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Sample records for gmp-dependent calcium-activated chloride

  1. ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification

    PubMed Central

    Stephan, Aaron B.; Shum, Eleen Y.; Hirsh, Sarah; Cygnar, Katherine D.; Reisert, Johannes; Zhao, Haiqing

    2009-01-01

    For vertebrate olfactory signal transduction, a calcium-activated chloride conductance serves as a major amplification step. However, the molecular identity of the olfactory calcium-activated chloride channel (CaCC) is unknown. Here we report a proteomic screen for cilial membrane proteins of mouse olfactory sensory neurons (OSNs) that identified all the known olfactory transduction components as well as Anoctamin 2 (ANO2). Ano2 transcripts were expressed specifically in OSNs in the olfactory epithelium, and ANO2::EGFP fusion protein localized to the OSN cilia when expressed in vivo using an adenoviral vector. Patch-clamp analysis revealed that ANO2, when expressed in HEK-293 cells, forms a CaCC and exhibits channel properties closely resembling the native olfactory CaCC. Considering these findings together, we propose that ANO2 constitutes the olfactory calcium-activated chloride channel. PMID:19561302

  2. The calcium-activated chloride channel Anoctamin 1 contributes to the regulation of renal function.

    PubMed

    Faria, Diana; Rock, Jason R; Romao, Ana M; Schweda, Frank; Bandulik, Sascha; Witzgall, Ralph; Schlatter, Eberhard; Heitzmann, Dirk; Pavenstädt, Hermann; Herrmann, Edwin; Kunzelmann, Karl; Schreiber, Rainer

    2014-06-01

    The role of calcium-activated chloride channels for renal function is unknown. By immunohistochemistry we demonstrate dominant expression of the recently identified calcium-activated chloride channels, Anoctamin 1 (Ano1, TMEM16A) in human and mouse proximal tubular epithelial (PTE) cells, with some expression in podocytes and other tubular segments. Ano1-null mice had proteinuria and numerous large reabsorption vesicles in PTE cells. Selective knockout of Ano1 in podocytes (Ano1-/-/Nphs2-Cre) did not impair renal function, whereas tubular knockout in Ano1-/-/Ksp-Cre mice increased urine protein excretion and decreased urine electrolyte concentrations. Purinergic stimulation activated calcium-dependent chloride currents in isolated proximal tubule epithelial cells from wild-type but not from Ano1-/-/Ksp-Cre mice. Ano1 currents were activated by acidic pH, suggesting parallel stimulation of Ano1 chloride secretion with activation of the proton-ATPase. Lack of calcium-dependent chloride secretion in cells from Ano1-/-/Ksp-Cre mice was paralleled by attenuated proton secretion and reduced endosomal acidification, which compromised proximal tubular albumin uptake. Tubular knockout of Ano1 enhanced serum renin and aldosterone concentrations, probably leading to enhanced compensatory distal tubular reabsorption, thus maintaining normal blood pressure levels. Thus, Ano1 has a role in proximal tubular proton secretion and protein reabsorption. The results correspond to regulation of the proton-ATPase by the Ano1-homolog Ist2 in yeast.

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

    PubMed

    Zhang, Weiping; Schmelzeisen, Steffen; Parthier, Daniel; Frings, Stephan; Möhrlen, Frank

    2015-01-01

    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.

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

    PubMed

    Zhang, Weiping; Schmelzeisen, Steffen; Parthier, Daniel; Frings, Stephan; Möhrlen, Frank

    2015-01-01

    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. PMID:26558388

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

    PubMed Central

    Parthier, Daniel; Frings, Stephan; Möhrlen, Frank

    2015-01-01

    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. PMID:26558388

  6. Calcium-activated chloride channels anoctamin 1 and 2 promote murine uterine smooth muscle contractility

    PubMed Central

    Bernstein, Kyra; Vink, Joy Y; Fu, Xiao Wen; Wakita, Hiromi; Danielsson, Jennifer; Wapner, Ronald; Gallos, George

    2014-01-01

    Objective To determine the presence of calcium activated chloride channels anoctamin 1 and 2 in human and murine uterine smooth muscle and evaluate the physiologic role for these ion channels in murine myometrial contractility. Study Design We performed reverse transcription polymerase chain reaction to determine if anoctamin 1 and 2 are expressed in human and murine uterine tissue to validate the study of this protein in mouse models. Immunohistochemical staining of anoctamin 1 and 2 was then performed to determine protein expression in murine myometrial tissue. The function of anoctamin 1 and 2 in murine uterine tissue was evaluated using electrophysiological studies, organ bath, and calcium flux experiments. Results Anoctamin 1 and 2 are expressed in human and murine USM cells. Functional studies show that selective antagonism of these channels promotes relaxation of spontaneous murine uterine smooth muscle contractions. Blockade of anoctamin 1 and 2 inhibits both agonist-induced and spontaneous transient inward currents and abolishes G-protein coupled receptor (oxytocin) mediated elevations in intracellular calcium. Conclusion The calcium activated chloride channels ANO 1 and 2 are present in human and murine myometrial tissue and may provide novel potential therapeutic targets to achieve effective tocolysis. PMID:24928056

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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 Ca2+ 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

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

    PubMed

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

    PubMed Central

    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 Ca2+ 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.

  12. Study of permeation and blocker binding in TMEM16A calcium-activated chloride channels.

    PubMed

    Reyes, J P; Huanosta-Gutiérrez, A; López-Rodríguez, A; Martínez-Torres, A

    2015-01-01

    We studied the effects of mutations of positively charged amino acid residues in the pore of X. tropicalis TMEM16A calcium-activated chloride channels: K613E, K628E, K630E; R646E and R761E. The activation and deactivation kinetics were not affected, and only K613E showed a lower current density. K628E and R761E affect anion selectivity without affecting Na(+) permeation, whereas K613E, R646E and the double mutant K613E + R646E affect anion selectivity and permeability to Na(+). Furthermore, altered blockade by the chloride channel blockers anthracene-9-carboxylic acid (A-9-C), 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and T16inh-A01 was observed. These results suggest the existence of 2 binding sites for anions within the pore at electrical distances of 0.3 and 0.5. These sites are also relevant for anion permeation and blockade.

  13. Anoctamin 1 induces calcium-activated chloride secretion and proliferation of renal cyst-forming epithelial cells.

    PubMed

    Buchholz, Bjoern; Faria, Diana; Schley, Gunnar; Schreiber, Rainer; Eckardt, Kai-Uwe; Kunzelmann, Karl

    2014-05-01

    Polycystic kidney diseases are characterized by multiple bilateral renal cysts that gradually enlarge and lead to a decline in renal function. Cyst enlargement is driven by transepithelial chloride secretion, stimulated by enhanced levels of cyclic adenosine monophosphate, which activates apical cystic fibrosis transmembrane conductance regulator chloride channels. However, chloride secretion by calcium-dependent chloride channels, activated through stimulation of purinergic receptors, also has a major impact. To identify the molecular basis of calcium-dependent chloride secretion in cyst expansion, we determined the role of anoctamin 1 and 6, two recently discovered calcium-activated chloride channels both of which are expressed in epithelial cells. We found that anoctamin 1, which plays a role in epithelial fluid secretion and proliferation, is strongly expressed in principal-like MDCK cells (PLCs) forming cysts within a collagen matrix, in an embryonic kidney cyst model, and in human autosomal dominant polycystic kidney disease tissue. Knockdown of anoctamin 1 but not anoctamin 6 strongly diminished the calcium-dependent chloride secretion of PLCs. Moreover, two inhibitors of anoctamin ion channels, tannic acid and a more selective inhibitor of anoctamin 1, significantly inhibited PLC cyst growth and cyst enlargement in an embryonic kidney cyst model. Knockdown of ANO1 by morpholino analogs also attenuated embryonic cyst growth. Thus, calcium-activated chloride secretion by anoctamin 1 appears to be a crucial component of renal cyst growth.

  14. Activation and inhibition of TMEM16A calcium-activated chloride channels.

    PubMed

    Ni, Yu-Li; Kuan, Ai-Seon; Chen, Tsung-Yu

    2014-01-01

    Calcium-activated chloride channels (CaCC) encoded by family members of transmembrane proteins of unknown function 16 (TMEM16) have recently been intensely studied for functional properties as well as their physiological roles as chloride channels in various tissues. One technical hurdle in studying these channels is the well-known channel rundown that frequently impairs the precision of electrophysiological measurements for the channels. Using experimental protocols that employ fast-solution exchange, we circumvented the problem of channel rundown by normalizing the Ca(2+)-induced current to the maximally-activated current obtained within a time period in which the channel rundown was negligible. We characterized the activation of the TMEM16A-encoded CaCC (also called ANO1) by Ca(2+), Sr(2+), and Ba(2+), and discovered that Mg(2+) competes with Ca(2+) in binding to the divalent-cation binding site without activating the channel. We also studied the permeability of the ANO1 pore for various anions and found that the anion occupancy in the pore-as revealed by the permeability ratios of these anions-appeared to be inversely correlated with the apparent affinity of the ANO1 inhibition by niflumic acid (NFA). On the other hand, the NFA inhibition was neither affected by the degree of the channel activation nor influenced by the types of divalent cations used for the channel activation. These results suggest that the NFA inhibition of ANO1 is likely mediated by altering the pore function but not through changing the channel gating. Our study provides a precise characterization of ANO1 and documents factors that can affect divalent cation activation and NFA inhibition of ANO1.

  15. Possibility of inhibition of calcium-activated chloride channel rescuing erectile failures in diabetes.

    PubMed

    Lau, L-C; Adaikan, P G

    2014-01-01

    Although calcium-activated chloride channel (CaCC) blockers, niflumic acid (NFA) and anthracene-9-carboxylic acid (A9C), have been shown as potential erectogenic agents in healthy corpus cavernosum (CC) tissues, the pharmacological characteristics of CaCC blockers in diabetic state are relatively unknown. This study compares the direct muscle relaxant property of NFA and A9C with their influence on contraction and nitrergic relaxation as elicited by electrical field stimulation in normal and 16-week-old diabetic rabbit CC (n=8). Mean blood glucose level in alloxan-treated rabbits was elevated threefold (21.9±0.5 mmol  l(-1) vs 7.1±0.2 mmol l(-1) in untreated rabbits; P<0.05). There was no significant alteration in the efficacies of NFA and A9C in eliciting a concentration-dependent relaxation of noradrenaline-induced cavernosum tone and in inhibiting neurogenic contraction of CC from diabetic rabbits. The capability of NFA (100 μM) and A9C (1 mM) in augmenting nitrergic transmission was also not adversely affected by diabetes. However, in CC from diabetic rabbits, A9C markedly increased nitrergic relaxation response to 1-10 Hz by 10.6-36.6% (vs -5.1-0.8% in nondiabetic control). CaCC sensitivity to A9C appears to be enhanced in diabetic CC tissue. Inhibiting the CaCC activity in diabetes-related ED may tip the balance between proerectile/relaxant and antierectile/contractile mechanisms in favor of cavernosum relaxation.

  16. Anion permeation in calcium-activated chloride channels formed by TMEM16A from Xenopus tropicalis.

    PubMed

    Reyes, J P; López-Rodríguez, A; Espino-Saldaña, A E; Huanosta-Gutiérrez, A; Miledi, R; Martínez-Torres, A

    2014-09-01

    Calcium-activated chloride channels (CaCC) formed by anoctamin1/TMEM16A subunits are ubiquitously expressed, and these channels are known to prevent polyspermy in amphibian oocytes. Here, we describe a TMEM16A clone isolated from Xenopus tropicalis oocytes (xtTMEM16A) and how the anion permeation properties are modified in single-site mutants of the ion pore. The anion permeability sequence was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate (relative permeabilities 5.6:3.0:2.1:1:0.2, respectively). Dose-response curves indicated that the voltage-dependent half-maximal concentration for Ca(2+) activation (K d of the Hill equation at +100 mV) was 120 nM in normal external Cl(-), whereas it was displaced leftward to 75 nM Ca(2+), when I(-) replaced Cl(-). The I(-):Cl(-) mole fraction (MF) of the external solution was varied in order to gain insight into the permeation mechanism of the pore. No anomaly in MF behavior was observed for conductance, but it was observed for current reversal potential, which deviated from the prediction of the Goldman-Hodgkin-Katz equation. Mutations of positively charged amino acids in the pore, R646 and R761, to glutamate resulted in reduction of the relative permeability to I(-). Data from the wild type and mutants could be well fitted by a three-barrier, two-site permeation model. This suggests a multi-ion pore with at least two binding sites for anions, with R646 mole fraction closer to the extracellular membrane surface--being important for the stability of both sites--and R761--located deeper within the membrane--mainly affecting the innermost binding site. Considerations of xtTMEM16A putative pore region topology are discussed in the light of two alternative topological models of the protein. PMID:24352628

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

    PubMed

    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.

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

    PubMed

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

    2014-06-30

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

  19. [Effects of calcium-activated chloride channels on vascular activity of rat cerebral basilar artery].

    PubMed

    Wang, Rui; Li, Li; Ma, Ke-Tao; Si, Jun-Qiang

    2014-06-25

    This study investigated the role of calcium-activated Cl⁻ channels (CaCCs) in mediating vasomotor activity of cerebral basilar artery (BA) of Wistar rat. Pressure myograph was used to examine the changes in diameter of isolated BA to vasoactive reagents. The results showed that (1) The rate of pressure-induced vasomotor activity was 78.6% (n = 28) in BA from 0 to 100 mmHg working pressure. The contractile phase of the response was faster than the relaxation phase; (2) The amplitude of contraction was (62.6 ± 6.4) µm (n = 22), the frequency of contraction was variable and the highest value was 8.0 ± 2.3 per 5 min at 60 mmHg working pressure (n = 22); (3) The pressure-induced vasomotor activity of BA was markedly attenuated when Ca²⁺ was removed from medium; (4) The pressure-induced vasomotor activity was blocked by voltage dependent Ca²⁺ channel blocker nimodipine; (5) The pressure-induced vasomotor was inhibited by CaCC antagonists NFA and NPPB. These results suggest that the pressure-induced vasomotor activity of isolated BA is associated with Ca²⁺ influx that activates CaCCs.

  20. Chlorotoxin does not inhibit volume-regulated, calcium-activated and cyclic AMP-activated chloride channels.

    PubMed

    Maertens, C; Wei, L; Tytgat, J; Droogmans, G; Nilius, B

    2000-02-01

    It was the aim of this study to look for a high-affinity and selective polypeptide toxin, which could serve as a probe for the volume-regulated anion channel (VRAC) or the calcium-activated chloride channel (CaCC). We have partially purified chlorotoxin, including new and homologous short chain insectotoxins, from the crude venom of Leiurus quinquestriatus quinquestriatus (Lqq) by means of gel filtration chromatography. Material eluting between 280 and 420 min, corresponding to fractions 15-21, was lyophilized and tested on VRAC and CaCC, using the whole-cell patch-clamp technique. We have also tested the commercially available chlorotoxin on VRAC, CaCC, the cystic fibrosis transmembrane conductance regulator (CFTR) and on the glioma specific chloride channel (GCC). VRAC and the correspondent current, I(Cl,swell), was activated in Cultured Pulmonary Artery Endothelial (CPAE) cells by a 25% hypotonic solution. Neither of the fractions 16-21 significantly inhibited I(Cl,swell) (n=4-5). Ca(2+)-activated Cl(-) currents, I(Cl,Ca), activated by loading T84 cells via the patch pipette with 1 microM free Ca(2+), were not inhibited by any of the tested fractions (15-21), (n=2-5). Chlorotoxin (625 nM) did neither effect I(Cl,swell) nor I(Cl,Ca) (n=4-5). The CFTR channel, transiently transfected in COS cells and activated by a cocktail containing IBMX and forskolin, was not affected by 1.2 microM chlorotoxin (n=5). In addition, it did not affect currents through GCC. We conclude that submicromolar concentrations of chlorotoxin do not block volume-regulated, Ca(2+)-activated and CFTR chloride channels and that it can not be classified as a general chloride channel toxin.

  1. Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle

    PubMed Central

    Remy, Kenneth E.; Danielsson, Jennifer; Funayama, Hiromi; Fu, Xiao Wen; Chang, Herng-Yu Sucie; Yim, Peter; Xu, Dingbang; Emala, Charles W.

    2013-01-01

    Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma. PMID:23997176

  2. The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons.

    PubMed

    Cho, Hawon; Yang, Young Duk; Lee, Jesun; Lee, Byeongjoon; Kim, Tahnbee; Jang, Yongwoo; Back, Seung Keun; Na, Heung Sik; Harfe, Brian D; Wang, Fan; Raouf, Ramin; Wood, John N; Oh, Uhtaek

    2012-05-27

    Nociceptors are a subset of small primary afferent neurons that respond to noxious chemical, thermal and mechanical stimuli. Ion channels in nociceptors respond differently to noxious stimuli and generate electrical signals in different ways. Anoctamin 1 (ANO1 also known as TMEM16A) is a Ca(2+)-activated chloride channel that is essential for numerous physiological functions. We found that ANO1 was activated by temperatures over 44 °C with steep heat sensitivity. ANO1 was expressed in small sensory neurons and was highly colocalized with nociceptor markers, which suggests that it may be involved in nociception. Application of heat ramps to dorsal root ganglion (DRG) neurons elicited robust ANO1-dependent depolarization. Furthermore, knockdown or deletion of ANO1 in DRG neurons substantially reduced nociceptive behavior in thermal pain models. These results indicate that ANO1 is a heat sensor that detects nociceptive thermal stimuli in sensory neurons and possibly mediates nociception.

  3. Calcium-activated chloride channels in bovine pulmonary artery endothelial cells.

    PubMed Central

    Nilius, B; Prenen, J; Szücs, G; Wei, L; Tanzi, F; Voets, T; Droogmans, G

    1997-01-01

    1. We characterized Ca(2+)-activated Cl- currents in calf pulmonary artery endothelial (CPAE) cells by using a combined patch clamp and fura-2 microfluorescence technique to simultaneously measure ionic currents and the intracellular Ca2+ concentration, [Ca2+]i. 2. Various procedures that increased [Ca2+]i, such as stimulation with ATP or ionomycin, or loading the cells with Ca2+ via the patch pipette, activated a strongly outwardly rectifying current with a reversal potential close to the Cl- equilibrium potential. Changing the extracellular Cl- concentration shifted this reversal potential as predicted for a Cl- current. Buffering Ca2+ rises with BAPTA prevented ATP from activating the current. 3. Ca(2+)-activated Cl- currents could be distinguished from volume-activated Cl- currents, which were sometimes coactivated in the same cell. The latter showed much less outward rectification, their activation was voltage independent, and they could be inhibited by exposing the cells to hypertonic solutions. 4. The permeability ratio for the Ca(2+)-activated conductance of the anions iodide:chloride: gluconate was 1.71 +/- 0.06:1:0.39 +/- 0.03 (n = 12). 5. This Ca(2+)-activated Cl- current, ICl, Ca, inactivated rapidly at negative potentials and activated slowly at positive potentials. Outward tail currents were slowly decaying, while inward tail currents decayed much faster. 6. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonic-acid (DIDS) and niflumic acid inhibited Icl,Ca in a voltage-dependent manner, i.e. they exerted a more potent block at positive potentials. The block by N-phenylanthracilic acid (NPA), 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and tamoxifen was voltage independent. Niflumic acid and tamoxifen were the most potent blockers. 7. The single-channel conductance was 7.9 +/- 0.7 pS (n = 15) at 300 mM extracellular Cl-. The channel open probability was high at positive potentials, but very small at negative potentials. 8. It is concluded that [Ca2+]i

  4. Location of Release Sites and Calcium-Activated Chloride Channels Relative to Calcium Channels at the Photoreceptor Ribbon Synapse

    PubMed Central

    Mercer, A. J.; Rabl, K.; Riccardi, G. E.; Brecha, N. C.; Stella, S. L.

    2011-01-01

    Vesicle release from photoreceptor ribbon synapses is regulated by L-type Ca2+ channels, which are in turn regulated by Cl− moving through calcium-activated chloride [Cl(Ca)] channels. We assessed the proximity of Ca2+ channels to release sites and Cl(Ca) channels in synaptic terminals of salamander photoreceptors by comparing fast (BAPTA) and slow (EGTA) intracellular Ca2+ buffers. BAPTA did not fully block synaptic release, indicating some release sites are <100 nm from Ca2+ channels. Comparing Cl(Ca) currents with predicted Ca2+ diffusion profiles suggested that Cl(Ca) and Ca2+ channels average a few hundred nanometers apart, but the inability of BAPTA to block Cl(Ca) currents completely suggested some channels are much closer together. Diffuse immunolabeling of terminals with an antibody to the putative Cl(Ca) channel TMEM16A supports the idea that Cl(Ca) channels are dispersed throughout the presynaptic terminal, in contrast with clustering of Ca2+ channels near ribbons. Cl(Ca) currents evoked by intracellular calcium ion concentration ([Ca2+]i) elevation through flash photolysis of DM-nitrophen exhibited EC50 values of 556 and 377 nM with Hill slopes of 1.8 and 2.4 in rods and cones, respectively. These relationships were used to estimate average submembrane [Ca2+]i in photoreceptor terminals. Consistent with control of exocytosis by [Ca2+] nanodomains near Ca2+ channels, average submembrane [Ca2+]i remained below the vesicle release threshold (∼400 nM) over much of the physiological voltage range for cones. Positioning Ca2+ channels near release sites may improve fidelity in converting voltage changes to synaptic release. A diffuse distribution of Cl(Ca) channels may allow Ca2+ influx at one site to influence relatively distant Ca2+ channels. PMID:21084687

  5. Bile acids stimulate chloride secretion through CFTR and calcium-activated Cl- channels in Calu-3 airway epithelial cells.

    PubMed

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

    2014-09-01

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

  6. Self-cleavage of Human CLCA1 Protein by a Novel Internal Metalloprotease Domain Controls Calcium-activated Chloride Channel Activation*♦

    PubMed Central

    Yurtsever, Zeynep; Sala-Rabanal, Monica; Randolph, David T.; Scheaffer, Suzanne M.; Roswit, William T.; Alevy, Yael G.; Patel, Anand C.; Heier, Richard F.; Romero, Arthur G.; Nichols, Colin G.; Holtzman, Michael J.; Brett, Tom J.

    2012-01-01

    The chloride channel calcium-activated (CLCA) family are secreted proteins that regulate both chloride transport and mucin expression, thus controlling the production of mucus in respiratory and other systems. Accordingly, human CLCA1 is a critical mediator of hypersecretory lung diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, that manifest mucus obstruction. Despite relevance to homeostasis and disease, the mechanism of CLCA1 function remains largely undefined. We address this void by showing that CLCA proteins contain a consensus proteolytic cleavage site recognized by a novel zincin metalloprotease domain located within the N terminus of CLCA itself. CLCA1 mutations that inhibit self-cleavage prevent activation of calcium-activated chloride channel (CaCC)-mediated chloride transport. CaCC activation requires cleavage to unmask the N-terminal fragment of CLCA1, which can independently gate CaCCs. Gating of CaCCs mediated by CLCA1 does not appear to involve proteolytic cleavage of the channel because a mutant N-terminal fragment deficient in proteolytic activity is able to induce currents comparable with that of the native fragment. These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface. PMID:23112050

  7. Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance regulator inhibit cAMP-activated but not calcium-activated chloride currents.

    PubMed Central

    Wagner, J A; McDonald, T V; Nghiem, P T; Lowe, A W; Schulman, H; Gruenert, D C; Stryer, L; Gardner, P

    1992-01-01

    Phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) by cAMP-dependent protein kinase leads to chloride flux in epithelial cells. Is CFTR also required for the calcium-dependent activation of chloride channels? We used antisense oligodeoxynucleotides to CFTR to reduce the expression of CFTR in colonic and tracheal epithelial cells. The antisense oligomers were a pair of adjacent 18-mers complementary to nucleotides 1-18 and 19-36 of CFTR mRNA. Sense and misantisense oligomers served as controls. A 48-h antisense treatment reduced the expression of CFTR protein as assayed by immunoprecipitation and autoradiography to 26% of the level in sense-treated T84 cells. Whole-cell patch clamp revealed that a 48-h antisense treatment of T84 and 56FHTE-8o- fetal tracheal epithelial cells reduced the cAMP-activated chloride current to approximately 10% of that in sense-treated cells. The half-life of functional CFTR is less than 24 h in these cells. In contrast, the calcium-activated chloride current was not affected by antisense treatment. Hence, the cAMP and calcium pathways are separate. CFTR is required for the cAMP pathway but not for the calcium pathway. Images PMID:1379720

  8. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

    PubMed Central

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701

  9. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.

    PubMed

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.

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

    PubMed

    Jia, Linghan; Liu, Wen; Guan, Lizhao; Lu, Min; Wang, KeWei

    2015-01-01

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

  11. Variomics screen identifies the re-entrant loop of the calcium-activated chloride channel ANO1 that facilitates channel activation.

    PubMed

    Bill, Anke; Popa, M Oana; van Diepen, Michiel T; Gutierrez, Abraham; Lilley, Sarah; Velkova, Maria; Acheson, Kathryn; Choudhury, Hedaythul; Renaud, Nicole A; Auld, Douglas S; Gosling, Martin; Groot-Kormelink, Paul J; Gaither, L Alex

    2015-01-01

    The calcium-activated chloride channel ANO1 regulates multiple physiological processes. However, little is known about the mechanism of channel gating and regulation of ANO1 activity. Using a high-throughput, random mutagenesis-based variomics screen, we generated and functionally characterized ∼6000 ANO1 mutants and identified novel mutations that affected channel activity, intracellular trafficking, or localization of ANO1. Mutations such as S741T increased ANO1 calcium sensitivity and rendered ANO1 calcium gating voltage-independent, demonstrating a critical role of the re-entrant loop in coupling calcium and voltage sensitivity of ANO1 and hence in regulating ANO1 activation. Our data present the first unbiased and comprehensive study of the structure-function relationship of ANO1. The novel ANO1 mutants reported have diverse functional characteristics, providing new tools to study ANO1 function in biological systems, paving the path for a better understanding of the function of ANO1 and its role in health and diseases.

  12. Intermediate-conductance calcium-activated potassium channel KCa3.1 and chloride channel modulate chemokine ligand (CCL19/CCL21)-induced migration of dendritic cells.

    PubMed

    Shao, Zhifei; Gaurav, Rohit; Agrawal, Devendra K

    2015-07-01

    The role of ion channels is largely unknown in chemokine-induced migration in nonexcitable cells such as dendritic cells (DCs). Here, we examined the role of intermediate-conductance calcium-activated potassium channel (KCa3.1) and chloride channel (CLC3) in lymphatic chemokine-induced migration of DCs. The amplitude and kinetics of chemokine ligand (CCL19/CCL21)-induced Ca(2+) influx were associated with chemokine receptor 7 expression levels, extracellular-free Ca(2+) and Cl(-), and independent of extracellular K(+). Chemokines (CCL19 and CCL21) and KCa3.1 activator (1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) induced plasma membrane hyperpolarization and K(+) efflux, which was blocked by 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, suggesting that KCa3.1 carried larger conductance than the inward calcium release-activated calcium channel. Blockade of KCa3.1, low Cl(-) in the medium, and low dose of 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) impaired CCL19/CCL21-induced Ca(2+) influx, cell volume change, and DC migration. High doses of DIDS completely blocked DC migration possibly by significantly disrupting mitochondrial membrane potential. In conclusion, KCa3.1 and CLC3 are critical in human DC migration by synergistically regulating membrane potential, chemokine-induced Ca(2+) influx, and cell volume.

  13. Variomics Screen Identifies the Re-entrant Loop of the Calcium-activated Chloride Channel ANO1 That Facilitates Channel Activation*

    PubMed Central

    Bill, Anke; Popa, M. Oana; van Diepen, Michiel T.; Gutierrez, Abraham; Lilley, Sarah; Velkova, Maria; Acheson, Kathryn; Choudhury, Hedaythul; Renaud, Nicole A.; Auld, Douglas S.; Gosling, Martin; Groot-Kormelink, Paul J.; Gaither, L. Alex

    2015-01-01

    The calcium-activated chloride channel ANO1 regulates multiple physiological processes. However, little is known about the mechanism of channel gating and regulation of ANO1 activity. Using a high-throughput, random mutagenesis-based variomics screen, we generated and functionally characterized ∼6000 ANO1 mutants and identified novel mutations that affected channel activity, intracellular trafficking, or localization of ANO1. Mutations such as S741T increased ANO1 calcium sensitivity and rendered ANO1 calcium gating voltage-independent, demonstrating a critical role of the re-entrant loop in coupling calcium and voltage sensitivity of ANO1 and hence in regulating ANO1 activation. Our data present the first unbiased and comprehensive study of the structure-function relationship of ANO1. The novel ANO1 mutants reported have diverse functional characteristics, providing new tools to study ANO1 function in biological systems, paving the path for a better understanding of the function of ANO1 and its role in health and diseases. PMID:25425649

  14. The Porcine Chloride Channel Calcium-Activated Family Member pCLCA4a Mirrors Lung Expression of the Human hCLCA4

    PubMed Central

    Plog, Stephanie; Grötzsch, Tanja; Klymiuk, Nikolai; Kobalz, Ursula; Gruber, Achim D.

    2012-01-01

    Pig models of cystic fibrosis (CF) have recently been established that are expected to mimic the human disease closer than mouse models do. The human CLCA (originally named chloride channels, calcium-activated) member hCLCA4 is considered a potential modifier of disease severity in CF, but its murine ortholog, mCLCA6, is not expressed in the mouse lung. Here, we have characterized the genomic structure, protein processing, and tissue expression patterns of the porcine ortholog to hCLCA4, pCLCA4a. The genomic structure and cellular protein processing of pCLCA4a were found to closely mirror those of hCLCA4 and mCLCA6. Similar to human lung, pCLCA4a mRNA was strongly expressed in porcine lungs, and the pCLCA4a protein was immunohistochemically detected on the apical membranes of tracheal and bronchial epithelial cells. This stands in sharp contrast to mouse mCLCA6, which has been detected exclusively in intestinal epithelia but not the murine lung. The results may add to the understanding of species-specific differences in the CF phenotype and support the notion that the CF pig model may be more suitable than murine models to study the role of hCLCA4. PMID:22205680

  15. Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels.

    PubMed

    Peters, Christian J; Yu, Haibo; Tien, Jason; Jan, Yuh Nung; Li, Min; Jan, Lily Yeh

    2015-03-17

    TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasoning that the positive charges on basic residues are likely contributors to anion selectivity, we performed whole-cell recordings of mutants with alanine substitution for basic residues within the putative pore region and identified four residues on four different putative transmembrane segments that significantly increased the permeability of the larger halides and thiocyanate relative to that of chloride. Because TMEM16A permeation properties are known to shift with changes in intracellular calcium concentration, we further examined the calcium dependence of anion selectivity. We found that WT TMEM16A but not mutants with alanine substitution at those four basic residues exhibited a clear decline in the preference for larger anions as intracellular calcium was increased. Having implicated these residues as contributing to the TMEM16A pore, we scrutinized candidate small molecules from a high-throughput CaCC inhibitor screen to identify two compounds that act as pore blockers. Mutations of those four putative pore-lining basic residues significantly altered the IC50 of these compounds at positive voltages. These findings contribute to our understanding regarding anion permeation of TMEM16A CaCC and provide valuable pharmacological tools to probe the channel pore.

  16. Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1)*

    PubMed Central

    Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S.; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P.

    2015-01-01

    Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted. PMID:26004777

  17. Differential expression of calcium-activated chloride channels (CLCA) gene family members in the small intestine of cystic fibrosis mouse models.

    PubMed

    Leverkoehne, Ina; Holle, Hannah; Anton, Friederike; Gruber, Achim D

    2006-08-01

    Members of the family of calcium-activated chloride channels (CLCA) have been implicated as modulators of the phenotype in cystic fibrosis (CF). Here, the expression levels of the murine mCLCA1, mCLCA2, mCLCA3 and mCLCA4 were quantified by real-time RT-PCR in the small intestines of CF (cftr (tm1Cam), cftr (TgH(neoim)1Hgu)) and wild type C57BL/6, BALB/c, DBA/2 and NMRI mice. Markedly different expression levels of all four CLCA homologs were observed between the different wild type strains. Expression of mCLCA1 and mCLCA4 was similar in CF versus wild type. In contrast, mCLCA3 mRNA copy numbers were increased up to threefold in all CF models. Immunohistochemical detection of mCLCA3 and PAS reactions on consecutive tissue sections identified a similar increase in mCLCA3 expressing goblet cells, suggesting that elevated mRNA copy numbers of mCLCA3 are due to goblet cell hyperplasia rather than transcriptional regulatory events. Increased mCLCA2 mRNA copy numbers, however, were considered more likely to be due to transcriptional upregulation. Changes in mRNA copy numbers were not associated with altered cell kinetics as determined by immunohistochemistry using antibodies to phospho-histone 3 and activated caspase-3. The results suggest that both mCLCA2 and mCLCA3 may act as modifiers of the intestinal phenotype in CF.

  18. Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1).

    PubMed

    Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P

    2015-07-10

    Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted.

  19. 9-Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential.

    PubMed

    Váczi, Krisztina; Hegyi, Bence; Ruzsnavszky, Ferenc; Kistamás, Kornél; Horváth, Balázs; Bányász, Tamás; Nánási, Péter P; Szentandrássy, Norbert; Magyar, János

    2015-01-01

    Understanding the role of ionic currents in shaping the cardiac action potential (AP) has great importance as channel malfunctions can lead to sudden cardiac death by inducing arrhythmias. Therefore, researchers frequently use inhibitors to selectively block a certain ion channel like 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC) for calcium-activated chloride current (ICl(Ca)). This study aims to explore which blocker is preferable to study ICl(Ca). Whole-cell voltage-clamp technique was used to record ICa,L, IKs, IKr and IK1, while action potentials were measured using sharp microelectrodes. DIDS- (0.2 mM) and 9-AC-sensitive (0.5 mM) currents were identical in voltage-clamp conditions, regardless of intracellular Ca(2+) buffering. DIDS-sensitive current amplitude was larger with the increase of stimulation rate and correlated well with the rate-induced increase of calcium transients. Both drugs increased action potential duration (APD) to the same extent, but the elevation of the plateau potential was more pronounced with 9-AC at fast stimulation rates. On the contrary, 9-AC did not influence either the AP amplitude or the maximal rate of depolarization (V max), but DIDS caused marked reduction of V max. Both inhibitors reduced the magnitude of phase-1, but, at slow stimulation rates, this effect of DIDS was larger. All of these actions on APs were reversible upon washout of the drugs. Increasing concentrations of 9-AC between 0.1 and 0.5 mM in a cumulative manner gradually reduced phase-1 and increased APD. 9-AC at 1 mM had no additional actions upon perfusion after 0.5 mM. The half-effective concentration of 9-AC was approximately 160 μM with a Hill coefficient of 2. The amplitudes of ICa,L, IKs, IKr and IK1 were not changed by 0.5 mM 9-AC. These results suggest that DIDS is equally useful to study ICl(Ca) during voltage-clamp but 9-AC is superior in AP measurements for studying the physiological role of

  20. Development and validation of HTS assay for screening the calcium-activated chloride channel modulators in TMEM16A stably expressed CHO cells.

    PubMed

    Qi, Jinlong; Wang, Yuan; Liu, Yani; Zhang, Fan; Guan, Bingcai; Zhang, Hailin

    2014-02-01

    Calcium-activated chloride channels (CaCCs), for example TMEM16A, are widely expressed in a variety of tissues and are involved in many important physiological functions. We developed and validated an atomic absorption spectroscopy (AAS)-based detection system for high-throughput screening (HTS) of CaCC modulators. With this assay, Cl(-) flux from CHO cells stably transfected with TMEM16A is assayed indirectly, by measuring excess silver ions (Ag(+)) in the supernatant of AgCl precipitates. The screening process involved four steps: (1) TMEM16A CHO cells were incubated in high-K(+) and high-Cl(-) buffer with test compounds, and with ionomycin as Ca(2+) ionophore, for 12 min; (2) cells were washed with a low-K(+), Cl(-)-free and Ca(2+)-free buffer; (3) CaCC/TMEM16A were activated in high-K(+), Cl(-)-free buffer with ionomycin (10 μmol L(-1)) for 12 min; and (4) excess Ag(+) concentration was measured using an ion channel reader (ICR, an AAS system). The assay can be used to screen CaCC activators and inhibitors at the same time. With this assay, positive control drugs, including NPPB, CaCCinh-A01, flufenamic acid (Flu) and Eact, all had good concentration-dependent effects on CaCC/TMEM16A. NPPB and CaCCinh-A01 inhibited the CaCC/TMEM16A currents completely at 300 μmol L(-1), with IC50 values of 39.35 ± 4.72 μmol L(-1) and 6.35 ± 0.27 μmol L(-1), respectively; and Eact, activated CaCC/TMEM16A, with an EC50 value of 3.92 ± 0.87 μmol L(-1).

  1. Noradrenaline activates a calcium-activated chloride conductance and increases the voltage-dependent calcium current in cultured single cells of rat portal vein.

    PubMed

    Pacaud, P; Loirand, G; Mironneau, C; Mironneau, J

    1989-05-01

    1. Membrane responses were recorded by a patch pipette technique in cultured cells isolated from rat portal vein. Using the whole-cell mode, pressure ejections of noradrenaline evoked depolarization (current clamp) and inward current (voltage clamp) at membrane potentials of -60 to -70 mV. The noradrenaline-induced response was reversibly blocked by prazosin indicating that the response was mediated by alpha 1-adrenoceptors. 2. The ionic mechanism of the noradrenaline-induced inward current was investigated in potassium-free caesium-containing solutions. Alteration of the chloride equilibrium potential produced similar changes in the reversal potential of the noradrenaline-induced current, indicating that noradrenaline opened chloride-selective channels. There was no evidence implicating sodium or calcium as the charge-carrying ion. 3. Caffeine applied in the bathing solution also induced a transient increase in chloride conductance but the noradrenaline-induced response was lost after application of caffeine. This is interpreted to mean that the increase in chloride conductance induced by noradrenaline and caffeine can occur as a consequence of a rise in intracellular calcium concentration depending on release of calcium from the same intracellular stores. 4. In the presence of caffeine, noradrenaline increased both the voltage-dependent calcium and chloride membrane conductances during application of repetitive depolarizing pulses. It is concluded that in isolated cells of the rat portal vein the depolarization in response to noradrenaline is mediated by an increase in chloride conductance depending on both the calcium release from intracellular stores and the increase of the voltage-dependent calcium current. PMID:2470458

  2. Lipoxin A4 Stimulates Calcium-Activated Chloride Currents and Increases Airway Surface Liquid Height in Normal and Cystic Fibrosis Airway Epithelia

    PubMed Central

    Al-Alawi, Mazen; Costello, Richard W.; McNally, Paul; Chiron, Raphaël; Harvey, Brian J.; Urbach, Valérie

    2012-01-01

    Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl− secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA4 is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA4 are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA4 produced a rapid and transient increase in intracellular Ca2+. We have investigated, the effect of LXA4 on Cl− secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA4 stimulated a rapid intracellular Ca2+ increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA4 stimulated whole-cell Cl− currents which were inhibited by NPPB (calcium-activated Cl− channel inhibitor), BAPTA-AM (chelator of intracellular Ca2+) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA4 increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA4 effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl− secretion. The LXA4 stimulation of intracellular Ca2+, whole-cell Cl− currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA4 in the stimulation of intracellular Ca2+ signalling leading to Ca2+-activated Cl− secretion and enhanced ASL height in non-CF and CF bronchial epithelia. PMID:22662206

  3. Immunohistochemical Localization of Cyclic GMP-Dependent Protein Kinase in Mammalian Brain

    NASA Astrophysics Data System (ADS)

    Lohmann, Suzanne M.; Walter, Ulrich; Miller, Penelope E.; Greengard, Paul; de Camilli, Pietro

    1981-01-01

    The distribution of cyclic GMP-dependent protein kinase in rat brain has been studied by an immunological approach involving radioimmunoassay and fluorescence immunohistochemistry. Data obtained by radioimmunoassay indicate that cyclic GMP-dependent protein kinase is 20- to 40-fold more concentrated in cerebellum than in other brain regions. Immunohistochemical experiments demonstrate that the high concentration of immunoreactivity of the protein kinase in cerebellum is attributable to Purkinje cells. Immunoreactivity in these cells is homogeneously distributed throughout the cell (perikarya, dendrites, and axons) with the exception of the nucleus. No other neurons either in the cerebellum or in other brain regions were stained by antiserum to the protein kinase. Immunoreactivity, however, was found throughout the brain on smooth muscle cells of blood vessels.

  4. Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth.

    PubMed

    Dhayade, Sandeep; Kaesler, Susanne; Sinnberg, Tobias; Dobrowinski, Hyazinth; Peters, Stefanie; Naumann, Ulrike; Liu, He; Hunger, Robert E; Thunemann, Martin; Biedermann, Tilo; Schittek, Birgit; Simon, Hans-Uwe; Feil, Susanne; Feil, Robert

    2016-03-22

    Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked to an increased risk of melanoma. Here, we have examined the potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination of biochemical assays and real-time monitoring of melanoma cells, we report a cGMP-dependent growth-promoting pathway in murine and human melanoma cells. We document that C-type natriuretic peptide (CNP), a ligand of the membrane-bound guanylate cyclase B, enhances the activity of cGMP-dependent protein kinase I (cGKI) in melanoma cells by increasing the intracellular levels of cGMP. Activation of this cGMP pathway promotes melanoma cell growth and migration in a p44/42 MAPK-dependent manner. Sildenafil treatment further increases intracellular cGMP concentrations, potentiating activation of this pathway. Collectively, our data identify this cGMP-cGKI pathway as the link between sildenafil usage and increased melanoma risk. PMID:26971999

  5. A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium-activated chloride secretion in human sweat gland epithelial cells.

    PubMed

    Ertongur-Fauth, Torsten; Hochheimer, Andreas; Buescher, Joerg Martin; Rapprich, Stefan; Krohn, Michael

    2014-11-01

    Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca(2+) -activated Cl(-) channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL-SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A-dimerization domain. Chloride flux assays using halide-sensitive YFP revealed that TMEM16A is functionally involved in Ca(2+) -dependent Cl(-) secretion in NCL-SG3 cells. Recombinant expression in NCL-SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca(2+) -activated Cl(-) permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland-specific Cl(-) secretion providing opportunities to develop sweat gland-specific therapeutics for treatment of sweating disorders.

  6. Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1.

    PubMed

    Piechowicz, Katarzyna A; Truong, Eric C; Javed, Kashif M; Chaney, Rachelle R; Wu, Johnny Y; Phuan, Puay W; Verkman, Alan S; Anderson, Marc O

    2016-12-01

    Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca(2+) activated Cl(-) channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 μM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ∼1 μM for inhibition of TMEM16A chloride conductance.

  7. Huntingtin-associated protein 1 (HAP1) is a cGMP-dependent kinase anchoring protein (GKAP) specific for the cGMP-dependent protein kinase Iβ isoform.

    PubMed

    Corradini, Eleonora; Burgers, Pepijn P; Plank, Michael; Heck, Albert J R; Scholten, Arjen

    2015-03-20

    Protein-protein interactions are important in providing compartmentalization and specificity in cellular signal transduction. Many studies have hallmarked the well designed compartmentalization of the cAMP-dependent protein kinase (PKA) through its anchoring proteins. Much less data are available on the compartmentalization of its closest homolog, cGMP-dependent protein kinase (PKG), via its own PKG anchoring proteins (GKAPs). For the enrichment, screening, and discovery of (novel) PKA anchoring proteins, a plethora of methodologies is available, including our previously described chemical proteomics approach based on immobilized cAMP or cGMP. Although this method was demonstrated to be effective, each immobilized cyclic nucleotide did not discriminate in the enrichment for either PKA or PKG and their secondary interactors. Hence, with PKG signaling components being less abundant in most tissues, it turned out to be challenging to enrich and identify GKAPs. Here we extend this cAMP-based chemical proteomics approach using competitive concentrations of free cyclic nucleotides to isolate each kinase and its secondary interactors. Using this approach, we identified Huntingtin-associated protein 1 (HAP1) as a putative novel GKAP. Through sequence alignment with known GKAPs and secondary structure prediction analysis, we defined a small sequence domain mediating the interaction with PKG Iβ but not PKG Iα. In vitro binding studies and site-directed mutagenesis further confirmed the specificity and affinity of HAP1 binding to the PKG Iβ N terminus. These data fully support that HAP1 is a GKAP, anchoring specifically to the cGMP-dependent protein kinase isoform Iβ, and provide further evidence that also PKG spatiotemporal signaling is largely controlled by anchoring proteins.

  8. cGMP-dependent protein kinase: linking foraging to energy homeostasis.

    PubMed

    Kaun, Karla R; Sokolowski, Marla B

    2009-01-01

    Successful foraging is necessary for procurement of nutritional resources essential for an animal's survival. Maintenance of foraging and food acquisition is dependent on the ability to balance food intake and energy expenditure. This review examines the role of cGMP-dependent protein kinase (PKG) as a regulator of foraging behaviour, food acquisition, and energy balance. The role of PKG in food-related behaviours is highly conserved among worms, flies, bees, ants, and mammals. A growing body of literature suggests that PKG plays an integral role in the component behaviours and physiologies underlying foraging behaviour. These include energy acquisition, nutrient absorption, nutrient allocation, nutrient storage, and energy use. New evidence suggests that PKG mediates both neural and physiological mechanisms underlying these processes. This review illustrates how investigating the role of PKG in energy homeostasis in a diversity of organisms can offer a broad perspective on the mechanisms mediating energy balance.

  9. Nitric oxide signaling modulates synaptic inhibition in the superior paraolivary nucleus (SPN) via cGMP-dependent suppression of KCC2

    PubMed Central

    Yassin, Lina; Radtke-Schuller, Susanne; Asraf, Hila; Grothe, Benedikt; Hershfinkel, Michal; Forsythe, Ian D.; Kopp-Scheinpflug, Cornelia

    2014-01-01

    Glycinergic inhibition plays a central role in the auditory brainstem circuitries involved in sound localization and in the encoding of temporal action potential firing patterns. Modulation of this inhibition has the potential to fine-tune information processing in these networks. Here we show that nitric oxide (NO) signaling in the auditory brainstem (where activity-dependent generation of NO is documented) modulates the strength of inhibition by changing the chloride equilibrium potential. Recent evidence demonstrates that large inhibitory postsynaptic currents (IPSCs) in neurons of the superior paraolivary nucleus (SPN) are enhanced by a very low intracellular chloride concentration, generated by the neuronal potassium chloride co-transporter (KCC2) expressed in the postsynaptic neurons. Our data show that modulation by NO caused a 15 mV depolarizing shift of the IPSC reversal potential, reducing the strength of inhibition in SPN neurons, without changing the threshold for action potential firing. Regulating inhibitory strength, through cGMP-dependent changes in the efficacy of KCC2 in the target neuron provides a postsynaptic mechanism for rapidly controlling the inhibitory drive, without altering the timing or pattern of the afferent spike train. Therefore, this NO-mediated suppression of KCC2 can modulate inhibition in one target nucleus (SPN), without influencing inhibitory strength of other target nuclei (MSO, LSO) even though they are each receiving collaterals from the same afferent nucleus (a projection from the medial nucleus of the trapezoid body, MNTB). PMID:24987336

  10. Activity of cGMP-Dependent Protein Kinase (PKG) Affects Sucrose Responsiveness and Habituation in "Drosophila melanogaster"

    ERIC Educational Resources Information Center

    Scheiner, Ricarda; Sokolowski, Marla B.; Erber, Joachim

    2004-01-01

    The cGMP-dependent protein kinase (PKG) has many cellular functions in vertebrates and insects that affect complex behaviors such as locomotion and foraging. The "foraging" ("for") gene encodes a PKG in "Drosophila melanogaster." Here, we demonstrate a function for the "for" gene in sensory responsiveness and nonassociative learning. Larvae of the…

  11. Brain Region-Specific Effects of cGMP-Dependent Kinase II Knockout on AMPA Receptor Trafficking and Animal Behavior

    ERIC Educational Resources Information Center

    Kim, Seonil; Pick, Joseph E.; Abera, Sinedu; Khatri, Latika; Ferreira, Danielle D. P.; Sathler, Matheus F.; Morison, Sage L.; Hofmann, Franz; Ziff, Edward B.

    2016-01-01

    Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO…

  12. Gibberelic acid and cGMP-dependent transcriptional regulation in Arabidopsis thaliana

    PubMed Central

    Bastian, René; Dawe, Adam; Meier, Stuart; Ludidi, Ndiko; Bajic, Vladimir B

    2010-01-01

    An ever increasing amount of transcriptomic data and analysis tools provide novel insight into complex responses of biological systems. Given these resources we have undertaken to review aspects of transcriptional regulation in response to the plant hormone gibberellic acid (GA) and its second messenger guanosine 3′,5′-cyclic monophosphate (cGMP) in Arabidopsis thaliana, both wild type and selected mutants. Evidence suggests enrichment of GA-responsive (GARE ) elements in promoters of genes that are transcriptionally upregulated in response to cGMP but downregulated in a GA insensitive mutant (ga1-3). In contrast, in the genes upregulated in the mutant, no enrichment in the GARE is observed suggesting that GARE motifs are diagnostic for GA-induced and cGMP-dependent transcriptional upregulation. Further, we review how expression studies of GA-dependent transcription factors and transcriptional networks based on common promoter signatures derived from ab initio analyses can contribute to our understanding of plant responses at the systems level. PMID:20118660

  13. Function of cGMP-dependent protein kinase II in volume load-induced diuresis.

    PubMed

    Schramm, Andrea; Schinner, Elisabeth; Huettner, Johannes P; Kees, Frieder; Tauber, Philipp; Hofmann, Franz; Schlossmann, Jens

    2014-10-01

    Atrial natriuretic peptide (ANP)/cGMPs cause diuresis and natriuresis. Their downstream effectors beyond cGMP remain unclear. To elucidate a probable function of cGMP-dependent protein kinase II (cGKII), we investigated renal parameters in different conditions (basal, salt diets, starving, water load) using a genetically modified mouse model (cGKII-KO), but did not detect any striking differences between WT and cGKII-KO. Thus, cGKII is proposed to play only a marginal role in the adjustment of renal concentration ability to varying salt loads without water restriction or starving conditions. When WT mice were subjected to a volume load (performed by application of a 10-mM glucose solution (3% of BW) via feeding needle), they exhibited a potent diuresis. In contrast, urine volume was decreased significantly in cGKII-KO. We showed that AQP2 plasma membrane (PM) abundance was reduced for about 50% in WT upon volume load, therefore, this might be a main cause for the enhanced diuresis. In contrast, cGKII-KO mice almost completely failed to decrease AQP2-PM distribution. This significant difference between both genotypes is not induced by an altered p-Ser256-AQP2 phosphorylation, as phosphorylation at this site decreases similarly in WT and KO. Furthermore, sodium excretion was lowered in cGKII-KO mice during volume load. In summary, cGKII is only involved to a minor extent in the regulation of basal renal concentration ability. By contrast, cGKII-KO mice are not able to handle an acute volume load. Our results suggest that membrane insertion of AQP2 is inhibited by cGMP/cGKII.

  14. The plant natriuretic peptide receptor is a guanylyl cyclase and enables cGMP-dependent signaling.

    PubMed

    Turek, Ilona; Gehring, Chris

    2016-06-01

    The functional homologues of vertebrate natriuretic peptides (NPs), the plant natriuretic peptides (PNPs), are a novel class of peptidic hormones that signal via guanosine 3',5'-cyclic monophosphate (cGMP) and systemically affect plant salt and water balance and responses to biotrophic plant pathogens. Although there is increasing understanding of the complex roles of PNPs in plant responses at the systems level, little is known about the underlying signaling mechanisms. Here we report isolation and identification of a novel Leucine-Rich Repeat (LRR) protein that directly interacts with A. thaliana PNP, AtPNP-A. In vitro binding studies revealed that the Arabidopsis AtPNP-A binds specifically to the LRR protein, termed AtPNP-R1, and the active region of AtPNP-A is sufficient for the interaction to occur. Importantly, the cytosolic part of the AtPNP-R1, much like in some vertebrate NP receptors, harbors a catalytic center diagnostic for guanylyl cyclases and the recombinant AtPNP-R1 is capable of catalyzing the conversion of guanosine triphosphate to cGMP. In addition, we show that AtPNP-A causes rapid increases of cGMP levels in wild type (WT) leaf tissue while this response is significantly reduced in the atpnp-r1 mutants. AtPNP-A also causes cGMP-dependent net water uptake into WT protoplasts, and hence volume increases, whereas responses of the protoplasts from the receptor mutant are impaired. Taken together, our results suggest that the identified LRR protein is an AtPNP-A receptor essential for the PNP-dependent regulation of ion and water homeostasis in plants and that PNP- and vertebrate NP-receptors and their signaling mechanisms share surprising similarities. PMID:26945740

  15. Type II cGMP-dependent Protein Kinase Mediates Osteoblast Mechanotransduction*S⃞

    PubMed Central

    Rangaswami, Hema; Marathe, Nisha; Zhuang, Shunhui; Chen, Yongchang; Yeh, Jiunn-Chern; Frangos, John A.; Boss, Gerry R.; Pilz, Renate B.

    2009-01-01

    Continuous bone remodeling in response to mechanical loading is critical for skeletal integrity, and interstitial fluid flow is an important stimulus for osteoblast/osteocyte growth and differentiation. However, the biochemical signals mediating osteoblast anabolic responses to mechanical stimulation are incompletely understood. In primary human osteoblasts and murine MC3T3-E1 cells, we found that fluid shear stress induced rapid expression of c-fos, fra-1, fra-2, and fosB/ΔfosB mRNAs; these genes encode transcriptional regulators that maintain skeletal integrity. Fluid shear stress increased osteoblast nitric oxide (NO) synthesis, leading to activation of cGMP-dependent protein kinase (PKG). Pharmacological inhibition of the NO/cGMP/PKG signaling pathway blocked shear-induced expression of all four fos family genes. Induction of these genes required signaling through MEK/Erk, and Erk activation was NO/cGMP/PKG-dependent. Treating cells with a membrane-permeable cGMP analog partly mimicked the effects of fluid shear stress on Erk activity and fos family gene expression. In cells transfected with small interfering RNAs (siRNA) specific for membrane-bound PKG II, shear- and cGMP-induced Erk activation and fos family gene expression was nearly abolished and could be restored by transducing cells with a virus encoding an siRNA-resistant form of PKG II; in contrast, siRNA-mediated repression of the more abundant cytosolic PKG I isoform was without effect. Thus, we report a novel function for PKG II in osteoblast mechanotransduction, and we propose a model whereby NO/cGMP/PKG II-mediated Erk activation and induction of c-fos, fra-1, fra-2, and fosB/ΔfosB play a key role in the osteoblast anabolic response to mechanical stimulation. PMID:19282289

  16. cGMP-dependent ABA-induced stomatal closure in the ABA-insensitive Arabidopsis mutant abi1-1.

    PubMed

    Dubovskaya, Lyudmila V; Bakakina, Yulia S; Kolesneva, Ekaterina V; Sodel, Dmitry L; McAinsh, Martin R; Hetherington, Alistair M; Volotovski, Igor D

    2011-07-01

    • The drought hormone abscisic acid (ABA) is widely known to produce reductions in stomatal aperture in guard cells. The second messenger cyclic guanosine 3', 5'-monophosphate (cGMP) is thought to form part of the signalling pathway by which ABA induces stomatal closure. • We have examined the signalling events during cGMP-dependent ABA-induced stomatal closure in wild-type Arabidopsis plants and plants of the ABA-insensitive Arabidopsis mutant abi1-1. • We show that cGMP acts downstream of hydrogen peroxide (H(2) O(2) ) and nitric oxide (NO) in the signalling pathway by which ABA induces stomatal closure. H(2) O(2) - and NO-induced increases in the cytosolic free calcium concentration ([Ca(2+) ](cyt) ) were cGMP-dependent, positioning cGMP upstream of [Ca(2+) ](cyt) , and involved the action of the type 2C protein phosphatase ABI1. Increases in cGMP were mediated through the stimulation of guanylyl cyclase by H(2) O(2) and NO. We identify nucleoside diphosphate kinase as a new cGMP target protein in Arabidopsis. • This study positions cGMP downstream of ABA-induced changes in H(2) O(2) and NO, and upstream of increases in [Ca(2+) ](cyt) in the signalling pathway leading to stomatal closure.

  17. Novel crosstalk to BMP signalling: cGMP-dependent kinase I modulates BMP receptor and Smad activity

    PubMed Central

    Schwappacher, Raphaela; Weiske, Jörg; Heining, Eva; Ezerski, Verena; Marom, Barak; Henis, Yoav I; Huber, Otmar; Knaus, Petra

    2009-01-01

    Integration of multiple signals into the canonical BMP/Smad pathway poses a big challenge during the course of embryogenesis and tissue homeostasis. Here, we show that cyclic guanosine 3′,5′-monophosphate (cGMP)-dependent kinase I (cGKI) modulates BMP receptors and Smads, providing a novel mechanism enhancing BMP signalling. cGKI, a key mediator of vasodilation and hypertension diseases, interacts with and phosphorylates the BMP type II receptor (BMPRII). In response to BMP-2, cGKI then dissociates from the receptors, associates with activated Smads, and undergoes nuclear translocation. In the nucleus, cGKI binds with Smad1 and the general transcription factor TFII-I to promoters of BMP target genes such as Id1 to enhance transcriptional activation. Accordingly, cGKI has a dual function in BMP signalling: (1) it modulates BMP receptor/Smad activity at the plasma membrane and (2) after redistribution to the nucleus, it further regulates transcription as a nuclear co-factor for Smads. Consequently, cellular defects caused by mutations in BMPRII, found in pulmonary arterial hypertension patients, were compensated through cGKI, supporting the positive action of cGKI on BMP-induced Smad signalling downstream of the receptors. PMID:19424179

  18. Phosphorylation of septin 3 on Ser-91 by cGMP-dependent protein kinase-I in nerve terminals

    PubMed Central

    2004-01-01

    The septins are a family of GTPase enzymes required for cytokinesis and play a role in exocytosis. Among the ten vertebrate septins, Sept5 (CDCrel-1) and Sept3 (G-septin) are primarily concentrated in the brain, wherein Sept3 is a substrate for PKG-I (cGMP-dependent protein kinase-I) in nerve terminals. There are two motifs for potential PKG-I phosphorylation in Sept3, Thr-55 and Ser-91, but phosphoamino acid analysis revealed that the primary site is a serine. Derivatization of phosphoserine to S-propylcysteine followed by N-terminal sequence analysis revealed Ser-91 as a major phosphorylation site. Tandem MS revealed a single phosphorylation site at Ser-91. Substitution of Ser-91 with Ala in a synthetic peptide abolished phosphorylation. Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Antibodies raised against a peptide containing phospho-Ser-91 detected phospho-Sept3 only in the cytosol of nerve terminals, whereas Sept3 was located in a peripheral membrane extract. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons. PMID:15107017

  19. Ca sup 2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes

    SciTech Connect

    Mery, P-F.; Fischmeister, R. ); Lohmann, S.M.; Walter, U. )

    1991-02-15

    Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca{sup 2+}-channel current (I{sub Ca}) through the opposite actions for two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of I{sub Ca} is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of I{sub Ca} by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate I{sub Ca} via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on I{sub Ca} was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK. Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function.

  20. Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice.

    PubMed

    Wincott, Charlotte M; Kim, Seonil; Titcombe, Roseann F; Tukey, David S; Girma, Hiwot K; Pick, Joseph E; Devito, Loren M; Hofmann, Franz; Hoeffer, Charles; Ziff, Edward B

    2013-01-01

    Activity-dependent trafficking of AMPA receptors to synapses regulates synaptic strength. Activation of the NMDA receptor induces several second messenger pathways that contribute to receptor trafficking-dependent plasticity, including the NO pathway, which elevates cGMP. In turn, cGMP activates the cGMP-dependent protein kinase type II (cGKII), which phosphorylates the AMPA receptor subunit GluA1 at serine 845, a critical step facilitating synaptic delivery in the mechanism of activity-dependent synaptic potentiation. Since cGKII is expressed in the striatum, amygdala, cerebral cortex, and hippocampus, it has been proposed that mice lacking cGKII may present phenotypic differences compared to their wild-type littermates in emotion-dependent tasks, learning and memory, and drug reward salience. Previous studies have shown that cGKII KO mice ingest higher amounts of ethanol as well as exhibit elevated anxiety levels compared to wild-type (WT) littermates. Here, we show that cGKII KO mice are significantly deficient in spatial learning while exhibiting facilitated motor coordination, demonstrating a clear dependence of memory-based tasks on cGKII. We also show diminished GluA1 phosphorylation in the postsynaptic density (PSD) of cGKII KO prefrontal cortex while in hippocampal PSD fractions, phosphorylation was not significantly altered. These data suggest that the role of cGKII may be more robust in particular brain regions, thereby impacting complex behaviors dependent on these regions differently.

  1. Natural Variation in the Thermotolerance of Neural Function and Behavior due to a cGMP-Dependent Protein Kinase

    PubMed Central

    Dawson-Scully, Ken; Armstrong, Gary A.B.; Kent, Clement; Robertson, R. Meldrum; Sokolowski, Marla B.

    2007-01-01

    Although it is acknowledged that genetic variation contributes to individual differences in thermotolerance, the specific genes and pathways involved and how they are modulated by the environment remain poorly understood. We link natural variation in the thermotolerance of neural function and behavior in Drosophila melanogaster to the foraging gene (for, which encodes a cGMP-dependent protein kinase (PKG)) as well as to its downstream target, protein phosphatase 2A (PP2A). Genetic and pharmacological manipulations revealed that reduced PKG (or PP2A) activity caused increased thermotolerance of synaptic transmission at the larval neuromuscular junction. Like synaptic transmission, feeding movements were preserved at higher temperatures in larvae with lower PKG levels. In a comparative assay, pharmacological manipulations altering thermotolerance in a central circuit of Locusta migratoria demonstrated conservation of this neuroprotective pathway. In this circuit, either the inhibition of PKG or PP2A induced robust thermotolerance of neural function. We suggest that PKG and therefore the polymorphism associated with the allelic variation in for may provide populations with natural variation in heat stress tolerance. for's function in behavior is conserved across most organisms, including ants, bees, nematodes, and mammals. PKG's role in thermotolerance may also apply to these and other species. Natural variation in thermotolerance arising from genes involved in the PKG pathway could impact the evolution of thermotolerance in natural populations. PMID:17712421

  2. Alterations in the Cerebellar (Phospho)Proteome of a Cyclic Guanosine Monophosphate (cGMP)-dependent Protein Kinase Knockout Mouse*

    PubMed Central

    Corradini, Eleonora; Vallur, Raghavan; Raaijmakers, Linsey M.; Feil, Susanne; Feil, Robert; Heck, Albert J. R.; Scholten, Arjen

    2014-01-01

    The cyclic nucleotide cyclic guanosine monophosphate (cGMP) plays an important role in learning and memory, but its signaling mechanisms in the mammalian brain are not fully understood. Using mass-spectrometry-based proteomics, we evaluated how the cerebellum adapts its (phospho)proteome in a knockout mouse model of cGMP-dependent protein kinase type I (cGKI). Our data reveal that a small subset of proteins in the cerebellum (∼3% of the quantified proteins) became substantially differentially expressed in the absence of cGKI. More changes were observed at the phosphoproteome level, with hundreds of sites being differentially phosphorylated between wild-type and knockout cerebellum. Most of these phosphorylated sites do not represent known cGKI substrates. An integrative computational network analysis of the data indicated that the differentially expressed proteins and proteins harboring differentially phosphorylated sites largely belong to a tight network in the Purkinje cells of the cerebellum involving important cGMP/cAMP signaling nodes (e.g. PDE5 and PKARIIβ) and Ca2+ signaling (e.g. SERCA3). In this way, removal of cGKI could be linked to impaired cerebellar long-term depression at Purkinje cell synapses. In addition, we were able to identify a set of novel putative (phospho)proteins to be considered in this network. Overall, our data improve our understanding of cerebellar cGKI signaling and suggest novel players in cGKI-regulated synaptic plasticity. PMID:24925903

  3. Aspects of calcium-activated chloride currents: a neuronal perspective.

    PubMed

    Scott, R H; Sutton, K G; Griffin, A; Stapleton, S R; Currie, K P

    1995-06-01

    Ca(2+)-activated Cl- channels are expressed in a variety of cell types, including central and peripheral neurones. These channels are activated by a rise in intracellular Ca2+ close to the cell membrane. This can be evoked by cellular events such as Ca2+ entry through voltage- and ligandgated channels or release of Ca2+ from intracellular stores. Additionally, these Ca(2+)-activated Cl currents (ICl(Ca)) can be activated by raising intracellular Ca2+ through artificial experimental procedures such as intracellular photorelease of Ca2+ from "caged" photolabile compounds (e.g. DM-nitrophen) or by treating cells with Ca2+ ionophores. The potential changes that result from activation of Ca(2+)-activated Cl- channels are dependent on resting membrane potential and the equilibrium potential for Cl-. Ca2+ entry during a single action potential is sufficient to produce substantial after potentials, suggesting that the activity of these Cl- channels can have profound effects on cell excitability. The whole cell ICl(Ca) can be identified by sensitivity to increased Ca2+ buffering capacity of the cell, anion substitution studies and reversal potential measurements, as well as by the actions of Cl- channel blockers. In cultured sensory neurones, there is evidence that the ICl(Ca) deactivates as Ca2+ is buffered or removed from the intracellular environment. To date, there is no evidence in mammalian neurones to suggest these Ca(2+)-sensitive Cl- channels undergo a process of inactivation. Therefore, ICl(Ca) can be used as a physiological index of intracellular Ca2+ close to the cell membrane. The ICl(Ca) has been shown to be activated or prolonged as a result of metabolic stress, as well as by drugs that disturb intracellular Ca2+ homeostatic mechanisms or release Ca2+ from intracellular stores. In addition to sensitivity to classic Cl- channel blockers such as niflumic acid, derivatives of stilbene (4,4'diisothiocyanostilbene-2,2'-disulphonic acid, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid) and benzoic acid (5-nitro 2-(3-phenylpropylamino) benzoic acid), ICl(Ca) are also sensitive to polyamine spider toxins and some of their analogues, particularly those containing the amino acid residue arginine. The physiological role of Ca(2+)-activated Cl- channels in neurones remains to be fully determined. The wide distribution of these channels in the nervous system, and their capacity to underlie a variety of events such as sustained or transient depolarization or hyperpolarizations in response to changes in intracellular Ca2+ and variations in intracellular Cl- concentration, suggest the roles may be subtle, but important.

  4. Cross regulation between cGMP-dependent protein kinase and Akt in vasodilatation of porcine pulmonary artery.

    PubMed

    Liu, Juan; Liu, Huixia; Li, Yanjing; Xu, Xiaojian; Chen, Zhengju; Liu, Limei; Yu, Xiaoxing; Gao, Yuansheng; Dou, Dou

    2014-11-01

    cGMP-dependent protein kinase (PKG) plays a crucial role in vasodilatation induced by cGMP-elevating agents. Akt has been demonstrated to be involved in modulating vasoreactivity. The present study was to determine the interaction between PKG and Akt and their influences on nitric oxide (NO)-induced vasodilatation. Isolated fourth-generation porcine pulmonary arteries were dissected from the lung and cut into rings in ice-cold modified Krebs-Ringer bicarbonate buffer. The relaxant responses of vessels were determined by organ chamber technique, cGMP was assayed by using enzyme-linked immunosorbent assay kit, the protein levels of phosphorylated Akt were examined by Western blotting, and the activity of phosphodiesterase type 5 (PDE5) was assayed by measuring the rate of cGMP degradation. Incubation with DETA NONOate (a stable NO donor) and 8-Br-cGMP (a cell membrane permeable analog of cGMP) attenuated Akt phosphorylation at Ser-473, which was prevented by Rp-8-Br-PET-cGMPS (a specific inhibitor of PKG) and calyculin A (an inhibitor of protein phosphatase 1 and 2A) but not by okadaic acid (a selective inhibitor of protein phosphatase 2A). Inhibition of Akt enhanced the relaxation and cGMP elevation of porcine pulmonary arteries induced by DETA NONOate or sodium nitroprusside, which was prevented by zaprinast, a specific inhibitor of PDE5. Incubation with LY294002 or Akt inhibitor reduced PDE5 activity in porcine pulmonary arteries. The present study indicates that PKG may attenuate Akt phosphorylation through protein phosphatase 1, which leads to an augmented cGMP elevation by inhibition of PDE5. The increased cGMP in turn activates PKG. Such a positive feedback may play an important role in NO-induced pulmonary vasodilatation.

  5. Nitric oxide increases mitochondrial respiration in a cGMP-dependent manner in the callus from Arabidopsis thaliana.

    PubMed

    Wang, Xiaomin; Li, Jisheng; Liu, Jie; He, Wenliang; Bi, Yurong

    2010-11-01

    Nitric oxide (NO) acts as a key molecule in many physiological processes in plants. In this study, the roles of NO in mitochondrial respiration were investigated in the calli from wild-type Arabidopsis and NO associated 1 mutant (Atnoa1) which has a reduced endogenous NO level. Long-term exposure of wild-type Arabidopsis callus to sodium nitroprusside (SNP) increased mitochondrial respiration in both cytochrome and alternative pathways. In Atnoa1 callus, the capacity of both the cytochrome pathway and the alternative pathway was lower than that in wild-type callus. Further study indicated that NO enhanced the transcript abundance of genes encoding mitochondrial respiration-chain proteins as well as the protein expression of the NADH-ubiquinone reductase 75 kDa subunit and the alternative oxidase 1/2 in wild-type and Atnoa1 calli. 2-Phenyl-4,4,5,5-tetremethy-limidazolinone-1-oxyl-3-oxide (PTIO), a NO scavenger, inhibited the effects of NO in both calli. Co-incubation of callus with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor, also abolished NO effects. The membrane-permeable cGMP analog 8Br-cGMP mimicked NO effects. Moreover, the alternative pathway showed a higher sensitivity to the cellular cGMP changes than the cytochrome pathway did in gene transcription, protein expression and O(2) consumption. Taken together, NO could enhance mitochondrial respiration in both cytochrome and alternative pathways in a cGMP-dependent manner in Arabidopsis.

  6. Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway

    PubMed Central

    Bibli, Sofia-Iris; Andreadou, Ioanna; Chatzianastasiou, Athanasia; Tzimas, Christos; Sanoudou, Despina; Kranias, Evangelia; Brouckaert, Peter; Coletta, Ciro; Szabo, Csaba; Kremastinos, Dimitrios Th.; Iliodromitis, Efstathios K.; Papapetropoulos, Andreas

    2015-01-01

    Aims H2S is known to confer cardioprotection; however, the pathways mediating its effects in vivo remain incompletely understood. The purpose of the present study is to evaluate the contribution of cGMP-regulated pathways in the infarct-limiting effect of H2S in vivo. Methods and results Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide (NaHS, an agent that generates H2S) increased cardiac cGMP and reduced the infarct size. The cGMP-dependent protein kinase (PKG)-I inhibitor DT2 abrogated the protective effect of NaHS, whereas the control peptide TAT or l-nitroarginine methyl ester (l-NAME) did not alter the effect of NaHS. Moreover, the KATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial KATP did not modify the NaHS response. NaHS enhanced phosphorylation of phospholamban (PLN), in a PKG-dependent manner. To further investigate the role of PLN in H2S-mediated cardioprotection, wild-type and PLN KO mice underwent I/R. NaHS did not exert cardioprotection in PLN KO mice. Unlike what was observed in rabbits, genetic or pharmacological inhibition of eNOS abolished the infarct-limiting effect of NaHS in mice. Conclusions Our findings demonstrate (i) that administration of NaHS induces cardioprotection via a cGMP/PKG/PLN pathway and (ii) contribution of nitric oxide to the H2S response is species-specific. PMID:25870184

  7. The Malaria Parasite Cyclic GMP-Dependent Protein Kinase Plays a Central Role in Blood-Stage Schizogony▿ † §

    PubMed Central

    Taylor, Helen M.; McRobert, Louisa; Grainger, Munira; Sicard, Audrey; Dluzewski, Anton R.; Hopp, Christine S.; Holder, Anthony A.; Baker, David A.

    2010-01-01

    A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for ≥6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria. PMID:19915077

  8. A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle

    PubMed Central

    Koltes, James E.; Mishra, Bishnu P.; Kumar, Dinesh; Kataria, Ranjit S.; Totir, Liviu R.; Fernando, Rohan L.; Cobbold, Rowland; Steffen, David; Coppieters, Wouter; Georges, Michel; Reecy, James M.

    2009-01-01

    Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle. PMID:19887637

  9. Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells.

    PubMed

    Zhu, Miaolin; Yao, Xiaoyuan; Wu, Min; Qian, Hai; Wu, Yan; Chen, Yongchang

    2016-02-01

    Our previous study demonstrated that type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) inhibited epidermal growth factor (EGF)-induced phosphorylation/activation of epidermal growth factor receptor (EGFR). Since human epidermal growth factor receptor 2 (HER2) has a similar molecular structure to EGFR, the present study was designed to investigate whether PKG II also inhibits HER2 activation. The human gastric cancer cell line HGC‑27 was infected with an adenoviral construct encoding cDNA of PKG II (Ad‑PKG II) to increase the expression of PKG II and treated with 8‑(4‑chlorophenylthio)guanosine‑3',5'‑cyclic monophosphate (8‑pCPT‑cGMP) to activate the kinase. Western blotting was performed to detect the tyrosine and serine/threonine phosphorylation of HER2. Co‑immunoprecipitation was performed in order to determine the binding between PKG II and HER2. In addition, a QuikChange Lightning Site‑Directed Mutagenesis kit was used to mutate threonine 686 of HER2 to glutamic acid or alanine. The results demonstrated that EGF treatment increased the tyrosine phosphorylation (activation) of HER2. Increasing the PKG II activity of HGC‑27 cells through infection with Ad‑PKG II and stimulation with 8‑pCPT‑cGMP inhibited the EGF‑induced tyrosine phosphorylation/activation of HER2. PKG II bound directly with HER2 and caused phosphorylation of threonine 686. When threonine 686 of HER2 was mutated to alanine, which could not be phosphorylated by PKG II, the inhibitory effect of PKG II on the activation of HER2 was eradicated. When threonine 686 of HER2 was mutated to glutamic acid, which mimicked the phosphorylation of this site, treatment with EGF had no stimulating effect on tyrosine phosphorylation/activation of the mutant HER2. The results suggested that PKG II inhibits EGF‑induced activation of HER2 through binding with and causing threonine 686 phosphorylation of this oncogenic protein. PMID:26676300

  10. Cyclic GMP-dependent protein kinase activation in the absence of negative inotropic effects in the rat ventricle

    PubMed Central

    MacDonell, Karen L; Diamond, Jack

    1997-01-01

    It has been suggested that activation of cyclic GMP-dependent protein kinase (PKG) is a necessary step in the chain of events leading to the production of negative inotropy by muscarinic receptor agonists in mammalian ventricles, and that some cyclic GMP-elevating agents, such as sodium nitroprusside (SNP), fail to exert a negative inotropic effect because they elevate cyclic GMP levels in a pool that does not activate the kinase. This hypothesis was tested in the present study by monitoring the effects of carbachol, SNP and atrial natriuretic peptide (ANP) on contractility, cyclic GMP content and PKG activity in rat intact ventricular preparations and freshly isolated ventricular cardiomyocytes.The presence of PKG in both the intact vehicle and in isolated ventricular cardiomyocytes was confirmed by MonoQ anion exchange chromatography and Western blotting. The elution profile indicated that the conditions of the PKG assay were selective for measuring PKG activity.Carbachol induced a marked negative inotropic effect in intact, perfused hearts and ventricular strips in the presence of isoproterenol. The negative inotropic effect of carbachol was not associated with significant changes in cyclic GMP content or PKG activity in intact ventricular tissue, or in PKG activity in isolated cardiomyocytes.SNP and ANP significantly increased cyclic GMP levels and activated PKG in intact ventricular preparations. Both drugs also activated PKG in isolated cardiomyocytes. However, neither drug had any negative inotropic effect in isoprenaline-stimulated perfused hearts and ANP did not change the contractility of isoprenaline-stimulated isolated cardiomyocytes.The results of this study demonstrate that the negative inotropic effects of muscarinic receptor agonists can occur in the absence of significant activation of PKG. Conversely, marked increases in ventricular cyclic GMP content and PKG activity caused by SNP or ANP were not accompanied by a negative inotropic effect

  11. Cyclic GMP-dependent and cyclic GMP-independent actions of nitric oxide on the renal afferent arteriole

    PubMed Central

    Trottier, Greg; Triggle, Chris R; O'Neill, Sean K; Loutzenhiser, Rodger

    1998-01-01

    The effects of exogenous NO and endothelial-derived NO (EDNO) on the afferent arteriole were investigated in the in vitro perfused hydronephrotic rat kidney. Vessels were pre-constricted with angiotensin II (0.1–0.3 nM) or KCl (30 mM). NO was infused directly into the renal artery at concentrations ranging from 30–9000 nM. ODQ (10, 30 μM) was administered to examine the effects of guanylyl cyclase inhibition. Kidneys were treated with ibuprofen (10 μM) to avoid actions of prostaglandins.During angiotensin II-induced vasoconstriction, NO elicited vasodilation at concentrations of 30–900 nM (EC50=200 nM) and ODQ caused a 10 fold shift in NO-sensitivity (EC50 1600 nM). During KCl-induced vasoconstriction, NO elicited a maximal dilation of 82±9% at 9000 nM (EC50 2000 nM) and ODQ had no effect. Thus in the presence of ODQ, the NO concentration-response curves for KCl- and angiotensin II-induced vasoconstriction were identical (P>0.2).To assess the possible role of cyclic GMP-independent mechanisms in the actions of EDNO, we compared the effects of L-NAME, ODQ and ODQ+L-NAME on acetylcholine-induced vasodilation. Angiotensin II reduced afferent arteriolar diameters from 16.7±0.5 to 8.1±0.8 microns and acetylcholine fully reversed this effect (16.9±0.5 microns). ODQ restored the angiotensin II response in the presence of acetylcholine (7.1±0.6 microns) and the subsequent addition of L-NAME had no further effect (6.8±0.7 microns). Similarly, L-NAME alone, fully reversed the actions of acetylcholine.Our findings indicate that exogenous NO is capable of eliciting renal afferent arteriolar vasodilation through both cyclic GMP-dependent and cyclic GMP-independent mechanisms. The cyclic GMP-independent action of NO did not require K+ channel activation, as it could be elicited in the presence of 30 mM KCl. Finally, although cyclic GMP-independent effects of exogenous NO could be demonstrated in our model, EDNO appears to act exclusively

  12. Reversal of radiation-induced cisplatin resistance in murine fibrosarcoma cells by selective modulation of the cyclic GMP-dependent transduction pathway.

    PubMed Central

    Eichholtz-Wirth, H.

    1995-01-01

    Cisplatin resistance, induced in murine fibrosarcoma cells (SSK) in vitro or in vivo by low-dose irradiation, can be overcome by activation of the cyclic GMP(cGMP)-dependent transduction pathway. This is mediated either by stimulating cGMP formation with sodium nitroprusside or by replacing cGMP with a selective activator of the cGMP-dependent protein kinase, 8-bromo-cGMP. The cyclic AMP-dependent transduction pathway is not involved in cisplatin resistance. Instead, activation of cAMP sensitises both parental and resistant SSK cells equally to the action of cisplatin. There is a 1.8 to 2.5-fold increase in drug toxicity, depending on the activating agent. Enhancement of cisplatin sensitivity is induced by specific inhibition of cAMP hydrolysis, increase in cAMP formation or by increasing the activation potential to cAMP-dependent protein kinase by specific cAMP analogues. Cells that have lost cisplatin resistance respond to cGMP- or cAMP-elevating agents in the same way as the parental SSK cells. The radiation sensitivity is unchanged in all cell lines, even after activation of cAMP or cGMP. These results suggest that specific DNA repair pathways are altered by radiation but affected only in cisplatin damage repair, which is regulated by cGMP. Although there is ample cooperativity and interaction between the cAMP- and the cGMP-dependent transduction pathways, specific substrate binding by cGMP appears to play an important role in radiation-induced cisplatin resistance. PMID:7640207

  13. Importance of NO/cGMP signalling via cGMP-dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol.

    PubMed

    Werner, Claudia; Raivich, Gennadij; Cowen, Michael; Strekalova, Tatyana; Sillaber, Inge; Buters, Jeroen T; Spanagel, Rainer; Hofmann, Franz

    2004-12-01

    Cyclic GMP is a second messenger for nitric oxide (NO) that acts as a mediator for many different physiological functions. The cGMP-dependent protein kinases (cGKs) mediate cellular signalling induced by NO and cGMP. Here, we explored the localization of cGMP-dependent protein kinase type II (cGKII) in the mouse brain. In situ hybridization revealed high levels of cGKII mRNA in cerebral cortex, thalamic nuclei, hypothalamic nuclei, and in several basal forebrain regions including medial septum, striatum and amygdala. The close link to NO and the distribution pattern of cGKII suggested that this enzyme might be involved in emotional reactions and responses to drugs of abuse. Therefore, cGKII knockout animals (cGKII-/-) were compared with littermate controls in behavioural tests (i) for emotion-linked and (ii) for acute and chronic ethanol responses. Deletion of cGKII did not influence aggressive behaviour but led to enhanced anxiety-like behaviour. In terms of acute responses to ethanol, cGKII-/- mice were hyposensitive to hypnotic doses of ethanol as measured by the loss of righting reflex, without an alteration in their blood alcohol elimination. In a two-bottle free choice test, cGKII-/- mice showed elevated alcohol consumption. No taste differences to sweet solutions were observed compared to control animals. In summary, our data show that cGKII activity modulates anxiety-like behaviour and neurobehavioural effects of alcohol.

  14. Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.

    PubMed

    Qin, Liying; Reger, Albert S; Guo, Elaine; Yang, Matthew P; Zwart, Peter; Casteel, Darren E; Kim, Choel

    2015-07-28

    cGMP-dependent protein kinase (PKG) Iα is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG Iα by interacting with G-kinase-anchoring proteins. The PKG Iα LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG Iα. To understand the molecular details of the PKG Iα LZ and C42-C42' disulfide bond, we determined crystal structures of the PKG Iα wild-type (WT) LZ and C42L LZ. Our data demonstrate that the C42-C42' disulfide bond dramatically stabilizes PKG Iα and that the C42L mutant mimics the oxidized WT LZ structurally.

  15. Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability

    PubMed Central

    Qin, Liying; Reger, Albert S.; Guo, Elaine; Yang, Matthew P.; Zwart, Peter; Casteel, Darren E.; Kim, Choel

    2016-01-01

    cGMP-dependent protein kinase (PKG) Iα is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG Iα by interacting with G-kinase-anchoring proteins. The PKG Iα LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG Iα. To understand the molecular details of the PKG Iα LZ and C42–C42′ disulfide bond, we determined crystal structures of the PKG Iα wild-type (WT) LZ and C42L LZ. Our data demonstrate that the C42–C42′ disulfide bond dramatically stabilizes PKG Iα and that the C42L mutant mimics the oxidized WT LZ structurally. PMID:26132214

  16. cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness.

    PubMed

    Langmesser, Sonja; Franken, Paul; Feil, Susanne; Emmenegger, Yann; Albrecht, Urs; Feil, Robert

    2009-01-01

    Many effects of nitric oxide (NO) are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3',5'-monophosphate (cGMP). cGMP activates cGMP-dependent protein kinases (PRKGs), which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1) in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS) duration and in non-REM sleep (NREMS) consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG) power in the delta frequency range (1-4 Hz) under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep.

  17. cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

    PubMed Central

    Steiner, Jennifer A; Carneiro, Ana Marin D; Wright, Jane; Matthies, Heinrich JG; Prasad, Harish C; Nicki, Christian K; Dostmann, Wolfgang R; Buchanan, Carrie C; Corbin, Jackie D; Francis, Sharron H; Blakely, Randy D

    2009-01-01

    Background The Na+/Cl--dependent serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport in vitro and an increased rate of SERT-mediated 5-HT clearance in vivo. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG) and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear. Results In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A) previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting endogenous PKGI eliminated

  18. cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

    PubMed

    Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B

    2014-10-01

    Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response. PMID:24752151

  19. cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae

    PubMed Central

    Dawson-Scully, Ken

    2016-01-01

    While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms. In this study, we characterize presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine the effects of high temperature stress on synaptic transmission. We investigated the neuroprotective role of PKG modulation both genetically using RNA interference (RNAi), and pharmacologically, to determine if and how PKG affects presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where PKG activation makes neurons more sensitive to temperature-induced failure of Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+ dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using RNAi demonstrated that decreased PKG expression was sufficient to confer thermoprotection. These results demonstrate that the PKG pathway regulates presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of presynaptic function during acute hyperthermia. PMID:27711243

  20. Yonkenafil: a novel phosphodiesterase type 5 inhibitor induces neuronal network potentiation by a cGMP-dependent Nogo-R axis in acute experimental stroke.

    PubMed

    Chen, Xuemei; Wang, Nannan; Liu, Yueyang; Liu, Yinglu; Zhang, Tianyu; Zhu, Lei; Wang, Yongfeng; Wu, Chunfu; Yang, Jingyu

    2014-11-01

    Yonkenafil is a novel phosphodiesterase type 5 (PDE5) inhibitor. Here we evaluated the effect of yonkenafil on ischemic injury and its possible mechanism of action. Male Sprague-Dawley rats underwent middle cerebral artery occlusion, followed by intraperitoneal or intravenous treatment with yonkenafil starting 2h later. Behavioral tests were carried out on day 1 or day 7 after reperfusion. Nissl staining, Fluoro-Jade B staining and electron microscopy studies were carried out 24h post-stroke, together with an analysis of infarct volume and severity of edema. Levels of cGMP-dependent Nogo-66 receptor (Nogo-R) pathway components, hsp70, apaf-1, caspase-3, caspase-9, synaptophysin, PSD-95/neuronal nitric oxide synthases (nNOS), brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) and nerve growth factor (NGF)/tropomyosin-related kinase A (TrkA) were also measured after 24h. Yonkenafil markedly inhibited infarction and edema, even when administration was delayed until 4h after stroke onset. This protection was associated with an improvement in neurological function and was sustained for 7d. Yonkenafil enlarged the range of penumbra, reduced ischemic cell apoptosis and the loss of neurons, and modulated the expression of proteins in the Nogo-R pathway. Moreover, yonkenafil protected the structure of synapses and increased the expression of synaptophysin, BDNF/TrkB and NGF/TrkA. In conclusion, yonkenafil protects neuronal networks from injury after stroke.

  1. Phosphoinositide Metabolism Links cGMP-Dependent Protein Kinase G to Essential Ca2+ Signals at Key Decision Points in the Life Cycle of Malaria Parasites

    PubMed Central

    Brochet, Mathieu; Collins, Mark O.; Smith, Terry K.; Thompson, Eloise; Sebastian, Sarah; Volkmann, Katrin; Schwach, Frank; Chappell, Lia; Gomes, Ana Rita; Berriman, Matthew; Rayner, Julian C.; Baker, David A.; Choudhary, Jyoti; Billker, Oliver

    2014-01-01

    Many critical events in the Plasmodium life cycle rely on the controlled release of Ca2+ from intracellular stores to activate stage-specific Ca2+-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP)-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca2+ required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca2+ signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5)-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca2+ effectors, PKG emerges as a unifying factor to control multiple cellular Ca2+ signals essential for malaria parasite development and transmission. PMID:24594931

  2. Endogenous expression of type II cGMP-dependent protein kinase mRNA and protein in rat intestine. Implications for cystic fibrosis transmembrane conductance regulator.

    PubMed Central

    Markert, T; Vaandrager, A B; Gambaryan, S; Pöhler, D; Häusler, C; Walter, U; De Jonge, H R; Jarchau, T; Lohmann, S M

    1995-01-01

    Certain pathogenic bacteria produce a family of heat stable enterotoxins (STa) which activate intestinal guanylyl cyclases, increase cGMP, and elicit life-threatening secretory diarrhea. The intracellular effector of cGMP actions has not been clarified. Recently we cloned the cDNA for a rat intestinal type II cGMP dependent protein kinase (cGK II) which is highly enriched in intestinal mucosa. Here we show that cGK II mRNA and protein are restricted to the intestinal segments from the duodenum to the proximal colon, with the highest amounts of cGK II protein in duodenum and jejunum. cGK II mRNA and protein decreased along the villus to crypt axis in the small intestine, whereas substantial amounts of both were found in the crypts of cecum. In intestinal epithelia, cGK II was specifically localized in the apical membrane, a major site of ion transport regulation. In contrast to cGK II, cGK I was localized in smooth muscle cells of the villus lamina propria. Short circuit current (ISC), a measure of Cl- secretion, was increased to a similar extent by STa and by 8-Br-cGMP, a selective activator of cGK, except in distal colon and in monolayers of T84 human colon carcinoma cells in which cGK II was not detected. In human and mouse intestine, the cyclic nucleotide-regulated Cl- conductance can be exclusively accounted for by the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Viewed collectively, the data suggest that cGK II is the mediator of STa and cGMP effects on Cl- transport in intestinal-epithelia. Images PMID:7543493

  3. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    PubMed

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-01-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

  4. Mode of Action of cGMP-dependent Protein Kinase-specific Inhibitors Probed by Photoaffinity Cross-linking Mass Spectrometry*

    PubMed Central

    Pinkse, Martijn W. H.; Rijkers, Dirk T. S.; Dostmann, Wolfgang R.; Heck, Albert J. R.

    2009-01-01

    The inhibitor peptide DT-2 (YGRKKRRQRRRPPLRKKKKKH) is the most potent and selective inhibitor of the cGMP-dependent protein kinase (PKG) known today. DT-2 is a construct of a PKG tight binding sequence (W45, LRKKKKKH, KI = 0.8 μm) and a membrane translocating sequence (DT-6, YGRKKRRQRRRPP, KI = 1.1 μm), that combined strongly inhibits PKG catalyzed phosphorylation (KI = 12.5 nm) with ∼1000-fold selectivity toward PKG over protein kinase A, the closest relative of PKG. However, the molecular mechanism behind this inhibition is not entirely understood. Using a combination of photoaffinity labeling, stable isotope labeling, and mass spectrometry, we have located the binding sites of PKG-specific substrate and inhibitor peptides. Covalent linkage of a PKG-specific substrate analogue was localized in the catalytic core on residues 356–372, also known as the glycine-rich loop, essential for ATP binding. By analogy, the individual inhibitor peptides W45 and DT-6 were also found to cross-link near the glycine-rich loop, suggesting these are both substrate competitive inhibitors. A bifunctional photoreactive analogue of DT-2 was found to generate dimers of PKG. This cross-linking induced covalent PKG dimerization was not observed for an N-terminal deletion mutant of PKG, which lacks the dimerization domain. In addition, non-covalent mass spectrometry was used to determine binding stoichiometry and binding order of the inhibitor peptides. Dimeric PKG binds two W45 and DT-6 peptides, whereas only one DT-2 molecule was observed to bind to the dimeric PKG. Taken together, these findings imply that (i) the two individual components making up DT-2 are both targeted against the substrate-binding site and (ii) binding of a single DT-2 molecule inactivates both PKG monomers simultaneously, which is an indication that (iii) in cGMP-activated PKG the catalytic centers of both subunits may be in each other's proximity. PMID:19369251

  5. Smooth muscle cell expression of type I cyclic GMP-dependent protein kinase is suppressed by continuous exposure to nitrovasodilators, theophylline, cyclic GMP, and cyclic AMP.

    PubMed Central

    Soff, G A; Cornwell, T L; Cundiff, D L; Gately, S; Lincoln, T M

    1997-01-01

    A key component of the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway in smooth muscle cells (SMC) is the type I GMP-dependent protein kinase (PK-G I). Activation of PK-G I mediates the reduction of cytoplasmic calcium concentrations and vasorelaxation. In this manuscript, we demonstrate that continuous exposure of SMC in culture to the nitrovasodilators S-nitroso-N-acetylpenicillamine (SNAP) or sodium nitroprusside (SNP) results in approximately 75% suppression of PK-G I mRNA by 48 h. PK-G I mRNA and protein were also suppressed by continuous exposure to cGMP analogues 8-bromo- and 8-(4-chlorophenylthio) guanosine-3,5-monophosphate or the cAMP analogue dibutyryl cAMP. These results suggest that activation of one or both of the cyclic nucleotide-dependent protein kinases mediates PK-G I mRNA suppression. Using isoform-specific cDNA probes, only the PK-G I alpha was detected in SMC, either at baseline or after suppression, while PK-G I beta was not detected, indicating that isoform switch was not contributing to the gene regulation. Using the transcription inhibitor actinomycin D, the PK-G I mRNA half-life in bovine SMC was observed to be 5 h. The half-life was not affected by the addition of SNAP to actinomycin D, indicating no effect on PK-G I mRNA stability. Nuclear runoff studies indicated a suppression of PK-G I gene transcription by SNAP. PK-G I suppression was also observed in vivo in rats given isosorbide dinitrate in the drinking water, with a dose-dependent suppression of PK-G I protein in the aorta. PK-G I antigen in whole rat lung extract was also suppressed by administration of isosorbide or theophylline in the drinking water. These data may contribute to our understanding of nitrovasodilator resistance, a phenomenon resulting from continuous exposure to nitroglycerin or other nitrovasodilators. PMID:9366573

  6. Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-serine 239 phosphorylation.

    PubMed

    Holt, Andrew W; Martin, Danielle N; Shaver, Patti R; Adderley, Shaquria P; Stone, Joshua D; Joshi, Chintamani N; Francisco, Jake T; Lust, Robert M; Weidner, Douglas A; Shewchuk, Brian M; Tulis, David A

    2016-09-01

    Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls

  7. Functions of volume-sensitive and calcium-activated chloride channels.

    PubMed

    Hoffmann, Else Kay; Holm, Niels Bjerre; Lambert, Ian Henry

    2014-04-01

    The review describes molecular and functional properties of the volume regulated anion channel and Ca(2+)-dependent Cl(-) channels belonging to the anoctamin family with emphasis on physiological importance of these channels in regulation of cell volume, cell migration, cell proliferation, and programmed cell death. Finally, we discuss the role of Cl(-) channels in various diseases.

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

    PubMed

    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.

  9. Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels

    PubMed Central

    Hermann, Anton; Sitdikova, Guzel F.; Weiger, Thomas M.

    2015-01-01

    All cells contain ion channels in their outer (plasma) and inner (organelle) membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells), alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle. In this chapter we summarize effects of oxidative stress and redox mechanisms on some ion channels, in particular on maxi calcium-activated potassium (BK) channels which play an outstanding role in a plethora of physiological and pathophysiological functions in almost all cells and tissues. We first elaborate on some general features of ion channel structure and function and then summarize effects of oxidative alterations of ion channels and their functional consequences. PMID:26287261

  10. The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

    PubMed Central

    Schleede, Justin; Blair, Seth S.

    2015-01-01

    The developing crossveins of the wing of Drosophila melanogaster are specified by long-range BMP signaling and are especially sensitive to loss of extracellular modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog). However, the role of the extracellular matrix in BMP signaling and Sog activity in the crossveins has been poorly explored. Using a genetic mosaic screen for mutations that disrupt BMP signaling and posterior crossvein development, we identify Gyc76C, a member of the receptor guanylyl cyclase family that includes mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP-dependent kinase Foraging, likely linked by cGMP, are necessary for normal refinement and maintenance of long-range BMP signaling in the posterior crossvein. This does not occur through cell-autonomous crosstalk between cGMP and BMP signal transduction, but likely through altered extracellular activity of Sog. We identify a novel pathway leading from Gyc76C to the organization of the wing extracellular matrix by matrix metalloproteinases, and show that both the extracellular matrix and BMP signaling effects are largely mediated by changes in the activity of matrix metalloproteinases. We discuss parallels and differences between this pathway and other examples of cGMP activity in both Drosophila melanogaster and mammalian cells and tissues. PMID:26440503

  11. Calcium Activities During Different Ion Exchange Separation Procedures

    NASA Astrophysics Data System (ADS)

    Zhang, Z.; Zhu, H.; Liu, Y.; Liu, F.; Zhang, C.; Sun, W.

    2014-12-01

    Calcium is a major element and participates in many geological processes. Investigations on stable calcium isotopic compositions of natural geological samples provide a great powerful tool to understand all kinds of those geological processes from a view of the field of isotope geochemistry. With the development of modern instruments and chemical separation techniques, calcium isotopic compositions could be determined even more precisely if the column chemistry brings no deviation. Usually, Calcium is separated from matrix elements using cation resin columns and the related chemical separation techniques seem to be robust. However, more detailed work still need to be done on matrix effects and calcium isotopic fractionations on column chemistry or during elution processes. If calcium is run on TIMS instruments, the interference effect could be lower and easier controlled, thus, the requirement to the chemistry is relatively not critic, but calcium fractionation on filaments could be much difficult to monitor. If calcium is run on MC-ICP-MS instruments, the interference effect could be huge and is really difficult to be recognized and subtracted, the requirement to the chemistry is much more critical in order to get a real result of the sample, but the instrument fractionation could be easier to monitor. Here we investigate calcium activities on several kinds of cation resins under different column/acid conditions. We seek to find a good balance between recovery and interference effect on column chemistry and are intend to set up a better chemical separation procedure to satisfy the instrument requirements for calcium. In addition, Calcium isotopic fractionation on column will also be discussed further here based on our previous and ongoing results.

  12. Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development

    PubMed Central

    Moon, Robert W.; Whalley, David; Bowyer, Paul W.; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K.; Howell, Steven A.; Grainger, Munira; Jones, Hayley M.; Ansell, Keith H.; Chapman, Timothy M.; Taylor, Debra L.; Osborne, Simon A.; Baker, David A.; Tatu, Utpal

    2015-01-01

    Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. PMID:26711771

  13. Chloride Test

    MedlinePlus

    ... Addison disease, or increased salt intake. If both chloride and sodium levels are high in a person on a ... anything else I should know? Drugs that affect sodium blood levels will also cause changes in chloride. In addition, swallowing large amounts of baking soda ...

  14. The Anti-fibrotic Actions of Relaxin Are Mediated Through a NO-sGC-cGMP-Dependent Pathway in Renal Myofibroblasts In Vitro and Enhanced by the NO Donor, Diethylamine NONOate

    PubMed Central

    Wang, Chao; Kemp-Harper, Barbara K.; Kocan, Martina; Ang, Sheng Yu; Hewitson, Tim D.; Samuel, Chrishan S.

    2016-01-01

    GMP-promoting effects of RLX, DEA/NO and RLX+DEA/NO (which all increased cGMP levels by 12-16-fold over basal levels; all p < 0.01 vs. vehicle-treated cells) were significantly inhibited by pre-treatment of ODQ (all p < 0.05 vs. the respective treatments alone). Conclusion: These findings confirmed that RLX mediates its TGF-β1-inhibitory and gelatinase-promoting effects via a NO-sGC-cGMP-dependent pathway, which was additively augmented by co-administration of DEA/NO. PMID:27065874

  15. Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases

    PubMed Central

    Sala-Rabanal, Monica; Yurtsever, Zeynep; Berry, Kayla N.; Brett, Tom J.

    2015-01-01

    Chloride transport proteins play critical roles in inflammatory airway diseases, contributing to the detrimental aspects of mucus overproduction, mucus secretion, and airway constriction. However, they also play crucial roles in contributing to the innate immune properties of mucus and mucociliary clearance. In this review, we focus on the emerging novel roles for a chloride channel regulator (CLCA1), a calcium-activated chloride channel (TMEM16A), and two chloride exchangers (SLC26A4/pendrin and SLC26A9) in chronic inflammatory airway diseases. PMID:26612971

  16. Vinyl chloride and polyvinyl chloride.

    PubMed

    Lewis, R

    1999-01-01

    Polyvinyl chloride (PVC) is an important plastic resin for construction, pipe and tubing, siding, and other uses. Exposures to vinyl chloride monomer during the early years of production resulted in an important sentinel health event: the recognition of an excess of a rare liver cancer, hepatic angiosarcoma, at facilities throughout the world. Several other syndromes, including acro-osteolysis, also have been associated with PVC, but less clearly with vinyl chloride. Extensive research ranging from large-scale epidemiologic studies to biomarker research into molecular mechanisms continues to provide valuable insight into the pathogenesis of occupational cancer.

  17. Interactions between permeation and gating in the TMEM16B/anoctamin2 calcium-activated chloride channel.

    PubMed

    Betto, Giulia; Cherian, O Lijo; Pifferi, Simone; Cenedese, Valentina; Boccaccio, Anna; Menini, Anna

    2014-06-01

    At least two members of the TMEM16/anoctamin family, TMEM16A (also known as anoctamin1) and TMEM16B (also known as anoctamin2), encode Ca(2+)-activated Cl(-) channels (CaCCs), which are found in various cell types and mediate numerous physiological functions. Here, we used whole-cell and excised inside-out patch-clamp to investigate the relationship between anion permeation and gating, two processes typically viewed as independent, in TMEM16B expressed in HEK 293T cells. The permeability ratio sequence determined by substituting Cl(-) with other anions (PX/PCl) was SCN(-) > I(-) > NO3 (-) > Br(-) > Cl(-) > F(-) > gluconate. When external Cl(-) was substituted with other anions, TMEM16B activation and deactivation kinetics at 0.5 µM Ca(2+) were modified according to the sequence of permeability ratios, with anions more permeant than Cl(-) slowing both activation and deactivation and anions less permeant than Cl(-) accelerating them. Moreover, replacement of external Cl(-) with gluconate, or sucrose, shifted the voltage dependence of steady-state activation (G-V relation) to more positive potentials, whereas substitution of extracellular or intracellular Cl(-) with SCN(-) shifted G-V to more negative potentials. Dose-response relationships for Ca(2+) in the presence of different extracellular anions indicated that the apparent affinity for Ca(2+) at +100 mV increased with increasing permeability ratio. The apparent affinity for Ca(2+) in the presence of intracellular SCN(-) also increased compared with that in Cl(-). Our results provide the first evidence that TMEM16B gating is modulated by permeant anions and provide the basis for future studies aimed at identifying the molecular determinants of TMEM16B ion selectivity and gating.

  18. A novel biophysical model on calcium and voltage dual dependent gating of calcium-activated chloride channel.

    PubMed

    Zhang, Suhua; Chen, Yafei; An, Hailong; Liu, Hui; Li, Junwei; Pang, Chunli; Ji, Qing; Zhan, Yong

    2014-08-21

    Ca(2+)-activated Cl(-) channels (CaCCs) are anion-selective channels and involved in physiological processes such as electrolyte/fluid secretion, smooth muscle excitability, and olfactory perception which critically depend on the Ca(2+) and voltage dual-dependent gating of channels. However, how the Ca(2+) and voltage regulate the gating of CaCCs still unclear. In this work, the authors constructed a biophysical model to illustrate the dual-dependent gating of CaCCs. For validation, we applied our model on both native CaCCs and exogenous TMEM16A which is thought to be the molecular basis of CaCCs. Our data show that the native CaCCs may share universal gating mechanism. We confirmed the assumption that by binding with the channel, Ca(2+) decreases the energy-barrier to open the channel, but not changes the voltage-sensitivity. For TMEM16A, our model indicates that the exogenous channels show different Ca(2+) dependent gating mechanism from the native ones. These results advance the understanding of intracellular Ca(2+) and membrane potential regulation in CaCCs, and shed new light on its function in aspect of physiology and pharmacology.

  19. Computational modeling of anoctamin 1 calcium-activated chloride channels as pacemaker channels in interstitial cells of Cajal.

    PubMed

    Lees-Green, Rachel; Gibbons, Simon J; Farrugia, Gianrico; Sneyd, James; Cheng, Leo K

    2014-04-15

    Interstitial cells of Cajal (ICC) act as pacemaker cells in the gastrointestinal tract by generating electrical slow waves to regulate rhythmic smooth muscle contractions. Intrinsic Ca(2+) oscillations in ICC appear to produce the slow waves by activating pacemaker currents, currently thought to be carried by the Ca(2+)-activated Cl(-) channel anoctamin 1 (Ano1). In this article we present a novel model of small intestinal ICC pacemaker activity that incorporates store-operated Ca(2+) entry and a new model of Ano1 current. A series of simulations were carried out with the ICC model to investigate current controversies about the reversal potential of the Ano1 Cl(-) current in ICC and to predict the characteristics of the other ion channels that are necessary to generate slow waves. The model results show that Ano1 is a plausible pacemaker channel when coupled to a store-operated Ca(2+) channel but suggest that small cyclical depolarizations may still occur in ICC in Ano1 knockout mice. The results predict that voltage-dependent Ca(2+) current is likely to be negligible during the slow wave plateau phase. The model shows that the Cl(-) equilibrium potential is an important modulator of slow wave morphology, highlighting the need for a better understanding of Cl(-) dynamics in ICC.

  20. Calcium-calmodulin does not alter the anion permeability of the mouse TMEM16A calcium-activated chloride channel.

    PubMed

    Yu, Yawei; Kuan, Ai-Seon; Chen, Tsung-Yu

    2014-07-01

    The transmembrane protein TMEM16A forms a Ca(2+)-activated Cl(-) channel that is permeable to many anions, including SCN(-), I(-), Br(-), Cl(-), and HCO3 (-), and has been implicated in various physiological functions. Indeed, controlling anion permeation through the TMEM16A channel pore may be critical in regulating the pH of exocrine fluids such as the pancreatic juice. The anion permeability of the TMEM16A channel pore has recently been reported to be modulated by Ca(2+)-calmodulin (CaCaM), such that the pore of the CaCaM-bound channel shows a reduced ability to discriminate between anions as measured by a shift of the reversal potential under bi-ionic conditions. Here, using a mouse TMEM16A clone that contains the two previously identified putative CaM-binding motifs, we were unable to demonstrate such CaCaM-dependent changes in the bi-ionic potential. We confirmed the activity of CaCaM used in our study by showing CaCaM modulation of the olfactory cyclic nucleotide-gated channel. We suspect that the different bi-ionic potentials that were obtained previously from whole-cell recordings in low and high intracellular [Ca(2+)] may result from different degrees of bi-ionic potential shift secondary to a series resistance problem, an ion accumulation effect, or both.

  1. Multiple effects of anthracene-9-carboxylic acid on the TMEM16B/anoctamin2 calcium-activated chloride channel.

    PubMed

    Cherian, O Lijo; Menini, Anna; Boccaccio, Anna

    2015-04-01

    Ca(2+)-activated Cl(-) currents (CaCCs) play important roles in many physiological processes. Recent studies have shown that TMEM16A/anoctamin1 and TMEM16B/anoctamin2 constitute CaCCs in several cell types. Here we have investigated for the first time the extracellular effects of the Cl(-) channel blocker anthracene-9-carboxylic acid (A9C) and of its non-charged analogue anthracene-9-methanol (A9M) on TMEM16B expressed in HEK 293T cells, using the whole-cell patch-clamp technique. A9C caused a voltage-dependent block of outward currents and inhibited a larger fraction of the current as depolarization increased, whereas the non-charged A9M produced a small, not voltage dependent block of outward currents. A similar voltage-dependent block by A9C was measured both when TMEM16B was activated by 1.5 and 13μM Ca(2+). However, in the presence of 1.5μM Ca(2+) (but not in 13μM Ca(2+)), A9C also induced a strong potentiation of tail currents measured at -100mV after depolarizing voltages, as well as a prolongation of the deactivation kinetics. On the contrary, A9M did not produce potentiation of tail currents, showing that the negative charge is required for potentiation. Our results provide the first evidence that A9C has multiple effects on TMEM16B and that the negative charge of A9C is necessary both for voltage-dependent block and for potentiation. Future studies are required to identify the molecular mechanisms underlying these complex effects of A9C on TMEM16B. Understanding these mechanisms will contribute to the elucidation of the structure and functional properties of TMEM16B channels.

  2. Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways.

    PubMed

    Gianotti, Ambra; Ferrera, Loretta; Philp, Amber R; Caci, Emanuela; Zegarra-Moran, Olga; Galietta, Luis J V; Flores, Carlos A

    2016-06-15

    Defective epithelial chloride secretion occurs in humans with cystic fibrosis (CF), a genetic defect due to loss of function of CFTR, a cAMP-activated chloride channel. In the airways, absence of an active CFTR causes a severe lung disease. In mice, genetic ablation of CFTR function does not result in similar lung pathology. This may be due to the expression of an alternative chloride channel which is activated by calcium. The most probable protein performing this function is TMEM16A, a calcium-activated chloride channel (CaCC). Our aim was to assess the relative contribution of CFTR and TMEM16A to chloride secretion in adult mouse trachea. For this purpose we tested pharmacological inhibitors of chloride channels in normal and CF mice. The amplitude of the cAMP-activated current was similar in both types of animals and was not affected by a selective CFTR inhibitor. In contrast, a CaCC inhibitor (CaCCinh-A01) strongly blocked the cAMP-activated current as well as the calcium-activated chloride secretion triggered by apical UTP. Although control experiments revealed that CaCCinh-A01 also shows inhibitory activity on CFTR, our results indicate that transepithelial chloride secretion in adult mouse trachea is independent of CFTR and that another channel, possibly TMEM16A, performs both cAMP- and calcium-activated chloride transport. The prevalent function of a non-CFTR channel may explain the absence of a defect in chloride transport in CF mice. PMID:27063443

  3. Mepiquat chloride

    Integrated Risk Information System (IRIS)

    Mepiquat chloride ; CASRN 24307 - 26 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  4. Methyl chloride

    Integrated Risk Information System (IRIS)

    Methyl chloride ; CASRN 74 - 87 - 3 ( 07 / 17 / 2001 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  5. Ethyl chloride

    Integrated Risk Information System (IRIS)

    Ethyl chloride ; CASRN 75 - 00 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  6. Benzyl chloride

    Integrated Risk Information System (IRIS)

    Benzyl chloride ; CASRN 100 - 44 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  7. Vinyl chloride

    Integrated Risk Information System (IRIS)

    Vinyl chloride ; CASRN 75 - 01 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  8. Acetyl chloride

    Integrated Risk Information System (IRIS)

    Acetyl chloride ; CASRN 75 - 36 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  9. Hydrogen chloride

    Integrated Risk Information System (IRIS)

    Hydrogen chloride ; CASRN 7647 - 01 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  10. Allyl chloride

    Integrated Risk Information System (IRIS)

    Allyl chloride ; CASRN 107 - 05 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  11. Trypsin-Sensitive, Rapid Inactivation of a Calcium-Activated Potassium Channel

    NASA Astrophysics Data System (ADS)

    Solaro, Christopher R.; Lingle, Christopher J.

    1992-09-01

    Most calcium-activated potassium channels couple changes in intracellular calcium to membrane excitability by conducting a current with a probability that depends directly on submembrane calcium concentration. In rat adrenal chromaffin cells, however, a large conductance, voltage- and calcium-activated potassium channel (BK) undergoes rapid inactivation, suggesting that this channel has a physiological role different than that of other BK channels. The inactivation of the BK channel, like that of the voltage-gated Shaker B potassium channel, is removed by trypsin digestion and channels are blocked by the Shaker B amino-terminal inactivating domain. Thus, this BK channel shares functional and possibly structural homologies with other inactivating voltage-gated potassium channels.

  12. Calcium-activated potassium channels in insect pacemaker neurons as unexpected target site for the novel fumigant dimethyl disulfide.

    PubMed

    Gautier, Hélène; Auger, Jacques; Legros, Christian; Lapied, Bruno

    2008-01-01

    Dimethyl disulfide (DMDS), a plant-derived insecticide, is a promising fumigant as a substitute for methyl bromide. To further understand the mode of action of DMDS, we examined its effect on cockroach octopaminergic neurosecretory cells, called dorsal unpaired median (DUM) neurons, using whole-cell patch-clamp technique, calcium imaging and antisense oligonucleotide strategy. At low concentration (1 microM), DMDS modified spontaneous regular spike discharge into clear bursting activity associated with a decrease of the amplitude of the afterhyperpolarization. This effect led us to suspect alterations of calcium-activated potassium currents (IKCa) and [Ca(2+)](i) changes. We showed that DMDS reduced amplitudes of both peak transient and sustained components of the total potassium current. IKCa was confirmed as a target of DMDS by using iberiotoxin, cadmium chloride, and pSlo antisense oligonucleotide. In addition, we showed that DMDS induced [Ca(2+)](i) rise in Fura-2-loaded DUM neurons. Using calcium-free solution, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxy-phenyl)ethyl]-acetamide (LOE 908) [an inhibitor of transient receptor potential (TRP)gamma], we demonstrated that TRPgamma initiated calcium influx. By contrast, omega-conotoxin GVIA (an inhibitor of N-type high-voltage-activated calcium channels), did not affect the DMDS-induced [Ca(2+)](i) rise. Finally, the participation of the calcium-induced calcium release mechanism was investigated using thapsigargin, caffeine, and ryanodine. Our study revealed that DMDS-induced elevation in [Ca(2+)](i) modulated IKCa in an unexpected bell-shaped manner via intracellular calcium. In conclusion, DMDS affects multiple targets, which could be an effective way to improve pest control efficacy of fumigation. PMID:17942746

  13. "Caged calcium" in Aplysia pacemaker neurons. Characterization of calcium-activated potassium and nonspecific cation currents

    PubMed Central

    1989-01-01

    We have studied calcium-activated potassium current, IK(Ca), and calcium-activated nonspecific cation current, INS(Ca), in Aplysia bursting pacemaker neurons, using photolysis of a calcium chelator (nitr-5 or nitr-7) to release "caged calcium" intracellularly. A computer model of nitr photolysis, multiple buffer equilibration, and active calcium extrusion was developed to predict volume-average and front-surface calcium concentration transients. Changes in arsenazo III absorbance were used to measure calcium concentration changes caused by nitr photolysis in microcuvettes. Our model predicted the calcium increments caused by successive flashes, and their dependence on calcium loading, nitr concentration, and light intensity. Flashes also triggered the predicted calcium concentration jumps in neurons filled with nitr-arsenazo III mixtures. In physiological experiments, calcium- activated currents were recorded under voltage clamp in response to flashes of different intensity. Both IK(Ca) and INS(Ca) depended linearly without saturation upon calcium concentration jumps of 0.1-20 microM. Peak membrane currents in neurons exposed to repeated flashes first increased and then declined much like the arsenazo III absorbance changes in vitro, which also indicates a first-order calcium activation. Each flash-evoked current rose rapidly to a peak and decayed to half in 3-12 s. Our model mimicked this behavior when it included diffusion of calcium and nitr perpendicular to the surface of the neuron facing the flashlamp. Na/Ca exchange extruding about 1 pmol of calcium per square centimeter per second per micromolar free calcium appeared to speed the decline of calcium-activated membrane currents. Over a range of different membrane potentials, IK(Ca) and INS(Ca) decayed at similar rates, indicating similar calcium stoichiometries independent of voltage. IK(Ca), but not INS(Ca), relaxes exponentially to a different level when the voltage is suddenly changed. We have estimated

  14. Large-Conductance Calcium-Activated Potassium Channels in Glomerulus: From Cell Signal Integration to Disease

    PubMed Central

    Tao, Jie; Lan, Zhen; Wang, Yunman; Hei, Hongya; Tian, Lulu; Pan, Wanma; Zhang, Xuemei; Peng, Wen

    2016-01-01

    Large-conductance calcium-activated potassium (BK) channels are currently considered as vital players in a variety of renal physiological processes. In podocytes, BK channels become active in response to stimuli that increase local cytosolic Ca2+, possibly secondary to activation of slit diaphragm TRPC6 channels by chemical or mechanical stimuli. Insulin increases filtration barrier permeability through mobilization of BK channels. In mesangial cells, BK channels co-expressed with β1 subunits act as a major component of the counteractive response to contraction in order to regulate glomerular filtration. This review aims to highlight recent discoveries on the localization, physiological and pathological roles of BK channels in glomerulus. PMID:27445840

  15. Large-Conductance Calcium-Activated Potassium Channels in Glomerulus: From Cell Signal Integration to Disease.

    PubMed

    Tao, Jie; Lan, Zhen; Wang, Yunman; Hei, Hongya; Tian, Lulu; Pan, Wanma; Zhang, Xuemei; Peng, Wen

    2016-01-01

    Large-conductance calcium-activated potassium (BK) channels are currently considered as vital players in a variety of renal physiological processes. In podocytes, BK channels become active in response to stimuli that increase local cytosolic Ca(2+), possibly secondary to activation of slit diaphragm TRPC6 channels by chemical or mechanical stimuli. Insulin increases filtration barrier permeability through mobilization of BK channels. In mesangial cells, BK channels co-expressed with β1 subunits act as a major component of the counteractive response to contraction in order to regulate glomerular filtration. This review aims to highlight recent discoveries on the localization, physiological and pathological roles of BK channels in glomerulus. PMID:27445840

  16. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    SciTech Connect

    Schallreuter, Karin U.; University of Bradford ). E-mail: K.Schallreuter@bradford.ac.uk; Gibbons, Nicholas C.J.; Elwary, Souna M.; Parkin, Susan M.; Wood, John M.

    2007-04-20

    The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10{sup -3}M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. {sup 45}Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H{sub 2}O{sub 2}-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m{sup 2} surface area with its calcium gradient in the 10{sup -3}M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.

  17. Calcium-activated potassium channels mask vascular dysfunction associated with oxidized LDL exposure in rabbit aorta.

    PubMed

    Bocker, J M; Miller, F J; Oltman, C L; Chappell, D A; Gutterman, D D

    2001-05-01

    Endothelium-dependent vasodilation is impaired in atherosclerosis. Oxidized low density lipoprotein (ox-LDL) plays an important role, possibly through alterations in G-protein activation. We examined the effect of acute exposure to ox-LDL on the dilator responses of isolated rabbit aorta segments. We sought also to evaluate the specificity of this dysfunction for dilator stimuli that traditionally operate through a Gi-protein mechanism. Aortic segments were prepared for measurement of isometric tension. After contraction with prostaglandin F2alpha, relaxation to thrombin, adenosine diphosphate (ADP), or the endothelium-independent agonists, sodium nitroprusside (SNP) or papaverine was examined. Maximal relaxation to thrombin was impaired in the presence of ox-LDL (17.7+/-3.7% p<0.05) compared to control (no LDL) (52.6+/-4.0%). Ox-LDL did not affect maximal relaxation to ADP or SNP. However, in the presence of charybdotoxin (CHTX: calcium-activated potassium channel inhibitor) ox-LDL impaired relaxation to ADP (17.4+/-3.2%). CHTX did not affect control (no LDL) responses to ADP (69.6+/-5.0%) or relaxation to thrombin or papaverine. In conclusion, ox-LDL impairs relaxation to thrombin, but in the case of ADP, calcium-activated potassium channels compensate to maintain this relaxation. PMID:11605770

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

    PubMed

    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.

  19. Calcium Activation of the Ca-ATPase Enhances Conformational Heterogeneity Between Nucleotide Binding and Phosphorylation Domains

    SciTech Connect

    Chen, Baowei; Squier, Thomas C.; Bigelow, Diana J.

    2004-04-13

    High-resolution crystal structures obtained in two conformations of the Ca-ATPase suggest that a large-scale rigid-body domain reorientation of approximately 50 involving the nucleotide-binding (N) domain is required to permit the transfer of the -phosphoryl group of ATP to Asp351 in the phosphorylation (P) domain during coupled calcium transport. However, variability observed in the orientation of the N-domain relative to the P-domain in both different crystal structures of the Ca-ATPase following calcium activation, and structures of other P-type ATPases, suggests the presence of conformational heterogeneity in solution which may be modulated by contact interactions within the crystal. Therefore, to address the extent of conformational heterogeneity between these domains in solution, we have used fluorescence resonance energy transfer (FRET) to measure the spatial separation and conformational heterogeneity between donor (i.e., 5-[[2-[(iodoacetyl)amino]ethyl]amino] naphthalene-1-sulfonic acid) and acceptor (i.e., fluorescein 5-isothiocyanate) chromophores covalently bound to the P- and N-domains, respectively, within the Ca-ATPase stabilized in different enzymatic states associated with the transport cycle. In comparison to the unliganded enzyme, the spatial separation and conformational heterogeneity between these domains is unaffected by enzyme phosphorylation. However, calcium-activation results in a 3.4 increase in the average spatial separation, which increases from 29.4 to 32.8 , in good agreement with the high-resolution structures where these sites are respectively separated by 31.6 (1 IWO.pdb) and 35.9 (1EUL.pdb). Thus, the crystal structures accurately reflect the average solution structures of the Ca-ATPase. However, there is substantial conformational heterogeneity for all enzyme states measured, indicating that formation of catalytically important transition states involves a subpopulation of enzyme intermediates. These results suggest that the

  20. Properties of a calcium-activated K(+) current on interneurons in the developing rat hippocampus.

    PubMed

    Aoki, T; Baraban, S C

    2000-06-01

    Calcium-activated potassium currents have an essential role in regulating excitability in a variety of neurons. Although it is well established that mature CA1 pyramidal neurons possess a Ca(2+)-activated K(+) conductance (I(K(Ca))) with early and late components, modulation by various endogenous neurotransmitters, and sensitivity to K(+) channel toxins, the properties of I(K(Ca)) on hippocampal interneurons (or immature CA1 pyramidal neurons) are relatively unknown. To address this problem, whole-cell voltage-clamp recordings were made from visually identified interneurons in stratum lacunosum-moleculare (L-M) and CA1 pyramidal cells in hippocampal slices from immature rats (P3-P25). A biphasic calcium-activated K(+) tail current was elicited following a brief depolarization from the holding potential (-50 mV). Analysis of the kinetic properties of I(K(Ca)) suggests that an early current component differs between these two cell types. An early I(K(Ca)) with a large peak current amplitude (200.8 +/- 13.2 pA, mean +/- SE), slow time constant of decay (70.9 +/- 3.3 ms), and relatively rapid time to peak (within 15 ms) was observed on L-M interneurons (n = 88), whereas an early I(K(Ca)) with a small peak current amplitude (112.5 +/- 7.3 pA), a fast time constant of decay (39.4 +/- 1.6 ms), and a slower time-to-peak (within 26 ms) was observed on CA1 pyramidal neurons (n = 85). Removal of extracellular calcium or addition of inorganic Ca(2+) channel blockers (cadmium, nickel, or cobalt) was used to demonstrate the calcium dependence of these currents. Addition of norepinephrine, carbachol, and a variety of channel toxins (apamin, iberiotoxin, verruculogen, paxilline, penitrem A, and charybdotoxin) were used to further distinguish between I(K(Ca)) on these two hippocampal cell types. Verruculogen (100 nM), carbachol (100 microM), apamin (100 nM), TEA (1 mM), and iberiotoxin (50 nM) significantly reduced early I(K(Ca)) on CA1 pyramidal neurons; early I(K(Ca)) on L

  1. The distribution of intermediate-conductance, calcium-activated, potassium (IK) channels in epithelial cells.

    PubMed

    Thompson-Vest, Nichola; Shimizu, Yasutake; Hunne, Billie; Furness, John B

    2006-02-01

    Intermediate-conductance, calcium-activated, potassium (IK) channels were first identified by their roles in cell volume regulation, and were later shown to be involved in control of proliferation of lymphocytes and to provide a K+ current for epithelial secretory activity. Until now, there has been no systematic investigation of IK channel localization within different epithelia. IK channel immunoreactivity was present in most epithelia, where it occurred in surface membranes of epithelial cells. It was found in all stratified epithelia, including skin, cornea, oral mucosa, vaginal mucosa, urothelium and the oesophageal lining. It occurred in the ducts of fluid-secreting glands, the salivary glands, lacrimal glands and pancreas, and in the respiratory epithelium. A low level of expression was seen in serous acinar cells. It was also found in other epithelia with fluid-exchange properties, the choroid plexus epithelium, the ependyma, visceral pleura and peritoneum, bile ducts and intestinal lining epithelium. However, there was little or no expression in vascular endothelial cells, kidney tubules or collecting ducts, lung alveoli, or in sebaceous glands. It is concluded that the channel is present in surface epithelia (e.g. skin) where it has a cell-protective role against osmotic challenge, and in epithelia where there is anion secretion that is facilitated by a K+ current-dependent hyperpolarization. It was also in some epithelial cells where its roles are as yet unknown. PMID:16441566

  2. A coarse-grained model to study calcium activation of the cardiac thin filament

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Schwartz, Steven

    2015-03-01

    Familial hypertrophic cardiomyopathy (FHC) is one of the most common heart disease caused by genetic mutations. Cardiac muscle contraction and relaxation involve regulation of crossbridge binding to the cardiac thin filament, which regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin (cTn) and tropomyosin (Tm). An atomistic model of cTn complex interacting with Tm has been studied by our group. A more realistic model requires the inclusion of the dynamics of actin filament, which is almost 6 times larger than cTn and Tm in terms of atom numbers, and extensive sampling of the model becomes very resource-demanding. By using physics-based protein united-residue force field, we introduce a coarse-grained model to study the calcium activation of the thin filament resulting from cTn's allosteric regulation of Tm dynamics on actin. The time scale is much longer than that of all-atom molecular dynamics simulation because of the reduction of the degrees of freedom. The coarse-grained model is a good template for studying cardiac thin filament mutations that cause FHC, and reduces the cost of computational resources.

  3. Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels.

    PubMed

    Castillo, Karen; Contreras, Gustavo F; Pupo, Amaury; Torres, Yolima P; Neely, Alan; González, Carlos; Latorre, Ramon

    2015-04-14

    Being activated by depolarizing voltages and increases in cytoplasmic Ca(2+), voltage- and calcium-activated potassium (BK) channels and their modulatory β-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxiliary β-subunits that are expressed together with the α (BK)-subunit in almost every tissue type where they are found. By measuring gating currents in BK channels coexpressed with chimeras between β1 and β3 or β2 auxiliary subunits, we were able to identify that the cytoplasmic regions of β1 are responsible for the modulation of the voltage sensors. In addition, we narrowed down the structural determinants to the N terminus of β1, which contains two lysine residues (i.e., K3 and K4), which upon substitution virtually abolished the effects of β1 on charge movement. The mechanism by which K3 and K4 stabilize the voltage sensor is not electrostatic but specific, and the α (BK)-residues involved remain to be identified. This is the first report, to our knowledge, where the regulatory effects of the β1-subunit have been clearly assigned to a particular segment, with two pivotal amino acids being responsible for this modulation.

  4. Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons.

    PubMed

    Sun, P; Zhang, Q; Zhang, Y; Wang, F; Wang, L; Yamamoto, R; Sugai, T; Kato, N

    2015-01-01

    It was previously shown that depression-like behavior is accompanied with suppression of the large-conductance calcium activated potassium (BK) channel in cingulate cortex pyramidal cells. To test whether BK channels are also involved in fear conditioning, we studied neuronal properties of amygdala principal cells in fear conditioned mice. After behavior, we made brain slices containing the amygdala, the structure critically relevant to fear memory. The resting membrane potential in lateral amygdala (LA) neurons obtained from fear conditioned mice (FC group) was more depolarized than in neurons from naïve controls. The frequencies of spikes evoked by current injections were higher in neurons from FC mice, demonstrating that excitability of LA neurons was elevated by fear conditioning. The depolarization in neurons from FC mice was shown to depend on BK channels by using the BK channel blocker charybdotoxin. Suppression of BK channels in LA neurons from the FC group was further confirmed on the basis of the spike width, since BK channels affect the descending phase of spikes. Spikes were broader in the FC group than those in the naïve control in a manner dependent on BK channels. Consistently, quantitative real-time PCR revealed a decreased expression of BK channel mRNA. The present findings suggest that emotional disorder manifested in the forms of fear conditioning is accompanied with BK channel suppression in the amygdala, the brain structure critical to this emotional disorder.

  5. Chloride in diet

    MedlinePlus

    ... found in table salt or sea salt as sodium chloride. It is also found in many vegetables. Foods ... Nutrition Board. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. National Academy Press, Washington, DC: 2005. ...

  6. CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT WITH SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

  7. A cyclic GMP-dependent signalling pathway regulates bacterial phytopathogenesis.

    PubMed

    An, Shi-Qi; Chin, Ko-Hsin; Febrer, Melanie; McCarthy, Yvonne; Yang, Jauo-Guey; Liu, Chung-Liang; Swarbreck, David; Rogers, Jane; Maxwell Dow, J; Chou, Shan-Ho; Ryan, Robert P

    2013-09-11

    Cyclic guanosine 3',5'-monophosphate (cyclic GMP) is a second messenger whose role in bacterial signalling is poorly understood. A genetic screen in the plant pathogen Xanthomonas campestris (Xcc) identified that XC_0250, which encodes a protein with a class III nucleotidyl cyclase domain, is required for cyclic GMP synthesis. Purified XC_0250 was active in cyclic GMP synthesis in vitro. The linked gene XC_0249 encodes a protein with a cyclic mononucleotide-binding (cNMP) domain and a GGDEF diguanylate cyclase domain. The activity of XC_0249 in cyclic di-GMP synthesis was enhanced by addition of cyclic GMP. The isolated cNMP domain of XC_0249 bound cyclic GMP and a structure-function analysis, directed by determination of the crystal structure of the holo-complex, demonstrated the site of cyclic GMP binding that modulates cyclic di-GMP synthesis. Mutation of either XC_0250 or XC_0249 led to a reduced virulence to plants and reduced biofilm formation in vitro. These findings describe a regulatory pathway in which cyclic GMP regulates virulence and biofilm formation through interaction with a novel effector that directly links cyclic GMP and cyclic di-GMP signalling.

  8. Distribution of High-Conductance Calcium-Activated Potassium Channels in Rat Vestibular Epithelia

    PubMed Central

    Schweizer, Felix E.; Savin, David; Luu, Cindy; Sultemeier, David R.; Hoffman, Larry F.

    2011-01-01

    Voltage- and calcium-activated potassium channels (BK) are important regulators of neuronal excitability. BK channels seem to be crucial for frequency tuning in nonmammalian vestibular and auditory hair cells. However, there are a paucity of data concerning BK expression in mammalian vestibular hair cells. We therefore investigated the localization of BK channels in mammalian vestibular hair cells, specifically in rat vestibular neuroepithelia. We find that only a subset of hair cells in the utricle and the crista ampullaris express BK channels. BK-positive hair cells are located mainly in the medial striolar region of the utricle, where they constitute at most 12% of hair cells, and in the central zone of the horizontal crista. A majority of BK-positive hair cells are encapsulated by a calretinin-positive calyx defining them as type I cells. The remainder are either type I cells encapsulated by a calretinin-negative calyx or type II hair cells. Surprisingly, the number of BK-positive hair cells in the utricle peaks in juvenile rats and declines in early adulthood. BK channels were not found in vestibular afferent dendrites or somata. Our data indicate that BK channel expression in the mammalian vestibular system differs from the expression pattern in the mammalian auditory and the nonmammalian vestibular system. The molecular diversity of vestibular hair cells indicates a functional diversity that has not yet been fully characterized. The predominance of BK-positive hair cells within the medial striola of juvenile animals suggests that they contribute to a scheme of highly lateralized coding of linear head movements during late development. PMID:19731297

  9. Calcium-dependent Dimerization of Human Soluble Calcium Activated Nucleotidase: Characterization of the Dimer Interface

    SciTech Connect

    Yang,M.; Horii, K.; Herr, A.; Kirley, T.

    2006-01-01

    Mammals express a protein homologous to soluble nucleotidases used by blood-sucking insects to inhibit host blood clotting. These vertebrate nucleotidases may play a role in protein glycosylation. The activity of this enzyme family is strictly dependent on calcium, which induces a conformational change in the secreted, soluble human nucleotidase. The crystal structure of this human enzyme was recently solved; however, the mechanism of calcium activation and the basis for the calcium-induced changes remain unclear. In this study, using analytical ultracentrifugation and chemical cross-linking, we show that calcium or strontium induce noncovalent dimerization of the soluble human enzyme. The location and nature of the dimer interface was elucidated using a combination of site-directed mutagenesis and chemical cross-linking, coupled with crystallographic analyses. Replacement of Ile{sup 170}, Ser{sup 172}, and Ser{sup 226} with cysteine residues resulted in calcium-dependent, sulfhydryl-specific intermolecular cross-linking, which was not observed after cysteine introduction at other surface locations. Analysis of a super-active mutant, E130Y, revealed that this mutant dimerized more readily than the wild-type enzyme. The crystal structure of the E130Y mutant revealed that the mutated residue is found in the dimer interface. In addition, expression of the full-length nucleotidase revealed that this membrane-bound form can also dimerize and that these dimers are stabilized by spontaneous oxidative cross-linking of Cys{sup 30}, located between the single transmembrane helix and the start of the soluble sequence. Thus, calcium-mediated dimerization may also represent a mechanism for regulation of the activity of this nucleotidase in the physiological setting of the endoplasmic reticulum or Golgi.

  10. Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels.

    PubMed

    Castillo, Karen; Contreras, Gustavo F; Pupo, Amaury; Torres, Yolima P; Neely, Alan; González, Carlos; Latorre, Ramon

    2015-04-14

    Being activated by depolarizing voltages and increases in cytoplasmic Ca(2+), voltage- and calcium-activated potassium (BK) channels and their modulatory β-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxiliary β-subunits that are expressed together with the α (BK)-subunit in almost every tissue type where they are found. By measuring gating currents in BK channels coexpressed with chimeras between β1 and β3 or β2 auxiliary subunits, we were able to identify that the cytoplasmic regions of β1 are responsible for the modulation of the voltage sensors. In addition, we narrowed down the structural determinants to the N terminus of β1, which contains two lysine residues (i.e., K3 and K4), which upon substitution virtually abolished the effects of β1 on charge movement. The mechanism by which K3 and K4 stabilize the voltage sensor is not electrostatic but specific, and the α (BK)-residues involved remain to be identified. This is the first report, to our knowledge, where the regulatory effects of the β1-subunit have been clearly assigned to a particular segment, with two pivotal amino acids being responsible for this modulation. PMID:25825713

  11. Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels

    PubMed Central

    Castillo, Karen; Contreras, Gustavo F.; Pupo, Amaury; Torres, Yolima P.; Neely, Alan; González, Carlos; Latorre, Ramon

    2015-01-01

    Being activated by depolarizing voltages and increases in cytoplasmic Ca2+, voltage- and calcium-activated potassium (BK) channels and their modulatory β-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxiliary β-subunits that are expressed together with the α (BK)-subunit in almost every tissue type where they are found. By measuring gating currents in BK channels coexpressed with chimeras between β1 and β3 or β2 auxiliary subunits, we were able to identify that the cytoplasmic regions of β1 are responsible for the modulation of the voltage sensors. In addition, we narrowed down the structural determinants to the N terminus of β1, which contains two lysine residues (i.e., K3 and K4), which upon substitution virtually abolished the effects of β1 on charge movement. The mechanism by which K3 and K4 stabilize the voltage sensor is not electrostatic but specific, and the α (BK)-residues involved remain to be identified. This is the first report, to our knowledge, where the regulatory effects of the β1-subunit have been clearly assigned to a particular segment, with two pivotal amino acids being responsible for this modulation. PMID:25825713

  12. Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons.

    PubMed

    Pérez, Guillermo J; Desai, Mayurika; Anderson, Seth; Scornik, Fabiana S

    2013-02-01

    We studied principal neurons from canine intracardiac (IC) ganglia to determine whether large-conductance calcium-activated potassium (BK) channels play a role in their excitability. We performed whole cell recordings in voltage- and current-clamp modes to measure ion currents and changes in membrane potential from isolated canine IC neurons. Whole cell currents from these neurons showed fast- and slow-activated outward components. Both current components decreased in the absence of calcium and following 1-2 mM tetraethylammonium (TEA) or paxilline. These results suggest that BK channels underlie these current components. Single-channel analysis showed that BK channels from IC neurons do not inactivate in a time-dependent manner, suggesting that the dynamic of the decay of the fast current component is akin to that of intracellular calcium. Immunohistochemical studies showed that BK channels and type 2 ryanodine receptors are coexpressed in IC principal neurons. We tested whether BK current activation in these neurons occurred via a calcium-induced calcium release mechanism. We found that the outward currents of these neurons were not affected by the calcium depletion of intracellular stores with 10 mM caffeine and 10 μM cyclopiazonic acid. Thus, in canine intracardiac neurons, BK currents are directly activated by calcium influx. Membrane potential changes elicited by long (400 ms) current injections showed a tonic firing response that was decreased by TEA or paxilline. These data strongly suggest that the BK current present in canine intracardiac neurons regulates action potential activity and could increase these neurons excitability.

  13. Calcium activated potassium channel expression during human iPS cell-derived neurogenesis.

    PubMed

    Linta, Leonhard; Boeckers, Tobias M; Kleger, Alexander; Liebau, Stefan

    2013-07-01

    The family of calcium activated potassium channels of low and intermediate conductance, known as SK channels, consists of four members (SK1-4). These channels are widely expressed throughout the organism and involved in various cellular processes, such as the afterhyperpolarization in excitable cells but also in differentiation processes of various tissues. To date, the role of SK channels in developmental processes has been merely a marginal focus of investigation, although it is well accepted that cell differentiation and maturation affect the expression patterns of certain ion channels. Recently, several studies from our laboratory delineated the influence of SK channel expression and their respective activity on cytoskeletal reorganization in neural and pluripotent stem cells and regulation of cell fate determination toward the cardiac lineage in human and mouse pluripotent stem cells. Herein, we have now analyzed SK channel expression patterns and distribution at various stages of human induced pluripotent stem cell-derived neurogenesis particularly focusing on undifferentiated iPS cells, neural progenitors and mature neurons. All family members could be detected starting at the iPS cell level and were differentially expressed during the subsequent maturation process. Intriguingly, we found obvious discrepancies between mRNA and protein expression pointing toward a complex regulatory mechanism. Inhibition of SK channels with either apamin or clotrimazol did not have any significant effects on the speed or amount of neurogenesis in vitro. The abundance and specific regulation of SK channel expression during iPS cell differentiation indicates distinct roles of these ion channels not only for the cardiac but also for neuronal cell differentiation and in vitro neurogenesis.

  14. Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons.

    PubMed

    Amjad, Asma; Hernandez-Clavijo, Andres; Pifferi, Simone; Maurya, Devendra Kumar; Boccaccio, Anna; Franzot, Jessica; Rock, Jason; Menini, Anna

    2015-04-01

    Pheromones are substances released from animals that, when detected by the vomeronasal organ of other individuals of the same species, affect their physiology and behavior. Pheromone binding to receptors on microvilli on the dendritic knobs of vomeronasal sensory neurons activates a second messenger cascade to produce an increase in intracellular Ca(2+) concentration. Here, we used whole-cell and inside-out patch-clamp analysis to provide a functional characterization of currents activated by Ca(2+) in isolated mouse vomeronasal sensory neurons in the absence of intracellular K(+). In whole-cell recordings, the average current in 1.5 µM Ca(2+) and symmetrical Cl(-) was -382 pA at -100 mV. Ion substitution experiments and partial blockade by commonly used Cl(-) channel blockers indicated that Ca(2+) activates mainly anionic currents in these neurons. Recordings from inside-out patches from dendritic knobs of mouse vomeronasal sensory neurons confirmed the presence of Ca(2+)-activated Cl(-) channels in the knobs and/or microvilli. We compared the electrophysiological properties of the native currents with those mediated by heterologously expressed TMEM16A/anoctamin1 or TMEM16B/anoctamin2 Ca(2+)-activated Cl(-) channels, which are coexpressed in microvilli of mouse vomeronasal sensory neurons, and found a closer resemblance to those of TMEM16A. We used the Cre-loxP system to selectively knock out TMEM16A in cells expressing the olfactory marker protein, which is found in mature vomeronasal sensory neurons. Immunohistochemistry confirmed the specific ablation of TMEM16A in vomeronasal neurons. Ca(2+)-activated currents were abolished in vomeronasal sensory neurons of TMEM16A conditional knockout mice, demonstrating that TMEM16A is an essential component of Ca(2+)-activated Cl(-) currents in mouse vomeronasal sensory neurons.

  15. Phosphonium chloride for thermal storage

    NASA Technical Reports Server (NTRS)

    Sutton, J. G.; Heimlich, P. F.; Tepper, E. H.

    1972-01-01

    Development of systems for storage of thermal energy is discussed. Application of phosphonium chloride for heat storage through reversible dissociation is described. Chemical, physical, and thermodynamic properties of phosphonium chloride are analyzed and dangers in using phosphonium chloride are explained.

  16. Chloride flux in phagocytes.

    PubMed

    Wang, Guoshun

    2016-09-01

    Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)-H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium-lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes. PMID:27558337

  17. Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1.

    PubMed

    Wulff, H; Gutman, G A; Cahalan, M D; Chandy, K G

    2001-08-24

    Selective and potent triarylmethane blockers of the intermediate conductance calcium-activated potassium channel, IKCa1, have therapeutic use in sickle cell disease and secretory diarrhea and as immunosuppressants. Clotrimazole, a membrane-permeant triarylmethane, blocked IKCa1 with equal affinity when applied externally or internally, whereas a membrane-impermeant derivative TRAM-30 blocked the channel only when applied to the cytoplasmic side, indicating an internal drug-binding site. Introduction of the S5-P-S6 region of the triarylmethane-insensitive small conductance calcium-activated potassium channel SKCa3 into IKCa1 rendered the channel resistant to triarylmethanes. Replacement of Thr(250) or Val(275) in IKCa1 with the corresponding SKCa3 residues selectively abolished triarylmethane sensitivity without affecting the affinity of the channel for tetraethylammonium, charybdotoxin, and nifedipine. Introduction of these two residues into SKCa3 rendered the channel sensitive to triarylmethanes. In a molecular model of IKCa1, Thr(250) and Val(275) line a water-filled cavity just below the selectivity filter. Structure-activity studies suggest that the side chain methyl groups of Thr(250) and Val(275) may lock the triarylmethanes in place via hydrophobic interactions with the pi-electron clouds of the phenyl rings. The heterocyclic moiety may project into the selectivity filter and obstruct the ion-conducting pathway from the inside.

  18. CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT OF CENTER WITH TOP OF SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

  19. Strontium-89 Chloride

    MedlinePlus

    ... ask your doctor or pharmacist for more information.Strontium-89 chloride is in a class of drugs known as radioisotopes. It delivers radiation to cancer sites and ultimately decreases bone pain. The length of treatment depends on the ...

  20. Mercuric chloride poisoning

    MedlinePlus

    ... Mercuric chloride is a very poisonous form of mercury. It is a type of mercury salt. There are different types of mercury poisonings . This article discusses poisoning from swallowing mercuric ...

  1. Hydrogen chloride test set

    NASA Technical Reports Server (NTRS)

    Workman, G. L.

    1976-01-01

    Detector uses tertiary amine, which makes reaction fairly specific for relatively small highly polarized hydrogen chloride molecule. Reaction is monitored by any microbalance capable of measuring extremely small mass differences in real time.

  2. Visinin-like neuronal calcium sensor proteins regulate the slow calcium-activated afterhyperpolarizing current in the rat cerebral cortex.

    PubMed

    Villalobos, Claudio; Andrade, Rodrigo

    2010-10-27

    Many neurons in the nervous systems express afterhyperpolarizations that are mediated by a slow calcium-activated potassium current. This current shapes neuronal firing and is inhibited by neuromodulators, suggesting an important role in the regulation of neuronal function. Surprisingly, very little is currently known about the molecular basis for this current or how it is gated by calcium. Recently, the neuronal calcium sensor protein hippocalcin was identified as a calcium sensor for the slow afterhyperpolarizing current in the hippocampus. However, while hippocalcin is very strongly expressed in the hippocampus, this protein shows a relatively restricted distribution in the brain. Furthermore, the genetic deletion of this protein only partly reduces the slow hyperpolarizing current in hippocampus. These considerations question whether hippocalcin can be the sole calcium sensor for the slow afterhyperpolarizing current. Here we use loss of function and overexpression strategies to show that hippocalcin functions as a calcium sensor for the slow afterhyperpolarizing current in the cerebral cortex, an area where hippocalcin is expressed at much lower levels than in hippocampus. In addition we show that neurocalcin δ, but not VILIP-2, can also act as a calcium sensor for the slow afterhyperpolarizing current. Finally we show that hippocalcin and neurocalcin δ both increase the calcium sensitivity of the afterhyperpolarizing current but do not alter its sensitivity to inhibition by carbachol acting through the Gαq-11-PLCβ signaling cascade. These results point to a general role for a subgroup of visinin-like neuronal calcium sensor proteins in the activation of the slow calcium-activated afterhyperpolarizing current.

  3. Prostaglandin induced changes in the tone of porcine retinal arterioles in vitro involve other factors than calcium activity in perivascular cells.

    PubMed

    Kudryavtseva, Olga; Aalkjær, Christian; Bek, Toke

    2015-09-01

    The cellular basis for the regulation of retinal blood flow is unknown, but recently a new type of perivascular cell (PVC) with pericyte characteristics was identified in the retinal arterial vascular wall located immediately external to the vascular smooth muscle cells. A possible involvement of this cell type in the regulation of retinal vascular tone might be elucidated by studying differences in the response after the addition of compounds stimulating respectively relaxation and contraction. The effects of PGE2 and PGF2α on vascular tone and calcium activity in PVCs in porcine retinal arterioles were studied in a confocal myograph after the addition of the ryanodine receptor blocker ryanodine, the L-type Ca(2+) channel blocker nifedipine, the non-specific cation channel blocker LOE908, the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) blocker CPA, and the inositol triphosphate receptor (IP3R) and transient receptor potential (TRP) ion channel blocker 2-APB. The Ca(2+) channel blockers nifedipine and LOE908 induced significant relaxation of retinal arterioles. After the addition of both PGE2 and PGF2α calcium activity in the PVCs was significantly reduced by both the SERCA inhibitor CPA and the IP3R antagonist 2-APB, but the changes in calcium activity were unrelated to the changes in tone induced by PGE2 and PGF2α. Changes in the tone of porcine retinal arterioles in vitro induced by PGE2 and PGF2α involve other factors than calcium activity in the perivascular cells.

  4. Chloride Channels of Intracellular Membranes

    PubMed Central

    Edwards, John C.; Kahl, Christina R.

    2010-01-01

    Proteins implicated as intracellular chloride channels include the intracellular ClC proteins, the bestrophins, the cystic fibrosis transmembrane conductance regulator, the CLICs, and the recently described Golgi pH regulator. This paper examines current hypotheses regarding roles of intracellular chloride channels and reviews the evidence supporting a role in intracellular chloride transport for each of these proteins. PMID:20100480

  5. The effect of apamin, a small conductance calcium activated potassium (SK) channel blocker, on a mouse model of neurofibromatosis 1.

    PubMed

    Kallarackal, Angy J; Simard, J Marc; Bailey, Aileen M

    2013-01-15

    Neurofibromatosis 1 (NF1) is a common genetic disorder known to cause a variety of physiological symptoms such as the formation of both benign and malignant tumors, and is also known to cause visuospatial learning deficits. Mouse models of NF1 show increased GTP activation of ras which may alter K+ channels. One candidate K+ channel that may contribute to deficits in NF1 is the SK (small conductance calcium-activated potassium) channel due to its role in regulation of long term potentiation (LTP), a mechanism of learning which has been shown to be impaired in Nf1(+/-) mice. We found that administration of apamin (SK antagonist) either through i.p. injection or micro-osmotic pump to Nf1(+/-) mice significantly improved performance on the water maze task in comparison to saline treated Nf1(+/-) mice on the third day of training and on the corresponding probe test. In this study we demonstrate a possible mechanism for the learning deficits seen in Nf1(+/-) mice and a possible drug therapy for rescuing these deficits. PMID:22983217

  6. Calcium activated K⁺ channels in the electroreceptor of the skate confirmed by cloning. Details of subunits and splicing.

    PubMed

    King, Benjamin L; Shi, Ling Fang; Kao, Peter; Clusin, William T

    2016-03-01

    Elasmobranchs detect small potentials using excitable cells of the ampulla of Lorenzini which have calcium-activated K(+) channels, first described in 1974. A distinctive feature of the outward current in voltage clamped ampullae is its apparent insensitivity to voltage. The sequence of a BK channel α isoform expressed in the ampulla of the skate was characterized. A signal peptide is present at the beginning of the gene. When compared to human isoform 1 (the canonical sequence), the largest difference was absence of a 59 amino acid region from the S8-S9 intra-cellular linker that contains the strex regulatory domain. The ampulla isoform was also compared with the isoform predicted in late skate embryos where strex was also absent. The BK voltage sensors were conserved in both skate isoforms. Differences between the skate and human BK channel included alternative splicing. Alternative splicing occurs at seven previously defined sites that are characteristic for BK channels in general and hair cells in particular. Skate BK sequences were highly similar to the Australian ghost shark and several other vertebrate species. Based on alignment of known BK sequences with the skate genome and transcriptome, there are at least two isoforms of Kcnma1α expressed in the skate. One of the β subunits (β4), which is known to decrease voltage sensitivity, was also identified in the skate genome and transcriptome and in the ampulla. These studies advance our knowledge of BK channels and suggest further studies in the ampulla and other excitable tissues. PMID:26687710

  7. The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury.

    PubMed

    Sevelsted Møller, Linda; Fialla, Annette Dam; Schierwagen, Robert; Biagini, Matteo; Liedtke, Christian; Laleman, Wim; Klein, Sabine; Reul, Winfried; Koch Hansen, Lars; Rabjerg, Maj; Singh, Vikrant; Surra, Joaquin; Osada, Jesus; Reinehr, Roland; de Muckadell, Ove B Schaffalitzky; Köhler, Ralf; Trebicka, Jonel

    2016-01-01

    The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury. PMID:27354175

  8. The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3.

    PubMed

    Terstappen, Georg C; Pellacani, Annalisa; Aldegheri, Laura; Graziani, Francesca; Carignani, Corrado; Pula, Giordano; Virginio, Caterina

    2003-07-31

    The effects of fluoxetine (Prozac) on the activity of human small-conductance calcium-activated potassium (SK) channels were investigated utilizing a functional fluorescence assay with bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC(4)(3)). Fluoxetine blocked SK channels stably expressed in HEK 293 cells in a concentration-dependent manner displaying half-maximal inhibitory concentrations (IC(50)) of 9 microM for hSK1, 7 microM for hSK2 and 20 microM for hSK3. The block of hSK3 channels was confirmed by whole cell patch-clamp recordings of the recombinant cells and human TE 671 cells. Fluoxetine also inhibited [(125)I]apamin binding in a concentration-dependent manner displaying IC(50) values of 63 microM for hSK1, 148 microM for hSK2 and 295 microM for hSK3. These results provide new information concerning the mechanism of therapeutic and/or side effects of one of the most widely used antidepressant drugs.

  9. The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury

    PubMed Central

    Sevelsted Møller, Linda; Fialla, Annette Dam; Schierwagen, Robert; Biagini, Matteo; Liedtke, Christian; Laleman, Wim; Klein, Sabine; Reul, Winfried; Koch Hansen, Lars; Rabjerg, Maj; Singh, Vikrant; Surra, Joaquin; Osada, Jesus; Reinehr, Roland; de Muckadell, Ove B. Schaffalitzky; Köhler, Ralf; Trebicka, Jonel

    2016-01-01

    The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury. PMID:27354175

  10. Chloride channels as drug targets

    PubMed Central

    Verkman, Alan S.; Galietta, Luis J. V.

    2013-01-01

    Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABAA (γ-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. PMID:19153558

  11. Modulation of Chloride Channel Functions by the Plant Lignan Compounds Kobusin and Eudesmin

    PubMed Central

    Jiang, Yu; Yu, Bo; Fang, Fang; Cao, Huanhuan; Ma, Tonghui; Yang, Hong

    2015-01-01

    Plant lignans are diphenolic compounds widely present in vegetables, fruits, and grains. These compounds have been demonstrated to have protective effect against cancer, hypertension and diabetes. In the present study, we showed that two lignan compounds, kobusin and eudesmin, isolated from Magnoliae Flos, could modulate intestinal chloride transport mediated by cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs). The compounds activated CFTR channel function in both FRT cells and in HT-29 cells. The modulating effects of kobusin and eudesmin on the activity of CaCCgie (CaCC expressed in gastrointestinal epithelial cells) were also investigated, and the result showed that both compounds could stimulate CaCCgie-mediated short-circuit currents and the stimulation was synergistic with ATP. In ex vivo studies, both compounds activated CFTR and CaCCgie chloride channel activities in mouse colonic epithelia. Remarkably, the compounds showed inhibitory effects toward ANO1/CaCC-mediated short-circuit currents in ANO1/CaCC-expressing FRT cells, with IC50 values of 100 μM for kobusin and 200 μM for eudesmin. In charcoal transit study, both compounds mildly reduced gastrointestinal motility in mice. Taken together, these results revealed a new kind of activity displayed by the lignan compounds, one that is concerned with the modulation of chloride channel function. PMID:26635857

  12. Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel

    PubMed Central

    Herrera, Gerald M; Pozo, Maria J; Zvara, Peter; Petkov, Georgi V; Bond, Chris T; Adelman, John P; Nelson, Mark T

    2003-01-01

    Small conductance, calcium-activated potassium (SK) channels have an important role in determining the excitability and contractility of urinary bladder smooth muscle. Here, the role of the SK isoform SK3 was examined by altering expression levels of the SK3 gene using a mouse model that conditionally overexpresses SK3 channels (SK3T/T). Prominent SK3 immunostaining was found in both the smooth muscle (detrusor) and urothelium layers of the urinary bladder. SK currents were elevated 2.4-fold in isolated myocytes from SK3T/T mice. Selective suppression of SK3 expression by dietary doxycycline (DOX) decreased SK current density in isolated myocytes, increased phasic contractions of isolated urinary bladder smooth muscle strips and exposed high affinity effects of the blocker apamin of the SK isoforms (SK1–3), suggesting an additional participation from SK2 channels. The role of SK3 channels in urinary bladder function was assessed using cystometry in conscious, freely moving mice. The urinary bladders of SK3T/T had significantly greater bladder capacity, and urine output exceeded the infused saline volume. Suppression of SK3 channel expression did not alter filling pressure, threshold pressure or bladder capacity, but micturition pressure was elevated compared to control mice. However, SK3 suppression did eliminate excess urine production and caused a marked increase in non-voiding contractions. The ability to examine bladder function in mice in which SK3 channel expression is selectively altered reveals that these channels have a significant role in the control of non-voiding contractions in vivo. Activation of these channels may be a therapeutic approach for management of non-voiding contractions, a condition which characterizes many types of urinary bladder dysfunctions including urinary incontinence. PMID:12813145

  13. Increased Expression of the Large Conductance, Calcium-Activated K+ (BK) Channel in Adult-Onset Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Donnelier, Julien; Braun, Samuel T.; Dolzhanskaya, Natalia; Ahrendt, Eva; Braun, Andrew P.; Velinov, Milen; Braun, Janice E. A.

    2015-01-01

    Cysteine string protein (CSPα) is a presynaptic J protein co-chaperone that opposes neurodegeneration. Mutations in CSPα (i.e., Leu115 to Arg substitution or deletion (Δ) of Leu116) cause adult neuronal ceroid lipofuscinosis (ANCL), a dominantly inherited neurodegenerative disease. We have previously demonstrated that CSPα limits the expression of large conductance, calcium-activated K+ (BK) channels in neurons, which may impact synaptic excitability and neurotransmission. Here we show by western blot analysis that expression of the pore-forming BKα subunit is elevated ~2.5 fold in the post-mortem cortex of a 36-year-old patient with the Leu116∆ CSPα mutation. Moreover, we find that the increase in BKα subunit level is selective for ANCL and not a general feature of neurodegenerative conditions. While reduced levels of CSPα are found in some postmortem cortex specimens from Alzheimer’s disease patients, we find no concomitant increase in BKα subunit expression in Alzheimer’s specimens. Both CSPα monomer and oligomer expression are reduced in synaptosomes prepared from ANCL cortex compared with control. In a cultured neuronal cell model, CSPα oligomers are short lived. The results of this study indicate that the Leu116∆ mutation leads to elevated BKα subunit levels in human cortex and extend our initial work in rodent models demonstrating the modulation of BKα subunit levels by the same CSPα mutation. While the precise sequence of pathogenic events still remains to be elucidated, our findings suggest that dysregulation of BK channels may contribute to neurodegeneration in ANCL. PMID:25905915

  14. Calcium-activated afterhyperpolarizations regulate synchronization and timing of epileptiform bursts in hippocampal CA3 pyramidal neurons.

    PubMed

    Fernández de Sevilla, David; Garduño, Julieta; Galván, Emilio; Buño, Washington

    2006-12-01

    Calcium-activated potassium conductances regulate neuronal excitability, but their role in epileptogenesis remains elusive. We investigated in rat CA3 pyramidal neurons the contribution of the Ca(2+)-activated K(+)-mediated afterhyperpolarizations (AHPs) in the genesis and regulation of epileptiform activity induced in vitro by 4-aminopyridine (4-AP) in Mg(2+)-free Ringer. Recurring spike bursts terminated by prolonged AHPs were generated. Burst synchronization between CA3 pyramidal neurons in paired recordings typified this interictal-like activity. A downregulation of the medium afterhyperpolarization (mAHP) paralleled the emergence of the interictal-like activity. When the mAHP was reduced or enhanced by apamin and EBIO bursts induced by 4-AP were increased or blocked, respectively. Inhibition of the slow afterhyperpolarization (sAHP) with carbachol, t-ACPD, or isoproterenol increased bursting frequency and disrupted burst regularity and synchronization between pyramidal neuron pairs. In contrast, enhancing the sAHP by intracellular dialysis with KMeSO(4) reduced burst frequency. Block of GABA(A-B) inhibitions did not modify the abnormal activity. We describe novel cellular mechanisms where 1) the inhibition of the mAHP plays an essential role in the genesis and regulation of the bursting activity by reducing negative feedback, 2) the sAHP sets the interburst interval by decreasing excitability, and 3) bursting was synchronized by excitatory synaptic interactions that increased in advance and during bursts and decreased throughout the subsequent sAHP. These cellular mechanisms are active in the CA3 region, where epileptiform activity is initiated, and cooperatively regulate the timing of the synchronized rhythmic interictal-like network activity. PMID:16971683

  15. Inhibition of vascular calcification by block of intermediate conductance calcium-activated potassium channels with TRAM-34.

    PubMed

    Freise, Christian; Querfeld, Uwe

    2014-07-01

    Vascular calcifications are a hallmark of advanced cardiovascular disease in patients with chronic kidney disease. A key event is the transition of contractile vascular smooth muscle cells (VSMC) into an osteoblast-like phenotype, promoting a coordinated process of vascular remodeling resembling bone mineralization. Intermediate-conductance calcium-activated potassium channels (KCa3.1) are expressed in various tissues including VSMC. Aiming for novel therapeutic targets in vascular calcification, we here studied effects of KCa3.1-inhibition on VSMC calcification by the specific KCa3.1 inhibitor TRAM-34. Calcification in the murine VSMC cell line MOVAS-1 and primary rat VSMC was induced by calcification medium (CM) containing elevated levels of PO4(3-) and Ca(2+). Cell signaling, calcification markers, and release of nitric oxide and alkaline phosphatase were assessed by luciferase reporter plasmids, RT-PCR and specific enzymatic assays, respectively. KCa3.1 gene silencing was achieved by siRNA experiments. TRAM-34 at 10nmol/l, decreased CM-induced calcification and induced NO release of VSMC accompanied by decreased TGF-β signaling. The CM-induced mRNA expressions of osterix, osteocalcin, matrix-metalloproteinases (MMP)-2/-9 were reduced by TRAM-34 while osteopontin expression was increased. Further, TRAM-34 attenuated the CM- and TNF-α-induced activation of NF-κB and reduced the release of MMP-2/-9 by VSMC. Finally, TRAM-34 abrogated CM-induced apoptosis and KCa3.1 gene silencing protected VSMC from CM-induced onset of calcification. In summary, TRAM-34 interferes with calcification relevant signaling of NF-κB and TGF-β thereby blocking the phenotypic transition/calcification of VSMC. We conclude that the results provide a rationale for further studies regarding a possible therapeutic role of KCa3.1 inhibition by TRAM-34 or other inhibitors in vascular calcification.

  16. 21 CFR 184.1297 - Ferric chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... hydrogen chloride. The pure material occurs as hydroscopic, hexagonal, dark crystals. Ferric chloride... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ferric chloride. 184.1297 Section 184.1297 Food... Specific Substances Affirmed as GRAS § 184.1297 Ferric chloride. (a) Ferric chloride (iron (III)...

  17. 21 CFR 184.1297 - Ferric chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... GRAS § 184.1297 Ferric chloride. (a) Ferric chloride (iron (III) chloride, FeC13, CAS Reg. No. 7705-08-0) may be prepared from iron and chlorine or from ferric oxide and hydrogen chloride. The pure... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ferric chloride. 184.1297 Section 184.1297...

  18. 21 CFR 184.1297 - Ferric chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... hydrogen chloride. The pure material occurs as hydroscopic, hexagonal, dark crystals. Ferric chloride... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ferric chloride. 184.1297 Section 184.1297 Food... Specific Substances Affirmed as GRAS § 184.1297 Ferric chloride. (a) Ferric chloride (iron (III)...

  19. 21 CFR 184.1297 - Ferric chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... hydrogen chloride. The pure material occurs as hydroscopic, hexagonal, dark crystals. Ferric chloride... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ferric chloride. 184.1297 Section 184.1297 Food... Specific Substances Affirmed as GRAS § 184.1297 Ferric chloride. (a) Ferric chloride (iron (III)...

  20. Benzalkonium Chloride and Glaucoma

    PubMed Central

    Kaufman, Paul L.; Kiland, Julie A.

    2014-01-01

    Abstract Glaucoma patients routinely take multiple medications, with multiple daily doses, for years or even decades. Benzalkonium chloride (BAK) is the most common preservative in glaucoma medications. BAK has been detected in the trabecular meshwork (TM), corneal endothelium, lens, and retina after topical drop installation and may accumulate in those tissues. There is evidence that BAK causes corneal and conjunctival toxicity, including cell loss, disruption of tight junctions, apoptosis and preapoptosis, cytoskeleton changes, and immunoinflammatory reactions. These same effects have been reported in cultured human TM cells exposed to concentrations of BAK found in common glaucoma drugs and in the TM of primary open-angle glaucoma donor eyes. It is possible that a relationship exists between chronic exposure to BAK and glaucoma. The hypothesis that BAK causes/worsens glaucoma is being tested experimentally in an animal model that closely reflects human physiology. PMID:24205938

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

    PubMed

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

    2014-05-01

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

  2. Reactor-chromatographic determination of vinyl chloride in polyvinyl chloride

    SciTech Connect

    Berezkin, V.G.

    1986-08-01

    The authors carry out a chromatographic study of the volatile products that evolve when various grades of domestic polyvinyl chloride are heated, to determine the concentration of residual monomer. To find vinyl chloride in complex mixtures of air pollutants the authors used sorptive reaction concentration of impurities. This new combination of methods is based on preliminary separation at the sampling stage of impurities that interfere in the analysis, followed by concentration of the desired components in a trap with an adsorbent, and chromatographic determination of the concentrated trace materials. The method obtains low vinyl chloride concentrations (down to 10/sup -4/-10/sup -5/ wt. %) with +/-5 relative error.

  3. A Synthetic Chloride Channel Relaxes Airway Smooth Muscle of the Rat

    PubMed Central

    Yau, Kwok-hei; Mak, Judith Choi-wo; Leung, Susan Wai-sum; Yang, Dan; Vanhoutte, Paul M.

    2012-01-01

    Synthetic ion channels may have potential therapeutic applications, provided they possess appropriate biological activities. The present study was designed to examine the ability of small molecule-based synthetic Cl– channels to modulate airway smooth muscle responsiveness. Changes in isometric tension were measured in rat tracheal rings. Relaxations to the synthetic chloride channel SCC-1 were obtained during sustained contractions to KCl. The anion dependency of the effect of SCC-1 was evaluated by ion substitution experiments. The sensitivity to conventional Cl– transport inhibitors was also tested. SCC-1 caused concentration-dependent relaxations during sustained contractions to potassium chloride. This relaxing effect was dependent on the presence of extracellular Cl– and HCO3−. It was insensitive to conventional Cl– channels/transport inhibitors that blocked the cystic fibrosis transmembrane conductance regulator and calcium-activated Cl– channels. SCC-1 did not inhibit contractions induced by carbachol, endothelin-1, 5-hydroxytryptamine or the calcium ionophore A23187. SCC-1 relaxes airway smooth muscle during contractions evoked by depolarizing solutions. The Cl– conductance conferred by this synthetic compound is distinct from the endogenous transport systems for chloride anions. PMID:23049786

  4. Role of calcium-activated potassium channels in the regulation of basal and agonist-elevated tones in isolated conduit arteries. Short communication.

    PubMed

    Pataricza, J; Márton, Z; Hegedus, Z; Krassói, Irén; Kun, A; Varró, A; Papp, J Gy

    2004-01-01

    Functional role of calcium-activated potassium (KCa) channels on the basal and agonist-elevated arterial tones was investigated in isolated rabbit aorta, porcine and canine coronary arteries as well as in human internal mammary artery. The vascular tones enhanced by contractile agents were increased further by preincubation of these conduit blood vessels with selective (charybdotoxin or iberiotoxin) or nonselective (tetraethylammonium) inhibitors of KCa channels. The basal tone (without an agonist) was increased only in the canine coronary artery. The results indicate a feed-back regulatory role of KCa channels counteracting the vasospasm of conduit arteries. PMID:16438119

  5. Studies Update Vinyl Chloride Hazards.

    ERIC Educational Resources Information Center

    Rawls, Rebecca

    1980-01-01

    Extensive study affirms that vinyl chloride is a potent animal carcinogen. Epidemiological studies show elevated rates of human cancers in association with extended contact with the compound. (Author/RE)

  6. Secreted CLCA1 modulates TMEM16A to activate Ca(2+)-dependent chloride currents in human cells.

    PubMed

    Sala-Rabanal, Monica; Yurtsever, Zeynep; Nichols, Colin G; Brett, Tom J

    2015-03-17

    Calcium-activated chloride channel regulator 1 (CLCA1) activates calcium-dependent chloride currents; neither the target, nor mechanism, is known. We demonstrate that secreted CLCA1 activates calcium-dependent chloride currents in HEK293T cells in a paracrine fashion, and endogenous TMEM16A/Anoctamin1 conducts the currents. Exposure to exogenous CLCA1 increases cell surface levels of TMEM16A and cellular binding experiments indicate CLCA1 engages TMEM16A on the surface of these cells. Altogether, our data suggest that CLCA1 stabilizes TMEM16A on the cell surface, thus increasing surface expression, which results in increased calcium-dependent chloride currents. Our results identify the first Cl(-) channel target of the CLCA family of proteins and establish CLCA1 as the first secreted direct modifier of TMEM16A activity, delineating a unique mechanism to increase currents. These results suggest cooperative roles for CLCA and TMEM16 proteins in influencing the physiology of multiple tissues, and the pathology of multiple diseases, including asthma, COPD, cystic fibrosis, and certain cancers.

  7. An XAFS study of nickel chloride in the ionic liquid 1-ethyl-3-methyl imidazolium chloride/ aluminum chloride

    SciTech Connect

    D Roeper; G Cheek; K Pandya; W OGrady

    2011-12-31

    Nickel chloride was studied with cyclic voltammetry and X-ray absorption spectroscopy in acidic and basic aluminum chloride/1-ethyl-3-methyl imidazolium chloride (EMIC) ionic liquids. Acidic melts display metal stripping peaks which are not observed in the basic melt. EXAFS analysis shows that the nickel is tetrahedrally coordinated with chloride ions in the basic solution. In the acidic solution the nickel is coordinated by six chloride ions that are also associated with aluminum ions.

  8. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in...

  9. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg. No. 7447-40-7) is a white... manufacturing practice. Potassium chloride may be used in infant formula in accordance with section 412(g)...

  10. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in...

  11. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium chloride. 184.1622 Section 184.1622 Food... Specific Substances Affirmed as GRAS § 184.1622 Potassium chloride. (a) Potassium chloride (KCl, CAS Reg... levels not to exceed current good manufacturing practice. Potassium chloride may be used in...

  12. 21 CFR 184.1138 - Ammonium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... from the filtrate on cooling. Alternatively, hydrogen chloride formed by the burning of hydrogen in... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ammonium chloride. 184.1138 Section 184.1138 Food... Specific Substances Affirmed as GRAS § 184.1138 Ammonium chloride. (a) Ammonium chloride (NH4Cl, CAS...

  13. 21 CFR 184.1138 - Ammonium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... from the filtrate on cooling. Alternatively, hydrogen chloride formed by the burning of hydrogen in... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ammonium chloride. 184.1138 Section 184.1138 Food... Specific Substances Affirmed as GRAS § 184.1138 Ammonium chloride. (a) Ammonium chloride (NH4Cl, CAS...

  14. 21 CFR 184.1138 - Ammonium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... from the filtrate on cooling. Alternatively, hydrogen chloride formed by the burning of hydrogen in... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ammonium chloride. 184.1138 Section 184.1138 Food... Specific Substances Affirmed as GRAS § 184.1138 Ammonium chloride. (a) Ammonium chloride (NH4Cl, CAS...

  15. 21 CFR 184.1138 - Ammonium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... from the filtrate on cooling. Alternatively, hydrogen chloride formed by the burning of hydrogen in... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ammonium chloride. 184.1138 Section 184.1138 Food... Specific Substances Affirmed as GRAS § 184.1138 Ammonium chloride. (a) Ammonium chloride (NH4Cl, CAS...

  16. 21 CFR 184.1138 - Ammonium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Alternatively, hydrogen chloride formed by the burning of hydrogen in chlorine is dissolved in water and then... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ammonium chloride. 184.1138 Section 184.1138 Food... GRAS § 184.1138 Ammonium chloride. (a) Ammonium chloride (NH4Cl, CAS Reg. No. 12125-02-9) is...

  17. Regeneration of zinc chloride hydrocracking catalyst

    DOEpatents

    Zielke, Clyde W.

    1979-01-01

    Improved rate of recovery of zinc values from the solids which are carried over by the effluent vapors from the oxidative vapor phase regeneration of spent zinc chloride catalyst is achieved by treatment of the solids with both hydrogen chloride and calcium chloride to selectively and rapidly recover the zinc values as zinc chloride.

  18. 21 CFR 184.1622 - Potassium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  19. CHLORIDE WASHER PERFORMACE TESTING

    SciTech Connect

    Coughlin, J; David Best, D; Robert Pierce, R

    2007-11-30

    Testing was performed to determine the chloride (Cl-) removal capabilities of the Savannah River National Laboratory (SRNL) designed and built Cl- washing equipment intended for HB-Line installation. The equipment to be deployed was tested using a cerium oxide (CeO2) based simulant in place of the 3013 plutonium oxide (PuO2) material. Two different simulant mixtures were included in this testing -- one having higher Cl- content than the other. The higher Cl- simulant was based on K-Area Interim Surveillance Inspection Program (KIS) material with Cl- content approximately equal to 70,000 ppm. The lower Cl- level simulant was comparable to KIS material containing approximately 8,000-ppm Cl- content. The performance testing results indicate that the washer is capable of reducing the Cl- content of both surrogates to below 200 ppm with three 1/2-liter washes of 0.1M sodium hydroxide (NaOH) solution. Larger wash volumes were used with similar results - all of the prescribed test parameters consistently reduced the Cl- content of the surrogate to a value below 200 ppm Cl- in the final washed surrogate material. The washer uses a 20-micron filter to retain the surrogate solids. Tests showed that 0.16-0.41% of the insoluble fraction of the starting mass passed through the 20-micron filter. The solids retention performance indicates that the fissile masses passing through the 20-micron filter should not exceed the waste acceptance criteria for discard in grout to TRU waste. It is recommended that additional testing be pursued for further verification and optimization purposes. It is likely that wash volumes smaller than those tested could still reduce the Cl- values to acceptable levels. Along with reduced wash volumes, reuse of the third wash volume (in the next run processed) should be tested as a wash solution minimization plan. A 67% reduction in the number of grouted paint pails could be realized if wash solution minimization testing returned acceptable results.

  20. 21 CFR 184.1297 - Ferric chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  1. Worker exposure to vinyl chloride and poly(vinyl chloride).

    PubMed

    Jones, J H

    1981-10-01

    The National Institute for Occupational Safety and Health (NIOSH) in early 1974 began industrial hygiene studies of vinyl chloride exposed workers. Three VC monomer plants, three VC polymerization plants, and seven PVC fabrication plants were surveyed. V polymerization plant workers and workers in one job category in VC monomer plants were exposed to average levels above 1 ppm. The highest average exposure was 22 ppm. NIOSH health hazard evaluation studies since these initial surveys have primarily shown nondetectable levels of vinyl chloride. A NIOSH control technology study in 1977 showed that exposure levels in VC polymerization plants had been drastically reduced but exposure levels above 1 ppm were still found in several cases.

  2. l-Nebiviololinium chloride dihydrate

    PubMed Central

    Tuchalski, Gisbert; Hänsicke, Andre; Reck, Günther; Emmerling, Franziska

    2008-01-01

    The hydro­chloride salt of chiral l-nebivolol {systematic name: (+)−(R,S,S,S)-bis­[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxy­ethyl]ammonium chloride dihydrate}, C22H26F2NO4 +·Cl−·2H2O, was obtained by chiral liquid chromatography as a dihydrate. The pyran rings adopt half-chair conformations. Hydrogen bonds between the cation, anions and water mol­ecules contribute to the formation of layers parallel to the ac plane. PMID:21200930

  3. Calcium-activated tenderization of strip loin, top sirloin, and top round steaks in diverse genotypes of cattle.

    PubMed

    Pringle, T D; Harrelson, J M; West, R L; Williams, S E; Johnson, D D

    1999-12-01

    Steers of known percentage Brahman (B) and Angus (A) breeding (100% A, n = 6; F1 B x A, n = 6; and 100% B, n = 6) were used to determine the effect of calcium chloride injection on the calpain proteinase system and meat tenderness. The steers were slaughtered in six replications (at either 9 or 14 mm of backfat, determined ultrasonically), with each breed type represented. Calpains and calpastatin activities were measured on fresh, prerigor longissimus muscle samples. Carcass data were collected after a 24-h chill, and the short loin (IMPS #180), top sirloin (IMPS #184), and top round (IMPS #168) were removed from both sides of each carcass. The cuts from the right side were then injected at 5% (wt/wt) with CaCl2 solution (2.2%). Longissimus muscle calpain and calpastatin activities were also measured at 48 h postmortem from the injected and control sides of each carcass. Warner-Bratzler shear force was measured on steaks from the three subprimals aged 1, 2, 5, 15, or 31 d. Marbling scores and USDA quality grades were higher (P<.05) in A than in F1 B x A and B carcasses. Calpastatin activity was higher (P<.05) in muscle from B than in muscle from A and F1 B x A steers, and postmortem storage (O vs 48 h) and CaCl2 injection reduced (P<.05) the activity of the calpains and calpastatin. Strip loin and top sirloin steaks from A and F1 B x A steers were more tender (P<.05) than steaks from B steers; however, top round steak tenderness did not differ (P>.05) across breed type. Calcium injection improved strip loin and top sirloin steak tenderness, but it did not affect top round steak tenderness. Collectively, these data show that CaC12 injection can be used to improve meat tenderness, with similar responses shown in cattle containing 0, 50, and 100% B inheritance. However, even with CaCl2 injection, B steaks are less tender than their A and F1 B x A counterparts. PMID:10641869

  4. Calcium-activated tenderization of strip loin, top sirloin, and top round steaks in diverse genotypes of cattle.

    PubMed

    Pringle, T D; Harrelson, J M; West, R L; Williams, S E; Johnson, D D

    1999-12-01

    Steers of known percentage Brahman (B) and Angus (A) breeding (100% A, n = 6; F1 B x A, n = 6; and 100% B, n = 6) were used to determine the effect of calcium chloride injection on the calpain proteinase system and meat tenderness. The steers were slaughtered in six replications (at either 9 or 14 mm of backfat, determined ultrasonically), with each breed type represented. Calpains and calpastatin activities were measured on fresh, prerigor longissimus muscle samples. Carcass data were collected after a 24-h chill, and the short loin (IMPS #180), top sirloin (IMPS #184), and top round (IMPS #168) were removed from both sides of each carcass. The cuts from the right side were then injected at 5% (wt/wt) with CaCl2 solution (2.2%). Longissimus muscle calpain and calpastatin activities were also measured at 48 h postmortem from the injected and control sides of each carcass. Warner-Bratzler shear force was measured on steaks from the three subprimals aged 1, 2, 5, 15, or 31 d. Marbling scores and USDA quality grades were higher (P<.05) in A than in F1 B x A and B carcasses. Calpastatin activity was higher (P<.05) in muscle from B than in muscle from A and F1 B x A steers, and postmortem storage (O vs 48 h) and CaCl2 injection reduced (P<.05) the activity of the calpains and calpastatin. Strip loin and top sirloin steaks from A and F1 B x A steers were more tender (P<.05) than steaks from B steers; however, top round steak tenderness did not differ (P>.05) across breed type. Calcium injection improved strip loin and top sirloin steak tenderness, but it did not affect top round steak tenderness. Collectively, these data show that CaC12 injection can be used to improve meat tenderness, with similar responses shown in cattle containing 0, 50, and 100% B inheritance. However, even with CaCl2 injection, B steaks are less tender than their A and F1 B x A counterparts.

  5. Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

    PubMed Central

    Heinze, Christoph; Seniuk, Anika; Sokolov, Maxim V.; Huebner, Antje K.; Klementowicz, Agnieszka E.; Szijártó, István A.; Schleifenbaum, Johanna; Vitzthum, Helga; Gollasch, Maik; Ehmke, Heimo; Schroeder, Björn C.; Hübner, Christian A.

    2014-01-01

    High blood pressure is the leading risk factor for death worldwide. One of the hallmarks is a rise of peripheral vascular resistance, which largely depends on arteriole tone. Ca2+-activated chloride currents (CaCCs) in vascular smooth muscle cells (VSMCs) are candidates for increasing vascular contractility. We analyzed the vascular tree and identified substantial CaCCs in VSMCs of the aorta and carotid arteries. CaCCs were small or absent in VSMCs of medium-sized vessels such as mesenteric arteries and larger retinal arterioles. In small vessels of the retina, brain, and skeletal muscle, where contractile intermediate cells or pericytes gradually replace VSMCs, CaCCs were particularly large. Targeted disruption of the calcium-activated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes eliminated CaCCs in all vessels studied. Mice lacking vascular TMEM16A had lower systemic blood pressure and a decreased hypertensive response following vasoconstrictor treatment. There was no difference in contractility of medium-sized mesenteric arteries; however, responsiveness of the aorta and small retinal arterioles to the vasoconstriction-inducing drug U46619 was reduced. TMEM16A also was required for peripheral blood vessel contractility, as the response to U46619 was attenuated in isolated perfused hind limbs from mutant mice. Out data suggest that TMEM16A plays a general role in arteriolar and capillary blood flow and is a promising target for the treatment of hypertension. PMID:24401273

  6. Integrative Approach for Computationally Inferring Interactions between the Alpha and Beta Subunits of the Calcium-Activated Potassium Channel (BK): a Docking Study

    PubMed Central

    González, Janneth; Gálvez, Angela; Morales, Ludis; Barreto, George E.; Capani, Francisco; Sierra, Omar; Torres, Yolima

    2013-01-01

    Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex. PMID:23492851

  7. Phenoxyethanol absorption by polyvinyl chloride.

    PubMed

    Lee, M G

    1984-12-01

    Phenoxyethanol was found to be absorbed by polyvinyl chloride administration sets during continuous irrigation therapy. Depending upon the conditions of administration up to 20% loss of potency could occur. Absorption of the drug by the rigid plastic luer-lock fitting of the set caused softening and decreased rigidity of the plastic.

  8. Method for the abatement of hydrogen chloride

    DOEpatents

    Winston, S.J.; Thomas, T.R.

    1975-11-14

    A method is described for reducing the amount of hydrogen chloride contained in a gas stream by reacting the hydrogen chloride with ammonia in the gas phase so as to produce ammonium chloride. The combined gas stream is passed into a condensation and collection vessel, and a cyclonic flow is created in the combined gas stream as it passes through the vessel. The temperature of the gas stream is reduced in the vessel to below the condensation temperature of ammonium chloride in order to crystallize the ammonium chloride on the walls of the vessel. The cyclonic flow creates a turbulence which breaks off the larger particles of ammonium chloride which are, in turn, driven to the bottom of the vessel where the solid ammonium chloride can be removed from the vessel. The gas stream exiting from the condensation and collection vessel is further cleaned and additional ammonium chloride is removed by passing through additional filters.

  9. Method for the abatement of hydrogen chloride

    DOEpatents

    Winston, Steven J.; Thomas, Thomas R.

    1977-01-01

    The present invention provides a method for reducing the amount of hydrogen chloride contained in a gas stream by reacting the hydrogen chloride with ammonia in the gas phase so as to produce ammonium chloride. The combined gas stream is passed into a condensation and collection vessel and a cyclonic flow is created in the combined gas stream as it passes through the vessel. The temperature of the gas stream is reduced in the vessel to below the condensation temperature of ammonium chloride in order to crystallize the ammonium chloride on the walls of the vessel. The cyclonic flow creates a turbulence which breaks off the larger particles of ammonium chloride which are, in turn, driven to the bottom of the vessel where the solid ammonium chloride can be removed from the vessel. The gas stream exiting from the condensation and collection vessel is further cleaned and additional ammonium chloride is removed by passing through additional filters.

  10. 21 CFR 582.5252 - Choline chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use....

  11. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use....

  12. 21 CFR 582.5252 - Choline chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use....

  13. 21 CFR 582.5446 - Manganese chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5446 Manganese chloride. (a) Product. Manganese chloride. (b) Conditions of use....

  14. 21 CFR 582.5446 - Manganese chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5446 Manganese chloride. (a) Product. Manganese chloride. (b) Conditions of use....

  15. 21 CFR 582.5446 - Manganese chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5446 Manganese chloride. (a) Product. Manganese chloride. (b) Conditions of use....

  16. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use....

  17. 21 CFR 582.5252 - Choline chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use....

  18. 21 CFR 582.5446 - Manganese chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5446 Manganese chloride. (a) Product. Manganese chloride. (b) Conditions of use....

  19. 21 CFR 582.5252 - Choline chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use....

  20. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use....

  1. 21 CFR 582.5446 - Manganese chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5446 Manganese chloride. (a) Product. Manganese chloride. (b) Conditions of use....

  2. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5622 Potassium chloride. (a) Product. Potassium chloride. (b) Conditions of use....

  3. 21 CFR 582.5252 - Choline chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use....

  4. 21 CFR 184.1446 - Manganese chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... GRAS § 184.1446 Manganese chloride. (a) Manganese chloride (MnCl2, CAS Reg. No. 7773-01-5) is a pink... manganous oxide, pyrolusite ore (MnO2), or reduced manganese ore in hydrochloric acid. The...

  5. 21 CFR 184.1446 - Manganese chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Specific Substances Affirmed as GRAS § 184.1446 Manganese chloride. (a) Manganese chloride (MnCl2, CAS Reg.... It is prepared by dissolving manganous oxide, pyrolusite ore (MnO2), or reduced manganese ore...

  6. 21 CFR 184.1446 - Manganese chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Specific Substances Affirmed as GRAS § 184.1446 Manganese chloride. (a) Manganese chloride (MnCl2, CAS Reg.... It is prepared by dissolving manganous oxide, pyrolusite ore (MnO2), or reduced manganese ore...

  7. Microbial reductive dehalogenation of vinyl chloride

    DOEpatents

    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.

  8. Microbial reductive dehalogenation of vinyl chloride

    DOEpatents

    Spormann, Alfred M.; Muller, Jochen A.; Rosner, Bettina M.; Von Abendroth, Gregory; Meshulam-Simon, Galit; McCarty, Perry L

    2011-11-22

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

  9. 21 CFR 184.1193 - Calcium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium chloride. 184.1193 Section 184.1193 Food... Specific Substances Affirmed as GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be...

  10. 21 CFR 184.1193 - Calcium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium chloride. 184.1193 Section 184.1193 Food... Specific Substances Affirmed as GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be...

  11. 21 CFR 184.1193 - Calcium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium chloride. 184.1193 Section 184.1193 Food... Specific Substances Affirmed as GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be...

  12. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance...

  13. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance...

  14. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b)...

  15. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is generally recognized as safe when used...

  16. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is generally recognized as safe when used...

  17. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance...

  18. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Zinc chloride. 182.8985 Section 182.8985 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8985 Zinc chloride. (a) Product. Zinc chloride. (b) Conditions of use. This substance is generally recognized as safe when used...

  19. 21 CFR 182.8252 - Choline chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Choline chloride. 182.8252 Section 182.8252 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized...

  20. 21 CFR 182.8252 - Choline chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Choline chloride. 182.8252 Section 182.8252 Food... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride. (b) Conditions of use. This substance is generally recognized...

  1. 21 CFR 172.180 - Stannous chloride.

    Code of Federal Regulations, 2010 CFR

    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...

  2. 21 CFR 182.8252 - Choline chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Choline chloride. 182.8252 Section 182.8252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252 Choline chloride. (a) Product. Choline chloride....

  3. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. 21 CFR 182.8985 - Zinc chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  5. 21 CFR 184.1426 - Magnesium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Magnesium chloride. 184.1426 Section 184.1426 Food... Specific Substances Affirmed as GRAS § 184.1426 Magnesium chloride. (a) Magnesium chloride (MgC12·6H2O, CAS... mineral bischofite. It is prepared by dissolving magnesium oxide, hydroxide, or carbonate in...

  6. 21 CFR 184.1426 - Magnesium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Magnesium chloride. 184.1426 Section 184.1426 Food... Specific Substances Affirmed as GRAS § 184.1426 Magnesium chloride. (a) Magnesium chloride (MgC12·6H2O, CAS... mineral bischofite. It is prepared by dissolving magnesium oxide, hydroxide, or carbonate in...

  7. 21 CFR 184.1426 - Magnesium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Magnesium chloride. 184.1426 Section 184.1426 Food... Specific Substances Affirmed as GRAS § 184.1426 Magnesium chloride. (a) Magnesium chloride (MgC12·6H2O, CAS... mineral bischofite. It is prepared by dissolving magnesium oxide, hydroxide, or carbonate in...

  8. 21 CFR 582.1193 - Calcium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Calcium chloride. 582.1193 Section 582.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1193 Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This...

  9. 21 CFR 582.6193 - Calcium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Calcium chloride. 582.6193 Section 582.6193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This substance is...

  10. 21 CFR 582.1193 - Calcium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Calcium chloride. 582.1193 Section 582.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1193 Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This...

  11. 21 CFR 582.6193 - Calcium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Calcium chloride. 582.6193 Section 582.6193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This substance is...

  12. 21 CFR 582.6193 - Calcium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  13. 21 CFR 582.1193 - Calcium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  14. 7 CFR 58.434 - Calcium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  15. 7 CFR 58.434 - Calcium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Calcium chloride. 58.434 Section 58.434 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.434 Calcium chloride. Calcium chloride, when used, shall meet the requirements of the...

  16. 7 CFR 58.434 - Calcium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Calcium chloride. 58.434 Section 58.434 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.434 Calcium chloride. Calcium chloride, when used, shall meet the requirements of the...

  17. 21 CFR 582.6193 - Calcium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Calcium chloride. 582.6193 Section 582.6193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This substance is...

  18. 7 CFR 58.434 - Calcium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Calcium chloride. 58.434 Section 58.434 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.434 Calcium chloride. Calcium chloride, when used, shall meet the requirements of the...

  19. 21 CFR 582.1193 - Calcium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Calcium chloride. 582.1193 Section 582.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1193 Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This...

  20. 7 CFR 58.434 - Calcium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Calcium chloride. 58.434 Section 58.434 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.434 Calcium chloride. Calcium chloride, when used, shall meet the requirements of the...

  1. 21 CFR 582.6193 - Calcium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Calcium chloride. 582.6193 Section 582.6193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This substance is...

  2. 21 CFR 582.1193 - Calcium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Calcium chloride. 582.1193 Section 582.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1193 Calcium chloride. (a) Product. Calcium chloride. (b) Conditions of use. This...

  3. 21 CFR 582.5622 - Potassium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. REMOVAL OF CHLORIDE FROM AQUEOUS SOLUTIONS

    DOEpatents

    Schulz, W.W.

    1959-08-01

    The removal of chlorides from aqueons solutions is described. The process involves contacting the aqueous chloride containing solution with a benzene solution about 0.005 M in phenyl mercuric acetate whereby the chloride anions are taken up by the organic phase and separating the organic phase from the aqueous solutions.

  5. 21 CFR 184.1426 - Magnesium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Magnesium chloride. 184.1426 Section 184.1426 Food... Specific Substances Affirmed as GRAS § 184.1426 Magnesium chloride. (a) Magnesium chloride (MgC12·6H2O, CAS... mineral bischofite. It is prepared by dissolving magnesium oxide, hydroxide, or carbonate in...

  6. 21 CFR 172.180 - Stannous chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Food Preservatives § 172.180 Stannous chloride. The food additive stannous chloride may be safely used... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Stannous chloride. 172.180 Section 172.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  7. 21 CFR 172.180 - Stannous chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Food Preservatives § 172.180 Stannous chloride. The food additive stannous chloride may be safely used... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Stannous chloride. 172.180 Section 172.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  8. 21 CFR 172.180 - Stannous chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food Preservatives § 172.180 Stannous chloride. The food additive stannous chloride may be safely used... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Stannous chloride. 172.180 Section 172.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  9. An XAFS Study of Tantalum Chloride in the Ionic Liquid 1-ethyl-3-methyl Imidazolium Chloride/ aluminum Chloride

    SciTech Connect

    D Roeper; K Pandya; G Cheek; W OGrady

    2011-12-31

    Tantalum chloride was studied with extended X-ray absorption fine structure spectroscopy (XAFS) in acidic and basic aluminum chloride/1-ethyl-3-methyl imidazolium chloride ionic liquids (ILs). Anhydrous Ta2Cl10 is more soluble in the basic solution than in the acidic solution and the X-ray absorption data shows that the coordination shell of chlorides around the tantalum is larger in the basic solution. In the acidic solution, tantalum has five chlorides in its coordination shell while in the basic solution; the tantalum is coordinated by seven chlorides. This indicates that the Lewis acidity of the tantalum chloride causes the Ta to coordinate differently in the acidic and the basic solutions.

  10. Chloride flux out of Yellowstone National Park

    USGS Publications Warehouse

    Norton, D.R.; Friedman, I.

    1985-01-01

    Monitoring of the chloride concentration, electrical conductivity, and discharge was carried out for the four major rivers of Yellowstone National Park from September 1982 to January 1984. Chloride flux out of the Park was determined from the measured values of chloride concentration and discharge. The annual chloride flux from the Park was 5.86 ?? 1010 g. Of this amount 45% was from the Madison River drainage basin, 32% from the Yellowstone River basin, 12% from the Snake River basin, and 11% from the Falls River basin. Of the annual chloride flux from the Yellowstone River drainage basin 36% was attributed to the Yellowstone Lake drainage basin. The geothermal contribution to the chloride flux was determined by subtracting the chloride contribution from rock weathering and atmospheric precipitation and is 94% of the total chloride flux. Calculations of the geothermal chloride flux for each river are given and the implications of an additional chloride flux out of the western Park boundary discussed. An anomalous increase in chloride flux out of the Park was observed for several weeks prior to the Mt. Borah earthquake in Central Idaho on October 28, 1983, reaching a peak value shortly thereafter. It is suggested that the rise in flux was a precursor of the earthquake. The information in this paper provides baseline data against which future changes in the hydrothermal systems can be measured. It also provides measurements related to the thermal contributions from the different drainage basins of the Park. ?? 1985.

  11. Salt, chloride, bleach, and innate host defense.

    PubMed

    Wang, Guoshun; Nauseef, William M

    2015-08-01

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

  12. Salt, chloride, bleach, and innate host defense

    PubMed Central

    Wang, Guoshun; Nauseef, William M.

    2015-01-01

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

  13. Salt, chloride, bleach, and innate host defense.

    PubMed

    Wang, Guoshun; Nauseef, William M

    2015-08-01

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

  14. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

    PubMed Central

    Carvalho-Costa, P.G.; Branco, L.G.S.; Leite-Panissi, C.R.A.

    2014-01-01

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress. PMID:25387672

  15. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent.

    PubMed

    Carvalho-Costa, P G; Branco, L G S; Leite-Panissi, C R A

    2014-12-01

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3',5'-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress. PMID:25387672

  16. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent.

    PubMed

    Carvalho-Costa, P G; Branco, L G S; Leite-Panissi, C R A

    2014-09-19

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3',5'-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress. PMID:25250589

  17. Synthetic Peptides as cGMP-Independent Activators of cGMP-Dependent Protein Kinase Iα.

    PubMed

    Moon, Thomas M; Tykocki, Nathan R; Sheehe, Jessica L; Osborne, Brent W; Tegge, Werner; Brayden, Joseph E; Dostmann, Wolfgang R

    2015-12-17

    PKG is a multifaceted signaling molecule and potential pharmaceutical target due to its role in smooth muscle function. A helix identified in the structure of the regulatory domain of PKG Iα suggests a novel architecture of the holoenzyme. In this study, a set of synthetic peptides (S-tides), derived from this helix, was found to bind to and activate PKG Iα in a cyclic guanosine monophosphate (cGMP)-independent manner. The most potent S-tide derivative (S1.5) increased the open probability of the potassium channel KCa1.1 to levels equivalent to saturating cGMP. Introduction of S1.5 to smooth muscle cells in isolated, endothelium-denuded cerebral arteries through a modified reversible permeabilization procedure inhibited myogenic constriction. In contrast, in endothelium-intact vessels S1.5 had no effect on myogenic tone. This suggests that PKG Iα activation by S1.5 in vascular smooth muscle would be sufficient to inhibit augmented arterial contractility that frequently occurs following endothelial damage associated with cardiovascular disease. PMID:26687482

  18. Model Vestibular Nuclei Neurons Can Exhibit a Boosting Nonlinearity Due to an Adaptation Current Regulated by Spike-Triggered Calcium and Calcium-Activated Potassium Channels.

    PubMed

    Schneider, Adam D

    2016-01-01

    In vitro studies have previously found a class of vestibular nuclei neurons to exhibit a bidirectional afterhyperpolarization (AHP) in their membrane potential, due to calcium and calcium-activated potassium conductances. More recently in vivo studies of such vestibular neurons were found to exhibit a boosting nonlinearity in their input-output tuning curves. In this paper, a Hodgkin-Huxley (HH) type neuron model, originally developed to reproduce the in vitro AHP, is shown to produce a boosting nonlinearity similar to that seen in vivo for increased the calcium conductance. Indicative of a bifurcation, the HH model is reduced to a generalized integrate-and-fire (IF) model that preserves the bifurcation structure and boosting nonliearity. By then projecting the neuron model's phase space trajectories into 2D, the underlying geometric mechanism relating the AHP and boosting nonlinearity is revealed. Further simplifications and approximations are made to derive analytic expressions for the steady steady state firing rate as a function of bias current, μ, as well as the gain (i.e. its slope) and the position of its peak at μ = μ*. Finally, although the boosting nonlinearity has not yet been experimentally observed in vitro, testable predictions indicate how it might be found. PMID:27427914

  19. Improvement of spatial learning by facilitating large-conductance calcium-activated potassium channel with transcranial magnetic stimulation in Alzheimer's disease model mice.

    PubMed

    Wang, Furong; Zhang, Yu; Wang, Li; Sun, Peng; Luo, Xianwen; Ishigaki, Yasuhito; Sugai, Tokio; Yamamoto, Ryo; Kato, Nobuo

    2015-10-01

    Transcranial magnetic stimulation (TMS) is fragmentarily reported to be beneficial to Alzheimer's patients. Its underlying mechanism was investigated. TMS was applied at 1, 10 or 15 Hz daily for 4 weeks to young Alzheimer's disease model mice (3xTg), in which intracellular soluble amyloid-β is notably accumulated. Hippocampal long-term potentiation (LTP) was tested after behavior. TMS ameliorated spatial learning deficits and enhanced LTP in the same frequency-dependent manner. Activity of the large conductance calcium-activated potassium (Big-K; BK) channels was suppressed in 3xTg mice and recovered by TMS frequency-dependently. These suppression and recovery were accompanied by increase and decrease in cortical excitability, respectively. TMS frequency-dependently enhanced the expression of the activity-dependently expressed scaffold protein Homer1a, which turned out to enhance BK channel activity. Isopimaric acid, an activator of the BK channel, magnified LTP. Amyloid-β lowering was detected after TMS in 3xTg mice. In 3xTg mice with Homer1a knocked out, amyloid-β lowering was not detected, though the TMS effects on BK channel and LTP remained. We concluded that TMS facilitates BK channels both Homer1a-dependently and -independently, thereby enhancing hippocampal LTP and decreasing cortical excitability. Reduced excitability contributed to amyloid-β lowering. A cascade of these correlated processes, triggered by TMS, was likely to improve learning in 3xTg mice.

  20. Model Vestibular Nuclei Neurons Can Exhibit a Boosting Nonlinearity Due to an Adaptation Current Regulated by Spike-Triggered Calcium and Calcium-Activated Potassium Channels

    PubMed Central

    Schneider, Adam D.

    2016-01-01

    In vitro studies have previously found a class of vestibular nuclei neurons to exhibit a bidirectional afterhyperpolarization (AHP) in their membrane potential, due to calcium and calcium-activated potassium conductances. More recently in vivo studies of such vestibular neurons were found to exhibit a boosting nonlinearity in their input-output tuning curves. In this paper, a Hodgkin-Huxley (HH) type neuron model, originally developed to reproduce the in vitro AHP, is shown to produce a boosting nonlinearity similar to that seen in vivo for increased the calcium conductance. Indicative of a bifurcation, the HH model is reduced to a generalized integrate-and-fire (IF) model that preserves the bifurcation structure and boosting nonliearity. By then projecting the neuron model’s phase space trajectories into 2D, the underlying geometric mechanism relating the AHP and boosting nonlinearity is revealed. Further simplifications and approximations are made to derive analytic expressions for the steady steady state firing rate as a function of bias current, μ, as well as the gain (i.e. its slope) and the position of its peak at μ = μ*. Finally, although the boosting nonlinearity has not yet been experimentally observed in vitro, testable predictions indicate how it might be found. PMID:27427914

  1. Detection of calcium activity in human monocytes by the fura-2 fluorescence method: in vitro differentiation sensitizes cells to dihydropyridine calcium channel modulators

    NASA Astrophysics Data System (ADS)

    Oraevsky, Alexander A.; Cabello, Olga A.; Shan, Qin; Tittel, Frank K.; Henry, Philip D.

    1994-07-01

    Dihydropyridine (DHP) calcium channel blockers have been shown to suppress atherogenesis in various species and controlled angiographic trials suggest that these drugs may retard the progression of occlusive coronary disease in humans. Because mononuclear leukocytes play a key role in the formation of early and advanced atheromatous lesions, we determined effects of DHP calcium channel modulators on calcium uptake by cells of the monocytic lineage. Human peripheral blood monocytes were evaluated before and after undergoing in vitro differentiation induced by two days of culture with fetal calf serum and FMLP. Changes in intracellular calcium activity were estimated with fura-2, a fluorescent calcium indicator. Freshly isolated (unactivated) monocytes were insensitive to DHP drugs both in the presence and absence of high potassium membrane depolarization. In contrast, nisoldipine, a DHP calcium channel blocker, and BAY K 8644, a DHP calcium channel activator, decreased and increased calcium uptake by KC1-depolarized differentiated monocytes. Results suggest that differentiation of monocytes to macrophages may involve a change in the expression and/or regulation of DHP- sensitive calcium channels.

  2. Chloride Transporting CLC Proteins1

    NASA Astrophysics Data System (ADS)

    Pusch, Michael

    In the early 1980s, Chris Miller and colleagues described a curious "double-barreled" chloride channel from the electric organ of Torpedo fish reconstituted in planar lipid bilayers (Miller and White, 1980). Single-channel openings occurred in "bursts" separated by long closures. A single burst was characterized by the presence of two open conductance levels of equal size and the gating (i.e., openings and closings) during a burst could be almost perfectly described as a superposition of two identical and independent conductances that switched between open and closed states with voltage-dependent rates α and β (Hanke and Miller, 1983) (Fig. 8.1).

  3. An XAFS Study of Niobium chloride in the ionic liquid 1-ethyl-3-methyl imidazolium chloride/ aluminum chloride

    SciTech Connect

    D Roeper; K Pandya; G Cheek; W OGrady

    2011-12-31

    Niobium chloride was studied with extended X-ray absorption fine structure spectroscopy (EXAFS) in acidic and basic aluminum chloride/1-ethyl-3-methyl imidazolium chloride (EMIC) ionic liquids. Although anhydrous Nb2Cl10 is more soluble in the basic melt than in the acidic melt, the EXAFS data shows that the coordination shell around the niobium does not change in the different ionic liquids. Both the acidic and basic melts show a coordination of five chlorides in the first shell. This indicates that in this series of ionic liquids, the Nb2Cl10 breaks up into two NbCl5 entities in both the acidic and the basic melts.

  4. Production of anhydrous aluminum chloride composition

    DOEpatents

    Vandergrift, G.F. III; Krumpelt, M.; Horwitz, E.P.

    1981-10-08

    A process is described for producing an anhydrous aluminum chloride composition from a water-based aluminous material such as a slurry of aluminum hydroxide in a multistage extraction process in which the aluminum ion is first extracted into an organic liquid containing an acidic extractant and then extracted from the organic phase into an alkali metal chloride or chlorides to form a melt containing a mixture of chlorides of alkali metal and aluminum. In the process, the organic liquid may be recycled. In addition, the process advantageously includes an electrolysis cell for producing metallic aluminum and the alkali metal chloride or chlorides may be recycled for extraction of the aluminum from the organic phase.

  5. [Sodium chloride 0.9%: nephrotoxic crystalloid?].

    PubMed

    Dombre, Vincent; De Seigneux, Sophie; Schiffer, Eduardo

    2016-02-01

    Sodium chloride 0.9%, often incorrectly called physiological saline, contains higher concentration of chloride compared to plasma. It is known that the administration of sodium chloride 0.9% can cause hyperchloremic metabolic acidosis in a reproducible manner. The elevated chloride concentration in 0.9% NaCl solution can also adversely affect renal perfusion. This effect is thought to be induced by hyperchloremia that causes renal artery vasoconstriction. For these reasons, the use of 0.9% NaCl solution is raising attention and some would advocate the use of a more "physiological" solution, such as balanced solutions that contain a level of chloride closer to that of plasma. Few prospective, randomized, controlled trials are available today and most were done in a perioperative setting. Some studies suggest that the chloride excess in 0.9% NaCl solution could have clinical consequences; however, this remains to be established by quality randomized controlled trials. PMID:26999998

  6. [Sodium chloride 0.9%: nephrotoxic crystalloid?].

    PubMed

    Dombre, Vincent; De Seigneux, Sophie; Schiffer, Eduardo

    2016-02-01

    Sodium chloride 0.9%, often incorrectly called physiological saline, contains higher concentration of chloride compared to plasma. It is known that the administration of sodium chloride 0.9% can cause hyperchloremic metabolic acidosis in a reproducible manner. The elevated chloride concentration in 0.9% NaCl solution can also adversely affect renal perfusion. This effect is thought to be induced by hyperchloremia that causes renal artery vasoconstriction. For these reasons, the use of 0.9% NaCl solution is raising attention and some would advocate the use of a more "physiological" solution, such as balanced solutions that contain a level of chloride closer to that of plasma. Few prospective, randomized, controlled trials are available today and most were done in a perioperative setting. Some studies suggest that the chloride excess in 0.9% NaCl solution could have clinical consequences; however, this remains to be established by quality randomized controlled trials.

  7. 21 CFR 184.1426 - Magnesium chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Magnesium chloride. 184.1426 Section 184.1426 Food... GRAS § 184.1426 Magnesium chloride. (a) Magnesium chloride (MgC12·6H2O, CAS Reg. No. 7786-30-3) is a... prepared by dissolving magnesium oxide, hydroxide, or carbonate in aqueous hydrochloric acid solution...

  8. Metal chloride cathode for a battery

    NASA Technical Reports Server (NTRS)

    Bugga, Ratnakumar V. (Inventor); Distefano, Salvador (Inventor); Bankston, C. Perry (Inventor)

    1991-01-01

    A method of fabricating a rechargeable battery is disclosed which includes a positive electrode which contains a chloride of a selected metal when the electrode is in its active state. The improvement comprises fabricating the positive electrode by: providing a porous matrix composed of a metal; providing a solution of the chloride of the selected metal; and impregnating the matrix with the chloride from the solution.

  9. Irreversible gettering of thionyl chloride

    SciTech Connect

    LeRoy Whinnery; Steve Goods; George Buffleben; Tim Sheppodd

    1999-11-01

    The authors have successfully demonstrated the irreversible gettering of SOCl{sub 2} by ZnO/ASZMTEDA carbon over a modest temperature range. While thionyl chloride decomposition was slow below {minus}20 C, lower temperatures are expected to be less of a problem than at higher temperatures. The approximately 30 cc of thionyl chloride in a typical D-cell would require 50 g of ZnO and 107 g of ASZMTEDA carbon. Fortunately, since it is unlikely to happen at all, it is common practice to assume only one cell will fail (leak) in a given battery pack. So, one charge of getter can protect the whole battery pack. In summary, ZnO/ASZMTEDA carbon fulfills all of the requirements of an ideal getter including: irreversible binding or reaction with SOCl{sub 2}, high volumetric uptake capacity, high efficiency, non-volatile, air stable, insensitive to poisoning, non-toxic, cheap, non-corrosive, and the gettering product is not a liquid or oil that could block further flow or accessibility. Future work in this area includes incorporation of the ZnO and carbon into a structural open-celled porous monolith, as well as, gettering for other types of batteries (e.g., Li/MnO{sub 2}).

  10. Enrofloxacin hydro-chloride dihydrate.

    PubMed

    Miranda-Calderón, Jorge E; Gutiérrez, Lilia; Flores-Alamo, Marcos; García-Gutiérrez, Ponciano; Sumano, Héctor

    2014-04-01

    The asymmetric unit of the title compound, C19H23FN3O3 (+)·Cl(-)·2H2O [systematic name: 4-(3-carb-oxy-1-cyclo-propyl-6-fluoro-4-oxo-1,4-di-hydro-quin-o-lin-7-yl)-1-ethyl-piperazin-1-ium chloride dihydrate], consists of two independent monocations of the protonated enrofloxacin, two chloride anions and four water mol-ecules. In the cations, the piperazinium rings adopt chair conformations and the dihedral angles between the cyclo-propyl ring and the 10-membered quinoline ring system are 56.55 (2) and 51.11 (2)°. An intra-molecular O-H⋯O hydrogen bond is observed in each cation. In the crystal, the components are connected via O-H⋯Cl, N-H⋯Cl and O-H⋯O hydrogen bonds, and a π-π inter-action between the benzene rings [centroid-centroid distance = 3.6726 (13) Å], resulting in a three-dimensional array.

  11. Arsenic removal by ferric chloride

    SciTech Connect

    Hering, J.G.; Chen, P.Y.; Wilkie, J.A.; Elimelech, M.; Liang, S.

    1996-04-01

    Bench-scale studies were conducted in model freshwater systems to investigate how various parameters affected arsenic removal during coagulation with ferric chloride and arsenic adsorption onto preformed hydrous ferric oxide. Parameters included arsenic oxidation state and initial concentration, coagulant dosage or adsorbent concentration, pH, and the presence of co-occurring inorganic solutes. Comparison of coagulation and adsorption experiments and of experimental results with predictions based on surface complexation modeling demonstrated that adsorption is an important (though not the sole) mechanism governing arsenic removal during coagulation. Under comparable conditions, better removal was observed with arsenic(V) [As(V)] than with arsenic(III) [As(III)] in both coagulation and adsorption experiments. Below neutral pH values, As(III) removal-adsorption was significantly decreased in the presence of sulfate, whereas only a slight decrease in As(V) removal-adsorption was observed. At high pH, removal-adsorption of As(V) was increased in the presence of calcium. Removal of As(V) during coagulation with ferric chloride is both more efficient and less sensitive than that of As(III) to variations in source water composition.

  12. Production of chlorine from chloride salts

    DOEpatents

    Rohrmann, Charles A.

    1981-01-01

    A process for converting chloride salts and sulfuric acid to sulfate salts and elemental chlorine is disclosed. A chloride salt and sulfuric acid are combined in a furnace where they react to produce a sulfate salt and hydrogen chloride. Hydrogen chloride from the furnace contacts a molten salt mixture containing an oxygen compound of vanadium, an alkali metal sulfate and an alkali metal pyrosulfate to recover elemental chlorine. In the absence of an oxygen-bearing gas during the contacting, the vanadium is reduced, but is regenerated to its active higher valence state by separately contacting the molten salt mixture with an oxygen-bearing gas.

  13. Fabrication Of Metal Chloride Cathodes By Sintering

    NASA Technical Reports Server (NTRS)

    Bugga, Ratnakumar V.; Di Stefano, Salvador; Bankston, C. Perry

    1992-01-01

    Transition-metal chloride cathodes for use in high-temperature rechargeable sodium batteries prepared by sintering transition-metal powders mixed with sodium chloride. Need for difficult and dangerous chlorination process eliminated. Proportions of transition metal and sodium chloride in mixture adjusted to suit specific requirements. Cathodes integral to sodium/metal-chloride batteries, which have advantages over sodium/sulfur batteries including energy densities, increased safety, reduced material and thermal-management problems, and ease of operation and assembly. Being evaluated for supplying electrical power during peak demand and electric vehicles.

  14. XAFS Studies of Ni Ta and Nb Chlorides in the Ionic Liquid 1-Ethyl-3-Methyl Imidazolium Chloride / Aluminum Chloride

    SciTech Connect

    W OGrady; D Roeper; K Pandya; G Cheek

    2011-12-31

    The structures of anhydrous nickel, niobium, and tantalum chlorides have been investigated in situ in acidic and basic ionic liquids (ILs) of 1-methyl-3-ethylimidazolium chloride (EMIC)/AlCl{sub 3} with X-ray absorption spectroscopy (XAS). The coordination of NiCl{sub 2} changes from tetrahedral in basic solution to octahedral in acidic solution. The NiCl{sub 2} is a strong Lewis acid in that it can induce the AlCl{sub 3} to share its chlorides in the highly acidic IL, forming a structure with six near Cl{sup -} ions and eight further distant Al ions which share the chloride ions surrounding the Ni{sup 2+}. When Nb{sub 2}Cl{sub 10}, a dimer, is added to the acidic or basic solution, the dimer breaks apart and forms two species. In the acid solution, two trigonal bipyramids are formed with five equal chloride distances, while in the basic solution, a square pyramid with four chlorides forming a square base and one shorter axial chloride bond. Ta{sub 2}Cl{sub 10} is also a dimer and divides into half in the acidic solution and forms two trigonal bipyramids. In the basic solution, the dimer breaks apart but the species formed is sufficiently acidic that it attracts two additional chloride ions and forms a seven coordinated tantalum species.

  15. The Intermediate Conductance Calcium-activated Potassium Channel KCa3.1 Regulates Vascular Smooth Muscle Cell Proliferation via Controlling Calcium-dependent Signaling*

    PubMed Central

    Bi, Dan; Toyama, Kazuyoshi; Lemaître, Vincent; Takai, Jun; Fan, Fan; Jenkins, David P.; Wulff, Heike; Gutterman, David D.; Park, Frank; Miura, Hiroto

    2013-01-01

    The intermediate conductance calcium-activated potassium channel KCa3.1 contributes to a variety of cell activation processes in pathologies such as inflammation, carcinogenesis, and vascular remodeling. We examined the electrophysiological and transcriptional mechanisms by which KCa3.1 regulates vascular smooth muscle cell (VSMC) proliferation. Platelet-derived growth factor-BB (PDGF)-induced proliferation of human coronary artery VSMCs was attenuated by lowering intracellular Ca2+ concentration ([Ca2+]i) and was enhanced by elevating [Ca2+]i. KCa3.1 blockade or knockdown inhibited proliferation by suppressing the rise in [Ca2+]i and attenuating the expression of phosphorylated cAMP-response element-binding protein (CREB), c-Fos, and neuron-derived orphan receptor-1 (NOR-1). This antiproliferative effect was abolished by elevating [Ca2+]i. KCa3.1 overexpression induced VSMC proliferation, and potentiated PDGF-induced proliferation, by inducing CREB phosphorylation, c-Fos, and NOR-1. Pharmacological stimulation of KCa3.1 unexpectedly suppressed proliferation by abolishing the expression and activity of KCa3.1 and PDGF β-receptors and inhibiting the rise in [Ca2+]i. The stimulation also attenuated the levels of phosphorylated CREB, c-Fos, and cyclin expression. After KCa3.1 blockade, the characteristic round shape of VSMCs expressing high l-caldesmon and low calponin-1 (dedifferentiation state) was maintained, whereas KCa3.1 stimulation induced a spindle-shaped cellular appearance, with low l-caldesmon and high calponin-1. In conclusion, KCa3.1 plays an important role in VSMC proliferation via controlling Ca2+-dependent signaling pathways, and its modulation may therefore constitute a new therapeutic target for cell proliferative diseases such as atherosclerosis. PMID:23609438

  16. Modulation by purines of calcium-activated non-selective cation channels in the outer hair cells of the guinea-pig cochlea.

    PubMed Central

    Van den Abbeele, T; Tran Ba Huy, P; Teulon, J

    1996-01-01

    1. The cell-attached and cell-free configurations of the patch-clamp technique were used to investigate whether external ATP and its derivatives modulate channel activity in outer hair cells freshly isolated from the guinea-pig cochlea. 2. Submicromolar concentrations of ATP stimulated a non-selective cation channel with a conductance of about 25 pS. The ATP-elicited stimulation was partly blocked by the membrane-permeant blocker 3',5-dichlorodiphenylamine-2-carboxylic acid (DCDPC), and mimicked by the calcium ionophore, ionomycin, suggesting that the channel activated by ATP is identical to a previously reported calcium-activated non-selective (CAN) cation channel. 3. The P2x agonist beta, gamma-methylene-ATP (beta, gamma-MeATP, 10 microM) and the P2Y agonist 2-methyl-thio-ATP (2-MeSATP, 1 microM) both activated CAN channels. The effect of ATP was inhibited by the P2 antagonist suramin but not by the P2Y antagonist Reactive Blue 2. These results suggest that both purinergic receptors are involved in the ATP-evoked response and that internal calcium acts as a second messenger for opening CAN channels. 4. In contrast, adenosine inhibited CAN channels. This effect was reproduced by the A2 agonist 5'-N-ethylcarboxyamidoadenosine (NECA) and the permeant cAMP analogue 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), but not by the A1 agonist N6-cyclo-hexyladenosine (CHA). CAN channels were also inhibited when the catalytic subunit of protein kinase A was applied internally on inside-out patches, suggesting that adenosine A2 receptor downregulates CAN channels via a cAMP-dependent phosphorylation. Images Figure 10 PMID:8814608

  17. The small conductance calcium-activated potassium channel 3 (SK3) is a molecular target for Edelfosine to reduce the invasive potential of urothelial carcinoma cells.

    PubMed

    Steinestel, Konrad; Eder, Stefan; Ehinger, Konstantin; Schneider, Juliane; Genze, Felicitas; Winkler, Eva; Wardelmann, Eva; Schrader, Andres J; Steinestel, Julie

    2016-05-01

    Metastasis is the survival-determining factor in urothelial carcinoma (UC) of the urinary bladder. The small conductance calcium-activated potassium channel 3 (SK3) enhances tumor cell invasion in breast cancer and malignant melanoma. Since Edelfosine, a glycerophospholipid with antitumoral properties, effectively inhibits SK3 channel activity, our goal was to evaluate SK3 as a potential molecular target to inhibit the gain of an invasive phenotype in UC. SK3 protein expression was analyzed in 208 tissue samples and UC cell lines. Effects of Edelfosine on SK3 expression and intracellular calcium levels as well as on cell morphology, cell survival and proliferation were assessed using immunoblotting, potentiometric fluorescence microscopy, and clonogenic/cell survival assay; furthermore, we analyzed the effect of Edelfosine and SK3 RNAi knockdown on tumor cell migration and invasion in vitro and in vivo. We found that SK3 is strongly expressed in muscle-invasive UC and in the RT112 cellular tumor model. Higher concentrations of Edelfosine have a strong antitumoral effect on UC cells, while 1 μM effectively inhibits migration/invasion of UC cells in vitro and in vivo comparable to the SK3 knockdown phenotype. Taken together, our results show strong expression of SK3 in muscle-invasive UC, consistent with the postulated role of the protein in tumor cell invasion. Edelfosine is able to effectively inhibit migration and invasion of UC cells in vitro and in vivo in an SK3-dependent way, pointing towards a possible role for Edelfosine as an antiinvasive drug to effectively inhibit UC cell invasion and metastasis.

  18. Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses

    PubMed Central

    Jacobson, David A; Mendez, Felipe; Thompson, Michael; Torres, Jacqueline; Cochet, Olivia; Philipson, Louis H

    2010-01-01

    Glucose-induced β-cell action potential (AP) repolarization is regulated by potassium efflux through voltage gated (Kv) and calcium activated (KCa) potassium channels. Thus, ablation of the primary Kv channel of the β-cell, Kv2.1, causes increased AP duration. However, Kv2.1−/− islet electrical activity still remains sensitive to the potassium channel inhibitor tetraethylammonium. Therefore, we utilized Kv2.1−/− islets to characterize Kv and KCa channels and their respective roles in modulating the β-cell AP. The remaining Kv current present in Kv2.1−/−β-cells is inhibited with 5 μm CP 339818. Inhibition of the remaining Kv current in Kv2.1−/− mouse β-cells increased AP firing frequency by 39.6% but did not significantly enhance glucose stimulated insulin secretion (GSIS). The modest regulation of islet AP frequency by CP 339818 implicates other K+ channels, possibly KCa channels, in regulating AP repolarization. Blockade of the KCa channel BK with slotoxin increased β-cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased β-cell AP amplitude by 30.6%. Interestingly, the KCa channel SK significantly contributes to Kv2.1−/− mouse islet AP repolarization. Inhibition of SK channels decreased AP firing frequency by 66% and increased AP duration by 67% only when Kv2.1 is ablated or inhibited and enhanced GSIS by 2.7-fold. Human islets also express SK3 channels and their β-cell AP frequency is significantly accelerated by 4.8-fold with apamin. These results uncover important repolarizing roles for both Kv and KCa channels and identify distinct roles for SK channel activity in regulating calcium- versus sodium-dependent AP firing. PMID:20643768

  19. Calcium-Activated SK Channels Influence Voltage-Gated Ion Channels to Determine the Precision of Firing in Globus Pallidus Neurons

    PubMed Central

    Deister, Christopher A.; Chan, C. Savio; Surmeier, D. James; Wilson, Charles J.

    2012-01-01

    Globus pallidus (GP) neurons fire rhythmically in the absence of synaptic input, suggesting that they may encode their inputs as changes in the phase of their rhythmic firing. Action potential afterhyperpolarization (AHP) enhances precision of firing by ensuring that the ion channels recover from inactivation by the same amount on each cycle. Voltage-clamp experiments in slices showed that the longest component of the GP neuron’s AHP is blocked by apamin, a selective antagonist of calcium-activated SK channels. Application of 100 nm apamin also disrupted the precision of firing in perforated-patch and cell-attached recordings. SK channel blockade caused a small depolarization in spike threshold and made it more variable, but there was no reduction in the maximal rate of rise during an action potential. Thus, the firing irregularity was not caused solely by a reduction in voltage-gated Na+ channel availability. Subthreshold voltage ramps triggered a large outward current that was sensitive to the initial holding potential and had properties similar to the A-type K+ current in GP neurons. In numerical simulations, the availability of both Na+ and A-type K+ channels during autonomous firing were reduced when SK channels were removed, and a nearly equal reduction in Na+ and K+ subthreshold-activated ion channel availability produced a large decrease in the neuron’s slope conductance near threshold. This change made the neuron more sensitive to intrinsically generated noise. In vivo, this change would also enhance the sensitivity of GP neurons to small synaptic inputs. PMID:19571136

  20. The small conductance calcium-activated potassium channel 3 (SK3) is a molecular target for Edelfosine to reduce the invasive potential of urothelial carcinoma cells.

    PubMed

    Steinestel, Konrad; Eder, Stefan; Ehinger, Konstantin; Schneider, Juliane; Genze, Felicitas; Winkler, Eva; Wardelmann, Eva; Schrader, Andres J; Steinestel, Julie

    2016-05-01

    Metastasis is the survival-determining factor in urothelial carcinoma (UC) of the urinary bladder. The small conductance calcium-activated potassium channel 3 (SK3) enhances tumor cell invasion in breast cancer and malignant melanoma. Since Edelfosine, a glycerophospholipid with antitumoral properties, effectively inhibits SK3 channel activity, our goal was to evaluate SK3 as a potential molecular target to inhibit the gain of an invasive phenotype in UC. SK3 protein expression was analyzed in 208 tissue samples and UC cell lines. Effects of Edelfosine on SK3 expression and intracellular calcium levels as well as on cell morphology, cell survival and proliferation were assessed using immunoblotting, potentiometric fluorescence microscopy, and clonogenic/cell survival assay; furthermore, we analyzed the effect of Edelfosine and SK3 RNAi knockdown on tumor cell migration and invasion in vitro and in vivo. We found that SK3 is strongly expressed in muscle-invasive UC and in the RT112 cellular tumor model. Higher concentrations of Edelfosine have a strong antitumoral effect on UC cells, while 1 μM effectively inhibits migration/invasion of UC cells in vitro and in vivo comparable to the SK3 knockdown phenotype. Taken together, our results show strong expression of SK3 in muscle-invasive UC, consistent with the postulated role of the protein in tumor cell invasion. Edelfosine is able to effectively inhibit migration and invasion of UC cells in vitro and in vivo in an SK3-dependent way, pointing towards a possible role for Edelfosine as an antiinvasive drug to effectively inhibit UC cell invasion and metastasis. PMID:26619845

  1. Cholinergic modulation of large-conductance calcium-activated potassium channels regulates synaptic strength and spine calcium in cartwheel cells of the dorsal cochlear nucleus.

    PubMed

    He, Shan; Wang, Ya-Xian; Petralia, Ronald S; Brenowitz, Stephan D

    2014-04-01

    Acetylcholine is a neuromodulatory transmitter that controls synaptic plasticity and sensory processing in many brain regions. The dorsal cochlear nucleus (DCN) is an auditory brainstem nucleus that integrates auditory signals from the cochlea with multisensory inputs from several brainstem nuclei and receives prominent cholinergic projections. In the auditory periphery, cholinergic modulation serves a neuroprotective function, reducing cochlear output under high sound levels. However, the role of cholinergic signaling in the DCN is less understood. Here we examine postsynaptic mechanisms of cholinergic modulation at glutamatergic synapses formed by parallel fiber axons onto cartwheel cells (CWCs) in the apical DCN circuit from mouse brainstem slice using calcium (Ca) imaging combined with two-photon laser glutamate uncaging onto CWC spines. Activation of muscarinic acetylcholine receptors (mAChRs) significantly increased the amplitude of both uncaging-evoked EPSPs (uEPSPs) and spine Ca transients. Our results demonstrate that mAChRs in CWC spines act by suppressing large-conductance calcium-activated potassium (BK) channels, and this effect is mediated through the cAMP/protein kinase A signaling pathway. Blocking BK channels relieves voltage-dependent magnesium block of NMDA receptors, thereby enhancing uEPSPs and spine Ca transients. Finally, we demonstrate that mAChR activation inhibits L-type Ca channels and thus may contribute to the suppression of BK channels by mAChRs. In summary, we demonstrate a novel role for BK channels in regulating glutamatergic transmission and show that this mechanism is under modulatory control of mAChRs.

  2. Cholinergic Modulation of Large-Conductance Calcium-Activated Potassium Channels Regulates Synaptic Strength and Spine Calcium in Cartwheel Cells of the Dorsal Cochlear Nucleus

    PubMed Central

    He, Shan; Wang, Ya-Xian; Petralia, Ronald S.

    2014-01-01

    Acetylcholine is a neuromodulatory transmitter that controls synaptic plasticity and sensory processing in many brain regions. The dorsal cochlear nucleus (DCN) is an auditory brainstem nucleus that integrates auditory signals from the cochlea with multisensory inputs from several brainstem nuclei and receives prominent cholinergic projections. In the auditory periphery, cholinergic modulation serves a neuroprotective function, reducing cochlear output under high sound levels. However, the role of cholinergic signaling in the DCN is less understood. Here we examine postsynaptic mechanisms of cholinergic modulation at glutamatergic synapses formed by parallel fiber axons onto cartwheel cells (CWCs) in the apical DCN circuit from mouse brainstem slice using calcium (Ca) imaging combined with two-photon laser glutamate uncaging onto CWC spines. Activation of muscarinic acetylcholine receptors (mAChRs) significantly increased the amplitude of both uncaging-evoked EPSPs (uEPSPs) and spine Ca transients. Our results demonstrate that mAChRs in CWC spines act by suppressing large-conductance calcium-activated potassium (BK) channels, and this effect is mediated through the cAMP/protein kinase A signaling pathway. Blocking BK channels relieves voltage-dependent magnesium block of NMDA receptors, thereby enhancing uEPSPs and spine Ca transients. Finally, we demonstrate that mAChR activation inhibits L-type Ca channels and thus may contribute to the suppression of BK channels by mAChRs. In summary, we demonstrate a novel role for BK channels in regulating glutamatergic transmission and show that this mechanism is under modulatory control of mAChRs. PMID:24719104

  3. A Small Conductance Calcium-Activated K+ Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

    PubMed Central

    Chotoo, Cavita K.; Silverman, Gary A.; Devor, Daniel C.; Luke, Cliff J.

    2013-01-01

    In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson’s disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. PMID:24040423

  4. Activation of endothelial and epithelial KCa2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles

    PubMed Central

    Kroigaard, Christel; Dalsgaard, Thomas; Nielsen, Gorm; Laursen, Britt E; Pilegaard, Hans; Köhler, Ralf; Simonsen, Ulf

    2012-01-01

    BACKGROUND AND PURPOSE Small (KCa2) and intermediate (KCa3.1) conductance calcium-activated potassium channels (KCa) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of KCa2.3 and KCa3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries. EXPERIMENTAL APPROACH Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. KCa2 and KCa3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole-cell patch clamp techniques. RESULTS While KCa2.3 expression was similar, KCa3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive KCa2.3 and KCa3.1 proteins were found in both endothelium and epithelium. KCa currents were present in HSAEpi cells and sensitive to the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM-34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the KCa2.3/ KCa3.1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the KCa2 channel blocker apamin, while the KCa3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01–1 µM). CONCLUSIONS AND IMPLICATIONS KCa2.3 and KCa3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. KCa2.3 channels contributed to endo- and epithelium-dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease. PMID:22506557

  5. Chloride substitution in sodium borohydride

    SciTech Connect

    Ravnsbaek, Dorthe B.; Rude, Line H.; Jensen, Torben R.

    2011-07-15

    The dissolution of sodium chloride and sodium borohydride into each other resulting in formation of solid solutions of composition Na(BH{sub 4}){sub 1-x}Cl{sub x} is studied. The dissolution reaction is facilitated by two methods: ball milling or combination of ball milling and annealing at 300 deg. C for three days of NaBH{sub 4}-NaCl samples in molar ratios of 0.5:0.5 and 0.75:0.25. The degree of dissolution is studied by Rietveld refinement of synchrotron radiation powder X-ray diffraction (SR-PXD) data. The results show that dissolution of 10 mol% NaCl into NaBH{sub 4}, forming Na(BH{sub 4}){sub 0.9}Cl{sub 0.1}, takes place during ball milling. A higher degree of dissolution of NaCl in NaBH{sub 4} is obtained by annealing resulting in solid solutions containing up to 57 mol% NaCl, i.e. Na(BH{sub 4}){sub 0.43}Cl{sub 0.57}. In addition, annealing results in dissolution of 10-20 mol% NaBH{sub 4} into NaCl. The mechanism of the dissolution during annealing and the decomposition pathway of the solid solutions are studied by in situ SR-PXD. Furthermore, the stability upon hydrogen release and uptake were studied by Sieverts measurements. - Graphical Abstract: Dissolution of sodium chloride and sodium borohydride into each other resulting in formation of solid solutions of composition Na(BH{sub 4}){sub 1-x}Cl{sub x} is studied. Dissolution is facilitated by two methods: ball milling or annealing at 300 deg. C for three days of NaBH{sub 4}-NaCl samples. Sample compositions and dissolution mechanism are studied by Rietveld refinement of synchrotron radiation powder X-ray diffraction data. Highlights: > Studies of dissolution of sodium chloride and sodium borohydride into each other. > Solid state diffusion facilitated by mechanical and thermal treatments. > Dissolution is more efficiently induced by heating than by mechanical treatment. > Mechanism for dissolution studied by Rietveld refinement of in situ SR-PXD data.

  6. Inhibition of ANO1/TMEM16A Chloride Channel by Idebenone and Its Cytotoxicity to Cancer Cell Lines.

    PubMed

    Seo, Yohan; Park, Jinhong; Kim, Minseo; Lee, Ho K; Kim, Jin-Hee; Jeong, Jin-Hyun; Namkung, Wan

    2015-01-01

    The expression levels of anoctamin 1 (ANO1, TMEM16A), a calcium-activated chloride channel (CaCC), are significantly increased in several tumors, and inhibition of ANO1 is known to reduce cell proliferation and migration. Here, we performed cell-based screening of a collection of natural products and drug-like compounds to identify inhibitors of ANO1. As a result of the screening, idebenone, miconazole and plumbagin were identified as novel ANO1 inhibitors. Electrophysiological studies showed that idebenone, a synthetic analog of coenzyme Q10, completely blocked ANO1 activity in FRT cells expressing ANO1 without any effect on intracellular calcium signaling and CFTR, a cAMP-regulated chloride channel. The CaCC activities in PC-3 and CFPAC-1 cells expressing abundant endogenous ANO1 were strongly blocked by idebenone. Idebenone inhibited cell proliferation and induced apoptosis in PC-3 and CFPAC-1 cells, but not in A549 cells, which do not express ANO1. These data suggest that idebenone, a novel ANO1 inhibitor, has potential for use in cancer therapy. PMID:26196390

  7. Chloride Analysis of RFSA Second Campaign Dissolver Solution

    SciTech Connect

    Holcomb, H.P.

    2001-05-17

    The dissolver solution from the second RFSA campaign was analyzed for chloride using the recently-developed turbidimetric method. Prior to chloride removal in head end, the solution contained 1625 ppm chloride. After chloride removal with Hg(I) and prior to feeding to solvent extraction, the solution contained only 75 ppm chloride. This report discusses those analysis results.

  8. Sodium-metal chloride batteries

    NASA Technical Reports Server (NTRS)

    Ratnakumar, B. V.; Attia, A. I.; Halpert, G.

    1992-01-01

    It was concluded that rapid development in the technology of sodium metal chloride batteries has been achieved in the last decade mainly due to the: expertise available with sodium sulfur system; safety; and flexibility in design and fabrication. Long cycle lives of over 1000 and high energy densities of approx. 100 Wh/kg have been demonstrated in both Na/FeCl2 and Na/NiCl2 cells. Optimization of porous cathode and solid electrolyte geometries are essential for further enhancing the battery performance. Fundamental studies confirm the capabilities of these systems. Nickel dichloride emerges as the candidate cathode material for high power density applications such as electric vehicle and space.

  9. Process for synthesis of beryllium chloride dietherate

    DOEpatents

    Bergeron, Charles; Bullard, John E.; Morgan, Evan

    1991-01-01

    A low temperature method of producing beryllium chloride dietherate through the addition of hydrogen chloride gas to a mixture of beryllium metal in ether in a reaction vessel is described. A reflux condenser provides an exit for hydrogen produced form the reaction. A distillation condenser later replaces the reflux condenser for purifying the resultant product.

  10. 75 FR 19657 - Barium Chloride From China

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  11. 21 CFR 184.1446 - Manganese chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Specific Substances Affirmed as GRAS § 184.1446 Manganese chloride. (a) Manganese chloride (MnCl2·4H2O, CAS... dichloride. It is prepared by dissolving manganous oxide, pyrolusite ore (MnO2), or reduced manganese ore...

  12. 21 CFR 184.1446 - Manganese chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Specific Substances Affirmed as GRAS § 184.1446 Manganese chloride. (a) Manganese chloride (MnCl2·4H2O, CAS... dichloride. It is prepared by dissolving manganous oxide, pyrolusite ore (MnO2), or reduced manganese ore...

  13. Calmodulin-dependent activation and inactivation of anoctamin calcium-gated chloride channels.

    PubMed

    Vocke, Kerstin; Dauner, Kristin; Hahn, Anne; Ulbrich, Anne; Broecker, Jana; Keller, Sandro; Frings, Stephan; Möhrlen, Frank

    2013-10-01

    Calcium-dependent chloride channels serve critical functions in diverse biological systems. Driven by cellular calcium signals, the channels codetermine excitatory processes and promote solute transport. The anoctamin (ANO) family of membrane proteins encodes three calcium-activated chloride channels, named ANO 1 (also TMEM16A), ANO 2 (also TMEM16B), and ANO 6 (also TMEM16F). Here we examined how ANO 1 and ANO 2 interact with Ca(2+)/calmodulin using nonstationary current analysis during channel activation. We identified a putative calmodulin-binding domain in the N-terminal region of the channel proteins that is involved in channel activation. Binding studies with peptides indicated that this domain, a regulatory calmodulin-binding motif (RCBM), provides two distinct modes of interaction with Ca(2+)/calmodulin, one at submicromolar Ca(2+) concentrations and one in the micromolar Ca(2+) range. Functional, structural, and pharmacological data support the concept that calmodulin serves as a calcium sensor that is stably associated with the RCBM domain and regulates the activation of ANO 1 and ANO 2 channels. Moreover, the predominant splice variant of ANO 2 in the brain exhibits Ca(2+)/calmodulin-dependent inactivation, a loss of channel activity within 30 s. This property may curtail ANO 2 activity during persistent Ca(2+) signals in neurons. Mutagenesis data indicated that the RCBM domain is also involved in ANO 2 inactivation, and that inactivation is suppressed in the retinal ANO 2 splice variant. These results advance the understanding of Ca(2+) regulation in anoctamin Cl(-) channels and its significance for the physiological function that anoctamin channels subserve in neurons and other cell types.

  14. Hydrocracking with molten zinc chloride catalyst containing 2-12% ferrous chloride

    DOEpatents

    Zielke, Clyde W.; Bagshaw, Gary H.

    1981-01-01

    In a process for hydrocracking heavy aromatic polynuclear carbonaceous feedstocks to produce hydrocarbon fuels boiling below about 475.degree. C. by contacting the feedstocks with hydrogen in the presence of a molten zinc chloride catalyst and thereafter separating at least a major portion of the hydrocarbon fuels from the spent molten zinc chloride catalyst, an improvement comprising: adjusting the FeCl.sub.2 content of the molten zinc chloride to from about 2 to about 12 mol percent based on the mixture of ferrous chloride and molten zinc chloride.

  15. Chloride transport in the cystic fibrosis enterocyte.

    PubMed

    Bijman, J; Veeze, H; Kansen, M; Tilly, B; Scholte, B; Hoogeveen, A; Halley, D; Sinaasappel, M; de Jonge, H

    1991-01-01

    Molecular mechanisms of intestinal chloride channel regulation and potential abnormalities in electrogenic chloride secretion in intestinal epithelium from cystic fibrosis (CF) patients were investigated by a combination of Ussing chamber, vesicle transport and off-cell patch-clamp analysis. Short circuit current (Isc) measurements in normal and CF rectal biopsies provided evidence for i) a defect in the cAMP-provoked activation of chloride secretion and a (hyper)expression of cAMP-dependent potassium secretion in all CF patients examined (n = 11); ii) a defect in the carbachol-provoked chloride secretion and a (hyper)expression of carbachol-induced potassium secretion in 6/11 patients; iii) a residual (but still impaired) carbachol-induced chloride secretion in 5/11 CF patients (including 2 sibs). The latter class of CF patients appeared to consist genetically of compound heterozygotes for the major delta-F508 deletion, suggesting a correlation between the nature of the mutation in the CF gene and the severity of the chloride secretory defect in CF intestine. In our search for a regulatory function of GTP-binding (G-) proteins detected previously in the luminal membrane of rat and human intestinal epithelial cells, evidence was found for the presence of a GTP[S]-activatable- and GDP[S]-inhibitable chloride conductance in the apical membrane of rat enterocytes and human colonocytes. In excised patches of human colonocyt membranes, this G-proteine-sensitive chloride conductance was identified further as a novel type of chloride channel (20pS; inwardly rectifying) that was different from the 33pS outwardly rectifying chloride channel activatable by cAMP-dependent proteinkinase (PK-A) and voltage depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Factors influencing electrochemical removal of chloride from concrete

    SciTech Connect

    Arya, C.; Sa`id-Shawqi, Q.; Vassie, P.R.W.

    1996-06-01

    Electrochemical chloride removal was studied using prisms made from concrete containing various levels of chlorides derived from sodium chloride added during mixing. The amount of chloride removed during the treatment was assessed by analyzing the anolyte. Chloride removal increased with increasing applied potential, number of reinforcing bars at a particular depth and initial chloride content of the concrete. A greater percentage of chloride was removed from prisms where the thickness of the chloride bearing layer of concrete was less than the depth of cover to the reinforcement. Where the thickness of the chloride bearing layer exceeded the cover to the reinforcement, the use of an external cathode significantly increased the total amount of chloride removed. Chloride removal from a face remote from the source of the chloride contamination (soffit desalination) was shown to be feasible.

  17. Large conductance calcium-activated potassium channels: their expression and modulation of glutamate release from nerve terminals isolated from rat trigeminal caudal nucleus and cerebral cortex.

    PubMed

    Samengo, Irene; Currò, Diego; Barrese, Vincenzo; Taglialatela, Maurizio; Martire, Maria

    2014-05-01

    Large conductance, calcium-activated potassium channels [big potassium (BK) channel] consist of a tetramer of pore-forming α-subunit and distinct accessory β-subunits (β1-4) that modify the channel's properties. In this study, we analyzed the effects of BK channel activators and blockers on glutamate and γ-aminobutyric acid (GABA) release from synaptosomes isolated from the cerebral cortices or trigeminal caudal nuclei (TCN) of rats. Real-time polymerase chain reaction was used to characterize BK channel α and β(1-4) subunit expression in the cortex and in the trigeminal ganglia (TG), whose neurons project primary terminal afferents into the TCN. Immunocytochemistry was used to localize these subunits on cortical and TCN synaptosomes. The BK channels regulating [(3)H]D-aspartate release from primary afferent nerve terminals projecting into the TCN displayed limited sensitivity to iberiotoxin, whereas those expressed on cortical synaptosomes were highly sensitive to this toxin. BK channels did not appear to be present on GABAergic nerve terminals from the TCN since [(3)H]-γ-aminobutyric acid release in this model was unaffected by BK channel activators or blockers. Gene expression studies revealed expression levels of the α subunit in the TG that were only 31.2 ± 2.1% of those found in cortical tissues. The β4 subunit was the accessory subunit expressed most abundantly in both the cortex and TG. Levels of β1 and β2 were low in both these areas although β2 expression in the TG was higher than that found in the cortex. Immunocytochemistry experiments showed that co-localization of α and β4 subunits (the accessory subunit most abundantly expressed in both brain areas) was more common in TCN synaptosomes than in cortical synaptosomes. On the basis of these findings, it is reasonable to hypothesize that BK channels expressed on glutamatergic terminals in the TCN and cortex have distinct pharmacological profiles, which probably reflect different α and

  18. Phosphorylation of synaptosomal cytoplasmic proteins: Inhibition of calcium-activated, phospholipid-dependent protein kinase (protein kinase c) by bay k 8644.

    PubMed

    Robinson, P J; Lovenberg, W

    1988-01-01

    The phosphorylation of specific substrates of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) was examined in striatal synaptosomal cytoplasm. The phosphoprotein substrata were termed group C phosphoprotems and were divided into two subgroups: group C(1) phosphoproteins (P83, P45A, P21 and P18) were found in both cytoplasm and synaptosomal membranes and, although stimulated by phosphatidylserine, only required exogamous calcium for their labeling; group C(2) phosphoproteins (P120, P96, P21.5, P18.5 and P16) were found predominantly in the cytoplasm and were absolutely dependent upon exogenous calcium and phosphatidylserme for their labeling. Several criteria were used to identify these proteins as specific protein kinase C substrates: (a) their phosphorylation was stimulated to a greater extent by Ca(2+) /phosphatidylserine/diolein than by Ca(2+) alone or Cal(2+) /calmodulin (group C(1)) or was completely dependent upon Ca(2+) /phosphatdylserine/diolein (group C(2)); (b) supermaximal concentrations of the cAMP-dependent protein kinase inhibitor were without effect; (c) their phosphorylation was stimulated by oleic acid, which selectively activates protein kinase C in the absence of Ca(2+); (d) NaCl, which inhibited cAMP- and Ca(2+)/calmodulindependent phosphorylation, slightly increased phosphorylation of group C(1) and slightly decreased phosphorylation of group C(2) phosphoproteins. Maximal phosphorylation of P96 and other group C phosphoproteins occurred within 60 s and was followed by a slow decay rate while substrata of calmodulin-dependent protein kinase were maximally labeled within 20-30 s and rapidly dephosphorylated. The phosphorylation of all group C phosphoproteins was inhibited by the calcium channel agomst BAY K 8644, however, group C(2) phosphoproteins were considerably more sensitive. The IC(50) for inhibition of P96 labeling was 19 ?M. but for P83 was 190 ?M. Group B phosphoproteins were also slightly inhibited, and the

  19. Embedded chloride detectors for roadways and bridges

    NASA Astrophysics Data System (ADS)

    Fuhr, Peter L.; Huston, Dryver R.; McPadden, Adam P.; Cauley, Robert F.

    1996-04-01

    The problems associated with the application of chloride-based deicing agents to roadways and specifically bridges include chemical pollution and accelerated corrosion of strength members (especially rebar) within the structure. In many instances, local ordinances are attempting to force state agencies to reduce, if not eliminate, the use of these chlorides (typically at the cost of increased driving hazards). With respect to the corrosion aspects of chloride application, cracks that occur in the roadway/bridge pavement allow water to seep into the pavement carrying the chloride to the rebar with the resultant increase in corrosion. In response to this problem, particularly in high roadsalt usage areas, a chloride/water impermeable membrane is placed above the rebar matrix so if/when roadway cracking occurs, the roadsalts won't be able to damage the rebar. Such a membrane is costly -- and the question of its in-service performance is questionable. In a joint effort between the University of Vermont and the Vermont Agency of Transportation, we are developing fiber optic chloride detectors which are capable of being embedded into the rebar-concrete roadway under this membrane. The sensing mechanism relies on spectroscopic analysis of a chemical reaction of chloride and reagents (which have been coated onto the ends of fibers). Laboratory results of these detectors and a usable system configuration are presented.

  20. Materials for Conoco zinc chloride hydrocracking process

    SciTech Connect

    Baylor, V.B.; Keiser, J.R.; DeVan, J.H.

    1980-01-01

    Use of zinc chloride to augment hydrogenation of coal and yield a high-octane gasoline product is the most significant feature of a coal liquefaction process being developed by Conoco Coal Development Company. The zinc chloride catalyst is regenerated in a fluidized sand bed, where the spent melt is mixed with air and hydrogen chloride at about 1000/sup 0/C. Recovery is completed at 370/sup 0/C in a condenser, where the zinc chloride is collected and the oxygen and sulfur are separated as H/sub 2/O and SO/sub 2/. The economic viability of the entire process is highly dependent on almost complete recovery of the zinc chloride. The severe environmental conditions of this recovery process cause unique materials problems. Although high-temperature oxidation and sulfidation are being studied in related programs, suitable materials to resist their combined effects along with those of chlorides have not yet been specifically addressed. Common engineering materials, such as the austenitic stainless steels and many nickel-base alloys, are unsuitable because of their inability to tolerate the elevated temperatures and sulfidation, respectively. The objectives of this task are to screen various metallic and ceramic materials for resistance to the zinc chloride recovery system environment and to determine the nature of the attack by exposing coupons to the simulated environment in the laboratory.

  1. Phenomics of Cardiac Chloride Channels

    PubMed Central

    Duan, Dayue Darrel

    2014-01-01

    Forward genetic studies have identified several chloride (Cl−) channel genes, including CFTR, ClC-2, ClC-3, CLCA, Bestrophin, and Ano1, in the heart. Recent reverse genetic studies using gene targeting and transgenic techniques to delineate the functional role of cardiac Cl− channels have shown that Cl− channels may contribute to cardiac arrhythmogenesis, myocardial hypertrophy and heart failure, and cardioprotection against ischemia reperfusion. The study of physiological or pathophysiological phenotypes of cardiac Cl− channels, however, is complicated by the compensatory changes in the animals in response to the targeted genetic manipulation. Alternatively, tissue-specific conditional or inducible knockout or knockin animal models may be more valuable in the phenotypic studies of specific Cl− channels by limiting the effect of compensation on the phenotype. The integrated function of Cl− channels may involve multiprotein complexes of the Cl− channel subproteome. Similar phenotypes can be attained from alternative protein pathways within cellular networks, which are influenced by genetic and environmental factors. The phenomics approach, which characterizes phenotypes as a whole phenome and systematically studies the molecular changes that give rise to particular phenotypes achieved by modifying the genotype under the scope of genome/proteome/phenome, may provide more complete understanding of the integrated function of each cardiac Cl− channel in the context of health and disease. PMID:23720326

  2. Binary Nucleation of Water and Sodium Chloride

    SciTech Connect

    Nemec, Thomas; Marsik, Frantisek; Palmer, Donald

    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.

  3. Vinyl chloride-associated liver disease.

    PubMed

    Berk, P D; Martin, J F; Young, R S; Creech, J; Selikoff, I J; Falk, H; Watanabe, P; Popper, H; Thomas, L

    1976-06-01

    Although polyvinyl chloride has been produced from vinyl chlride monomer for more than 40 years, recognition of toxicity among vinyl chloride polymerization workers is more recent. In the mid 1960s, workers involved in cleaning polymerization tanks were found to have acro-osteolysis. In 1974, the same population of workers was found to be at risk for an unusual type of hepatic fibrosis and angiosarcoma of the liver. We describe two cases of vinyl chloride-associated liver injury, one of hepatic fibrosis and one of angiosarcoma. Histologic features of these lesions are similar to the hepatic fibrosis and angiosarcomas resulting from chronic exposure to inorganic arsenicals. Preliminary studies suggest that the toxicity of vinyl chloride may result from formation, during high-dose exposure, of active metabolites by mixed function oxidases of the liver. Epidemiologic studies indicate an increased incidence not only of liver disease, but also of cancers of the brain, lung, and possibly other organs.

  4. Catastrophic event modeling. [lithium thionyl chloride batteries

    NASA Technical Reports Server (NTRS)

    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.

  5. Lithium thionyl chloride high rate discharge

    NASA Technical Reports Server (NTRS)

    Klinedinst, K. A.

    1980-01-01

    Improvements in high rate lithium thionyl chloride power technology achieved by varying the electrolyte composition, operating temperature, cathode design, and cathode composition are discussed. Discharge capacities are plotted as a function of current density, cell voltage, and temperature.

  6. Crystal structure of 4-carbamoylpyridinium chloride.

    PubMed

    Fellows, Simon M; Prior, Timothy J

    2016-04-01

    The hydro-chloride salt of isonicotinamide, C6H7N2O(+)·Cl(-), has been synthesized from a dilute solution of hydro-chloric acid in aceto-nitrile. The compound displays monoclinic symmetry (space group C2/c) at 150 K, similar to the related hydro-chloride salt of nicotinamide. The asymmetric unit contains one protonated isonicotinamide mol-ecule and a chloride anion. An array of hydrogen-bonding inter-actions, including a peculiar bifurcated pyridinium-chloride inter-action, results in linear chains running almost perpendicularly in the [150] and [1-50] directions within the structure. A description of the hydrogen-bonding network and comparison with similar compounds are presented. PMID:27375858

  7. Crystal structure of 4-carbamoylpyridinium chloride

    PubMed Central

    Fellows, Simon M.; Prior, Timothy J.

    2016-01-01

    The hydro­chloride salt of isonicotinamide, C6H7N2O+·Cl−, has been synthesized from a dilute solution of hydro­chloric acid in aceto­nitrile. The compound displays monoclinic symmetry (space group C2/c) at 150 K, similar to the related hydro­chloride salt of nicotinamide. The asymmetric unit contains one protonated isonicotinamide mol­ecule and a chloride anion. An array of hydrogen-bonding inter­actions, including a peculiar bifurcated pyridinium–chloride inter­action, results in linear chains running almost perpendicularly in the [150] and [1-50] directions within the structure. A description of the hydrogen-bonding network and comparison with similar compounds are presented. PMID:27375858

  8. Qualitative Determination of Nitrate with Triphenylbenzylphosphonium Chloride.

    ERIC Educational Resources Information Center

    Berry, Donna A.; Cole, Jerry J.

    1984-01-01

    Discusses two procedures for the identification of nitrate, the standard test ("Brown Ring" test) and a new procedure using triphenylbenzylphosphonium chloride (TPBPC). Effectiveness of both procedures is compared, with the TPBPC test proving to be more sensitive and accurate. (JM)

  9. The 5-(4-Ethynylophenoxy) isophthalic chloride

    NASA Technical Reports Server (NTRS)

    Hergenrother, P. M.; Jensen, B. J. (Inventor)

    1986-01-01

    Sulfone-ester polymers containing pendent ethynyl groups and a direct and multistep process for preparing them are disclosed. The multistep process involves the conversion of a pendent bromo group to the ethynyl group while the direct route involves reating hydroxy-terminated sulfone oligomer or polymers with a stoichiometric amount of 5-(4-ethynylphenoxy) isophthaloyl chloride. The 5-(4-ethynylphenoxy) isophthaloyl chloride and the process for preparing it are also disclosed.

  10. Copper chloride cathode for a secondary battery

    NASA Technical Reports Server (NTRS)

    Bugga, Ratnakumar V. (Inventor); Distefano, Salvador (Inventor); Nagasubramanian, Ganesan (Inventor); Bankston, Clyde P. (Inventor)

    1990-01-01

    Higher energy and power densities are achieved in a secondary battery based on molten sodium and a solid, ceramic separator such as a beta alumina and a molten catholyte such as sodium tetrachloroaluminate and a copper chloride cathode. The higher cell voltage of copper chloride provides higher energy densities and the higher power density results from increased conductivity resulting from formation of copper as discharge proceeds.

  11. Structure of complexes between aluminum chloride and other chlorides, 2: Alkali-(chloroaluminates). Gaseous complexes

    NASA Technical Reports Server (NTRS)

    Hargittai, M.

    1980-01-01

    The structural chemistry of complexes between aluminum chloride and other metal chlorides is important both for practice and theory. Condensed-phase as well as vapor-phase complexes are of interest. Structural information on such complexes is reviewed. The first emphasis is given to the molten state because of its practical importance. Aluminum chloride forms volatile complexes with other metal chlorides and these vapor-phase complexes are dealt with in the second part. Finally, the variations in molecular shape and geometrical parameters are summarized.

  12. Membrane potential, chloride exchange, and chloride conductance in Ehrlich mouse ascites tumour cells.

    PubMed

    Hoffmann, E K; Simonsen, L O; Sjøholm, C

    1979-11-01

    1. The steady-state tracer exchange flux of chloride was measured at 10-150 mM external chloride concentration, substituting either lactate or sucrose for chloride. The chloride flux saturates in both cases with a K 1/2 about 50 and 15 mM, respectively. 2. The inhibitory effect of other monovalent anions on the chloride transport was investigated by measuring the 36Cl- efflux into media where either bromide, nitrate, or thiocyanate had been substituted for part of the chloride. The sequence of increasing affinity for the chloride transport system was found to be: Br- less than Cl- less than SCN- = NO3-. 3. The chloride steady-state exchange flux in the presence of nitrate can be described by Michaelis-Menten kinetics with nitrate as a competitive inhibitor of the chloride flux. 4. The apparent activation energy (EA) was determined to be 67 +/- 6.2 kJ/mole, and was constant between 7 and 38 degrees C. 5. The membrane potential (Vm) was measured as a function of the concentration of external K+, substituting K+ for Na+. The transference number of K+ (tK) was estimated from the slope of Vm vs. log10 (K+)e, and tCl and tNa were calculated, neglecting current carried by ions other than Cl-, K+, and Na+. The diffusional net flux of K+ was calculated from the steady-state exchange flux of 42K+, assuming the flux ratio equation to be valid. From this value the K+ conductance and the Na+ and Cl- conductances were calculated. The experiments showed that GCl, GNa, and GK are all about 14 muS/cm2. 6. The net (conductive) chloride permeability derived from the chloride conductance was 4 x 10(-8) cm/sec compared with the apparent permeability of 6 x 10(-7) cm/sec as calculated from the chloride tracer exchange flux. These data suggest that about 95% of the chloride transport is mediated by an electrically silent exchange diffusion. 7. Comparable effects of phloretin (0.25 mM) on the net (conductive) permeability and the apparent permeability to chloride (about 80% inhibition

  13. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Code of Federal Regulations, 2010 CFR

    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...

  14. 21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-69-1) is the chloride salt of metallic tin that contains...

  15. 21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-0969-091) is the chloride salt of metallic tin that contains...

  16. 21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-69-1) is the chloride salt of metallic tin that contains...

  17. 21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-0969-091) is the chloride salt of metallic tin that contains...

  18. 21 CFR 178.3290 - Chromic chloride complexes.

    Code of Federal Regulations, 2010 CFR

    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...

  19. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Hydrogen chloride, refrigerated liquid. 179.102-17... Hydrogen chloride, refrigerated liquid. Each tank car used to transport hydrogen chloride, refrigerated... on or after March 16, 2009 used for the transportation of hydrogen chloride, refrigerated...

  20. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Hydrogen chloride, refrigerated liquid. 179.102-17... Hydrogen chloride, refrigerated liquid. Each tank car used to transport hydrogen chloride, refrigerated... on or after March 16, 2009 used for the transportation of hydrogen chloride, refrigerated...

  1. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Hydrogen chloride, refrigerated liquid. 179.102-17... Hydrogen chloride, refrigerated liquid. Each tank car used to transport hydrogen chloride, refrigerated... on or after March 16, 2009 used for the transportation of hydrogen chloride, refrigerated...

  2. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Hydrogen chloride, refrigerated liquid. 179.102-17... Hydrogen chloride, refrigerated liquid. Each tank car used to transport hydrogen chloride, refrigerated... on or after March 16, 2009 used for the transportation of hydrogen chloride, refrigerated...

  3. Maturation of rat proximal tubule chloride permeability.

    PubMed

    Baum, Michel; Quigley, Raymond

    2005-12-01

    We have previously shown that neonate rabbit tubules have a lower chloride permeability but comparable mannitol permeability compared with adult proximal tubules. The surprising finding of lower chloride permeability in neonate proximals compared with adults impacts net chloride transport in this segment, which reabsorbs 60% of the filtered chloride in adults. However, this maturational difference in chloride permeability may not be applicable to other species. The present in vitro microperfusion study directly examined the chloride and mannitol permeability using in vitro perfused rat proximal tubules during postnatal maturation. Whereas there was no maturational change in mannitol permeability, chloride permeability was 6.3 +/- 1.3 x 10(-5) cm/s in neonate rat proximal convoluted tubule and 16.1 +/- 2.3 x 10(-5) cm/s in adult rat proximal convoluted tubule (P < 0.01). There was also a maturational increase in chloride permeability in the rat proximal straight tubule (5.1 +/- 0.6 x 10(-5) cm/s vs. 9.3 +/- 0.6 x 10(-5) cm/s, P < 0.01). There was no maturational change in bicarbonate-to-chloride permeabilities (P(HCO3)/P(Cl)) in the rat proximal straight tubules (PST) and proximal convoluted tubules (PCT) or in the sodium-to-chloride permeability (P(Na)/P(Cl)) in the proximal straight tubule; however, there was a significant maturational decrease in proximal convoluted tubule P(Na)/P(Cl) with postnatal development (1.31 +/- 0.12 in neonates vs. 0.75 +/- 0.06 in adults, P < 0.001). There was no difference in the transepithelial resistance measured by current injection and cable analysis in the PCT, but there was a maturational decrease in the PST (7.2 +/- 0.8 vs. 4.6 +/- 0.1 ohms x cm2, P < 0.05). These studies demonstrate there are maturational changes in the rat paracellular pathway that impact net NaCl transport during development. PMID:16051720

  4. Atmospheric chloride: Its implication for foliar uptake and damage

    NASA Astrophysics Data System (ADS)

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

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

  5. Thermoluminescence of ultra-high dilutions of lithium chloride and sodium chloride

    NASA Astrophysics Data System (ADS)

    Rey, Louis

    2003-05-01

    Ultra-high dilutions of lithium chloride and sodium chloride (10 -30 g cm -3) have been irradiated by X- and γ-rays at 77 K, then progressively rewarmed to room temperature. During that phase, their thermoluminescence has been studied and it was found that, despite their dilution beyond the Avogadro number, the emitted light was specific of the original salts dissolved initially.

  6. Fermentation of cucumbers brined with calcium chloride instead of sodium chloride

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Generation of waste water containing sodium chloride from cucumber fermentation tank yards could be eliminated if cucumbers were fermented in brines that did not contain this salt. To determine if this is feasible, cucumbers were fermented in brines that contained only calcium chloride to maintain f...

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

    USGS Publications Warehouse

    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).

  8. Commercial scale cucumber fermentations brined with calcium chloride instead of sodium chloride

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 instead of NaCl...

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

    PubMed Central

    Eckhardt, M.-C.; Nielsen, P. E.

    2016-01-01

    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. PMID:27635272

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

    PubMed

    Gils, C; Eckhardt, M-C; Nielsen, P E; Nybo, M

    2016-01-01

    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. PMID:27635272

  11. Effect of mercuric chloride and methylmercury chloride exposure on tissue concentrations of six essential minerals

    SciTech Connect

    Bogden, J.D.; Kemp, F.W.; Troiano, R.A.; Jortner, B.S.; Timpone, C.; Giuliani, D.

    1980-04-01

    There are few data on the effects of mercury exposure on tissue concentrations of essential minerals. Male Sprague-Dawley rats were exposed to mercuric chloride and methylmercury chloride administered via the drinking water. Subsequently, the kidneys, spleen, liver, and brain were analyzed for mercury, calcium, copper, magnesium, manganese, iron, and zinc by atomic absorption spectrophotometry. Significant differences from controls were found for brain copper, kidney copper, and kidney zinc in the mercuric chloride-exposed animals; and for brain iron, kidney copper, kidney iron, kidney magnesium, spleen magnesium, and liver manganese in the methylmercury chloride-exposed rats. There was a fivefold higher mean kidney copper concentration in the mercuric chloride-exposed group; this may be related to the induction of renal metallothionein synthesis by mercury. Increased kidney copper may be a manifestation of heavy metal-induced renal toxicity. Both inorganic and methylmercury exposure produce significant changes in tissue concentrations of some essential minerals.

  12. Mechanism for forming hydrogen chloride and sodium sulfate from sulfur trioxide, water, and sodium chloride

    NASA Technical Reports Server (NTRS)

    Anderson, A. B.

    1984-01-01

    A molecular orbital study of sodium sulfate and hydrogen chloride formation from sulfur trioxide, water, and sodium chloride shows no activation barrier, in agreement with recent experimental work of Kohl, Fielder, and Stearns. Two overall steps are found for the process. First, gas-phase water reacts with sulfur trioxide along a pathway involving a linear O-H-O transition state yielding closely associated hydroxyl and bisulfite which rearrange to become a hydrogen sulfate molecule. Then the hydrogen sulfate molecule transfers a hydrogen atom to a surface chloride in solid sodium chloride while an electron and a sodium cation simultaneously transfer to yield sodium bisulfate and gas-phase hydrogen chloride. This process repeats. Both of these steps represent well-known reactions for which mechanisms have not been previously determined.

  13. Advanced intermediate temperature sodium copper chloride battery

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  14. Vinyl chloride loss during laboratory holding time.

    PubMed

    Soule, R; Symonik, D; Jones, D; Turgeon, D; Gerbec, B

    1996-06-01

    Because vinyl chloride is a potent human carcinogen, it is important that analytical results from groundwater samples accurately reflect levels of exposure to groundwater users. This study investigated the current allowable holding time of 14 days to determine if vinyl chloride is lost from samples during this time. Samples containing an initial concentration of 2 microg/liter of vinyl chloride showed progressive, increasing losses when held for 1, 2, 7, and 14 days. Due to the inherent variability of low-level laboratory results, the most statistically significant loss (alpha = 0.05) was seen for samples held for 14 days. No statistically significant differences in degradation pattern were noted between analytical detectors used (PID versus Hall) or sample type (lab versus field). There also was a loss of vinyl chloride observed during sample collection and handling. These results suggest that analytical variability at low concentrations and the establishment of health-based guidelines near the analytical detection limit require multiple samples be collected from a single location when highly accurate results are needed. These findings should be considered in public health exposure assessments and the implementation of health-based recommendations at sites with vinyl chloride groundwater contamination.

  15. Dynamic Electrochemical Measurement of Chloride Ions.

    PubMed

    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. Dynamic Electrochemical Measurement of Chloride Ions.

    PubMed

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

    2016-01-01

    This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver chloride electrode is used extensively for potentiometric measurement of chloride ions concentration in electrolyte. In this measurement, 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. PMID:26889572

  17. Combining sulfate electrowinning with chloride leaching

    NASA Astrophysics Data System (ADS)

    Fletcher, A. W.; Sudderth, R. B.; Olafson, S. M.

    1991-08-01

    Although the chloride leaching of copper sulfide concentrates has proved highly efficient, electrowinning from chloride solutions presents many difficulties, notably in cell design and the handling of the powder product. Sulfate electrowinning,on the other hand, continues to improve and has played a significant part in the widespread adoption of the solvent extraction-electrowinning process for copper recovery from low-grade ores. It has been found that the two steps can be combined by introducing a novel solvent extraction process after chloride leaching. This article presents the results of laboratory tests to prove the feasibility of this approach and discusses how it can be integrated into a commercially viable flow sheet.

  18. Is sodium chloride worth its salt?

    PubMed

    McIntosh, Euan; Andrews, Peter J

    2013-06-11

    The choice of fluid for resuscitation of the brain-injured patient remains controversial, and the 'ideal' resuscitation fluid has yet to be identified. Large volumes of hypotonic solutions must be avoided because of the risk of cerebral swelling and intracranial hypertension. Traditionally, 0.9% sodium chloride has been used in patients at risk of intracranial hypertension, but there is increasing recognition that 0.9% saline is not without its problems. Roquilly and colleagues show a reduction in the development of hyperchloremic acidosis in brain-injured patients given 'balanced' solutions for maintenance and resuscitation compared with 0.9% sodium chloride. In this commentary, we explore the idea that we should move away from 0.9% sodium chloride in favor of a more 'physiological' solution.

  19. Reactivity of vinyl chloride ionic clusters

    NASA Astrophysics Data System (ADS)

    Martrenchard, S.; Dedonder-Lardeux, C.; Dimicoli, I.; Grégoire, G.; Jouvet, C.; Mons, M.; Solgadi, D.

    1998-12-01

    The reactivity of vinyl chloride ionic clusters has been investigated by the Threshold PhotoElectron PhotoIon COincidences technique. In the case of the dimer, the competition between the three reactive channels (HCl, Cl ṡ and CH 2Cl elimination) has been studied. The main reactive channel is HCl elimination which proceeds through a 0.2 eV barrier. This elimination reaction is still observed in the trimer but not in larger clusters. For these clusters, cooling by evaporation of neutral vinyl chloride monomers seems to be the favored channel that hinders the HCl elimination step.

  20. Alkyl Chlorides as Hydrogen Bond Acceptors

    SciTech Connect

    Nadas, Janos I; Vukovic, Sinisa; Hay, Benjamin

    2012-01-01

    To gain an understanding of the role of an alkyl chloride as a hydrogen bond acceptor, geometries and interaction energies were calculated at the MP2/aug-cc-pVDZ level of theory for complexes between ethyl chloride and representative hydrogen donor groups. The results establish that these donors, which include hydrogen cyanide, methanol, nitrobenzene, pyrrole, acetamide, and N-methylurea, form X-H {hor_ellipsis} Cl hydrogen bonds (X = C, N, O) of weak to moderate strength, with {Delta}E values ranging from -2.8 to -5.3 kcal/mol.

  1. Measuring Sodium Chloride Contents of Aerosols

    NASA Technical Reports Server (NTRS)

    Sinha, M. P.; Friedlander, S. K.

    1986-01-01

    Amount of sodium chloride in individual aerosol particles measured in real time by analyzer that includes mass spectrometer. Analyzer used to determine mass distributions of active agents in therapeutic or diagnostic aerosols derived from saline solutions and in analyzing ocean spray. Aerosol particles composed of sodium chloride introduced into oven, where individually vaporized on hot wall. Vapor molecules thermally dissociated, and some of resulting sodium atoms ionized on wall. Ions leave oven in burst and analyzed by spectrometer, which is set to monitor sodium-ion intensity.

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

    PubMed

    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 <30 mM TMEM16A current activates with a monoexponential time course, but above 30 mM, [Cl(-)]o ICl activation displays fast and slow 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

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

    PubMed

    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 <30 mM TMEM16A current activates with a monoexponential time course, but above 30 mM, [Cl(-)]o ICl activation displays fast and slow 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.

  4. 29 CFR 1915.1017 - Vinyl chloride.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Vinyl chloride. 1915.1017 Section 1915.1017 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Toxic and Hazardous...

  5. 29 CFR 1915.1017 - Vinyl chloride.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Vinyl chloride. 1915.1017 Section 1915.1017 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Toxic and Hazardous...

  6. 21 CFR 582.5985 - Zinc chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc chloride. 582.5985 Section 582.5985 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

  7. Mercuric chloride (HgCl2)

    Integrated Risk Information System (IRIS)

    Mercuric chloride ( HgCl2 ) ; CASRN 7487 - 94 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonc

  8. Absorption media for irreversibly gettering thionyl chloride

    DOEpatents

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

    2002-01-01

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

  9. 21 CFR 182.8252 - Choline chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Choline chloride. 182.8252 Section 182.8252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252...

  10. 21 CFR 182.8252 - Choline chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Choline chloride. 182.8252 Section 182.8252 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8252...

  11. 75 FR 20625 - Barium Chloride From China

    Federal Register 2010, 2011, 2012, 2013, 2014

    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:...

  12. 21 CFR 173.400 - Dimethyldialkylammonium chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... chloride. The additive may contain residues of isopropyl alcohol not in excess of 18 percent by weight when... 1990, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies... Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, and from the American Oil Chemists' Society,...

  13. 21 CFR 173.400 - Dimethyldialkylammonium chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... chloride. The additive may contain residues of isopropyl alcohol not in excess of 18 percent by weight when... 1990, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies... Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, and from the American Oil Chemists' Society,...

  14. 21 CFR 173.400 - Dimethyldialkylammonium chloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... chloride. The additive may contain residues of isopropyl alcohol not in excess of 18 percent by weight when... 1990, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies... Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, and from the American Oil Chemists' Society,...

  15. 21 CFR 173.400 - Dimethyldialkylammonium chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... chloride. The additive may contain residues of isopropyl alcohol not in excess of 18 percent by weight when... 1990, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies... Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, and from the American Oil Chemists' Society,...

  16. MERCURIC CHLORIDE CAPTURE BY ALKALINE SORBENTS

    EPA Science Inventory

    The paper gives results of bench-scale mechanistic studies of mercury/sorbent reactions that showed that mercuric chloride (HgC12) is readily adsorbed by alkaline sorbents, which may offers a less expensive alternative to the use of activated carbons. A laboratory-scale, fixed-b...

  17. CLC chloride channels in Caenorhabditis elegans.

    PubMed

    Schriever, A M; Friedrich, T; Pusch, M; Jentsch, T J

    1999-11-26

    The genome of the nematode Caenorhabditis elegans encodes six putative chloride channels (CeCLC-1 through CeCLC-6) that represent all three known branches of the mammalian CLC gene family. Using promoter fragments to drive the expression of the green fluorescent protein, CeCLC-2, -3, and -4 expression was studied in transgenic C. elegans. CeCLC-4 was specifically expressed in the large H-shaped excretory cell, where it was co-expressed with CeCLC-3, which is also expressed in other cells, including neurons, muscles, and epithelial cells. Also, CeCLC-2 was expressed in several cells of the nervous system, intestinal cells, and vulval muscle cells. Similar to mammalian CLC proteins, only two nematode CLC channels elicited detectable plasma membrane currents in Xenopus oocytes. CeCLC-3 currents were inwardly rectifying and were activated by positive prepulses. Its complex gating behavior can be explained by two gates, at least one of which depends on extracellular anions. In this respect it resembles some mammalian chloride channels with which it also shares a preference of chloride over iodide. C. elegans thus provides new opportunities to understand common mechanisms underlying structure and function in CLC channels and will allow for a genetic dissection of chloride channels in this simple model organism. PMID:10567397

  18. 21 CFR 582.3845 - Stannous chloride.

    Code of Federal Regulations, 2010 CFR

    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 §...

  19. Controlling chloride ions diffusion in concrete.

    PubMed

    Zeng, Lunwu; Song, Runxia

    2013-11-28

    The corrosion of steel in concrete is mainly due to the chemical reaction between the chloride ions and iron ions. Indeed, this is a serious threaten for reinforced concrete structure, especially for the reinforced concrete structure in the sea. So it is urgent and important to protect concrete against chloride ions corrosion. In this work, we report multilayer concrete can cloak chloride ions. We formulated five kinds of concrete A, B, C, D and E, which are made of different proportion of cement, sand and glue, and fabricated six-layer (ABACAD) cylinder diffusion cloak and background media E. The simulation results show that the six-layer mass diffusion cloak can protect concrete against chloride ions penetration, while the experiment results show that the concentration gradients are parallel and equal outside the outer circle in the diffusion flux lines, the iso-concentration lines are parallel outside the outer circle, and the concentration gradients in the inner circle are smaller than those outside the outer circle.

  20. Controlling chloride ions diffusion in concrete

    PubMed Central

    Zeng, Lunwu; Song, Runxia

    2013-01-01

    The corrosion of steel in concrete is mainly due to the chemical reaction between the chloride ions and iron ions. Indeed, this is a serious threaten for reinforced concrete structure, especially for the reinforced concrete structure in the sea. So it is urgent and important to protect concrete against chloride ions corrosion. In this work, we report multilayer concrete can cloak chloride ions. We formulated five kinds of concrete A, B, C, D and E, which are made of different proportion of cement, sand and glue, and fabricated six-layer (ABACAD) cylinder diffusion cloak and background media E. The simulation results show that the six-layer mass diffusion cloak can protect concrete against chloride ions penetration, while the experiment results show that the concentration gradients are parallel and equal outside the outer circle in the diffusion flux lines, the iso-concentration lines are parallel outside the outer circle, and the concentration gradients in the inner circle are smaller than those outside the outer circle. PMID:24285220

  1. Solvothermal synthesis of strontium phosphate chloride nanowire

    NASA Astrophysics Data System (ADS)

    Lam, W. M.; Wong, C. T.; Li, Z. Y.; Luk, K. D. K.; Chan, W. K.; Yang, C.; Chiu, K. Y.; Xu, B.; Lu, W. W.

    2007-08-01

    Strontium phosphate chloride nanowire was synthesized via a solvothermal treatment of strontium tri-polyphosphate and Collin salt in 1,4-dioxane at 150 °C. The effects of 1,4-dioxane concentration on particle morphology, crystallinity and phase purity were investigated in this study. The specimen morphology was analyzed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). When the concentration of 1,4-dioxane was below 10%, micron-sized whisker was the dominant form. At 20-25% concentration of 1,4-dioxane, strontium phosphate chloride single-crystalline nanowire was 31±12 nm in diameter and 1.43±0.6 μm in length with an aspect ratio of 52.28±29.41. X-ray diffraction (XRD) pattern of this nanowire matched with that of strontium phosphate chloride (JCPDS #083-0973). When 1,4-dioxane concentration exceeded 25%, nanorod aggregate was the dominant form instead of nanowire. At 20-25% 1,4-dioxane concentration suitable strontium concentration combine with high chemical potential environment favors the formation of nanowires. By adding 1,4-dioxane impure phase such as β-strontium hydrogen phosphate, nanorod formation was suppressed. This method provides an efficient way to synthesize high aspect ratio strontium phosphate chloride nanowire. It has potential bioactive nanocomposite, high mechanical performance bioactive bone cement filler and fluorescent material applications.

  2. 21 CFR 582.3845 - Stannous chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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 §...

  3. 21 CFR 172.180 - Stannous chloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Stannous chloride. 172.180 Section 172.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food Preservatives § 172.180...

  4. 21 CFR 582.3845 - Stannous chloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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 §...

  5. 21 CFR 582.3845 - Stannous chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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 §...

  6. 21 CFR 582.3845 - Stannous chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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 §...

  7. Hydrolysis of ferric chloride in solution

    SciTech Connect

    Lussiez, G.; Beckstead, L.

    1996-11-01

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

  8. Process for drying calcium chloride generated in high chloride flue gas desulfurization systems

    SciTech Connect

    Gleason, R.J.; Sui, C.T.

    1982-03-30

    Some flue gas desulfurization processes applied to fuels containing high chloride concentrations are utilizing, or plan to utilize, by-product gypsum from the process stream. The utilization of such a process results in a calcium chloride buildup in the flue gas desulfurization system from fuels or water resource containing significant chlorides which interferes with the absorption and utilization of the lime or limestone reagent. In this invention, a method is used to convert the calcium chloride to a dry material by utilizing flue gas at elevated temperatures, normally found before an air preheater on steam generators used to produce power or any other conventional large size steam boilers. The monohydrate is produced at temperatures above 3500 F. By applying this drying process with a power plant system, energy consumed for this drying operation is very efficient.

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

    NASA Astrophysics Data System (ADS)

    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. 21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either...) is the chloride salt of metallic tin that contains two molecules of water. It is prepared...

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

    PubMed

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

    2013-10-01

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

  12. Determination of mercurous chloride and total mercury in mercury ores

    USGS Publications Warehouse

    Fahey, J.J.

    1937-01-01

    A method for the determination of mercurous chloride and total mercury on the same sample is described. The mercury minerals are volatilized in a glass tube and brought into intimate contact with granulated sodium carbonate. The chlorine is fixed as sodium chloride, determined with silver nitrate, and computed to mercurous chloride. The mercury is collected on a previously weighed gold coil and weighed.

  13. Making Positive Electrodes For Sodium/Metal Chloride Cells

    NASA Technical Reports Server (NTRS)

    Bugga, Ratnakumar V.; Distefano, Salvador; Bankston, C. Perry

    1992-01-01

    High coulombic yields provided by sodium/metal chloride battery in which cathode formed by impregnating sintered nickel plaque with saturated solution of nickel chloride. Charge/discharge cycling of nickel chloride electrode results in very little loss of capacity. Used in spacecraft, electric land vehicles, and other applications in which high-energy-density power systems required.

  14. 42 CFR 84.250 - Vinyl chloride respirators; description.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Vinyl chloride respirators; description. 84.250... Respirators § 84.250 Vinyl chloride respirators; description. Vinyl chloride respirators, including all completely assembled respirators which are designed for use as respiratory protection during entry into...

  15. 42 CFR 84.250 - Vinyl chloride respirators; description.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Vinyl chloride respirators; description. 84.250... Respirators § 84.250 Vinyl chloride respirators; description. Vinyl chloride respirators, including all completely assembled respirators which are designed for use as respiratory protection during entry into...

  16. Benzalkonium chloride. Health hazard evaluation report

    SciTech Connect

    Bernholc, N.M.

    1984-01-01

    Health hazards associated with the use of benzalkonium chlorides (BAC) are reviewed. Benzalkonium chloride is extensively used as a cationic disinfectant. It is found in a great many over-the-counter and prescription eye products, disinfectants, shampoos, and deodorants, and is used in concentrations that range from 0.001 to 0.01% in eyedrops, up to 2.5% in concentrated liquid disinfectants. Solutions of 0.03 to 0.04% BAC may cause temporary eye irritation in humans but are unlikely to cause any skin response except in persons allergic to quaternary ammonium compounds. Inhalation of a vaporized 10% solution of BAC produced a bronchospasmodic reaction in a previously sensitized individual. At present no other human health effects from BAC have been documented or inferred from exposure to such dilute concentrations.

  17. Liver fibrosis in asymptomatic polyvinyl chloride workers.

    PubMed

    Hsiao, Tun-Jen; Wang, Jung-Der; Yang, Pei-Ming; Yang, Pei-Cheng; Cheng, Tsun-Jen

    2004-09-01

    This study was designed to determine whether vinyl chloride monomer (VCM) exposure is associated with liver fibrosis. A total of 347 workers with occupational exposure to VCM were systemically examined using liver ultrasonography and routine liver function tests. Vinyl chloride monomer cumulative dose (ppm-month) was estimated by summing the products of air VCM concentration levels and months of employment. Liver fibrosis was defined in subjects with precirrhosis and cirrhosis of liver diagnosed using ultrasonography. Significantly increased risks of developing liver fibrosis were found in workers who had history of high exposure jobs (odds ratio 5.5, 95% confidence interval 1.7-25.4) when compared with workers who did not have history of high exposure jobs. We concluded that there was an increased risk of developing liver fibrosis in PVC workers who had high exposure to VCM.

  18. Calcium chloride rhenate(VII) dihydrate.

    PubMed

    Jarek, Urszula; Hołyńska, Małgorzata; Rlepokura, Katarzyna; Lis, Tadeusz

    2007-09-01

    The crystal structure of calcium chloride rhenate(VII) dihydrate, CaCl(ReO4).2H2O, investigated at 85 K, consists of calcium cations, chloride anions, rhenate(VII) anions and water molecules. In the nearly tetrahedral rhenate(VII) anion, all constituent atoms lie on special positions of m2m (Re) and m (O) site symmetries. The Cl- anion and water O atom lie on special positions of m2m and 2 site symmetries, respectively. The Ca2+ ion, also on a special position (m2m), is eight-coordinated in a distorted square-antiprismatic coordination mode. The crystal has a layered structure stabilized by Ca-O coordination bonds and O-H...Cl hydrogen bonds.

  19. Precipitation of metal nitrides from chloride melts

    SciTech Connect

    Slater, S.A.; Miller, W.E.; Willit, J.L.

    1996-12-31

    Precipitation of actinides, lanthanides, and fission products as nitrides from molten chloride melts is being investigated for use as a final cleanup step in treating radioactive salt wastes generated by electrometallurgical processing of spent nuclear fuel. The radioactive components (eg, fission products) need to be removed to reduce the volume of high-level waste that requires disposal. To extract the fission products from the salt, a nitride precipitation process is being developed. The salt waste is first contacted with a molten metal; after equilibrium is reached, a nitride is added to the metal phase. The insoluble nitrides can be recovered and converted to a borosilicate glass after air oxidation. For a bench-scale experimental setup, a crucible was designed to contact the salt and metal phases. Solubility tests were performed with candidate nitrides and metal nitrides for which there are no solubility data. Experiments were performed to assess feasibility of precipitation of metal nitrides from chloride melts.

  20. Gasometric titration for dimethylaluminum chloride analysis.

    PubMed

    Wang, Lin; Maligres, Peter; Eckenroad, Kyle; Simmons, Bryon

    2016-06-01

    A gasometric titration method was developed to quantitate active alkylaluminum content in dimethylaluminum chloride solution to perform the stoichiometry calculation for the reaction charge. The procedure was reproducible with good precision, and the results showed good correlation with ICP-MS method. The gasometric titration is a simple, inexpensive alternative to analysis via ICP-MS which provides more selective analysis of methylaluminum species without the need for inertion.

  1. Radio-Purification of Neodymium Chloride

    SciTech Connect

    Hans, S.; Yeh, M.; Cumming, J. B.; Hahn, R. L.

    2011-04-27

    Organometallic liquid scintillator becomes one of the man detection mediums for neutrino experiment. Liquid-liquid extraction is the method of choice for loading metallic ions of interest into the organic solvents at BNL. High purity of all starting materials is essential for the optimization of synthesis. A newly developed 'self-scavenging' technique was applied to purify undesired radioisotopes from the starting metal compound and found to effectively remove thorium and such containments from the neodymium chloride for SNO+.

  2. Removing Chlorides From Metallurgical-Grade Silicon

    NASA Technical Reports Server (NTRS)

    Breneman, W. C.; Coleman, L. M.

    1982-01-01

    Process for making low-cost silicon for solar cells is further improved. Silane product recycled to feed stripper column converts some of heavy impurities to volatile ones that pass off at top of column with light wastes. Impurities--chlorides of arsenic, phosphorus, and boron-would otherwise be carried to subsequent distillations where they would be difficult to remove. Since only a small amount of silane is recycled, silicon production efficiency remains high.

  3. Method for the regeneration of spent molten zinc chloride

    DOEpatents

    Zielke, Clyde W.; Rosenhoover, William A.

    1981-01-01

    In a process for regenerating spent molten zinc chloride which has been used in the hydrocracking of coal or ash-containing polynuclear aromatic hydrocarbonaceous materials derived therefrom and which contains zinc chloride, zinc oxide, zinc oxide complexes and ash-containing carbonaceous residue, by incinerating the spent molten zinc chloride to vaporize the zinc chloride for subsequent condensation to produce a purified molten zinc chloride: an improvement comprising the use of clay in the incineration zone to suppress the vaporization of metals other than zinc. Optionally water is used in conjunction with the clay to further suppress the vaporization of metals other than zinc.

  4. Boldine action against the stannous chloride effect.

    PubMed

    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

  5. Understanding microwave vessel contamination by chloride species.

    PubMed

    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. PMID:27474275

  6. Understanding microwave vessel contamination by chloride species.

    PubMed

    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.

  7. An autopsy case of zinc chloride poisoning.

    PubMed

    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

  8. Watershed scale chloride storage across a gradient of urbanization

    NASA Astrophysics Data System (ADS)

    Wellen, C. C.; Oswald, C. J.; Oni, S. K.

    2014-12-01

    Sodium chloride is the main de-icing agent used during the winter in Canada and the northern United States. However, little is known about the long term fate, residence time, and ecological effects of chloride. This talk integrates work taking place across three sites in Southern Ontario, Canada: Hamilton Harbour, the Toronto lakeshore, and Lake Simcoe. We quantify chloride inputs, outputs, and changes in storage for a number of watersheds across a gradient of urbanization. For the three winter months (January, February, March), we show that stream water chloride concentrations approach those of brackish waters for urban watersheds. Chloride is also highly persistent, with stream water chloride concentrations decreasing from the winter months and approaching baseline levels only in July. These baseline levels are greater than 100 mg Cl/l in the urban watersheds, suggesting high levels of chloride storage in soil and groundwater. Using road salt application rates and groundwater levels and chloride concentrations, we estimate the magnitude and residence time of the chloride pools in a number of watersheds across a gradient of urbanization. Our results suggest that the magnitude and residence time of chloride storage varies with urbanization and other factors. We show that summer baseflow concentrations do approach the EPA's chronic exposure guideline of 230 mg Cl/l, implying more work is needed to understand the in stream and downstream ecological effects of chloride.

  9. Mechanistic characterization of chloride interferences in electrothermal atomization systems

    USGS Publications Warehouse

    Shekiro, J.M.; Skogerboe, R.K.; Taylor, H.E.

    1988-01-01

    A computer-controlled spectrometer with a photodiode array detector has been used for wavelength and temperature resolved characterization of the vapor produced by an electrothermal atomizer. The system has been used to study the chloride matrix interference on the atomic absorption spectrometric determination of manganese and copper. The suppression of manganese and copper atom populations by matrix chlorides such as those of calcium and magnesium is due to the gas-phase formation of an analyte chloride species followed by the diffusion of significant fractions of these species from the atom cell prior to completion of the atomization process. The analyte chloride species cannot be formed when matrix chlorides with metal-chloride bond dissociation energies above those of the analyte chlorides are the principal entitles present. The results indicate that multiple wavelength spectrometry used to obtain temperature-resolved spectra is a viable tool in the mechanistic characterization of interference effects observed with electrothermal atomization systems. ?? 1988 American Chemical Society.

  10. Properties of a new liquid desiccant solution - Lithium chloride and calcium chloride mixture

    SciTech Connect

    Ertas, A.; Anderson, E.E.; Kiris, I. )

    1992-09-01

    Desiccants, broadly classified as solid and liquid desiccants, have the property of extracting and retaining moisture from air brought into contact with them. By using either type, moisture in the air is removed and the resulting dry air can be used for air-conditioning or drying purposes. Because of its properties, lithium chloride is the most stable liquid desiccant and has a large dehydration concentration (30% to 45%), but its cost is relatively high ($9.00-13.00 per kg). It is expected that lithium chloride will reduce the relative humidity to as low as 15%. Calcium chloride is the cheapest (45 cents per kg) and most readily available desiccant, but it has the disadvantage of being unstable depending on the air inlet conditions and the concentration of the desiccant in the solution. To stabilize calcium chloride and to decrease the high cost of lithium chloride, the two can be mixed in different weight combinations. The main objective of this research is to measure the physical properties of different combinations of this mixture such as density, viscosity, and vapor pressure which are necessary for analysis of heat and mass transfer in a packed tower desiccant-air contact system. The solubility of this new liquid desiccant under certain temperature-concentrations will also be studied.

  11. Solution-Derived, Chloride-Containing Minerals as a Waste Form for Alkali Chlorides

    SciTech Connect

    Riley, Brian J.; Crum, Jarrod V.; Matyas, Josef; McCloy, John S.; Lepry, William C.

    2012-10-01

    Sodalite [Na8(AlSiO4)6Cl2] and cancrinite [(Na,K)6Ca2Al6Si6O24Cl4] are environmentally stable, chloride-containing minerals and are a logical waste form option for the mixed alkali chloride salt waste stream that is generated from a proposed electrochemical separations process during nuclear fuel reprocessing. Due to the volatility of chloride salts at moderate temperatures, the ideal processing route for these salts is a low-temperature approach such as the sol-gel process. The sodalite structure can be easily synthesized by the sol-gel process; however, it is produced in the form of a fine powder with particle sizes on the order of 1–10 µm. Due to the small particle size, these powders require additional treatment to form a monolith. In this study, the sol-gel powders were pressed into pellets and fired to achieve > 90% of theoretical density. The cancrinite structure, identified as the best candidate mineral form in terms of waste loading capacity, was only produced on a limited basis following the sol-gel process and converted to sodalite upon firing. Here we discuss the sol-gel process specifics, chemical durability of select waste forms, and the steps taken to maximize chloride-containing phases, decrease chloride loss during pellet firing, and increase pellet densities.

  12. Natural Variation in "Drosophila" Larval Reward Learning and Memory Due to a cGMP-Dependent Protein Kinase

    ERIC Educational Resources Information Center

    Kaun, Karla R.; Hendel, Thomas; Gerber, Bertram; Sokolowski, Marla B.

    2007-01-01

    Animals must be able to find and evaluate food to ensure survival. The ability to associate a cue with the presence of food is advantageous because it allows an animal to quickly identify a situation associated with a good, bad, or even harmful food. Identifying genes underlying these natural learned responses is essential to understanding this…

  13. Ozone and nitric oxide induce cGMP-dependent and -independent transcription of defence genes in tobacco.

    PubMed

    Pasqualini, Stefania; Meier, Stuart; Gehring, Chris; Madeo, Laura; Fornaciari, Marco; Romano, Bruno; Ederli, Luisa

    2009-03-01

    Here, we analyse the temporal signatures of ozone (O3)-induced hydrogen peroxide(H2O2) and nitric oxide (NO) and the role of the second messenger guanosine3′,5′-cyclic monophosphate (cGMP) in transcriptional changes of genes diagnostic for biotic and abiotic stress responses. Within 90 min O3 induced H2O2 and NO peaks and we demonstrate that NO donors cause rapid H2O2 accumulation in tobacco (Nicotiana tabacum) leaf. Ozone also causes highly significant, late (> 2 h) and sustained cGMP increases, suggesting that the second messenger may not be required in all early (< 2 h) responses to O3,but is essential and sufficient for the induction of some O3-dependent pathways.This hypothesis was tested resolving the time course of O3-induced transcript accumulation of alternative oxidase (AOX1a), glutathione peroxidase (GPX),aminocyclopropancarboxylic acid synthase (ACS2) that is critical for the synthesis of ethylene, phenylalanine ammonia lyase (PALa) and the pathogenesis-related protein PR1a.The data show that early O3 and NO caused transcriptional activation of the scavenger encoding proteins AOX1a, GPX and the induction of ethylene production through ACS2 are cGMP independent. By contrast, the early response of PALa and the late response of PR1a show critical dependence on cGMP.

  14. Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa.

    PubMed

    Matsuyama, Bruno Y; Krasteva, Petya V; Baraquet, Claudine; Harwood, Caroline S; Sondermann, Holger; Navarro, Marcos V A S

    2016-01-12

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ(54)-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ's AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP-complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.

  15. Identification of the different sources of chlorides in streams by regression analysis using chloride-discharge relationships

    SciTech Connect

    Albek, E.

    1999-12-01

    Chloride-discharge relationships at several stations on Turkish streams are investigated, both qualitatively and quantitatively, to identify natural and anthropogenic sources of chloride. Simple expressions are used to distinguish among sources. Linear regression analysis is conducted to estimate parameters of the models. Five groups of stations are distinguished respective to different sources of chloride and change of chloride concentration with stream discharge. Emphasis is placed on the identification of anthropogenic sources of chloride to aid in water pollution control strategies. The polluted Sakarya River and its primary tributary, the Porsuk Stream, are studied in detail to trace chloride behavior along the waterway and to assess the level of pollution from cities discharging to the streams. Among natural sources of chloride, evaporite sediment sources are examined in detail.

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

    SciTech Connect

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

    2006-01-15

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

  17. Substituent effects on ferrocenes in aluminum chloride-butylpyridinium chloride molten-salt mixtures

    SciTech Connect

    Edgecombe, A.L.; Fowler, J.S.; Gibbard, H.F. ); Slocum, D.W. ); Phillips, J. )

    1990-02-01

    The visible absorption spectra and reduction potentials of 11 ferrocenes containing electron-withdrawing substituents were determined in an N-n-butylpyridinium chloride-aluminum chloride molten salt. When the substituent(s) on the cyclopentadienyl ring(s) of ferrocene were varied, the reduction potential was caused to range over 1.25 V, and the wavelength for maximum absorption of visible light was varied by nearly 200 nm. These changes are greater than have been observed for similar ferrocenes in other nonaqueous solvents. Evidence is presented for specific interactions of particular ferrocenes with the molten salt.

  18. Chloride Fluxes in Isolated Dialyzed Barnacle Muscle Fibers

    PubMed Central

    DiPolo, R.

    1972-01-01

    Chloride outflux and influx has been studied in single isolated muscle fibers from the giant barnacle under constant internal composition by means of a dialysis perfusion technique. Membrane potential was continually recorded. The chloride outfluxes and influxes were 143 and 144 pmoles/cm2-sec (mean resting potential: 58 mv, temperature: 22°–24°C) with internal and external chloride concentrations of 30 and 541 mM, respectively. The chloride conductance calculated from tracer measurements using constant field assumptions is about fourfold greater than that calculated from published electrical data. Replacing 97% of the external chloride ions by propionate reduces the chloride efflux by 51%. Nitrate ions applied either to the internal or external surface of the membrane slows the chloride efflux. The external pH dependence of the chloride efflux follows the external pH dependence of the membrane conductance, in the range pH 3.9–4.7, increasing with decreasing pH. In the range pH 5–9, the chloride efflux increased with increasing pH, in a manner similar to that observed in frog muscle fibers. The titration curve for internal pH changes in the range 4.0–7.0 was quantitatively much different from that for external pH change, indicating significant asymmetry in the internal and external pH dependence of the chloride efflux. PMID:5074810

  19. Twenty years of fluorescence imaging of intracellular chloride

    PubMed Central

    Arosio, Daniele; Ratto, Gian Michele

    2014-01-01

    Chloride homeostasis has a pivotal role in controlling neuronal excitability in the adult brain and during development. The intracellular concentration of chloride is regulated by the dynamic equilibrium between passive fluxes through membrane conductances and the active transport mediated by importers and exporters. In cortical neurons, chloride fluxes are coupled to network activity by the opening of the ionotropic GABAA receptors that provides a direct link between the activity of interneurons and chloride fluxes. These molecular mechanisms are not evenly distributed and regulated over the neuron surface and this fact can lead to a compartmentalized control of the intracellular concentration of chloride. The inhibitory drive provided by the activity of the GABAA receptors depends on the direction and strength of the associated currents, which are ultimately dictated by the gradient of chloride, the main charge carrier flowing through the GABAA channel. Thus, the intracellular distribution of chloride determines the local strength of ionotropic inhibition and influences the interaction between converging excitation and inhibition. The importance of chloride regulation is also underlined by its involvement in several brain pathologies, including epilepsy and disorders of the autistic spectra. The full comprehension of the physiological meaning of GABAergic activity on neurons requires the measurement of the spatiotemporal dynamics of chloride fluxes across the membrane. Nowadays, there are several available tools for the task, and both synthetic and genetically encoded indicators have been successfully used for chloride imaging. Here, we will review the available sensors analyzing their properties and outlining desirable future developments. PMID:25221475

  20. The Structure of Nickel Chloride in the Ionic Liquid 1-Ethyl-3-methyl Imidazolium Chloride/Aluminum Chloride: X-ray Absorption Spectroscopy

    SciTech Connect

    D Roeper; K Pandya; G Cheek; W OGrady

    2011-12-31

    The structure of anhydrous nickel chloride in the ionic liquid 1-ethyl-3-methyl imidazolium chloride and aluminum chloride has been investigated with extended X-ray absorption fine structure (EXAFS) in both Lewis acid and Lewis base solutions. The EXAFS data of NiCl{sub 2} {center_dot} 6H{sub 2}O crystals were also recorded and analyzed to demonstrate the difference file technique. The difference file technique is used to obtain the structural information for the very closely spaced coordination shells of chloride and oxygen in NiCl{sub 2} {center_dot} 6H{sub 2}O and they are found to agree very closely with the X-ray diffraction data. The difference file technique is then used to analyze the nickel chloride in the ionic liquid solutions. Even though anhydrous NiCl{sub 2} is more soluble in the basic solution than in the acidic solution, the EXAFS data show a single coordination of four chlorides in a tetrahedron around the nickel atom in the basic solution. In a weak acid solution, there are six chlorides in a single octahedral coordination shell around the nickel. However, in a strong acid solution, in addition to the octahedral chloride-coordination shell, there is a second coordination shell of eight aluminum atoms in the form of a simple cube.

  1. [Experimental chronic phenylmercuric chloride poisoning in pigs].

    PubMed

    Raszyk, J; Docekalová, H; Rubes, J; Navrátil, S; Masek, J; Rodák, L

    1992-07-01

    Four gilts, sisters from one litter, aged 70 days and weighing 20-24 kg, were used for a trial. Two experimental gilts (P) were administered an experimental feed mixture containing phenylmercury chloride (40 mg/kg). Two control gilts (K) were fed the same mixture but without phenylmercury chloride. P gilts began to lag behind in their growth from day 60 of the experiment, they manifested nonphysiological postures (dog's sitting posture), paresis of hind limbs and uncoordinated movements. P gilts had cloudy, orange-brown urine from day 70 and from day 75 they began to suffer from diarrhoea. Mercury (Hg) contents in urine and blood serum of P gilts were irregularly variable: urine 0.58-2.15 mg/l, blood serum 0.02-0.37 mg/l. Hg content in excrements of P gilts fluctuated from 23 to 26 mg/kg. Vitamin A concentrations in blood serum and liver decreased in P gilts. Phenylmercury chloride feeding caused mutagenic changes in peripheral lymphocytes of P gilts (an increase in the number of aberrant cells from 2-3% to 8-9%) and reduced IgA, IgM and IgG immunoglobulin levels in blood serum. Pathological lesions were observed in the colon, kidneys and liver. None of the above-mentioned changes were observed in K gilts. Increased resistance to the negative effects of Hg was found in one experimental gilt. In comparison with K gilts, Hg concentrations in P gilts after 130 days of the experiment increased as follows: 427 times in kidneys, 333 times in liver, 106 times in guts, 71 times in pancreas, 53 times in ovaries, 50 times in muscles, 47 times in bristles and 16 times in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Active lithium chloride cell for spacecraft power

    NASA Technical Reports Server (NTRS)

    Fleischmann, C. W.; Horning, R. J.

    1988-01-01

    An active thionyl chloride high rate battery is under development for spacecraft operations. It is a 540kC (150 Ah) battery capable of pulses up to 75A. This paper describes the design and initial test data on a 'state-of-the-art' cell that has been selected to be the baseline for the prototype cell for that battery. Initial data indicate that the specification can be met with fresh cells. Data for stored cells and additional environmental test data are in the process of being developed.

  3. REMOVAL OF CHLORIDE FROM AQUEOUS SOLUTIONS

    DOEpatents

    Hyman, M.L.; Savolainen, J.E.

    1960-01-01

    A method is given for dissolving reactor fuel elements in which the uranium is associated with a relatively inert chromium-containing alloy such as stainless steel. An aqueous mixture of acids comprising 2 to 2.5 molar hydrochloric acid and 4 to 8 molar nitric acid is employed in dissolving the fuel element. In order io reduce corrosion in subsequent processing of the resulting solution, chloride values are removed from the solution by contacting it with concentrated nitric acid at an elevated temperature.

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

    SciTech Connect

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

    2003-05-13

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

  5. 40 CFR 61.65 - Emission standard for ethylene dichloride, vinyl chloride and polyvinyl chloride plants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...(d), there is to be no discharge to the atmosphere from any relief valve on any equipment in vinyl... emissions from loading and unloading lines in vinyl chloride service which are opened to the atmosphere... unloading operation and before opening a loading or unloading line to the atmosphere, the quantity of...

  6. 40 CFR 61.65 - Emission standard for ethylene dichloride, vinyl chloride and polyvinyl chloride plants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...(d), there is to be no discharge to the atmosphere from any relief valve on any equipment in vinyl... emissions from loading and unloading lines in vinyl chloride service which are opened to the atmosphere... unloading operation and before opening a loading or unloading line to the atmosphere, the quantity of...

  7. Enrofloxacin hydro­chloride dihydrate

    PubMed Central

    Miranda-Calderón, Jorge E.; Gutiérrez, Lilia; Flores-Alamo, Marcos; García-Gutiérrez, Ponciano; Sumano, Héctor

    2014-01-01

    The asymmetric unit of the title compound, C19H23FN3O3 +·Cl−·2H2O [systematic name: 4-(3-carb­oxy-1-cyclo­propyl-6-fluoro-4-oxo-1,4-di­hydro­quin­o­lin-7-yl)-1-ethyl­piperazin-1-ium chloride dihydrate], consists of two independent monocations of the protonated enrofloxacin, two chloride anions and four water mol­ecules. In the cations, the piperazinium rings adopt chair conformations and the dihedral angles between the cyclo­propyl ring and the 10-membered quinoline ring system are 56.55 (2) and 51.11 (2)°. An intra­molecular O—H⋯O hydrogen bond is observed in each cation. In the crystal, the components are connected via O—H⋯Cl, N—H⋯Cl and O—H⋯O hydrogen bonds, and a π–π inter­action between the benzene rings [centroid–centroid distance = 3.6726 (13) Å], resulting in a three-dimensional array. PMID:24826167

  8. Radiolytic preparation of anhydrous tin (2) chloride

    NASA Technical Reports Server (NTRS)

    Philipp, W. H.; Marsik, S. J.

    1973-01-01

    Anhydrous tin (2) chloride (SnCl2) is prepared by radiolysis with high energy electrons of a tin (4) chloride (SnCl4) solution in heptane. The SnCl4 is reduced to insoluble SNCl2. The energy yield, G(SnCl2), molecules of SnCl2, produced per 100 eV, increases with SnCl4 concentration from 1.6 at 0.15 M SnCl4 to 3.1 at 3.0 M SnCl4. Other parameters such as temperature total dose and beam current have little influence on G(SnCl2). The method may be used to prepare other metal halides if the higher valence, more covalent metal halide is soluble in aliphatic hydrocarbons and the lower more ionic metal halide is insoluble. The reaction mechanism is discussed; the radiolysis of both heptane and SnCl4 is involved. At high SnCl4 concentration G(SnCl2) appears to be limited by the yield of SnC13 radicals.

  9. Vinyl chloride-induced hepatic angiosarcoma.

    PubMed

    Falk, H

    1987-01-01

    In early 1974, an alert plant physician reported the occurrence of several cases of the otherwise rare hepatic angiosarcoma (HAS) at a single polyvinyl chloride (PVC) production facility in Louisville, Kentucky (U.S.A.). Upon further investigation, the relative risk for HAS at this plant appeared to be approximately 5,000, strongly indicating a causal relationship with some factor at the plant. Epidemiologic studies at this and other PVC polymerization plants identified vinyl chloride monomer (VCM) as the causative agent. Experimental studies reported in early 1974 confirmed VCM as a hepatic carcinogen capable of producing HAS and other tumors. Follow-up epidemiologic studies revealed that: 1) HAS is the end stage of a progressive liver disease consisting of hepatocytic and sinusoidal cell hyperplasia, sinusoidal dilatation, and hepatic fibrosis; 2) over 100 cases of VCM-induced HAS have occurred worldwide; and 3) an increased risk of lung cancer has been reported in some cohort studies of PVC polymerization workers, although this outcome may be related to PVC dust or factors other than VCM. A national study of HAS in the United States identified 3 other causes of HAS: Thorotrast, inorganic arsenic, and androgenic-anabolic steroids. Of 168 cases found to occur during 1964 through 1974, 42 cases (25%) were associated with the 4 known etiologic agents, while 126 cases (75%) were of unknown etiology.

  10. Processing of mercurous chloride in reduced gravity

    NASA Astrophysics Data System (ADS)

    Watson, C.; Singh, N. B.; Thomas, A.; Nelson, A. E.; Rolin, T. O.; Griffin, J.; Haulenbeek, G.; Daniel, N.; Seaquist, J.; Cacioppo, C.; Weber, Jerry; Zugrav, Maria I.; Naumann, R. J.

    1996-07-01

    In a joint experiment between the Northrop-Grumman Science and Technology Center and the University of Alabama in Huntsville, Consortium for Materials Development in Space, single crystals of mercurous chloride were grown in the Space Experiment Facility (SEF) transparent furnace that was flown on Spacehab 4 in May 1996. Mercurous chloride is an acousto-optical material with an unusually low acoustic velocity and high acousto-optical figure of merit. Single crystals of this material can be readily grown in normal gravity by closed-tube physical vapor transport, but the crystals generally contain structural inhomogeneities which degrade the optical performance. The nature and cause of these defects are not completely understood, but their degree appears to correlate with the Rayleigh number that characterizes the convective transport during their growth; hence, it is suspected that uncontrolled convection may play a role in the defect structure. The objective of the flight experiment was to reduce the convective flows by several orders of magnitude to see if the structural inhomogeneities can be reduced or eliminated. This paper will describe the physical and thermal properties of the SEF furnace, the ampule design and loading procedure, and the ground testing, and will also present the preliminary flight results.

  11. Open cycle lithium chloride cooling system

    NASA Astrophysics Data System (ADS)

    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.

  12. Antagonists for acute oral cadmium chloride intoxication

    SciTech Connect

    Basinger, M.A.; Jones, M.M.; Holscher, M.A.; Vaughn, W.K.

    1988-01-01

    An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

  13. The sodium chloride primary pressure gauge

    NASA Technical Reports Server (NTRS)

    Ruoff, A. L.; Chhabildas, L. C.

    1976-01-01

    The failure of a central force model for sodium chloride is discussed. It is noted that it does not closely satisfy the Cauchy conditions at low temperatures, and that it fails the central force requirement of the Love condition. The available shock data for sodium chloride and its analysis is examined, and two reasons why the Hugoniot transformation pressure is likely to be less than 231 kbar are discussed. The important (but unjustified) theoretical assumptions made in converting Hugoniot to isothermal data is discussed; it is noted that serious error can enter for very large pressures for a given material and that at such high pressures the isothermal data should thus be considered only semiquantitative even if the Hugoniot data itself is accurate. An alternate method of estimating the isothermal transformation pressure from the Hugoniot transformation pressure is used. This method is based on the temperature derivative of the transformation pressure. On this basis it is concluded that an upper bound for the isothermal transformation of NaCl (to a CsCl-type structure) at room temperature is 257 kbar; it is noted that the actual value may be considerably less than this.

  14. Cesium chloride compatibility testing program: Final report

    SciTech Connect

    Bryan, G.H.

    1989-11-01

    The US Department of Energy is considering the geologic disposal of the doubly encapsulated cesium chloride (CsCl) produced at the Waste Encapsulation and Storage Facility (WESF). Reliable estimates of long-term corrosion of the inner capsule material by the CsCl under repository storage conditions are needed to assess the hazards associated with geologic disposal of the fission product Cs. The Cesium Chloride Compatibility Program was carried out at PNL to obtain the short-term corrosion data required to accurately estimate long-term attack. In the compatibility tests six standard WESF CsCl capsules were placed vertically in individual insulated containers and allowed to self-heat to a nominal maximum 316L SS/CsCl interface temperature of 450{degree}C. The capsules were held at temperature for times ranging from 0.25 to 6 years. When a test was completed, the capsule was removed from the container and sectioned. Four samples were cut from the inner capsule at prescribed locations and subjected to metallographic examination. Corrosion was determined from photomicrographs of the samples. 16 refs., 41 figs., 16 tabs.

  15. The DELTA 181 lithium thionyl chloride battery

    NASA Astrophysics Data System (ADS)

    Sullivan, Ralph M.; Brown, Lawrence E.; Leigh, A. P.

    In 1986, the Johns Hopkins University/Applied Physics Laboratory (JHU/APL) undertook the development of a sensor module for the DELTA 181 spacecraft, a low earth orbit (LEO) mission of less than two months duration. A large lithium thionyl chloride battery was developed as the spacecraft's primary power source, the first known such use for this technology. The exceptionally high energy density of the lithium thionyl chloride cell was the primary driver for its use, resulting in a completed battery with a specific energy density of 120 Wh/lb. Safety requirements became the primary driver shaping all aspects of the power system design and development due to concerns about the potential hazards of this relatively new, high-energy technology. However, the program was completed without incident. The spacecraft was launched on February 8, 1988, from Kennedy Space Center (KSC) with over 60,000 Wh of battery energy. It reentered on April 2, 1988, still operating after 55 days, providing a successful, practical, and visible demonstration of the use of this technology for spacecraft applications.

  16. Picosecond dynamics from lanthanide chloride melts

    NASA Astrophysics Data System (ADS)

    Kalampounias, Angelos G.

    2012-12-01

    The picosecond dynamics of molten lanthanide chlorides is studied by means of vibrational spectroscopy. Polarized Raman spectra of molten LaCl3, NdCl3, GdCl3, DyCl3, HoCl3 and YCl3 are fitted to a model enabling to obtain the times of vibrational dephasing, tν and vibrational frequency modulation tω. Our aim is to find possible sensitive indicators of short-time dynamics. It has been found that all lanthanide chlorides exhibit qualitative similarities in the vibrational relaxation and frequency modulation times in the molten state. It appears that the vibrational correlation functions of all melts comply with the Rothschild approach assuming that the environmental modulation is described by a stretched exponential decay. The evolution of the dispersion parameter α indicates the deviation of the melts from the model simple liquid and the similar local environment in which the oscillator is placed and with which it is coupled. The "packing" of the anions around central La3+ cation seems to be the key factor for the structure and the dynamics of the melts. The results are discussed in the framework of the current phenomenological status of the field.

  17. 21 CFR 522.1862 - Sterile pralidoxime chloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Before administration of the sterile pralidoxime chloride, atropine is administered intravenously at a... milligram of atropine per pound of body weight administered intramuscularly. Then the appropriate dosage...

  18. 21 CFR 522.1862 - Sterile pralidoxime chloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Before administration of the sterile pralidoxime chloride, atropine is administered intravenously at a... milligram of atropine per pound of body weight administered intramuscularly. Then the appropriate dosage...

  19. Purification of aqueous plutonium chloride solutions via precipitation and washing.

    SciTech Connect

    Stroud, M. A.; Salazar, R. R.; Abney, Kent David; Bluhm, E. A.; Danis, J. A.

    2003-01-01

    Pyrochemical operations at Los Alamos Plutonium Facility (TA-55) use high temperature melt s of calcium chloride for the reduction of plutonium oxide to plutonium metal and hi gh temperature combined melts of sodium chloride and potassium chloride mixtures for the electrorefining purification of plutonium metal . The remaining plutonium and americium are recovered from thes e salts by dissolution in concentrated hydrochloric acid followed by either solvent extraction or io n exchange for isolation and ultimately converted to oxide after precipitation with oxalic acid . Figur e 1 illustrates the current aqueous chloride flow sheet used for plutonium processing at TA-55 .

  20. On Barium Oxide Solubility in Barium-Containing Chloride Melts

    NASA Astrophysics Data System (ADS)

    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.

  1. VOLATILE CHLORIDE PROCESS FOR THE RECOVERY OF METAL VALUES

    DOEpatents

    Hanley, W.R.

    1959-01-01

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

  2. Interpretation of postmortem vitreous concentrations of sodium and chloride.

    PubMed

    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

  3. Ion chromatographic determination of chloride in mustard sauces.

    PubMed

    López Agüero, E; Bosch Bosch, N; Barrera Vázquez, C; López Ruiz, B

    1999-11-01

    A new, simple, precise, and rapid ion chromatography (IC) method has been developed to determine chloride in mustard sauces using a mixture of phthalic acid, acetone, and water adjusted to pH 5.0 as eluent. Conductometric detection was carried out. The retention time for chloride was 1.5 min. Linearity was obtained up to a concentration level of 100 mg/L NaCl. The method was statistically evaluated for accuracy and precision after being used to assay the chloride from mustard sauces. Within the same samples, the chloride levels obtained by IC were compared with the sodium concentrations quantified by atomic absorption spectrophotometry.

  4. Developmental toxicity of copper chloride, methylene chloride, and 6-aminonicotinamide to embryos of the grass shrimp Palaemonetes pugio

    SciTech Connect

    Rayburn, J.R.; Fisher, W.S.

    1999-05-01

    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, copper chloride, and 6-aminonicotinamide, three known teratogenic chemicals. Two exposure periods were used, 4 d and 12 d, and both periods extended through hatching. The average 4-d LC50 values for methylene chloride, copper chloride, and 6-aminonicotinamide were 0.071% v/v, 1.82 mg/L, and 0.21 mg/ml, respectively. The average 12-d LC50 values for methylene chloride, copper chloride, and 6-aminonicotinamide were 0.031% v/v, 1.44 mg/L, and 0.057 mg/ml, respectively. Eye malformations were observed with embryos exposed to concentrations greater than 3 mg/L copper chloride or greater than 0.07% v/v methylene chloride. Very few abnormalities were observed in embryos exposed to 6-aminonicotinamide. Abnormal larval development was found with exposure to copper chloride at concentrations greater than 1 mg/L. The sensitivity and low variability found here further supports the development of these relatively simple methods using grass shrimp embryos. Establishment of sublethal developmental endpoints warrants further investigation because of their potential correspondence to mechanisms of toxic action.

  5. [Gustatory sensitivity to sodium chloride and potassium chloride and certain parameters of sodium metabolism in patients with bronchial asthma].

    PubMed

    Mineev, V N; Suparnovich, I Iu

    2008-01-01

    The aim of the study was to determine threshold gustatory sensitivity (TGS) to sodium chloride and potassium chloride in patients with bronchial asthma (BA) taking into account a number of factors responsible for the enhanced risk of development and progress of this disease. Forty five practically healthy subjects were compared with 139 asthmatic patients; a separate group comprised patients treated permanently with oral glucocorticoids and those having non-pulmonary allergy. Chemically pure solutions of sodium and potassium chlorides were used in the dripping test to assess TGS. Asthmatic patients had enhanced TGS to sodium chloride compared with healthy subjects. TGS values were especially high in non-allergic bronchial asthma and minimal in allergic asthma when they were unrelated to the phase of the disease. TGS to potassium chloride in asthmatic patients also differed from that in healthy subjects; more patients were bitter-insensitive or sensitive only to high concentrations of potassium chloride. Patients treated with systemic glucocorticoids had the highest TGS to sodium chloride. Patients with non-pulmonary allergy and allergic BA had very similar TGS to potassium chloride. TGS to sodium chloride in the former was lower than in healthy subjects and patients with allergic BA. Asthmatic patients had a higher sodium ion concentration in erythrocytes than normal subjects; it reached maximum values in persons used to add salt to fully cooked food.

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

    PubMed Central

    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. Lead electrowinning in an acid chloride medium

    NASA Astrophysics Data System (ADS)

    Expósito, E.; Iniesta, J.; González-García, J.; Montiel, V.; Aldaz, A.

    The results of an investigation of the electrowinning of lead employing a chloride medium are reported. The electro-deposition lead reaction was studied by voltammetric methods and scanning electron microscope (SEM) microphotographs of the electro-deposited lead were taken. The effects of current density, temperature, catholyte flow and H + concentration were investigated at laboratory scale to optimise operating conditions in order to found adequate values for industrial purposes of the parameters energetic cost and production. For a working current density of 100 mA/cm 2 the current efficiency, energy consumption and production were 90%, 1.32 kW h/kg Pb and 83.4 kg Pb/m 2 per day, respectively.

  8. [Survey of plasticizers in polyvinyl chloride toys].

    PubMed

    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.

  9. Poly(vinyl chloride) processes and products.

    PubMed

    Wheeler, R N

    1981-10-01

    Poly(vinyl chloride) resins are produced by four basic processes: suspension, emulsion, bulk and solution polymerization. PVC suspensions resins are usually relatively dust-free and granular with varying degrees of particle porosity. PVC emulsion resins are small particle powders containing very little free monomer. Bulk PVC resins are similar to suspension PVC resins, though the particles tend to be more porous. Solution PVC resins are smaller in particle size than suspension PVC with high porosity particles containing essentially no free monomer. The variety of PVC resin products does not lend itself to broad generalizations concerning health hazards. In studying occupational hazards the particular PVC process and the product must be considered and identified in the study.

  10. Unsteady growth of ammonium chloride dendrites

    NASA Astrophysics Data System (ADS)

    Martyushev, L. M.; Terentiev, P. S.; Soboleva, A. S.

    2016-02-01

    Growth of ammonium chloride dendrites from aqueous solution is experimentally investigated. The growth rate υ and the radius ρ of curvature of branches are measured as a function of the relative supersaturation Δ for steady and unsteady growth conditions. It is shown that the experimental results are quantitatively described by the dependences ρ=a/Δ+b, υ=сΔ2, where the factors for primary branches are a=(1.3±0.2)·10-7 m, b=(2.5±0.4)·10-7 m, and c=(2.2±0.3)·10-4 m/s. The factor c is found to be approximately 7 times smaller for the side branches than that for the primary branches.

  11. Unsteady growth of ammonium chloride dendrites

    NASA Astrophysics Data System (ADS)

    Martyushev, L. M.; Terentiev, P. S.; Soboleva, A. S.

    2016-02-01

    Growth of ammonium chloride dendrites from aqueous solution is experimentally investigated. The growth rate υ and the radius ρ of curvature of branches are measured as a function of the relative supersaturation Δ for steady and unsteady growth conditions. It is shown that the experimental results are quantitatively described by the dependences ρ=a/Δ+b, υ=cΔ2, where the factors for primary branches are a=(1.3±0.2)·10-7 m, b=(2.5±0.4)·10-7 m, and c=(2.2±0.3)·10-4 m/s. The factor c is found to be approximately 7 times smaller for the side branches than that for the primary branches.

  12. Dynamics of vitreous and molten zinc chloride

    SciTech Connect

    Price, D.L.; Saboungi, M.L.; Susman, S.; Volin, K.J. ); Wright, A.C. . J.J. Thomson Physical Lab.)

    1991-09-01

    The dynamics of vitreous and molten zinc chloride have been studied with inelastic neutron scattering at the Intense Pulsed Neutron Source. The results are analyzed in terms of the scattering function S(Q,E) and the effective vibrational density of states G(E). The vibrational spectra of both glass and liquid are dominated by broad features centered at 15 and 35 MeV which are identified with F{sub 2} modes of ZnCl{sub 4}{sup 2{minus}} tetrahedra. The other two normal modes are not observed because of inadequate resolution and broadening and overlap resulting from coupling between tetrahedra. The behavior of ZnCl{sub 2} is contrasted with other tetrahedrally coordinated glasses that have been studied with the same technique. 15 refs,. 5 figs., 1 tab.

  13. Unexpected Stable Stoichiometries of Sodium Chlorides

    NASA Astrophysics Data System (ADS)

    Zhang, Weiwei; Oganov, Artem R.; Goncharov, Alexander F.; Zhu, Qiang; Boulfelfel, Salah Eddine; Lyakhov, Andriy O.; Stavrou, Elissaios; Somayazulu, Maddury; Prakapenka, Vitali B.; Konôpková, Zuzana

    2013-12-01

    Sodium chloride (NaCl), or rocksalt, is well characterized at ambient pressure. As a result of the large electronegativity difference between Na and Cl atoms, it has highly ionic chemical bonding (with 1:1 stoichiometry dictated by charge balance) and B1-type crystal structure. By combining theoretical predictions and diamond anvil cell experiments, we found that new materials with different stoichiometries emerge at high pressures. Compounds such as Na3Cl, Na2Cl, Na3Cl2, NaCl3, and NaCl7 are theoretically stable and have unusual bonding and electronic properties. To test this prediction, we synthesized cubic and orthorhombic NaCl3 and two-dimensional metallic tetragonal Na3Cl. These experiments establish that compounds violating chemical intuition can be thermodynamically stable even in simple systems at nonambient conditions.

  14. Processing of mercurous chloride in space

    NASA Astrophysics Data System (ADS)

    Watson, C.; Singh, N. B.; Thomas, A.; Nelson, A. E.; Rolin, T. O.; Griffin, J.; Haulenbeek, G.; Daniel, N.; Seaquist, J.; Cacioppo, C.; Weber, Jerry; Zugrav, Maria I.; Naumann, R. J.

    1997-07-01

    Mercurous chloride is an acoustical optical material with an unusually low acoustic velocity and high acousto-optical figure of merit, which makes it an interesting candidate for optical delay lines and Bragg cells for optical signal processors. It also has a broad range of spectral transmissivity which makes it an ideal candidate for wide band acoustically tuned optical filter (ATOF) applications. Single crystals of this material can be readily grown in normal gravity by closed-tube physical vapor transport, but the crystals appear to contain structural inhomogeneities which degrade the optical performance. The nature of these defects is not known, but their degree appears to correlate with the Rayleigh number that characterizes their growth; hence, it is suspected that uncontrolled convection may play a role in the defect structure. This prompted a space flight experiment to determine if these defects could be further reduced by virtually eliminating the buoyancy-driven convective flows which are always present to a degree in normal gravity. Single crystals of mercurous chloride (Hg2Cl2) were grown in the Space Experiment Facility (SEF) transparent furnace developed by the University of Alabama in Huntsville, Consortium for Materials Development in Space. The Northrop- Grumman Science and Technology Center provided the highly purified starting material and analyzed the crystals that were grown. This experiment was flown on Spacehab 4 (STS-77) in May 1996. The SEF is a transparent furnace which allowed the progress of the growth to be recorded by video. Extensive furnace profiling and modeling has been carried out to relate the growth front location to the thermal environment and to the crystal quality. The results of the flight experiment as well as the ground control experiments are presented.

  15. Pharmacodynamics of benzyl chloride in rats.

    PubMed

    Saxena, S; Abdel-Rahman, M S

    1989-09-01

    In today's world of high industrialization, toxicity and pollution have become common terms of references. Both laymen and experts are becoming increasingly concerned about various health hazards created by occupational and industrial wastes dumped in and around public places. Benzyl chloride (BCl) was one of the chemicals dumped by Hooker Chemicals in Love Canal, N.Y. Benzyl chloride (BCl) is extensively used in industry in the manufacture of dyes, perfumes, resins, and synthetic tannins. It has been found at various dump sites and industrial wastes, which has led to potential hazards to health. This study was conducted to investigate the pharmacodynamics of BCl in rats. Rats were given 14C-BCl in corn oil by gavage. The peak plasma level was reached at 30 min and began to decline. BCl elimination pattern follows a two compartment model. The distribution half-life (alpha-phase) was 1.3 hr while the half-life of elimination (beta-phase) was 58.53 hr. Distribution studies after 48 hr of BCl administration revealed that the concentration of radioisotopes was highest in the stomach, gastric content, ileum, and duodenum followed by liver, adrenal, bone marrow, whole blood, pancreas, lung, esophagus, skin, kidney, heart, thymus, fat, testes, spleen, brain, and carcass. Approximately 76% of the initial dose was excreted by kidney during the 72 hr studies. About 7% was detected in expired air as 14CO2, while less than 1.3% was present as 14C-BCl or 14C-BCl metabolites in expired air during 72 hr. Metabolism studies revealed that S-benzyl-N-acetyl cysteine, benzyl alcohol, and benzaldehyde were the metabolites present in the urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2802671

  16. The electrowinning of copper from a cupric chloride solution

    NASA Astrophysics Data System (ADS)

    Lin, H. K.; Wu, X. J.; Rao, P. D.

    1991-08-01

    In this work, the Eh pCl diagram of the CuCl-H2O system was established, and the kinetics of copper dissolution in cupric chloride solution were studied with an emphasis on possible difficulties that may occur during copper electrowinning. The results were used to guide an investigation of copper electrowinning from cupric chloride solution.

  17. TOXICOLOGY OF MONO- AND DI-ALKYLTIN CHLORIDES

    EPA Science Inventory

    Mono- and di-alkyltin chlorides are reactive compounds used in the production of stabilizers for polyvinyl chloride (PVC) plastics, primarily used for water distribution pipes. Health effects data were compiled or developed by the manufacturers for the EPA's HPV Challenge progra...

  18. TOXICOLOGY OF MONO- AND DI-ALKYLTIN CHLORIDES.

    EPA Science Inventory

    Mono- and di-alkyltin chlorides are reactive compounds used in the production of stabilizers for polyvinyl chloride (PVC) plastics, primarily used for water distribution pipes. Health effects data were compiled or developed by the manufacturers for the EPA's HPV Challenge progra...

  19. Calcium chloride: a new solution for frozen coal

    SciTech Connect

    Boley, D.G.

    1984-01-01

    Proved in emergency situations as fast and economical, calcium chloride can be used in conjunction with other techniques for effective prevention of coal freezing. Calcium chloride solution depresses the freezing point, and should the temperature drop below this point, the ice that does form has a far lower compressive strength than ice normally exhibits.

  20. 21 CFR 172.165 - Quaternary ammonium chloride combination.

    Code of Federal Regulations, 2010 CFR

    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...

  1. Microwave Mapping Demonstration Using the Thermochromic Cobalt Chloride Equilibrium

    ERIC Educational Resources Information Center

    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…

  2. 46 CFR 151.50-75 - Ferric chloride solution.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Ferric chloride solution. 151.50-75 Section 151.50-75... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-75 Ferric chloride solution... solution must be lined with rubber, corrosion resistant plastic, or a material approved by the...

  3. 46 CFR 151.50-75 - Ferric chloride solution.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Ferric chloride solution. 151.50-75 Section 151.50-75... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-75 Ferric chloride solution... solution must be lined with rubber, corrosion resistant plastic, or a material approved by the...

  4. Molybdenum In Cathodes Of Sodium/Metal Chloride Cells

    NASA Technical Reports Server (NTRS)

    Bugga, Ratnakumar V.; Attia, Alan I.; Halpert, Gerald

    1992-01-01

    Cyclic voltammetric curves of molybdenum wire in NaAlCl4 melt indicate molybdenum chloride useful as cathode material in rechargeable sodium/metal chloride electrochemical cells. Batteries used in electric vehicles, for electric-power load leveling, and other applications involving high energy and power densities.

  5. 21 CFR 172.165 - Quaternary ammonium chloride combination.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN CONSUMPTION Food Preservatives § 172.165 Quaternary ammonium chloride combination. The food... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Quaternary ammonium chloride combination. 172.165 Section 172.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  6. 21 CFR 172.165 - Quaternary ammonium chloride combination.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN CONSUMPTION Food Preservatives § 172.165 Quaternary ammonium chloride combination. The food... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Quaternary ammonium chloride combination. 172.165 Section 172.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  7. 21 CFR 172.165 - Quaternary ammonium chloride combination.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN CONSUMPTION Food Preservatives § 172.165 Quaternary ammonium chloride combination. The food... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Quaternary ammonium chloride combination. 172.165 Section 172.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  8. Behavior and products of mechano-chemical dechlorination of polyvinyl chloride and poly (vinylidene chloride).

    PubMed

    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.

  9. Review of pulmonary effects of poly(vinyl chloride) and vinyl chloride exposure.

    PubMed

    Lilis, R

    1981-10-01

    The contributions of several recent reports to the definition of pulmonary effects of PVC dust inhalation are reviewed. Granulomatous reaction, with inclusion of PVC particles in macrophages and histocytes, and associated interstitial pulmonary fibrosis have been found to lead to exertional dyspnoea, diffuse micronodular chest radiographic opacities and restrictive pulmonary dysfunction. The effects of vinyl chloride (VC) monomer (gas) on proteins and the immunologic mechanisms triggered by the altered protein are possible mechanisms for the development in some cases of interstitial pulmonary fibrosis secondary to VC exposure. Vinyl chloride, a confirmed carcinogen, has been associated with, among other malignant tumors, a significant increase in the incidence of lung cancer. The magnitude of this effect has not yet been completely evaluated.

  10. Measurements of the partial electronic conductivity in lithium chloride - potassium chloride molten salts

    SciTech Connect

    Reynolds, G.J.; Huggins, R.A.; Lee, M.C.Y.

    1983-05-01

    The partial electronic conductivity of the lithium chloride-potassium chloride eutectic molten salt electrolyte has been studied as a function of lithium activity, temperature and melt composition using the Wagner asymmetric d-c polarization technique. Measurements were made over the temperature range 383-465/sup 0/C and at lithium activities extending from 1.95 X 10/sup -7/ to unity. The results confirmed the applicability of this technique to molten salt systems. The partial electronic conductivity was shown to be much greater than the partial hole conductivity over the range of lithium activities investigated, and was found to increase monotonically with temperature and lithium activity, but decreased on addition of excess LiCl to the eutectic composition. Approximate values of self-discharge currents for cells utilizing an ''Al/LiAl'' negative electrode and a LiCl-KCl molten salt electrolyte have been calculated.

  11. Determination of the heat capacities of Lithium/BCX (bromide chloride in thionyl chloride) batteries

    NASA Technical Reports Server (NTRS)

    Kubow, Stephen A.; Takeuchi, Kenneth J.; Takeuchi, Esther S.

    1989-01-01

    Heat capacities of twelve different Lithium/BCX (BrCl in thionyl chloride) batteries in sizes AA, C, D, and DD were determined. Procedures and measurement results are reported. The procedure allowed simple, reproducible, and precise determinations of heat capacities of industrially important Lithium/BCX cells, without interfering with performance of the cells. Use of aluminum standards allowed the accuracy of the measurements to be maintained. The measured heat capacities were within 5 percent of calculated heat capacity values.

  12. [Properties of benzethonium chloride in micellar solutions and the effect of added sodium chloride].

    PubMed

    Kopecký, F; Kopecká, B; Kaclík, P

    2006-07-01

    Aqueous solutions of the antimicrobially effective quaternary ammonium salt benzethonium chloride (hyamine 1622) were studied using UV spectrophotometry and partially conductometry. The spectra of micellar solutions of benzethonium chloride revealed a concentration-dependent bathochromic and hyperchromic shift of a weak UV absorption band in the region 250-300 nm. This served to elaborate the spectrophotometric determination of the critical micellar concentration (CMC) of benzethonium chloride and the concentration of free benzethonium cations in micellar solutions without an addition of NaCl and with a constant addition of NaCl 0.003, 0.1 and 0.15 mol/l. Premicellar associations were not observed and in NaCl-free solutions CMC 0.0028 mol/l was spectrophotometrically determined. An addition of NaCl resulted in an increased hyperchromic effect and strengthening of micellization, manifested by a more than ten-times decrease in the CMC as well as the concentration of free benzethonium cations in micellar solutions. The courses of the determined concentrations of free benzethonium cations in the solutions both without and with the presence of NaCl were quite similar; their maximal values were always just a little higher than the corresponding CMC and with a further growth of the total concentration of benzethonium chloride there was, on the other hand, a marked decrease in the concentration of its free cations in micellar solution. Possible effects of a decreased concentration of free benzethonium cations due to an added electrolyte on antimicrobial activity and formation of ionic pairs are discussed.

  13. Conversion of bacteriorhodopsin into a chloride ion pump

    SciTech Connect

    Sasaki, J.; Chon, Y.S.; Kandori, H.

    1995-07-07

    In the light-driven proton pump bacteriorhodopsin, proton transfer from the retinal Schiff base to aspartate-85 is the crucial reaction of the transport cycle. In halorhodopsin, a light-driven chloride ion pump, the equivalent of residue 85 is threonine. When aspartate-85 was replaced with threonine, the mutated bacteriorhodopsin became a chloride ion pump when expressed in Halobacterium salinarium and, like halorhodopsin, actively transported chloride ions in the direction opposite from the proton pump. Chloride was bound to it, as revealed by large shifts of the absorption maximum of the chromophore, and its photointermediates included a red-shifted state in the millisecond time domain, with its amplitude and decay rate dependent on chloride concentration. Bacteriorhodopsin and halorhodopsin thus share a common transport mechanism, and the interaction of residue 85 with the retinal Schiff base determines the ionic specificity. 28 refs., 4 figs.

  14. Method for synthesizing pollucite from chabazite and cesium chloride

    DOEpatents

    Pereira, Candido

    1999-01-01

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

  15. Method for synthesizing pollucite from chabazite and cesium chloride

    DOEpatents

    Pereira, C.

    1999-02-23

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

  16. Atmospheric corrosion and chloride deposition on metal surfaces

    SciTech Connect

    Matthes, Steven A.; Holcomb, Gordon R.; Cramer, Stephen D.; Covino, Bernard S., Jr.; Bullard, Sophie J.

    2004-01-01

    Atmospheric corrosion and chloride deposition on metal surfaces was studied at an unpolluted coastal (marine) site, an unpolluted rural inland site, and a polluted urban site. Chloride deposition by both wet (precipitation) and dry deposition processes over a multi-year period was measured using ion chromatography analysis of incident precipitation and precipitation runoff from the surface of metal samples. Chloride deposition was measured on zinc, copper, lead, mild steel, and non-reactive blank panels, as well as two panels coated with thermal-sprayed zinc alloys. Chloride deposition measured by runoff chemistry was compared with chloride deposition measurements made by the ASTM wet candle technique. Corrosion mass loss as a function of distance from the ocean is presented for copper and mild steel in bold exposures on the west coast.

  17. Apparatus and method for making metal chloride salt product

    DOEpatents

    Miller, William E.; Tomczuk, Zygmunt; Richmann, Michael K.

    2007-05-15

    A method of producing metal chlorides is disclosed in which chlorine gas is introduced into liquid Cd. CdCl.sub.2 salt is floating on the liquid Cd and as more liquid CdCl.sub.2 is formed it separates from the liquid Cd metal and dissolves in the salt. The salt with the CdCl.sub.2 dissolved therein contacts a metal which reacts with CdCl.sub.2 to form a metal chloride, forming a mixture of metal chloride and CdCl.sub.2. After separation of bulk Cd from the salt, by gravitational means, the metal chloride is obtained by distillation which removes CdCl.sub.2 and any Cd dissolved in the metal chloride.

  18. Monoclonal Antibodies to the Apical Chloride Channel in Necturus Gallbladder Inhibit the Chloride Conductance

    NASA Astrophysics Data System (ADS)

    Finn, Arthur L.; Tsai, Lih-Min; Falk, Ronald J.

    1989-10-01

    Monoclonal antibodies raised by injecting Necturus gallbladder cells into mice were tested for their ability to inhibit the apical chloride conductance induced by elevation of cellular cAMP. Five of these monoclonal antibodies bound to the apical cells, as shown by indirect immunofluorescence microscopy, and inhibited the chloride conductance; one antibody that bound only to subepithelial smooth muscle, by indirect immunofluorescence microscopy, showed no inhibition of chloride transport. The channel or a closely related molecule is present in the membrane whether or not the pathway is open, since, in addition to inhibiting the conductance of the open channel, the antibody also bound to the membrane in the resting state and prevented subsequent opening of the channel. The antibody was shown to recognize, by ELISA, epitopes from the Necturus gallbladder and small intestine. Finally, by Western blot analysis of Necturus gallbladder homogenates, the antibody was shown to recognize two protein bands of Mr 219,000 and Mr 69,000. This antibody should permit isolation and characterization of this important ion channel.

  19. Acute lethal and teratogenic effects of tributyltin chloride and copper chloride on mahi mahi (Coryphaena hippurus) eggs and larvae.

    PubMed

    Adema-Hannes, Rachel; Shenker, Jonathan

    2008-10-01

    Acute and chronic bioassays were used to evaluate the lethal and sublethal effects of copper chloride and tributyltin chloride on mahi mahi (Coryphaena hippurus) embryos, a pelagic life stage often found in the surface microlayer where anthropogenic contaminants can accumulate. Acute bioassay testing determined the median lethal concentration (LC50) for the test organism after 48 h of exposure. Chronic toxicity tests were used to determine the measurement of sublethal parameters, such as developmental abnormalities after 72-h exposures to the toxicants. Embryos were collected 4 h postfertilization and subsequently exposed to 1, 5, 25, 50, and 100 microg/L of copper chloride and 3, 10, 20, 30, and 50 microg/L of tributyltin chloride. Analysis of hatch rate percentage determined that the mean 48-h LC50 of copper chloride and tributyltin chloride was 32.8 and 16.7 microg/L, respectively, based on the pooled data of four experiments with four replicates for each metal. Consistent abnormalities, such as yolk sac swelling, spinal deformities, and decreased hatch rates, were observed for each metal. Teratogenic responses to copper chloride and tributyltin chloride demonstrate the need to investigate further the impacts of pollution in the open oceans to a species indigenous to, and commercially important to, the Florida (USA) coasts. This information could then lead to the future development of a surface microlayer bioassay using mahi mahi embryos. PMID:18419170

  20. Acetogenic microbial degradation of vinyl chloride

    USGS Publications Warehouse

    Bradley, P.M.; Chapelle, F.H.

    2000-01-01

    Under methanogenic conditions, microbial degradation of [1,2-14C]vinyl chloride (VC) resulted in significant (14 ?? 3% maximum recovery) but transient recovery of radioactivity as 14C-acetate. Subsequently, 14C- acetate was degraded to 14CH4 and 14CO2 (18 ?? 2% and 54 ?? 3% final recoveries, respectively). In contrast, under 2-bromoethanesulfonic acid (BES) amended conditions, 14C-acetate recovery remained high (27 ?? 1% maximum recovery) throughout the study, no 14CH4 was produced, and the final recovery of 14CO2 was only 35 ?? 4%. These results demonstrate that oxidative acetogenesis may be an important mechanism for anaerobic VC biodegradation. Moreover, these results (1) demonstrate that microbial degradation of VC to CH4 and CO2 may involve oxidative acetogenesis followed by acetotrophic methanogenesis and (2) suggest that oxidative acetogenesis may be the initial step in the net oxidation of VC to CO2 reported previously under Fe(III)-reducing, SO4-reducing, and humic acids- reducing conditions.Under methanogenic conditions, microbial degradation of [1,2-14C]vinyl chloride (VC) resulted in significant (14 ?? 3% maximum recovery) but transient recovery of radioactivity as 14C-acetate. Subsequently, 14C-acetate was degraded to 14CH4 and 14CO2 (18 ?? 2% and 54 ?? 3% final recoveries respectively). In contrast, under 2-bromoethanesulfonic acid (BES) amended conditions, 14C-acetate recovery remained high (27 ?? 1% maximum recovery) throughout the study, no 14CH4 was produced, and the final recovery of 14CO2 was only 35 ?? 4%. These results demonstrate that oxidative acetogenesis may be an important mechanism for anaerobic VC biodegradation. Moreover, these results (1) demonstrate that microbial degradation of VC to CH4 and CO2 may involve oxidative acetogenesis followed by acetotrophic methanogenesis and (2) suggest that oxidative acetogenesis may be the initial step in the net oxidation of VC to CO2 reported previously under Fe(III)-reducing, SO4-reducing, and

  1. Fate and effects of methylene chloride in activated sludge.

    PubMed Central

    Klecka, G M

    1982-01-01

    Activated sludge obtained from a municipal wastewater treatment plant was acclimated to methylene chloride at concentrations between 1 and 100 mg/liter by continuous exposure to the compound for 9 to 11 days. Acclimated cultures were shown to mineralize methylene chloride to carbon dioxide and chloride. Rates of methylene chloride degradation were 0.14, 2.3, and 7.4 mg of CH2Cl2 consumed per h per g of mixed-liquor suspended solids for cultures incubated in the presence of 1, 10, and 100 mg/liter, respectively. Concentrations of methylene chloride between 10 and 1,000 mg/liter had no significant effect on O2 consumption or glucose metabolism by activated sludge. A hypothetical model was developed to examine the significance of volatilization and biodegradation for the removal of methylene chloride from an activated sludge reactor. Application of the model indicated that the rate of biodegradation was approximately 12 times greater than the rate of volatilization. Thus, biodegradation may be the predominant process determining the fate of methylene chloride in activated sludge systems continuously exposed to the compound. PMID:7138008

  2. Chlormequat chloride retards rat embryo growth in vitro.

    PubMed

    Xiagedeer, Bayindala; Wu, Shuang; Liu, Yingjuan; Hao, Weidong

    2016-08-01

    Chlormequat chloride is the most widely used plant growth regulator in agriculture to promote sturdier growth of grain crops by avoidance of lodging. Therefore, human exposure to chlormequat chloride is very common, but its developmental toxicity has not been studied. Thus, we investigated the developmental toxicity of chlormequat chloride by applying rat whole embryo culture (WEC) model, limb bud micromass culture and 3T3 fibroblast cytotoxicity test. Chlormequat chloride at 150μg/ml (0.93mM) retarded the rat embryo growth without causing significant morphological malformations and at 500μg/ml (3.1mM) caused both retardation and morphological malformation of the embryos. However, the proliferation and differentiation of limb bud cells were not affected by chlormequat chloride at as high as up to 1000μg/ml (6.2mM) applied. This concentration of chlormequat chloride did not affect the cell viability as examined by 3T3 fibroblast cytotoxicity test either, suggesting that cellular toxicity may not play a role in chlormequat induced inhibition of rat embryo growth. Collectively, our results demonstrated that chlormequat chloride may affect embryo growth and development without inhibiting cell viability.

  3. Strong emission of methyl chloride from tropical plants.

    PubMed

    Yokouchi, Yoko; Ikeda, Masumi; Inuzuka, Yoko; Yukawa, Tomohisa

    2002-03-14

    Methyl chloride is the largest natural source of ozone-depleting chlorine compounds, and accounts for about 15 per cent of the present atmospheric chlorine content. This contribution was likely to have been relatively greater in pre-industrial times, when additional anthropogenic sources-such as chlorofluorocarbons-were absent. Although it has been shown that there are large emissions of methyl chloride from coastal lands in the tropics, there remains a substantial shortfall in the overall methyl chloride budget. Here we present observations of large emissions of methyl chloride from some common tropical plants (certain types of ferns and Dipterocarpaceae), ranging from 0.1 to 3.7 microg per gram of dry leaf per hour. On the basis of these preliminary measurements, the methyl chloride flux from Dipterocarpaceae in southeast Asia alone is estimated at 0.91 Tg yr-1, which could explain a large portion of missing methyl chloride sources. With continuing tropical deforestation, natural sources of chlorine compounds may accordingly decrease in the future. Conversely, the abundance of massive ferns in the Carboniferous period may have created an atmosphere rich in methyl chloride.

  4. An Apical-Membrane Chloride Channel in Human Tracheal Epithelium

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    1986-06-01

    The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

  5. Urinary sodium and chloride during renal salt retention.

    PubMed

    Sherman, R A; Eisinger, R P

    1983-09-01

    One hundred ten episodes of renal salt retention (urinary sodium and/or chloride less than 10 mEq/L) were studied retrospectively to determine the significance of discordance of urinary sodium from chloride. In 16 episodes the urinary sodium exceeded chloride by at least 15 mEq/L. This disparity was associated with the necessity for urinary excretion of substantial quantities of poorly reabsorbed anions (penicillin, ketones, or diatrizoate), a rapidly falling serum bicarbonate level (due to resolving metabolic or developing respiratory alkalosis), or substantial renal insufficiency (serum creatinine greater than 3 mg/dL). In 14 of 110 episodes, urinary chloride exceeded urinary sodium by at least 15 mEq/L. These patients were more often oliguric and had a higher mean serum chloride than patients without this dissociation. In patients with oliguria, hyponatremia, or metabolic alkalosis, measurement of urinary sodium or chloride alone will, in a substantial number of cases, fail to detect renal salt retention. When evidence is sought for renal salt retention, both urinary sodium and chloride should be determined. PMID:6613992

  6. Anomalous chloride flux discharges from Yellowstone National Park

    USGS Publications Warehouse

    Friedman, I.; Norton, D.R.

    1990-01-01

    The chloride concentration of some thermal springs in and adjacent to Yellowstone National Park is constant through time although their discharge varies seasonally. As a result the chloride flux from these springs increases during periods of increased discharge. We believe that this is caused by changes in the height of the local groundwater table, which affects the discharge of the springs but not their chloride concentration. The discharge from Mammoth Hot Springs varies seasonally, but its chloride concentration remains constant. We take this as evidence that this major thermal feature is derived from orifices that are tapping the local water table close to its surface. Three of the four major rivers (Yellowstone, Snake and Falls) exiting the Park also show an increased chloride flux during the spring runoff that cannot be explained solely by the contribution of snowmelt, nor by release of hot-spring-derived chloride stored in the soil during the winter and released in the spring. The increased chloride flux in these rivers is attributed to their draining shallow hot springs similar to those mentioned above. In contrast to the Yellowstone, Snake and Falls Rivers, the Firehole and Gibbon Rivers, which unite to form the Madison River and which collectively drain several major geyser basins, display a poor correlation between chloride flux and discharge. The cause, we believe, is that a large part of the thermal water input to these two rivers originated at great depths where the seasonal variation in the height of the water table had a negligible effect on hot spring discharge. Monitoring of seasonal discharge and chloride concentration of thermal features yields information on the depths at which these thermal features tap the local water table. ?? 1990.

  7. [Effect of methylrosanilinium chloride to MRSA nasal carriers].

    PubMed

    Ogino, J; Murakami, Y; Yamada, T

    1992-03-01

    Since the end of 1987, we have noticed an increasing incidence of Methicillin resistant Staphylococcus aureus (MRSA) among the inpatients of Yamanashi Medical College Hospital. MRSA strains were identified in 70-80 percent of the specimens obtained from patients with Staphylococcus aureus. From 1988 we performed yearly bacteriological examinations of the nares of medical personnel at Yamanashi Medical College Hospital. We treated nasal carriers with OFLX drop lotion or Povidone-iodine applied to the nares. In 1991 we treated eight nasal carriers, who had been unsuccessfully treated with Povidone-iodine, with 0.01% Methylrosanilinium Chloride ointment which was applied to the nares once a day for two weeks. A post-bacteriological examination again revealed that MRSA vanished from the nares of six nasal carriers. The minimum inhibitory concentration (MIC) of Methylrosanilinium Chloride was determined by the agar plate dilution method. The 100% MICs of MSSA were 1.0 microgram/ml and of MRSA were 1.0 microgram/ml by Methylrosanilinium Chloride. Moreover we examined the MICs of Methylrosanilinium Chloride against MRSA under the existing 5% Albumin, and consequently the 100% MICs were 4.0 micrograms/ml. Therefore a 0.01% Methylrosanilinium Chloride has sufficient efficacy against MRSA. The reaction of the skin and nasal mucosa to Methylrosanilinium Chloride was examined by using three groups of guinea pigs. 0.1% and 0.01% Methylrosanilinium Chloride ointment and hydrophylic poloid were applied to the nares and skin once a day for two weeks. Post-observation with an opticmicroscope revealed no significant findings. Methylrosanilinium Chloride shows good anti-Staphylococcus aureus ability. Further investigation is needed to determine if Methylrosanilinium Chloride has additional clinical application.

  8. Chloride transport across placental microvillous membranes measured by fluorescence

    SciTech Connect

    Illsley, N.P.; Glaubensklee, C.; Davis, B.; Verkman, A.S. )

    1988-12-01

    Chloride transport across human placental microvillous vesicle membrane was investigated using the fluorescent probe SPQ (6-methoxy-N(3-sulfopropyl)quinolinium). Chloride influx (J{sub Cl}) was calculated from the initial rate of quenching of intravesicular SPQ fluorescence by chloride. J{sub Cl} measured by SPQ fluorescence was not significantly different from J{sub Cl} measured by uptake of {sup 36}Cl; SPQ did not affect measurements of J{sub Cl}. J{sub Cl} was increased 51% by a 58-mV membrane potential. Voltage-stimulated J{sub Cl} showed a saturable dependence on chloride concentration with a dissociation constant (K{sub d}) of 18 {plus minus} 5 mM and was inhibited by diphenylamine-2-carboxylate with an apparent inhibitory constant of 0.13 {plus minus} 0.03 mM. The activation energy calculated for voltage-stimulated J{sub Cl} was 4.6 {plus minus} 0.6 kcal/mol. J{sub Cl} was also stimulated by a reduction in the external pH from 7.0 to 5.5 (internal pH = 70). pH-stimulated chloride influx was increased by trans-HCO{sub 3} and was inhibited by dihydro-4,4{prime}-diisothiocyano-2,2{prime}-disulfonic stilbene. Uptake of {sup 36}Cl into microvillous vesicles was stimulated by trans-Cl. pH-stimulated J{sub Cl} showed a saturable dependence on chloride with a K{sub d} of 38 {plus minus} 6 mM but was not affected by membrane potential. No evidence was found for Na- or K-coupled chloride cotransport. These findings demonstrate the presence of a saturable chloride conductance and an electroneutral chloride-bicarbonate exchanger in the placental microvillous membrane.

  9. Anomalous chloride flux discharges from Yellowstone National Park

    NASA Astrophysics Data System (ADS)

    Friedman, Irving; Norton, Daniel R.

    1990-08-01

    The chloride concentration of some thermal springs in and adjacent to Yellowstone National Park is constant through time although their discharge varies seasonally. As a result the chloride flux from these springs increases during periods of increased discharge. We believe that this is caused by changes in the height of the local groundwater table, which affects the discharge of the springs but not their chloride concentration. The discharge from Mammoth Hot Springs varies seasonally, but its chloride concentration remains constant. We take this as evidence that this major thermal feature is derived from orifices that are tapping the local water table close to its surface. Three of the four major rivers (Yellowstone, Snake and Falls) exiting the Park also show an increased chloride flux during the spring runoff that cannot be explained solely by the contribution of snowmelt, nor by release of hot-spring-derived chloride stored in the soil during the winter and released in the spring. The increased chloride flux in these rivers is attributed to their draining shallow hot springs similar to those mentioned above. In contrast to the Yellowstone, Snake and Falls Rivers, the Firehole and Gibbon Rivers, which unite to form the Madison River and which collectively drain several major geyser basins, display a poor correlation between chloride flux and discharge. The cause, we believe, is that a large part of the thermal water input to these two rivers originated at great depths where the seasonal variation in the height of the water table had a negligible effect on hot spring discharge. Monitoring of seasonal discharge and chloride concentration of thermal features yields information on the depths at which these thermal features tap the local water table.

  10. Regulation of neuronal chloride homeostasis by neuromodulators.

    PubMed

    Mahadevan, Vivek; Woodin, Melanie A

    2016-05-15

    KCC2 is the central regulator of neuronal Cl(-) homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G-protein-coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn(2+) receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5-hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A-type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR-signals are novel endogenous Cl(-) extrusion enhancers that may regulate KCC2 function. PMID:26876607

  11. Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride

    SciTech Connect

    Harvey, R.A.; Alcid, D.V.; Greco, R.S.

    1982-09-01

    Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

  12. The leaching of chalcopyrite with cupric chloride

    NASA Astrophysics Data System (ADS)

    Hirato, Tetsuji; Majima, Hiroshi; Awakura, Yasuhiro

    1987-03-01

    A comparative study of electrochemical leaching and chemical leaching of chalcopyrite was performed mainly at 343 K to elucidate the leaching mechanism of chalcopyrite with CuCl2. Also, the morphology of the leached chalcopyrite surface was studied by using a single chalcopyrite crystal. The leaching with CuCl2 produced a porous elemental sulfur layer on the chalcopyrite surface, showing a similar morphology to that produced during leaching with FeCl3. The leaching kinetics were found to be linear over an extended period, followed by an acceleration stage, as a result of an increase in the reaction surface area. The leaching rate of chalcopyrite was proportional to C(CuCl2)0.5, whereas it was inversely proportional to C(CuCl)0.5. The mixed potential of chalcopyrite exhibited a 66 mV decade-1 dependency upon C(CuCl2), and—69 mV decade-1 upon C(CuCl). Based on these observations together with other findings, an electrochemical mechanism involving the oxidation of chalcopyrite and CuCl{-/2} and the reduction of CuCl+ was proposed. The Tafel plot between the mixed potential and the current density obtained by converting the rate of chemical leaching gave a straight line whose slope was in good agreement with that of the electrochemical leaching. These findings strongly support the electrochemical mechanism of chalcopyrite leaching with cupric chloride.

  13. Ferric Chloride-induced Murine Thrombosis Models.

    PubMed

    Li, Wei; Nieman, Marvin; Sen Gupta, Anirban

    2016-01-01

    Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and chronic autoimmune rheumatologic disorders. Thrombi are the cause of most heart attacks, strokes and extremity loss, making thrombosis an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation and subsequent coagulation, targeting these systems therapeutically has important clinical significance for developing safer treatments. Due to the complexities of the hemostatic system, in vitro experiments cannot replicate the blood-to-vessel wall interactions; therefore, in vivo studies are critical to understand pathological mechanisms of thrombus formation. To this end, various thrombosis models have been developed in mice. Among them, ferric chloride (FeCl3) induced vascular injury is a widely used model of occlusive thrombosis that reports platelet activation and aggregation in the context of an aseptic closed vascular system. This model is based on redox-induced endothelial cell injury, which is simple and sensitive to both anticoagulant and anti-platelets drugs. The time required for the development of a thrombus that occludes blood flow gives a quantitative measure of vascular injury, platelet activation and aggregation that is relevant to thrombotic diseases. We have significantly refined this FeCl3-induced vascular thrombosis model, which makes the data highly reproducible with minimal variation. Here we describe the model and present representative data from several experimental set-ups that demonstrate the utility of this model in thrombosis research. PMID:27684194

  14. Chloride Regulation in the Pain Pathway

    PubMed Central

    Price, Theodore J; Cervero, Fernando; Gold, Michael S; Hammond, Donna L; Prescott, Steven A

    2009-01-01

    Melzack and Wall’s Gate Control Theory of Pain laid the theoretical groundwork for a role of spinal inhibition in endogenous pain control. While the Gate Control Theory was based on the notion that spinal inhibition is dynamically regulated, mechanisms underlying the regulation of inhibition have turned out to be far more complex than Melzack and Wall could have ever imagined. Recent evidence indicates that an exquisitely sensitive form of regulation involves changes in anion equilibrium potential (Eanion), which subsequently impacts fast synaptic inhibition mediated GABAA, and to a lesser extent, glycine receptor activation, the prototypic ligand gated anion channels. The cation-chloride co-transporters (in particular NKCC1 and KCC2) have emerged as proteins that play a critical role in the dynamic regulation of Eanion which in turn appears to play a critical role in hyperalgesia and allodynia following peripheral inflammation or nerve injury. This review summarizes the current state of knowledge in this area with particular attention to how such findings relate to endogenous mechanisms of hyperalgesia and allodynia and potential applications for therapeutics based on modulation of intracellular Cl− gradients or pharmacological interventions targeting GABAA receptors PMID:19167425

  15. Chloride, bromide and iodide scintillators with europium

    DOEpatents

    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.

  16. Processing of mercurous chloride in reduced gravity

    SciTech Connect

    Watson, C.; Thomas, A.

    1996-12-31

    In a joint experiment between the Northrop-Grumman Science and Technology Center and the University of Alabama in Huntsville, Consortium for Materials Development in Space (UAH/CMDS), single crystals of mercurous chloride (Hg{sub 2}Cl{sub 2}) were grown in the Space Experiment Facility (SEF) transparent furnace that was flown on Spacelab 4 (STS-77) in May 1996. Single crystals of this material can be readily grown in normal gravity by closed-tube physical vapor transport, but the crystals generally contain structural inhomogeneities which degrade the optical performance. The nature and cause of these defects are not completely understood, but their degree appears to correlate with the Rayleigh number that characterizes the convective transport during their growth; hence, it is suspected that uncontrolled convection may play a role in the defect structure. The objective of the flight experiment was to reduce the convective flows by several orders of magnitude to see if the structural inhomogeneities can be reduced or eliminated. This paper will describe the physical and thermal properties of the SEF furnace, the ampoule design and loading procedure, and the ground testing, and will also present the preliminary flight results.

  17. Kinetics of radiational hydrosilylation of vinyl chloride by methyldichlorosilane

    SciTech Connect

    Bryantseva, N.V.; Lugovoi, Yu.M.; Garsiya, I.K.; Shostenko, A.G.

    1988-03-01

    The main product of the radiational interaction of methyldichlorosilane with vinyl chloride is 2-chloroethylmethyldichlorosilane, formed according to a radical-chain addition scheme. The energy of activation of the addition reaction of the methyldichlorosilyl radical to vinyl chloride is 14 +/- 4 kJ/mole. Its low value is explained by the p..pi..-d..pi.. interaction in the transition state of the reaction. This interaction also explains the similar values of the energies of activation of the radical addition reactions of methyldichlorosilane to 1-hexene and vinyl chloride.

  18. Acid copper sulfate plating bath: Control of chloride and copper

    SciTech Connect

    Borhani, K.J.

    1992-08-01

    Plated-through holes in high-reliability printed wiring boards require a ductile copper plate of uniform consistency. The level of control of the chemical constituents in the electroplating solutions dictates the physical properties of the copper plate. To improve the control of the chemical bath constituents, in-situ methods for electrochemically determining copper and chloride in acid copper sulfate baths were developed. A solid-state ion-selective electrode was used for the chloride ion and proved to be more reproducible than conventional silver chloride turbidimetric methods. The use of a copper solid-state ion-selective electrode in-situ was also successful in this application.

  19. Aggregate influence on chloride ion diffusion into concrete

    SciTech Connect

    Hobbs, D.W.

    1999-12-01

    An attempt is made to predict the probable effect of the aggregate on chloride ion diffusion into saturated concrete. It is shown that if the chloride ion diffusion coefficient of an aggregate ranges from 0.2 to 10 times that of the cement past matrix, then this could result in variations in the concrete chloride ion diffusion coefficient of up to 10:1. Such a variation is equivalent to a change in free water-cement ration from 0.77 to 0.45.

  20. Copper Chloride Cathode For Liquid-Sodium Cell

    NASA Technical Reports Server (NTRS)

    Bugga, Ratnakumar V.; Distefano, Salvador; Nagasubramanian, Ganesan; Bankston, Clyde P.

    1990-01-01

    Rechargeable liquid-sodium cell with copper chloride cathode offers substantial increase in energy density over cells made with other cathode materials. Unit has theoretical maximum energy density of 1135 W.h/kg. Generates electricity by electrochemical reaction of molten sodium and solid copper chloride immersed in molten electrolyte, sodium tetrachloroaluminate at temperature of equal to or greater than 200 degrees C. Wall of alumina tube separates molten electrolyte from molten sodium anode. Copper chloride cathode embedded in pores of sintered nickel cylinder or directly sintered.

  1. Method for the production of uranium chloride salt

    DOEpatents

    Westphal, Brian R.; Mariani, Robert D.

    2013-07-02

    A method for the production of UCl.sub.3 salt without the use of hazardous chemicals or multiple apparatuses for synthesis and purification is provided. Uranium metal is combined in a reaction vessel with a metal chloride and a eutectic salt- and heated to a first temperature under vacuum conditions to promote reaction of the uranium metal with the metal chloride for the production of a UCl.sub.3 salt. After the reaction has run substantially to completion, the furnace is heated to a second temperature under vacuum conditions. The second temperature is sufficiently high to selectively vaporize the chloride salts and distill them into a condenser region.

  2. The ionic product of water in concentrated tetramethylammonium chloride solutions.

    PubMed

    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.

  3. Urinary thiodiglycolic acid levels for vinyl chloride monomer-exposed polyvinyl chloride workers.

    PubMed

    Cheng, T J; Huang, Y F; Ma, Y C

    2001-11-01

    Thiodiglycolic acid (TdGA) is the major metabolite of vinyl chloride monomer (VCM) detected in human urine. Although urinary TdGA has been reported to be associated with ambient VCM exposure, the relationship between urinary TdGA and a low level of air VCM is not clear. Questionnaires were administered to 16 polyvinyl chloride manufacturing workers to obtain a detailed history of occupation and lifestyle. For each worker, personal air monitoring for VCM was performed and a time-weighted average for VCM exposure was calculated. The urinary TdGA levels at the end of a work shift, and at the commencement of the next shift, were also assessed for each worker. Urine analysis revealed that TdGA levels at the beginning of the next shift were higher than those at the end of that shift. Workers experiencing a VCM exposure greater than 5 ppm in air revealed a urinary TdGA level significantly greater than those experiencing a VCM exposure of less than 5 ppm (P < 0.05). The best fit of regression for urinary TdGA on air VCM was Y = 1.06 + 0.57X for urine collected at the commencement of the following work shift, where X is the air VCM concentration and Y is the urinary TdGA concentration (r2 = 0.65, P < 0.01). We conclude that the urinary TdGA level is best detected at the commencement of the next shift and that it can be used as an exposure marker for polyvinyl chloride workers when the air VCM level to which they are exposed is greater than 5 ppm.

  4. Molecular dynamics simulations of threadlike cetyltrimethylammonium chloride micelles: effects of sodium chloride and sodium salicylate salts.

    PubMed

    Wang, Zuowei; Larson, Ronald G

    2009-10-22

    We use atomistic molecular dynamics simulations to probe the effects of added sodium chloride (NaCl) and sodium salicylate (NaSal) salts on the spherical-to-threadlike micelle shape transition in aqueous solutions of cetyltrimethylammonium chloride (CTAC) surfactants. Long threadlike micelles are found to be unstable and break into spherical micelles at low concentrations of NaCl, but remain stable for 20 ns above a threshold value of [NaCl] approximately 3.0 M, which is about 2.5 times larger than the experimental salt concentration at which the transition between spherical and rodlike micelles occurs. The chloride counterions associate weakly on the surface of the CTAC micelles with the degree of counterion dissociation decreasing slightly with increasing [NaCl] on spherical micelles, but dropping significantly on the threadlike micelles at high [NaCl]. This effect indicates that the electrolyte ions drive the micellar shape transition by screening the electrostatic repulsions between the micellar headgroups. The aromatic salicylate counterions, on the other hand, penetrate inside the micelle with their hydrophilic groups staying in the surfactant headgroup region and the hydrophobic groups partially embedded into the hydrophobic core of the micelle. The strong association of the salicylate ions with the surfactant headgroups leads to dense packing of the surfactant molecules, which effectively reduces the surface area per surfactant, and increases intramicellar ordering of the surfactant headgroups, favoring the formation of long threadlike micelles. Simulation predictions of the geometric and electrostatic properties of the spherical and threadlike micelles are in good agreement with experiments.

  5. A Synthetic Chloride Channel Restores Chloride Conductance in Human Cystic Fibrosis Epithelial Cells

    PubMed Central

    Wang, Fei; Yao, Xiaoqiang; Yang, Dan

    2012-01-01

    Mutations in the gene-encoding cystic fibrosis transmembrane conductance regulator (CFTR) cause defective transepithelial transport of chloride (Cl−) ions and fluid, thereby becoming responsible for the onset of cystic fibrosis (CF). One strategy to reduce the pathophysiology associated with CF is to increase Cl− transport through alternative pathways. In this paper, we demonstrate that a small synthetic molecule which forms Cl− channels to mediate Cl− transport across lipid bilayer membranes is capable of restoring Cl− permeability in human CF epithelial cells; as a result, it has the potential to become a lead compound for the treatment of human diseases associated with Cl− channel dysfunction. PMID:22514656

  6. The management of Frey's syndrome with aluminium chloride hexahydrate antiperspirant.

    PubMed Central

    Black, M. J.; Gunn, A.

    1990-01-01

    Nine patients suffering from gustatory sweating (Frey's syndrome) following parotidectomy have been treated by topical applications of aluminium chloride hexahydrate. Treatment has successfully controlled gustatory sweating using application intervals varying from 1 to 50 days. Images Figure 1 PMID:2301903

  7. [Biochemical changes in rats under the influence of cesium chloride].

    PubMed

    Mel'nykova, N M; Iermishev, O V

    2013-01-01

    Cesium is lately accumulated actively in the environment, but its influence on human and animal organism is the least studied among heavy metals. It is shown that the action of cesium chloride in rats caused significant changes in blood chemistry, which are characterized by a decrease of total protein content, pH, an increase in the level of urea, creatinine, glucose and total hemoglobin. The results showed that potassium content in all the studied organs and tissues of poisoned rats decreases under the action of cesium chloride. Histological examination of the heart tissue in rats poisoned with cesium chloride indicates the onset of pathology of cardiovascular system. It was found out that use of the drug "Asparkam" reduces the negative effect of cesium chloride on the body of rats.

  8. Vinyl chloride removal from an air stream by biotrickling filter.

    PubMed

    Faraj, S H Esmaeili; Esfahany, M Nasr; Kadivar, M; Zilouei, H

    2012-01-01

    A biofiltration process was used for degradation of vinyl chloride as a hazardous material in the air stream. Three biotrickling filters in series-parallel allowing uniform feed and moisture distribution all over the bed were used. Granular activated carbon mixed with compost was employed as carrier bed. The biological culture consisted of mixture of activated sludge from PVC wastewater treatment plant. Concurrent flow of gas and liquid was used in the bed. Results indicated that during the operation period of 110 days, the biotrickling bed was able to remove over 35% of inlet vinyl chloride. Maximum elimination capacity was calculated to be 0.56 g.m(-3).hr(-1). The amount of chlorine accumulated in the circulating liquid due to the degradation of vinyl chloride was measured to be equal to the vinyl chloride removed from the air stream.

  9. Electrical, thermal and abusive tests on lithium thionyl chloride cells

    NASA Technical Reports Server (NTRS)

    Frank, H. A.

    1980-01-01

    Electrical characterizations, thermal characterizations, and outer limits tests of lithium thionyl chloride cells are discussed. Graphs of energy density vs power density and heat rate vs time are presented along with results of forced reversal and high rate discharge tests.

  10. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats.

    PubMed Central

    Smith, D F

    1976-01-01

    1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion. PMID:1260219

  11. Electrolysis of dilute sodium chloride solution in a diaphragm cell

    SciTech Connect

    Kubasov, V.L.; Ivanter, I.A.; Druzhinin, E.A.; Vorob'eva, V.B.

    1986-02-10

    In some cases, as in the production of iodine and bromine, dilute solutions of sodium chloride remain unutilized. In view of the existence of large amounts of unutilized spent sodium chloride solutions and their harmful effect when discharged into the environment, it is desirable to develop a process for production of chlorine and alkali with high current efficiencies, satisfying industrial requirements, from dilute sodium chloride solutions. The authors have therefore studied electrolysis of solutions containing 160 and 180 kg/m/sup 3/ of sodium chloride, having pH of 11.0-11.5, close in composition to solutions from the Cheleken chemical factory. The chlorine and alkali current efficiencies and the compositions of the anolyte, catholyte, and anode gas were determined.

  12. Chloride supporting electrolytes for all-vanadium redox flow batteries.

    PubMed

    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

  13. Tested Demonstrations. A Chemiluminescence Demonstration - Oxalyl Chloride Oxidation.

    ERIC Educational Resources Information Center

    Gilber, George L., Ed.

    1979-01-01

    This inexpensive, effective chemiluminescence demonstration requires minimal preparation. It is based on the oxidation of oxalyl chloride by hydrogen peroxide in the presence of an appropriate fluorescent sensitizer. The reaction mechanism is not completely understood. (BB)

  14. Automatic electrochemical ambient air monitor for chloride and chlorine

    DOEpatents

    Mueller, Theodore R.

    1976-07-13

    An electrochemical monitoring system has been provided for determining chloride and chlorine in air at levels of from about 10-1000 parts per billion. The chloride is determined by oxidation to chlorine followed by reduction to chloride in a closed system. Chlorine is determined by direct reduction at a platinum electrode in 6 M H.sub.2 SO.sub.4 electrolyte. A fully automated system is utilized to (1) acquire and store a value corresponding to electrolyte-containing impurities, (2) subtract this value from that obtained in the presence of air, (3) generate coulometrically a standard sample of chlorine mixed with air sample, and determine it as chlorine and/or chloride, and (4) calculate, display, and store for permanent record the ratio of the signal obtained from the air sample and that obtained with the standard.

  15. Thermodynamic calculation of self-diffusion in sodium chloride

    NASA Astrophysics Data System (ADS)

    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.

  16. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats.

    PubMed

    Smith, D F

    1976-04-01

    1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion. PMID:1260219

  17. Chloride supporting electrolytes for all-vanadium redox flow batteries.

    PubMed

    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.

  18. SUBSTITUTION OF CADMIUM CYANIDE ELECTROPLATING WITH ZINC CHLORIDE ELECTROPLATING

    EPA Science Inventory

    The study evaluated the zinc chloride electroplating process as a substitute for cadmium cyanide electroplating in the manufacture of industrial connectors and fittings at Aeroquip Corporation. The process substitution eliminates certain wastes, specifically cadmium and cyanide, ...

  19. Heterogeneous Reaction gaseous chlorine nitrate and solid sodium chloride

    NASA Technical Reports Server (NTRS)

    Timonen, Raimo S.; Chu, Liang T.; Leu, Ming-Taun

    1994-01-01

    The heterogeneous reaction of gaseous chlorine nitrate and solid sodium chloride was investigated over a temperature range of 220 - 300 K in a flow-tube reactor interfaced with a differentially pumped quadrupole mass spectrometer.

  20. Vinyl chloride: still a cause for concern.

    PubMed Central

    Kielhorn, J; Melber, C; Wahnschaffe, U; Aitio, A; Mangelsdorf, I

    2000-01-01

    Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL. Images Figure 1 Figure 2 PMID:10905993