor protein prestin to reduce the membrane component of the impedance, the patch-clamp technique in whole-cell configuration was used to measure the nonlinear capacitance (NLC) of isolated OHCs and, as control, prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9AC significantly reduced the NLC of both OHCs and HEK293 cells. Intracellular 9AC did not influence the blocking effect of the extracellular applied drug. These results suggest that 9AC interacts directly with prestin, reducing the effective stiffness of the motor, and that the interaction is extracellular.

  6. Expression of calcium-activated chloride channels Ano1 and Ano2 in mouse taste cells.

    Science.gov (United States)

    Cherkashin, Alexander P; Kolesnikova, Alisa S; Tarasov, Michail V; Romanov, Roman A; Rogachevskaja, Olga A; Bystrova, Marina F; Kolesnikov, Stanislav S

    2016-02-01

    Specialized Ca(2+)-dependent ion channels ubiquitously couple intracellular Ca(2+) signals to a change in cell polarization. The existing physiological evidence suggests that Ca(2+)-activated Cl(-) channels (CaCCs) are functional in taste cells. Because Ano1 and Ano2 encode channel proteins that form CaCCs in a variety of cells, we analyzed their expression in mouse taste cells. Transcripts for Ano1 and Ano2 were detected in circumvallate (CV) papillae, and their expression in taste cells was confirmed using immunohistochemistry. When dialyzed with CsCl, taste cells of the type III exhibited no ion currents dependent on cytosolic Ca(2+). Large Ca(2+)-gated currents mediated by TRPM5 were elicited in type II cells by Ca(2+) uncaging. When TRPM5 was inhibited by triphenylphosphine oxide (TPPO), ionomycin stimulated a small but resolvable inward current that was eliminated by anion channel blockers, including T16Ainh-A01 (T16), a specific Ano1 antagonist. This suggests that CaCCs, including Ano1-like channels, are functional in type II cells. In type I cells, CaCCs were prominently active, blockable with the CaCC antagonist CaCCinh-A01 but insensitive to T16. By profiling Ano1 and Ano2 expressions in individual taste cells, we revealed Ano1 transcripts in type II cells only, while Ano2 transcripts were detected in both type I and type II cells. P2Y agonists stimulated Ca(2+)-gated Cl(-) currents in type I cells. Thus, CaCCs, possibly formed by Ano2, serve as effectors downstream of P2Y receptors in type I cells. While the role for TRPM5 in taste transduction is well established, the physiological significance of expression of CaCCs in type II cells remains to be elucidated.

  7. Expression of calcium-activated chloride channels Ano1 and Ano2 in mouse taste cells.

    Science.gov (United States)

    Cherkashin, Alexander P; Kolesnikova, Alisa S; Tarasov, Michail V; Romanov, Roman A; Rogachevskaja, Olga A; Bystrova, Marina F; Kolesnikov, Stanislav S

    2016-02-01

    Specialized Ca(2+)-dependent ion channels ubiquitously couple intracellular Ca(2+) signals to a change in cell polarization. The existing physiological evidence suggests that Ca(2+)-activated Cl(-) channels (CaCCs) are functional in taste cells. Because Ano1 and Ano2 encode channel proteins that form CaCCs in a variety of cells, we analyzed their expression in mouse taste cells. Transcripts for Ano1 and Ano2 were detected in circumvallate (CV) papillae, and their expression in taste cells was confirmed using immunohistochemistry. When dialyzed with CsCl, taste cells of the type III exhibited no ion currents dependent on cytosolic Ca(2+). Large Ca(2+)-gated currents mediated by TRPM5 were elicited in type II cells by Ca(2+) uncaging. When TRPM5 was inhibited by triphenylphosphine oxide (TPPO), ionomycin stimulated a small but resolvable inward current that was eliminated by anion channel blockers, including T16Ainh-A01 (T16), a specific Ano1 antagonist. This suggests that CaCCs, including Ano1-like channels, are functional in type II cells. In type I cells, CaCCs were prominently active, blockable with the CaCC antagonist CaCCinh-A01 but insensitive to T16. By profiling Ano1 and Ano2 expressions in individual taste cells, we revealed Ano1 transcripts in type II cells only, while Ano2 transcripts were detected in both type I and type II cells. P2Y agonists stimulated Ca(2+)-gated Cl(-) currents in type I cells. Thus, CaCCs, possibly formed by Ano2, serve as effectors downstream of P2Y receptors in type I cells. While the role for TRPM5 in taste transduction is well established, the physiological significance of expression of CaCCs in type II cells remains to be elucidated. PMID:26530828

  8. Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons

    OpenAIRE

    Dibattista, Michele; Amjad, Asma; Maurya, Devendra Kumar; Sagheddu, Claudia; Montani, Giorgia; Tirindelli, Roberto; Menini, Anna

    2012-01-01

    The rodent vomeronasal organ plays a crucial role in several social behaviors. Detection of pheromones or other emitted signaling molecules occurs in the dendritic microvilli of vomeronasal sensory neurons, where the binding of molecules to vomeronasal receptors leads to the influx of sodium and calcium ions mainly through the transient receptor potential canonical 2 (TRPC2) channel. To investigate the physiological role played by the increase in intracellular calcium concentration in the api...

  9. The CLC-2 Chloride Channel Modulates ECM Synthesis, Differentiation, and Migration of Human Conjunctival Fibroblasts via the PI3K/Akt Signaling Pathway

    Science.gov (United States)

    Sun, Lixia; Dong, Yaru; Zhao, Jing; Yin, Yuan; Zheng, Yajuan

    2016-01-01

    Recent evidence suggests that chloride channels are critical for cell proliferation, migration, and differentiation. We examined the effects of transforming growth factor (TGF)-β1 on chloride channel expression and associations with human conjunctival fibroblast (HConF) biology. To investigate the potential role of chloride channel (CLC)-2 in migration, transition to myofibroblasts and extracellular matrix (ECM) synthesis of HconF, a small interfering RNA (siRNA) approach was applied. TGF-β1-induced migration and transition of fibroblasts to myofibroblasts characterized by α-smooth muscle actin (α-SMA) expression, supported by increased endogenous expression of CLC-2 protein and mRNA transcripts. ECM (collagen I and fibronectin) synthesis in HConF was enhanced by TGF-β1. CLC-2 siRNA treatment reduced TGF-β1-induced cell migration, transition of fibroblasts to myofibroblasts, and ECM synthesis of HConF. CLC-2 siRNA treatment in the presence of TGF-β1 inhibited phosphorylation of PI3K and Akt in HConF. These findings demonstrate that CLC-2 chloride channels are important for TGF-β1-induced migration, differentiation, and ECM synthesis via PI3K/Akt signaling in HConF. PMID:27294913

  10. Maturation of calcium-dependent GABA, glycine, and glutamate release in the glycinergic MNTB-LSO pathway.

    Directory of Open Access Journals (Sweden)

    Javier Alamilla

    Full Text Available The medial nucleus of the trapezoid body (MNTB is a key nucleus in high-fidelity temporal processing that underlies sound localization in the auditory brainstem. While the glycinergic principal cells of the MNTB project to all primary nuclei of the superior olive, during development the projection from MNTB to the lateral superior olive (LSO is of interest because this immature inhibitory projection is known to undergo tonotopic refinement during an early postnatal period, and because during this period individual MNTB terminals in the LSO transiently release glycine GABA and glutamate. Developmental changes in calcium-dependent release are understood to be required to allow various auditory nuclei to follow high frequency activity; however, little is known about maturation of calcium-dependent release in the MNTB-LSO pathway, which has been presumed to have less stringent requirements for high-fidelity temporal following. In acute brainstem slices of rats age postnatal day 1 to 15 we recorded whole-cell responses in LSO principal neurons to electrical stimulation in the MNTB in order to measure sensitivity to external calcium, the contribution of different voltage-gated calcium channel subtypes to vesicular release, and the maturation of these measures for both GABA/glycine and glutamate transmission. Our results establish that release of glutamate at MNTB-LSO synapses is calcium-dependent. Whereas no significant developmental changes were evident for glutamate release, GABA/glycine release underwent substantial changes over the first two postnatal weeks: soon after birth L-type, N-type, and P/Q-type voltage-gated calcium channels (VGCCs together mediated release, but after hearing onset P/Q-type VGCCs predominated. Blockade of P/Q-type VGCCs reduced the estimated quantal number for GABA/gly and glutamate transmission at P5-8 and the frequency of evoked miniature glycinergic events at P12-15, without apparent effects on spontaneous release of

  11. Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Roberts, Stephen K; McAinsh, Martin; Cantopher, Hanna; Sandison, Sean

    2014-01-01

    Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA) revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

  12. Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Stephen K Roberts

    Full Text Available Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

  13. The H-loop in the Second Nucleotide-binding Domain of the Cystic Fibrosis Transmembrane Conductance Regulator is Required for Efficient Chloride Channel Closing

    OpenAIRE

    Kloch, Monika; Milewski, Michał; Nurowska, Ewa; Dworakowska, Beata; Cutting, Garry R; Dołowy, Krzysztof

    2010-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that functions as a cAMP-activated chloride channel. The recent model of CFTR gating predicts that the ATP binding to both nucleotide-binding domains (NBD1 and NBD2) of CFTR is required for the opening of the channel, while the ATP hydrolysis at NBD2 induces subsequent channel closing. In most ABC proteins, efficient hydrolysis of ATP requires the presence of the invariant histidine res...

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

    Directory of Open Access Journals (Sweden)

    Yan Xu

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

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

    Science.gov (United States)

    Xu, Yan; Furutani, Shogo; Ihara, Makoto; Ling, Yun; Yang, Xinling; Kai, Kenji; Hayashi, Hideo; Matsuda, Kazuhiko

    2015-01-01

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

  16. Donnan effect on chloride ion distribution as a determinant of body fluid composition that allows action potentials to spread via fast sodium channels

    Directory of Open Access Journals (Sweden)

    Kurbel Sven

    2011-05-01

    Full Text Available Abstract Proteins in any solution with a pH value that differs from their isoelectric point exert both an electric Donnan effect (DE and colloid osmotic pressure. While the former alters the distribution of ions, the latter forces water diffusion. In cells with highly Cl--permeable membranes, the resting potential is more dependent on the cytoplasmic pH value, which alters the Donnan effect of cell proteins, than on the current action of Na/K pumps. Any weak (positive or negative electric disturbances of their resting potential are quickly corrected by chloride shifts. In many excitable cells, the spreading of action potentials is mediated through fast, voltage-gated sodium channels. Tissue cells share similar concentrations of cytoplasmic proteins and almost the same exposure to the interstitial fluid (IF chloride concentration. The consequence is that similar intra- and extra-cellular chloride concentrations make these cells share the same Nernst value for Cl-. Further extrapolation indicates that cells with the same chloride Nernst value and high chloride permeability should have similar resting membrane potentials, more negative than -80 mV. Fast sodium channels require potassium levels >20 times higher inside the cell than around it, while the concentration of Cl- ions needs to be >20 times higher outside the cell. When osmotic forces, electroneutrality and other ions are all taken into account, the overall osmolarity needs to be near 280 to 300 mosm/L to reach the required resting potential in excitable cells. High plasma protein concentrations keep the IF chloride concentration stable, which is important in keeping the resting membrane potential similar in all chloride-permeable cells. Probable consequences of this concept for neuron excitability, erythrocyte membrane permeability and several features of circulation design are briefly discussed.

  17. [Activity of Ca(2+)-dependent neutral proteinases in rat organs under cobalt and mercury chloride injection].

    Science.gov (United States)

    Kaliman, P A; Samokhin, A A; Samokhina, L M

    2003-01-01

    The activity of Ca(2+)-dependent neutral proteinases in rats under cobalt and mercury chloride injection was investigated. The calpains activity increase in the lungs, heart, liver and kidneys was revealed after 2 h cobalt chloride action. The mercury chloride gives a reliable increase of calcium-dependent neutral proteinases only in the kidneys. PMID:14574747

  18. Ca(2+)-activated chloride channel activity during Ca(2+) alternans in ventricular myocytes.

    Science.gov (United States)

    Kanaporis, Giedrius; Blatter, Lothar A

    2016-11-01

    Cardiac alternans, defined beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias. We investigated mechanisms of cardiac alternans in single rabbit ventricular myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. A strong correlation between beat-to-beat alternations of AP morphology and CaT alternans was observed. During CaT alternans application of voltage clamp protocols in form of pre-recorded APs revealed a prominent Ca(2+)-dependent membrane current consisting of a large outward component coinciding with AP phases 1 and 2, followed by an inward current during AP repolarization. Approximately 85% of the initial outward current was blocked by Cl(-) channel blocker DIDS or lowering external Cl(-) concentration identifying it as a Ca(2+)-activated Cl(-) current (ICaCC). The data suggest that ICaCC plays a critical role in shaping beat-to-beat alternations in AP morphology during alternans.

  19. Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine

    DEFF Research Database (Denmark)

    Steendahl, Joen; Sørensen, Charlotte Mehlin; Salomonsson, Max;

    2003-01-01

    preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of DIDS (0.6 and 1.25 micromol/min) attenuated the ANG II-induced vasoconstriction to approximately 35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 micromol/min) and 2......The aim of the present study was to investigate the role of Ca2+-activated Cl- channels in the renal vasoconstriction elicited by angiotensin II (ANG II) and norepinephrine (NE). Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry. Ratiometric photometry of fura 2...... fluorescence was used to estimate intracellular free Ca2+ concentration ([Ca2+]i) in isolated preglomerular vessels from rat kidneys. Renal arterial injection of ANG II (2-4 ng) and NE (20-40 ng) produced a transient decrease in RBF. Administration of ANG II (10-7 M) and NE (5 x 10-6 M) to the isolated...

  20. Characterization of a critical role for CFTR chloride channels in cardioprotection against ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Sunny Yang XIANG; Linda L YE; LI-lu Marie DUAN; Li-hui LIU; Zhi-dong GE; John A AUCHAMPACH; Garrett J GROSS; Dayue Darrel DUAN

    2011-01-01

    Aim: To further characterize the functional role of cystic fibrosis transmembrane conductance regulator (CFTR) in early and late (second window) ischemic preconditioning (IPC)- and postcondtioning (POC)-mediated cardioprotection against ischemia/reperfusion (I/R) injury.Methods: CFTR knockout (CFTR-/-) mice and age- and gender-matched wild-type (CFTR+/+) and heterozygous (CFTR+/-) mice were used.In in vivo studies, the animals were subjected to a 30-min coronary occlusion followed by a 40-min reperfusion. In ex vivo (isolate heart) studies, a 45-min global ischemia was applied. To evaluate apoptosis, the level of activated caspase 3 and TdT-mediated dUTP-X nick end labeling (TUNEL) were examined.Results: In the in vivo I/R models, early IPC significantly reduced the myocardial infarct size in wild-type (CFTR+/+) (from 40.4%±5.3% to 10.4%±2.0%, n=8, P<0.001) and heterozygous (CFTR+/-) littermates (from 39.4%±2.4% to 15.4%±5.1%, n=6, P<0.001) but failed to protect CFTR knockout (CFTR-/-) mice from I/R induced myocardial infarction (46.9%±6.2% vs 55.5%±7.8%, n=6, P>0.5). Similar results were observed in the in vivo late IPC experiments. Furthermore, in both in vivo and ex vivo I/R models, POC significantly reduced myocardial infarction in wild-type mice, but not in CFTR knockout mice. In ex vivo I/R models, targeted inactivation of CFTRgene abolished the protective effects of IPC against I/R-induced apoptosis.Conclusion: These results provide compelling evidence for a critical role for CFTR Cl- channels in IPC- and POC-mediated cardioprotection against I/R-induced myocardial injury.

  1. Spermidine-Induced Improvement of Reconsolidation of Memory Involves Calcium-Dependent Protein Kinase in Rats

    Science.gov (United States)

    Girardi, Bruna Amanda; Ribeiro, Daniela Aymone; Signor, Cristiane; Muller, Michele; Gais, Mayara Ana; Mello, Carlos Fernando; Rubin, Maribel Antonello

    2016-01-01

    In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus.…

  2. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace of Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Tanaya Chatterjee

    Full Text Available Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX and Accessory cholera enterotoxin (Ace secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC inhibitors, namely CaCCinh-A01, digallic acid (DGA and tannic acid. Biophysical studies indicate that the unfolding (induced by urea free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders.

  3. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

    Science.gov (United States)

    Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

    2015-01-01

    Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID:26540279

  4. Adenosine regulates a chloride channel via protein kinase C and a G protein in a rabbit cortical collecting duct cell line.

    OpenAIRE

    Schwiebert, E. M.; Karlson, K H; Friedman, P A; Dietl, P.; Spielman, W S; Stanton, B.A.

    1992-01-01

    We examined the regulation by adenosine of a 305-pS chloride (Cl-) channel in the apical membrane of a continuous cell line derived from rabbit cortical collecting duct (RCCT-28A) using the patch clamp technique. Stimulation of A1 adenosine receptors by N6-cyclohexyladenosine (CHA) activated the channel in cell-attached patches. Phorbol 12,13-didecanoate and 1-oleoyl 2-acetylglycerol, activators of protein kinase C (PKC), mimicked the effect of CHA, whereas the PKC inhibitor H7 blocked the ac...

  5. The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker

    OpenAIRE

    Min-Jon Lin; George Hsiao; Ching-Chyuan Su; Wen-Shan Zei; Tzu-Rong Su

    2012-01-01

    The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the prese...

  6. AB095. Increased expression of TMEM16A/Ano1 chloride channel associated with diabetic erectile dysfunction

    Science.gov (United States)

    Ruan, Yajun; Chen, Yingwei; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weimin; Liu, Jihong; Ye, Zhangqun

    2016-01-01

    Objective To investigate the presence, location and functional role of TMEM16A/anotamin-1 (Ano1) calcium-activated chloride channel (CaCC) in the penile of rats with diabetic erectile dysfunction. Methods Eight-week-old male Sprague-Dawley (SD) rats were administrated streptozotocin (diabetic) or citrate buffer (control) randomly. Erectile function was measured by cavernous nerve electrostimulation at 12th week after diabetes was induced. The effect of Ano1 specific inhibitor—T16Ainh-A01 on intracavernous pressure (ICP) was evaluated. Then the penile tissues were harvested for molecular exploration. Real-time PCR and Western Blotting were used to assess the expression of Ano1 in penile tissues. Immunofluorescent labelling of penile tissue allowed localization of Ano1. Cavernous smooth muscle cell (CSMC) was cultured in high glucose medium. The change of Ano1 was measured using Western Blotting. The proliferation of CSMC was evaluated by cell counting kit-8 (CCK-8). Results Erectile function was impaired in diabetic rats. The expression of Ano1 was increased in rats with diabetic erectile dysfunction at mRNA and protein levels. Immunofluorescent labelling revealed the presence of Ano1 mainly in cavernous smooth muscle cells. The inhibition of Ano1 increased the ICP of DED rats. High glucose in vitro enhanced the proliferation of CSMC and the expression level of Ano1. Conclusions Ano1 is expressed in rat penile tissue and is increased with diabetes mellitus. The inhibition of Ano1 increased the ICP of DED rats. The alerted Ano1 may be associated with diabetic erectile dysfunction. It is a potential therapy target for ED in the future.

  7. Relationship of Intracellular Free Ca2+ Concentration and Calcium-activated Chloride Channels of Pulmonary Artery Smooth Muscle Cells in Rats under Hypoxic Conditions

    Institute of Scientific and Technical Information of China (English)

    YANG Zhao; ZHANG Zhenxiang; XU Yongjian; LI Yaqing; YE Tao

    2006-01-01

    To investigate the relationship between intracellular free Ca2+ concentration ([Ca2+]i)and calcium-activated chloride (Clca) channels of pulmonary artery smooth muscle cells (PASMCs) in rats under acute and chronic hypoxic conditions, acute hypoxia-induced contraction was observed in rat pulmonary artery by using routine blood vascular perfusion in vitro. The fluorescence Ca2+indicator Fura-2/AM was used to observe [Ca2+]i of rat PASMCs under normal and chronic hypoxic condition. The effect of Clca channels on PASMCs proliferation was assessed by MTT assay.The Clca channel blockersniflumic acid (NFA) and indaryloxyacetic acid (IAA-94) exerted inhibitory effects on acute hypoxia-evoked contractions in the pulmonary artery. Under chronic hypoxic condition, [Ca2+ ]i was increased. Under normoxic condition, [Ca2+]i was (123.63±18.98) nmol/L, and in hypoxic condition, [Ca2+]i was (281. 75±16.48) nmol/L (P<0.01). Under normoxic condition, [Ca2+]i showed no significant change and no effect on Clca channels was observed (P>0. 05). Chronic hypoxia increased [Ca2+]i which opened Clca channels. The NFA and IAA-94blocked the channels and decreased [Ca2+]i from (281. 75±16.48) nmol/L to (117.66±15.36)nmol/L (P<0.01). MTT assay showed that under chronic hypoxic condition NFA and IAA-94 decreased the value of absorbency (A value) from 0. 459±0. 058 to 0. 224±0. 025 (P<0.01).Hypoxia increased [Ca2+]i which opened Clca channels and had a positive-feedback in [Ca2+]i. Thismay play an important role in hypoxic pulmonary hypertension. Under chronic hypoxic condition,Clca channel may play a part in the regulation of proliferation of PASMCs.

  8. Structures of CaV2 Ca2+/CaM-IQ Domain Complexes Reveal Binding Modes That Underlie Calcium-Dependent Inactivation And Facilitation

    International Nuclear Information System (INIS)

    Calcium influx drives two opposing voltage-activated calcium channel (CaV) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca2+/calmodulin (Ca2+/CaM) lobes produce CDI and CDF through interactions with the CaVα1 subunit IQ domain. Curiously, Ca2+/CaM lobe modulation polarity appears inverted between CaV1s and CaV2s. Here, we present crystal structures of CaV2.1, CaV2.2, and CaV2.3 Ca2+/CaM-IQ domain complexes. All display binding orientations opposite to CaV1.2 with a physical reversal of the CaM lobe positions relative to the IQ α-helix. Titration calorimetry reveals lobe competition for a high-affinity site common to CaV1 and CaV2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal CaV2 Ca2+/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of CaV feedback modulation and indicate that CaV1 and CaV2 IQ domains bear a dedicated CDF site that exchanges Ca2+/CaM lobe occupants

  9. 公丁香提取物抑制CFTR氯离子通道的发现与研究%The extract of clove inhibits CFTR chloride channel

    Institute of Scientific and Technical Information of China (English)

    栾剑; 张耀方; 杨红

    2015-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial chloride chan‐nel .In recent years ,the blockers of CFTR become the new hot spot in the treatment of secretory di‐arrhea .The aim of this research is using high‐throughput screening techniques screened blockers of CFTR chloride channel from traditional Chinese medicine .In this study ,after 40000 fractions of Chi‐nese herbal medicine have been screened ,clove extract was found .In cell‐based fluorescence assays and voltage clamp experiments ,the best active fraction‐E06 significantly blocks CFTR chloride chan‐nel .Therefore ,clove extract screened from traditional Chinese medicine blocks CFTR chloride chan‐nel and provides a theoretical basis for the in‐depth study of anti‐diarrheal drugs .%囊性纤维化跨膜电导调节因子(CFTR)是一种上皮细胞顶膜中表达的氯离子通道,是近年来治疗分泌型腹泻的新热点。利用高通量筛选技术,自中国传统中药中筛选能够抑制CFTR氯离子通道的中药组分。结果显示,自500种中草药的40000种中药组分中筛选到公丁香。经细胞荧光实验和电压膜片钳实验验证公丁香最佳活性孔———E06对CFTR具有明显的抑制作用,IC50=103 mg/L 。本研究结果为深入探讨公丁香的抗泻药物研发提供理论依据。

  10. Rattlesnake Phospholipase A2 Increases CFTR-Chloride Channel Current and Corrects ∆F508CFTR Dysfunction: Impact in Cystic Fibrosis.

    Science.gov (United States)

    Faure, Grazyna; Bakouh, Naziha; Lourdel, Stéphane; Odolczyk, Norbert; Premchandar, Aiswarya; Servel, Nathalie; Hatton, Aurélie; Ostrowski, Maciej K; Xu, Haijin; Saul, Frederick A; Moquereau, Christelle; Bitam, Sara; Pranke, Iwona; Planelles, Gabrielle; Teulon, Jacques; Herrmann, Harald; Roldan, Ariel; Zielenkiewicz, Piotr; Dadlez, Michal; Lukacs, Gergely L; Sermet-Gaudelus, Isabelle; Ollero, Mario; Corringer, Pierre-Jean; Edelman, Aleksander

    2016-07-17

    Deletion of Phe508 in the nucleotide binding domain (∆F508-NBD1) of the cystic fibrosis transmembrane regulator (CFTR; a cyclic AMP-regulated chloride channel) is the most frequent mutation associated with cystic fibrosis. This mutation affects the maturation and gating of CFTR protein. The search for new high-affinity ligands of CFTR acting as dual modulators (correctors/activators) presents a major challenge in the pharmacology of cystic fibrosis. Snake venoms are a rich source of natural multifunctional proteins, potential binders of ion channels. In this study, we identified the CB subunit of crotoxin from Crotalus durissus terrificus as a new ligand and allosteric modulator of CFTR. We showed that CB interacts with NBD1 of both wild type and ∆F508CFTR and increases their chloride channel currents. The potentiating effect of CB on CFTR activity was demonstrated using electrophysiological techniques in Xenopus laevis oocytes, in CFTR-HeLa cells, and ex vivo in mouse colon tissue. The correcting effect of CB was shown by functional rescue of CFTR activity after 24-h ΔF508CFTR treatments with CB. Moreover, the presence of fully glycosylated CFTR was observed. Molecular docking allowed us to propose a model of the complex involving of the ABCβ and F1-like ATP-binding subdomains of ΔF508-NBD1. Hydrogen-deuterium exchange analysis confirmed stabilization in these regions, also showing allosteric stabilization in two other distal regions. Surface plasmon resonance competition studies showed that CB disrupts the ∆F508CFTR-cytokeratin 8 complex, allowing for the escape of ∆F508CFTR from degradation. Therefore CB, as a dual modulator of ΔF508CFTR, constitutes a template for the development of new anti-CF agents. PMID:27241308

  11. A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Takashi Nakano

    2010-02-01

    Full Text Available Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD, the combination with dopamine switches LTD to long-term potentiation (LTP, which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32, as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA, protein phosphatase 2A (PP2A, and the phosphorylation site at threonine 75 of DARPP-32 (Thr75 served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B-CK1 (casein kinase 1-Cdk5 (cyclin-dependent kinase 5-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP. The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The

  12. Ca2+-induced activation and irreversible inactivation of chloride channels in the perfused plasmalemma of Nitellopsis obtusa.

    Science.gov (United States)

    Kataev, A A; Zherelova, O M; Berestovsky, G N

    1984-12-01

    Experiments were carried out on the algal cells with removed tonoplast using both continuous intracellular perfusion and voltage clamp on plasmalemma. The transient plasmalemma current induced by depolarization disappeared upon perfusion with the Ca2+-chelating agent, EGTA, since the voltage-dependent calcium channels lost their ability to activate. Subsequent replacement of the perfusion medium containing EGTA by another with Ca2+ for clamped plasmalemma (-100 mV) induced an inward C1- current which showed both activation and inactivation. The maximal amplitude of the current at [C1-]in = 15 mmol/l (which is similar to that in native cells) was approximately twice that in electrically excited cell in vivo. The inactivation of C1 channels in the presence of internal Ca2+ was irreversible and had a time constant of 1-3 min. This supports our earlier suggestion (Lunevsky et al. 1983) that the inactivation of C1 channels in an intact cell (with a time constant of 1-3 s) is due to a decrease in Ca2+ concentration rather than to the activity of their own inactivation mechanism. The C1 channel selectivity sequence was following: C1- much greater than CH3SO-4 approximately equal to K+ much greater than SO2-4 (PK/PSO4 approximately 10). Activation of one half the channels occurs at a Ca2+ concentration of 2 X 10(-5) mol/l. Sr2+ also (though to a lesser extent) activated C1 channels but had to be present in a much more higher concentration than Ca2+. Mg2+ and Ba2+ appeared ineffective. Ca2+ activation did not, apparently, require participation of water-soluble intermediator including ATP. Thus, C1 channel functioning is controlled by Ca2+-, Sr2+-sensitive elements of the subplasmalemma cytoskeleton. PMID:6099298

  13. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

    Energy Technology Data Exchange (ETDEWEB)

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

    2010-09-21

    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

  14. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

    Full Text Available Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1 is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for

  15. Two highly homologous members of the ClC chloride channel family in both rat and human kidney.

    OpenAIRE

    Kieferle, S; Fong, P; Bens, M.; Vandewalle, A; Jentsch, T J

    1994-01-01

    We have cloned two closely related putative Cl- channels from both rat kidney (designated rClC-K1 and rClC-K2) and human kidney (hClC-Ka and hClC-Kb) by sequence homology to the ClC family of voltage-gated Cl- channels. While rClC-K1 is nearly identical to ClC-K1, a channel recently isolated by a similar strategy, rClC-K2 is 80% identical to rClC-K1 and is encoded by a different gene. hClC-Ka and hClC-Kb show approximately 90% identity, while being approximately 80% identical to the rat prote...

  16. Altered expression of renal bumetanide-sensitive sodium-pota-ssium-2 chloride cotransporter and Cl- channel -K2 gene in angiotensin Ⅱ-infused hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    YE Tao; LIU Zhi-quan; SUN Chao-feng; ZHENG Yong; MA Ai-qun; FANG Yuan

    2005-01-01

    Background Little information is available regarding the effect of angiotensin Ⅱ (Ang Ⅱ) on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2), the thiazide-sensitive sodium-chloride cotransporter (NCC), and the Cl- channel (CLC)-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2. Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold (P<0.05).There were no changes in NCC mRNA or protein expression in AngII-treated rats versus control. Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na+ and Cl- reabsorption in response to Ang Ⅱ.

  17. Sodium chloride salinity reduces Cd uptake by edible amaranth (Amaranthus mangostanus L.) via competition for Ca channels.

    Science.gov (United States)

    Mei, XiuQin; Li, SongSong; Li, QuSheng; Yang, YuFeng; Luo, Xuan; He, BaoYan; Li, Hui; Xu, ZhiMin

    2014-07-01

    Soil salinity is known to enhance cadmium (Cd) accumulation in crops. However, the mechanism by which this occurs independent of the surrounding soil remains unclear. In this study, root adsorption and uptake of salt cations and Cd by edible amaranth under NaCl salinity stress were investigated in hydroponic cultures with 0, 40, 80, 120, and 160mM of NaCl and 27nM Cd. The dominant Cd species in the nutrient solution changed from free Cd(2+) to Cd chlorocomplexes as NaCl salinity increased. High salinity significantly reduced K, Ca, and Cd root adsorption and K, Ca, Mg, and Cd uptake. High salinity decreased root adsorption of Cd by 43 and 58 percent and Cd uptake by 32 and 36 percent in salt-tolerant and salt-sensitive cultivars, respectively. Transformation of Cd from free ion to chlorocomplexes is unlikely to have significantly affected Cd uptake by the plant because of the very low Cd concentrations involved. Application of Ca ion channel blocker significantly reduced Na, K, Ca, Mg, and Cd uptake by the roots, while blocking K ion channels significantly reduced Na and K uptake but not Ca, Mg, and Cd uptake. These results suggest that Na was absorbed by the roots through both Ca and K ion channels, while Cd was absorbed by the roots mainly through Ca ion channels and not K ion channels. Salinity caused a greater degree of reduction in Cd adsorption and uptake in the salt-sensitive cultivar than in the salt-tolerant cultivar. Thus, competition between Na and Cd for Ca ion channels can reduce Cd uptake at very low Cd concentrations in the nutrient solution.

  18. Effects of glycoprotein Ⅱb/Ⅲa antagonists and chloride channel blockers on platelet cytoplasmic free calcium

    Institute of Scientific and Technical Information of China (English)

    YIN Song-mei; XIE Shuang-feng; NIE Da-nian; LI Yi-qing; LI Hai-ming; MA Li-ping; WANG Xiu-ju; WU Yu-dan; FENG Jian-hong

    2005-01-01

    @@ Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱb/Ⅲa (GP Ⅱb/Ⅲa) is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GPⅡb/Ⅲa is the process of thrombosis. Ca2+ is an important intracellular second messenger in platelet activation. It has been reported that GPⅡb/Ⅲa receptors were involved in the calcium influx of activated platelet, and GPⅡb/Ⅲa receptor had characteristics of calcium channel or an adjacent calcium channel.

  19. Expression and Function of CLC and Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels in Renal Epithelial Tubule Cells: Pathophysiological Implications

    OpenAIRE

    Alain Vandewalle

    2007-01-01

    Cl- channels play important roles in the regulation of a variety of functions, includingelectrical excitability, cell volume regulation, transepithelial transport and acidification ofcellular organelles. They are expressed in plasma membranes or reside in intracellularorganelles. A large number of Cl- channels with different functions have been identified.Some of them are highly expressed in the kidney. They include members of the CLC Clchannelfamily: ClC-K1 (or ClC-Ka), ClC-K2 (or ClC-Kb) an...

  20. Cell swelling activates ATP-dependent voltage-gated chloride channels in M-1 mouse cortical collecting duct cells.

    Science.gov (United States)

    Meyer, K; Korbmacher, C

    1996-09-01

    In the present study we used whole-cell patch clamp recordings to investigate swelling-activated Cl-currents (ICl-swell) in M-1 mouse cortical collecting duct (CCD) cells. Hypotonic cell swelling reversibly increased the whole-cell Cl- conductance by about 30-fold. The I-V relationship was outwardly-rectifying and ICl-swell displayed a characteristic voltage-dependence with relatively fast inactivation upon large depolarizing and slow activation upon hyperpolarizing voltage steps. Reversal potential measurements revealed a selectivity sequence SCN- > I- > Br- > Cl- > > gluconate. ICl-swell was inhibited by tamoxifen, NPPB (5-nitro-2(3-phenylpropylamino)-benzoate), DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid), flufenamic acid, niflumic acid, and glibenclamide, in descending order of potency. Extracellular cAMP had no significant effect. ICl-swell was Ca2+ independent, but current activation depended on the presence of a high-energy gamma-phosphate group from intracellular ATP or ATP gamma S. Moreover, it depended on the presence of intracellular Mg2+ and was inhibited by staurosporine, which indicates that a phosphorylation step is involved in channel activation. Increasing the cytosolic Ca2+ concentration by using ionomycin stimulated Cl- currents with a voltage dependence different from that of ICl-swell. Analysis of whole-cell current records during early onset of ICl-swell and during final recovery revealed discontinuous step-like changes of the whole-cell current level which were not observed under nonswelling conditions. A single-channel I-V curve constructed using the smallest resolvable current transitions detected at various holding potentials and revealed a slope conductance of 55, 15, and 8 pS at +120, 0, and -120 mV, respectively. The larger current steps observed in these recordings had about 2, 3, or 4 times the size of the putative single-channel current amplitude, suggesting a coordinated gating of several individual channels or channel

  1. Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis)

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, S.E.; Van Bakel, I.; Craig, I.W. [Univ. of Oxford (United Kingdom)] [and others

    1995-10-10

    Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, and eventual renal failure. We have previously used positional cloning to identify the 3{prime} part of a novel kidney-specific gene (initially termed hClC-K2, but now referred to as CLCN5), which is deleted in patients from one pedigree segregating Dent disease. Mutations that disrupt this gene have been identified in other patients with this disorder. Here we describe the isolation and characterization of the complete open reading frame of the human CLCN5 gene, which is predicted to encode a protein of 746 amino acids, with significant homology to all known members of the ClC family of voltage-gated chloride channels. CLCN5 belongs to a distinct branch of this family, which also includes the recently identified genes CLCN3 and CLCN4. We have shown that the coding region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and have determined the sequence of each exon-intron boundary. The elucidation of the coding sequence and exon-intron organization of CLCN5 will both expedite the evaluation of structure/function relationships of these ion channels and facilitate the screening of other patients with renal tubular dysfunction for mutations at this locus. 31 refs., 5 figs.

  2. The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker.

    Science.gov (United States)

    Su, Tzu-Rong; Zei, Wen-Shan; Su, Ching-Chyuan; Hsiao, George; Lin, Min-Jon

    2012-01-01

    The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia. PMID:22536291

  3. The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker

    Directory of Open Access Journals (Sweden)

    Tzu-Rong Su

    2012-01-01

    Full Text Available The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker. An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation and reduce the tetanic fade (20 Hz stimulations observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia.

  4. Structures of Ca(V) Ca**2+/CaM-IQ Domain Complexes Reveal Binding Modes That Underlie Calcium-Dependent Inactivation And Facilitation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, E.Y.; Rumpf, C.H.; Fujiwara, Y.; Cooley, E.S.; Petegem, F.Van; Minor, D.L., Jr.

    2009-05-20

    Calcium influx drives two opposing voltage-activated calcium channel (Ca{sub V}) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca{sup 2+}/calmodulin (Ca{sup 2+}/CaM) lobes produce CDI and CDF through interactions with the Ca{sub V}{alpha}{sub 1} subunit IQ domain. Curiously, Ca{sup 2+}/CaM lobe modulation polarity appears inverted between Ca{sub V}1s and Ca{sub V}2s. Here, we present crystal structures of Ca{sub V}2.1, Ca{sub V}2.2, and Ca{sub V}2.3 Ca{sup 2+}/CaM-IQ domain complexes. All display binding orientations opposite to Ca{sub V}1.2 with a physical reversal of the CaM lobe positions relative to the IQ {alpha}-helix. Titration calorimetry reveals lobe competition for a high-affinity site common to Ca{sub V}1 and Ca{sub V}2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal Ca{sub V}2 Ca{sup 2+}/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of Ca{sub V} feedback modulation and indicate that Ca{sub V}1 and Ca{sub V}2 IQ domains bear a dedicated CDF site that exchanges Ca{sup 2+}/CaM lobe occupants.

  5. Extracts from plants used in Mexican traditional medicine activate Ca(2+)-dependent chloride channels in Xenopus laevis oocytes.

    Science.gov (United States)

    Rojas, A; Mendoza, S; Moreno, J; Arellano, R O

    2003-01-01

    The two-electrode voltage-clamp technique was employed to investigate the effects of chloroform-methanol (1:1) extracts derived from five medicinal plants on Xenopus laevis oocytes. When evaluated at concentrations of 1 to 500 microg/ml, the extracts prepared from the aerial parts of Baccharis heterophylla H.B.K (Asteraceae), Chenopodium murale L. (Chenopodiaceae), Desmodium grahami Gray (Leguminosae) and Solanum rostratum Dun (Solanaceae) produced concentration-dependent oscillatory inward currents in the oocytes, while the extract of Gentiana spathacea did not induce any response. The reversal potential of the currents elicited by the active extracts was -17 +/- 2 mV and was similar to the chloride equilibrium potential in oocytes. These ionic responses were independent of extracellular calcium. However, they were eliminated by overnight incubation with BAPTA-AM (10 microM), suggesting that the currents were dependent on intracellular Ca2+ increase. Thus the plant extracts activate the typical oscillatory Ca(2+)-dependent Cl- currents generated in the Xenopus oocyte membrane more probably via a mechanism that involves release of Ca2+ from intracellular reservoirs. These observations suggest that Xenopus oocyte electrophysiological recording constitutes a suitable assay for the study of the mechanisms of action of herbal medicines.

  6. Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels

    DEFF Research Database (Denmark)

    Poulsen, Kristian Arild; Andersen, E C; Hansen, C F;

    2010-01-01

    Changes in cell volume and ion gradients across the plasma membrane play a pivotal role in the initiation of apoptosis. Here we explore the kinetics of apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT......3728 inhibited AVD and completely abolished the differences in AVD, ionic movements, and caspase 3 activation between WT and MDR EATC. Finally, the maximal capacity of volume-regulated anion channel was found to be strongly repressed in MDR EATC. Together, these data suggest that impairment of AVD...

  7. A forward genetic screen reveals that calcium-dependent protein kinase 3 regulates egress in Toxoplasma.

    Directory of Open Access Journals (Sweden)

    Erin Garrison

    Full Text Available Egress from the host cell is a crucial and highly regulated step in the biology of the obligate intracellular parasite, Toxoplasma gondii. Active egress depends on calcium fluxes and appears to be a crucial step in escaping the attack from the immune system and, potentially, in enabling the parasites to shuttle into appropriate cells for entry into the brain of the host. Previous genetic screens have yielded mutants defective in both ionophore-induced egress and ionophore-induced death. Using whole genome sequencing of one mutant and subsequent analysis of all mutants from these screens, we find that, remarkably, four independent mutants harbor a mis-sense mutation in the same gene, TgCDPK3, encoding a calcium-dependent protein kinase. All four mutations are predicted to alter key regions of TgCDPK3 and this is confirmed by biochemical studies of recombinant forms of each. By complementation we confirm a crucial role for TgCDPK3 in the rapid induction of parasite egress and we establish that TgCDPK3 is critical for formation of latent stages in the brains of mice. Genetic knockout of TgCDPK3 confirms a crucial role for this kinase in parasite egress and a non-essential role for it in the lytic cycle.

  8. Calcium dependent plasticity applied to repetitive transcranial magnetic stimulation with a neural field model.

    Science.gov (United States)

    Wilson, M T; Fung, P K; Robinson, P A; Shemmell, J; Reynolds, J N J

    2016-08-01

    The calcium dependent plasticity (CaDP) approach to the modeling of synaptic weight change is applied using a neural field approach to realistic repetitive transcranial magnetic stimulation (rTMS) protocols. A spatially-symmetric nonlinear neural field model consisting of populations of excitatory and inhibitory neurons is used. The plasticity between excitatory cell populations is then evaluated using a CaDP approach that incorporates metaplasticity. The direction and size of the plasticity (potentiation or depression) depends on both the amplitude of stimulation and duration of the protocol. The breaks in the inhibitory theta-burst stimulation protocol are crucial to ensuring that the stimulation bursts are potentiating in nature. Tuning the parameters of a spike-timing dependent plasticity (STDP) window with a Monte Carlo approach to maximize agreement between STDP predictions and the CaDP results reproduces a realistically-shaped window with two regions of depression in agreement with the existing literature. Developing understanding of how TMS interacts with cells at a network level may be important for future investigation. PMID:27259518

  9. Subcellular targeting of nine calcium-dependent protein kinase isoforms from Arabidopsis

    Science.gov (United States)

    Dammann, Christian; Ichida, Audrey; Hong, Bimei; Romanowsky, Shawn M.; Hrabak, Estelle M.; Harmon, Alice C.; Pickard, Barbara G.; Harper, Jeffrey F.; Evans, M. L. (Principal Investigator)

    2003-01-01

    Calcium-dependent protein kinases (CDPKs) are specific to plants and some protists. Their activation by calcium makes them important switches for the transduction of intracellular calcium signals. Here, we identify the subcellular targeting potentials for nine CDPK isoforms from Arabidopsis, as determined by expression of green fluorescent protein (GFP) fusions in transgenic plants. Subcellular locations were determined by fluorescence microscopy in cells near the root tip. Isoforms AtCPK3-GFP and AtCPK4-GFP showed a nuclear and cytosolic distribution similar to that of free GFP. Membrane fractionation experiments confirmed that these isoforms were primarily soluble. A membrane association was observed for AtCPKs 1, 7, 8, 9, 16, 21, and 28, based on imaging and membrane fractionation experiments. This correlates with the presence of potential N-terminal acylation sites, consistent with acylation as an important factor in membrane association. All but one of the membrane-associated isoforms targeted exclusively to the plasma membrane. The exception was AtCPK1-GFP, which targeted to peroxisomes, as determined by covisualization with a peroxisome marker. Peroxisome targeting of AtCPK1-GFP was disrupted by a deletion of two potential N-terminal acylation sites. The observation of a peroxisome-located CDPK suggests a mechanism for calcium regulation of peroxisomal functions involved in oxidative stress and lipid metabolism.

  10. Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal neurons.

    Science.gov (United States)

    Pivovarova, Natalia B; Stanika, Ruslan I; Watts, Charlotte A; Brantner, Christine A; Smith, Carolyn L; Andrews, S Brian

    2008-03-01

    In central neurons, over-stimulation of NMDA receptors leads to excessive mitochondrial calcium accumulation and damage, which is a critical step in excitotoxic death. This raises the possibility that low susceptibility to calcium overload-induced mitochondrial damage might characterize excitotoxicity-resistant neurons. In this study, we have exploited two complementary models of preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium-dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have further identified adaptations in mitochondrial calcium handling that account for enhanced mitochondrial integrity. In both models, enhanced tolerance was associated with improved preservation of mitochondrial membrane potential and structure. In the first model, which exhibited modest neuroprotection, mitochondria-dependent calcium deregulation was delayed, even though cytosolic and mitochondrial calcium loads were quantitatively unchanged, indicating that enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast, the second model, which exhibited strong neuroprotection, displayed further delayed calcium deregulation and reduced mitochondrial damage because downregulation of NMDA receptor surface expression depressed calcium loading. Reducing calcium entry also modified the chemical composition of the calcium-buffering precipitates that form in calcium-loaded mitochondria. It thus appears that reduced mitochondrial calcium loading is a major factor underlying the robust neuroprotection seen in highly tolerant cells. PMID:18036152

  11. Similar expression patterns of bestrophin-4 and cGMP dependent Ca2+-activated chloride channel activity in the vasculature

    DEFF Research Database (Denmark)

    Bouzinova, Elena V.; Larsen, Per; Matchkov, Vladimir;

    2008-01-01

    (abstract by Matchkov et. al) that siRNA mediated downregulation of bestrophin-4 is associated with the disappearance of a recently demonstrated2 cGMP-dependent Ca2+-activated Cl- current in vascular smooth muscle cells (SMCs). Here we study the distribution of bestrophin-4-and cGMP dependent Cl- channel...... expressed epitope) Western blot detected a ~65 kDa band in cell lysates from rat mesenteric small arteries and aorta, which was not seen in pulmonary arteries and when preincubated with the immunizing peptide. The distribution of bestrophin-4 mRNA and protein has a pattern similar to the cGMP-dependent Cl......- current in SMCs of different origins. Immunohistochemistry identified bestrophin-4 both in endothelial and SMCs of the vascular tree in the brain, heart, kidney and mesentery, but not in the lungs. We suggest that bestrophin-4 is important for the cGMP dependent, Ca2+ activated Cl- conductance in many...

  12. Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization.

    Directory of Open Access Journals (Sweden)

    Ara G Hovanessian

    Full Text Available BACKGROUND: Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in tumorigenesis and angiogenesis. Emerging evidence suggests that the cell-surface expressed nucleolin is a strategic target for an effective and nontoxic cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS: By monitoring the expression of nucleolin mRNA, and by measuring the level of nucleolin protein recovered from the surface and nucleus of cells, here we show that the presence of nucleolin at the cell surface is dependent on the constant induction of nucleolin mRNA. Indeed, inhibitors of RNA transcription or translation block expression of surface nucleolin while no apparent effect is observed on the level of nucleolin in the nucleus. The estimated half-life of surface nucleolin is less than one hour, whereas that of nuclear nucleolin is more than 8 hours. Nucleolin mRNA induction is reduced markedly in normal fibroblasts that reach confluence, while it occurs continuously even in post-confluent epithelial tumor cells consistent with their capacity to proliferate without contact inhibition. Interestingly, cold and heat shock induce nucleolin mRNA concomitantly to enhanced mRNA expression of the heat shock protein 70, thus suggesting that surface nucleolin induction also occurs in response to an environmental insult. At the cell surface, one of the main functions of nucleolin is to shuttle specific extracellular ligands by an active transport mechanism, which we show here to be calcium dependent. CONCLUSION/SIGNIFICANCE: Our results demonstrate that the expression of surface nucleolin is an early metabolic event coupled with tumor cell proliferation and stress response. The fact that surface nucleolin is constantly and abundantly expressed on the surface of tumor cells, makes them a preferential target for the inhibitory action of anticancer agents that target

  13. Calcium-Dependent Protein Kinase CPK21 Functions in Abiotic Stress Response in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Sandra Franz; Britta Ehlert; Anja Liese; Joachim Kurth; Anne-Claire Cazalé; Tina Romeis

    2011-01-01

    Calcium-dependent protein kinases(CDPKs)comprise a family of plant serine/threonine protein kinases in which the calcium sensing domain and the kinase effector domain are combined within one molecule.So far,a biological function in abiotic stress signaling has only been reported for few CDPK isoforms,whereas the underlying biochemical mechanism for these CDPKs is still mainly unknown.Here,we show that CPK21 from Arabidopsis thaliana is biochemically activated in vivo in response to hyperosmotic stress.Loss-of-function seedlings of cpk21 are more tolerant to hyperosmotic stress and mutant plants show increased stress responses with respect to marker gene expression and metabolite accumulation.In transgenic Arabidopsis complementation lines in the cpk21 mutant background,in which either CPK21 wildtype,or a full-length enzyme variant carrying an amino-acid substitution were stably expressed,stress responsitivity was restored by CPK21 but not with the kinase inactive variant.The biochemical characterization of in planta synthesized and purified CPK21 protein revealed that within the calcium-binding domain,N-terminal EF1- and EF2-motifs compared to C-terminal EF3- and EF4-motifs differ in their contribution to calcium-regulated kinase activity,suggesting a crucial role for the N-terminal EF-hand pair.Our data provide evidence for CPK21 contributing in abiotic stress signaling and suggest that the N-terminal EF-hand pair is a calcium-sensing determinant controlling specificity of CPK21 function.

  14. Up-Regulation of Interleukin-9 and the Interleukin-9-Associated Calcium-Activated Chloride Channel hCLCA1 in Nasal Mucosa Following In Vivo Allergen Challenge

    Directory of Open Access Journals (Sweden)

    Hauber Hans-Peter

    2007-03-01

    Full Text Available Interleukin (IL-9 is a pleiotropic T helper 2-type cytokine that has been shown to be up-regulated in allergic airway disease, including asthma. IL-9 has been demonstrated to be a potent stimulus for the production and secretion of mucus from airway epithelial cells via induction of a calcium-activated chloride channel, hCLCA1. The objective of this study was to investigate the expression of IL-9 and hCLCA1 following allergen challenge in the nasal mucosa of allergic rhinitis patients. Nasal biopsies were obtained from allergic rhinitis patients out of allergen season both before (baseline and after local antigen challenge with either ragweed or diluent (control. Immunohistochemistry and in situ hybridization were used to assess IL-9 protein and hCLCA1 messenger ribonucleic acid. Eosinophils and T cells were detected using immunohistochemistry. IL-9 and hCLCA1 were very low at baseline, and expression was significantly up-regulated following ragweed challenge. Whereas the number of eosinophils increased after allergen challenge, T-cell counts did not change significantly. The results of this study demonstrate the relationship between specific allergen challenge and expression of both IL-9 and hCLCA1, suggesting a possible mechanism for the increased production of mucus from airway epithelial cells in allergic rhinitis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-05-01

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

  16. 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

    International Nuclear Information System (INIS)

    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

  17. Calcium-dependent and calcium-sensitizing pathways in the mature and immature ductus arteriosus.

    Science.gov (United States)

    Clyman, Ronald I; Waleh, Nahid; Kajino, Hiroki; Roman, Christine; Mauray, Francoise

    2007-10-01

    Studies performed in sheep and baboons have shown that after birth, the normoxic muscle media of ductus arteriosus (DA) becomes profoundly hypoxic as it constricts and undergoes anatomic remodeling. We used isolated fetal lamb DA (pretreated with inhibitors of prostaglandin and nitric oxide production) to determine why the immature DA fails to remain tightly constricted during the hypoxic phase of remodeling. Under normoxic conditions, mature DA constricts to 70% of its maximal active tension (MAT). Half of its normoxic tension is due to Ca(2+) entry through calcium L-channels and store-operated calcium (SOC) channels. The other half is independent of extracellular Ca(2+) and is unaffected by inhibitors of sarcoplasmic reticulum (SR) Ca(2+) release (ryanodine) or reuptake [cyclopiazonic acid (CPA)]. The mature DA relaxes slightly during hypoxia (to 60% MAT) due to decreases in calcium L-channel-mediated Ca(2+) entry. Inhibitors of Rho kinase and tyrosine kinase inhibit both Ca(2+)-dependent and Ca(2+)-independent DA tension. Although Rho kinase activity may increase during gestation, immature DA develop lower tensions than mature DA, primarily because of differences in the way they process Ca(2+). Calcium L-channel expression increases with advancing gestation. Under normoxic conditions, differences in calcium L-channel-mediated Ca(2+) entry account for differences in tension between immature (60% MAT) and mature (70% MAT) DA. Under hypoxic conditions, differences in both calcium L-channel-dependent and calcium L-channel-independent Ca(2+) entry, account for differences in tension between immature (33% MAT) and mature (60% MAT) DA. Stimulation of Ca(2+) entry through reverse-mode Na(+)/Ca(2+) exchange or CPA-induced SOC channel activity constrict the DA and eliminate differences between immature and mature DA during both hypoxia and normoxia.

  18. Effects of calcium-activated chloride channels on proliferation of pulmonary artery smooth muscle cells in rats under chronic hypoxic condition

    Institute of Scientific and Technical Information of China (English)

    Zhao Yang; Zhenxiang Zhang; Yongjian Xu; Tao Wang; Dan Ma; Tao Ye

    2008-01-01

    Objective: To investigate the effects of calcium-activated chloride (C1Ca) channels on proliferation of pulmonary artery smooth muscle cells(PASMCs) in rats under chronic hypoxic condition. Methods:The cultured PASMCs were placed under normoxic and chronic hypoxic conditions:The cells were observed by light and electron microscope; The cell cycles were observed by flow-cytometry; Immunocytochemistry staining was used to detect the expressions of PCNA, c-los and c-jun of PASMCs; Cytoplasmic free Ca2+ con-centration ([Ca2+]) in PASMCs was investigated by fluorescent quantitation using fluorospectrophotometer. Results:The PASMCs were contractile phenotype under normoxic conditions. Observation by transmission electron microscope: In kytoplasm of contractile phenotype cells, myofilament bundles were abundant and the content of cell organs such as Golgi's bodies were rare. The PASMCs were synthetic phenotype under chronic hypoxic condition. There were inereased free ribosomes, dilated rough endoplasmic reticulums, highly developed Golgi complexes, decreased or disappeared thick filaments and dense body in kytoplasm of synthetic phenotype cells. After NFA and IAA-94, the situations were reversed The number of S4,GzM PASMCs were significantly increased in chronic hypoxic condition; The NFA and IAA-94 were shown to significantly decrease them from (28.6±1.0)% to (16.0±1.6)% and the number of G0G1 PASMCs significantly increased from (71.4 ±1.9)% to (83.9±1.6)% (P< 0.01). In chronic hypoxic conditions, the expression of proliferating cell nucleus antigen was significantly increased; The NFA and IAA-94 were shown to significantly decrease it from (81±6)% to (27±7)%(P<0.01). The expression of c-los and c-jun were significantly increased in-chronic hypoxic conditions; The NFA and IAA-94 were shown to significantly decrease them from 0.15 ± 0.02, 0.32 ± 0.05 to 0.05 ± 0.01, 0.12±0.05, respectively (P< 0.01); Under chronic hypoxic conditions, [Ca2+]. Was increased

  19. Chloride channels in toad skin

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Rasmussen, B E

    1982-01-01

    - ions through this pathway. Experimental analysis of the gating kinetics is rendered difficult owing to a contamination of the gated currents by cellular ion redistribution currents. To obtain insight into the effects of accumulation-depletion currents on voltage clamp currents of epithelial membranes......, a mathematical model of the epithelium has been developed for computer analysis. By assuming that the apical membrane Cl- permeability is governed by a single gating variable (Hodgkin-Huxley kinetics), the model predicts fairly well steady-state current-voltage curves, the time course of current activations from...... a closed state, and the dependence of unidirectional fluxes on potential. Other predictions of the model do not agree with experimental findings, and it is suggested that the gating kinetics are governed by rate coefficients that also depend on the holding potential. Evidence is presented that Cl...

  20. Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery

    DEFF Research Database (Denmark)

    Hangaard, Lise; Jessen, Peter B; Kamaev, Dmitrii;

    2015-01-01

    The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca(2+)-activated K(+) channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on [Ca(2+)]out...

  1. Layer by layer growth of silver chloride nanoparticle within the pore channels of SBA-15/SO3H mesoporous silica (AgClNP/SBA-15/SO3K): Synthesis, characterization and antibacterial properties

    Science.gov (United States)

    Rostamnia, Sadegh; Doustkhah, Esmail; Estakhri, Saba; Karimi, Ziba

    2016-02-01

    The growth of silver chloride nanoparticles within the pore channels of functionalized SBA-15 mesoporous was achieved by sequential dipping steps in alternating bath of potassium chloride and silver nitrate under ultrasound irradiation at pH=9. The effects of sequential dipping steps in growth of the AgCl nanoparticles have been studied. The growth and formation of AgCl nanoparticles inside the sulfonated SBA-15 were characterized by X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Antibacterial activity of the synthesized materials was investigated against Escherichia coli (E.coli) using the conventional diffusion-disc method. The materials showed high antibacterial activity.

  2. Membrane depolarization induces calcium-dependent secretion of tissue plasminogen activator.

    Science.gov (United States)

    Gualandris, A; Jones, T E; Strickland, S; Tsirka, S E

    1996-04-01

    Tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to active plasmin, is produced in the rat and mouse hippocampus and participates in neuronal plasticity. To help define the role of tPA in the nervous system, we have analyzed the regulation of its expression in the neuronal cell line PC12. In control cultures, tPA activity is exclusively cell-associated, and no activity is measurable in the culture medium. When the cells are treated with depolarizing agents, such as KCI, tPA activity becomes detectable in the medium. The increased secreted tPA activity is not accompanied by an increase in tPA mRNA levels, and it is not blocked by protein synthesis inhibitors. In contrast, tPA release is abolished by Ca2+ channel blockers, suggesting that chemically induced membrane depolarization stimulates the secretion of preformed enzyme. Moreover, KCI has a similar effect in vivo when administered to the murine brain via an osmotic pump: tPA activity increases along the CA2-CA3 regions and dentate gyrus of the hippocampal formation. These results demonstrate a neuronal activity-dependent secretory mechanism that can rapidly increase the amount of tPA in neuronal tissue.

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

    Science.gov (United States)

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

    2016-09-01

    ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. PMID:27574292

  4. The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel%川陈皮素对囊性纤维化跨膜传导调节因子的激活作用

    Institute of Scientific and Technical Information of China (English)

    杨爽; 于波; 张耀方; 王雪; 杨红

    2013-01-01

    Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity.CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q.Nobiletin potently activated CFTR chloride channel activity in a dose-and time-dependent manner.The CFTR blocker CFTRinh-172 could completely reverse the effect.Preliminary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way.In addition,ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion.Nobiletin may be a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.%本实验利用荧光淬灭实验和膜片钳技术在稳定表达人CFTR和荧光绿蛋白突变体EYFP/H148Q的Fischer大鼠甲状腺上皮细胞(Fischer rat thyroid,FRT)上,测定川陈皮素(nobiletin)对囊性纤维化跨膜传导因子(cystic fibrosis transmembrane conductance regulator,CFTR)氯离子通道的激活作用.结果发现,川陈皮素以剂量依赖的方式激活CFTR氯离子通道的C1-转运活性,且这种活性是快速、可逆的,并能够被CFTR特异性抑制剂CFTRinh-172完全抑制.初步的分子机制研究表明,川陈皮素是以与CFTR直接作用来激活通道活性的.进一步的研究结果显示,川陈皮素能够有效刺激小鼠气管黏膜下腺液体分泌速度.因此,川陈皮素可能发展成为治疗包括支气管扩张在内的CFTR相关疾病的先导药物.

  5. Genome-wide analysis of the calcium-dependent protein kinase gene family inGossypium raimondii

    Institute of Scientific and Technical Information of China (English)

    LI Li-bei; YU Ding-wei; ZHAO Feng-li; PANG Chao-you; SONG Mei-zhen; WEI Heng-ling; FAN Shu-li; YU Shu-xun

    2015-01-01

    Plant calcium-dependent protein kinases (CDPKs) play important roles in diverse physiological processes by regulating the downstream components of calcium signaling. To date, only a few species of the plant CDPK gene family have been functionaly identiifed. In addition, there has been no systematic analysis of the CDPK family in cotton. Here, 41 putative cotton CDPK (GrCDPK) genes were identiifedvia bioinformatics analysis of the entire genome ofGossypium raimondi and were classiifed into four groups based on evolutionary relatedness. Gene structure analysis indicated that most of these GrCDPK genes share a similar intron-exon structure (7 or 8 exons), strongly supporting their close evolutionary relationships. Chromosomal distributions and phylogenetics analysis showed that 13 pairs of GrCDPK genes arosevia segmental duplication events. Furthermore, using microarray data of upland cotton (G. hirsutumL.), comparative proifles analysis of these GhCDPKs indicated that some of the encoding genes might be involved in the responses to multiple abiotic stresses and play important regulatory roles during cotton ifber development. This study is the ifrst genome-wide analysis of the CDPK family in cotton, and it wil provide valuable information for the further functional characterization of cotton CDPK genes.

  6. Calcium-dependent trichosanthin-induced generation of reactive oxygen species involved in apoptosis of human choriocarcinoma cells

    Science.gov (United States)

    Zhang, Chunyang; Ma, Hui; Chen, Die Yan

    2001-04-01

    The type-I ribosome-inactivating protein trichosanthin (TCS) has a broad spectrum of biological and pharmacological activities, including abortifacient, anti-tumor and anti-HIV. We found for the first time that TCS induced production of reactive oxygen species (ROS) in JAR cells by using fluorescent probe 2',7'-dichlorofluorescin diacetate with confocal laser scanning microscopy. TCS-induced ROS showed dependence on the increase in intracellular calcium and on the presence of extracellular calcium. The production of ROS increased rapidly after the application of TCS, which paralleled TCS-indued increase in intracellular calcium monitored using fluo 3-AM, suggesting that TCS-induced ROS might mediate by the increase in intracellular Ca2PLU concentration. Simultaneous observation of the nuclear morphological changes and production of ROS in JAR cells with two-photon laser scanning microscopy and confocal laser scanning microscopy revealed that ROS involved in the apoptosis of JAR cells, which was confirmed by that antioxidant (alpha) -tocopherol prevented TCS-induced ROS formation and cell death. The finding that calcium-dependent TCS-induced ROS involved in the apoptosis of JAR cells might provide new insight into the anti-tumor and anti-HIV mechanism of TCS.

  7. Genome-wide survey and expression analysis of the calcium-dependent protein kinase gene family in cassava.

    Science.gov (United States)

    Hu, Wei; Hou, Xiaowan; Xia, Zhiqiang; Yan, Yan; Wei, Yunxie; Wang, Lianzhe; Zou, Meiling; Lu, Cheng; Wang, Wenquan; Peng, Ming

    2016-02-01

    Calcium-dependent protein kinases (CPKs) play important roles in regulating plant tolerance to abiotic stress and signal transduction; however, no data are currently available regarding the CPK family in cassava. Herein, we identified 27 CPK genes from cassava based on our previous genome sequencing data. Phylogenetic analysis showed that cassava CPKs could be clustered into three groups, which was further supported by gene structure and conserved protein motif analyses. Global expression analysis suggested that MeCPK genes showed distinct expression patterns in different tissues between wild subspecies and cultivated varieties, indicating their involvement in the functional diversity of different varieties. Transcriptomics, interaction networks, and co-expression assays revealed a broad transcriptional response of cassava CPKs and CPK-mediated networks to drought stress and their differential expression profiles in different varieties, implying their contribution to drought stress tolerance in cassava. Expression analysis of eight MeCPK genes suggested a comprehensive response to osmotic stress, salt, cold, abscisic acid, and H2O2, which indicated that cassava CPKs might be convergence points for different signaling pathways. This study provides a basis for crop improvements and understanding of abiotic stress responses and signal transduction mediated by CPKs in cassava. PMID:26272723

  8. Chloride : The queen of electrolytes?

    NARCIS (Netherlands)

    Berend, Kenrick; van Hulsteijn, Leonard Hendrik; Gans, Rijk O. B.

    2012-01-01

    Background: Channelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms and have been documented extensively over the past decade. In contrast, despite the important role of chloride in serum, textbooks in general d

  9. Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II

    NARCIS (Netherlands)

    P.J. French (Pim); J. Bijman (Jan); M.J. Edixhoven (Marcel); A.B. Vaandrager (Arie); B.J. Scholte (Bob); S.M. Lohmann (Suzanne); A.C. Nairn; H.R. de Jonge (Hugo)

    1995-01-01

    textabstractType II cGMP-dependent protein kinase (cGKII) isolated from pig intestinal brush borders and type I alpha cGK (cGKI) purified from bovine lung were compared for their ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR)-Cl- channel in excis

  10. Characterization and expression analysis of calcium-dependent protein kinase genes in rice(Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    WANG Jiaojiao; GUO Li; XIAO Kai

    2007-01-01

    Under abiotic stress,the calcium-dependent protein kinases (CDPKs) in plant species are activated by the fluctuated Ca2+ levels in cytoplasm and thereby provide a mechanism to decode calcium signals.In this paper,twenty-two rice CDPK genes were identified based on scanning the rice genome released in National Center for Biotechnology Information (NCBI).It was found that there were dramatic differences on the DNA length,cDNA length,open reading frame (ORF) and the translated amino acids among the rice CDPK genes,with the highest diversity on the DNA length.Calculations of the exon/intron numbers and the lengths of exon and intron revealed that all of the rice CDPK genes had the longest exon at the position of exon 1,but the lengths of introns in different genes showed different patterns.The gene structure and phylogenetic analysis indicated that the rice CDPK genes had derived at least from two different ancestors during the evolution.The expression analysis elucidated that the rice CDPK genes showed different patterns under normal growth (CK) and salt stress condition,including constitutively expression (OsCDPK4,OsCDPK18,OsCDPK19 and OsCDPK24),down- or up-regulated in roots by salt stress (OsCDPK10 and OsCDPK16),up-regulated in leaves by salt stress (OsCDPK6,OsCDPK20 and OsCDPK13),and no detected transcripts under CK and salt stress condition.There-fore,the members of rice CDPK gene family should be evolutionally divergent and several members could play an important role in transducing the signal of salt stress.

  11. Enhanced expression of a calcium-dependent protein kinase from the moss Funaria hygrometrica under nutritional starvation

    Indian Academy of Sciences (India)

    Doyel Mitra; Man Mohan Johri

    2000-12-01

    Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an interesting class of kinases which are activated by calcium binding. They have been implicated in a diverse array of responses to hormonal and environmental stimuli. In order to dissect the role of CDPKs in the moss Funaria hygrometrica, a polymerase chain reaction (PCR)-based approach was adopted to clone the gene. Using degenerate PCR primers against conserved regions of CDPKs, a 900 bp amplicon was obtained from the genomic DNA of Funaria. Southern hybridization under low stringency conditions indicated the presence of several CDPK related sequences in the Funaria genome. This observation is consistent with reports of multigene families of CDPKs in other plants. The 900 bp fragment was subsequently used to isolate a 2.2 kb partial genomic clone of the CDPK gene from Funaria. The genomic clone encodes an open reading frame (ORF) of 518 amino acids. Interestingly, unlike other CDPK genes from plants, the entire 1.5 kb ORF is not interrupted by introns. The deduced amino acid sequence of the Funaria gene shows extensive homology with CDPKs from higher plants, 73% identity with the Fragaria CDPK and 71% identity with CDPK isoform 7 of Arabidopsis. Phylogenetic analysis revealed that the Funaria CDPK is closer to the CDPKs from higher plants like strawberry and Arabidopsis as compared to those from lower plants such as the liverwort Marchantia, the green alga Chlamydomonas or another moss Tortula. Northern analysis shows enhanced expression of the CDPK transcript within 24–48 h of starvation for nitrogen, phosphorus or sulphur. So far the only other kinase which is known to be induced by nutrient starvation in plants is the wpk 4 which is a snf-1 related kinase (SnRKs). To our knowledge this is the first report that implicates a CDPK in the starvation response.

  12. The calcium-dependent protease of Loxosceles gaucho venom acts preferentially upon red cell band 3 transmembrane protein

    Directory of Open Access Journals (Sweden)

    Barretto O.C. de O.

    2003-01-01

    Full Text Available Eighty micrograms red blood cell (RBC ghosts from patients who had previously exhibited the cutaneous form of loxoscelism (presenting localized dermonecrosis and the viscerocutaneous form of loxoscelism (presenting dermonecrosis, hemoglobinuria, hematuria, and jaundice and from controls were incubated with 2.5 µg crude Loxosceles gaucho venom in 5 mM phosphate buffer, pH 7.4, at 37ºC. Among all membrane proteins, quantitative proteolysis of the important integral transmembrane protein 3 increased with venom dose and with incubation time from 30 to 120 min, as demonstrated by gel densitometry. Similar quantitative data were obtained for RBC ghosts from patients and from control subjects, a fact that argues against the possibility of genetic factors favoring the hemolytic viscerocutaneous form. These data suggest that the clinical forms may be different types of the same disease, with the viscerocutaneous form being the result of large amounts of intravascularly injected venom and the superficial form being the result of in situ venom action. Since protein 3 is a housekeeping integral membrane protein, whose genetic deficiency leads to hemolytic anemia, it is reasonable to relate it to the hemolysis which occurs in the viscerocutaneous form of loxoscelism. The venom protease responsible for the process was not inhibited after 120-min incubation by 0.2 mM paramethylsulfonyl fluoride or by 0.2 mM N-ethylmaleimide but was inhibited by 25 mM ethylenediaminetetraacetic acid (a calcium-chelating agent in 5 mM phosphate buffer at pH 7.4, which suggests that the enzyme is a calcium-dependent metalloprotease.

  13. The TRPV5/6 calcium channels contain multiple calmodulin binding sites with differential binding properties.

    NARCIS (Netherlands)

    Kovalevskaya, N.V.; Bokhovchuk, F.M.; Vuister, G.W.

    2012-01-01

    The epithelial Ca(2+) channels TRPV5/6 (transient receptor potential vanilloid 5/6) are thoroughly regulated in order to fine-tune the amount of Ca(2+) reabsorption. Calmodulin has been shown to be involved into calcium-dependent inactivation of TRPV5/6 channels by binding directly to the distal C-t

  14. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2012-02-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 +\\/- 8 muM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCalpha and PKA, but had no effect on p42\\/p44 MAPK and PKCdelta. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE ( approximately 65%), an inhibitor of PKCalpha and to a smaller extent by inhibition of p38 MAPK with SB202190 ( approximately 15%). Berberine treatment induced an increase in association between PKCalpha and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCalpha-dependent pathway.

  15. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2011-01-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 ± 8 μM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCα and PKA, but had no effect on p42\\/p44 MAPK and PKCδ. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE (∼65%), an inhibitor of PKCα and to a smaller extent by inhibition of p38 MAPK with SB202190 (∼15%). Berberine treatment induced an increase in association between PKCα and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCα-dependent pathway.

  16. Expressional changes of chloride channel in human temporal foci with intractable epilepsy%氯通道在难治性颞叶癫痫病灶内的表达变化

    Institute of Scientific and Technical Information of China (English)

    冯亚波; 姚红; 满晓; 杜怡峰; 陈春富; 尚伟; 郭华; 迟兆富

    2009-01-01

    目的 研究ClC-2、ClC-3氯通道在难治性癫痫病灶中表达的变化,并探讨这种分布和表达变化的意义.方法 取20例难治性癫痫患者手术切除的病灶及20例脑血管畸形患者手术切除的正常脑组织,分别采用SABC法对ClC-2、ClC_3氯通道免疫组化染色,采用RT-PCR方法检测ClC-2、ClC-3氯通道mRNA.RT-PCR凝胶电泳图像应用1D Image Analysis Software分析.结果 ClC-2、ClC-3氯通道在癫痫灶和正常脑组织中皆有表达,但RT-PCR半定量分析显示:在癫痫灶中ClC-2氯通道表达的相对密度(0.34±0.16)低于正常脑组织(0.81±0.11),差异具有显著性(P<0.05);而ClC-3氯通道在癫痫灶中的表达的相对密度(0.83±0.09)高于正常脑组织(0.53±0.14),差异具有显著性(P<0.05).结论 难治性癫痫病灶中ClC-2通道表达减少,ClC-3通道表达增加,可能是难治性癫痫发作频发且难以控制的原因之一,也可能为癫痫发作的继发性改变.%Objective To investigate the expressional changes of voltage-gated chloride channel CIC-2, CIC-3 in human temporal foci with intractable epilepsy. Methods The specimens were obtained from 20 patients with intractable temporal lobe epilepsy and 20 patients with arteriovenous malformation as control, lmmunohisto-chemistry and RT-PCR was used to detect the expression of CIC-2, CIC-3 chloride channel. The gel eleclrophore-sis images of RT-PCR were analysised by 1D Image Analysis Software. Results Chloride channel CIC-2 and CIC-3 expressed both in epileptic foci and the normal. Serni-quantitive RT-PCR showed that the relative density of CIC-2 mRNA expression in epileptic foci(0. 34 ±0. 16) was lower than that in the normal (0. 81 ±0. 11 ) (P< 0. 05 ) ;the relative density of CIC-3 mRNA in epileptic foci ( 0. 83 ± 0. 09 ) was higher than that in the normal (0.53 ±0. 14)(P<0.05). Conclusion The decrease of CIC-2 and the increase of CIC-3 in epileptic foci may be one of the reasons why the seizures in intractable

  17. 呼吸道上皮细胞钠/氯离子通道与支气管哮喘%Epithelial sodium and chloride channels and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    王雯; 吉宏龙

    2015-01-01

    支气管哮喘(简称哮喘)是一种慢性气道疾病,表现为气道高反应性和气道炎症导致的可逆性气道阻塞.研究显示,呼吸道上皮细胞钠/氯离子通道(ENaC/CFTR)调节黏液纤毛系统从而参与了慢性气道疾病的发病机制.ENaC及CFTR共同调节黏液的水质层,从而影响气道纤毛清除能力.调节上皮通道蛋白的特异性拮抗剂或激活剂将为哮喘和其他慢性气道疾病的预防和治疗开拓新的研究前景.%Bronchial asthma (asthma) is a chronic respiratory disease characterized by reversible airway obstruction with bronchial hyper-responsiveness and inflammation.Airway cilia system is implicated in the pathogenesis of chronic airway diseases.Epithelial sodium channels (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR) are closely related to the mucociliary clearance.ENaC and CFTR jointly adjust the water layer of mucus, which affects the airway cilia clearance ability.Specific antagonists or activating agents of ENaC and CFTR could be novel pharmaceutical interventions for the prevention and treatment of asthma as well as other chronic airway diseases.

  18. Role of chloride channel inhibitors in oxidative stress-induced lens epithelial cell apoptosis%氯通道阻断剂对氧化应激诱导晶状体上皮细胞凋亡影响

    Institute of Scientific and Technical Information of China (English)

    庄晓东; 陈水花; 翁景宁

    2014-01-01

    Objective To observe the effect of chloride channels in cell damage induced by oxidative stress and to probe into its possible mechanisms.Methods 500 μmol/L tert-butyl hydroperoxide (t-BHP) was used to induce HLE B-3 cells apoptosis,the cells treated by only t-BHP were used as t-BHP-induced group,and the cells cultured by regular method were used as control group,chloride channel blockers (NPPB or DIDS) with the concentrations of 5,100 and 200 μmol/L were added into the medium for 12h respectively and with or without 500 μmol/L t-BHP-induced the cells at the same time to induce the apoptosis in experimental groups.MTT method was used to observe the cell viability.Apoptosis was measured via the Annexin V-FITC and PI staining,the intracellular free Ca2+ concentration was determined by Fluo-3 fluorometry.AO/EB double fluorescent staining was observed under the fluorescent microscope,and the cells were collected respectively after different treatments for measuring MDA level and SOD with the corresponding detection kit according to the manufactures instructions.Results Compared with t-BHP-induced group,apoptosis rate and the intracellular free Ca2+ concentration in culture medium decreased after the treatment of NPPB or DIDS (100 and 200μmol/L),cell viability in these group were significantly higher than ones of t-BHP-induced group (P <0.01).Chloride channel blockers relieved cell injury caused by t-BHP,MDA content were lower than those in t-BHP-induced group (P <0.01),and SOD activity and ATP content were higher than that in t-BHP-induced group (P <0.01).Conclusions Blockage of chloride channels by DIDS and NPPB rescued HLE B-3 cells from t-BHP-induced apoptosis,the mechanism might be related to inhibiting the calcium overload and improve the imbalance of redox homeostasis.%目的 观察氯通道阻断剂5-硝基-2 (3-苯丙胺)苯甲酸(NPPB)和二异硫氰基芪-2,2’-二磺酸(DIDS)对氧化应激诱导的晶状体上皮细胞(HLE-B3)凋亡的影响,初

  19. The calcium-dependent protein kinase 3 of toxoplasma influences basal calcium levels and functions beyond egress as revealed by quantitative phosphoproteome analysis.

    Directory of Open Access Journals (Sweden)

    Moritz Treeck

    2014-06-01

    Full Text Available Calcium-dependent protein kinases (CDPKs are conserved in plants and apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress from the host cell in the presence of a calcium-ionophore. The targets and the pathways that the kinase controls, however, are not known. To identify pathways regulated by TgCDPK3, we measured relative phosphorylation site usage in wild type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry using stable isotope-labeling with amino acids in cell culture (SILAC. This revealed known and novel phosphorylation events on proteins predicted to play a role in host-cell egress, but also a novel function of TgCDPK3 as an upstream regulator of other calcium-dependent signaling pathways, as we also identified proteins that are differentially phosphorylated prior to egress, including proteins important for ion-homeostasis and metabolism. This observation is supported by the observation that basal calcium levels are increased in parasites where TgCDPK3 has been inactivated. Most of the differential phosphorylation observed in CDPK3 mutants is rescued by complementation of the mutants with a wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed hyperphosphorylation of two targets of a related calcium-dependent kinase (TgCDPK1, as well as TgCDPK1 itself, indicating that this latter kinase appears to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1 partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this conclusion. These results show that TgCDPK3 plays a pivotal role in regulating tachyzoite functions including, but not limited to, egress.

  20. Evaluation of the basic functions of six calcium-dependent protein kinases in Toxoplasma gondii using CRISPR-Cas9 system.

    Science.gov (United States)

    Wang, Jin-Lei; Huang, Si-Yang; Li, Ting-Ting; Chen, Kai; Ning, Hong-Rui; Zhu, Xing-Quan

    2016-02-01

    Toxoplasma gondii, an important protozoan parasite, infects almost all warm-blooded animals and humans. Although treatments in T. gondii are limited by the lack of effective drugs, some calcium-dependent kinases were demonstrated as the promising drug targets to chemotherapy against T. gondii due to their essential roles in T. gondii and absence from their hosts. The objectives of the present study were to investigate the functions of six calcium-dependent protein kinases (CDPK4, CDPK4A, CDPK5, CDPK6, CDPK8, and CDPK9) in T. gondii to assess whether they are suitable for designing as drug targets. We used the CRISPR-Cas9 system to disrupt six CDPK genes successfully by insertion of DHFR* at the guide RNA-targeted region in the six endogenous CDPK loci and successfully obtained the six knockout (KO)-CDPK strains. The biological characteristics of the six strains were evaluated by plaque assays, invasion, egress, replication, and virulence assays, respectively. The results indicated that there was no significant difference between the six KO-CDPK strains and wild-type strain in virulence and the lytic cycle including invasion, egress, and replication. The conclusion was the six CDPKs are not essential for T. gondii lytic cycle and also not virulence factors for mice, suggesting that the six CDPKs may participate in other functions in T. gondii. PMID:26499803

  1. Mutation of neuronal channels of sodium and chloride associated with generalized epilepsy with febrile seizures plus (gefs+ Mutaciones de los canales neuronales de sodio y cloro asociadas a epilepsia generalizada con convulsiones febriles plus

    Directory of Open Access Journals (Sweden)

    Gabriel Bedoya Berrío

    2004-02-01

    Full Text Available Generalized Epilepsy with Febrile Seizures Plus (GEFS+ is a frequent entity characterized by generalized seizures with a wide phenotypic variety; the age of onset is 3 months and it persists beyond 6 years. Seizures may or may not be induced by fever. The disease has shown an autosomic dominant trait, incomplete penetrance and association with mutations on the genes that encode voltage-dependent sodium channels and the chloride neuronal channels on the central nervous system. The wide spectrum GEFS+ phenotype has been related with others entities such as Severe Myoclonic Epilepsy of Infancy (SMEI and Intractable Childhood Epilepsy with Frequent Generalized Tonic-Clonic Seizures (ICEGTC; they have mutations in common with GEFS+ according to several recently published articles. This review compiles up to date information about EGCF+ with the aim of giving the reader a knowledge of this entity and of its association with mutations that participate in its pathogenesis. La Epilepsia Generalizada Con Convulsiones Febriles Plus (EGCF+, es una entidad relativamente común. Se caracteriza por convulsiones de tipo generalizado con una gran variabilidad fenotípica; se presenta desde los 3 meses de edad y persiste más allá de los 6 años; las convulsiones pueden ser precipitadas por fiebre pero se presentan también sin ella. La enfermedad se ha asociado a herencia autosómica dominante con penetrancia incompleta, en la que intervienen mutaciones de los genes que codifican los canales iónicos de sodio dependientes del voltaje y de los canales iónicos de cloro en las neuronas del Sistema Nervioso Central (SNC. El amplio fenotipo de la EGCF+ se ha encontrado en asociación con otras entidades como la Epilepsia Mioclónica Severa del Lactante (EMSL y la Epilepsia Generalizada Tónico-Clónica Intratable de la Infancia (EGTCII, las cuales han presentado mutaciones comunes con las de la EGCF+, según informes recientemente publicados. Esta revisi

  2. Cystic fibrosis transmembrane conductance regulator: a chloride channel gated by ATP binding and hydrolysis%囊性纤维化跨膜电导调节体:ATP结合和水解门控Cl-通道

    Institute of Scientific and Technical Information of China (English)

    BOMPADRE; Silvia; G; HWANG; Tzyh-Chang

    2007-01-01

    囊性纤维化跨膜电导调节体(cystic fibrosis transmembrane conductance regulator,CFTR)是一种Cl-通道,属于ATP结合(ATP-binding cassette,ABC)转运体超家族.CFTR功能缺陷是高加索人种中普遍存在的致死性常染色体隐性遗传疾病囊性纤维化(cystic fibrosis,CF)发生的主要原因.这种疾病患者各组织上皮细胞内Cl-转运失调.目前,与CF相关的不同突变超过1 400种.CFTR调节(regulatory,R)域负责调控,核苷酸结合域(nucleotide-binding domains,NBDs)NBD1和NBD2负责ATP结合和水解门控.近期研究发现CFTR的NBDs与其它ABC蛋白一样可以二聚化.二聚化过程中,NBD1和NBD2首-尾相连,一个NBD上的WalkerA和B模块与另一个NBD提供的标签序列(signature sequence)形成ATP结合袋(ATP-binding pockets,ABPs)ABP1和ABP2.ABPs中与ATP结合相关的氨基酸突变实验揭示,ABP1和ABP2在CFTR的ATP依赖门控中发挥不同作用.ABP2由NBD2上的Walk A和B模块与NBD1提供的标签序列形成,它与ATP结合催化通道开放,而ABP1单独与ATP结合不能促进通道开放,只能稳定通道构象.有一些CFTR突变相关疾病的特征就是门控失调,进一步深入研究CFTR的NBD1和NBD2如何通过相互作用而达到通道门控,将为药理学研究提供更多所需的机制信息,有利于为CF治疗的药物设计铺平道路.%The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that belongs to the ATP-binding cassette (ABC) transporter superfamily. Defective function of CFTR is responsible for cystic fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasian populations. The disease is manifested in defective chloride transport across the epithelial cells in various tissues. To date, more than 1400 different mutations have been identified as CF-associated. CFTR is regulated by phosphorylation in its regulatory (R) domain, and gated by ATP binding and hydrolysis at its two nucleotide-binding domains (NBD1

  3. Role of Mitochondria-rich Cells for Passive Chloride Transport, discussion of Ussing's Contribution to Our Understanding of Shunt Pathways in Epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Kristensen, Poul; Nedergaard, Signe Nielsen;

    2001-01-01

    Toad skin, Mitochondria-rich cells, Chloride channels, Epithelial shunt pathways, Leaky epithelia, Recirculation theory of isotonic transport......Toad skin, Mitochondria-rich cells, Chloride channels, Epithelial shunt pathways, Leaky epithelia, Recirculation theory of isotonic transport...

  4. Influence of salinity on the localization of Na+/K +-ATPase, Na+/K+/2Cl- cotransporter (NKCC) and CFTR anion channel in chloride cells of the Hawaiian goby (Stenogobius hawaiiensis)

    Science.gov (United States)

    McCormick, S.D.; Sundell, K.; Bjornsson, Bjorn Thrandur; Brown, C.L.; Hiroi, J.

    2003-01-01

    Na+/K+-ATPase, Na+/K+/2Cl- cotransporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CFTR) are the three major transport proteins thought to be involved in chloride secretion in teleost fish. If this is the case, the levels of these transporters should be high in chloride cells of seawater-acclimated fish. We therefore examined the influence of salinity on immunolocalization of Na +/K+-ATPase, NKCC and CFTR in the gills of the Hawaiian goby (Stenogobius hawaiiensis). Fish were acclimated to freshwater and 20??? and 30??? seawater for 10 days. Na+/K +-ATPase and NKCC were localized specifically to chloride cells and stained throughout most of the cell except for the nucleus and the most apical region, indicating a basolateral/tubular distribution. All Na+/K +-ATPase-positive chloride cells were also positive for NKCC in all salinities. Salinity caused a slight increase in chloride cell number and size and a slight decrease in staining intensity for Na+/K +-ATPase and NKCC, but the basic pattern of localization was not altered. Gill Na+/K+-ATPase activity was also not affected by salinity. CFTR was localized to the apical surface of chloride cells, and only cells staining positive for Na+/K+-ATPase were CFTR-positive. CFTR-positive cells greatly increased in number (5-fold), area stained (53%) and intensity (29%) after seawater acclimation. In freshwater, CFTR immunoreactivity was light and occurred over a broad apical surface on chloride cells, whereas in seawater there was intense immunoreactivity around the apical pit (which was often punctate in appearance) and a light subapical staining. The results indicate that Na+/K +-ATPase, NKCC and CFTR are all present in chloride cells and support current models that all three are responsible for chloride secretion by chloride cells of teleost fish.

  5. Chloride regulates afferent arteriolar contraction in response to depolarization

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  6. 硫化氢激活H9c2心肌细胞容积调节性氯通道%Hydrogen Sulfide Activated Volume-Regulated Chloride Channel in H9c2 Cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    杨春涛; 左婉红; 赵斌; 赵磊; 蔡典其; 陈丽新; 王立伟; 冯鉴强; 廖新学

    2012-01-01

    目的 观察硫化氨(H2S)对H9c2心肌细胞容积调节性氯通道(VRCC)的影响.方法 培养大鼠H9c2 心肌细胞,用H2S供体硫氢化钠(NaHS)处理H9c2心肌细胞.分别应用Western blot和全细胞膜片钳技术分析蛋白的表达和VRCC的开放和关闭.结果 等张灌流液处理的H9c2心肌细胞可记录到微弱的背景氯电流.低张灌流液处理可明显增加H9c2心肌细胞的氯电流(P<0.0l),高张灌流液处理则可减弱这种增强作用(P<0.05).Western blot检测显示H9c2心肌细胞上存在ClC-3氯通道蛋白的表达.用400 μmol/L NaHS处理0~30 min可激活H9c2心肌细胞上的氯通道,高张灌流液处理抑制NaHS处理诱导的氯通道激活.400μmol/L NaHS处理0~30min对H9c2心肌细胞ClC-3氯通道蛋白的表达无明显影响(P>0.05).结论 H9c2心肌细胞存在VRCC和ClC-3氯通道蛋白的表达,H2S处理可激活VRCC而不影响ClC-3氯通道蛋白的表达.%Aim To investigate the effect of hydrogen sulfide (H2S) on volume-regulated chloride channel (VRCC). Methods H9c2 cardiomyoeytes were cultured and treated with sodium hydrosulfide (NaHS, a H2S donor). Expression of C1C-3 protein and VRCC chloride current (/c-VRCc) were measured by Western blot assay and whole cell patch clamp, respectively. Results When H9c2 cardiomyocytes were placed in the isotonic solution, la was slightly activated. Hypotonicity obviously enhanced la(P 0. 05). Conclusions Both VRCC and C1C-3 protein were expressed in H9c2 cardiomyocytes. H2S activated VRCC in a ClC-3-independent manner.

  7. Development of new highly potent imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1.

    Science.gov (United States)

    Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Béatrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline

    2015-11-13

    Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were then identified, which were able to block TgCDPK1 enzymatic activity at low nanomolar concentrations, with a good selectivity profile against a panel of mammalian kinases. The potential of these inhibitors was confirmed in vitro on T. gondii growth, with EC50 values of 100 nM and 70 nM, respectively. These best candidates also displayed low toxicity to mammalian cells and were selected for further in vivo investigations on murine model of acute toxoplasmosis.

  8. A maize calcium-dependent protein kinase gene, ZmCPK4, positively regulated abscisic acid signaling and enhanced drought stress tolerance in transgenic Arabidopsis.

    Science.gov (United States)

    Jiang, Shanshan; Zhang, Dan; Wang, Li; Pan, Jiaowen; Liu, Yang; Kong, Xiangpei; Zhou, Yan; Li, Dequan

    2013-10-01

    Calcium-dependent protein kinases (CDPKs) play essential roles in calcium-mediated signal transductions in plant response to abiotic stress. Several members have been identified to be regulators for plants response to abscisic acid (ABA) signaling. Here, we isolated a subgroup I CDPK gene, ZmCPK4, from maize. Quantitative real time PCR (qRT-PCR) analysis revealed that the ZmCPK4 transcripts were induced by various stresses and signal molecules. Transient and stable expression of the ZmCPK4-GFP fusion proteins revealed ZmCPK4 localized to the membrane. Moreover, overexpression of ZmCPK4 in the transgenic Arabidopsis enhanced ABA sensitivity in seed germination, seedling growth and stomatal movement. The transgenic plants also enhanced drought stress tolerance. Taken together, the results suggest that ZmCPK4 might be involved in ABA-mediated regulation of stomatal closure in response to drought stress. PMID:23911729

  9. Intracellular chloride concentration of the mouse vomeronasal neuron

    OpenAIRE

    Kim, Sangseong; Ma, Limei; Unruh, Jay; McKinney, Sean; Yu, C. Ron

    2015-01-01

    Background The vomeronasal organ (VNO) is specialized in detecting pheromone and heterospecific cues in the environment. Recent studies demonstrate the involvement of multiple ion channels in VNO signal transduction, including the calcium-activated chloride channels (CACCs). Opening of CACCs appears to result in activation of VNO neuron through outflow of Cl− ions. However, the intracellular Cl− concentration remains undetermined. Results We used the chloride ion quenching dye, MQAE, to measu...

  10. Heterologous expression and biochemical characterization of two calcium-dependent protein kinase isoforms CaCPK1 and CaCPK2 from chickpea.

    Science.gov (United States)

    Syam Prakash, S R; Jayabaskaran, Chelliah

    2006-11-01

    In plants, calcium-dependent protein kinases (CPKs) constitute a unique family of enzymes consisting of a protein kinase catalytic domain fused to carboxy-terminal autoregulatory and calmodulin-like domains. We isolated two cDNAs encoding calcium-dependent protein kinase isoforms (CaCPK1 and CaCPK2) from chickpea. Both isoforms were expressed as fusion proteins in Escherichia coli. Biochemical analyses have identified CaCPK1 and CaCPK2 as Ca(2+)-dependent protein kinases since both enzymes phosphorylated themselves and histone III-S as substrate only in the presence of Ca(2+). The kinase activity of the recombinant enzymes was calmodulin independent and sensitive to CaM antagonists W7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide] and calmidazoilum. Phosphoamino acid analysis revealed that the isoforms transferred the gamma-phosphate of ATP only to serine residues of histone III-S and their autophosphorylation occurred on serine and threonine residues. These two isoforms showed considerable variations with respect to their biochemical and kinetic properties including Ca(2+) sensitivities. The recombinant CaCPK1 has a pH and temperature optimum of pH 6.8-8.6 and 35-42 degrees C, respectively, whereas CaCPK2 has a pH and temperature optimum of pH 7.2-9 and 35-42 degrees C, respectively. Taken together, our results suggest that CaCPK1 and CaCPK2 are functional serine/threonine kinases and may play different roles in Ca(2+)-mediated signaling in chickpea plants.

  11. A toxic extract of the marine phytoflagellate Prymnesium parvum induces calcium-dependent release of glutamate from rat brain synaptosomes.

    Science.gov (United States)

    Mariussen, Espen; Nelson, George Nicholas; Fonnum, Frode

    2005-01-01

    Blooms of the marine phytoflagellate Prymnesium parvum produced mass mortality of fish in Norway and many other parts of the world. The effects of a purified algae extract of P. parvum on transmitter release from rat brain synaptosomes were studied to characterize its toxic action. Synaptosomes are detached nerve terminals and represent a simple system that has retained the machinery for uptake, synthesis, storage, and release of neurotransmitters. A crude methanol extract of P. parvum was purified by reverse-phase column for fast protein liquid chromatography (FPLC). The purified extract stimulated Ca2+-dependent spontaneous release of glutamate in a concentration-dependent manner. The release was increased by addition of extracellular Ca2+. The release of glutamate was suppressed by the Ca2+-channel blockers flunarizine (10 microM), diltiazem (10 microM), and verapamil (10 microM). The stimulation of release of glutamate from rat brain synaptosomes induced by the toxin may be due to an ionophorelike property of the algae extract such as previously reported for the potent algal toxin maitotoxin. At high concentrations the toxin primarily acts as a powerful lytic agent. PMID:15739805

  12. Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus.

    Science.gov (United States)

    Cui, Rui; Wang, Yizhuo; Wang, Liu; Li, Guiming; Lan, Ke; Altmeyer, Ralf; Zou, Gang

    2016-08-01

    Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants and young children worldwide, yet no vaccine or effective antiviral treatment is available. To search for new anti-RSV agents, we developed a cell-based assay that measures inhibition of RSV-induced cytopathic effect (CPE) and identified cyclopiazonic acid (CPA), an intracellular calcium ATPase inhibitor as a RSV inhibitor (EC50 values 4.13 μM) by screening of natural product library. CPA inhibited the replication of RSV strains belonging to both A and B subgroups and human parainfluenza virus type 3, but not Enterovirus 71. Mechanism of action study by time-of-addition assay and minigenome assay revealed that CPA acts at the step of virus genome replication and/or transcription. Moreover, two other calcium ATPase inhibitors (Thapsigargin and BHQ) and calcium ionophores (A23187 and ionomycin), but not calcium channel blockers (nifedipine, nimodipine, and tetrandrine), also had similar effect. These results indicate that an increase in intracellular calcium concentration is detrimental to RSV replication. Thus, our findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. PMID:27210812

  13. Migration and Phagocytic Ability of Activated Microglia During Post-natal Development is Mediated by Calcium-Dependent Purinergic Signalling.

    Science.gov (United States)

    Sunkaria, Aditya; Bhardwaj, Supriya; Halder, Avishek; Yadav, Aarti; Sandhir, Rajat

    2016-03-01

    Microglia play an important role in synaptic pruning and controlled phagocytosis of neuronal cells during developmental stages. However, the mechanisms that regulate these functions are not completely understood. The present study was designed to investigate the role of purinergic signalling in microglial migration and phagocytic activity during post-natal brain development. One-day-old BALB/c mice received lipopolysaccharide (LPS) and/or a purinergic analogue (2-methylthioladenosine-5'-diphosphate; 2MeSADP), intracerebroventrically (i.c.v.). Combined administration of LPS and 2MeSADP resulted in activation of microglia as evident from increased expression of ionised calcium-binding adapter molecule 1 (Iba1). Activated microglia showed increased expression of purinergic receptors (P2Y2, P2Y6 and P2Y12). LPS either alone or in combination with 2MeSADP induced the expression of Na(+)/Ca(2+) exchanger (NCX-1) and P/Q-type Ca(2+) channels along with MARCKS-related protein (MRP), which is an integral component of cell migration machinery. In addition, LPS and 2MeSADP administration induced the expression of microglial CD11b and DAP12 (DNAX-activation protein 12), which are known to be involved in phagocytosis of neurons during development. Interestingly, administration of thapsigargin (TG), a specific Ca(2+)-ATPase inhibitor of endoplasmic reticulum, prevented the LPS/2MeSADP-induced microglial activation and migration by down-regulating the expression of Iba1 and MRP, respectively. Moreover, TG also reduced the LPS/2MeSADP-induced expression of CD11b/DAP12. Taken together, the findings reveal for the first time that Ca(2+)-mediated purinergic receptors regulate the migration and phagocytic ability of microglia during post-natal brain development. PMID:25575683

  14. Chloride equilibrium potential in salamander cones

    Directory of Open Access Journals (Sweden)

    Bryson Eric J

    2004-12-01

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

  15. Research Advances in Calcium-dependent Protein Kinases of Apicomplexa%顶复门原虫钙依赖蛋白激酶的研究进展

    Institute of Scientific and Technical Information of China (English)

    张念章; 陈佳; 王萌; 朱兴全; 黄思扬

    2013-01-01

    钙依赖蛋白激酶(Calcium-dependent protein kinases,CDPKs)是一类大的蛋白激酶家族,属于丝氨酸/苏氨酸类蛋白激酶,广泛存在于各种植物和原生动物中,参与多种生命活动的调控.随着生物信息学、分子生物学及基因工程的迅速发展,对顶复门原虫CDPKs的研究日益增多.研究结果表明,这类蛋白家族成员参与调控寄生虫入侵、外出宿主细胞、配子形成、宿主体内移行等顶复门原虫生活史的多个重要时期,其特殊的分子结构或可成为研究抗寄生虫疫苗或药物的候选靶标.本文以疟原虫、弓形虫和艾美耳球虫CDPKs为重点,综述了顶复门原虫CDPKs的结构、功能及生物学意义,展望了顶复门原虫CDPKs的研究和应用前景,以期为研究顶复门原虫的致病机理及研发抗原虫生物制剂提供参考.%Calcium-dependent protein kinases (CDPKs) are a large gene family, which is one kind of serine-threonine protein kinases. CDPKs have a diverse array of functions in various plants and many protozoa. With the development of bioinformatics, molecular biology and gene engineering, increasing numbers of researches about CDPKs were published recently. Increasing evidence suggests that CDPKs can regulate many crucial steps of parasite's life cycle including host cell invasion and egress, gamete formation, and gliding motility. The special structure compared with proteins in human and mammal makes CDPKs an ideal target for novel vaccine and anti-parasite therapeutic drugs. This article reviews the structures, functions and applications of Apicomplexa 's CDPKs focusing on Plasmodium, Toxoplasma gondii and Eimeria, and prospects the research and application tendency, in order to provide references for the research of the pathogene-sis and biological agents against Apicomplexan parasites.

  16. Chloride ingress prediction

    DEFF Research Database (Denmark)

    Frederiksen, Jens Mejer; Geiker, Mette Rica

    2008-01-01

    Prediction of chloride ingress into concrete is an important part of durability design of reinforced concrete structures exposed to chloride containing environment. This paper presents experimentally based design parameters for Portland cement concretes with and without silica fume and fly ash in...

  17. Calcium-dependence of Donnan potentials in glycerinated rabbit psoas muscle in rigor, at and beyond filament overlap; a role for titin in the contractile process

    DEFF Research Database (Denmark)

    Coomber, S J; Bartels, E M; Elliott, G F

    2011-01-01

    contracts and breaks the microelectrode. Therefore the rigor state was studied. There is no reason to suppose a priori that a similar voltage switch does not occur during contraction, however. Calcium dependence is still apparent in muscles stretched beyond overlap (sarcomere length>3.8 μm) and is also seen...... mediated by the titin kinase in the M-line region and may involve the extensible PEVK region of titin. There is great interest in the electric charge on proteins in muscle within the structural system. We suggest how changes in these charges may control the calcium activation process. We also suggest some......In glycerinated rabbit psoas muscle, Donnan potential measurements demonstrated that the net electric charge on the actin-myosin matrix undergoes a sharp switch-like transition at pCa(50) = 6.8. The potentials are 2 mV less negative at the lower pCa(2+) (P <0.001). If ATP is present, the muscle...

  18. Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture.

    Science.gov (United States)

    Kuhlenschmidt, Theresa B; Rutaganira, Florentine U; Long, Shaojun; Tang, Keliang; Shokat, Kevan M; Kuhlenschmidt, Mark S; Sibley, L David

    2016-01-01

    Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium parvum might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit C. parvum CDPK1 and block C. parvum growth in tissue culture in vitro. Although these compounds potently inhibited kinase activity in vitro, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in Toxoplasma gondii, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for C. parvum host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in C. parvum that are worthy of further exploration. PMID:26552986

  19. Calcium-dependent and calcium-independent signals in the conglutinin-binding assay (KgBa) for immune complexes. Influence of anti-collagen-antibodies

    DEFF Research Database (Denmark)

    Holmskov, U; Haas, Henning de; Teisner, B;

    1992-01-01

    A solid phase ELISA conglutinin-binding assay (KgBa) was evaluated for the detection of circulating immune complexes. ELISA wells were coated with purified bovine conglutinin and incubated with test sera. Bound IgG was detected with enzyme labelled anti-immunoglobulin. Heat aggregated IgG which had...... been "solubilized" (i.e., complement treated by incubation with serum) was employed as a reference. The binding of the complement-reacted IgG to solid phase conglutinin was found to be calcium-dependent and inhibitable with N-acetyl-D-glucosamine (GlcNAc). Prolonged incubation (4 days) of aggregated Ig......G with serum at 37 degrees C abolished the binding to conglutinin, a finding consistent with the complete degradation of deposited C3b to C3c and C3d. The solubilized IgG that bound to solid phase conglutinin was found by gel chromatography to be of high molecular weight (greater than 600 kDa). Binding of Ig...

  20. Chloride ingress prediction

    DEFF Research Database (Denmark)

    Frederiksen, Jens Mejer; Geiker, Mette Rica

    2008-01-01

    makes physical sense for the design engineer, i.e. the achieved chloride diffusion coefficients at 1 year and 100 years, D1 and D100 respectively, and the corresponding achieved chloride concentrations at the exposed concrete surface, C1 and C100. Data from field exposure supports the assumption of time...... dependent surface chloride concentrations and the diffusion coefficients. Model parameters for Portland cement concretes with and without silica fume and fly ash in marine atmospheric and submerged South Scandinavian environment are suggested in a companion paper based on 10 years field exposure data....

  1. Genome-wide Identification and Expression Analysis of Calcium-dependent Protein Kinase and Its Closely Related Kinase Genes in Capsicum annuum

    Directory of Open Access Journals (Sweden)

    hanyang ecai

    2015-09-01

    Full Text Available As Ca2+ sensors and effectors, calcium-dependent protein kinases (CDPKs play important roles in regulating the downstream components of calcium signaling, which are ubiquitously involved in plant growth, development, and response to environmental cues. However, no CDPKs have been characterized in Capsicum annuum thus far. Herein, a comprehensive analysis of genes encoding pepper CDPKs and CDPK-related protein kinases (CRKs was performed, and 31 CDPK genes and five closely related kinase genes were identified, which were phylogenetically divided into four distinct subfamilies and unevenly distributed across nine chromosomes. Conserved sequence and exon-intron structures were found to be shared by pepper CDPKs within the same subfamily, and the expansion of the CaCPK family in pepper was found to be due to segmental duplication events. Five CDPKs in the Capsicum annuum variety CM334 were found to be mutated in the Chiltepin variety, and one CDPK present in CM334 was lost in Chiltepin. The majority of CDPK and CRK genes were expressed in different pepper tissues and developmental stages, and 10, 12, and eight CDPK genes were transcriptionally modified by salt, heat, and Ralstonia solanacearum stresses, respectively. Furthermore, these genes were found to respond specifically to one stress as well as respond synergistically to two stresses or three stresses, suggesting that these CDPK genes might be involved in the specific or synergistic response of pepper to salt, heat, and R. solanacearum. Our results lay the foundation for future functional characterization of pepper CDPK and its closely related gene families.

  2. Calcium-dependent protein kinase (CDPK) and CDPK-related kinase (CRK) gene families in tomato: genome-wide identification and functional analyses in disease resistance.

    Science.gov (United States)

    Wang, Ji-Peng; Xu, You-Ping; Munyampundu, Jean-Pierre; Liu, Tian-Yu; Cai, Xin-Zhong

    2016-04-01

    Calcium-dependent protein kinases (CDPKs) and CDPK-related kinases (CRKs) play multiple roles in plant. Nevertheless, genome-wide identification of these two families is limited to several plant species, and role of CRKs in disease resistance remains unclear. In this study, we identified the CDPK and CRK gene families in genome of the economically important crop tomato (Solanum lycopersicum L.) and analyzed their function in resistance to various pathogens. Twenty-nine CDPK and six CRK genes were identified in tomato genome. Both SlCDPK and SlCRK proteins harbored an STKc_CAMK type protein kinase domain, while only SlCDPKs contained EF-hand type Ca(2+) binding domain(s). Phylogenetic analysis revealed that plant CRK family diverged early from CDPKs, and shared a common ancestor gene with subgroup IV CDPKs. Subgroup IV SlCDPK proteins were basic and their genes contained 11 introns, which were distinguished from other subgroups but similar to CRKs. Subgroup I SlCDPKs generally did not carry an N-terminal myristoylation motif while those of the remaining subgroups and SlCRKs universally did. SlCDPK and SlCRK genes were differently responsive to pathogenic stimuli. Furthermore, silencing analyses demonstrated that SlCDPK18 and SlCDPK10 positively regulated nonhost resistance to Xanthomonas oryzae pv. oryzae and host resistance to Pseudomonas syringae pv. tomato (Pst) DC3000, respectively, while SlCRK6 positively regulated resistance to both Pst DC3000 and Sclerotinia sclerotiorum in tomato. In conclusion, CRKs apparently evolved from CDPK lineage, SlCDPK and SlCRK genes regulate a wide range of resistance and SlCRK6 is the first CRK gene proved to function in plant disease resistance. PMID:26520101

  3. Calcium-dependent isolation of the 36-kilodalton substrate of pp60/sup src/-kinase. Fractionation of the phosphorylated and unphosphorylated species

    Energy Technology Data Exchange (ETDEWEB)

    Soric, J.; Gordon, J.A.

    1986-11-05

    In this paper, the authors present a new and simple purification of the 36-kDa protein, a major substrate of both viral and growth factor-receptor associated tyrosine protein kinases, and its complex from normal and Schmidt-Ruppin strain Rous sarcoma virus-transformed chicken embryo fibroblasts that employs a DEAE-Sephacel column and introduces the calcium-dependent adsorption of 36-kDa protein. The use of EGTA step gradients differentially elutes the 36-kDa molecules from the DEAE-Sephacel column. An average total yield of the 36-kDa protein in all fractions approached 80% and represented 0.78% of the (/sup 35/S)methionine-labeled cellular protein. A purity of 95-99% was obtained with a yield of 60% in the central elution fractions from normal or Rous sarcoma virus-transformed chicken embryo fibroblasts. Furthermore, 2 mM EGTA elutes poorly phosphorylated molecules while heavily phosphorylated 36-kDa protein requires 4 or 6 M EGTA; a small residual fraction is released at 8-10 mM EGTA. If the EGTA step gradients were neutralized with Ca/sup 2 +/ ion, elution of the 36-kDa protein is inhibited. Tyrosine phosphorylation of the 36-kDa protein is increased 2-3-fold following a short term incubation of whole cells with micromolar vanadate. The elution pattern (but not intensity) of the 36-kDa protein obtained from lysates of vanadate-treated cells was identical to untreated cell lysates. The additional phosphorylation appears to result from a recruitment of unphosphorylated 36-kDa protein as the position (but not intensity) of the phosphorylated tryptic peptides is unchanged. They conclude that the function of the 36-kDa protein may be calcium ion-dependent and may be influenced by the phosphorylation state of the protein.

  4. TaCPK2-A, a calcium-dependent protein kinase gene that is required for wheat powdery mildew resistance enhances bacterial blight resistance in transgenic rice.

    Science.gov (United States)

    Geng, Shuaifeng; Li, Aili; Tang, Lichuan; Yin, Lingjie; Wu, Liang; Lei, Cailin; Guo, Xiuping; Zhang, Xin; Jiang, Guanghuai; Zhai, Wenxue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin; Mao, Long

    2013-08-01

    Calcium-dependent protein kinases (CPKs) are important Ca2+ signalling components involved in complex immune and stress signalling networks; but the knowledge of CPK gene functions in the hexaploid wheat is limited. Previously, TaCPK2 was shown to be inducible by powdery mildew (Blumeria graminis tritici, Bgt) infection in wheat. Here, its functions in disease resistance are characterized further. This study shows the presence of defence-response and cold-response cis-elements on the promoters of the A subgenome homoeologue (TaCPK2-A) and D subgenome homoeologue (TaCPK2-D), respectively. Their expression patterns were then confirmed by quantitative real-time PCR (qRT-PCR) using genome-specific primers, where TaCPK2-A was induced by Bgt treatment while TaCPK2-D mainly responded to cold treatment. Downregulation of TaCPK2-A by virus-induced gene silencing (VIGS) causes loss of resistance to Bgt in resistant wheat lines, indicating that TaCPK2-A is required for powdery mildew resistance. Furthermore, overexpression of TaCPK2-A in rice enhanced bacterial blight (Xanthomonas oryzae pv. oryzae, Xoo) resistance. qRT-PCR analysis showed that overexpression of TaCPK2-A in rice promoted the expression of OsWRKY45-1, a transcription factor involved in both fungal and bacterial resistance by regulating jasmonic acid and salicylic acid signalling genes. The opposite effect was found in wheat TaCPK2-A VIGS plants, where the homologue of OsWRKY45-1 was significantly repressed. These data suggest that modulation of WRKY45-1 and associated defence-response genes by CPK2 genes may be the common mechanism for multiple disease resistance in grass species, which may have undergone subfunctionalization in promoters before the formation of hexaploid wheat. PMID:23918959

  5. A small synthetic molecule functions as a chloride-bicarbonate dual-transporter and induces chloride secretion in cells.

    Science.gov (United States)

    Liu, Peng-Yun; Li, Shing-To; Shen, Fang-Fang; Ko, Wing-Hung; Yao, Xiao-Qiang; Yang, Dan

    2016-05-31

    A C2 symmetric small molecule composed of l-phenylalanine and isophthalamide was found to function as a Cl(-)/HCO3(-) dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers. PMID:27188496

  6. Calcium channel activity of purified human synexin and structure of the human synexin gene

    International Nuclear Information System (INIS)

    Synexin is a calcium-dependent membrane binding protein that not only fuses membranes but also acts as a voltage-dependent calcium channel. The authors have isolated and sequenced a set of overlapping cDNA clones for human synexin. The derived amino acid sequence of synexin reveals strong homology in the C-terminal domain with a previously identified class of calcium-dependent membrane binding proteins. These include endonexin II, lipocortin I, calpactin I heavy chain (p36), protein II, and calelectrin 67K. The Mr 51,000 synexin molecule can be divided into a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Analysis of the entire structure reveals possible insights into such diverse properties as voltage-sensitive calcium channel activity, ion selectivity, affinity for phospholipids, and membrane fusion

  7. Chloride removal from vitrification offgas

    International Nuclear Information System (INIS)

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

  8. Ion Channels, Natural Nanovalves

    OpenAIRE

    Eisenberg, Bob

    2012-01-01

    Ion channels are proteins with holes down their middle that control the flow of ions and electric current across otherwise impermeable biological membranes. The flow of sodium, potassium, calcium (divalent), and chloride ions have been central issues in biology for more than a century. The flow of current is responsible for the signals of the nervous system that propagate over long distances (meters). The concentration of divalent calcium ions is a 'universal' signal that controls many differ...

  9. [Degradation of succinylcholine chloride].

    Science.gov (United States)

    Németh, G; Török, I; Paál, T

    1993-05-01

    Quantitative thin-layer chormatographic method has been developed for the investigation of the degradation of injection formulations containing succinylcholinium chloride. The method is based on the denistometric determination of the main degradation product, choline at 430 nm after visualization with iodine vapour. The stability of the injection was investigated under various storage conditions and it has been stated that considerable decomposition takes place during as short a period as one week. PMID:8362654

  10. Fungal colonization with Pneumocystis correlates to increasing chloride channel accessory 1 (hCLCA1 suggesting a pathway for up-regulation of airway mucus responses, in infant lungs

    Directory of Open Access Journals (Sweden)

    Francisco J. Pérez

    2014-01-01

    Full Text Available Fungal colonization with Pneumocystis is associated with increased airway mucus in infants during their primary Pneumocystis infection, and to severity of COPD in adults. The pathogenic mechanisms are under investigation. Interestingly, increased levels of hCLCA1 – a member of the calcium-sensitive chloride conductance family of proteins that drives mucus hypersecretion – have been associated with increased mucus production in patients diagnosed with COPD and in immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1 expression was examined in autopsied infant lungs. Respiratory viruses that may potentially increase mucus, were also examined. hCLCA1 expression was measured using actin-normalized Western-blot, and the burden of Pneumocystis organisms was quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died in the community. Respiratory viruses were diagnosed using RT-PCR for RSV, metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus. hCLCA1 levels in virus positive samples were comparable to those in virus-negative samples. An association between Pneumocystis and increased hCLCA1 expression was documented (P=0.028. Additionally, increasing Pneumocystis burden correlated with increasing hCLCA1 protein expression levels (P=0.017. Results strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related airway responses in infant lungs. Further characterization of this immunocompetent host-Pneumocystis-interaction, including assessment of potential clinical significance, is warranted.

  11. Dynamic [Cl{sup -}]{sub i} measurement with chloride sensing quantum dots nanosensor in epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yuchi; Mao Hua; Wong, Lid B, E-mail: ywang@biotechplex.com [BioTechPlex Corporation, 1205 Linda Vista Drive Suite A, San Marcos, CA 92078 (United States); Cytoptics Corporation, 1205 Linda Vista Drive Suite B, San Marcos, CA 92078 (United States)

    2010-02-05

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

  12. Combined single channel and single molecule detection identifies subunit composition of STIM1-activated transient receptor potential canonical (TRPC) channels.

    Science.gov (United States)

    Asanov, Alexander; Sampieri, Alicia; Moreno, Claudia; Pacheco, Jonathan; Salgado, Alfonso; Sherry, Ryan; Vaca, Luis

    2015-01-01

    Depletion of intracellular calcium ion stores initiates a rapid cascade of events culminating with the activation of the so-called Store-Operated Channels (SOC) at the plasma membrane. Calcium influx via SOC is essential in the initiation of calcium-dependent intracellular signaling and for the refilling of internal calcium stores, ensuring the regeneration of the signaling cascade. In spite of the significance of this evolutionary conserved mechanism, the molecular identity of SOC has been the center of a heated controversy spanning over the last 20 years. Initial studies positioned some members of the transient receptor potential canonical (TRPC) channel superfamily of channels (with the more robust evidence pointing to TRPC1) as a putative SOC. Recent evidence indicates that Stromal Interacting Molecule 1 (STIM1) activates some members from the TRPC family of channels. However, the exact subunit composition of TRPC channels remains undetermined to this date. To identify the subunit composition of STIM1-activated TRPC channels, we developed novel method, which combines single channel electrophysiological measurements based on the patch clamp technique with single molecule fluorescence imaging. We termed this method Single ion Channel Single Molecule Detection technique (SC-SMD). Using SC-SMD method, we have obtained direct evidence of the subunit composition of TRPC channels activated by STIM1. Furthermore, our electrophysiological-imaging SC-SMD method provides evidence at the molecular level of the mechanism by which STIM1 and calmodulin antagonize to modulate TRPC channel activity.

  13. Zebrafish calls for reinterpretation for the roles of P/Q calcium channels in neuromuscular transmission

    OpenAIRE

    Hua WEN; Linhoff, Michael W.; Hubbard, Jeffrey M; Nelson, Nathan R.; Stensland, Donald; Dallman, Julia; Mandel, Gail; Brehm, Paul

    2013-01-01

    A long-held tenet of neuromuscular transmission is that calcium-dependent neurotransmitter release is mediated by N-type calcium channels in frog but P/Q-type channels in mammals. The N-type assignment in frog is based principally on pharmacological sensitivity to ω-conotoxin GVIA. Our studies show that zebrafish neuromuscular transmission is also sensitive to ω-conotoxin GVIA. However, positional cloning of a mutant line with compromised neuromuscular function identified a mutation in a P/Q-...

  14. Valyl benzyl ester chloride

    Directory of Open Access Journals (Sweden)

    Grzegorz Dutkiewicz

    2010-02-01

    Full Text Available In the title compound (systematic name: 1-benzyloxy-3-methyl-1-oxobutan-2-aminium chloride, C12H18NO2+·Cl−, the ester group is approximately planar, with a maximum deviation of 0.040 (2 Å from the least-squares plane, and makes a dihedral angle of 28.92 (16° with the phenyl ring. The crystal structure is organized by N—H...Cl hydrogen bonds which join the two components into a chain along the b axis. Pairs of chains arranged antiparallel are interconnected by further N—H...Cl hydrogen bonds, forming eight-membered rings. Similar packing modes have been observed in a number of amino acid ester halides with a short unit-cell parameter of ca 5.5 Å along the direction in which the chains run.

  15. The disturbance of hippocampal calcium-dependent responses in rats with PTSD-like behavior%创伤后应激障碍样行为异常大鼠海马钙依赖性反应紊乱

    Institute of Scientific and Technical Information of China (English)

    王庆松; 王正国; 朱佩芳

    2003-01-01

    Aim To investigating hippocampal calcium and calcium-dependent responses in rats with posttraumtic stress disorder(PTSD)-like behavior and to further understand the neurobiological mechanisms involved in the long-term neuropsychological sequelae in PTSD.Methods 240 male Wistar rats were divided randomly into 3 groups.Group SE (n=96) for rats with PTSD-like behavior by constant pulsating current of 100 μ A with intratrain frequencies of 16 Hz, pulsating duration of 1 ms,train duration of 10 s and interstimulus interval of 7 min for 5 days with 8 times per day.Group CE (n=96) for control of electrode implanted in hippocampus without stimulation, and Group NC (n=48) for normal control.Neurochemistry,flow cytometer,fluorescence labeling technique and Western blotting were adopted to detect activities of Na+-K+-ATPase and Ca2+-ATPase, levels of intracellular calcium and free calmodulin (CaM),and the total CaM expression.Results The Na+-K+-ATPase activity in mitochondria of hippocampal cells in Group SE rats was significantly decreased at 12 h [( 0.56± 0.17) mmol/kg@ s,F=4.438,P< 0.05],and still lower than group NC at 48 h after the last stimulation [( 0.61± 0.17) mmol/kg@ s, P=0.026],while the Ca2+-ATPase activity was also significantly decreased at 48 h [(0.53± 0.14) mmol/kg@ s, F=4.999, P< 0.05] and 72 h post-stimulation [(0.61± 0.17) mmol/kg@ s, P=0.027 vs group NC].The intracellular free calcium levels were markedly increased than control groups from 12 to 48 hours (F=16.355,P< 0.01),and still elevated at 72 hour after the final stimulation [(290 ± 70) nmol/L,P=0.03 vs group NC].Meanwhile,the mean channel fluorescence of intracellular free CaM decreased remarkably synchronously (F=10.655,P< 0.05), while the Western analysis demonstrated the total hippocampal CaM expression was significantly elevated at 48 hour after the last stimulation in group SE rats (F=16.247,P< 0.05).Conclusion The lasting increased levels of intracellular free calcium and expression of

  16. 40 CFR 61.65 - Emission standard for ethylene dichloride, vinyl chloride and polyvinyl chloride plants.

    Science.gov (United States)

    2010-07-01

    ... dichloride, vinyl chloride and polyvinyl chloride plants. 61.65 Section 61.65 Protection of Environment... dichloride, vinyl chloride and polyvinyl chloride plants. An owner or operator of an ethylene dichloride, vinyl chloride, and/or polyvinyl chloride plant shall comply with the requirements of this section....

  17. The role of a conserved acidic residue in calcium-dependent protein folding for a low density lipoprotein (LDL)-A module: implications in structure and function for the LDL receptor superfamily.

    Science.gov (United States)

    Guo, Ying; Yu, Xuemei; Rihani, Kayla; Wang, Qing-Yin; Rong, Lijun

    2004-04-16

    One common feature of the more than 1,000 complement-type repeats (or low density lipoprotein (LDL)-A modules) found in LDL receptor and the other members of the LDL receptor superfamily is a cluster of five highly conserved acidic residues in the C-terminal region, DXXXDXXDXXDE. However, the role of the third conserved aspartate of these LDL-A modules in protein folding and ligand recognition has not been elucidated. In this report, using a model LDL-A module and several experimental approaches, we demonstrate that this acidic residue, like the other four conserved acidic residues, is involved in calcium-dependent protein folding. These results suggest an alternative calcium coordination conformation for the LDL-A modules. The proposed model provides a plausible explanation for the conservation of this acidic residue among the LDL-A modules. Furthermore, the model can explain why mutations of this residue in human LDL receptor cause familial hypercholesterolemia. PMID:14749324

  18. RFI channels

    Science.gov (United States)

    Mceliece, R. J.

    1980-01-01

    A class of channel models is presented which exhibit varying burst error severity much like channels encountered in practice. An information-theoretic analysis of these channel models is made, and conclusions are drawn that may aid in the design of coded communication systems for realistic noisy channels.

  19. Nicotine enhancement of dopamine release by a calcium-dependent increase in the size of the readily releasable pool of synaptic vesicles.

    Science.gov (United States)

    Turner, Timothy J

    2004-12-15

    A major factor underlying compulsive tobacco use is nicotine-induced modulation of dopamine release in the mesolimbic reward pathway (Wise and Rompre, 1989). An established biochemical mechanism for nicotine-enhanced dopamine release is by activating presynaptic nicotinic acetylcholine receptors (nAChRs) (Wonnacott, 1997). Prolonged application of 10(-7) to 10(-5) m nicotine to striatal synaptosomes promoted a sustained efflux of [3H]dopamine. This nicotine effect was mediated by non-alpha7 nAChRs, because it was blocked by 5 mum mecamylamine but was resistant to 100 nm alpha-bungarotoxin (alphaBgTx). Dopamine release was diminished by omitting Na+ or by applying peptide calcium channel blockers, indicating that nAChRs trigger release by depolarizing the nerve terminals. However, because alpha7 receptors rapidly desensitize in the continuous presence of agonists, a repetitive stimulation protocol was used to evaluate the possible significance of desensitization. This protocol produced a transient increase in [3H]dopamine released by depolarization and a significant increase in the response to hypertonic solutions that measure the size of the readily releasable pool (RRP) of synaptic vesicles. The nicotine-induced increase in the size of the readily releasable pool was blocked by alphaBgTx and by the calmodulin antagonist calmidazolium, suggesting that Ca2+ entry through alpha7 nAChRs specifically enhances synaptic vesicle mobilization at dopamine terminals. Thus, nicotine enhances dopamine release by two complementary actions mediated by discrete nAChR subtypes and suggest that the alpha7 nAChR-mediated pathway is tightly and specifically coupled to refilling of the RRP of vesicles in dopamine terminals.

  20. Sodium chloride, potassium chloride, and virulence in Listeria monocytogenes.

    OpenAIRE

    MYERS, E. R.; Dallmier, A W; Martin, S E

    1993-01-01

    Virulence, as determined in a mouse model, and the virulence factor activities of catalase, superoxide dismutase, and listeriolysin O were examined in a parental strain (10403S) and in a nonhemolytic mutant strain (DP-L224) of Listeria monocytogenes. The cells were propagated in media containing various concentrations of sodium chloride or potassium chloride. Strains 10403S and DP-L224 exhibited significant increases in catalase activity and listeriolysin O activity when grown in medium conta...

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

    Science.gov (United States)

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

    2014-08-01

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

  2. The Structure and Function of Calcium-dependent Protein Kinases in Plants%植物中钙依赖蛋白激酶(CDPKs)的结构与功能

    Institute of Scientific and Technical Information of China (English)

    陈硕; 陈珈

    2001-01-01

    In plant cells, Ca2+ as a secondary messenger, can affect cellular metabolism through the activation of Calcium-dependent protein kinases (CDPKs). CDPKs are wildly distributed in plants and algae, and also in some protistas. They are the most deeply studied kinases in plant tissues. The phylogenetic distribution, subcellular localization, structural characteristics, biochemical properties and physiological functions in plant cells are reviewed. The research perspective in this field is also discussed.%在植物细胞中,钙离子作为第二信使,通过钙依赖蛋白激酶(CDPKs)发挥功能是其传递信号的主要途径之一。CDPKs广泛存在于植物体内,是目前植物体内研究最深入的蛋白激酶。在简要阐述CDPKs于植物体内的分布定位的基础上,介绍了CDPKs的结构特点、生化性质及其在植物细胞生理功能中的作用,并就该领域的研究前景作了展望。

  3. Arabidopsis CALCIUM-DEPENDENT PROTEIN KINASE8 and CATALASE3 Function in Abscisic Acid-Mediated Signaling and H2O2 Homeostasis in Stomatal Guard Cells under Drought Stress.

    Science.gov (United States)

    Zou, Jun-Jie; Li, Xi-Dong; Ratnasekera, Disna; Wang, Cun; Liu, Wen-Xin; Song, Lian-Fen; Zhang, Wen-Zheng; Wu, Wei-Hua

    2015-05-01

    Drought is a major threat to plant growth and crop productivity. Calcium-dependent protein kinases (CDPKs, CPKs) are believed to play important roles in plant responses to drought stress. Here, we report that Arabidopsis thaliana CPK8 functions in abscisic acid (ABA)- and Ca(2+)-mediated plant responses to drought stress. The cpk8 mutant was more sensitive to drought stress than wild-type plants, while the transgenic plants overexpressing CPK8 showed enhanced tolerance to drought stress compared with wild-type plants. ABA-, H2O2-, and Ca(2+)-induced stomatal closing were impaired in cpk8 mutants. Arabidopsis CATALASE3 (CAT3) was identified as a CPK8-interacting protein, confirmed by yeast two-hybrid, coimmunoprecipitation, and bimolecular fluorescence complementation assays. CPK8 can phosphorylate CAT3 at Ser-261 and regulate its activity. Both cpk8 and cat3 plants showed lower catalase activity and higher accumulation of H2O2 compared with wild-type plants. The cat3 mutant displayed a similar drought stress-sensitive phenotype as cpk8 mutant. Moreover, ABA and Ca(2+) inhibition of inward K(+) currents were diminished in guard cells of cpk8 and cat3 mutants. Together, these results demonstrated that CPK8 functions in ABA-mediated stomatal regulation in responses to drought stress through regulation of CAT3 activity. PMID:25966761

  4. Stability of succinylcholine chloride injection.

    Science.gov (United States)

    Schmutz, C W; Mühlebach, S F

    1991-03-01

    The stability of succinylcholine chloride injection prepared by a hospital pharmacy was studied under a wide variety of conditions. Batches of succinylcholine chloride injection 10 mg/mL containing sodium chloride, methyl-4-hydroxybenzoate, hydrochloric acid, and water were prepared. Samples were tested for the effect of initial pH (3.0 and 4.2) and sterilization (steam treatment at 100 degrees C for 30 minutes and 121 degrees C for 20 minutes) on stability after three weeks; long-term stability under refrigeration (12, 17, and 23 months of storage at 4 degrees C); and the effect of storage temperature (4-6 degrees C, 20-26 degrees C, 35 degrees C, and 70 degrees C) and light exposure at various intervals up to 12 months. Samples were analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Unlike heating at 121 degrees C, heating at 100 degrees C produced no significant loss of succinylcholine chloride, independent of the initial pH. Succinylcholine chloride was hydrolyzed only minimally over 23 months if the solution was stored at 4-6 degrees C. A 10% loss of drug content occurred if solutions were kept at 20-26 degrees C for five months, at 35 degrees C for one month, or at 70 degrees C for one day. Initial degradation was slowed if the solution was protected from light. The assessments by TLC proved to be more sensitive than the HPLC measurements. Succinylcholine chloride injection sterilized at 100 degrees C for 30 minutes can be stored for up to five months at room temperature if protected from light. The preparation is stable for at least two years under refrigeration. PMID:2028996

  5. Chloride in vesicular trafficking and function.

    Science.gov (United States)

    Stauber, Tobias; Jentsch, Thomas J

    2013-01-01

    Luminal acidification is of pivotal importance for the physiology of the secretory and endocytic pathways and its diverse trafficking events. Acidification by the proton-pumping V-ATPase requires charge compensation by counterion currents that are commonly attributed to chloride. The molecular identification of intracellular chloride transporters and the improvement of methodologies for measuring intraorganellar pH and chloride have facilitated the investigation of the physiology of vesicular chloride transport. New data question the requirement of chloride for pH regulation of various organelles and furthermore ascribe functions to chloride that are beyond merely electrically shunting the proton pump. This review surveys the currently established and proposed intracellular chloride transporters and gives an overview of membrane-trafficking steps that are affected by the perturbation of chloride transport. Finally, potential mechanisms of membrane-trafficking modulation by chloride are discussed and put into the context of organellar ion homeostasis in general. PMID:23092411

  6. Electrochemical Chloride extraction using external electrodes?

    DEFF Research Database (Denmark)

    Ottosen, Lisbeth M.; Pedersen, Anne Juul

    2006-01-01

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

  7. Chloride binding of cement-based materials subjected to external chloride environment - A review

    OpenAIRE

    Yuan, Q.; Shi, C; Schutter, G. de; Audenaert, K.; Deng, D.

    2009-01-01

    This paper reviews the chloride binding of cement-based materials subjected to external chloride environments. Chloride ion exist either in the pore solution, chemically bound to the hydration products, or physically held to the surface of the hydration products. Chloride binding of cement-based material is very complicated and influenced by many factors, such as chloride concentration, cement composition, hydroxyl concentration, cation of chloride salt, temperature, supplementary cementing m...

  8. The Effect of Silver Chloride Formation on the Kinetics of Silver Dissolution in Chloride Solution

    Science.gov (United States)

    Ha, Hung; Payer, Joe

    2011-01-01

    The precipitation and growth of AgCl on silver in physiological NaCl solution were investigated. AgCl was found to form at bottom of scratches on the surface which may be the less effective sites for diffusion or the favorable sites for heterogeneous nucleation. Patches of silver chloride expanded laterally on the substrate until a continuous film formed. The ionic transport path through this newly formed continuous film was via spaces between AgCl patches. As the film grew, the spaces between AgCl patches closed and ion transport was primarily via micro-channels running through AgCl patches. The decrease of AgCl layer conductivity during film growth were attributed to the clogging of micro-channels or decrease in charge carrier concentration inside the micro-channels. Under thin AgCl layer, i.e. on the order of a micrometer, the dissolution of silver substrate was under mixed activation-Ohmic control. Under thick AgCl layer, i.e. on the order of tens of micrometers, the dissolution of silver substrate was mediated by the Ohmic resistance of AgCl layer. PMID:21516171

  9. The Effect of Silver Chloride Formation on the Kinetics of Silver Dissolution in Chloride Solution.

    Science.gov (United States)

    Ha, Hung; Payer, Joe

    2011-02-28

    The precipitation and growth of AgCl on silver in physiological NaCl solution were investigated. AgCl was found to form at bottom of scratches on the surface which may be the less effective sites for diffusion or the favorable sites for heterogeneous nucleation. Patches of silver chloride expanded laterally on the substrate until a continuous film formed. The ionic transport path through this newly formed continuous film was via spaces between AgCl patches. As the film grew, the spaces between AgCl patches closed and ion transport was primarily via micro-channels running through AgCl patches. The decrease of AgCl layer conductivity during film growth were attributed to the clogging of micro-channels or decrease in charge carrier concentration inside the micro-channels. Under thin AgCl layer, i.e. on the order of a micrometer, the dissolution of silver substrate was under mixed activation-Ohmic control. Under thick AgCl layer, i.e. on the order of tens of micrometers, the dissolution of silver substrate was mediated by the Ohmic resistance of AgCl layer.

  10. Cyclodextrin induces calcium-dependent lysosomal exocytosis.

    Directory of Open Access Journals (Sweden)

    Fannie W Chen

    Full Text Available Cyclodextrins (CDs have long been used to manipulate cellular cholesterol levels both in vitro and in vivo, but their direct effects at a cellular level are not well characterized. Recently, CDs have garnered much interest because of their ability to clear stored cholesterol from Niemann Pick Type C (NPC cells and markedly prolong the life of NPC1 disease mice. Here, we investigate the hypothesis that treatment with 2-hydroxypropyl- β-cyclodextrin (HPB-CD stimulates lysosomal exocytosis in a calcium-enhanced manner. We propose that this exocytosis is the mechanism by which HPB-CD ameliorates the endolysosomal cholesterol storage phenotype in NPC cells. These findings have significant implications for the use of HPB-CD in biochemical assays and data interpretation as well as for their use for the treatment for NPC and other disorders.

  11. 1,5-Diaminotetrazolium chloride

    Directory of Open Access Journals (Sweden)

    Ling-Qiao Meng

    2010-04-01

    Full Text Available The title compound, CH5N6+·Cl−, crystallized with two indepedent 1,5-diaminotetrazolium cations and two independent chloride anions in the asymmetric unit. In the crystal, there are a number of N—H...Cl hydrogen-bonding interactions, which generate a three-dimensional network.

  12. Microbial reductive dehalogenation of vinyl chloride

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-11

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

  13. Progress of Carbonation in Chloride Contaminated Concretes

    OpenAIRE

    Wang, Yaocheng; Basheer, P.A.M.; Nanukuttan, S; Bai, Y.

    2016-01-01

    Concretes used in marine environment are generally under the cyclic effect of CO2 and chloride ions (Cl-). To date, the influence of carbonation on ingress of chloride ions in concretes has been widely studied; in comparison, study on the influence of Cl- on the progress of carbonation is limited. During the study, concretes were exposed to independent and combined mechanisms of carbonation and chloride ingress regimes. Profiles of apparent pH and chloride concentration were used to indicate ...

  14. Chloride sublimation of gold-arsenic concentrates

    International Nuclear Information System (INIS)

    Present article is devoted to chloride sublimation of gold-arsenic concentrates. The results of studies of chloride sublimation of gold-arsenic comprising concentrates of Chore deposit of Tajikistan are considered. It is found that by application sodium chloride for gold-arsenic comprising concentrates it is possible to extract gold and silver from flotation concentrates.

  15. 21 CFR 172.180 - Stannous chloride.

    Science.gov (United States)

    2010-04-01

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

  16. Dengue virus M protein C-terminal peptide (DVM-C) forms ion channels.

    Science.gov (United States)

    Premkumar, A; Horan, C R; Gage, P W

    2005-03-01

    A chemically synthesized peptide consisting of the C-terminus of the M protein of the Dengue virus type 1 strain Singapore S275/90 (DVM-C) produced ion channel activity in artificial lipid bilayers. The channels had a variable conductance and were more permeable to sodium and potassium ions than to chloride ions and more permeable to chloride ions than to calcium ions. Hexamethylene amiloride (100 microM) and amantadine (10 microM), blocked channels formed by DVM-C. Ion channels may play an important role in the life cycle of many viruses and drugs that block these channels may prove to be useful antiviral agents.

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

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1994-01-01

    M]. These maneuvers had no effect on renin release, while 1.5 mM calcium caused a stimulation, which was not inhibited by 50 mM sucrose. Isosmotic increases in the chloride concentration to 25, 60, and 132 mM resulted in prompt stimulations of renin release. Similarly, iodide and nitrate stimulated renin release. We...... of chloride channels followed by a drop in the intracellular chloride concentration. The stimulation caused by the high calcium concentration may be a toxic effect or may be due to stimulation of the fusion between granules and cell membrane in a way analogous to other secretory cells.......The intracellular concentrations of calcium and chloride have been suggested to be involved in the control of renin secretion from juxtaglomerular (JG) cells. We have tested these propositions on permeabilized JG cells. Rat glomeruli with attached JG cells were isolated by the magnetic iron...

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

    Directory of Open Access Journals (Sweden)

    Ailín C Rogers

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

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses to norepineph...

  20. Shock compression of polyvinyl chloride

    Science.gov (United States)

    Neogi, Anupam; Mitra, Nilanjan

    2016-04-01

    This study presents shock compression simulation of atactic polyvinyl chloride (PVC) using ab-initio and classical molecular dynamics. The manuscript also identifies the limits of applicability of classical molecular dynamics based shock compression simulation for PVC. The mechanism of bond dissociation under shock loading and its progression is demonstrated in this manuscript using the density functional theory based molecular dynamics simulations. The rate of dissociation of different bonds at different shock velocities is also presented in this manuscript.

  1. 人类胞内氯离子通道蛋白3在原核细胞及真核细胞内的表达%The expression of human intracellular chloride channel protein 3 in eukaryotic and prokaryotic cells

    Institute of Scientific and Technical Information of China (English)

    李春雨; 潘林鑫; 刘晓颖; 范礼斌

    2014-01-01

    目的研究人类胞内氯离子通道蛋白3(CLIC3)在真核细胞中的定位和表达,及其GST融合蛋白在原核细胞中的表达。方法以含人CLIC3的全长cDNA序列的质粒为模板,PCR扩增CLIC3片段,构建真核表达载体pcDNA3.1-CLIC3-FLAG,检测其定位及表达;构建原核表达载体pGEX-5X-3-CLIC3,转化到大肠杆菌 BL21菌株,IPTG诱导融合蛋白GST-CLIC3表达。结果细胞免疫荧光结果表明 CLIC3在COS7细胞质和细胞核中均有分布;Western blot结果显示CLIC3在HEK-293T细胞中能有效表达;考马斯亮蓝染色结果表明融合蛋白GST-CLIC3在BL21菌株中能有效表达。结论人类的CLIC3蛋白COS7、HEK-293T及大肠杆菌BL21菌株均能有效表达,为进一步了解CLIC3的功能奠定了一定的基础。%Objective To investigate the expression and localization of the human chloride channel protein 3 (CLIC3) in eukaryotic cells, and the expression of GST fusion protein in prokaryotic cells. Methods Plasmids containing full length of human CLIC3 cDNA was used as PCR template to construct the prokaryotic and eukaryotic expression vectors. The pcDNA3. 1-CLIC3-FLAG was transfected into COS7 and HEK-293T cells respectively to detect the localization and expression of CLIC3. The pGEX-5X-3-CLIC3 was transformed into E. coli BL21 to inves-tigate the expression of fusion protein GST-CLIC3 . Results The immunofluorescence results indicated that CLIC3 was distributed in both cytoplasm and nucleus of COS7 cells;Western blot showed CLIC3 could be effectively ex-pressed in HEK-293T cells;Coomassie blue staining proved GST-CLIC3 could be expressed in E. coli BL21. Con-clusion Human CLIC3 protein can be expressed effectively both in eukaryotic and prokaryotic cells, which is im-portant for further research on the function of human CLIC3 .

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

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

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

  3. The effect of verapamil and diltiazem on cardiac stimulant effect of adrenaline and calcium chloride on isolated frog heart

    Directory of Open Access Journals (Sweden)

    Lakhavat Sudhakar, Naveen Kumar T, Tadvi NA, Venkata Rao Y

    2013-04-01

    Full Text Available Background: Calcium channel blockers block voltage dependent L-type of calcium channel and thus reduce the frequency of opening of these channels in response to depolarization. The result is a marked decrease in transmembrane calcium current associated with long lasting relaxation of vascular smooth muscle, reduction in contractility in cardiac muscle, decrease in pacemaker activity in the SA node and decrease in conduction velocity in the AV node. Among Calcium channel blockers verapamil, is cardio selective, nifedipine is vascular smooth muscle selective, while diltiazem exhibits intermediate selectivity. Methods: In the present study, the effect of two Ca++ channel blocker, Verapamil and Diltiazem were compared on the isolated frog heart by using adrenaline & calcium chloride as standard on frog heart contractility. Results and conclusion: Adrenaline and calcium chloride increased the amplitude of contraction of isolated perfused frog heart. The L- type of Ca2+ channel blockers verapamil and diltiazem produced dose dependent (2mg, 4mg, 8mg, and 16mg reduction in the amplitude of contraction produced by calcium chloride in isolated perfused frog heart. There was no statistical significant difference (p > 0.05 between the inhibitory effect of diltiazem and verapamil on calcium chloride induced contraction of isolated frog heart.

  4. Simple chloride sensors for continuous groundwater monitoring

    DEFF Research Database (Denmark)

    Thorn, Paul; Mortensen, John

    2012-01-01

    The development of chloride sensors which can be used for continuous, on-line monitoring of groundwater could be very valuable in the management of our coastal water resources. However, sensor stability, drift, and durability all need to be addressed in order for the sensors to be used...... in continuous application. This study looks at the development of a simple, inexpensive chloride electrode, and evaluates its performance under continuous use, both in the laboratory and in a field test in a monitoring well. The results from the study showed a consistent response to changing chloride...... sensor remained responsive even at low chloride concentrations, where the conductivity electrode was no longer responding to changing chloride levels. With the results, it is believed that the simple chloride sensor could be used for continuous monitoring of groundwater quality....

  5. [Model of the selective calcium channel of characean algae].

    Science.gov (United States)

    Lunevskiĭ, V Z; Zherelova, O M; Aleksandrov, A A; Vinokurov, M G; Berestovskiĭ, G N

    1980-01-01

    The present work was intended to further investigate the selective filter of calcium channel on both a cell membrane and reconstructed channels. For the studies on cell membranes, an inhibitor of chloride channels was chosen (ethacrynic acid) to pass currents only through the calcium channels. On both the cells and reconstructed channels, permeability of ions of different crystal radii and valencies was investigated. The obtained results suggest that the channel represents a wide water pore with a diameter larger than 8 A into which ions go together with the nearest water shell. The values of the maximal currents are given by electrostatic interaction of the ions with the anion center of the channel. A phenomenological two-barrier model of the channel is given which describes the movement of all the ions studied. PMID:6251921

  6. ENVIRONMENTAL EXPOSURE TO VINYL CHLORIDE

    Directory of Open Access Journals (Sweden)

    Henryka Langauer-Lewowicka

    2010-09-01

    Full Text Available Vinyl chloride (VC monomer is a wellknown carcinogenic and mutagenic substance causes liver damages, angiosarcoma of the liver, acro – osteolysis, sclerodermalike changes in workers chronically exposed to this gas. There are following VC emitors to the environment: VC production plants, polymerization facilities and planes where polyvinyl products are fabricated. Because of that, the general population is coming into VC contact through polluted air, food and water. VC concentration in all mentioned sites is very low, often not detectable. There was found any health risk for the general population. The VC air concentration in the vicinity to antropogenic emitors is always higher. Such a situation may causes undesirable health effect for residents living in the neighbourhood. Epidemiological studies are performed to detect the adverse VC effect in selected cohorts. Non of the study did not confirmed cases of angiosarcoma among residents living near a vinyl chloride sites. VC production is growing permanently, so VC emission will be higher. Because of that health monitoring of general population and especially of selected groups seems to be necessary in the future.

  7. Green process to recover magnesium chloride from residue solution of potassium chloride production plant

    Institute of Scientific and Technical Information of China (English)

    Lin WANG; Yunliang HE; Yanfei WANG; Ying BAO; Jingkang WANG

    2008-01-01

    The green process to recover magnesium chlor-ide from the residue solution of a potassium chloride pro-duction plant, which comes from the leach solution of a potash mine in Laos, is designed and optimized. The res-idue solution contains magnesium chloride above 25 wt-%, potassium chloride and sodium chloride together below 5 wt-% and a few other ions such as Br-, SO2-4and Ca2+. The recovery process contains two steps: the previous impurity removal operation and the two-stage evapora-tion-cooling crystallization procedure to produce magnes-ium chloride. The crystallized impurity carnallite obtained from the first step is recycled to the potassium chloride plant to recover the potassium salt. The developed process is a zero discharge one and thus fulfills the requirements for green chemical industrial production. The produced magnesium chloride is up to industrial criteria.

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

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

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

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

    CERN Document Server

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

    2014-01-01

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

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

    OpenAIRE

    Gai-Fei Peng; Nai-Qian Feng; Qi-Ming Song

    2014-01-01

    The influence of a chloride-ion adsorption agent (Cl agent in short), composed of zeolite, calcium aluminate hydrate and calcium nitrite, on the ingress of chloride ions into concrete and mortar has been experimentally studied. The permeability of concrete was measured, and the chloride ion content in mortar was tested. The experimental results reveal that the Cl agent could adsorb chloride ions effectively, which had penetrated into concrete and mortar. When the Cl agent was used at a dosage...

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

    OpenAIRE

    H. Guan; Love, A. J.; C. T. Simmons; Makhnin, O.; A. S. Kayaalp

    2010-01-01

    Chloride is commonly used as an environmental tracer for studying water flow and solute transport in the environment. It is especially useful for estimating groundwater recharge based on the commonly used chloride mass balance (CMB) method. Strong spatial variability in chloride deposition in coastal areas is one difficulty encountered in appropriately applying the method. A high-resolution bulk chloride deposition map in the coastal region is thus needed. The aim of this study is to construc...

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

    OpenAIRE

    H. Guan; Love, A. J.; C. T. Simmons; Makhnin, O.; A. S. Kayaalp

    2010-01-01

    Chloride is commonly used as an environmental tracer for studying water flow and solute transport in the environment. It is especially useful for estimating groundwater recharge based on the commonly used chloride mass balance (CMB) method. Strong spatial variability in chloride deposition in coastal areas is one difficulty encountered in appropriately applying the method. A high-resolution bulk chloride deposition map in the coastal region is thus needed. The aim of this st...

  13. Endothelin induces two types of contractions of rat uterus: phasic contractions by way of voltage-dependent calcium channels and developing contractions through a second type of calcium channels

    Energy Technology Data Exchange (ETDEWEB)

    Kozuka, M.; Ito, T.; Hirose, S.; Takahashi, K.; Hagiwara, H.

    1989-02-28

    Effects of endothelin on nonvascular smooth muscle have been examined using rat uterine horns and two modes of endothelin action have been revealed. Endothelin (0.3 nM) caused rhythmic contractions of isolated uterus in the presence of extracellular calcium. The rhythmic contractions were completely inhibited by calcium channel antagonists. These characteristics of endothelin-induced contractions were very similar to those induced by oxytocin. Binding assays using /sup 125/I-endothelin showed that endothelin and the calcium channel blockers did not compete for the binding sites. However, endothelin was unique in that it caused, in addition to rhythmic contractions, a slowly developing monophasic contraction that was insensitive to calcium channel blockers. This developing contraction became dominant at higher concentrations of endothelin and was also calcium dependent.

  14. Endothelin induces two types of contractions of rat uterus: phasic contractions by way of voltage-dependent calcium channels and developing contractions through a second type of calcium channels

    International Nuclear Information System (INIS)

    Effects of endothelin on nonvascular smooth muscle have been examined using rat uterine horns and two modes of endothelin action have been revealed. Endothelin (0.3 nM) caused rhythmic contractions of isolated uterus in the presence of extracellular calcium. The rhythmic contractions were completely inhibited by calcium channel antagonists. These characteristics of endothelin-induced contractions were very similar to those induced by oxytocin. Binding assays using 125I-endothelin showed that endothelin and the calcium channel blockers did not compete for the binding sites. However, endothelin was unique in that it caused, in addition to rhythmic contractions, a slowly developing monophasic contraction that was insensitive to calcium channel blockers. This developing contraction became dominant at higher concentrations of endothelin and was also calcium dependent

  15. Brands & Channels

    Institute of Scientific and Technical Information of China (English)

    Alice Yang

    2009-01-01

    @@ "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.

  16. Paradoxical Contribution of SK3 and GIRK Channels to the Activation of Mouse Vomeronasal Organ

    OpenAIRE

    Kim, Sangseong; Ma, Limei; Jensen, Kristi L.; Kim, Michelle M.; Bond, Chris T.; Adelman, John P.; Yu, C. Ron

    2012-01-01

    The vomeronasal organ (VNO) plays an essential role in intraspecies communication for terrestrial vertebrates. The ionic mechanisms of VNO activation remain unclear. We find that the calcium–activated potassium channel SK3 and G–protein activated potassium channel GIRK are part of an independent pathway for VNO activation. In slice preparations, the potassium channels attenuate inward currents carried by TRPC2 and calcium–activated chloride channels (CACCs). In intact tissue preparations, par...

  17. Glucose stimulates calcium-activated chloride secretion in small intestinal cells.

    Science.gov (United States)

    Yin, Liangjie; Vijaygopal, Pooja; MacGregor, Gordon G; Menon, Rejeesh; Ranganathan, Perungavur; Prabhakaran, Sreekala; Zhang, Lurong; Zhang, Mei; Binder, Henry J; Okunieff, Paul; Vidyasagar, Sadasivan

    2014-04-01

    The sodium-coupled glucose transporter-1 (SGLT1)-based oral rehydration solution (ORS) used in the management of acute diarrhea does not substantially reduce stool output, despite the fact that glucose stimulates the absorption of sodium and water. To explain this phenomenon, we investigated the possibility that glucose might also stimulate anion secretion. Transepithelial electrical measurements and isotope flux measurements in Ussing chambers were used to study the effect of glucose on active chloride and fluid secretion in mouse small intestinal cells and human Caco-2 cells. Confocal fluorescence laser microscopy and immunohistochemistry measured intracellular changes in calcium, sodium-glucose linked transporter, and calcium-activated chloride channel (anoctamin 1) expression. In addition to enhancing active sodium absorption, glucose increased intracellular calcium and stimulated electrogenic chloride secretion. Calcium imaging studies showed increased intracellular calcium when intestinal cells were exposed to glucose. Niflumic acid, but not glibenclamide, inhibited glucose-stimulated chloride secretion in mouse small intestines and in Caco-2 cells. Glucose-stimulated chloride secretion was not seen in ileal tissues incubated with the intracellular calcium chelater BAPTA-AM and the sodium-potassium-2 chloride cotransporter 1 (NKCC1) blocker bumetanide. These observations establish that glucose not only stimulates active Na absorption, a well-established phenomenon, but also induces a Ca-activated chloride secretion. This may explain the failure of glucose-based ORS to markedly reduce stool output in acute diarrhea. These results have immediate potential to improve the treatment outcomes for acute and/or chronic diarrheal diseases by replacing glucose with compounds that do not stimulate chloride secretion.

  18. Chloride ingress in cement paste and mortar

    DEFF Research Database (Denmark)

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

    1999-01-01

    modelled on Fick's law modified by a term for chloride binding. Inclusion of chloride binding significantly improves the profile shape of the modelled ingress profiles. The presence of fine aggregate and formation of interfacial transition zones at paste-aggregate boundaries does not significantly affect...

  19. Chloride ingress in cement paste and mortar

    DEFF Research Database (Denmark)

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

    1999-01-01

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

  20. 75 FR 19657 - Barium Chloride From China

    Science.gov (United States)

    2010-04-15

    ... Commission found that the domestic interested party group response to its notice of institution (74 FR 31757... COMMISSION Barium Chloride From China AGENCY: United States International Trade Commission. ACTION: Notice of... chloride from China. SUMMARY: The Commission hereby gives notice that it will proceed with a full...

  1. Chloride binding site of neurotransmitter sodium symporters

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  2. Chronopotentiometric chloride sensing using transition time measurement

    NARCIS (Netherlands)

    Abbas, Y.; Graaf, de D.B.; Olthuis, W.; Berg, van den A.

    2013-01-01

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

  3. Chemische contaminanten in diervoeder additief Choline Chloride

    NARCIS (Netherlands)

    Traag, W.A.; Hoogenboom, L.A.P.; Jong, de J.; Egmond, van H.J.; Dam, ten G.

    2010-01-01

    Dit briefrapport beschrijft de resultaten van een onderzoek naar chemische contaminanten in Choline Chloride. De doelstellingen waren: 1) Inzicht te verkrijgen in het voorkomen van (gebromeerde) vlamvertragers en broomdioxines in het diervoederadditief Choline Chloride en het, op basis van de result

  4. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

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

    2004-01-01

    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

  5. Diffusion behavior of chloride ions in concrete

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, T.; Gjoerv, O.E. [Norwegian Univ. of Science and Technology, Trondheim (Norway). Div. of Building Materials

    1996-06-01

    In the present paper, an analysis of the diffusion behavior of chloride ions in concrete is presented. In concentrated electrolytic aqueous solutions such as seawater or that typically used in laboratory experiments, the effect of ionic interaction may significantly reduce the chemical potential and thus the driving force of the diffusing species. Because of different drift velocities of the cations and chloride ions in the solution, the lagging motion of the cations will also retard the drift velocity of the chlorides. In addition, both the electrical double layer forming on the solid surface and the chemical binding may significantly interfere with the transport of the chloride ions. As a result, the diffusion behavior of the chloride ions in concrete is a more complex and complicated transport process than what can be described by Fick`s law of diffusion.

  6. External control of anodic dissolution mechanisms of 100Cr6 in nitrate/chloride mixed electrolytes

    Directory of Open Access Journals (Sweden)

    ANDREAS LESCH

    2011-08-01

    Full Text Available The anodic dissolution of 100Cr6 steel in neutral electrolytes containing sodium chloride and sodium nitrate was investigated potentiodynamically and galvanodynamically with a rotating disc electrode at room temperature. The total concentration of the mixed electrolyte was 3 mol L-1 with variation of chloride/nitrate mole ratios. The potentiodynamic linear sweep voltammograms (LSVs in mixed electrolytes are similar to the LSVs in pure chloride electrolyte at lower current densities and switch to behaviour observed in pure nitrate electrolytes at higher current densities. Provided that both anions are present, it seems that the dissolution reactions at the steel anode are determined by the interface layer only. The effect of these layers on surface quality and current efficiency was also investigated in a flow channel applying galvanostatic pulses. An evidence for different dissolution mechanisms can be seen with an important influence of duty cycle and flow conditions. This allows external control of the desired dissolution mechanism in mixed electrolytes.

  7. Chloride Transport in Undersea Concrete Tunnel

    Directory of Open Access Journals (Sweden)

    Yuanzhu Zhang

    2016-01-01

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

  8. Shelf life of unrefrigerated succinylcholine chloride injection.

    Science.gov (United States)

    Boehm, J J; Dutton, D M; Poust, R I

    1984-02-01

    The shelf life of succinylcholine chloride injection at several pH values when stored at room temperature was evaluated. Solutions containing 20 mg/ml of succinylcholine chloride were stored at 25 and 40 degrees C. The reaction was studied at pH values ranging from 3.0 to 4.5. At two-week intervals, the solutions were assayed by high-pressure liquid chromatography. The initial amount of succinylcholine chloride in all samples was 100.1 +/- 2.37% of label claim. Hydrolysis of succinylcholine chloride in unbuffered solutions followed apparent zero-order kinetics. The pH range of maximum stability was found to be from 3.75 to 4.50. Succinylcholine chloride decomposed at a considerably higher rate at 40 degrees C. Allowing for the effects of pH adjustment during manufacture and degradation during shipping, losses of 7.0% and 9.0% potency can be expected after storage at 25 degrees C for four and six weeks, respectively. Succinylcholine Chloride Injection, USP, should be stored in the refrigerator; if unbuffered succinylcholine chloride injection complying with USP pH limits must be stored at room temperature, it should not be kept for longer than four weeks. PMID:6702837

  9. Channel Networks

    Science.gov (United States)

    Rinaldo, Andrea; Rodriguez-Iturbe, Ignacio; Rigon, Riccardo

    This review proceeds from Luna Leopold's and Ronald Shreve's lasting accomplishments dealing with the study of random-walk and topologically random channel networks. According to the random perspective, which has had a profound influence on the interpretation of natural landforms, nature's resiliency in producing recurrent networks and landforms was interpreted to be the consequence of chance. In fact, central to models of topologically random networks is the assumption of equal likelihood of any tree-like configuration. However, a general framework of analysis exists that argues that all possible network configurations draining a fixed area are not necessarily equally likely. Rather, a probability P(s) is assigned to a particular spanning tree configuration, say s, which can be generally assumed to obey a Boltzmann distribution: P(s) % e^-H(s)/T, where T is a parameter and H(s) is a global property of the network configuration s related to energetic characters, i.e. its Hamiltonian. One extreme case is the random topology model where all trees are equally likely, i.e. the limit case for T6 4 . The other extreme case is T 6 0, and this corresponds to network configurations that tend to minimize their total energy dissipation to improve their likelihood. Networks obtained in this manner are termed optimal channel networks (OCNs). Observational evidence suggests that the characters of real river networks are reproduced extremely well by OCNs. Scaling properties of energy and entropy of OCNs suggest that large network development is likely to effectively occur at zero temperature (i.e. minimizing its Hamiltonian). We suggest a corollary of dynamic accessibility of a network configuration and speculate towards a thermodynamics of critical self-organization. We thus conclude that both chance and necessity are equally important ingredients for the dynamic origin of channel networks---and perhaps of the geometry of nature.

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

    Directory of Open Access Journals (Sweden)

    H. Guan

    2010-05-01

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

  11. Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes

    Directory of Open Access Journals (Sweden)

    Ravshan Z. Sabirov

    2011-12-01

    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.

  12. Reliability-Based Planning of Chloride Measurements

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Engelund, S.

    1996-01-01

    on measurements of the chloride content obtained from the given structure. In the present paper optimal planning of measurements of the chloride content in reinforced concrete structures is considered. It is shown how optimal experimental plans can be obtained using FORM-analysis. Bayesian statistics are used......In reinforced concrete structures corrosion is initiated when the chloride concentration around the reinforcement exceeds a threshold value. If corrosion starts then expensive repairs can be necessary. The estimation of the probability that corrosion has been initiated in a given structure is based...

  13. Binary Nucleation of Water and Sodium Chloride

    Energy Technology Data Exchange (ETDEWEB)

    Nemec, Thomas [Institute of Thermomechanics ASCR, Prague, Czech Republic; Marsik, Frantisek [Institute of Thermomechanics ASCR, Prague, Czech Republic; Palmer, Donald [ORNL

    2005-01-01

    Nucleation processes in the binary water-sodium chloride system are investigated in the sense of the classical nucleation theory (CNT). The CNT is modified to be able to handle the electrolytic nature of the system and is employed to investigate the acceleration of the nucleation process due to the presence of sodium chloride in the steam. This phenomenon, frequently observed in the Wilson zone of steam turbines, is called early condensation. Therefore, the nucleation rates of the water-sodium chloride mixture are of key importance in the power cycle industry.

  14. Glutamate transporters combine transporter- and channel-like features

    NARCIS (Netherlands)

    Slotboom, DJ; Konings, WN; Lolkema, JS

    2001-01-01

    Glutamate transporters in the mammalian central nervous system have a unique position among secondary transport proteins as they exhibit glutamate-gated chloride-channel activity in addition to glutamate-transport activity. In this article, the available data on the structure of the glutamate transp

  15. GmCLC1 Confers Enhanced Salt Tolerance through Regulating Chloride Accumulation in Soybean.

    Science.gov (United States)

    Wei, Peipei; Wang, Longchao; Liu, Ailin; Yu, Bingjun; Lam, Hon-Ming

    2016-01-01

    The family of chloride channel proteins that mediate Cl(-) transportation play vital roles in plant nutrient supply, cellular action potential and turgor pressure adjustment, stomatal movement, hormone signal recognition and transduction, Cl(-) homeostasis, and abiotic and biotic stress tolerance. The anionic toxicity, mainly caused by chloride ions (Cl(-)), on plants under salt stress remains poorly understood. In this work, we investigated the function of soybean Cl(-)/H(+) antiporter GmCLC1 under salt stress in transgenic Arabidopsis thaliana, soybean, and yeast. We found that GmCLC1 enhanced salt tolerance in transgenic A. thaliana by reducing the Cl(-) accumulation in shoots and hence released the negative impact of salt stress on plant growth. Overexpression of GmCLC1 in the hairy roots of soybean sequestered more Cl(-) in their roots and transferred less Cl(-) to their shoots, leading to lower relative electrolyte leakage values in the roots and leaves. When either the soybean GmCLC1 or the yeast chloride transporter gene, GEF1, was transformed into the yeast gef1 mutant, and then treated with different chloride salts (MnCl2, KCl, NaCl), enhanced survival rate was observed. The result indicates that GmCLC1 and GEF1 exerted similar effects on alleviating the stress of diverse chloride salts on the yeast gef1 mutant. Together, this work suggests a protective function of GmCLC1 under Cl(-) stress. PMID:27504114

  16. Hydrogeologic Processes Impacting Storage, Fate, and Transport of Chloride from Road Salt in Urban Riparian Aquifers.

    Science.gov (United States)

    Ledford, Sarah H; Lautz, Laura K; Stella, John C

    2016-05-17

    Detrimental effects of road salt runoff on urban streams are compounded by its facilitated routing via storm drains, ditches, and flood channels. Elevated in-stream salinity may also result from seasonal storage and discharge of chloride in groundwater, and previous work has hypothesized that groundwater discharge to streams may have the effect of diluting stream chloride concentrations in winter and enriching them in summer. However, the hydrogeological processes controlling these patterns have not been thoroughly investigated. Our research focuses on an urban stream and floodplain system in Syracuse, NY, to understand how groundwater and surface water exchange impacts chloride storage, fate, and transport. We created a 3D groundwater flow and solute transport model of the floodplain, calibrated to the distributions of floodplain hydraulic heads and groundwater fluxes to the stream throughout the reach. We used a sensitivity analysis to calibrate and evaluate the influence of model parameters, and compared model outputs to field observations. The main source mechanism of chloride to the floodplain aquifer was high-concentration, overbank flood events in winter that directly recharged groundwater. The modeled residence time and storage capacity of the aquifer indicate that restoration projects designed to promote floodplain reconnection and the frequency of overbank flooding in winter have the potential to temporarily store chloride in groundwater, buffer surface water concentrations, and reduce stream concentrations following periods of road salting.

  17. Hydrogeologic Processes Impacting Storage, Fate, and Transport of Chloride from Road Salt in Urban Riparian Aquifers.

    Science.gov (United States)

    Ledford, Sarah H; Lautz, Laura K; Stella, John C

    2016-05-17

    Detrimental effects of road salt runoff on urban streams are compounded by its facilitated routing via storm drains, ditches, and flood channels. Elevated in-stream salinity may also result from seasonal storage and discharge of chloride in groundwater, and previous work has hypothesized that groundwater discharge to streams may have the effect of diluting stream chloride concentrations in winter and enriching them in summer. However, the hydrogeological processes controlling these patterns have not been thoroughly investigated. Our research focuses on an urban stream and floodplain system in Syracuse, NY, to understand how groundwater and surface water exchange impacts chloride storage, fate, and transport. We created a 3D groundwater flow and solute transport model of the floodplain, calibrated to the distributions of floodplain hydraulic heads and groundwater fluxes to the stream throughout the reach. We used a sensitivity analysis to calibrate and evaluate the influence of model parameters, and compared model outputs to field observations. The main source mechanism of chloride to the floodplain aquifer was high-concentration, overbank flood events in winter that directly recharged groundwater. The modeled residence time and storage capacity of the aquifer indicate that restoration projects designed to promote floodplain reconnection and the frequency of overbank flooding in winter have the potential to temporarily store chloride in groundwater, buffer surface water concentrations, and reduce stream concentrations following periods of road salting. PMID:27077530

  18. Effects of lithium chloride on outward potassium currents in acutely isolated hippocampal CA1 pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chaofeng; DU Huizhi; YANG Pin

    2006-01-01

    Although lithium possesses neuroprotective functions, the molecular mechanism underlying its actions has not been fully elucidated. In the present paper, the effects of lithium chloride on voltage-dependent potassium currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied using the whole-cell patch-clamp technique. Depolarizing test pulses activated two components of outward potassium currents: a rapidly activating and inactivating component, IA and a delayed component, IK. Results showed that lithium chloride increased the amplitude of IA in a concentration-dependent manner. Half enhancement concentration (EC50) was 22.80±5.45 μmol·L-1. Lithium chloride of 25 μmol·L-1 shifted the steady-state activation curve and inactivation curve of IA to more negative potentials, but mainly affected the activation kinetics. The amplitude and the activation processes of IK were not affected by lithium chloride. The effects of lithium chloride on potassium channel appear to possess neuroprotective properties by Ca2+-lowing effects modulate neuronal excitability by activating IA in rat hippocampal neurons.

  19. Surface adsorption in strontium chloride ammines

    DEFF Research Database (Denmark)

    Ammitzbøll, Andreas L.; Lysgaard, Steen; Klukowska, Agata;

    2013-01-01

    An adsorbed state and its implications on the ab- and desorption kinetics of ammonia in strontium chloride ammine is identified using a combination of ammonia absorption measurements, thermogravimetric analysis, and density functional theory calculations. During thermogravimetric analysis, ammoni...

  20. Catastrophic event modeling. [lithium thionyl chloride batteries

    Science.gov (United States)

    Frank, H. A.

    1981-01-01

    A mathematical model for the catastrophic failures (venting or explosion of the cell) in lithium thionyl chloride batteries is presented. The phenomenology of the various processes leading to cell failure is reviewed.

  1. M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission.

    Science.gov (United States)

    Sun, Jianli; Kapur, Jaideep

    2012-08-15

    Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M-type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M-type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN-A-343, increased the frequency of mEPSCs, but did not alter their amplitude. The M-channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M-channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium-free external medium. Blocking P/Q- and N-type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M-channels increases presynaptic calcium-dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M-channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN-A-343 and XE991; these effects were consistent with the closure of M-channels. Muscarinic activation inhibits M-channels in CA3 pyramidal neurons and its efferents – Schaffer collateral, which causes the depolarization, activates voltage-gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons. PMID:22674722

  2. Telomerization of Vinyl Chloride with Chloroform Initiated by Ferrous Chloride-Dimethylacetamide under Ultrasonic Conditions

    Directory of Open Access Journals (Sweden)

    Hua Qian

    2015-01-01

    Full Text Available Telomerization of vinyl chloride with chloroform was investigated using ferrous chloride-dimethylacetamide system, and 42.1% yield, more than four times the one reported before, was achieved. The addition of ultrasound further improved the reaction and yield was raised to 51.9% with trace byproducts at highly reduced reaction time and temperature. Ferrous chloride-dimethylacetamide under ultrasonic irradiation acts as a very efficient catalyst system for the 1 : 1 telomerization.

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

    OpenAIRE

    H. Guan; Love, A. J.; C. T. Simmons; A. S. Kayaalp

    2009-01-01

    Chloride is commonly used as an environmental tracer for studying water flow and solute transport in the environment. It is especially useful for estimating groundwater recharge based on the commonly used chloride mass balance (CMB) method. Strong spatial variability in chloride deposition in coastal areas is one difficulty encountered in appropriately applying the CMB approach. Furthermore, intensive vegetation clearance for agriculture, for example during the European settlement in many...

  4. Estimating the chloride transport in cement paste

    OpenAIRE

    Princigallo, A.

    2012-01-01

    A method was developed to measure the diffusion coefficient of chloride ions in cement paste based on an analytical solution to Fick’s 2nd law in a cylindrical coordinate system. This natural method yielded diffusivity results within as little as a month. Testing time was reduced by exploiting the three-dimensional inward flux in the specimen. In an attempt to determine the saturation concentration, dense portland cement pastes were exposed to a concentrated chloride solution. The method prov...

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

    Directory of Open Access Journals (Sweden)

    Gai-Fei Peng

    2014-04-01

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

  6. Effect of Chloride Type on Penetration of Chloride Ions in Concrete

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The influence of chloride type on the diffusivity of chloride ions in concrete was studied by experiment. The result shows that the glectric resistance of concrete and the chloride diffusion coefficient are influenced by chloride type. For the same water/cement ratio (W/C), the diffusion coefficient D in KCl solution is larger than that in NaCl solution; however, the concrete resistance in KCl solution is smaller than that in NaCl solution. The experimental result is analyzed with theory of diffusion.

  7. Channeling experiment

    International Nuclear Information System (INIS)

    Channeling of water flow and tracer transport in real fractures in a granite body at Stripa have been investigated experimentally. The experimental site was located 360 m below the ground level. Two kinds of experiments were performed. In the single hole experiments, 20 cm diameter holes were drilled about 2.5 m into the rock in the plane of the fracture. Specially designed packers were used to inject water into the fracture in 5 cm intervals all along the fracture trace in the hole. The variation of the injection flowrates along the fracture were used to determine the transmissivity variations in the fracture plane. Detailed photographs were taken from inside the hole and the visual fracture aperture was compared with the injection flowrates in the same locations. Geostatistical methods were used to evaluate the results. Five holes were measured in great detail. In addition 7 holes were drilled and scanned by simpler packer systems. A double hole experiment was performed where two parallel holes were drilled in the same fracture plane at nearly 2 m distance. Pressure pulse tests were made between the holes in both directions. Tracers were injected in 5 locations in one hole and monitored for in many locations in the other hole. The single hole experiment and the double hole experiment show that most of the fracture planes are tight but that there are open sections which form connected channels over distances of at least 2 meters. It was also found in the double hole experiment that the investigated fracture was intersected by at least one fracture between the two holes which diverted a large amount of the injected tracers to several distant locations at the tunnel wall. (authours)

  8. 21 CFR 178.3290 - Chromic chloride complexes.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Chromic chloride complexes. 178.3290 Section 178... SANITIZERS Certain Adjuvants and Production Aids § 178.3290 Chromic chloride complexes. Myristo chromic chloride complex and stearato chromic chloride complex may be safely used as release agents in the...

  9. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Hydrogen chloride, refrigerated liquid. 179.102-17...) § 179.102-17 Hydrogen chloride, refrigerated liquid. Each tank car used to transport hydrogen chloride... on or after March 16, 2009 used for the transportation of hydrogen chloride, refrigerated...

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

    Directory of Open Access Journals (Sweden)

    H. Guan

    2009-09-01

    Full Text Available Chloride is commonly used as an environmental tracer for studying water flow and solute transport in the environment. It is especially useful for estimating groundwater recharge based on the commonly used chloride mass balance (CMB method. Strong spatial variability in chloride deposition in coastal areas is one difficulty encountered in appropriately applying the CMB approach. Furthermore, intensive vegetation clearance for agriculture, for example during the European settlement in many coastal areas of Australia, may have perturbed catchment chloride balance conditions for appropriate use in CMB applications. In order to deal with these issues, a high resolution chloride deposition map in the coastal region is needed. In this study, we examined geographic, orographic, and atmospheric factors influencing chloride deposition in the Mount Lofty Ranges (MLR, a coastal hilly area of approximately 9000 km2 spatial extent in South Australia, using partial correlation and regression analyses. The results indicate that coastal distance, and terrain aspect and slope are two most significant factors controlling chloride deposition. Coastal distance accounts for 65% spatial variability in chloride deposition, with terrain aspect and slope for 8%. The deposition gradient is about 0.08 gm-2 year-1 km-1 as one progresses inland. The results are incorporated into a published de-trended residual kriging approach (ASOADeK to produce a 1 km×1 km resolution annual chloride deposition map and a bulk precipitation chloride concentration map. The average uncertainty of the deposition map is about 30% in the western MLR, and over 50% in the eastern MLR. The maps will form a very useful basis for examining catchment chloride balances for use in the CMB application in the study area.

  11. 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

    2011-01-01

    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.

  12. Congenital Chloride Diarrhea: Diagnosis by Easy-Accessible Chloride Measurement in Feces

    Directory of Open Access Journals (Sweden)

    C. Gils

    2016-01-01

    Full Text Available Background. Congenital chloride diarrhea (CCD is an autosomal recessive disorder caused by mutations in the genes encoding the intestinal Cl−/HCO3- exchanger and is clinically characterized by watery, profound diarrhea, electrolyte disturbances, and metabolic alkalosis. The CCD diagnosis is based on the clinical symptoms and measurement of high chloride concentration in feces (>90 mmol/L and is confirmed by DNA testing. Untreated CCD is lethal, while long-term clinical outcome improves when treated correctly. Case Presentation. A 27-year-old woman had an emergency caesarian due to pain and discomfort in gestational week 36 + 4. The newborn boy had abdominal distension and yellow fluid per rectum. Therapy with intravenous glucose and sodium chloride decreased his stool frequency and improved his clinical condition. A suspicion of congenital chloride diarrhea was strongly supported using blood gas analyzer to measure an increased chloride concentration in the feces; the diagnosis was confirmed by DNA testing. Discussion. Measurement of chloride in feces using an ordinary blood gas analyzer can serve as a preliminary analysis when congenital chloride diarrhea is suspected. This measurement can be easily performed with a watery feces composition. An easy-accessible chloride measurement available will facilitate the diagnostics and support the initial treatment if CCD is suspected.

  13. Plant Ion Channels: Gene Families, Physiology, and Functional Genomics Analyses

    Science.gov (United States)

    Ward, John M.; Mäser, Pascal; Schroeder, Julian I.

    2016-01-01

    Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization-and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide–gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport. PMID:18842100

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

    Directory of Open Access Journals (Sweden)

    Shi-Cong Cui

    2001-10-01

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

  15. Dynamic Electrochemical Measurement of Chloride Ions.

    Science.gov (United States)

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

    2016-02-05

    This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver chloride electrode is used extensively for potentiometric measurement of chloride ions concentration in electrolyte. In this measurement, long-term and continuous monitoring is limited due to the inherent drift and the requirement of a stable reference electrode. We utilized the chronopotentiometric approach to minimize drift and avoid the use of a conventional reference electrode. A galvanostatic pulse is applied to an Ag/AgCl electrode which initiates a faradic reaction depleting the Cl- ions near the electrode surface. The transition time, which is the time to completely deplete the ions near the electrode surface, is a function of the ion concentration, given by the Nernst equation. The square root of the transition time is in linear relation to the chloride ion concentration. Drift of the response over two weeks is negligible (59 µM/day) when measuring 1 mM [Cl-]using a current pulse of 10 Am(-2). This is a dynamic measurement where the moment of transition time determines the response and thus is independent of the absolute potential. Any metal wire can be used as a pseudo-reference electrode, making this approach feasible for long-term measurement inside concrete structures.

  16. Calcium Occupancy of N-terminal Sites within Calmodulin Induces Inhibition of the Ryanodine Receptor Calcium Release Channel

    Energy Technology Data Exchange (ETDEWEB)

    Boschek, Curt B; Jones, Terry E; Squier, Thomas C; Bigelow, Diana J

    2007-08-01

    Calmodulin (CaM) regulates calcium release from intracellular stores in skeletal muscle through its association with the ryanodine receptor (RyR1) calcium release channel, where CaM association enhances channel opening at resting calcium levels and its closing at micromolar calcium levels associated with muscle contraction. A high-affinity CaM-binding sequence (RyRp) has been identified in RyR1, which corresponds to a 30-residue sequence (i.e., K3614 – N3643) located within the central portion of the primary sequence. However, it is currently unclear whether the identified CaM-binding sequence a) senses calcium over the physiological range of calcium-concentrations associated with RyR1 regulation or b) plays a structural role unrelated to the calcium-dependent modulation of RyR1 function. Therefore, we have measured the calcium-dependent activation of the individual domains of CaM in association with RyRp and their relationship to the CaM-dependent regulation of RyR1. These measurements utilize an engineered CaM, permitting the site-specific incorporation of N-(1-pyrene) maleimide at either T34C (PyN-CaM) or T110C (PyC-CaM) in the N- and C-domains, respectively. Consistent with prior measurements, we observe a high-affinity association between both apo- and calcium-activated CaM and RyRp. Upon association with RyRp, fluorescence changes in PyN-CaM or PyC-CaM permit the measurement of the calcium-activation of these individual domains. Fluorescence changes upon calcium-activation of PyC-CaM in association with RyRp are indicative of high-affinity calcium-dependent activation of the C-terminal domain of CaM bound to RyRp at resting calcium levels and the activation of the N-terminal domain at levels of calcium associated cellular activation. In comparison, occupancy of calcium-binding sites in the N-domain of CaM mirrors the calcium-dependence of RyR1 inhibition observed at activating calcium levels, where [Ca]1/2 = 4.3 0.4 μM, suggesting a direct regulation of Ry

  17. Channel strategy adaptation

    OpenAIRE

    Rangan, V. Kasturi; Nueno, Jose L

    1999-01-01

    Using transaction cost theory, considerable research in marketing has focused on the conditions under which firms would use direct or vertically integrated versus indirect or arms length channels of distribution. Data from the field, however, indicate that channel configurations are more varied and complex, with multiple channels and composite channels being just as common as direct and indirect channels. In an attempt to explain this variety, this paper revisits the influence on channel stru...

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

    CERN Document Server

    Cohen-Adad, R

    1991-01-01

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

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

    International Nuclear Information System (INIS)

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

  20. Patch clamp studies on root cell vacuoles of a salt-tolerant and a salt-sensitive plantago species : regulation of channel activity by salt stress.

    Science.gov (United States)

    Maathuis, F J; Prins, H B

    1990-01-01

    Plantago media L. and Plantago maritima L. differ in their strategy toward salt stress, a major difference being the uptake and distribution of ions. Patch clamp techniques were applied to root cell vacuoles to study the tonoplast channel characteristics. In both species the major channel found was a 60 to 70 picosiemens channel with a low ion selectivity. The conductance of this channel for Na(+) was the same as for K(+), P(K) (+)/P(Na) (+) = 1, whereas the cation/anion selectivity (P(K) (+)/P(c1) (-)) was about 5. Gating characteristics were voltage and calcium dependent. An additional smaller channel of 25 picosiemens was present in P. maritima. In the whole vacuole configuration, the summation of the single channel currents resulted in slowly activated inward currents (t((1/2)) = 1.2 second). Inwardly directed, ATP-dependent currents could be measured against a DeltapH gradient of 1.5 units over the tonoplast. This observation strongly indicated the physiological intactness of the used vacuoles. The open probability of the tonoplast channels dramatically decreased when plants were grown on NaCl, although single channel conductance and selectivity were not altered.

  1. Liquid crystalline critical dynamics in decylammonium chloride

    CERN Document Server

    Lee, K W; Lee, C E; Kang, K H; Rhee, C; Kang, J K

    1999-01-01

    Collective chain dynamics and phase transitions in a model biomembrane, decylammonium chloride (C sub 1 sub 0 H sub 2 sub 1 NH sub 3 Cl), were studied by means of proton nuclear magnetic resonance. Our measurements sensitively reflect the critical dynamics associated with the smectic C to smectic A transition of the lipid bilayer.

  2. 75 FR 20625 - Barium Chloride From China

    Science.gov (United States)

    2010-04-20

    ... established a schedule for the conduct of this review (74 FR 62587, November 30, 2010). Subsequently, counsel... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Barium Chloride From China AGENCY: United States International Trade Commission. ACTION:...

  3. Chloride migration in concrete with superabsorbent polymers

    DEFF Research Database (Denmark)

    Hasholt, Marianne Tange; Jensen, Ole Mejlhede

    2015-01-01

    Superabsorbent polymers (SAP) can be used as a means for internal curing of concrete. In the present study, the development of transport properties of concrete with SAP is investigated. The chloride migration coefficient according to NT BUILD 492 is used as a measure of this. Twenty concrete...

  4. Determination of chloride in uranium solutions

    Energy Technology Data Exchange (ETDEWEB)

    Danse, A.; Stoch, H.; Steele, T.W.

    1967-05-15

    Thiocyanate is first removed by precipitation with a small excess of a copper solution, and the cations are removed by passing the filtrate through a cation-exchange resin. The chloride is determined in the eluate by a potentiometric titration in which silver nitrate solution is used.

  5. Amperometric Sensor for Detection of Chloride Ions

    Directory of Open Access Journals (Sweden)

    Rene Kizek

    2008-09-01

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

  6. Gebromeerde vlamvertragers en broomdioxines in Choline Chloride

    NARCIS (Netherlands)

    Egmond, van H.J.; Traag, W.A.; Hoogenboom, L.A.P.

    2008-01-01

    Sinds begin 2008 worden in het Nationaal Plan Diervoeder Choline Chloride monsters (= diervoeder additief) gevonden waarbij de DR CALUX screenings-assay een sterk verdacht signaal geeft, maar bij de GC-HRMS geen dioxines en dl-PCB's worden gevonden. Dit rapport beschrijft de resultaten van nader ond

  7. 21 CFR 582.3845 - Stannous chloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Stannous chloride. 582.3845 Section 582.3845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives §...

  8. Mobile radio channels

    CERN Document Server

    Pätzold, Matthias

    2011-01-01

    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

  9. Investigation of factors influencing chloride extraction efficiency during electrochemical chloride extraction from reinforcing concrete

    Science.gov (United States)

    Sharp, Stephen R.

    2005-11-01

    Electrochemical chloride extraction (ECE) is an accelerated bridge restoration method similar to cathodic protection, but operates at higher current densities and utilizes a temporary installation. Both techniques prolong the life of a bridge by reducing the corrosion rate of the reinforcing bar when properly applied. ECE achieves this by moving chlorides away from the reinforcement and out of the concrete while simultaneously increasing the alkalinity of the electrolyte near the reinforcing steel. Despite the proven success, significant use of ECE has not resulted in part due to an incomplete understanding in the following areas: (1) An estimation of the additional service life that can be expected following treatment when the treated member is again subjected to chlorides; (2) The cause of the decrease in current flow and, therefore, chloride removal rate during treatment; (3) Influence of water-to-cement (w/c) ratio and cover depth on the time required for treatment. This dissertation covers the research that is connected to the last two areas listed above. To begin examining these issues, plain carbon steel reinforcing bars (rebar) were embedded in portland cement concrete slabs of varying water-to-cement (w/c) ratios and cover depths, and then exposed to chlorides. A fraction of these slabs had sodium chloride added as an admixture, with all of the slabs subjected to cyclical ponding with a saturated solution of sodium chloride. ECE was then used to remove the chlorides from these slabs while making electrical measurements in the different layers between the rebar (cathode) and the titanium mat (anode) to follow the progress of the ECE process. During this study, it was revealed that the resistance of the outer concrete surface layer increases during ECE, inevitably restricting current flow, while the resistance of the underlying concrete decreases or remains constant. During ECE treatment, a white residue formed on the surface of the concrete. Analyses of the

  10. Viscosity and density tables of sodium chloride solutions

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-04-01

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

  11. Channel nut tool

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Marvin

    2016-01-12

    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.

  12. Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets.

    Science.gov (United States)

    Vasconcelos, Luiz H C; Souza, Iara L L; Pinheiro, Lílian S; Silva, Bagnólia A

    2016-01-01

    Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance, and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation. PMID:27065858

  13. Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    LUIZ HENRIQUE CÉSAR VASCONCELOS

    2016-03-01

    Full Text Available Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus and Web of Science to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation.

  14. Kinetics of Vinyl Chloride Polymerization with Mixture of Initiators

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Kinetic models for the rate constants of vinyl chloride polymerization in the presence of initiator mixtures were proposed. They may be used to design the initiator recipes for the vinyl chloride polymerization with uniform rate at different temperatures at which various grades of poly(vinyl chloride) will be prepared.

  15. Removal of iron contaminant from zirconium chloride solution

    International Nuclear Information System (INIS)

    This patent describes a process for eliminating iron contaminant from an aqueous zirconium chloride solution that has been contaminated with FeCl3 in a plant in which zirconium and hafnium chloride solutions are separated by a main MINK solvent extraction system and the FeCl3 is normally removed from the zirconium chloride solution by a secondary MINK solvent extraction system

  16. Increased excitability of acidified skeletal muscle: role of chloride conductance.

    Science.gov (United States)

    Pedersen, Thomas H; de Paoli, Frank; Nielsen, Ole B

    2005-02-01

    Generation of the action potentials (AP) necessary to activate skeletal muscle fibers requires that inward membrane currents exceed outward currents and thereby depolarize the fibers to the voltage threshold for AP generation. Excitability therefore depends on both excitatory Na+ currents and inhibitory K+ and Cl- currents. During intensive exercise, active muscle loses K+ and extracellular K+ ([K+]o) increases. Since high [K+]o leads to depolarization and ensuing inactivation of voltage-gated Na+ channels and loss of excitability in isolated muscles, exercise-induced loss of K+ is likely to reduce muscle excitability and thereby contribute to muscle fatigue in vivo. Intensive exercise, however, also leads to muscle acidification, which recently was shown to recover excitability in isolated K(+)-depressed muscles of the rat. Here we show that in rat soleus muscles at 11 mM K+, the almost complete recovery of compound action potentials and force with muscle acidification (CO2 changed from 5 to 24%) was associated with reduced chloride conductance (1731 +/- 151 to 938 +/- 64 microS/cm2, P < 0.01) but not with changes in potassium conductance (405 +/- 20 to 455 +/- 30 microS/cm2, P < 0.16). Furthermore, acidification reduced the rheobase current by 26% at 4 mM K+ and increased the number of excitable fibers at elevated [K+]o. At 11 mM K+ and normal pH, a recovery of excitability and force similar to the observations with muscle acidification could be induced by reducing extracellular Cl- or by blocking the major muscle Cl- channel, ClC-1, with 30 microM 9-AC. It is concluded that recovery of excitability in K(+)-depressed muscles induced by muscle acidification is related to reduction in the inhibitory Cl- currents, possibly through inhibition of ClC-1 channels, and acidosis thereby reduces the Na+ current needed to generate and propagate an AP. Thus short term regulation of Cl- channels is important for maintenance of excitability in working muscle. PMID:15684096

  17. Revised Model of Chloride Diffusion in Concrete Bridge by Considering Complex Action of Load and Chloride Binding Capacity

    OpenAIRE

    Xiang, Yiqiang; Guo, DongMei

    2014-01-01

    Coastal concrete bridges will suffer from deterioration of RC structural performance and resistance attenuation because of the chloride penetration and other environment factors. This article discusses current different chloride diffusion models and puts forward the revised model of chloride diffusion in concrete bridge by considering the complex action of load influence and chloride-binding capacity. Comparison of numerical predicted values and relative experimental tests show the presented ...

  18. The Earliest Ion Channels

    Science.gov (United States)

    Pohorille, A.; Wilson, M. A.; Wei, C.

    2009-12-01

    Supplying protocells with ions required assistance from channels spanning their membrane walls. The earliest channels were most likely short proteins that formed transmembrane helical bundles surrounding a water-filled pore. These simple aggregates were capable of transporting ions with efficiencies comparable to those of complex, contemporary ion channels. Channels with wide pores exhibited little ion selectivity but also imposed only modest constraints on amino acid sequences of channel-forming proteins. Channels with small pores could have been selective but also might have required a more precisely defined sequence of amino acids. In contrast to modern channels, their protocellular ancestors had only limited capabilities to regulate ion flux. It is postulated that subsequent evolution of ion channels progressed primarily to acquire precise regulation, and not high efficiency or selectivity. It is further proposed that channels and the surrounding membranes co-evolved.

  19. Gramicidin Channels: Versatile Tools

    Science.gov (United States)

    Andersen, Olaf S.; Koeppe, Roger E., II; Roux, Benoît

    Gramicidin channels are miniproteins in which two tryptophan-rich subunits associate by means of transbilayer dimerization to form the conducting channels. That is, in contrast to other ion channels, gramicidin channels do not open and close; they appear and disappear. Each subunit in the bilayer-spanning channel is tied to the bilayer/solution interface through hydrogen bonds that involve the indole NH groups as donors andwater or the phospholipid backbone as acceptors. The channel's permeability characteristics are well-defined: gramicidin channels are selective for monovalent cations, with no measurable permeability to anions or polyvalent cations; ions and water move through a pore whose wall is formed by the peptide backbone; and the single-channel conductance and cation selectivity vary when the amino acid sequence is varied, even though the permeating ions make no contact with the amino acid side chains. Given the plethora of available experimental information—for not only the wild-type channels but also for channels formed by amino acid-substituted gramicidin analogues—gramicidin channels continue to provide important insights into the microphysics of ion permeation through bilayer-spanning channels. For similar reasons, gramicidin channels constitute a system of choice for evaluating computational strategies for obtaining mechanistic insights into ion permeation through the more complex channels formed by integral membrane proteins.

  20. Multi-Channel Retailing

    Directory of Open Access Journals (Sweden)

    Dirk Morschett, Dr.,

    2005-01-01

    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.

  1. BARRIER PROPERTIES OF VINYLIDENE CHLORIDE COPOLYMERS

    Institute of Scientific and Technical Information of China (English)

    LI Yuesheng; WENG Zhixue; HUANG Zhiming; PAN Zuren

    1996-01-01

    The permeability coefficients of a series of copolymers of vinylidene chloride (VDC)with methyl acrylate (MA), butyl acrylate (BA) or vinyl chloride (VC) (as comonomer)to oxygen and carbon dioxide have been measured at 1.0 MPa and 30℃, while those to water vapor have been measured at 30℃ and 100% relative humidity. All the copolymers are semicrystalline. VDC/MA copolymers have lower melting temperature compared with VDC/BA copolymers, while that melting temperature of VDC/VC copolymer is higher than that of VDC/acrylate copolymers with the same VDC content. The barrier property of the copolymers is predominantly controlled by crystallite, free volume fraction, and cohesive energy. The permeability coefficients of VDC/MA copolymers to oxygen, carbon dioxide, and water vapor were successfully correlated with the ratio of free volume to cohesive energy.

  2. STABILISATION OF SILTY CLAY SOIL USING CHLORIDE

    Directory of Open Access Journals (Sweden)

    TAMADHER T. ABOOD

    2007-04-01

    Full Text Available The object of this paper is to investigate the effect of adding different chloride compounds including (NaCl, MgCl2, CaCl2 on the engineering properties of silty clay soil. Various amounts of salts (2%, 4%, and 8% were added to the soil to study the effect of salts on the compaction characteristics, consistency limits and compressive strength. The main findings of this study were that the increase in the percentage of each of the chloride compounds increased the maximum dry density and decrease the optimum moisture content. The liquid limit, plastic limit and plasticity index decreased with the increase in salt content. The unconfinedcompressive strength increased as the salt content increased.

  3. Chloride migration in concrete with superabsorbent polymers

    OpenAIRE

    Hasholt, Marianne Tange; Jensen, Ole Mejlhede

    2015-01-01

    Superabsorbent polymers (SAP) can be used as a means for internal curing of concrete. In the present study, the development of transport properties of concrete with SAP is investigated. The chloride migration coefficient according to NT BUILD 492 is used as a measure of this. Twenty concrete mixtures aretested 7, 14, and 28 days after casting. The development of degree of hydration is followed for 20 corresponding paste mixtures.Both when SAP is added with extra water to compensate the SAP wa...

  4. A Duplex Stainless Steel for Chloride Environments

    Science.gov (United States)

    Sridhar, N.; Kolts, J.; Flasche, L. H.

    1985-03-01

    This paper examines the effects of microstructural changes on the corrosion, stress corrosion cracking and corrosion fatigue resistance of a duplex stainless steel to chloride environments. The microstructural changes can be precipitation of phases such as sigma and carbides, or changes in the distribution of austenite and ferrite. The former can be important in hot forming operations while the latter is important in welding. The methods of minimizing these deleterious effects can sometimes be different from those used for austenitic stainless steel.

  5. Electrodeposition of Zinc from Chloride Solution

    OpenAIRE

    NAIK, Yanjerappa Arthoba; VENKATESHA, Thimmappa Venkatarangaiah

    2002-01-01

    The electroplating of zinc is carried out in the presence of 3,4,5-Trimethoxy benzaldehyde from a chloride bath. The bath constituents are optimized through Hull cell experiments. Operating parameters such as pH, temperature, and current density are also optimized. The current efficiency and throwing power are measured at different current densities. Polarization study is carried out under galvanostatic conditions. Corrosion resistance test indicated good protection of steel by the ...

  6. (tert-Butyl(2-hydroxyethylammonium chloride

    Directory of Open Access Journals (Sweden)

    Cintya Valerio-Cárdenas

    2014-07-01

    Full Text Available In the cation of the title molecular salt, C6H16NO+·Cl−, the N—C—C—O torsion angle is 176.5 (2°. In the crystal, the cations and chloride ions are linked by N—H...O and O—H...O hydrogen bonds, generating a two-dimensional network parallel to (100.

  7. Influence of chloride admixtures on cement matrix durability

    International Nuclear Information System (INIS)

    The influence of various inorganic salts, as chloride admixtures to Portland cement, on the mechanical properties and the durability of the matrix has been studied. The salts used in this study are chromium, nickel and cadmium chlorides. Improved compressive strength values are obtained which have been correlated to the stable metal hydroxide formation in high pH environment. Under static water conditions at 500C, hydrolyzed chloride ions exhibit adverse effects on the matrix durability through rapid release of calcium as calcium chloride in the initial period of leaching. On the contrary, enhanced matrix durability is obtained on long term leaching in the case of cement containing chromium chloride

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

    Directory of Open Access Journals (Sweden)

    T. William Bentley

    2015-05-01

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

  9. The dystrophin complex controls bk channel localization and muscle activity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Hongkyun Kim

    2009-12-01

    Full Text Available Genetic defects in the dystrophin-associated protein complex (DAPC are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC components from humans to Caenorhabditis elegans suggest a similar molecular function. C. elegans DAPC mutants exhibit a unique locomotory deficit resulting from prolonged muscle excitation and contraction. Here we show that the C. elegans DAPC is essential for proper localization of SLO-1, the large conductance, voltage-, and calcium-dependent potassium (BK channel, which conducts a major outward rectifying current in muscle under the normal physiological condition. Through analysis of mutants with the same phenotype as the DAPC mutants, we identified the novel islo-1 gene that encodes a protein with two predicted transmembrane domains. We demonstrate that ISLO-1 acts as a novel adapter molecule that links the DAPC to SLO-1 in muscle. We show that a defect in either the DAPC or ISLO-1 disrupts normal SLO-1 localization in muscle. Consistent with observations that SLO-1 requires a high calcium concentration for full activation, we find that SLO-1 is localized near L-type calcium channels in muscle, thereby providing a mechanism coupling calcium influx with the outward rectifying current. Our results indicate that the DAPC modulates muscle excitability by localizing the SLO-1 channel to calcium-rich regions of C. elegans muscle.

  10. A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice

    OpenAIRE

    Cormet-Boyaka, Estelle; Jeong S Hong; Berdiev, Bakhram K.; James A Fortenberry; Rennolds, Jessica; Clancy, J. P.; Benos, Dale J.; Boyaka, Prosper N.; Sorscher, Eric J.

    2009-01-01

    Cystic fibrosis (CF) is most frequently associated with deletion of phenylalanine at position 508 (ΔF508) in the CF transmembrane conductance regulator (CFTR) protein. The ΔF508-CFTR mutant protein exhibits a folding defect that affects its processing and impairs chloride-channel function. This study aimed to determine whether CFTR fragments approximately half the size of wild-type CFTR and complementary to the portion of CFTR bearing the mutation can specifically rescue the processing of end...

  11. Boldine action against the stannous chloride effect.

    Science.gov (United States)

    Reiniger, I W; Ribeiro da Silva, C; Felzenszwalb, I; de Mattos, J C; de Oliveira, J F; da Silva Dantas, F J; Bezerra, R J; Caldeira-de-Araújo, A; Bernardo-Filho, M

    1999-12-15

    Peumus boldus extract has been used in popular medicine in the treatment of biliar litiase, hepatic insufficiency and liver congestion. Its effects are associated to the substance boldine that is present in its extract. In the present work, we evaluated the influence of boldine both in: (i) the structural conformation of a plasmid pUC 9.1 through gel electrophoresis analysis; and in (ii) the survival of the strain of Escherichia coli AB1157 submitted to reactive oxygen species (ROS), generated by a Fenton like reaction, induced by stannous chloride. Our results show a reduction of the lethal effect induced by stannous chloride on the survival of the E. coli culture in the presence of boldine. The supercoiled form of the plasmid is not modified by stannous chloride in the presence of boldine. We suggest that the protection induced by boldine could be explained by its anti-oxidant mechanism. In this way, the boldine could be reacting with stannous ions, protecting them against the oxidation and, consequently, avoiding the generation of ROS. PMID:10624900

  12. Potassium chloride production by microcline chlorination

    Energy Technology Data Exchange (ETDEWEB)

    Orosco, Pablo, E-mail: porosco@unsl.edu.ar [Instituto de Investigaciones en Tecnología Química (INTEQUI), Chacabuco y Pedernera, San Luis (Argentina); Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, San Luis (Argentina); Ruiz, María del Carmen [Instituto de Investigaciones en Tecnología Química (INTEQUI), Chacabuco y Pedernera, San Luis (Argentina)

    2015-08-10

    Highlights: • Use of chlorination for the KCl production. • The reagents used were microcline, hydromagnesite and chlorine. • Isothermal and non-isothermal assays were performed in Cl{sub 2}–N{sub 2} mixture. • The chlorination generated KCl at 700 °C. • The chlorination products promote KCl formation. - Abstract: The potassium chloride is one of the most important fertilizers used in agriculture. The current demand of this salt makes interesting the study of potassium chloride production from unconventional potassium resources. In this work the potassium chloride production by chlorination of microcline was investigated. The starting reagents were microcline, hydromagnesite and chlorine. Non-isothermal and isothermal chlorination assays were carried out in a thermogravimetric device adapted to work in corrosive atmospheres. The temperature effect on potassium extraction and the phase transformations produced during chlorination of microcline were studied. The reagents and reaction products were analyzed by X-ray fluorescence (XRF) and X-ray diffraction (XRD). The experimental results indicated that by chlorination of microcline an important extraction of potassium in the temperature range from 800 to 900 °C was produced. Moreover, at 800 °C the forsterite, enstatite and magnesium aluminate spinel phases were generated.

  13. Understanding microwave vessel contamination by chloride species.

    Science.gov (United States)

    Recchia, Sandro; Spanu, Davide; Bianchi, Davide; Dossi, Carlo; Pozzi, Andrea; Monticelli, Damiano

    2016-10-01

    Microwaves are widely used to assist digestion, general sample treatment and synthesis. The use of aqua regia is extensively adopted for the closed vessel mineralization of samples prior to trace element detection, leading to the contamination of microwave vessels by chlorine containing species. The latter are entrapped in the polymeric matrix of the vessels, leading to memory effects that are difficult to remove, among which the risk of silver incomplete recoveries by removal of the sparingly soluble chloride is the predominant one. In the present paper, we determined by mass spectrometry that hydrogen chloride is the species entrapped in the polymeric matrix and responsible for vessel contamination. Moreover, several decontamination treatments were considered to assess their efficiency, demonstrating that several cleaning cycles with water, nitric acid or silver nitrate in nitric acid were inefficient in removing chloride contamination (contamination reduction around 90%). Better results (≈95% decrease) were achieved by a single decontamination step in alkaline environment (sodium hydroxide or ammonia). Finally, a thermal treatment in a common laboratory oven (i.e. without vacuum and ventilation) was tested: a one hour heating at 150°C leads to a 98.5% decontamination, a figure higher than the ones obtained by wet treatments which requires comparable time. The latter treatment is a major advancement with respect to existing treatments as it avoids the need of a vacuum oven for at least 17h as presently proposed in the literature.

  14. An autopsy case of zinc chloride poisoning.

    Science.gov (United States)

    Kondo, Takeshi; Takahashi, Motonori; Watanabe, Seiya; Ebina, Masatomo; Mizu, Daisuke; Ariyoshi, Koichi; Asano, Migiwa; Nagasaki, Yasushi; Ueno, Yasuhiro

    2016-07-01

    Ingestion of large amounts of zinc chloride causes corrosive gastroenteritis with vomiting, abdominal pain, and diarrhea. Some individuals experience shock after ingesting large amounts of zinc chloride, resulting in fatality. Here, we present the results of an administrative autopsy performed on a 70-year-old man who ingested zinc chloride solution and died. After drinking the solution, he developed vomiting, abdominal pain, and diarrhea, and called for an ambulance. Except for tachycardia, his vital signs were stable at presentation. However, he developed hypotension and severe metabolic acidosis and died. The patient's blood zinc concentration on arrival was high at 3030μg/dL. Liver cirrhosis with cloudy yellow ascites was observed, however, there were no clear findings of gastrointestinal perforation. The gastric mucosa was gray-brown, with sclerosis present in all gastric wall layers. Zinc staining was strongly positive in all layers. There was almost no postmortem degeneration of the gastric mucosal epithelium, and hypercontracture of the smooth muscle layer was observed. Measurement of the zinc concentration in the organs revealed the highest concentration in the gastric mucosa, followed by the pancreas and spleen. Clinically, corrosive gastroenteritis was the cause of death. However, although autopsy revealed solidification in the esophagus and gastric mucosa, there were no findings in the small or large intestine. Therefore, metabolic acidosis resulting from organ damage was the direct cause of death. PMID:27497327

  15. 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

    2006-01-01

    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 www.imtech.res.in/raghava/vgichan/.

  16. Chloride permeability of rat brain membrane vesicles correlates with thiamine triphosphate content.

    Science.gov (United States)

    Bettendorff, L; Hennuy, B; De Clerck, A; Wins, P

    1994-07-25

    Incubation of rat brain homogenates with thiamine or thiamine diphosphate (TDP) leads to a synthesis of thiamine triphosphate (TTP). In membrane vesicles subsequently prepared from the homogenates, increased TTP content correlates with increased 36Cl- uptake. A hyperbolic relationship was obtained with a K0.5 of 0.27 nmol TTP/mg protein. In crude mitochondrial fractions from the brains of animals previously treated with thiamine or sulbutiamine, a positive correlation between 36Cl- uptake and TTP content was found. These results, together with other results previously obtained with the patch-clamp technique, suggest that TTP is an activator of chloride channels having a large unit conductance. PMID:7953714

  17. The Accelerated Test of Chloride Permeability of Concrete

    Institute of Scientific and Technical Information of China (English)

    TAN Ke-feng; ODD E Gjφrv

    2003-01-01

    The availability of accelerated chloride permeability test and the effect of w/c ratio, incorporation of silica fume, maximum aggregate size and aggregate type on the chloride permeability were studied. The mathematic analysis certifies that there is a linear relationship between accelerated test and natural diffusion. Test results show that the chloride permeability of concrete increases as w/c ratio increases whilst a limited amount of replacement of cement with silica fume, the chloride permeability decreases dramatically. The maximum aggregate size in the range of 8 to 25 mm seems also affect chloride permeability but with a much less significant level. The chloride permeability of silica fume lightweight aggregate concrete is very low, especially the concrete made with dry lightweight concrete. The chloride permeability can be evaluated by this accelerated test method.

  18. 40 CFR 61.64 - Emission standard for polyvinyl chloride plants.

    Science.gov (United States)

    2010-07-01

    ... Standard for Vinyl Chloride § 61.64 Emission standard for polyvinyl chloride plants. An owner or operator of a polyvinyl chloride plant shall comply with the requirements of this section and § 61.65. (a... is not to exceed 0.02 g vinyl chloride/kg (0.04 lb vinyl chloride/ton) of polyvinyl chloride...

  19. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium channel blockers are a type of medicine used ...

  20. Dynamic channel allocation

    OpenAIRE

    Kaminsky, Andrew D.

    2003-01-01

    Approved for public release; distribution in unlimited. Dynamic Channel Allocation (DCA) offers the possibility of capturing unused channel capacity by allocating unused resources between competing network nodes. This can reduce or possibly eliminate channels sitting idle while information awaits transmission. This holds potential for increasing throughput on bandwidth constrained networks. The purpose of this thesis is to examine the techniques used to allocate channels on demand and acc...

  1. Critical assessment of OmpF channel selectivity: merging information from different experimental protocols

    International Nuclear Information System (INIS)

    The ion selectivity of a channel can be quantified in several ways by using different experimental protocols. A wide, mesoscopic channel, the OmpF porin of the outer membrane of E. coli, serves as a case study for comparing and analysing several measures of the channel cation-anion permeability in chlorides of alkali metals (LiCl, NaCl, KCl, CsCl). We show how different insights can be gained and integrated to rationalize the global image of channel selectivity. To this end, reversal potential, channel conductance and bi-ionic potential (two different salts with a common anion on each side of the channel but with the same concentration) experiments are discussed in light of an electrodiffusion model based on the Poisson-Nernst-Planck formalism. Measurements and calculations based on the atomic crystal structure of the channel show that each protocol displays a particular balance between the different sources of selectivity.

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

    DEFF Research Database (Denmark)

    Kristensen, P; Larsen, Erik Hviid

    1978-01-01

    Substitution of chloride in the outside bathing medium of the toad skin with bromide, iodide, nitrate and sulphate leads to a reduction in the apparent exchange diffusion of chloride across this tissue, and also to a reduction of the chloride current recorded during hyperpolarization. A series...... of inhibitors (thiocyanate, furosemide, phloretin, and acetazolamide) also affects chloride exchange diffusion, hyperpolarization current as well as chloride influx during hyperpolarization. Although in some cases, effects on the short circuit current were also observed none of the effects on chloride transport....... On the basis of these findings, and the results reported in the previous paper (Hviid Larsen and Kristensen 1977) it is considered probable that the membrane molecules responsible to chloride exchange diffusion under short circuit conditions, are rearranged under the influence of a hyperpolarizing clamping...

  3. Anti-chloride permeability and anti-chloride corrodibility of a green high performance concrete admixture in concrete

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yongbao; LIU Xinrong; LIU Dongyan; CHEN Jiangong; HUANG Xiongjun

    2003-01-01

    The effects of green high performance concrete (GHPC) admixture on the anti-chloride permeability and anti- chloride corrodibility of concrete are studied by a series of experiments designed on the basis of the diffusion principle and electrochemical principle. The GHPC admixture consists of fly ash, gangue, slag, red mud, etc., of which the mass fraction of industrial residues is over 96 %. The anti-permeabilities and anti-corrodibilities of the tested GHPC and normal concrete (NC) are evaluated by the Diffusion Coefficients of chloride which was obtained by measuring the concentration of chloride in the tested systems by the voltage difference method. It is found that the adoption of GHPC admixture greatly improves the anti-chloride permeability and anti-chloride corrodibility by modifying the inner structure and contracting the porosity of concrete to the reduce considerably the diffusion rate of chloride. The admixture is desirable regarding its engineering performances as well as economical and environmental interests.

  4. Desynched channels on IRCnet

    CERN Document Server

    Hansen, Michael

    2008-01-01

    In this paper we describe what a desynchronised channel on IRC is. We give procedures on how to create such a channel and how to remove desynchronisation. We explain which types of desynchronisation there are, what properties desynchronised channels have, and which properties can be exploited.

  5. Quantum Binary Symmetric Channels

    Institute of Scientific and Technical Information of China (English)

    陈小余; 仇佩亮

    2001-01-01

    Quantum binary symmetric channels are defined via the invariance of fidelity under unitary transformations ofthe input density operators. In this definition, they not only include the most studied case of the depolarizingchannel but also other channels. We investigate the character of the latter and find the maximum of the coherentinformation to estimate the capacities of the channels.

  6. Quantum Multiple Access Channel

    Institute of Scientific and Technical Information of China (English)

    侯广; 黄民信; 张永德

    2002-01-01

    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.

  7. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    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...

  8. KV7 potassium channels

    DEFF Research Database (Denmark)

    Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A

    2014-01-01

    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...

  9. Regulation of Shaker-type potassium channels by hypoxia. Oxygen-sensitive K+ channels in PC12 cells.

    Science.gov (United States)

    Conforti, L; Millhorn, D E

    2000-01-01

    Little is known about the molecular composition of the O2-sensitive K+ (Ko2) channels. The possibility that these channels belong to the Shaker subfamily (Kv1) of voltage-dependent K+ (Kv) channels has been raised in pulmonary artery (PA) smooth muscle cells. Numerous findings suggest that the Ko2 channel in PC12 cells is a Kv1 channel, formed by the Kv1.2 alpha subunit. The Ko2 channel in PC12 cells is a slow-inactivating voltage-dependent K+ channel of 20 pS conductance. Other Kv channels, also expressed in PC12 cells, are not inhibited by hypoxia. Selective up-regulation by chronic hypoxia of the Kv1.2 alpha subunit expression correlates with an increase O2-sensitivity of the K+ current. Other Kv1 alpha subunit genes encoding slow-inactivating Kv channels, such as Kv1.3, Kv2.1, Kv3.1 and Kv3.2 are not modulated by chronic hypoxia. The Ko2 current in PC12 cells is blocked by 5 mM externally applied tetraethylammonium chloride (TEA) and by charydbotoxin (CTX). The responses of the Kv1.2 K+ channel to hypoxia have been studied in the Xenopus oocytes and compared to those of Kv2.1, also proposed as Ko2 channel in PA smooth muscle cells. Two-electrode voltage clamp experiments show that hypoxia induces inhibition of K+ current amplitude only in oocytes injected with Kv1.2 cRNA. These data indicate that Kv1.2 K+ channels are inhibited by hypoxia. PMID:10849667

  10. An increase in [Ca2+]i activates basolateral chloride channels and inhibits apical sodium channels in frog skin epithelium

    DEFF Research Database (Denmark)

    Brodin, Birger; Rytved, K A; Nielsen, R

    1996-01-01

    The aim of this study was to investigate the mechanisms by which increases in free cytosolic calcium ([Ca2+]i) cause a decrease in macroscopic sodium absorption across principal cells of the frog skin epithelium. [Ca2+]i was measured with fura-2 in an epifluorescence microscope set-up, sodium...

  11. TRESK background K(+ channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Gabriella Braun

    Full Text Available TRESK (TWIK-related spinal cord K(+ channel, KCNK18 is a major background K(+ channel of sensory neurons. Dominant-negative mutation of TRESK is linked to familial migraine. This important two-pore domain K(+ channel is uniquely activated by calcineurin. The calcium/calmodulin-dependent protein phosphatase directly binds to the channel and activates TRESK current several-fold in Xenopus oocytes and HEK293 cells. We have recently shown that the kinase, which is responsible for the basal inhibition of the K(+ current, is sensitive to the adaptor protein 14-3-3. Therefore we have examined the effect of the 14-3-3-inhibited PAR-1/MARK, microtubule-associated-protein/microtubule affinity-regulating kinase on TRESK in the Xenopus oocyte expression system. MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium-dependent activation. Several other serine-threonine kinase types, generally involved in the modulation of other ion channels, failed to influence TRESK current recovery. MARK2 phosphorylated the primary determinant of regulation, the cluster of three adjacent serine residues (S274, 276 and 279 in the intracellular loop of mouse TRESK. In contrast, serine 264, the 14-3-3-binding site of TRESK, was not phosphorylated by the kinase. Thus MARK2 selectively inhibits TRESK activity via the S274/276/279 cluster, but does not affect the direct recruitment of 14-3-3 to the channel. TRESK is the first example of an ion channel phosphorylated by the dynamically membrane-localized MARK kinases, also known as general determinants of cellular polarity. These results raise the possibility that microtubule dynamics is coupled to the regulation of excitability in the neurons, which express TRESK background potassium channel.

  12. On 1-qubit channels

    OpenAIRE

    Uhlmann, Armin

    2000-01-01

    The entropy H_T(rho) of a state rho with respect to a channel T and the Holevo capacity of the channel require the solution of difficult variational problems. For a class of 1-qubit channels, which contains all the extremal ones, the problem can be significantly simplified by associating an Hermitian antilinear operator theta to every channel of the considered class. The concurrence of the channel can be expressed by theta and turns out to be a flat roof. This allows to write down an explicit...

  13. On 1-qubit channels

    CERN Document Server

    Uhlmann, A

    2001-01-01

    The entropy H_T(rho) of a state rho with respect to a channel T and the Holevo capacity of the channel require the solution of difficult variational problems. For a class of 1-qubit channels, which contains all the extremal ones, the problem can be significantly simplified by associating an Hermitian antilinear operator theta to every channel of the considered class. The concurrence of the channel can be expressed by theta and turns out to be a flat roof. This allows to write down an explicit expression for H_T. Its maximum would give the Holevo (1-shot) capacity.

  14. Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis.

    Science.gov (United States)

    Vidadala, Rama Subba Rao; Rivas, Kasey L; Ojo, Kayode K; Hulverson, Matthew A; Zambriski, Jennifer A; Bruzual, Igor; Schultz, Tracey L; Huang, Wenlin; Zhang, Zhongsheng; Scheele, Suzanne; DeRocher, Amy E; Choi, Ryan; Barrett, Lynn K; Siddaramaiah, Latha Kallur; Hol, Wim G J; Fan, Erkang; Merritt, Ethan A; Parsons, Marilyn; Freiberg, Gail; Marsh, Kennan; Kempf, Dale J; Carruthers, Vern B; Isoherranen, Nina; Doggett, J Stone; Van Voorhis, Wesley C; Maly, Dustin J

    2016-07-14

    New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activity in vitro and in vivo. Unfortunately, 1 has potent human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q-T syndrome, and consequently presents a cardiotoxicity risk. Here, we describe the identification of an optimized TgCDPK1 inhibitor 32, which does not have a hERG liability and possesses a favorable pharmacokinetic profile in small and large animals. 32 is CNS-penetrant and highly effective in acute and latent mouse models of T. gondii infection, significantly reducing the amount of parasite in the brain, spleen, and peritoneal fluid and reducing brain cysts by >85%. These properties make 32 a promising lead for the development of a new antitoxoplasmosis therapy. PMID:27309760

  15. Source and Channel Coding for Correlated Sources Over Multiuser Channels

    OpenAIRE

    Gunduz, Deniz; Erkip, Elza; Goldsmith, Andrea; Poor, H. Vincent

    2008-01-01

    Source and channel coding over multiuser channels in which receivers have access to correlated source side information is considered. For several multiuser channel models necessary and sufficient conditions for optimal separation of the source and channel codes are obtained. In particular, the multiple access channel, the compound multiple access channel, the interference channel and the two-way channel with correlated sources and correlated receiver side information are considered, and the o...

  16. C. elegans TRP channels.

    Science.gov (United States)

    Xiao, Rui; Xu, X Z Shawn

    2011-01-01

    Transient receptor potential (TRP) channels represent a superfamily of cation channels found in all eukaryotes. The C. elegans genome encodes seventeen TRP channels covering all of the seven TRP subfamilies. Genetic analyses in C. elegans have implicated TRP channels in a wide spectrum of behavioral and physiological processes, ranging from sensory transduction (e.g. chemosensation, touch sensation, proprioception and osmosensation) to fertilization, drug dependence, organelle biogenesis, apoptosis, gene expression, and neurotransmitter/hormone release. Many C. elegans TRP channels share similar activation and regulatory mechanisms with their vertebrate counterparts. Studies in C. elegans have also revealed some previously unrecognized functions and regulatory mechanisms of TRP channels. C. elegans represents an excellent genetic model organism for the study of function and regulation of TRP channels in vivo. PMID:21290304

  17. Chloride diffusion in partially saturated cementitious material

    DEFF Research Database (Denmark)

    Nielsen, Erik Pram; Geiker, Mette Rica

    2003-01-01

    The paper proposes a combined application of composite theory and Powers' model for microstructural development for the estimation of the diffusion coefficient as a function of the moisture content of a defect-free cementitious material. Measurements of chloride diffusion in mortar samples (440 kg....../m(3) rapid-hardening Portland cement, w/c = 0.5, maturity minimum 6 months) stored at 65% and 85% RH, as well as in vacuum-saturated mortar samples, illustrate the applicability of the method. (C) 2003 Elsevier Science Ltd. All rights reserved....

  18. Oral cadmium chloride intoxication in mice

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, J B; Svendsen, P

    1988-01-01

    Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect....... Thus, orally administered DDC enhanced cadmium-induced duodenal and ileal tissue damage and inhibition of peristalsis, as indicated by an increased intestinal transit time. At low cadmium doses, the whole-body retention of cadmium was increased by oral DDC administration. Intraperitoneally administered...

  19. N-(2-Benzoylethylpropan-2-aminium chloride

    Directory of Open Access Journals (Sweden)

    Abdullah Aydın

    2012-09-01

    Full Text Available In the title salt, C12H18NO+·Cl−, N—H...Cl interactions between the free chloride anions and the organic cations connect the molecules into hydrogen-bond dimers, forming a R22(8 motif. The dimers are linked by C—H...O hydrogen bonds into chains extending along [301]. The carbonyl group is co-planar with the phenyl ring [C—C—C=O torsion angle = −3.3 (7°]. The side chain has an E conformation.

  20. Calcium-Dependent Protein Kinase Genes in Corn Roots

    Science.gov (United States)

    Takezawa, D.; Patil, S.; Bhatia, A.; Poovaiah, B. W.

    1996-01-01

    Two cDNAs encoding Ca-2(+) - Dependent Protein Kinases (CDPKs), Corn Root Protein Kinase 1 and 2 (CRPK 1, CRPK 2) were isolated from the root tip library of corn (Zea mays L., cv. Merit) and their nucleotide sequences were determined. Deduced amino acid sequences of both the clones have features characteristic of plant CDPKS, including all 11 conserved serine/threonine kinase subdomains, a junction domain and a calmodulin-like domain with four Ca-2(+), -binding sites. Northern analysis revealed that CRPKI mRNA is preferentially expressed in roots, especially in the root tip; whereas, the expression of CRPK2 mRNA was very low in all the tissues tested. In situ hybridization experiments revealed that CRPKI mRNA is highly expressed in the root apex, as compared to other parts of the root. Partially purified CDPK from the root tip phosphorylates syntide-2, a common peptide substrate for plant CDPKs, and the phosphorylation was stimulated 7-fold by the addition of Ca-2(+). Our results show that two CDPK isoforms are expressed in corn roots and they may be involved in the Ca-2(+)-dependent signal transduction process.

  1. Mitochondria, calcium-dependent neuronal death and neurodegenerative disease.

    OpenAIRE

    Duchen, M R

    2012-01-01

    Understanding the mechanisms of neuronal dysfunction and death represents a major frontier in contemporary medicine, involving the acute cell death in stroke, and the attrition of the major neurodegenerative diseases, including Parkinson's, Alzheimer's, Huntington's and Motoneuron diseases. A growing body of evidence implicates mitochondrial dysfunction as a key step in the pathogenesis of all these diseases, with the promise that mitochondrial processes represent valuable potential therapeut...

  2. Gelsolin mediates calcium-dependent disassembly of Listeria actin tails

    Science.gov (United States)

    Larson, Laura; Arnaudeau, Serge; Gibson, Bruce; Li, Wei; Krause, Ryoko; Hao, Binghua; Bamburg, James R.; Lew, Daniel P.; Demaurex, Nicolas; Southwick, Frederick

    2005-01-01

    The role of intracellular Ca2+ in the regulation of actin filament assembly and disassembly has not been clearly defined. We show that reduction of intracellular free Ca2+ concentration ([Ca2+]i) to <40 nM in Listeria monocytogenes-infected, EGFP–actin-transfected Madin–Darby canine kidney cells results in a 3-fold lengthening of actin filament tails. This increase in tail length is the consequence of marked slowing of the actin filament disassembly rate, without a significant change in assembly rate. The Ca2+-sensitive actin-severing protein gelsolin concentrates in the Listeria rocket tails at normal resting [Ca2+]i and disassociates from the tails when [Ca2+]i is lowered. Reduction in [Ca2+]i also blocks the severing activity of gelsolin, but not actin-depolymerizing factor (ADF)/cofilin microinjected into Listeria-infected cells. In Xenopus extracts, Listeria tail lengths are also calcium-sensitive, markedly shortening on addition of calcium. Immunodepletion of gelsolin, but not Xenopus ADF/cofilin, eliminates calcium-sensitive actin-filament shortening. Listeria tail length is also calcium-insensitive in gelsolin-null mouse embryo fibroblasts. We conclude that gelsolin is the primary Ca2+-sensitive actin filament recycling protein in the cell and is capable of enhancing Listeria actin tail disassembly at normal resting [Ca2+]i (145 nM). These experiments illustrate the unique and complementary functions of gelsolin and ADF/cofilin in the recycling of actin filaments. PMID:15671163

  3. Interactions between chloride ingress and carbonation in cementitious materials

    OpenAIRE

    SAILLIO, Mickael; BARBERON, Fabien; BAROGHEL BOUNY, Véronique; GEGOUT, Philippe; PLATRET, Gérard; D'ESPINOSE DE LA CAILLERIE, JB

    2011-01-01

    Carbonation and chloride attacks are the major causes of reinforced concrete (RC) structure deterioration by initiation of steel rebar corrosion. These attacks are usually studied separately in the literature. Chloride-induced corrosion takes place mainly in marine environment or in the case of contact with deicing salts, while carbonation is systematically present in all RC structures at a variable degree. Since carbonation leads to significant microstructure changes, the effect of chloride ...

  4. Surface Chloride Concentration of Concrete under Shallow Immersion Conditions

    OpenAIRE

    Jun Liu; Kaifeng Tang; Dong Pan; Zongru Lei; Weilun Wang; Feng Xing

    2014-01-01

    Deposition of chloride ions in the surface layer of concrete is investigated in this study. In real concrete structure, chloride ions from the service environment can penetrate into concrete and deposit in the surface layer, to form the boundary condition for further diffusion towards the interior. The deposit amount of chloride ions in the surface layer is normally a function of time, rather than a constant. In the experimental investigation, concrete specimens with different mix proportions...

  5. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Kramer Gerhard

    2009-01-01

    Full Text Available Abstract This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom ( are derived for the degraded case with one receiver. Schemes to achieve the for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable is given for the general case.

  6. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Shlomo Shamai (Shitz

    2009-01-01

    Full Text Available This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom (s.d.o.f. are derived for the degraded case with one receiver. Schemes to achieve the s.d.o.f. for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable s.d.o.f. is given for the general case.

  7. N,N-Dimethyldehydroabietylammonium chloride ethanol monosolvate

    Directory of Open Access Journals (Sweden)

    Xiu-Zhi Huang

    2013-06-01

    Full Text Available The title compound {systematic name: 1-[(1R,4aS,10aR-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl]-N,N-dimethylmethanaminium chloride ethanol monosolvate}, C22H36N+·Cl−·C2H6O, was synthesized from dehydroabietylamine by N-methylation with formaldehyde/formic acid and transformation into the hydrochloride. The dehydroabietyl moiety exhibits the usual conformation with the two cyclohexane rings in chair and half-chair conformations and a trans-ring junction. The crystal structure is built up from columns of the dehydroabietyl moieties stacked along the a axis. These columns are held together by the chloride ions via N—H...Cl and C—H...Cl interactions, which establish a two-dimensional network parallel to (010. The ethanol solvent molecules are located between the columns and anchored via O—H...Cl hydrogen bonds.

  8. Open cycle lithium chloride cooling system

    Science.gov (United States)

    Lenz, T. G.; Loef, G. O. G.; Iyer, R.; Wenger, J.

    1983-05-01

    A lithium chloride open cycle absorption chiller has been designed, built and tested. Solution reconcentration takes place in a small counter current packed column supplied with solar heated air. Removal of noncondensable gases that enter the chiller dissolved in the strong solution and the make-up refrigerant streams is accomplished by a liquid-jet ejector and a small vacuum pump. Cooling capacities approaching 1.4 tons and COP levels of 0.58 have been achieved at non-optimum operating conditions. Test results from preliminary system operation suggest that mass transfer processes in both the packed column reconcentrator and the absorber are controlled by concentration gradients in the lithium chloride solution. Liquid phase controlled mass transfer dictates an operating strategy different from the previously assumed gas phase controlled process to obtain maximum rates of evaporation in the packed column. Determination of optimal operating conditions leading to decreased electrical power consumption and improved cooling capacity and coefficient of performance will require further analysis and testing.

  9. Synthesis and structure characterization of diethyldiallylammonium chloride

    Institute of Scientific and Technical Information of China (English)

    刘立华; 龚竹青; 郑雅杰

    2003-01-01

    The unsaturated quaternary ammonium salt diethyldiallylammonium chloride(DEDAAC) was synthesized in a two-step synthetic method. The influences of the adding method of raw materials and temperature on the yields of diethylallylamine (DEAA), and drying and temperature on the synthesis of DEDAAC were investigated. The content of in-process product DEAA was determined by non-aqueous titration. The structure of product DEDAAC was identified with IR, 1 H NMR and elemental analysis. The results show that adding allyl chloride and sodium hydroxide alternately can increase the yield of DEAA and decrease by-products. In further synthesizing of DEDAAC from DEAA, the step of drying DEAA is very necessary. When DEAA is dried by solid sodium hydroxide, good columnar crystals with a high purity(mp 199.5-201.0 ℃) are obtained; when DEAA is undried or the content of water in DEAA is above 20%, only platelets with bad quality are obtained even without crystals. The suitable synthesis conditions for DEAA and DEDAAC are 35 ℃, 6 h and 40 ℃, 36 h, respectively, and their yields are 69.7% and 67.3%, respectively.

  10. Fault locator of an allyl chloride plant

    Directory of Open Access Journals (Sweden)

    Savković-Stevanović Jelenka B.

    2004-01-01

    Full Text Available Process safety analysis, which includes qualitative fault event identification, the relative frequency and event probability functions, as well as consequence analysis, was performed on an allye chloride plant. An event tree for fault diagnosis and cognitive reliability analysis, as well as a troubleshooting system, were developed. Fuzzy inductive reasoning illustrated the advantages compared to crisp inductive reasoning. A qualitative model forecast the future behavior of the system in the case of accident detection and then compared it with the actual measured data. A cognitive model including qualitative and quantitative information by fuzzy logic of the incident scenario was derived as a fault locator for an ally! chloride plant. The obtained results showed the successful application of cognitive dispersion modeling to process safety analysis. A fuzzy inductive reasoner illustrated good performance to discriminate between different types of malfunctions. This fault locator allowed risk analysis and the construction of a fault tolerant system. This study is the first report in the literature showing the cognitive reliability analysis method.

  11. Correction of chloride transport and mislocalization of CFTR protein by vardenafil in the gastrointestinal tract of cystic fibrosis mice.

    Directory of Open Access Journals (Sweden)

    Barbara Dhooghe

    Full Text Available Although lung disease is the major cause of mortality in cystic fibrosis (CF, gastrointestinal (GI manifestations are the first hallmarks in 15-20% of affected newborns presenting with meconium ileus, and remain major causes of morbidity throughout life. We have previously shown that cGMP-dependent phosphodiesterase type 5 (PDE5 inhibitors rescue defective CF Transmembrane conductance Regulator (CFTR-dependent chloride transport across the mouse CF nasal mucosa. Using F508del-CF mice, we examined the transrectal potential difference 1 hour after intraperitoneal injection of the PDE5 inhibitor vardenafil or saline to assess the amiloride-sensitive sodium transport and the chloride gradient and forskolin-dependent chloride transport across the GI tract. In the same conditions, we performed immunohistostaining studies in distal colon to investigate CFTR expression and localization. F508del-CF mice displayed increased sodium transport and reduced chloride transport compared to their wild-type littermates. Vardenafil, applied at a human therapeutic dose (0.14 mg/kg used to treat erectile dysfunction, increased chloride transport in F508del-CF mice. No effect on sodium transport was detected. In crypt colonocytes of wild-type mice, the immunofluorescence CFTR signal was mostly detected in the apical cell compartment. In F508del-CF mice, a 25% reduced signal was observed, located mostly in the subapical region. Vardenafil increased the peak of intensity of the fluorescence CFTR signal in F508del-CF mice and displaced it towards the apical cell compartment. Our findings point out the intestinal mucosa as a valuable tissue to study CFTR transport function and localization and to evaluate efficacy of therapeutic strategies in CF. From our data we conclude that vardenafil mediates potentiation of the CFTR chloride channel and corrects mislocalization of the mutant protein. The study provides compelling support for targeting the cGMP signaling pathway in CF

  12. Interpretation of postmortem vitreous concentrations of sodium and chloride.

    Science.gov (United States)

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

    2016-06-01

    Vitreous fluid can be used to analyze sodium and chloride levels in deceased persons, but it remains unclear to what extent such results can be used to diagnose antemortem sodium or chloride imbalances. In this study we present vitreous sodium and chloride levels from more than 3000 cases. We show that vitreous sodium and chloride levels both decrease with approximately 2.2mmol/L per day after death. Since potassium is a well-established marker for postmortem interval (PMI) and easily can be analyzed along with sodium and chloride, we have correlated sodium and chloride levels with the potassium levels and present postmortem reference ranges relative the potassium levels. We found that virtually all cases outside the reference range show signs of antemortem hypo- or hypernatremia. Vitreous sodium or chloride levels can be the only means to diagnose cases of water or salt intoxication, beer potomania or dehydration. We further show that postmortem vitreous sodium and chloride strongly correlate and in practice can be used interchangeably if analysis of one of the ions fails. It has been suggested that vitreous sodium and chloride levels can be used to diagnose drowning or to distinguish saltwater from freshwater drowning. Our results show that in cases of freshwater drowning, vitreous sodium levels are decreased, but that this mainly is an effect of postmortem diffusion between the eye and surrounding water rather than due to the drowning process, since the decrease in sodium levels correlates with immersion time. PMID:27105154

  13. On Barium Oxide Solubility in Barium-Containing Chloride Melts

    Science.gov (United States)

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

    2016-08-01

    Oxide solubility in chloride melts depends on temperature and composition of molten solvent. The solubility of barium oxide in the solvents with barium chloride content is essentially higher than that in molten alkali chlorides. Spectral data demonstrate the existence of oxychloride ionic groupings in such melts. This work presents the results of the BaO solubility in two molten BaCl2-NaCl systems with different barium chloride content. The received data together with earlier published results revealed the main regularities of BaO solubility in molten BaO-BaCl2-MCl systems.

  14. Catalytic Conversion of Cellulose to Levulinic Acid by Metal Chlorides

    Directory of Open Access Journals (Sweden)

    Beixiao Zhang

    2010-08-01

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

  15. Durability of cracked fibre reinforced concrete structures exposed to chlorides

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan De Place; Ekman, Tom; Hansen, Kurt Kielsgaard

    1999-01-01

    is used as environmental load. The chloride penetration is characterized both qualitatively (UV-test) and quantitatively (chloride profile) and by microscopy. The test programme involves three different concrete qualities. Both steel fibres and polypropylene fibres are used in the concrete beams as well......Durability studies are carried out by subjecting FRC-beams to combined mechanical and environmental load. Mechanical load is obtained by exposing beams to 4-point bending until a predefined crack width is reached, using a newly developed test setup. Exposure to a concentrated chloride solution...... as main reinforcement. The effect of the cracks, the fibres and the concrete quality on the chloride penetration is studied....

  16. Channel capacity and error exponents of variable rate adaptive channel coding for Rayleigh fading channels

    OpenAIRE

    Lau, KN

    1999-01-01

    We have evaluated the information theoretical performance of variable rate adaptive channel coding for Rayleigh fading channels. The channel states are detected at the receiver and fed back to the transmitter by means of a noiseless feedback link. Based on the channel state informations, the transmitter can adjust the channel coding scheme accordingly. Coherent channel and arbitrary channel symbols with a fixed average transmitted power constraint are assumed. The channel capacity and the err...

  17. Targeting ion channels in cystic fibrosis.

    Science.gov (United States)

    Mall, Marcus A; Galietta, Luis J V

    2015-09-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause a characteristic defect in epithelial ion transport that plays a central role in the pathogenesis of cystic fibrosis (CF). Hence, pharmacological correction of this ion transport defect by targeting of mutant CFTR, or alternative ion channels that may compensate for CFTR dysfunction, has long been considered as an attractive approach to a causal therapy of this life-limiting disease. The recent introduction of the CFTR potentiator ivacaftor into the therapy of a subgroup of patients with specific CFTR mutations was a major milestone and enormous stimulus for seeking effective ion transport modulators for all patients with CF. In this review, we discuss recent breakthroughs and setbacks with CFTR modulators designed to rescue mutant CFTR including the common mutation F508del. Further, we examine the alternative chloride channels TMEM16A and SLC26A9, as well as the epithelial sodium channel ENaC as alternative targets in CF lung disease, which remains the major cause of morbidity and mortality in patients with CF. Finally, we will focus on the hurdles that still need to be overcome to make effective ion transport modulation therapies available for all patients with CF irrespective of their CFTR genotype. PMID:26115565

  18. Quantum broadcast channels

    CERN Document Server

    Yard, J; Devetak, I; Yard, Jon; Hayden, Patrick; Devetak, Igor

    2006-01-01

    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...

  19. [Transport of large organic ions through syringomycin channels in the membranes containing dipole modifiers].

    Science.gov (United States)

    Efimova, S S; Ostroumova, O S; Malev, V V; Shchagina, L V

    2011-01-01

    The effect of the membrane dipole potential (Phid) on a conductance and a steady-state number of functioning channels formed by cyclic lipodepsipeptide syringomycin E (SRE) in bilayer lipid membranes made from phosphocholine and bathed in 0.4 M solution of sodium salts of aspartate, gluconate and chloride was shown. The magnitude of Phid was varied with the introduction to membrane bathing solutions of phloretin, which reduces the Phid, and RH 421, increasing the Phid. It was established that in all studied systems the increase in the membrane dipole potential cause a decrease in the steady-state number of open channels. In the systems containing sodium salts of aspartate (Asp) or gluconate (Glc), changes in the number of functioning channels are in an order of magnitude smaller than in systems containing sodium chloride. At the same time, the conductance (g) of single SRE-channels on the membranes bathed in NaCI solution increases with the increase in Phid, and in the systems containing NaAsp or NaGlc the conductance of single channels does not depend on the Phid. The latter is due to the lack of cation/anion selectivity of the SRE-channels in these systems. The different channel-forming activity of SRE in the experimental systems is defined by the gating charge of the channel and the partition coefficient of the dipole modifiers between the lipid and aqueous phases.

  20. HIPPI and Fibre Channel

    International Nuclear Information System (INIS)

    The High-Performance Parallel Interface (HIPPI) and Fibre Channel are near-gigabit per second data communications interfaces being developed in ANSI standards Task Group X3T9.3. HIPPI is the current interface of choice in the high-end and supercomputer arena, and Fibre Channel is a follow-on effort. HIPPI came from a local area network background, and Fibre Channel came from a mainframe to peripheral interface background

  1. Noncanonical binding of calmodulin to aquaporin-0: implications for channel regulation.

    Science.gov (United States)

    Reichow, Steve L; Gonen, Tamir

    2008-09-10

    Aquaporins (AQPs) are a family of ubiquitous membrane channels that conduct water across cell membranes. AQPs form homotetramers containing four functional and independent water pores. Aquaporin-0 (AQP0) is expressed in the eye lens, where its water permeability is regulated by calmodulin (CaM). Here we use a combination of biochemical methods and NMR spectroscopy to probe the interaction between AQP0 and CaM. We show that CaM binds the AQP0 C-terminal domain in a calcium-dependent manner. We demonstrate that only two CaM molecules bind a single AQP0 tetramer in a noncanonical fashion, suggesting a form of cooperativity between AQP0 monomers. Based on these results, we derive a structural model of the AQP0/CaM complex, which suggests CaM may be inhibitory to channel permeability by capping the vestibules of two monomers within the AQP0 tetramer. Finally, phosphorylation within AQP0's CaM binding domain inhibits the AQP0/CaM interaction, suggesting a temporal regulatory mechanism for complex formation. PMID:18786401

  2. THE COMPATIBILITY OF BLENDS OF POLY(VINYL CHLORIDE) OR CHLORINATED POLY(VINYL CHLORIDE) WITH POLY(METHYL METHACRYLATE)

    Institute of Scientific and Technical Information of China (English)

    WANG Qingguo; CHENG Rongshi

    1988-01-01

    IR spectral shifts of carbonyl vibrational absorption for ethyl acetate, which acts analogically as the structural unit of poly(methyl methacrylate), in cyclohexane, chloroform, chlorinated paraffins, poly(vinyl chloride) and chlorinated poly(vinyl chloride) were measured. The results suggest that there are specific interactions between the carbonyl groups and the chlorinated hydrocarbons which could be responsible for the apparent compatibility of poly(vinyl chloride) -poly(methyl methacrylate) and chlorinated poly(vinyl chloride) -poly(methyl methacrylate) blends. Additionally, the effects of the preparation mode of blend films on phase separation and observed compatibility are discussed.

  3. [Survey of plasticizers in polyvinyl chloride toys].

    Science.gov (United States)

    Abe, Yutaka; Yamaguchi, Miku; Mutsuga, Motoh; Hirahara, Yoshichika; Kawamura, Yoko

    2012-01-01

    Plasticizers in 101 samples of polyvinyl chloride (PVC) toys on the Japanese market were surveyed. No phthalates were detected in designated toys, though bis(2-ethylhexyl)phthalate, diisononyl phthalate, diisobutyl phthalate, dibutyl phthalate, diisodecyl phthalate and benzyl butyl phthalate were detected in more than half of other toys. 2,2,4-Tributyl-1,3-pentanediol diisobutylate, o-acetyl tributyl citrate, adipates and diacetyl lauroyl glycerol, which are alternative plasticizers to phthalates, were detected. The results of structural analysis confirmed the presence of di(2-ethylhexyl)terephthalate, tributyl citrate, diisononyl 1,2-cyclohexanedicarboxylate and neopentyl glycol esters; these have not previonsly been reported in Japan. There appears to be a shift in plasticizers used for designated toys from phthalates to new plasticizers, and the number of different plasticizers is increasing.

  4. Estimating the chloride transport in cement paste

    Directory of Open Access Journals (Sweden)

    Princigallo, A.

    2012-06-01

    Full Text Available A method was developed to measure the diffusion coefficient of chloride ions in cement paste based on an analytical solution to Fick’s 2nd law in a cylindrical coordinate system. This natural method yielded diffusivity results within as little as a month. Testing time was reduced by exploiting the three-dimensional inward flux in the specimen. In an attempt to determine the saturation concentration, dense portland cement pastes were exposed to a concentrated chloride solution. The method proved to be useful for exploring cement hydration-induced changes in the diffusion coefficient of cement paste.

    Se ha desarrollado un método para medir el coeficiente de difusión de los iones cloruro en la pasta de cemento, partiendo de una aplicación analítica de la segunda ley de Fick en un sistema de coordinadas cilíndrico. Este método, que es natural, demostró ser capaz de producir resultados de difusividad en tan solo un mes. Se consiguió reducir el tiempo de ensayo mediante el aprovechamiento de la tridimensionalidad del flujo desde el exterior al interior de la probeta. A fin de determinar la concentración de saturación, se sometieron las pastas de cemento Portland a una disolución de cloruros concentrada. Este método resultó ser útil en el estudio de los cambios del coeficiente de difusión de la pasta de cemento provocados por las reacciones de hidratación que tienen lugar en esta.

  5. A linearization of quantum channels

    Science.gov (United States)

    Crowder, Tanner

    2015-06-01

    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. Experimental and numerical investigation of chloride ingress in cracked concrete

    NARCIS (Netherlands)

    Šavija, B.

    2014-01-01

    Chloride induced corrosion of reinforcing steel is recognized as the most common deterioration mechanism affecting reinforced concrete structures. As such, it has been in focus of research for more than thirty years. Numerous studies of chloride ingress, corrosion initiation, and corrosion propagati

  7. Hydrophobic treatment of concrete as protection against chloride penetration

    NARCIS (Netherlands)

    Vries, J. de; Polder, R.B.; Borsje, H.

    1996-01-01

    Hydrophobic treatment makes a concrete surface absorb less water and less chloride. Hydrophobic treatment was studied as a protection agninst chloride penetration from deicing salts. Test methods were designed. Nine hydrophobic products were tested, of which three complied to the requirements on fin

  8. Microwave Mapping Demonstration Using the Thermochromic Cobalt Chloride Equilibrium

    Science.gov (United States)

    Nguyen, Vu D.; Birdwhistell, Kurt R.

    2014-01-01

    An update to the thermochromic cobalt(II) chloride equilibrium demonstration is described. Filter paper that has been saturated with aqueous cobalt(II) chloride is heated for seconds in a microwave oven, producing a color change. The resulting pink and blue map is used to colorfully demonstrate Le Châtelier's principle and to illuminate the…

  9. Local impermeant anions establish the neuronal chloride concentration

    DEFF Research Database (Denmark)

    Glykys, J; Dzhala, V; Egawa, K;

    2014-01-01

    Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of γ-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulat...

  10. Chlorides behavior in raw fly ash washing experiments

    International Nuclear Information System (INIS)

    Chloride in fly ash from municipal solid waste incinerators (MSWIs) is one of the obstructive substances in recycling fly ash as building materials. As a result, we have to understand the behavior of chlorides in recycling process, such as washing. In this study, we used X-ray absorption near edge structure (XANES) and X-ray diffraction (XRD) to study the chloride behavior in washed residue of raw fly ash (RFA). We found that a combination of XRD and XANES, which is to use XRD to identify the situation of some compounds first and then process XANES data, was an effective way to explain the chlorides behavior in washing process. Approximately 15% of the chlorine in RFA was in the form of NaCl, 10% was in the form of KCl, 51% was CaCl2, and the remainder was in the form of Friedel's salt. In washing experiments not only the mole percentage but also the amount of soluble chlorides including NaCl, KCl and CaCl2 decreases quickly with the increase of liquid to solid (L/S) ratio or washing frequency. However, those of insoluble chlorides decrease slower. Moreover, Friedel's salt and its related compound (11CaO.7Al2O3.CaCl2) were reliable standards for the insoluble chlorides in RFA, which are strongly related to CaCl2. Washing of RFA promoted the release of insoluble chlorides, most of which were in the form of CaCl2.

  11. Monte Carlo calculation of chloride diffusion in concrete

    International Nuclear Information System (INIS)

    Coefficient of chloride diffusion is calculated by applying the Fick's second law of diffusion to a chloride concentration profile. Then from the signal strength for various chlorine gamma-ray energies was then calculated at the detector of the portable D-D neutron generator based PGNAA setup. (author)

  12. 21 CFR 172.165 - Quaternary ammonium chloride combination.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION Food Preservatives § 172.165 Quaternary ammonium chloride combination. The food... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Quaternary ammonium chloride combination. 172.165 Section 172.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  13. Contribution on creep polygonization study in crystals. Creep of single crystalline silver chloride and sodium chloride

    International Nuclear Information System (INIS)

    Subgrain formation and their influence on plastic behavior of materials has been studied in the case of single crystals of silver chloride and sodium chloride crept at high temperature (T > 0.5 Tmelting). It is shown that the creep rate ε is a function of the mean subgrain diameter d. For secondary creep ε ∝ dk with k = 2 for NaCl and AgCl. During secondary creep, the substructure changes continuously: sub-boundaries migrate and sub-grains rotate. We find that sub-boundaries migration accounts for 35 pc of the total strain and that subgrain misorientation θ increases linearly with strain ε: θ ∝ 0.14 ε. The stability of permanent creep seems related to the power that the substructure is able to dissipate. The possible subgrain formation mechanisms are examined. It is shown that subgrain formation is closely related to the geometrical conditions of deformation and to the heterogeneities of this later. (author)

  14. Behavior and products of mechano-chemical dechlorination of polyvinyl chloride and poly (vinylidene chloride).

    Science.gov (United States)

    Xiao, Xiao; Zeng, Zigao; Xiao, Songwen

    2008-02-28

    The mechano-chemical (MC) dechlorination of polyvinyl chloride (PVC) and polyvinylidene chloride (PVDC) was performed by mechanical milling PVC/PVDC powder with zinc powder in a planetary ball mill, and the products of dechlorination were characterized by Infrared spectra (IR), X-ray diffraction (XRD), Raman spectroscopy, gas chromatography-mass spectrometry (GC-MS), and 13C solid-state nuclear magnetic resonance (NMR). The experimental results show that PVC/PVDC can be easily dechlorinated by milling with zinc powder, and formed various kinds of inorganic and organic products. Inorganic compounds included Zn2OCl(2).2H2O, Zn5(OH)8Cl2.H2O etc., and organic products involved diamond-like carbon, carbyne fragment, polyacetylene etc. Organic products formed following the paths of dechlorination, dehydrochlorination, crosslink, and oxidation. The mechano-chemical dechlorination process of PVC/PVDC may be an effective approach for carbyne synthesizing in the appropriate condition.

  15. RFI channels, 2

    Science.gov (United States)

    Mceliece, R. J.

    1981-01-01

    The cutoff parameters for a class of channel models exhibiting burst noise behavior were calculated and the performance of interleaved coding strategies was evaluated. It is concluded that, provided the channel memory is large enough and is properly exploited, interleaved coding is nearly optimal.

  16. PHASE EQUILIBRIUM FOR THE TERNARY SYSTEM VINYL CHLORIDE-CHLORINATED POLYETHYLENE-POLY (VINYL CHLORIDE)

    Institute of Scientific and Technical Information of China (English)

    LOU Jianfeng; WENG Zhixue; HUANG Zhiming; PAN Zuren

    1991-01-01

    Swelling capacity of vinyl chloride (VC) in chlorinated polyethylene (CPE) with 25- 40 wt% Cl at temperature 30- 57 ℃ was studied and their relationships were correlated with Langmuir and Freundlich adsorption equations. A ternary phase diagram for VC-CPE-PVC was also established.In-situ polymerization conditions of CPE-g -VC were proposed and CPE content control was analyzed for the manufacturing process of CPE-g-VC graft product based on results of phase equilibrium study.

  17. Athermalized channeled spectropolarimeter enhancement.

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Julia Craven; Way, Brandyn Michael; Mercier, Jeffrey Alan; Hunt, Jeffery P.

    2013-09-01

    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.

  18. Channelling versus inversion

    DEFF Research Database (Denmark)

    Gale, A.S.; Surlyk, Finn; Anderskouv, Kresten

    2013-01-01

    . Within this channel were smaller erosional structures (<10 m deep) that truncate originally horizontal bedding, are floored by hardgrounds, and locally have a basal fill of granular phosphorite. The entire channel system was progressively infilled by chalk, as demonstrated by the expanded succession of...... the lower Campanian Culver Chalk Formation. The beds of the channel fill are cut by small step faults, resulting from gravitational collapse. Complete burial had taken place by the base of the upper Campanian Portsdown Chalk Formation, which is of even thickness across the region. The structures are......Evidence from regional stratigraphical patterns in Santonian−Campanian chalk is used to infer the presence of a very broad channel system (5 km across) with a depth of at least 50 m, running NNW−SSE across the eastern Isle of Wight; only the western part of the channel wall and fill is exposed...

  19. Reconciling the Krogh and Ussing interpretations of epithelial chloride transport - presenting a novel hypothesis for the physiological significance of the passive cellular chloride uptake.

    Science.gov (United States)

    Larsen, Erik Hviid

    2011-07-01

    In 1937, August Krogh discovered a powerful active Cl(-) uptake mechanism in frog skin. After WWII, Hans Ussing continued the studies on the isolated skin and discovered the passive nature of the chloride uptake. The review concludes that the two modes of transport are associated with a minority cell type denoted as the γ-type mitochondria-rich (MR) cell, which is highly specialized for epithelial Cl(-) uptake whether the frog is in the pond of low [NaCl] or the skin is isolated and studied by Ussing chamber technique. One type of apical Cl(-) channels of the γ-MR cell is activated by binding of Cl(-) to an external binding site and by membrane depolarization. This results in a tight coupling of the uptake of Na(+) by principal cells and Cl(-) by MR cells. Another type of Cl(-) channels (probably CFTR) is involved in isotonic fluid uptake. It is suggested that the Cl(-) channels serve passive uptake of Cl(-) from the thin epidermal film of fluid produced by mucosal glands. The hypothesis is evaluated by discussing the turnover of water and ions of the epidermal surface fluid under terrestrial conditions. The apical Cl(-) channels close when the electrodiffusion force is outwardly directed as it is when the animal is in the pond. With the passive fluxes eliminated, the Cl(-) flux is governed by active transport and evidence is discussed that this is brought about by an exchange of cellular HCO(3) (-) with Cl(-) of the outside bath driven by an apical H(+) V-ATPase. PMID:21288306

  20. The earliest ion channels in protocellular membranes

    Science.gov (United States)

    Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

    indicates that their structures are unique and stable. In addition, it is also believed that the trichotoxin channel displays some selectivity between potassium and chloride ions. This makes trichotoxin and antiamoebin ideal models of the earliest ion channels that could provide insight into the origins of ion conductance and selectivity. In the absence of crystal structure of the trichotoxin and antiamoebin channels, we propose their molecular models based on experimentally determined number of monomers forming the bundles. We use molecular dynamics simulations to validate the models in terms of their conductance and selectivity. On the basis of our simulations we show that the emergence of channels built of small, α-helical peptides was protobiologically plausible and did not require highly specific amino acid sequences, which is a convenient evolutionary trait. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. To this end, we will discuss how the amino acid sequence and structure of primitive channels give rise to the phenomena of ionic conductance and selectivity across the earliest cell walls, which were essential functions for the emergence and early evolution of protocells. Furthermore, we will argue that 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.

  1. The Earliest Ion Channels in Protocellular Membranes

    Science.gov (United States)

    Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

    2010-01-01

    indicates that their structures are unique and stable. In addition, it is also believed that the trichotoxin channel displays some selectivity between potassium and chloride ions. This makes trichotoxin and antiamoebin ideal models of the earliest ion channels that could provide insight into the origins of ion conductance and selectivity. In the absence of crystal structure of the trichotoxin and antiamoebin channels, we propose their molecular models based on experimentally determined number of monomers forming the bundles. We use molecular dynamics simulations to validate the models in terms of their conductance and selectivity. On the basis of our simulations we show that the emergence of channels built of small, alpha-helical peptides was protobiologically plausible and did not require highly specific amino acid sequences, which is a convenient evolutionary trait. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. To this end, we will discuss how the amino acid sequence and structure of primitive channels give rise to the phenomena of ionic conductance and selectivity across the earliest cell walls, which were essential functions for the emergence and early evolution of protocells. Furthermore, we will argue that 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.

  2. Comparative effects of hydrogen chloride gas on tomato and chrysanthemum. I. Distribution and accumulation of chloride following exposure. II. Pathological anatomy of hydrogen chloride gas injury

    Energy Technology Data Exchange (ETDEWEB)

    Shriner, D.S.

    1969-01-01

    Hydrogen chloride (HCl) gas damage to plants has not been a historically important problem. However, recent practices in a number of industries, particularly glass manufacturing and pyrolysis of waste plastics, have increased the seriousness of the problem. Studies were carried out under carefully controlled exposure conditions to determine the effects of HCl gas on a relatively sensitive and a relatively resistant plant species. The macroscopic symptoms of most importance in acute damage to tomato and chrysanthemum are glazing of the lower surface, and a bifacial bronzing of interveinal and marginal areas of leaves. Microscopically, glazing was shown to be caused by a collapse of the lower epidermal cells and a partial disorganization of the spongy mesophyll of leaves. Bronzing was shown to be caused by the further collapse of the spongy mesophyll, and in some cases the palisade mesophyll and upper epidermis. Analysis of plant tissues for their free chloride content following an exposure to HCl gas was done with cell-free water extracts which were titrated on an automatic chloride titrator. On the basis of such studies, evidence suggest that the mechanism of accumulation of chlorides in plants is similar to that of fluorides, and that in subacute doses, chlorides are translocated toward the extremities of the foliar portions of the plant. In areas where a number of different types of pollution sources exist, and symptomotology is not definitive in pinpointing the source, chloride analysis of plant tissues should prove valuable as an aid to diagnosis if HCl gas was suspected.

  3. Physiology of Epithelial Chloride and Fluid Secretion

    OpenAIRE

    Frizzell, Raymond A.; Hanrahan, John W.

    2012-01-01

    Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epi...

  4. Studies on Hypokalemia Induced by Trimethyltin Chloride

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To determine the possible relationship between plasma potassium concentration and severity of acute trimethyltin chloride (TMT) poisoning and to assess the mechanism of TMT induced hypokalemia. Methods SD rats were treated with various dosages of TMT (ip). All the indices were measured and analysed for determing their possible relations with plasma K+. Results With increase of dosage, the plasma K+ level dropped rapidly, and deaths appeared more quickly. The LDs0 of TMT (ip) was 14.7 mg/kgbw. In the low dosage group (10 mg/kgbw), the plasma K+ level dropped slowly with the lowest dosage on day 6 (4.85 mmol/L). It rose again on day 11 (5.06 mmol/L), and recoverd on day 28. The poisoning signs corresponded with decline of the span of K+ level. The plasma Na+ level dropped half an hour after TMT treatment, but recovered 24 h later. In the high dosage group (46.4 mg/kgbw), the levels of plasma K+ and Na+ fell rapidly within half an hour (P<0.05), the intracellular potassium concentration of RBC did not decrerase obviously (P>0.05), the activities of Na+-K+-ATPase and Mg2+-ATPase in RBC membrane were depressed remarkably (P<0.01, P<0.05, respectively), the plasma aldosterone concentrations rose as high as tenfold (P<0.01), the arterial blood pH fell from 7.434 to 7.258 (P<0.01),pCO2 was raised from 29.62 to 45.33 mmHg (P<0.01). In the 24 h urine test, when rats were treated with TMT (21.5 mg/kgbw, ip), urine volume, urinary potassium, sodium and chloride increased significantly in comparison with those in the controls (P<0.01). Conclusion TMT could induce hypokalemia in SD rats. The available evidence suggests that TMT can induce acute renal leakage of potassium. At the same time, a significant rise of plasma aldosterone may play an important role in promoting potassium leakage from kidney to result in severe hypokalemia with inhaling acid-base abnormalities produced, which aggravate the poisoning symptoms. In the end the rats would die of respiratory

  5. [3H]PN200-110 and [3H]ryanodine binding and reconstitution of ion channel activity with skeletal muscle membranes

    International Nuclear Information System (INIS)

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

  6. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille

    2015-01-01

    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....

  7. Redetermination of 1-carboxycyclohexan-1-aminium chloride

    Directory of Open Access Journals (Sweden)

    Teresa González

    2009-02-01

    Full Text Available The crystal structure of the title compound, C7H14NO2+·Cl−, was reported previously [Chacko, Srinivasan & Zand (1975. J. Cryst. Mol. Struct. 5, 353–357] from Weissenberg photographic data with R = 0.113. It has now been redetermined, providing a significant increase in the precision of the derived geometric parameters, viz. mean σ(C—C = 0.003 Å in the present work compared with 0.021 Å for the previous work. The complete cation is generated by crystallographic mirrror symmetry, with three C atoms, two O atoms and the N atom lying on the reflecting plane; the chloride anion also has m site symmetry. The crystal structure is established by a two-dimensional network of O—H...Cl and N—H...Cl hydrogen bonds, generating C12(4 and C12(7 chains, and R24(8 and R24(14 rings.

  8. Chloride, bromide and iodide scintillators with europium

    Energy Technology Data Exchange (ETDEWEB)

    Zhuravleva, Mariya; Yang, Kan

    2016-09-27

    A halide scintillator material is disclosed where the halide may comprise chloride, bromide or iodide. The material is single-crystalline and has a composition of the general formula ABX.sub.3 where A is an alkali, B is an alkali earth and X is a halide which general composition was investigated. In particular, crystals of the formula ACa.sub.1-yEu.sub.yI.sub.3 where A=K, Rb and Cs were formed as well as crystals of the formula CsA.sub.1-yEu.sub.yX.sub.3 (where A=Ca, Sr, Ba, or a combination thereof and X=Cl, Br or I or a combination thereof) with divalent Europium doping where 0.ltoreq.y.ltoreq.1, and more particularly Eu doping has been studied at one to ten mol %. The disclosed scintillator materials are suitable for making scintillation detectors used in applications such as medical imaging and homeland security.

  9. NQR in tert-butyl chloride

    Science.gov (United States)

    Brunetti, Aldo H.

    2004-03-01

    Tert-butyl chloride has been broadly studied experimentally through various techniques such as X-ray crystallography, DTA, and NMR. It was also studied experimentally through nuclear quadrupole resonance (NQR), but this study was limited and incomplete. In this paper, we present a more detailed study of TBC through the NQR of 35Cl. Our results show that near 120 K, the onset of the CH 3 groups semirotations around symmetry axis C3 takes place with an activation energy U=16.1 kJ mol -1. This intramolecular movement produces a T1 minimum near 148 K and is the dominant mechanism of the nuclear spin-lattice relaxation in phase III of this compound. In phase II of TBC, we show that there are not only methyl groups semirotations, but also semirotations of the whole molecule around a different axis from the symmetry axis C' 3 (C-Cl bond) with an activation energy of E=10.4 kJ mol -1.

  10. Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs

    OpenAIRE

    Desaphy, Jean-François; Carbonara, Roberta; Costanza, Teresa; Conte Camerino, Diana

    2014-01-01

    Although the sodium channel blocker mexiletine is considered the first-line drug in myotonia, some patients experiment adverse effects, while others do not gain any benefit. Other antimyotonic drugs are thus needed to offer mexiletine alternatives. In the present study, we used a previously-validated rat model of myotonia congenita to compare six marketed sodium channel blockers to mexiletine. Myotonia was induced in the rat by injection of anthracen-9-carboxylic acid, a muscle chloride chann...

  11. A Simple Water Channel

    Science.gov (United States)

    White, A. S.

    1976-01-01

    Describes a simple water channel, for use with an overhead projector. It is run from a water tap and may be used for flow visualization experiments, including the effect of streamlining and elementary building aerodynamics. (MLH)

  12. 28-Channel rotary transformer

    Science.gov (United States)

    Mclyman, W. T.

    1981-01-01

    Transformer transmits power and digital data across rotating interface. Array has many parallel data channels, each with potential l megabaud data rate. Ferrite-cored transformers are spaced along rotor; airgap between them reduces crosstalk.

  13. Channelized Streams in Iowa

    Data.gov (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...

  14. CHANNEL ESTIMATION TECHNIQUE

    DEFF Research Database (Denmark)

    2015-01-01

    A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over the communicat......A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over the...... communication channel. The method further includes determining a sequence of second coefficient estimates of the communication channel based on a decomposition of the first coefficient estimates in a dictionary matrix and a sparse vector of the second coefficient estimates, the dictionary matrix including...

  15. Sensing with Ion Channels

    CERN Document Server

    Martinac, Boris

    2008-01-01

    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.

  16. TRP channels in disease.

    Science.gov (United States)

    Jordt, S E; Ehrlich, B E

    2007-01-01

    The transient receptor potential (TRP) channels are a large family of proteins with six main subfamilies termed the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin) groups. The sheer number of different TRPs with distinct functions supports the statement that these channels are involved in a wide range of processes ranging from sensing of thermal and chemical signals to reloading intracellular stores after responding to an extracellular stimulus. Mutations in TRPs are linked to pathophysiology and specific diseases. An understanding of the role of TRPs in normal physiology is just beginning; the progression from mutations in TRPs to pathophysiology and disease will follow. In this review, we focus on two distinct aspects of TRP channel physiology, the role of TRP channels in intracellular Ca2+ homeostasis, and their role in the transduction of painful stimuli in sensory neurons. PMID:18193640

  17. Denitrification of fertilizer wastewater at high chloride concentration

    DEFF Research Database (Denmark)

    Ucisik, Ahmed Süheyl; Henze, Mogens

    Wastewater from fertilizer industry is characterized by high contents of chloride concentration, which normally vary between 60 and 76 g/l. Experiments with bilogical denitrification were performed in lab-scale "fill and draw" reactors with synthetic wastewater with chloride concentrations up to 77.......4 g/l. The results of the experiments showed that biological denitrification was feasible at the extreme environmental conditions prevailing in fertilizer wastewater. Stable continuous biological denitrfication of the synthetic high chloride wastewater was performed up to 77.4 g Cl/l at 37 degree C...

  18. Calcium chloride in stabilised soil roads and runways

    Directory of Open Access Journals (Sweden)

    Harsh Vardhan

    1952-09-01

    Full Text Available Mudless, dustless, hard and all weather driving surfaces is a serious requirement of the forces.  surfacing by mixtures of definite amounts of locally available stone, gravel, sand, clay and Silt to which calculated amount of calcium chloride is added quickly compact and ultimately harden like concrete. This provides an easy, quick and economic- means of meeting the requirement.  Necessity of such surfaces, use and action of calcium chloride and resulting effects are discussed. Different methods of construction and application of calcium chloride are briefly related.

  19. Durability Analysis of Subway Station in Chloride Environment

    Directory of Open Access Journals (Sweden)

    Yang LuFeng

    2013-02-01

    Full Text Available In this study, a finite element model for chloride ions transport in saturated concrete was proposed based on the Fick’s second law of diffusion. The governing partial differential equation was solved numerically in space as a boundary-value problem and in time as an initial-value problem by means of the finite element formulations. The maximum allowable value of chloride diffusion coefficient within different locations of subway station with service life of 100a was achieved and suggestions for durability analysis of subway station in chloride environment were also proposed.

  20. The ionic product of water in concentrated tetramethylammonium chloride solutions.

    Science.gov (United States)

    Sipos, P; Bódi, I; May, P M; Hefter, G T

    1997-04-01

    The ionic product of water, pK(w) = - log[H(+)][OH(-)] has been determined in aqueous solutions of tetramethylammonium chloride over the concentration range of 0.1-5.5 M at 25 degrees C using high-precision glass electrode potentiometric titrations. pK(w) data relating to aqueous potassium and sodium chlorides at ionic strengths up to 5 M are markedly lower than the tetramethylammonium chloride results. These differences are almost certainly due to weak associations between potassium and (especially) sodium and hydroxide ions.

  1. Ionometric determination of chloride ion in circulating and waste waters

    Energy Technology Data Exchange (ETDEWEB)

    Bebeshko, G.I.; Afanas' eva, V.I.; Danielova, I.I.; Dmitriev, M.A.; Radchenko, A.F.

    1986-09-01

    The authors attempt to develop selective ionometric methods to determine chloride ion in waste and circulating waters from technological ore processing, containing significant amounts of sulfide ion and various flotation reagents. These waters contain practically no cations that form hard to dissolve compounds with chloride ion such as Ag/sup +/, Cu/sup +/, Hg/sup +/ or Pb/sup 2 +/. The chloride ion concentration in water varies between 10 and 100 mg/liter. Information is shown on the concentration of the main anions and flotation reagents in waters that were analyzed.

  2. Stochastic Modeling of Reinforced Concrete Structures Exposed to Chloride Attack

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Frier, Christian

    2003-01-01

    concentration and reinforcement cover depth are modeled by stochastic fields. The paper contains a description of the parameters to be included in a stochastic model and a proposal for the information needed to obtain values for the parameters in order to be ab le to perform reliability investigations...... the reinforcement exceeds a critical threshold value. In the present paper a stochastic model is described by which the chloride content in a reinforced concrete structure can be estimated. The chloride ingress is modeled by a 2-dimensional diffusion process and the diffusion coefficient, surface chloride...

  3. Physics of Ion Channels

    OpenAIRE

    Kuyucak, Serdar; Bastug, Turgut

    2003-01-01

    We review the basic physics involved in transport of ions across membrane channels in cells. Electrochemical forces that control the diffusion of ions are discussed both from microscopic and macroscopic perspectives. A case is made for use of Brownian dynamics as the minimal phenomenological model that provides a bridge between experiments and more fundamental theoretical approaches. Application of Brownian and molecular dynamics methods to channels with known molecular structures is discussed.

  4. Identification Via Quantum Channels

    OpenAIRE

    Winter, Andreas

    2012-01-01

    We review the development of the quantum version of Ahlswede and Dueck's theory of identification via channels. As is often the case in quantum probability, there is not just one but several quantizations: we know at least two different concepts of identification of classical information via quantum channels, and three different identification capacities for quantum information. In the present summary overview we concentrate on conceptual points and open problems, referring the reader to the ...

  5. Quantum Feedback Channels

    OpenAIRE

    Bowen, Garry

    2002-01-01

    In Shannon information theory the capacity of a memoryless 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 memo...

  6. Chaos in quantum channels

    OpenAIRE

    Hosur, Pavan; Qi, Xiao-Liang; Roberts, Daniel; Yoshida, Beni(Institute for Quantum Information & Matter and Walter Burke Institute for Theoretical Physics, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, U.S.A.)

    2016-01-01

    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 channe...

  7. Course on Ionic Channels

    CERN Document Server

    1986-01-01

    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...

  8. Applicability of boron-doped diamond electrode to the degradation of chloride-mediated and chloride-free wastewaters

    International Nuclear Information System (INIS)

    The electrochemical degradation of chloride-mediated and chloride-free dye wastewaters was investigated on a boron-doped diamond (BDD) electrode in comparison with that on a dimensionally stable anode (DSA), and the applicability of BDD electrode to the degradation of these two kinds of wastewaters was explored. In chloride-free wastewater, the electrochemical degradation efficiency of dye on BDD electrode was much higher than that on DSA, with a chemical oxygen demand (COD) removal of 100% and 26% for BDD and DSA, respectively. In chloride-mediated dye wastewater, COD removal was faster than that in chloride-free wastewater on both BDD and DSA electrodes with COD removal efficiencies higher than 95%, whereas the rate of COD removal on DSA was faster than that on BDD electrode. The investigation indicates that DSA is more suitable than BDD electrode in degradation of originally chloride contained dye wastewaters for the sake of energy and time saving. However, for chloride-free dye wastewaters, with the aim of environmental protection, BDD electrode is more appropriate to realize complete mineralization. At the same time, the secondary pollution can be avoided

  9. Adsorption of Tetradecylpyridinium Chloride on Aqueous Surfaces of Sodium Chloride Solutions

    OpenAIRE

    Fujio, Katsuhiko; Hayashi, Koji; Suzuki, Maki

    2014-01-01

    Surface tension of aqueous NaCl solutions of tetradecylpyridinium chloride (TPC) has been measured by the drop weight method at different NaCl concentrations from 0 to 1.000 mol dm−3 at 25◦C. Surface excess densities of tetradecylpyridinium ion (TP+), Cl− and Na+ have been obtained as functions of TPC concentration at different NaCl concentrations by applying the Gibbs adsorption isotherm to the surface tension data below the critical micelle concentration (CMC) of TPC. Surface excess densiti...

  10. Adsorption of Dodecylpyridinium Chloride on Aqueous Surfaces of Sodium Chloride Solutions

    OpenAIRE

    Fujio, Katsuhiko; TAKEUCHI, Kumiko; Suzuki, Maki

    2012-01-01

    Surface tension of aqueous NaCl solutions of dodecylpyridinium chloride (DPC) has been measured by the drop weight method at different NaCl concentrations from 0 to 1.000 mol dm-3 at 25℃. Applying the Gibbs adsorption isotherm to the surface tension data at DPC concentrations below the critical micelle concentration (CMC), surface excess densities of dodecylpyridinium ion (DP+), Cl- and Na+ have been obtained as functions of DPC concentration at different NaCl concentrations. Surface excess d...

  11. Channelling the Emperor: what really killed Napoleon?

    Science.gov (United States)

    Mari, Francesco; Bertol, Elisabetta; Fineschi, Vittorio; Karch, Steven B

    2004-08-01

    Arsenic was present in Napoleon's hair before he arrived on Saint Helena and the findings at necropsy are consistent only with the diagnosis of ulcerating, regionally invasive, gastric carcinoma. The question of whether Napoleon died of, or merely with, arsenic poisoning is illuminated by developments in the treatment of promyelocytic leukaemia. Arsenic trioxide induces remission in many, but treatment can be complicated by QT prolongation, torsades de pointes and sudden death. At clinically relevant concentrations, arsenic blocks both I(Kr) and I(ks) channels and, at the same time, activates I(K-ATP) channels. The balance of these forces is easily disrupted, and QT prolongation is worsened by hypokalaemia. Napoleon was chronically treated with tartar emetic for gastrointestinal symptoms, and the day before he died he was given a huge dose of calomel (mercurous chloride) as a purgative. Both treatments would have caused potassium wastage. In addition, the Emperor was being treated with a decoction containing 'bark'-presumably 'Jesuit's bark'. The quinine in Jesuit's bark is another cause of QT prolongation. It is likely that the immediate cause of the Emperor's death was torsades de pointes, brought on by chronic exposure to arsenic and a medication error.

  12. Functional reconstitution and channel activity measurements of purified wildtype and mutant CFTR protein.

    Science.gov (United States)

    Eckford, Paul D W; Li, Canhui; Bear, Christine E

    2015-03-09

    The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a unique channel-forming member of the ATP Binding Cassette (ABC) superfamily of transporters. The phosphorylation and nucleotide dependent chloride channel activity of CFTR has been frequently studied in whole cell systems and as single channels in excised membrane patches. Many Cystic Fibrosis-causing mutations have been shown to alter this activity. While a small number of purification protocols have been published, a fast reconstitution method that retains channel activity and a suitable method for studying population channel activity in a purified system have been lacking. Here rapid methods are described for purification and functional reconstitution of the full-length CFTR protein into proteoliposomes of defined lipid composition that retains activity as a regulated halide channel. This reconstitution method together with a novel flux-based assay of channel activity is a suitable system for studying the population channel properties of wild type CFTR and the disease-causing mutants F508del- and G551D-CFTR. Specifically, the method has utility in studying the direct effects of phosphorylation, nucleotides and small molecules such as potentiators and inhibitors on CFTR channel activity. The methods are also amenable to the study of other membrane channels/transporters for anionic substrates.

  13. Identification of a Natural Green Light Absorbing Chloride Conducting Channelrhodopsin from Proteomonas sulcata.

    Science.gov (United States)

    Wietek, Jonas; Broser, Matthias; Krause, Benjamin S; Hegemann, Peter

    2016-02-19

    Chloride conducting channelrhodopsins (ChloCs) are new members of the optogenetic toolbox that enable neuronal inhibition in target cells. Originally, ChloCs have been engineered from cation conducting channelrhodopsins (ChRs), and later identified in a cryptophyte alga genome. We noticed that the sequence of a previously described Proteomonas sulcata ChR (PsChR1) was highly homologous to the naturally occurring and previously reported ChloCs GtACR1/2, but was not recognized as an anion conducting channel. Based on electrophysiological measurements obtained under various ionic conditions, we concluded that the PsChR1 photocurrent at physiological conditions is strongly inward rectifying and predominantly carried by chloride. The maximum activation was noted at excitation with light of 540 nm. An initial spectroscopic characterization of purified protein revealed that the photocycle and the transport mechanism of PsChR1 differ significantly from cation conducting ChRs. Hence, we concluded that PsChR1 is an anion conducting ChR, now renamed PsACR1, with a red-shifted absorption suited for multicolor optogenetic experiments in combination with blue light absorbing cation conducting ChRs.

  14. Morphodynamics of Floodplain Chute Channels

    Science.gov (United States)

    David, S. R.; Edmonds, D. A.

    2015-12-01

    Floodplain chute channel formation is a key process that can enable rivers to transition from single-thread to multi-thread planform geometries. Floodplain chute channels are usually incisional channels connecting topographic lows across point bars and in the floodplain. Surprisingly, it is still not clear what conditions promote chute channel formation and what governs their morphodynamic behavior. Towards this end we have initiated an empirical and theoretical study of floodplain chute channels in Indiana, USA. Using elevation models and satellite imagery we mapped 3064 km2 of floodplain in Indiana, and find that 37.3% of mapped floodplains in Indiana have extensive chute channel networks. These chute channel networks consist of two types of channel segments: meander cutoffs of the main channel and chute channels linking the cutoffs together. To understand how these chute channels link meander cutoffs together and eventually create floodplain channel networks we use Delft3D to explore floodplain morphodynamics. Our first modeling experiment starts from a generic floodplain prepopulated with meander cutoffs to test under what conditions chute channels form.We find that chute channel formation is optimized at an intermediate flood discharge. If the flood discharge is too large the meander cutoffs erosively diffuse, whereas if the floodwave is too small the cutoffs fill with sediment. A moderately sized floodwave reworks the sediment surrounding the topographic lows, enhancing the development of floodplain chute channels. Our second modeling experiments explore how floodplain chute channels evolve on the West Fork of the White River, Indiana, USA. We find that the floodplain chute channels are capable of conveying the entire 10 yr floodwave (Q=1330m3/s) leaving the inter-channel areas dry. Moreover, the chute channels can incise into the floodplain while the margins of channels are aggrading, creating levees. Our results suggest that under the right conditions

  15. Nickel Chloride Promoted Glaser Coupling Reaction in Hot Water

    Institute of Scientific and Technical Information of China (English)

    Pin Hua LI; Lei WANG; Min WANG; Jin Can YAN

    2004-01-01

    A Glaser coupling reaction of terminal alkynes in the presence of nickel chloride without any organics and bases in hot water has been developed, which produces the corresponding homo-coupling products in good yields.

  16. Methyltrioctylammonium chloride catalysed sonochemical synthesis of acridine diones

    Indian Academy of Sciences (India)

    Bhupinder Kaur; Harish Kumar

    2013-09-01

    The greener, clean and efficient protocol for the synthesis of acridine diones derivatives has been achieved by reacting aromatic aldehyde, dimedone and amines using methyltrioctylammonium chloride (Aliquate 336) as a catalyst under ultrasonic irradiations.

  17. Use of saturated sodium chloride solution as a tissue fixative

    Directory of Open Access Journals (Sweden)

    A. Al-Saraj

    2010-01-01

    Full Text Available The present study was carried out to examine the capability of saturated sodium chloride solution as a fixative agent instead of formalin which is regarded as a carcinogenic material. For this purpose 3 rabbits were used and their livers, kidneys and spleens were exposed and removed. Neutral buffered formalin solution, saturated sodium chloride solution and distilled water were used as fixatives for specimens obtained from the first, second and third rabbits respectively. Routine histological technique was performed to prepare a stained histological sections for light microscopic examination. The result showed that the tissue sections which were obtained by using sodium chloride have the same histological features and without any artifacts when they compared with the results obtained using formalin fixation method. We conclude that the saturated sodium chloride solution can be used as a fixative agent in some circumstances when no any fixative agent is available.

  18. Thermodynamic calculation of self-diffusion in sodium chloride

    Science.gov (United States)

    Zhang, Baohua; Li, Chengbo; Shan, Shuangming

    2016-05-01

    Using the available pressure-volume-temperature equation of state of sodium chloride, we show that the self-diffusion coefficients of sodium and chloride in sodium chloride as a function of temperature and pressure can be successfully reproduced in terms of bulk elastic and expansivity data. We use a thermodynamic model that interconnects point-defect parameters with bulk properties. Our calculated diffusion coefficients and point-defect parameters, including activation enthalpy, activation entropy, and activation volume, well agree with reported experimental results when uncertainties are considered. Furthermore, the ionic conductivity of sodium chloride inferred from our predicted diffusivities of sodium through the Nernst-Einstein equation is compared with previous experimental data.

  19. Catalytic Decomposition of Methylene Chloride by Sulfated Titania Catalysts

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Catalytic decomposition of methylene chloride in air below 300℃ was studied.Sulfated titania was very effective in converting 959ppm methylene chloride selectively to CO,CO2 and HCl.Complete decomposition of methylene chloride was achieved at low temperature(275℃).It was found that the acidic property of catalyst was a determinant factor for the catalytic activity.The presence of water vapor in the feed stream remarkably reduced the catalytic activity,which could be due to the blockage of acidic sites on the surface of catalyst by water molecules.A bifunctional catalyst comprising copper oxide was developed to improve the selectivity of catalytic oxidation,which indicated that copper oxide can promote the deep oxidation of methylene chloride.The crystal form of TiO2 imposes an important influence upon the catalytic oxidation.

  20. Chloride supporting electrolytes for all-vanadium redox flow batteries.

    Science.gov (United States)

    Kim, Soowhan; Vijayakumar, M; Wang, Wei; Zhang, Jianlu; Chen, Baowei; Nie, Zimin; Chen, Feng; Hu, Jianzhi; Li, Liyu; Yang, Zhenguo

    2011-10-28

    This paper examines vanadium chloride solutions as electrolytes for an all-vanadium redox flow battery. The chloride solutions were capable of dissolving more than 2.3 M vanadium at varied valence states and remained stable at 0-50 °C. The improved stability appeared due to the formation of a vanadium dinuclear [V(2)O(3)·4H(2)O](4+) or a dinuclear-chloro complex [V(2)O(3)Cl·3H(2)O](3+) in the solutions over a wide temperature range. The all-vanadium redox flow batteries with the chloride electrolytes demonstrated excellent reversibility and fairly high efficiencies. Only negligible, if any, gas evolution was observed. The improved energy capacity and good performance, along with the ease in heat management, would lead to substantial reduction in capital cost and life-cycle cost, making the vanadium chloride redox flow battery a promising candidate for stationary applications. PMID:21922094

  1. Stochastic modeling of reinforced concrete structures exposed to chloride attack

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Frier, Christian

    2004-01-01

    For many reinforced concrete structures corrosion of reinforcement is an important problem since it can result in expensive maintenance and repair actions. Further, a significant reduction of the load-bearing capacity can occur. One mode of corrosion initiation is that the chloride content around...... the reinforcement exceeds a critical threshold value. In the present paper a stochastic model is described by which the chloride content in a reinforced concrete structure can be estimated. The chloride ingress is modeled by a 2-dimensional diffusion process and the diffusion coefficient, surface chloride...... concentration and reinforcement cover depth are modeled by stochastic fields. The paper contains a description of the parameters to be included in a stochastic model and a proposal for the information needed to obtain values for the parameters in order to be able to perform reliability investigations...

  2. Chloride supporting electrolytes for all-vanadium redox flow batteries.

    Science.gov (United States)

    Kim, Soowhan; Vijayakumar, M; Wang, Wei; Zhang, Jianlu; Chen, Baowei; Nie, Zimin; Chen, Feng; Hu, Jianzhi; Li, Liyu; Yang, Zhenguo

    2011-10-28

    This paper examines vanadium chloride solutions as electrolytes for an all-vanadium redox flow battery. The chloride solutions were capable of dissolving more than 2.3 M vanadium at varied valence states and remained stable at 0-50 °C. The improved stability appeared due to the formation of a vanadium dinuclear [V(2)O(3)·4H(2)O](4+) or a dinuclear-chloro complex [V(2)O(3)Cl·3H(2)O](3+) in the solutions over a wide temperature range. The all-vanadium redox flow batteries with the chloride electrolytes demonstrated excellent reversibility and fairly high efficiencies. Only negligible, if any, gas evolution was observed. The improved energy capacity and good performance, along with the ease in heat management, would lead to substantial reduction in capital cost and life-cycle cost, making the vanadium chloride redox flow battery a promising candidate for stationary applications.

  3. Solidification of spent TBP solvent with aluminium chloride compounds

    International Nuclear Information System (INIS)

    The new techniques for processing spent TBP was investigated. It was proved that treatment of TBP containing DBP with aluminium chloride resulted in the formation of aluminium phosphate suitable for long term storage and final disposal

  4. Reinforcement corrosion in alkaline chloride media with reduced oxygen concentrations

    International Nuclear Information System (INIS)

    It is commonly considered that the corrosion of steel in concrete is controlled by the oxygen content of the pore solution and there are service life models that relate the corrosion rate to the amount of oxygen. It is also commonly believed that in water saturated conditions the oxygen content in the pores is negligible and that underwater there is no risk of depassivation and the corrosion rate is very low. However, the available data on corrosion rates in immersed conditions do not indicate such performance; on the contrary corrosion develops when sufficient chloride reaches the reinforcement. In the present paper, results are presented for tests performed in alkaline chloride solutions that were purged with nitrogen to reduce the oxygen content. The results indicate that at very low oxygen concentrations, corrosion may develop in the presence of chlorides. The presence or absence of corrosion is influenced by the amount of chloride, the corrosion potential and the steel surface condition. (authors)

  5. Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels.

    Science.gov (United States)

    Zemkova, Hana; Tomić, Melanija; Kucka, Marek; Aguilera, Greti; Stojilkovic, Stanko S

    2016-04-01

    Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage-insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling.

  6. Voltage-gated potassium channel Kvl.3 in rabbit ciliary epithelium regulates the membrane potential via coupling intracellular calcium

    Institute of Scientific and Technical Information of China (English)

    LI Yan-feng; ZHUO Ye-hong; BI Wei-na; BAI Yu-jing; LI Yan-na; WANG Zhi-jian

    2008-01-01

    Background The cell layer of the ciliary epithelium is responsible for aqueous humor secretion and maintenance.Ion channels play an important role in these processes.The main aim of this study was to determine whether the well-characterized members of the Kvl family (Kv1.3) contribute to the Kv currents in ciliary epithelium.Methods New Zealand White rabbits were maintained in a 12 hours light/dark cycle.Ciliary epithelium samples were isolated from the rabbits.We used Western blotting and immunocytochemistry to identify the expression and location of a voltage-gated potassium channel Kvl.3 in ciliary body epithelium.Membrane potential change after adding of Kv1.3 inhibitor margatoxin (MgTX) was observed with a fluorescence method.Results Western blotting and immunocytochemical studies showed that the Kv1.3 protein expressed in pigment ciliary epithelium and nonpigment ciliary epithelium,however it seemed to express more in the apical membrane of the nonpigmented epithelial cells.One nmol/L margatoxin,a specific inhibitor of Kv1.3 channels caused depolarization of the cultured nonpigmented epithelium (NPE) membrane potential.The cytosotic calcium increased after NPE cell depolarization,this increase of cytosolic calcium was partially blocked by 12.5 μmol/L dantrolene and 10 μmol/L nifedipine.These observations suggest that Kv1.3 channels modulate ciliary epithelium potential and effect calcium dependent mechanisms.Conclusion Kv1.3 channels contribute to K+ efflux at the membrane of rabbit ciliary epithelium.

  7. Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel

    International Nuclear Information System (INIS)

    Highlights: → Both Ca++-Calmodulin (CaM) and Ca++-free CaM bind to the C-terminal region of Nav1.1. → Ca++ and CaM have both opposite and convergent effects on INav1.1. → Ca++-CaM modulates INav1.1 amplitude. → CaM hyperpolarizes the voltage-dependence of activation, and increases the inactivation rate. → Ca++ alone antagonizes CaM for both effects, and depolarizes the voltage-dependence of inactivation. -- Abstract: Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a stably transfected HEK-293 cell line. The C-terminal region of the channel, as a fusion protein or in the yeast two-hybrid system, interacted with CaM via a consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1 cells showed that CaM overexpression increased peak current in a calcium-dependent way. CaM had no effect on the voltage-dependence of fast inactivation, and accelerated the inactivation kinetics. Elevating Ca++ depolarized the voltage-dependence of fast inactivation and slowed down the fast inactivation kinetics, and for high concentrations this effect competed with the acceleration induced by CaM alone. Similarly, the depolarizing action of calcium antagonized the hyperpolarizing shift of the voltage-dependence of activation due to CaM overexpression. Fluorescence spectroscopy measurements suggested that Ca++ could bind the Nav1.1 C-terminal region with micromolar affinity.

  8. Chlorides behavior in raw fly ash washing experiments

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Fenfen, E-mail: zhu@hse.gcoe.kyoto-u.ac.jp [Department of Urban and Environmental Engineering, Graduate School of Engineering, Katsura Campus, Kyoto University, Nishikyo-ku, Kyoto 615-8540 (Japan); Takaoka, Masaki; Oshita, Kazuyuki [Department of Urban and Environmental Engineering, Graduate School of Engineering, Katsura Campus, Kyoto University, Nishikyo-ku, Kyoto 615-8540 (Japan); Kitajima, Yoshinori; Inada, Yasuhiro [High Energy Accelerator Research Organization (KEK), Institute of Material Structure Science (IMSS), Oho 1-1, Tsukuba, Ibaraki 305-0801 (Japan); Morisawa, Shinsuke; Tsuno, Hiroshi [Department of Urban and Environmental Engineering, Graduate School of Engineering, Katsura Campus, Kyoto University, Nishikyo-ku, Kyoto 615-8540 (Japan)

    2010-06-15

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

  9. Determination of chloride in geological samples by ion chromatography

    Science.gov (United States)

    Wilson, S.A.; Gent, C.A.

    1983-01-01

    Samples of silicate rocks are prepared by sodium carbonate fusion and then treated by ion chromatography. The method was tested for geological standards with chloride concentration between 0.003 and 3%. Observed chloride concentrations comparedd favorably with literature values. The relative standard deviation and detection limit for the method were 8% and 7 ppm, respectively. Up to 30 determination per 24-hour period were possible. ?? 1983.

  10. Optical Studies on Sol-Gel Derived Lead Chloride Crystals

    OpenAIRE

    Rejeena, I; Lillibai, B; Nithyaja, B; Nampoori, P.N V; P. Radhakrishnan

    2013-01-01

    Optical characterization of lead chloride crystals prepared by sol-gel method is reported. The relevant sol-gel technique is used for the preparation of PbCl2 samples with five different types. In this paper, we report the absorption and fluorescence behaviour of pure, UV& IR irradiated and electric & magnetic field applied lead chloride crystal samples in solution phase at two different concentrations. Optical bandgap and emission studies of these crystals are also done.

  11. Macrocycle Synthesis by Chloride-Templated Amide Bond Formation.

    Science.gov (United States)

    Martí-Centelles, Vicente; Burguete, M Isabel; Luis, Santiago V

    2016-03-01

    A new family of pseudopeptidic macrocyclic compounds has been prepared involving an anion-templated amide bond formation reaction at the macrocyclization step. Chloride anion was found to be the most efficient template in the macrocyclization process, producing improved macrocyclization yields with regard to the nontemplated reaction. The data suggest a kinetic effect of the chloride template, providing an appropriate folded conformation of the open-chain precursor and reducing the energy barrier for the formation of the macrocyclic product. PMID:26820908

  12. cis-Dichloridobis(1,10-phenanthrolinechromium(III chloride

    Directory of Open Access Journals (Sweden)

    Xiaoli Gao

    2011-02-01

    Full Text Available In the title complex, [CrCl2(C12H8N22]Cl, the CrIII ion is situated on a twofold rotation axis and displays a slightly distorted octahedral CrCl2N4 coordination geometry. The Cr environment is composed of a cis arrangement of two 1,10-phenanthroline and two chloride ligands. The chloride counter-anion exhibits half-occupation and is equally disordered over two positions.

  13. Recovering germanium from coal ash by chlorination with ammonium chloride

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new process of enriching germanium from coal ash was developed. The process involves in mixing the coal ash and ammonium chloride and then roasting the mixture to produce germanium chloride that is then absorbed by dilute hydrochloric acid and hydrolyzed to germanium oxide. The germanium recovery reached to 80.2% at the optimum condition: mass ratio of NH4Cl/coal ash is 0.15, roasting temperature 400℃ and roasting time 90 min.

  14. Aqueous Chloride Operations Overview: Plutonium and Americium Purification/Recovery

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, Kyle Shelton [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kimball, David Bryan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Skidmore, Bradley Evan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-28

    These are a set of slides intended for an information session as part of recruiting activities at Brigham Young University. It gives an overview of aqueous chloride operations, specifically on plutonium and americium purification/recovery. This presentation details the steps taken perform these processes, from plutonium size reduction, dissolution, solvent extraction, oxalate precipitation, to calcination. For Americium recovery, it details the CLEAR (chloride extraction and actinide recovery) Line, oxalate precipitation and calcination.

  15. Effect of kaolin treatment temperature on mortar chloride permeability

    OpenAIRE

    Puertas, F.; Mejía de Gutiérrez, R.; J. Torres

    2007-01-01

    The present paper discusses the results of chloride resistance tests conducted on ordinary Portland cement (OPC) mortars containing a Colombian kaolin pre-treated at temperatures of from 600 to 800 ºC. The resulting metakaolin (MK) was added to OPC mortar mixes in proportions of 10 and 20% by cement weight. The mortars were compared for physical and chemical properties, including capillary absorption, chloride permeability and pore microstructure as assessed by mercury porosimetry....

  16. Extraction and immobilization of simulated pyrometallurgical chloride waste in Zeolite

    International Nuclear Information System (INIS)

    Zeolites are effective media for the removal and immobilization of fission products waste from pyrometallurgical reprocessing of nuclear fuels. In the present study, equilibration experiments between zeolite 4A and a simulated: pyrometallurgical chloride waste were carried out. Several batches of equilibration were carried out by varying the zeolite to salt (Z/S) ratio. The effects of Z/S on the extraction behaviour of the waste chloride salts were explored. (author)

  17. The effect of chloride and sulfate on Completely Recyclable Concrete

    OpenAIRE

    Arvaniti, E.; De Schepper, M.; De Belie, N.; De Buysser, K.; Van Driessche, I.

    2013-01-01

    Completely Recyclable Concrete (CRC) is intended to be recycled as raw material within the cement production from a predesign stage. However, concrete contributions that are exposed to aggressive environments (e.g. industrial and seaside buildings), could carry elements such as chlorides, sulfur and alkalis after demolition, which will end up in the recycled material. The aim of this study is to better understand the influence of chloride and sulfur in CRC on the final clinker properties. The...

  18. Hafnium extraction from acidic chloride solutions by Cyanex 923

    Energy Technology Data Exchange (ETDEWEB)

    El-Ammouri, E.; Distin, P.A. [McGill Univ., Montreal (Canada)

    1996-08-01

    Hafnium extraction from hydrochloric acid/lithium chloride solutions into Cyanex 923 in kerosene has been studied. Variables investigated were hydrochloric acid, total chloride and hafnium concentrations in the aqueous phase, and extractant/modifier (isodecanol) levels in the organic phase. Hafnium is considered to load as the tetrachloride complex forming a disolvate with Cyanex 923. Results are compared with equivalent data for zirconium extraction. 14 refs., 7 figs., 2 tabs.

  19. Computational modelling of chloride ion transport in reinforced concrete

    OpenAIRE

    Meijers, S.J.H.; Bijen, J.M.J.M.; De Borst, R.; Fraaij, A.L.A.

    2001-01-01

    Exposure to a saline environment is a major threat with respect to the durability of reinforced concrete structures. The chloride ions, which are present in seawater and de-icing salts, are able to penetrate the concrete up to the depth of the reinforcement. They can eventually trigger a pitting corrosion process. The assessment of a corrosion-free service life of concrete structures is of paramount economic interest. However, the modelling of the ingress of chloride ions is complicated due t...

  20. Large Scale Synthesis of Carbon Nanofibres on Sodium Chloride Support

    OpenAIRE

    Ravindra Rajarao; Badekai Ramachandra Bhat

    2012-01-01

    Large scale synthesis of carbon nanofibres (CNFs) on a sodium chloride support has been achieved. CNFs have been synthesized using metal oxalate (Ni, Co and Fe) as catalyst precursors at 680 C by chemical vapour deposition method. Upon pyrolysis, this catalyst precursors yield catalyst nanoparticles directly. The sodium chloride was used as a catalyst support, it was chosen because of its non‐toxic and water soluble nature. Problems, such as the detrimental effect of CNFs, the detrimental ef...

  1. Durability Analysis of Subway Station in Chloride Environment

    OpenAIRE

    Yang LuFeng; Yu Bo; Hong Bin

    2013-01-01

    In this study, a finite element model for chloride ions transport in saturated concrete was proposed based on the Fick’s second law of diffusion. The governing partial differential equation was solved numerically in space as a boundary-value problem and in time as an initial-value problem by means of the finite element formulations. The maximum allowable value of chloride diffusion coefficient within different locations of subway station with service life of 100a was achieved and suggestions ...

  2. Influence of cracks on chloride penetration in concrete

    OpenAIRE

    Audenaert, K.; Schutter, G. de; MARSAVINA, L

    2009-01-01

    Chloride initiated reinforcement corrosion is the main durability problem for concrete structures in a marine environment. If the chlorides reach the reinforcement steel, it will depassivate and start to corrode in presence of air and water. Since the corrosion products have a larger volume than the initial products, concrete stresses are induced, leading to spalling and degradation of the concrete structures. If cracks, caused by early drying, thermal effects, shrinkage movements or overstre...

  3. Chloride ion transport performance in slag mortar under fatigue loading

    Institute of Scientific and Technical Information of China (English)

    WANG CaiHui; SUN Wei; JIANG JinYang; HAN JianDe; YE BangTu

    2012-01-01

    The transport performance of chloride ion in slag cement mortar was investigated experimentally.In the self-designed experiment,fatigue loading was coupled simultaneously with ion transportation process,the diffusion law of chloride ion was obtained by titration and the AE (acoustic emission) technique was employed to detect the real-time damage distribution in the mortar specimen.The results for fatigue stress levels of 0.3,0.4 and 0.5 and slag contents of 0,10%,30% and 50% showed that fatigue loading accelerated the diffusion of chloride ion in mortar and the acceleration effect increased with the increase in stress levels.Slag addition was found to improve anti-chloride ion erosion performance effectively with the best substitution level at 30%,because the inhibition effect of slag on chloride ion diffusion diminished when the slag content exceeded 30%.The comparative experiments indicated that dynamic load has a significant effect on the transport performance of chloride ion in slag cement mortar.

  4. Removal of chloride from electric arc furnace dust.

    Science.gov (United States)

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

    2011-06-15

    Electric arc furnace (EAF) dust with high chloride content increases the threat of dioxin emissions and the high chloride content reduces the value of recycled zinc oxide produced by EAF dust recycling plants. This study conducts a number of laboratory experiments to determine the technical feasibility of a new dechlorination method. These methods consist of a series of roasting processes and water washing processes. In the roasting process, EAF dust was heated in a tube furnace to evaluate the parameters of atmospheric conditions, roasting temperature, and roasting time. Results indicate that sulfation roasting is more efficient in reducing chloride content than other roasting processes. The water washing process can totally remove water-soluble chloride at a solid to liquid ratio of 1:10. However, the remaining water-insoluble substance is difficult to dechlorinate. For example, lead chloride forms a hydroxyl-halide (PbOHCl) and lead chloride carbonate (Pb(2)CO(3)Cl(2)) agglutinative matrix that is hard to wash away.

  5. Congenital chloride diarrhea: a review of twelve Arabian children

    Directory of Open Access Journals (Sweden)

    Elrefae F

    2013-06-01

    Full Text Available Fawaz Elrefae,1 Ahmed Farag Elhassanien,2 Hesham Abdel-Aziz Alghiaty3 1Pediatric Gastroenterology, Al-Adan Hospital, Kuwait; 2Faculty of Medicine, Elmansoura University, El Mansoura, El Dakahleya, Egypt; 3Faculty of Medicine, Benha University, Egypt Background: Congenital chloride diarrhea (CCD, a rare autosomal recessive disorder, is characterized by sustained watery diarrhea (due to defect of active Chloride/HCO3 exchange in the ileum and colon with high fecal chloride. Objective: To spotlight the common presentation of CCD for early management and prevention of complications. Subjects and methods: This is a retrospective case series study of patients diagnosed as CCD who were followed up in the pediatric department of Al-Adan Hospital, Kuwait. Results: Twelve patients diagnosed with CCD were born to consanguineous parents; had antenatal history of intrauterine growth retardation (IUGR; polyhydramnios; and distended hypoechoic fetal bowel; and presented with abdominal distension, hypotonia and muscle wasting. 90% of patients had maternal hypertension and 75% of patients had absence of normal meconium at birth. Our patients showed a decrease in serum sodium, potassium, chloride and urine chloride. Conclusion: A high level of suspicion for an early diagnosis of CCD should be considered for any infant presenting with chronic diarrhea, especially in the presence of consanguineous marriage, and the characteristic features in antenatal ultrasound. Thus, allowing for early investigations and appropriate management. Keywords: congenital chloride diarrhea, children, chronic diarrhea, metabolic alkalosis, prenatal diagnosis

  6. Stabilizing Plutonium oxide material containing Chloride salts at PFP

    International Nuclear Information System (INIS)

    PFP had over 900 items, weighing more than 1100 kg consisting of impure plutonium oxides referred to as high chloride content plutonium oxides. Tests were conducted to examine items for physical characteristics. After 17 years of storage, the inner food-pack cans maintained integrity with very little evidence of corrosion. Items were washed with water to remove chloride salts. Chloride was readily soluble with plutonium concentrations less than 0.05 g/L in wash solution from all but one of seven items. Washed material was calcined at 1000 C. The calcined material passed the storage test for less than 0.5% water. Unopened items were examined using gamma energy analysis to determine if a prompt gamma (n, x) interaction could be used to screen out items with low chloride concentrations. The prompt gamma was not measurable. A 2168 keV gamma from the (α, x) interaction with chloride correlated within 10% of the chloride concentration measured from washing the item with water

  7. MEMS in microfluidic channels.

    Energy Technology Data Exchange (ETDEWEB)

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.

    2004-03-01

    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.

  8. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

    In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area. PMID:17059356

  9. Channel Identification Machines

    Directory of Open Access Journals (Sweden)

    Aurel A. Lazar

    2012-01-01

    Full Text Available We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

  10. DEVELOPMENTAL TOXICITY OF COPPER CHLORIDE, METHYLENE CHLORIDE,AND 6-AMINONICOTINAMIDE TO EMBRYOS OF THE GRASS SHRIMPPALAEMONETES PUGIO

    Science.gov (United States)

    Embryos of estuarine grass shrimp Palaemonetes pugio have demonstrated sensitivity to various solvents and petroleum products, indicating utility for evaluating estuarine contamination. Testing was performed to establish concentration-response curves for methylene chloride, cop...

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

    International Nuclear Information System (INIS)

    γ-Aminobutyric acid (GABA) receptor-mediated 36chloride (36Cl-) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated 36Cl- uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated 36Cl- uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated 36Cl- uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br->Cl-≥NO3->I-≥SCN->>C3H5OO-≥ClO4->F-, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl- channel. 43 references, 4 figures, 3 tables

  12. Ab initio Investigations of the Equilibria between Trichlorothioacetyl Chloride, Tetrachlorothiirane, and Trichloroethenesulfenyl Chloride, their Reactants and Decomposition Products

    DEFF Research Database (Denmark)

    Pedersen, Kim Vestergaard; Christensen, Henrik; Shim, Irene;

    2004-01-01

    Trichlorothioacetyl chloride 1, tetrachlorothiirane 2, and trichloroethenesulfenyl chloride 3 and the equilibria between them have been investigated by ab initio Hartree-Fock (HF), Møller-Plesset second order perturbation (MP2) calculations, and by Gaussian-3 theory, G3(MP2). The transition state...... of the isomerization reactions have been identified. Also investigated were possible reactions leading to the isomers and their possible decomposition products. The results show that the unobserved isomerization reactions are feasible....

  13. Technical note: Could benzalkonium chloride be a suitable alternative to mercuric chloride for preservation of seawater samples?

    OpenAIRE

    Gloël, J.; Robinson, C.; Tilstone, G. H.; Tarran, G.; J. Kaiser

    2015-01-01

    Instrumental equipment unsuitable or unavailable for fieldwork as well as lack of ship space can necessitate the preservation of seawater samples prior to analysis in a shore-based laboratory. Mercuric chloride (HgCl2) is routinely used for such preservation, but its handling and subsequent disposal incur environmental risks and significant expense. There is therefore a strong motivation to find less hazardous alternatives. Benzalkonium chloride (BAC) has been used previousl...

  14. Technical Note: Could benzalkonium chloride be a suitable alternative to mercuric chloride for preservation of seawater samples?

    OpenAIRE

    Gloël, J.; Robinson, C.; Tilstone, G. H.; Tarran, G.; J. Kaiser

    2015-01-01

    Instrumental equipment unsuitable or unavailable for fieldwork as well as lack of ship space can necessitate the preservation of seawater samples prior to analysis in a shore-based laboratory. Mercuric chloride (HgCl2) is routinely used for such preservation, but its handling and subsequent disposal incur significant risks and expense. Benzalkonium chloride (BAC) has been used previously for freshwater samples. Here, we assess BAC as a less hazardous alterna...

  15. 40 CFR 61.63 - Emission standard for vinyl chloride plants.

    Science.gov (United States)

    2010-07-01

    ... formation and purification: The concentration of vinyl chloride in each exhaust gas stream from any... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Emission standard for vinyl chloride... for Vinyl Chloride § 61.63 Emission standard for vinyl chloride plants. An owner or operator of...

  16. QKD Quantum Channel Authentication

    CERN Document Server

    Kosloski, J T

    2006-01-01

    Several simple yet secure protocols to authenticate the quantum channel of various QKD schemes, by coupling the photon sender's knowledge of a shared secret and the QBER Bob observes, are presented. It is shown that Alice can encrypt certain portions of the information needed for the QKD protocols, using a sequence whose security is based on computational-complexity, without compromising all of the sequence's entropy. It is then shown that after a Man-in-the-Middle attack on the quantum and classical channels, there is still enough entropy left in the sequence for Bob to detect the presence of Eve by monitoring the QBER. Finally, it is shown that the principles presented can be implemented to authenticate the quantum channel associated with any type of QKD scheme, and they can also be used for Alice to authenticate Bob.

  17. Dequantization Via Quantum Channels

    Science.gov (United States)

    Andersson, Andreas

    2016-10-01

    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. Dequantization Via Quantum Channels

    Science.gov (United States)

    Andersson, Andreas

    2016-08-01

    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.

  19. Entanglement-saving channels

    Science.gov (United States)

    Lami, L.; Giovannetti, V.

    2016-03-01

    The set of Entanglement Saving (ES) quantum channels is introduced and characterized. These are completely positive, trace preserving transformations which when acting locally on a bipartite quantum system initially prepared into a maximally entangled configuration, preserve its entanglement even when applied an arbitrary number of times. In other words, a quantum channel ψ is said to be ES if its powers ψn are not entanglement-breaking for all integers n. We also characterize the properties of the Asymptotic Entanglement Saving (AES) maps. These form a proper subset of the ES channels that is constituted by those maps that not only preserve entanglement for all finite n but which also sustain an explicitly not null level of entanglement in the asymptotic limit n → ∞. Structure theorems are provided for ES and for AES maps which yield an almost complete characterization of the former and a full characterization of the latter.

  20. Chaos in quantum channels

    CERN Document Server

    Hosur, Pavan; Roberts, Daniel A; Yoshida, Beni

    2015-01-01

    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.

  1. Voltage-Gated Proton Channels

    OpenAIRE

    DeCoursey, Thomas E.

    2008-01-01

    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dime...

  2. The neutron channeling phenomenon.

    Science.gov (United States)

    Khanouchi, A; Sabir, A; Boulkheir, M; Ichaoui, R; Ghassoun, J; Jehouani, A

    1997-01-01

    Shields, used for protection against radiation, are often pierced with vacuum channels for passing cables and other instruments for measurements. The neutron transmission through these shields is an unavoidable phenomenon. In this work we study and discuss the effect of channels on neutron transmission through shields. We consider an infinite homogeneous slab, with a fixed thickness (20 lambda, with lambda the mean free path of the neutron in the slab), which contains a vacuum channel. This slab is irradiated with an infinite source of neutrons on the left side and on the other side (right side) many detectors with windows equal to 2 lambda are placed in order to evaluate the neutron transmission probabilities (Khanouchi, A., Aboubekr, A., Ghassoun, J. and Jehouani, A. (1994) Rencontre Nationale des Jeunes Chercheurs en Physique. Casa Blanca Maroc; Khanouchi, A., Sabir, A., Ghassoun, J. and Jehouani, A. (1995) Premier Congré International des Intéractions Rayonnements Matière. Eljadida Maroc). The neutron history within the slab is simulated by the Monte Carlo method (Booth, T. E. and Hendricks, J. S. (1994) Nuclear Technology 5) and using the exponential biasing technique in order to improve the Monte Carlo calculation (Levitt, L. B. (1968) Nuclear Science and Engineering 31, 500-504; Jehouani, A., Ghassoun, J. and Aboubker, A. (1994) In Proceedings of the 6th International Symposium on Radiation Physics, Rabat, Morocco). Then different geometries of the vacuum channel have been studied. For each geometry we have determined the detector response and calculated the neutron transmission probability for different detector positions. This neutron transmission probability presents a peak for the detectors placed in front of the vacuum channel. This study allowed us to clearly identify the neutron channeling phenomenon. One application of our study is to detect vacuum defects in materials. PMID:9463884

  3. Effect of genistein on voltage-gated potassium channels in guinea pig proximal colon smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Shi-Ying Li; Bin-Bin Huang; Shou Ouyang

    2006-01-01

    AIM: To investigate the action of genistein (GST), a broad spectrum tyrosine kinase inhibitor, on voltagegated potassium channels in guinea pig proximal colon smooth muscle cells.METHODS: Smooth muscle cells in guinea pig proximal colon were enzymatically isolated. Nystatin-perforated whole cell patch clamp technique was used to record potassium currents including fast transient outward current (IKto) and delayed rectifier current (IKdr), two of which were isolated pharmacologically with 10 mmol/L tetraethylammonium or 5 mmol/L 4-aminopyridine.Contamination of calcium-dependent potassium currents was minimized with no calcium and 0.2 mmol/L CdCl2 in an external solution.RESULTS: GST (10-100 μmol/L) reversibly and dosedependently reduced the peak amplitude of IKto with an IC50value of 22.0±6.9 μmol/L. To a lesser extent, IKdr was also inhibited in both peak current and sustained current.GST could not totally block the outward potassium current as a fraction of the outWard potassium current,which was insensitive to GST. GST had no effect on the steady-state activation (n = 6) and inactivation kinetics(n =6) of IKto. Sodium orthovanadate (1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited GST-induced inhibition (P< 0.05).CONCLUSION: GST can dose-dependently and reversibly block voltage-gated potassium channels in guinea pig proximal colon smooth muscle cells.

  4. BLIND CHANNEL ESTIMATION IN DELAY DIVERSITY FOR FREQUENCY SELECTIVE CHANNELS

    Institute of Scientific and Technical Information of China (English)

    Zhao Zheng; Jia Ying; Yin Qinye

    2003-01-01

    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.

  5. K(v)7 channels: function, pharmacology and channel modulators.

    Science.gov (United States)

    Dalby-Brown, William; Hansen, Henrik H; Korsgaard, Mads P G; Mirza, Naheed; Olesen, Søren-P

    2006-01-01

    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.

  6. Characterization of the lanthanum chloride scintillation detector

    International Nuclear Information System (INIS)

    This paper reports about the investigations on the performance of the new earth-rare halide Scintillator, the LaCl3:10%Ce, which has been discovered with attractive scintillation properties: fast, efficient, and high-energy resolution. The combination of good brightness and linear response has naturally resulted in a very good energy resolution, whereas the fast decay time promoted counting applications at very high rate and very fast timing resolution. Energy resolutions of (2.99±0.02) %, (8.66±0.02) %, and (2.05±0.01) % have been achieved by exciting the detector with 662 keV 137Cs, 122 keV 152Eu, and 1332.5 keV 60Co sources respectively, at room temperature. The variations of the resolution as a function of both shaping time and high voltage have been studied and found to be relatively linear. The timing resolution was also studied. The value of 1.07 ns FWHM has been recorded with LaCl3:10%Ce and BaF2 detectors operating in coincidence mode, using 1333.5 keV γ-ray 60Co peak. Compared to similar studies, this timing resolution was worse than expected even if the exciting radioactive sources used in the two experiments were different. The efficiency values of (0.24±0.01)%, (0.01±0.01)% and (0.09±0.01)% were obtained with laboratory 137Cs, 152Eu, 60Co isotopes respectively. These detector efficiency values were very low, due to the smaller detector sizes used in these earlier crystals and to the large detector-source-distance used in this experiment. The Lanthanum Chloride Scintillator detector is hygroscopic and relatively expensive compared to established scintillators. In addition, it carries internal contamination in 138La and 227Ac for larger thicknesses. Nevertheless, the energy resolution figures achieved, twice as good as that of NaI(Tl), are in good agreement with those reported elsewhere. They credit the scintillation detectors as good challengers of semiconductor-based detectors, allowing their application fields to be extended. (author)

  7. [Pulmonary manifestations of polyvinyl chloride exposure].

    Science.gov (United States)

    Süyür, Hüseyin; Bayram, Nazan; Aydın, Neriman; Uyar, Meral; Gündoğdu, Nevhiz; Elbek, Osman

    2011-01-01

    There is currently no national data on the effects of polyvinyl chloride (PVC) exposure on pulmonary function. In this study we recruited workers and administrative staff from two PVC plants between July 2008 and July 2009. A questionnaire, pulmonary function tests, carbon monoxide diffusion capacity, and peak flows were recorded. Particulate matter analyses were performed by the Adana Central Laboratory of the Directorate of Occupational Health and Safety. Data were analyzed with SPSS 13.0 software. Nine of the 147 subjects were female. The incidence of a cough was more common in the administrative group. Of the study population, 59.1% were smokers. Tobacco addiction significantly increased cough and dyspnea [OR= 1.10 (1.00-1.20, 95% CI) p= 0.007 and OR= 1.08 (1.02-1.14, 95% CI), p= 0.008, respectively]. Dust exposure was correlated with the incidence of a cough [OR= 0.20 (0.04-0.80, 95% CI) p= 0.008]. The period of work correlated with sputum production [OR= 1.00 (1.00-1.02, 95% CI) p= 0.044]. The FVC% was significantly higher in the administrative group, and FEV1/FVC and DLCO were higher in the exposed group. Tobacco addiction increased the risk of airflow limitation, as evaluated by FEV1/FVC < 70% and FEF25-75 < 50% [OR= 1.15 (1.06-1.25, 95% CI) p= 0.001 and OR= 1.09 (1.02-1.17, 95% CI) p= 0.010, respectively]. Tobacco addiction and increasing duration of work had a negative influence on DLCO in the exposed group (r= -0.270, p= 0.025 and r= -0.210, p= 0.037). In the exposed group PEF variability was significantly greater on workdays, compared with rest days. This study shows that tobacco consumption has a greater affect on the airways than PVC dust exposure. A median of 36 months exposure to PVC dust had no significant impact on pulmonary function parameters, except for DLCO and PEF variability.

  8. A novel human Cl(-) channel family related to Drosophila flightless locus.

    Science.gov (United States)

    Suzuki, Makoto; Mizuno, Atsuko

    2004-05-21

    Large conductance chloride (maxi-Cl(-)) currents have been recorded in some cells, but there is still little information on the molecular nature of the channel underlying this conductance. We report here that tweety, a gene located in Drosophila flightless, has a structure similar to those of known channels and that human homologues of tweety (hTTYH1-3) are novel maxi-Cl(-) channels. hTTYH3 mRNA was found to be distributed in excitable tissues. The whole cell current of hTTYH3 was large enough to be discriminated from the control but emerged only after treatment with ionomycin. Analysis of pore mutants suggested that positively charged amino acids contributed to anion selectivity. Like a maxi-Cl(-) channel in situ, the hTTYH3 single channel showed 26-picosiemen linear current voltage, complex kinetics, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid sensitivity, subconductance, and the permeability order of I(-) > Br(-) > Cl(-). Similarly, hTTYH2 encoded an ionomycin-induced maxi-Cl(-) channel, but TTYH1 encoded a Ca(2+)-independent and swelling-activated maxi-Cl(-) channel. Therefore, the hTTYH family encoded maxi-Cl(-) channels of mammals. Further studies on the hTTYH family should lead to the elucidation of physiological and pathophysiological roles of novel Cl(-) channel molecules. PMID:15010458

  9. Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

    Directory of Open Access Journals (Sweden)

    Ikemoto Tatsunori

    2009-08-01

    Full Text Available Abstract Background Although magnesium ions (Mg2+ are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+. To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short, tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

  10. Henry’s constant of carbon dioxide-aqueous deep eutectic solvent (choline chloride/ethylene glycol, choline chloride/glycerol, choline chloride/malonic acid) systems

    International Nuclear Information System (INIS)

    Highlights: • A new set of Henry’s constant for the system carbon dioxide-aqueous deep eutectic solvents were measured. • The DESs used were: ethaline, glyceline, and maline. • The measured data were reported as functions of temperature and composition. • The measured data were represented satisfactorily by the applied correlations. -- Abstract: In this study, we present a new set of Henry’s constant data for the system carbon dioxide-aqueous deep eutectic solvent (DES) (20 to 80 wt% DES) at T = (303.15, 308.15, and 313.15) K. The DESs used were choline chloride-based: ethaline (choline chloride/ethylene glycol), glyceline (choline chloride/glycerol), and maline (choline chloride/malonic acid). A differential Henry’s coefficient model was used to describe the behaviour of Henry’s constant, and correlate it with temperature and concentration of DES in the aqueous DES solution. The correlation was found satisfactory such that the proposed model can be used in engineering calculations with reasonable accuracy

  11. The Chloride Anion Acts as a Second Messenger in Mammalian Cells - Modifying the Expression of Specific Genes

    Directory of Open Access Journals (Sweden)

    Ángel G. Valdivieso

    2016-01-01

    Full Text Available Background/Aims: Cystic Fibrosis (CF is caused by mutations in the CFTR gene, encoding a cAMP-activated chloride (Cl- channel. We have previously demonstrated that the expression of several genes can be modulated by the CFTR activity; among them, SRC, MTND4, CISD1, and IL1B. However, the CFTR signalling mechanism involved in the expression of CFTR-dependent genes is unknown. The aim of this work was to determine if intracellular chloride (Cl-i might function as a second messenger modulating the expression of specific genes. Methods: Differential display (DD was applied to IB3-1 cells (CF cells, cultured under conditions that produce different intracellular Cl- concentrations ([Cl-]i, to analyse their expression profile. Results: Several differentially expressed gene products were observed by using DD, suggesting the presence of chloride-dependent gene expression. Two cDNA fragments, derived from differentially expressed mRNAs and showing opposed response to Cl-‚ were isolated, cloned, sequenced and its Cl- dependency validated by reverse transcription quantitative-PCR (RT-qPCR. We identified the gene RPS27, which encodes the multifunctional ribosomal protein RPS27, also known as metallopanstimulin-1 (MPS-1, and the gene GLRX5, encoding glutaredoxin-related protein 5, as chloride-dependent genes. RPS27 was negatively regulated with increased [Cl-]i, approximately from 25-75 mM Cl- (EC50 = 46 ± 7 mM, and positively regulated from 75-125 mM Cl- (EC50 = 110 ± 11 mM (biphasic response. In contrast, GLRX5 was positively modulated by [Cl-]i, showing a typical sigmoidal dose-response curve from 0-50 mM Cl-, reaching a plateau after 50 mM Cl- (EC50 ∼ 34 mM. Conclusion: The results suggest the existence of chloride-dependent genes. The Cl- anion, therefore, might act as a second messenger for channels or receptors able to modulate the intracellular Cl- concentration, regulating in turn the expression of specific genes.

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

    OpenAIRE

    Joon Woo Park; Ki Yong Ann; Chang-Geun Cho

    2015-01-01

    The corrosion resistance of steel in alkali-activated slag (AAS) mortar was evaluated by a monitoring of the galvanic current and half-cell potential with time against a chloride-contaminated environment. For chloride transport, rapid chloride penetration test was performed, and chloride binding capacity of AAS was evaluated at a given chloride. The mortar/paste specimens were manufactured with ground granulated blast-furnace slag, instead of Portland cement, and alkali activators were added ...

  13. Simulation of Chloride Diffusion in Cracked Concrete with Different Crack Patterns

    OpenAIRE

    Xiao-Yong Wang; Li-Na Zhang

    2016-01-01

    Chloride-induced corrosion of steel rebar is one of the primary durability problems for reinforced concrete structures in marine environment. Furthermore, if the surfaces of concrete structures have cracks, additional chloride can penetrate into concrete through cracked zone. For chloride ingression into cracked concrete, former researches mainly focus on influence of crack width on chloride diffusion coefficients. Other crack characteristics, such as chloride depth, crack shape (equal-width ...

  14. Commercial Scale Cucumber Fermentations Brined with Calcium Chloride Instead of Sodium Chloride.

    Science.gov (United States)

    Pérez-Díaz, I M; McFeeters, R F; Moeller, L; Johanningsmeier, S D; Hayes, J; Fornea, D S; Rosenberg, L; Gilbert, C; Custis, N; Beene, K; Bass, D

    2015-12-01

    Development of low salt cucumber fermentation processes present opportunities to reduce the amount of sodium chloride (NaCl) that reaches fresh water streams from industrial activities. The objective of this research was to translate cucumber fermentation brined with calcium chloride (CaCl2 ) instead of NaCl to commercial scale production. Although CaCl2 brined cucumber fermentations were stable in laboratory experiments, commercial scale trials using 6440 L open-top tanks rapidly underwent secondary cucumber fermentation. It was understood that a limited air purging routine, use of a starter culture and addition of preservatives to the cover brine aids in achieving the desired complete cucumber fermentation. The modified process was used for subsequent commercial trials using 12490 and 28400 L open-top tanks packed with variable size cucumbers and from multiple lots, and cover brines containing CaCl2 and potassium sorbate to equilibrated concentrations of 100 and 6 mM, respectively. Lactobacillus plantarum LA0045 was inoculated to 10(6) CFU/mL, and air purging was applied for two 2-3 h periods per day for the first 10 d of fermentation and one 2-3 h period per day between days 11 and 14. All fermentations were completed, as evidenced by the full conversion of sugars to lactic acid, decrease in pH to 3.0, and presented microbiological stability for a minimum of 21 d. This CaCl2 process may be used to produce fermented cucumbers intended to be stored short term in a manner that reduces pollution and waste removal costs. PMID:26512798

  15. Commercial Scale Cucumber Fermentations Brined with Calcium Chloride Instead of Sodium Chloride.

    Science.gov (United States)

    Pérez-Díaz, I M; McFeeters, R F; Moeller, L; Johanningsmeier, S D; Hayes, J; Fornea, D S; Rosenberg, L; Gilbert, C; Custis, N; Beene, K; Bass, D

    2015-12-01

    Development of low salt cucumber fermentation processes present opportunities to reduce the amount of sodium chloride (NaCl) that reaches fresh water streams from industrial activities. The objective of this research was to translate cucumber fermentation brined with calcium chloride (CaCl2 ) instead of NaCl to commercial scale production. Although CaCl2 brined cucumber fermentations were stable in laboratory experiments, commercial scale trials using 6440 L open-top tanks rapidly underwent secondary cucumber fermentation. It was understood that a limited air purging routine, use of a starter culture and addition of preservatives to the cover brine aids in achieving the desired complete cucumber fermentation. The modified process was used for subsequent commercial trials using 12490 and 28400 L open-top tanks packed with variable size cucumbers and from multiple lots, and cover brines containing CaCl2 and potassium sorbate to equilibrated concentrations of 100 and 6 mM, respectively. Lactobacillus plantarum LA0045 was inoculated to 10(6) CFU/mL, and air purging was applied for two 2-3 h periods per day for the first 10 d of fermentation and one 2-3 h period per day between days 11 and 14. All fermentations were completed, as evidenced by the full conversion of sugars to lactic acid, decrease in pH to 3.0, and presented microbiological stability for a minimum of 21 d. This CaCl2 process may be used to produce fermented cucumbers intended to be stored short term in a manner that reduces pollution and waste removal costs.

  16. Effect of n-tetradecanol on the extraction of iron(III), cobalt(II), and zinc(II) chlorides with tri-n-dodecylammonium chloride

    International Nuclear Information System (INIS)

    Equations are proposed to describe the reduction in the partition coefficients of metal chlorides in amine extractant systems following the addition of alcohols. The equations include two empirical factors: solvation parameters for amine chloride and the compound undergoing extraction. These parameters can be found from independent data. The equations have been used to describe the extraction of micro amounts of iron(III), cobalt(II), and zinc(II) chlorides by tridodecylammonium chloride in the presence of n-tetradecanol

  17. Chemistry in Microfluidic Channels

    Science.gov (United States)

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

    2011-01-01

    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…

  18. Beyond the Manual Channel

    DEFF Research Database (Denmark)

    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...

  19. TRP channels: an overview

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd

    2005-01-01

    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....

  20. All channels open

    NARCIS (Netherlands)

    Frank Huysmans; Jos de Haan

    2010-01-01

    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