WorldWideScience

Sample records for channel sulfonylurea sensitivity

  1. Human α-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel: Molecular cloning, expression and biological properties

    OpenAIRE

    Heron, Lisa; Virsolvy, Anne; Peyrollier, Karine; Gribble, Fiona M.; Le Cam, Alphonse; Ashcroft, Frances M.; Bataille, Dominique

    1998-01-01

    Sulfonylureas are a class of drugs commonly used in the management of non-insulin-dependent diabetes mellitus. Their therapeutic action results primarily from their ability to inhibit ATP-sensitive potassium (KATP) channels in the plasma membrane of pancreatic β cells and thereby stimulate insulin release. A key question is whether an endogenous ligand for the KATP channel exists that is able to mimic the inhibitory effects of sulfonylureas. We describe here the cloning of the cDNA encoding h...

  2. Mice lacking sulfonylurea receptor 2 (SUR2) ATP sensitive potassium channels are resistant to acute cardiovascular stress

    OpenAIRE

    Stoller, Douglas; Kakkar, Rahul; Smelley, Matthew; Chalupsky, Karel; Earley, Judy U.; Shi, Nian-Qing; Makielski, Jonathan C.; McNally, Elizabeth M.

    2007-01-01

    Adenosine triphosphate sensitive potassium (KATP) channels are thought to mediate stress response by sensing intracellular ATP concentration. Cardiomyocyte KATP channels are composed of the pore-forming Kir6.2 subunit and the regulatory sulfonylurea receptor 2 (SUR2). We studied the response to acute isoproterenol in SUR2 null mice as a model of acute adrenergic stress and found that the episodic coronary vasospasm observed at baseline in SUR2 null mice was alleviated. Similar results were ob...

  3. ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone

    International Nuclear Information System (INIS)

    The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide names from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and 86Rb+ flux techniques. Galanin hyperpolarizes and reduces spontaneous electrical activity by activating a population of APT-sensitive K+ channels with a single-channel conductance of 30 pS (at -60 mV). Galanin-induced hyperpolarization and reduction of spike activity are reversed by the hypoglycemia-inducing sulfonylurea glibenclamine. Glibenclamide blocks the galanin-activated ATP-sensitive K+ channel. 86Rb+ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. The half-maximum value of activation is found at 1.6 nM. Galanin-induced 86Rb+ efflux is abolished by glibenclamide. The half-maximum value of inhibition is found at 0.3 nM, which is close to the half-maximum value of inhibition of the ATP-dependent K+ channel reported earlier. 86Rb+ efflux studies confirm the electrophysiological demonstration that galanin activates and ATP-dependent K+ channel

  4. Phosphatidylinositol 4,5-biphosphate (PIP2) modulates syntaxin-1A binding to sulfonylurea receptor 2A to regulate cardiac ATP-sensitive potassium (KATP) channels.

    Science.gov (United States)

    Xie, Li; Liang, Tao; Kang, Youhou; Lin, Xianguang; Sobbi, Roozbeh; Xie, Huanli; Chao, Christin; Backx, Peter; Feng, Zhong-Ping; Shyng, Show-Ling; Gaisano, Herbert Y

    2014-10-01

    Cardiac sarcolemmal syntaxin (Syn)-1A interacts with sulfonylurea receptor (SUR) 2A to inhibit ATP-sensitive potassium (KATP) channels. Phosphatidylinositol 4,5-bisphosphate (PIP2), a ubiquitous endogenous inositol phospholipid, known to bind Kir6.2 subunit to open KATP channels, has recently been shown to directly bind Syn-1A in plasma membrane to form Syn-1A clusters. Here, we sought to determine whether the interaction between Syn-1A and PIP2 interferes with the ability of Syn-1A to bind SUR2A and inhibit KATP channel activity. We found that PIP2 dose-dependently reduced SUR2A binding to GST-Syn-1A by in vitro pulldown assays. FRET studies in intact cells using TIRFM revealed that increasing endogenous PIP2 levels led to increased Syn-1A (-EGFP) cluster formation and a severe reduction in availability of Syn-1A molecules to interact with SUR2A (-mCherry) molecules outside the Syn-1A clusters. Correspondingly, electrophysiological studies employing SUR2A/Kir6.2-expressing HEK cells showed that increasing endogenous or exogenous PIP2 diminished the inhibitory effect of Syn-1A on KATP currents. The physiological relevance of these findings was confirmed by ability of exogenous PIP2 to block exogenous Syn-1A inhibition of cardiac KATP currents in inside-out patches of mouse ventricular myocytes. The effect of PIP2 on physical and functional interactions between Syn-1A and KATP channels is specific and not observed with physiologic concentrations of other phospholipids. To unequivocally demonstrate the specificity of PIP2 interaction with Syn-1A and its impact on KATP channel modulation by Syn-1A, we employed a PIP2-insensitive Syn-1A-5RK/A mutant. The Syn-1A-5RK/A mutant retains the ability to interact with SUR2A in both in vitro binding and in vivo FRET assays, although as expected the interaction is no longer disrupted by PIP2. Interestingly, at physiological PIP2 concentrations, Syn-1A-5RK/A inhibited KATP currents to a greater extent than Syn-1A-WT, indicating

  5. Sulfonylureas suppress the stimulatory action of Mg-nucleotides on Kir6.2/SUR1 but not Kir6.2/SUR2A KATP channels: A mechanistic study

    OpenAIRE

    Proks, Peter; de Wet, Heidi; Ashcroft, Frances M

    2014-01-01

    Sulfonylureas, which stimulate insulin secretion from pancreatic β-cells, are widely used to treat both type 2 diabetes and neonatal diabetes. These drugs mediate their effects by binding to the sulfonylurea receptor subunit (SUR) of the ATP-sensitive K+ (KATP) channel and inducing channel closure. The mechanism of channel inhibition is unusually complex. First, sulfonylureas act as partial antagonists of channel activity, and second, their effect is modulated by MgADP. We analyzed the molecu...

  6. ATP-sensitive K/sup +/ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone

    Energy Technology Data Exchange (ETDEWEB)

    de Weille, J.; Schmid-Antomarchi, H.; Fosset, M.; Lazdunski, M.

    1988-02-01

    The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide names from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and /sup 86/Rb/sup +/ flux techniques. Galanin hyperpolarizes and reduces spontaneous electrical activity by activating a population of APT-sensitive K/sup +/ channels with a single-channel conductance of 30 pS (at -60 mV). Galanin-induced hyperpolarization and reduction of spike activity are reversed by the hypoglycemia-inducing sulfonylurea glibenclamine. Glibenclamide blocks the galanin-activated ATP-sensitive K/sup +/ channel. /sup 86/Rb/sup +/ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. The half-maximum value of activation is found at 1.6 nM. Galanin-induced /sup 86/Rb/sup +/ efflux is abolished by glibenclamide. The half-maximum value of inhibition is found at 0.3 nM, which is close to the half-maximum value of inhibition of the ATP-dependent K/sup +/ channel reported earlier. /sup 86/Rb/sup +/ efflux studies confirm the electrophysiological demonstration that galanin activates and ATP-dependent K/sup +/ channel.

  7. Optical control of insulin release using a photoswitchable sulfonylurea

    OpenAIRE

    Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C.; Frank, James A.; Marchetti, Piero; Bugliani, Marco; Shapiro, A. M. James; Trapp, Stefan; Rutter, Guy A.; Hodson, David J.; Trauner, Dirk

    2014-01-01

    Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which...

  8. Sulfonylureas suppress the stimulatory action of Mg-nucleotides on Kir6.2/SUR1 but not Kir6.2/SUR2A KATP channels: a mechanistic study.

    Science.gov (United States)

    Proks, Peter; de Wet, Heidi; Ashcroft, Frances M

    2014-11-01

    Sulfonylureas, which stimulate insulin secretion from pancreatic β-cells, are widely used to treat both type 2 diabetes and neonatal diabetes. These drugs mediate their effects by binding to the sulfonylurea receptor subunit (SUR) of the ATP-sensitive K(+) (KATP) channel and inducing channel closure. The mechanism of channel inhibition is unusually complex. First, sulfonylureas act as partial antagonists of channel activity, and second, their effect is modulated by MgADP. We analyzed the molecular basis of the interactions between the sulfonylurea gliclazide and Mg-nucleotides on β-cell and cardiac types of KATP channel (Kir6.2/SUR1 and Kir6.2/SUR2A, respectively) heterologously expressed in Xenopus laevis oocytes. The SUR2A-Y1206S mutation was used to confer gliclazide sensitivity on SUR2A. We found that both MgATP and MgADP increased gliclazide inhibition of Kir6.2/SUR1 channels and reduced inhibition of Kir6.2/SUR2A-Y1206S. The latter effect can be attributed to stabilization of the cardiac channel open state by Mg-nucleotides. Using a Kir6.2 mutation that renders the KATP channel insensitive to nucleotide inhibition (Kir6.2-G334D), we showed that gliclazide abolishes the stimulatory effects of MgADP and MgATP on β-cell KATP channels. Detailed analysis suggests that the drug both reduces nucleotide binding to SUR1 and impairs the efficacy with which nucleotide binding is translated into pore opening. Mutation of one (or both) of the Walker A lysines in the catalytic site of the nucleotide-binding domains of SUR1 may have a similar effect to gliclazide on MgADP binding and transduction, but it does not appear to impair MgATP binding. Our results have implications for the therapeutic use of sulfonylureas. PMID:25348414

  9. A Bentazon and Sulfonylurea-sensitive Mutant in Rice and its Application in Hybrid Rice

    International Nuclear Information System (INIS)

    A rice bentazon-lethal mutant 8077S obtained by radiation, is being utilized in developing new hybrid rice systems. Genetic analysis revealed that the bentazon-lethal mutant was controlled by a single recessive gene, which is named bel. The mutant can be killed at the seedling stage by bentazon with a lethal dosage at 300 mg/l or above, while this dosage is safe for its F1 hybrids and all other normal rice. This mutant is also sensitive to all the tested sulfonylurea herbicides and this sensitivity is also controlled by bel. Interestingly, another rice bentazon-lethal mutant Norin8m also obtained by radiation in Japan, was controlled by the allelic locus of bel, which is named as bsl. These two mutant genes were cloned by map-based cloning. Both mutant alleles had a single-base deletion respectively. There is a G deletion in the bel. and a C deletion in the bsl. The wild-type gene bel. encodes a novel cytochrome P450 monooxgenase, named CYP81A6. Otherwise, the use of photo-thermogenic male sterility (P/TGMS) system in two-line hybrid rice breeding is affected greatly by the sterility instability of P/TGMS lines caused by temperature fluctuation beyond their critical temperatures for fertility reversion. To prevent the hybrid seed contamination, we have developed three bentazon-lethal P/TGMS lines using 8077S by backcross and three new hybrid rice varieties using these P/TGMS lines had been registered. When these P/TGMS lines selfed by temperature fluctuation, the seedlings from the selfed seeds can be killed by spraying bentazon at seedling stage but the hybrid seedlings are safety. These new hybrid rice varieties have been cultivated in five provinces in China. (author)

  10. Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

    OpenAIRE

    Park, Jeong-Kwon; Kim, Sang-Pyo; Song, Dae-Kyu

    2008-01-01

    OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity i...

  11. Glucose modulates rat substantia nigra GABA release in vivo via ATP-sensitive potassium channels.

    OpenAIRE

    During, M J; Leone, P.; Davis, K. E.; Kerr, D; Sherwin, R S

    1995-01-01

    Glucose modulates beta cell insulin secretion via effects on ATP-sensitive potassium (KATP) channels. To test the hypothesis that glucose exerts a similar effect on neuronal function, local glucose availability was varied in awake rats using microdialysis in the substantia nigra, the brain region with the highest density of KATP channels. 10 mM glucose perfusion increased GABA release by 111 +/- 42%, whereas the sulfonylurea, glipizide, increased GABA release by 84 +/- 20%. In contrast, perfu...

  12. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations

    DEFF Research Database (Denmark)

    Pearson, Ewan R; Flechtner, Isabelle; Njølstad, Pål R;

    2006-01-01

    BACKGROUND: Heterozygous activating mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, cause 30 to 58 percent of cases of diabetes diagnosed in patients under six months of age. Patients present with ketoacidosis or severe hyperglycemia and are treated...... with insulin. Diabetes results from impaired insulin secretion caused by a failure of the beta-cell K(ATP) channel to close in response to increased intracellular ATP. Sulfonylureas close the K(ATP) channel by an ATP-independent route. METHODS: We assessed glycemic control in 49 consecutive patients with Kir6...... insulin secretion only in the presence of sulfonylureas. CONCLUSIONS: Sulfonylurea therapy is safe in the short term for patients with diabetes caused by KCNJ11 mutations and is probably more effective than insulin therapy. This pharmacogenetic response to sulfonylureas may result from the closing...

  13. ATP-sensitive K(+) channels in rat colonic epithelium.

    Science.gov (United States)

    Pouokam, Ervice; Bader, Sandra; Brück, Brigitta; Schmidt, Bärbel; Diener, Martin

    2013-06-01

    ATP-sensitive K(+) (KATP) channels couple the metabolic state of a cell to its electrical activity. They consist of a hetero-octameric complex with pore-forming Kir6.x (Kir6.1, Kir6.2) and regulatory sulfonylurea receptor (SUR) subunits. Functional data indicate that KATP channels contribute to epithelial K(+) currents at colonic epithelia. However, their molecular identity and their properties are largely unknown. Therefore, changes in short-circuit current (I sc) induced by the KATP channel opener pinacidil (5 10(-4) mol l(-1)) were measured in Ussing chambers under control conditions and in the presence of different blockers of KATP channels. The channel subunits expressed by the colonic epithelium were identified by immunohistochemistry and by RT-PCR. The K(+) channel opener, when administered at the serosal side, induced an increase in I sc consistent with the induction of transepithelial Cl(-) secretion after activation of basolateral K(+) channels, whereas mucosal administration of pinacidil resulted in a negative I sc. The increase in I sc evoked by serosal pinacidil was inhibited by serosal administration of glibenclamide (5 10(-4) mol l(-1)) and gliclazide (10(-6) mol l(-1)), but was resistant even against a high concentration (10(-2) mol l(-1)) of tolbutamide. In contrast, none of these inhibitors (administered at the mucosal side) reduced significantly the negative I sc induced by mucosal pinacidil. Instead, pinacidil inhibited Cl(-) currents across apical Cl(-) channels in basolaterally depolarized epithelia indicating that the negative I sc induced by mucosal pinacidil is due to a transient inhibition of Cl(-) secretion. In mRNA prepared from isolated colonic crypts, messenger RNA for both pore-forming subunits, Kir6.1 and Kir6.2, and two regulatory subunits (SUR1 and SUR2B) was found. Expression within the colonic epithelium was confirmed for these subunits by immunohistochemistry. In consequence, KATP channels are present in the basolateral membrane

  14. Molecular determinants of ATP-sensitive potassium channel MgATPase activity: diabetes risk variants and diazoxide sensitivity.

    Science.gov (United States)

    Fatehi, Mohammad; Carter, Chris R J; Youssef, Nermeen; Hunter, Beth E; Holt, Andrew; Light, Peter E

    2015-01-01

    ATP-sensitive K(+) (KATP) channels play an important role in insulin secretion. KATP channels possess intrinsic MgATPase activity that is important in regulating channel activity in response to metabolic changes, although the precise structural determinants are not clearly understood. Furthermore, the sulfonylurea receptor 1 (SUR1) S1369A diabetes risk variant increases MgATPase activity, but the molecular mechanisms remain to be determined. Therefore, we hypothesized that residue-residue interactions between 1369 and 1372, predicted from in silico modelling, influence MgATPase activity, as well as sensitivity to the clinically used drug diazoxide that is known to increase MgATPase activity. We employed a point mutagenic approach with patch-clamp and direct biochemical assays to determine interaction between residues 1369 and 1372. Mutations in residues 1369 and 1372 predicted to decrease the residue interaction elicited a significant increase in MgATPase activity, whereas mutations predicted to possess similar residue interactions to wild-type (WT) channels elicited no alterations in MgATPase activity. In contrast, mutations that were predicted to increase residue interactions resulted in significant decreases in MgATPase activity. We also determined that a single S1369K substitution in SUR1 caused MgATPase activity and diazoxide pharmacological profiles to resemble those of channels containing the SUR2A subunit isoform. Our results provide evidence, at the single residue level, for a molecular mechanism that may underlie the association of the S1369A variant with type 2 diabetes. We also show a single amino acid difference can account for the markedly different diazoxide sensitivities between channels containing either the SUR1 or SUR2A subunit isoforms. PMID:26181369

  15. Mechanism of sulfonylurea herbicide resistance in the broadleaf weed, Kochia scoparia

    International Nuclear Information System (INIS)

    Selection of kochia (Kochia scoparia) biotypes resistant to the sulfonylurea herbicide chlorsulfuron has occurred through the continued use of this herbicide in monoculture cereal-growing areas in the United States. The apparent sulfonylurea resistance observed in kochia was confirmed in greenhouse tests. Fresh and dry weight accumulation in the resistance kochia was 2- to >350-fold higher in the presence of four sulfonylurea herbicides as compared to the susceptible biotype. Acetolactate synthase (ALS) activity isolated from sulfonylurea-resistant kochia was less sensitive to inhibition by three classes of ALS-inhibiting herbicides, sulfonylureas, imidazolinones, and sulfonanilides. The decrease in ALS sensitivity to inhibition (as measured by the ratio of resistant I50 to susceptible I50) was 5- to 28-fold, 2- to 6-fold, and 20-fold for sulfonylurea herbicides, imidazolinone herbicides, and a sulfonanilide herbicide, respectively. No differences were observed in the ALS-specific activities or the rates of [14C]chlorsulfuron uptake, translocation, and metabolism between susceptible and resistant kochia biotypes. The Km values for pyruvate using ALS from susceptible and resistant kochia were 2.13 and 1.74 mM, respectively. Based on these results, the mechanism of sulfonylurea resistance in this kochia biotype is due solely to a less sulfonylurea-sensitive ALS enzyme

  16. The G53D Mutation in Kir6.2 (KCNJ11) Is Associated with Neonatal Diabetes and Motor Dysfunction in Adulthood that Is Improved with Sulfonylurea Therapy

    OpenAIRE

    Koster, Joseph C.; Cadario, Francesco; Peruzzi, Cinzia; Colombo, Carlo; Colin G. Nichols; Barbetti, Fabrizio

    2007-01-01

    Context: Mutations in the Kir6.2 subunit (KCNJ11) of the ATP-sensitive potassium channel (KATP) underlie neonatal diabetes mellitus. In severe cases, Kir6.2 mutations underlie developmental delay, epilepsy, and neonatal diabetes (DEND). All Kir6.2 mutations examined decrease the ATP inhibition of KATP, which is predicted to suppress electrical activity in neurons (peripheral and central), muscle, and pancreas. Inhibitory sulfonylureas (SUs) have been used successfully to treat diabetes in pat...

  17. Regulation of ATP-sensitive K+ channels in insulinoma cells: Activation by somatostatin and protein kinase C and the role of cAMP

    International Nuclear Information System (INIS)

    The actions of somatostatin and of the phorbol ester 4β-phorbol 12-myristate 13-acetate (PMA) were studied in rat insulinoma (RINm5F) cells by electrophysiological and 86Rb+ flux techniques. Both PMA and somatostatin hyperpolarize insulinoma cells by activating ATP-sensitive K+ channels. The presence of intracellular GTP is required for the somatostatin effects. PMA- and somatostatin-induced hyperpolarization and channel activity are inhibited by the sulfonylurea glibenclamide. Glibenclamide-sensitive 86Rb+ efflux from insulinoma cells is stimulated by somatostatin in a dose-dependent manner (half maximal effect at 0.7 nM) and abolished by pertussis toxin pretreatment. Mutual roles of a GTP-binding protein, of protein kinase C, and of cAMP in the regulation of ATP-sensitive K+ channels are discussed

  18. Characterization of dihydropyridine-sensitive calcium channels

    International Nuclear Information System (INIS)

    The structural and regulatory properties of the dihydropyridine-sensitive calcium channel were studied by isolating protein components of the channel complex from both cardiac and skeletal muscle. Hydrodynamic characterization of the (+)-(3H)PN200-110-labeled cardiac calcium channel revealed that the protein components of the complex had a total molecular mass of 370,000 daltons, a Stokes radius of 86 angstrom, and a frictional ratio of 1.3. A technique is described for the rapid incorporation of the CHAPS solubilized skeletal muscle calcium channel complex into phospholipid vesicles. 45Ca2+ uptake into phospholipid vesicles containing calcium channels was inhibited by phenylalkalamine calcium antagonists. Wheat germ lectin followed by DEAE chromatography of the CHAPS solubilized complex resulted in the dissociation of regulatory components of the complex from channel components. The DEAE preparation gave rise to 45Ca2+ uptake that was not inhibited by verapamil but was inhibited by GTPgS activated G0. The inhibition of 45Ca2+ uptake by verapamil was restored by co-reconstitution of wash fractions from wheat germ lectin chromatography. Phosphorylation of polypeptides in this fraction by polypeptide-dependent protein kinase prevented the restoration of verapamil sensitivity. The partial purification of an endogenous skeletal muscle ADP-ribosyltransferase is also described. ADP-ribosylation of the α2 subunit of the calcium channel complex is enhanced by polylysine and inhibited by GTPγS, suggesting that regulation of this enzyme is under the control of GTP binding proteins. These results suggest a complex model, involving a number of different protein components, for calcium channel regulation in skeletal muscle

  19. Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones

    OpenAIRE

    Kyeong Won Lee; Yun Hyi Ku; Min Kim; Byung Yong Ahn; Sung Soo Chung; Kyong Soo Park

    2011-01-01

    Background Sulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARγ transcriptional activity and on the glucose uptake via PPARγ. Methods Transcription reporter assays using Cos7 cells were performed to determine...

  20. Sulfonylurea herbicides – methodological challenges in setting aquatic limit values

    DEFF Research Database (Denmark)

    Rosenkrantz, Rikke Tjørnhøj; Baun, Anders; Kusk, Kresten Ole

    Lemna spp. have been shown to be up to 1000 times more sensitive to some sulfonylurea herbicides (SUs) than the green alga (e.g., P. subcapitata) which is commonly used as a representative organism for aquatic primary producers in environmental risk assessments. When the compounds are evaluated...

  1. [Risk and benefit of sulfonylureas--their role in view of new treatment options for type 2 diabetes].

    Science.gov (United States)

    Rustenbeck, Ingo

    2016-02-01

    Currently, the therapy with oral antidiabetic drugs undergoes major changes. The use of sulfonylureas is in marked decline. The major argument in favor of newer oral antidiabetic drugs is the lower risk of hypoglycemia. At the present time however, it is unclear whether DDP4 inhibitors or SGLT2 inhibitors lead to better outcomes with respect to cardiovascular events and overall mortality. Most evidence on the therapeutic use of sulfonylureas has been gained with glibenclamide and to some degree sulfonylureas and glibenclamide have become synonymous. Since sulfonylureas vary considerably in their affinity for the K(ATP) channel subtypes and in their pharmacokinetic properties, the epidemiological evidence that outcomes tend to be less favorable with glibenclamide than with glimepiride or gliclazide has gained some attention. Beyond debate is the efficacy of metformin to diminish cardiovascular events in type 2 diabetes, probably due to effects beyond the lowering of blood glucose. PMID:26983335

  2. Mechanisms underlying KCNQ1channel cell volume sensitivity

    DEFF Research Database (Denmark)

    Hammami, Sofia

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

  3. Inhibition of ATP-sensitive potassium channels by haloperidol

    OpenAIRE

    Yang, Shi-Bing; Proks, Peter; Ashcroft, Frances M.; Rupnik, Marjan

    2004-01-01

    Chronic haloperidol treatment has been associated with an increased incidence of glucose intolerance and type-II diabetes mellitus. We studied the effects of haloperidol on native ATP-sensitive potassium (KATP) channels in mouse pancreatic β cells and on cloned Kir6.2/SUR1 channels expressed in HEK293 cells.The inhibitory effect of haloperidol on the KATP channel was not mediated via the D2 receptor signaling pathway, as both D2 agonists and antagonists blocked the channel.KATP currents were ...

  4. Running out of time: the decline of channel activity and nucleotide activation in adenosine triphosphate-sensitive K-channels.

    Science.gov (United States)

    Proks, Peter; Puljung, Michael C; Vedovato, Natascia; Sachse, Gregor; Mulvaney, Rachel; Ashcroft, Frances M

    2016-08-01

    KATP channels act as key regulators of electrical excitability by coupling metabolic cues-mainly intracellular adenine nucleotide concentrations-to cellular potassium ion efflux. However, their study has been hindered by their rapid loss of activity in excised membrane patches (rundown), and by a second phenomenon, the decline of activation by Mg-nucleotides (DAMN). Degradation of PI(4,5)P2 and other phosphoinositides is the strongest candidate for the molecular cause of rundown. Broad evidence indicates that most other determinants of rundown (e.g. phosphorylation, intracellular calcium, channel mutations that affect rundown) also act by influencing KATP channel regulation by phosphoinositides. Unfortunately, experimental conditions that reproducibly prevent rundown have remained elusive, necessitating post hoc data compensation. Rundown is clearly distinct from DAMN. While the former is associated with pore-forming Kir6.2 subunits, DAMN is generally a slower process involving the regulatory sulfonylurea receptor (SUR) subunits. We speculate that it arises when SUR subunits enter non-physiological conformational states associated with the loss of SUR nucleotide-binding domain dimerization following prolonged exposure to nucleotide-free conditions. This review presents new information on both rundown and DAMN, summarizes our current understanding of these processes and considers their physiological roles.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377720

  5. Differential polyamine sensitivity in inwardly rectifying Kir2 potassium channels.

    Science.gov (United States)

    Panama, Brian K; Lopatin, Anatoli N

    2006-03-01

    Recent studies have shown that Kir2 channels display differential sensitivity to intracellular polyamines, and have raised a number of questions about several properties of inward rectification important to the understanding of their physiological roles. In this study, we have carried out a detailed characterization of steady-state and kinetic properties of block of Kir2.1-3 channels by spermine. High-resolution recordings from outside-out patches showed that in all Kir2 channels current-voltage relationships display a 'crossover' effect upon change in extracellular K+. Experiments at different concentrations of spermine allowed for the characterization of two distinct shallow components of rectification, with the voltages for half-block negative (V1(1/2)) and positive (V2(1/2)) to the voltage of half-block for the major steep component of rectification (V0(1/2)). While V1(1/2) and V2(1/2) voltages differ significantly between Kir2 channels, they were coupled to each other according to the equation V1(1/2)-V2(1/2) = constant, strongly suggesting that similar structures may underlie both components. In Kir2.3 channels, the V2(1/2) was approximately 50 mV positive to V0(1/2), leading to a pattern of outward currents distinct from that of Kir2.1 and Kir2.2 channels. The effective valency of spermine block (Z0) was highest in Kir2.2 channels while the valencies in Kir2.1 and Kir2.3 channels were not significantly different. The voltage dependence of spermine unblock was similar in all Kir2 channels, but the rates of unblock were approximately 7-fold and approximately 16-fold slower in Kir2.3 channels than those in Kir2.1 and Kir2.2 when measured at high and physiological extracellular K+, respectively. In all Kir2 channels, the instantaneous phase of activation was present. The instantaneous phase was difficult to resolve at high extracellular K+ but it became evident and accounted for nearly 30-50% of the total current when recorded at physiological extracellular K

  6. Synthesis and Herbicidal Activity of Novel Sulfonylurea Derivatives

    Institute of Scientific and Technical Information of China (English)

    CAO Gang; WANG Mei-yi; WANG Ming-zhong; WANG Su-hua; LI Yong-hong; LI Zheng-ming

    2011-01-01

    Sulfonylurea herbicides have been applied worldwide in agriculture. Some sulfonylurea residues might exist in soil longer than that people expected. However, flupyrsulfuron-methyl-sodium which was firstly reported as a new 5-substituted sulfonylurea herbicide has less than one month residual life. Therefore, 5-substituted benzenesulfonylureas are potential molecules to regulate its residual situation. In order to develop new sulfonylurea derivatives,the substituent on the critical 5-posotion of the benzene ring was optimized. On the basis of our former work on sulfonylureas which contains a characteristic mono-substituted pyrimidine moiety, twenty-six new sulfonylurea derivatives were synthesized and their structures were confirmed by 1H NMR, 31p NMR and elemental analysis. The greenhouse bioassay tests show that some title compounds exhibit potent herbicidal activity.

  7. Voltage-Sensitive Ion Channels Biophysics of Molecular Excitability

    CERN Document Server

    Leuchtag, H. Richard

    2008-01-01

    Voltage-sensitive ion channels are macromolecules embedded in the membranes of nerve and muscle fibers of animals. Because of their physiological functions, biochemical structures and electrical switching properties, they are at an intersection of biology, chemistry and physics. Despite decades of intensive research under the traditional approach of gated structural pores, the relation between the structure of these molecules and their function remains enigmatic. This book critically examines physically oriented approaches not covered in other ion-channel books. It looks at optical and thermal as well as electrical data, and at studies in the frequency domain as well as in the time domain. Rather than presenting the reader with only an option of mechanistic models at an inappropriate pseudo-macroscopic scale, it emphasizes concepts established in organic chemistry and condensed state physics. The book’s approach to the understanding of these unique structures breaks with the unproven view of ion channels as...

  8. Heisenberg's Limit Phase Sensitivity in The Presence of Decoherence Channels

    OpenAIRE

    Nosraty, Farzam

    2015-01-01

    In the present study, time evolution of quantum Cramer-Rao bound of entangled N00N state, as phase sensitivity, is determined by the aid of quantum estimation theory in the presence decoherence channels. Also, the dynamic quantum process as decoherence approach is characterized by quantum fisher information flow and entanglement amount in order to distinguish between Markovian and Non-Markovian process. The comparison between quantum fisher information and quantum fisher information flow assi...

  9. Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones

    Directory of Open Access Journals (Sweden)

    Kyeong Won Lee

    2011-08-01

    Full Text Available BackgroundSulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ, one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARγ transcriptional activity and on the glucose uptake via PPARγ.MethodsTranscription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARγ transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 µM were used as treatment, and rosiglitazone at 1 and 10 µM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARγ were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 µM, glimepiride (100 µM or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake.ResultsSulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARγ transcriptional activity, gliquidone being the most potent PPARγ agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARγ transcriptional activity and glucose uptake were reduced compared to those after treatment with rosiglitazone alone. This competitive effect of glimepiride was observed only at high concentrations that are not achieved with clinical doses.ConclusionSulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARγ. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARγ agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations.

  10. Engineering vanilloid-sensitivity into the rat TRPV2 channel.

    Science.gov (United States)

    Zhang, Feng; Hanson, Sonya M; Jara-Oseguera, Andres; Krepkiy, Dmitriy; Bae, Chanhyung; Pearce, Larry V; Blumberg, Peter M; Newstead, Simon; Swartz, Kenton J

    2016-01-01

    The TRPV1 channel is a detector of noxious stimuli, including heat, acidosis, vanilloid compounds and lipids. The gating mechanisms of the related TRPV2 channel are poorly understood because selective high affinity ligands are not available, and the threshold for heat activation is extremely high (>50°C). Cryo-EM structures of TRPV1 and TRPV2 reveal that they adopt similar structures, and identify a putative vanilloid binding pocket near the internal side of TRPV1. Here we use biochemical and electrophysiological approaches to investigate the resiniferatoxin(RTx) binding site in TRPV1 and to explore the functional relationships between TRPV1 and TRPV2. Collectively, our results support the interaction of vanilloids with the proposed RTx binding pocket, and demonstrate an allosteric influence of a tarantula toxin on vanilloid binding. Moreover, we show that sensitivity to RTx can be engineered into TRPV2, demonstrating that the gating and permeation properties of this channel are similar to TRPV1. PMID:27177419

  11. Engineering vanilloid-sensitivity into the rat TRPV2 channel

    Science.gov (United States)

    Zhang, Feng; Hanson, Sonya M; Jara-Oseguera, Andres; Krepkiy, Dmitriy; Bae, Chanhyung; Pearce, Larry V; Blumberg, Peter M; Newstead, Simon; Swartz, Kenton J

    2016-01-01

    The TRPV1 channel is a detector of noxious stimuli, including heat, acidosis, vanilloid compounds and lipids. The gating mechanisms of the related TRPV2 channel are poorly understood because selective high affinity ligands are not available, and the threshold for heat activation is extremely high (>50°C). Cryo-EM structures of TRPV1 and TRPV2 reveal that they adopt similar structures, and identify a putative vanilloid binding pocket near the internal side of TRPV1. Here we use biochemical and electrophysiological approaches to investigate the resiniferatoxin(RTx) binding site in TRPV1 and to explore the functional relationships between TRPV1 and TRPV2. Collectively, our results support the interaction of vanilloids with the proposed RTx binding pocket, and demonstrate an allosteric influence of a tarantula toxin on vanilloid binding. Moreover, we show that sensitivity to RTx can be engineered into TRPV2, demonstrating that the gating and permeation properties of this channel are similar to TRPV1. DOI: http://dx.doi.org/10.7554/eLife.16409.001 PMID:27177419

  12. Applications of isotopic tracer in analysis of residual sulfonylurea herbicide

    International Nuclear Information System (INIS)

    The analysis technique of the agrochemical residue by isotopic tracer is significantly increased, and obtained substantial development. The progress of the isotopic analysis in four kinds of sulfonylurea herbicide residues was reviewed in this paper. (authors)

  13. Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

    Science.gov (United States)

    Leonard, C E; Bilker, W B; Brensinger, C M; Han, X; Flory, J H; Flockhart, D A; Gagne, J J; Cardillo, S; Hennessy, S

    2016-05-01

    Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia. PMID:26566262

  14. A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

    Science.gov (United States)

    Kajma, Anna; Szewczyk, Adam

    2012-10-01

    Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). PMID:22406520

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

    Science.gov (United States)

    Conforti, L; Millhorn, D E

    2000-01-01

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

  16. Impairment of skeletal muscle adenosine triphosphate–sensitive K+ channels in patients with hypokalemic periodic paralysis

    OpenAIRE

    Tricarico, Domenico; Servidei, Serenella; Tonali, Pietro; Jurkat-Rott, Karin; Camerino, Diana Conte

    1999-01-01

    The adenosine triphosphate (ATP)–sensitive K+ (KATP) channel is the most abundant K+ channel active in the skeletal muscle fibers of humans and animals. In the present work, we demonstrate the involvement of the muscular KATP channel in a skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle biopsies excised from three patients with HOPP carrying the R528H mutation of the dihydropyridin...

  17. Potentiation of Sulfonylurea Action by an EPAC-selective cAMP Analog in INS-1 Cells: Comparison of Tolbutamide and Gliclazide and a Potential Role for EPAC Activation of a 2-APB-sensitive Ca2+ Influx

    OpenAIRE

    Jarrard, Rachel E.; Wang, Yuchen; Salyer, Amy E.; Pratt, Evan P. S.; Soderling, Ian M.; Guerra, Marcy L.; Lange, Allison M.; Broderick, Hilary J.; Hockerman, Gregory H.

    2013-01-01

    Tolbutamide and gliclazide block the KATP channel Kir6.2/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells. We examined the ability of the EPAC-selective cAMP analog 8-pCPT-2′-O-Me-cAMP-AM to potentiate the action of these drugs and the mechanism that might account for it. Insulin secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1...

  18. Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, P.M.; Wohllk, N.; Huang, E. [Univ. of Texas, Houston, TX (United States)] [and others

    1996-09-01

    Familial persistent hyperinsulinemic hypoglycemia of infancy is a disorder of glucose homeostasis and is characterized by unregulated insulin secretion and profound hypoglycemia. Loss-of-function mutations in the second nucleotide-binding fold of the sulfonylurea receptor, a subunit of the pancreatic-islet {beta}-cell ATP-dependent potassium channel, has been demonstrated to be causative for persistent hyperinsulinemic hypoglycemia of infancy. We now describe three additional mutations in the first nucleotide-binding fold of the sulfonylurea-receptor gene. One point mutation disrupts the highly conserved Walker A motif of the first nucleotide-binding-fold region. The other two mutations occur in noncoding sequences required for RNA processing and are predicted to disrupt the normal splicing pathway of the sulfonylurea-receptor mRNA precursor. These data suggest that both nucleotide-binding-fold regions of the sulfortylurea receptor are required for normal regulation of {beta}-cell ATP-dependent potassium channel activity and insulin secretion. 32 refs., 4 figs., 1 tab.

  19. Phosphorylation-dependent changes in nucleotide binding, conformation, and dynamics of the first nucleotide binding domain (NBD1) of the sulfonylurea receptor 2B (SUR2B).

    Science.gov (United States)

    de Araujo, Elvin D; Alvarez, Claudia P; López-Alonso, Jorge P; Sooklal, Clarissa R; Stagljar, Marijana; Kanelis, Voula

    2015-09-11

    The sulfonylurea receptor 2B (SUR2B) forms the regulatory subunit of ATP-sensitive potassium (KATP) channels in vascular smooth muscle. Phosphorylation of the SUR2B nucleotide binding domains (NBD1 and NBD2) by protein kinase A results in increased channel open probability. Here, we investigate the effects of phosphorylation on the structure and nucleotide binding properties of NBD1. Phosphorylation sites in SUR2B NBD1 are located in an N-terminal tail that is disordered. Nuclear magnetic resonance (NMR) data indicate that phosphorylation of the N-terminal tail affects multiple residues in NBD1, including residues in the NBD2-binding site, and results in altered conformation and dynamics of NBD1. NMR spectra of NBD1 lacking the N-terminal tail, NBD1-ΔN, suggest that phosphorylation disrupts interactions of the N-terminal tail with the core of NBD1, a model supported by dynamic light scattering. Increased nucleotide binding of phosphorylated NBD1 and NBD1-ΔN, compared with non-phosphorylated NBD1, suggests that by disrupting the interaction of the NBD core with the N-terminal tail, phosphorylation also exposes the MgATP-binding site on NBD1. These data provide insights into the molecular basis by which phosphorylation of SUR2B NBD1 activates KATP channels. PMID:26198630

  20. Molecular physiology of pH-sensitive background K(2P) channels.

    Science.gov (United States)

    Lesage, Florian; Barhanin, Jacques

    2011-12-01

    Background K(2P) channels are tightly regulated by different stimuli including variations of external and internal pH. pH sensitivity relies on proton-sensing residues that influence channel gating and activity. Gene inactivation in the mouse is a revealing implication of K(2P) channels in many physiological functions ranging from hormone secretion to central respiratory adaptation. Surprisingly, only a few phenotypic traits of these mice have yet been directly related to the pH sensitivity of K(2P) channels. PMID:22170960

  1. SENSITIVE EFFECTS OF POTASSIUM AND CALCIUM CHANNEL BLOCKING AND ATP-SENSITIVE POTASSIUM CHANNEL ACTIVATORS ON SEMINAL VESICLE SMOOTH MUSCLE CONTRACTIONS

    Directory of Open Access Journals (Sweden)

    H SADRAEI

    2000-12-01

    Full Text Available Background. Seminal vesicle smooth muscle contraction is mediated through sympathetic and parasympathetic neurons activity. Although seminal vesicle plays an important role in male fertility, but little attention is given to mechanism involved in contraction of this organ.
    Methods. In this study effects of drugs which activate ATP - sensitive K channels and blockers of K and Ca channels were examined on contraction of guinea - pig isolated seminal vesicle due to electrical filled stimulation (EFS, noradrenaline, carbachol and KCI.
    Results. The K channel blocker tetraethyl ammonium potentate the EFS responses at all frequencies, while, the ATP - sensitive K channel inhibitor glibenclamide and the K channel opener levcromakalim, diazoxide, minoxidil and Ca channel blocker nifedipine all had relaxant effect on guinea - pig seminal vesicle.
    Discussion. This study indicate that activities of K and Ca channels is important in regulation of seminal vesicle contraction due to nerve stimulation, noradrenaline or carbachol.

  2. Portulaca oleracea inhibit vincristine induced peripheral neuropathy: involvement of ATP-sensitive K+ channels

    Directory of Open Access Journals (Sweden)

    L. Mohana Rupa

    2014-06-01

    Conclusion: The results of the present study reveal the antinociceptive effect of P. oleracea in vincristine induced peripheral neuropathy and involving ATP-sensitive potassium channels pathway. [Int J Basic Clin Pharmacol 2014; 3(3.000: 474-478

  3. Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis

    OpenAIRE

    1989-01-01

    The ability of glycolysis, oxidative phosphorylation, the creatine kinase system, and exogenous ATP to suppress ATP-sensitive K+ channels and prevent cell shortening were compared in patch-clamped single guinea pig ventricular myocytes. In cell-attached patches on myocytes permeabilized at one end with saponin, ATP-sensitive K+ channels were activated by removing ATP from the bath, and could be closed equally well by exogenous ATP or substrates for endogenous ATP production by glycolysis (wit...

  4. Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing Thiadiazol Moiety

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Thirteen novel sulfonylureas containing thiadiazole moiety were synthesized in a two-step reaction. Their structures were determined using IR, 1H NMR, HRFTMS, and elemental analysis. Herbicidal activities of these compounds were determined in the green house bio-assay. The results show that four compounds among them exhibit some activity toward four tested herbs.

  5. Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Schroll, Jeppe B; Wetterslev, Jørn;

    2014-01-01

    BACKGROUND: Guidelines recommend metformin as the first-line oral treatment for type 2 diabetes. We conducted a systematic review to assess whether the use of second- and third-generation sulfonylurea agents is associated with benefits and harms in terms of patient-important outcomes compared with...

  6. Gold nanoparticles embedded silicon channel biosensor for improved sensitivity

    Science.gov (United States)

    Chang, H. Y.; Arshad, M. K. Md.; M. Nuzaihan M., N.; Fathil, M. F. M.; Hashim, U.

    2016-07-01

    This project discusses the fabrication steps of a biosensor device on silicon-on-insulator (SOI) wafer. Conventional photolithography technique is used to fabricate the device. The gold nanoparticles (GNPs) are then used to enhance the sensitivity of the device. By incorporating the GNPs, it is expected to get higher current compared with the device without GNPs due to better conductivity of gold and higher volume-to-ratio. Hence, with the addition of GNPs, it may boost up the signal and enhance the sensitivity of the device.

  7. Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Hong-shuo SUN; Zhong-ping FENG

    2013-01-01

    ATP-sensitive potassium (KATP) channels are weak,inward rectifiers that couple metabolic status to cell membrane electrical activity,thus modulating many cellular functions.An increase in the ADP/ATP ratio opens KATP channels,leading to membrane hyperpolarization.KATP channels are ubiquitously expressed in neurons located in different regions of the brain,including the hippocampus and cortex.Brief hypoxia triggers membrane hyperpolarization in these central neurons.In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the KATP channels increases ischemic infarction,and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults.These findings provide the basis for a practical strategy whereby activation of endogenous KATP channels reduces cellular damage resulting from cerebral ischemic stroke.KATP channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future.

  8. Integrated cooling channels in position-sensitive silicon detectors

    CERN Document Server

    Andricek, L; Garcia, I; Gomis, P; Marinas, C; Ninkovic, J; Rosello, M Perello; Villarejo, M A; Vos, M

    2016-01-01

    We present an approach to construct position-sensitive silicon detectors with an integrated cooling circuit. Tests on samples demonstrate that a very modest liquid flow very effectively cool the devices up to a power dissipation of over 10~W/cm$^2$. The liquid flow is found to have a negligible impact on the mechanical performance. A finite-element simulation predicts the cooling performance to an accuracy of approximately 10~\\%.

  9. Receptor-mediated glutamate release from volume sensitive channels in astrocytes

    Science.gov (United States)

    Takano, Takahiro; Kang, Jian; Jaiswal, Jyoti K.; Simon, Sanford M.; Lin, Jane H.-C.; Yu, Yufei; Li, Yuxing; Yang, Jay; Dienel, Gerald; Zielke, H. Ronald; Nedergaard, Maiken

    2005-11-01

    Several lines of work have shown that astrocytes release glutamate in response to receptor activation, which results in a modulation of local synaptic activity. Astrocytic glutamate release is Ca2+-dependent and occurs in conjunction with exocytosis of glutamate containing vesicles. However, astrocytes contain a millimolar concentration of cytosolic glutamate and express channels permeable to small anions, such as glutamate. Here, we tested the idea that astrocytes respond to receptor stimulation by dynamic changes in cell volume, resulting in volume-sensitive channel activation, and efflux of cytosolic glutamate. Confocal imaging and whole-cell recordings demonstrated that astrocytes exhibited a transient Ca2+-dependent cell volume increase, which activated glutamate permeable channels. HPLC analysis revealed that glutamate was released in conjunction with other amino acid osmolytes. Our observations indicate that volume-sensitive channel may constitute a previously uncharacterized target for modulation of astrocyte-neuronal interactions. electrophysiology | exocytosis | neurotransmitters | osmolarity | synapses

  10. Estimating the Sensitivity of Mechanosensitive Ion Channels to Membrane Strain and Tension

    OpenAIRE

    Charras, G. T.; Williams, B. A.; Sims, S. M.; Horton, M.A.

    2004-01-01

    Bone adapts to its environment by a process in which osteoblasts and osteocytes sense applied mechanical strain. One possible pathway for the detection of strain involves mechanosensitive channels and we sought to determine their sensitivity to membrane strain and tension. We used a combination of experimental and computational modeling techniques to gain new insights into cell mechanics and the regulation of mechanosensitive channels. Using patch-clamp electrophysiology combined with video m...

  11. Research Note—A Comparison of Within-Household Price Sensitivity Across Online and Offline Channels

    OpenAIRE

    Junhong Chu; Pradeep Chintagunta; Javier Cebollada

    2008-01-01

    We use a unique data set to estimate the price sensitivities of households in online and offline shopping channels when the same households shop across channels. We observe households that shop interchangeably at the online and the offline stores in the same grocery chain and investigate their purchase behavior in specific product categories. Although nearly 90% of households in our sample shop both at online and offline stores, we find that, across 12 vastly different product categories, the...

  12. Dual Regulation of Voltage-Sensitive Ion Channels by PIP2

    Directory of Open Access Journals (Sweden)

    AldoARodríguez Menchaca

    2012-09-01

    Full Text Available Over the past 16 years, there has been an impressive number of ion channels shown to be sensitive to the major phosphoinositide in the plasma membrane, phosphatidilinositol 4,5-bisphosphate (PIP2. Among them are voltage-gated channels, which are crucial for both neuronal and cardiac excitability. Voltage-gated calcium (Cav channels were shown to be regulated bidirectionally by PIP2. On one hand, PIP2 stabilized their activity by reducing current rundown but on the other hand it produced a voltage-dependent inhibition by shifting the activation curve to more positive voltages. For voltage-gated potassium (Kv channels PIP2 was first shown to prevent N-type inactivation. Careful examination of the effects of PIP2 on the activation mechanism of Kv1.2 has shown a similar bidirectional regulation as in the Cav channels. The two effects could be distinguished kinetically, in terms of their sensitivities to PIP2 and by distinct molecular determinants. The rightward shift of the Kv1.2 voltage dependence implicated basic residues in the S4-S5 linker and was consistent with stabilization of the inactive state of the voltage sensor. A third type of a voltage-gated ion channel modulated by PIP2 is the hyperpolarization-activated cyclic nucleotide-gated (HCN channel. PIP2 has been shown to enhance the opening of HCN channels by shifting their voltage-dependent activation toward depolarized potentials. The sea urchin HCN channel, SpIH, showed again a PIP2-mediated bidirectional effect but in reverse order than the depolarization-activated Cav and Kv channels: a voltage-dependent potentiation, like the mammalian HCN channels, but also an inhibition of the cGMP-induced current activation. Just like the Kv1.2 channels, distinct molecular determinants underlied the PIP2 dual effects on SpIH channels. The dual regulation of these very different ion channels, all of which are voltage dependent, points to conserved mechanisms of regulation of these channels by PIP2.

  13. Study on the bioactivity changes of hydroxylated sulfonylureas derivatives: A possible metabolism

    Institute of Scientific and Technical Information of China (English)

    Shu Rong Ban; Cong Wei Niu; Wen Bin Chen; Zhi Hong Yu; Si Wu; Chen Wang; Zhen Xi

    2007-01-01

    Some new sulfonylureas and their hydroxylation products had been synthesized from 2-amino-4-methylpyrimidine. Their bioactivities against E. Coli AHAS Ⅱ in vitro were tested and the results indicated that the hydroxylation decreased the inhibition activities of sulfonylureas significantly. Subsequently herbicidal tests against stem-growth of barnyard grass and root-growth of rape confirmed the above conclusion. The preliminary molecular docking studies were also carried out to investigate the binding modes of non-hydroxylated and hydroxylated sulfonylureas with AHAS.

  14. [The use of gliclazide in individualized sulfonylurea therapy].

    Science.gov (United States)

    Winkler, Gábor

    2014-04-01

    In addition to the common blood glucose lowering effect, sulfonylurea compounds are different in many aspects from each other. Based on earlier findings the second generation gliclazide has special advantages within this group. Although the number of experimental and clinical observations on gliclazide is continuously increasing, these novel findings are not in the focus anymore due to the appearance of new antidiabetics. This article reviews recent experimental (effect on receptors, the absence of Epac2 activation, antioxidant properties, possible incentive of factors participating in beta-cell differentiation) and pharmacogenomic data, and compares them with clinical observations obtained from gliclazide treatment (hypoglycemias, parameters of cardiovascular outcome). The data underline the advantages of gliclazide, the highly pancreas-selective nature, preservation of the ischemic precondition, favourable hemodynamic properties and potential reduction of the beta-cell loss as compared to other compounds of the group. However, gliclazide is not free from disadvantages characteristic to sulfonylureas in general (blood glucose independent insulin stimulation, beta-cell depletion). Comparing gliclazide with other derivatives of the group, the above data indicate individual benefits for the application when sulfonylurea compound is the drug of choice. PMID:24681676

  15. Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis.

    Science.gov (United States)

    Zhang, Xiaohui; Zhang, Xiaohua; Xiong, Yiqun; Xu, Chaoying; Liu, Xinliang; Lin, Jian; Mu, Guiping; Xu, Shaogang; Liu, Wenhe

    2016-09-01

    The sarcolemmal ATP-sensitive K+ (sarcKATP) channel plays a cardioprotective role during stress. However, the role of the sarcKATP channel in the apoptosis of cardiomyocytes and association with mitochondrial calcium remains unclear. For this purpose, we developed a model of LPS-induced sepsis in neonatal rat cardiomyocytes (NRCs). The TUNEL assay was performed in order to detect the apoptosis of cardiac myocytes and the MTT assay was performed to determine cellular viability. Exposure to LPS significantly decreased the viability of the NRCs as well as the expression of Bcl-2, whereas it enhanced the activity and expression of the apoptosis-related proteins caspase-3 and Bax, respectively. The sarcKATP channel blocker, HMR-1098, increased the apoptosis of NRCs, whereas the specific sarcKATP channel opener, P-1075, reduced the apoptosis of NRCs. The mitochondrial calcium uniporter inhibitor ruthenium red (RR) partially inhibited the pro-apoptotic effect of HMR-1098. In order to confirm the role of the sarcKATP channel, we constructed a recombinant adenovirus vector carrying the sarcKATP channel mutant subunit Kir6.2AAA to inhibit the channel activity. Kir6.2AAA adenovirus infection in NRCs significantly aggravated the apoptosis of myocytes induced by LPS. Elucidating the regulatory mechanisms of the sarcKATP channel in apoptosis may facilitate the development of novel therapeutic targets and strategies for the management of sepsis and cardiac dysfunction. PMID:27430376

  16. Sulfonylurea herbicide-resistant Monochoria vaginalis in Korean rice culture.

    Science.gov (United States)

    Kuk, Yong In; Jung, Ha Il; Kwon, Oh Do; Lee, Do Jin; Burgos, Nilda R; Guh, Ja Ock

    2003-09-01

    Nine Monochoria vaginalis Pres1 accessions from Chonnam province, Korea were tested for resistance to the sulfonylurea herbicide, imazosulfuron, in whole-plant response bioassay. All accessions were confirmed resistant (R) to imazosulfuron. The GR50 (imazosulfuron concentration that reduced shoot dry weight by 50%) values of R accessions were 1112-3172 (accession #9) times higher than that of the standard susceptible (S) accession. Accession #9 exhibited cross-resistance to other sulfonylurea herbicides, bensulfuron-methyl, cyclosulfamuron and pyrazosulfuron-ethyl, but not to the imidazolinone herbicides, imazapyr and imazaquin. The R biotype could be controlled by other herbicides with different modes of action, such as mefenacet and pyrazolate, applied to soil at recommended rates. Foliar-applied herbicides, 2,4-D and bentazone, also controlled both the R and S biotypes. Sulfonylurea-based mixtures, except ethoxysulfuron plus fentrazamide, did not control resistant M. vaginalis. Rice yield was reduced 70% by resistant M. vaginalis that escaped pyrazosulfuron-ethyl plus molinate, compared with hand weeding in direct-seeded rice culture. In contrast, rice yield was reduced 44% by resistant M. vaginalis that survived the pyrazosulfuron-ethyl plus molinate treatment, compared with pyrazolate plus butachlor in transplanted rice culture. In vitro acetolactate synthase (ALS) activity of the R biotype was 183, 35, 130 and 31 times more resistant to imazosulfuron, bensulfuron-methyl, cyclosulfamuron and pyrazosulfuron-ethyl, respectively, than the S biotype. Imidazolinone herbicides, imazapyr and imazaquin had similar effect on in vitro ALS activity of the R and S biotypes. The in vivo ALS activity of the R biotype was also less affected than the S biotype by the sulfonylurea herbicides imazosulfuron and pyrazosulfuron-ethyl. Results of in vitro and in vivo ALS assays indicate that the resistance mechanism of M. vaginalis to sulfonylurea herbicides may be due, in part, to

  17. Development of Pressure-Sensitive Channel Chip for Micro Gas Flows

    Science.gov (United States)

    Matsuda, Yu; Yamaguchi, Hiroki; Niimi, Tomohide

    2012-05-01

    Optical measurement techniques are useful for experimental studies on micro gas flows, which enable us to non-intrusively measure the flows with a high spatial resolution. The pressure-sensitive paint (PSP) technique, which is based on the emission of photons from luminophore, is a potential diagnostic tool for pressure measurement of micro gas flows. However, measurements by conventional PSPs are limited to the sub-millimeter order spatial resolution of ca. 200 μm, indicating the difficulty of the micro scale measurements. The present study proposes pressure-sensitive channel chip (PSCC) which is a micro channel with the capability of measuring pressure. We focused on the poly (dimethylsiloxane) (PDMS) micro-molding technique, which is one of the most popular techniques to fabricate a micro channel easily. Moreover, PDMS is a polymer used as a binder in PSP because of high optical transparency, gas permeability, and gas diffusivity. Thus, we developed a micro channel by the PDMS micro-molding technique with mixing a pressure-sensitive luminophore into PDMS: i.e. a micro channel fabricated by PSP, which is named PSCC. A flow through a micro converging-diverging nozzle with the throat width of 120 μm was demonstrated. The pressure distribution on the nozzle surface was successfully obtained by PSCC.

  18. Development of Pressure-Sensitive Channel Chip for Micro Gas Flows

    International Nuclear Information System (INIS)

    Optical measurement techniques are useful for experimental studies on micro gas flows, which enable us to non-intrusively measure the flows with a high spatial resolution. The pressure-sensitive paint (PSP) technique, which is based on the emission of photons from luminophore, is a potential diagnostic tool for pressure measurement of micro gas flows. However, measurements by conventional PSPs are limited to the sub-millimeter order spatial resolution of ca. 200 μm, indicating the difficulty of the micro scale measurements. The present study proposes pressure-sensitive channel chip (PSCC) which is a micro channel with the capability of measuring pressure. We focused on the poly (dimethylsiloxane) (PDMS) micro-molding technique, which is one of the most popular techniques to fabricate a micro channel easily. Moreover, PDMS is a polymer used as a binder in PSP because of high optical transparency, gas permeability, and gas diffusivity. Thus, we developed a micro channel by the PDMS micro-molding technique with mixing a pressure-sensitive luminophore into PDMS: i.e. a micro channel fabricated by PSP, which is named PSCC. A flow through a micro converging-diverging nozzle with the throat width of 120 μm was demonstrated. The pressure distribution on the nozzle surface was successfully obtained by PSCC.

  19. HIV-gp120 activates large-conductance apamin-sensitive potassium channels in rat astrocytes.

    Science.gov (United States)

    Bubien, J K; Benveniste, E N; Benos, D J

    1995-06-01

    Central nervous system (CNS) involvement usually occurs in individuals infected with human immunodeficiency virus type 1 (HIV-1). Evidence is now accumulating that neurons and astrocytes may be functionally compromised by exposure to viral components or cellular factors released from HIV-1-infected macrophages and/or microglia. We have previously reported that the HIV coat protein gp120 stimulates Na+/H+ exchange in primary cultured rat astrocytes, which, ultimately, results in the activation of a K+ conductance. In this report we characterize the electrophysiological and biophysical properties of the channels responsible for the gp120-induced increase in K+ conductance. These K+ channels had a relatively large unitary conductance (147 pS), were not gated by voltage, were sensitive to changes in H+ concentration at their cytosolic face, were specifically inhibited by apamin, and were insensitive to charybdotoxin and tetraethylammonium. The activation of these channels by gp120 is referable to cellular alkalinization subsequent to Na+/H+ exchange stimulation; gp120 failed to activate these K+ channels in the absence of external Na+ or in the presence of amiloride, an inhibitor of Na+/H+ exchange. Subsequent K+ loss from the astrocyte into the restricted extracellular space surrounding neurons can then lead to neuronal depolarization, activation of voltage-sensitive Ca2+ channels, and, eventually, cell death. Thus abnormal activation of astrocyte K+ channels by gp120 may contribute to the CNS pathophysiology associated with HIV-1 infection. PMID:7611364

  20. EXAMINATION OF THE ANTICONVULSANT PROPERTIES OF VOLTAGE-SENSITIVE CALCIUM CHANNEL INHIBITORS IN AMYGDALA KINDLED SEIZURES

    Science.gov (United States)

    Representatives from three different classes of voltage-sensitive calcium (VSC) channel inhibitors were assessed for their protection against amygdala kindled seizures. dult male long Evans rats (n=12) were implanted with electrodes in the amygdala and were stimulated once daily ...

  1. Insecticide sensitivity of native chloride and sodium channels in a mosquito cell line.

    Science.gov (United States)

    Jenson, Lacey J; Anderson, Troy D; Bloomquist, Jeffrey R

    2016-06-01

    The aim of this study was to investigate the utility of cultured Anopheles gambiae Sua1B cells for insecticide screening applications without genetic engineering or other treatments. Sua1B cells were exposed to the known insecticidal compounds lindane and DIDS, which inhibited cell growth at micromolar concentrations. In patch clamp studies, DIDS produced partial inhibition (69%) of chloride current amplitudes, and an IC50 of 5.1μM was determined for Sua1B cells. A sub-set of chloride currents showed no response to DIDS; however, inhibition (64%) of these currents was achieved using a low chloride saline solution, confirming their identity as chloride channels. In contrast, lindane increased chloride current amplitude (EC50=116nM), which was reversed when cells were bathed in calcium-free extracellular solution. Voltage-sensitive chloride channels were also inhibited by the presence of fenvalerate, a type 2 pyrethroid, but not significantly blocked by type 1 allethrin, an effect not previously shown in insects. Although no evidence of fast inward currents typical of sodium channels was observed, studies with fenvalerate in combination with veratridine, a sodium channel activator, revealed complete inhibition of cell growth that was best fit by a two-site binding model. The high potency effect was completely inhibited in the presence of tetrodotoxin, a specific sodium channel blocker, suggesting the presence of some type of sodium channel. Thus, Sua1B cells express native insect ion channels with potential utility for insecticide screening. PMID:27155485

  2. Study of OPERA sensitivity in the νμ → νe oscillation channel

    International Nuclear Information System (INIS)

    We report on the study of the sensitivity in the νμ → νe oscillation channel of the OPERA detector at the Gran Sasso Laboratory along the CNGS neutrino beamline. An identification procedure for νe events was defined and a full Monte Carlo simulation was used in order to simulate the detection of real events and evaluate the identification efficiency. A cut on the reconstructed neutrino energy was studied with the purpose of improving the sensitivity on the νμ → νe oscillation parameters. Finally a further analysis of the OPERA sensitivity in (3+1)-neutrino mixing model was performed.

  3. Developing Some Structural Hydraulic Sensitivity Indicators and Utilizing Them in Flow Analysis of Irrigation Channels

    Directory of Open Access Journals (Sweden)

    S. Kouchakzadeh

    2006-10-01

    Full Text Available The sensitivity analysis approach should be regarded as a new means which has recently been proposed for assessing flow of the irrigation networks. This approach uses the flow steady state equations and the physical conditions of irrigation channels to evaluate the response of the system to input perturbations. In this paper, some structural hydraulic sensitivity indicators were developed and utilized in studying the flow of an irrigation channel. For evaluating the efficiency of indicators and proposed analysis method, a real case was simulated by SOBEK model. Using the simulation results and introduced indicators, the flow regulation and distribution process within channel was studied. The results indicated a successful application of sensitivity indicators in evaluating system's potential in relation to alternative operational scenarios. With the calculation of these indicators, a comprehensive information system could be provided and applied in the analysis of the response potential of channel to structural perturbations, estimation of structure setting accuracy, and in the choice of suitable operation frequency there of.

  4. Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets

    DEFF Research Database (Denmark)

    Maedler, Kathrin; Størling, Joachim; Sturis, Jeppe;

    2004-01-01

    -regulated kinase (ERK) 1/2, an effect that was abrogated by 3 micromol/l NN414. Similarly, 1 micromol/l of the mitogen-activated protein kinase/ERK kinase 1/2 inhibitor PD098059 or 1 micromol/l of the l-type Ca(2+) channel blocker nimodipine prevented glucose- and IL-1beta-induced ERK activation, beta......Increasing evidence indicates that a progressive decrease in the functional beta-cell mass is the hallmark of both type 1 and type 2 diabetes. The underlying causes, beta-cell apoptosis and impaired secretory function, seem to be partly mediated by macrophage production of interleukin (IL)-1beta...... and/or high-glucose-induced beta-cell production of IL-1beta. Treatment of type 1 and type 2 diabetic patients with the potassium channel opener diazoxide partially restores insulin secretion. Therefore, we studied the effect of diazoxide and of the novel potassium channel opener NN414, selective for...

  5. The Basal Thermal Sensitivity of the TRPV1 Ion Channel Is Determined by PKCβII

    OpenAIRE

    Li, Lin; Hasan, Raquibul; Zhang, Xuming

    2014-01-01

    Peripheral nociceptors are excited by the activation of membrane receptors and ion channels. The heat-sensitive TRPV1 ion channel responds to various noxious chemical and thermal stimuli, causing pain and itch. Here, we show that TRPV1 is coexpressed with PKCβII in a subset of mouse sensory neurons and that, in these neurons, TRPV1 binds directly to PKCβII, leading to the activation and translocation of PKCβII. Activated PKCβII, in turn, significantly increases the responsiveness of TRPV1 by ...

  6. Molecular identification of O2 sensors and O2-sensitive potassium channels in the pulmonary circulation.

    Science.gov (United States)

    Archer, S L; Weir, E K; Reeve, H L; Michelakis, E

    2000-01-01

    Small, muscular pulmonary arteries (PAs) constrict within seconds of the onset of alveolar hypoxia, diverting blood flow to better-ventilated lobes, thereby matching ventilation to perfusion and optimizing systemic PO2. This hypoxic pulmonary vasoconstriction (HPV) is enhanced by endothelial derived vasoconstrictors, such as endothelin, and inhibited by endothelial derived nitric oxide. However, the essence of the response is intrinsic to PA smooth muscle cells in resistance arteries (PASMCs). HPV is initiated by inhibition of the Kv channels in PASMCs which set the membrane potential (EM). It is currently uncertain whether this reflects an initial inhibitory effect of hypoxia on the K+ channels or an initial release of intracellular Ca2+, which then inhibits K+ channels. In either scenario, the resulting depolarization activates L-type, voltage gated Ca2+ channels, which raises cytosolic calcium levels [Ca2+]i and causes vasoconstriction. Nine families of Kv channels are recognized from cloning studies (Kv1-Kv9), each with subtypes (i.e. Kv1.1-1.6). The contribution of an individual Kv channel to the whole-cell current (IK) is difficult to determine pharmacologically because Kv channel inhibitors are nonspecific. Furthermore, the PASMC's IK is an ensemble, reflecting activity of several channels. The K+ channels which set EM, and inhibition of which initiates HPV, conduct an outward current which is slowly inactivating, and which is blocked by the Kv inhibitor 4-aminopyridine (4-AP) but not by inhibitors of Ca(2+)- or ATP-sensitive K+ channels. Using anti-Kv antibodies to immunolocalize and inhibit Kv channels, we showed that the PASMC contains numerous types of Kv channels from the Kv1 and Kv2 families., Furthermore Kv1.5 and Kv2.1 may be important in determining the EM and play a role as effectors of HPV in PASMCs. While the Kv channels in PASMCs are the "effectors" of HPV, it is uncertain whether they are intrinsically O2-sensitive or are under the control of

  7. The TRPM2 ion channel is required for sensitivity to warmth.

    Science.gov (United States)

    Tan, Chun-Hsiang; McNaughton, Peter A

    2016-08-25

    Thermally activated ion channels are known to detect the entire thermal range from extreme heat (TRPV2), painful heat (TRPV1, TRPM3 and ANO1), non-painful warmth (TRPV3 and TRPV4) and non-painful coolness (TRPM8) through to painful cold (TRPA1). Genetic deletion of each of these ion channels, however, has only modest effects on thermal behaviour in mice, with the exception of TRPM8, the deletion of which has marked effects on the perception of moderate coolness in the range 10-25 °C. The molecular mechanism responsible for detecting non-painful warmth, in particular, is unresolved. Here we used calcium imaging to identify a population of thermally sensitive somatosensory neurons which do not express any of the known thermally activated TRP channels. We then used a combination of calcium imaging, electrophysiology and RNA sequencing to show that the ion channel generating heat sensitivity in these neurons is TRPM2. Autonomic neurons, usually thought of as exclusively motor, also express TRPM2 and respond directly to heat. Mice in which TRPM2 had been genetically deleted showed a striking deficit in their sensation of non-noxious warm temperatures, consistent with the idea that TRPM2 initiates a 'warm' signal which drives cool-seeking behaviour. PMID:27533035

  8. Sensitivity of the sea circulation to the atmospheric forcing in the Sicily Channel

    Science.gov (United States)

    Omrani, Hiba; Arsouze, Thomas; Béranger, Karine; Boukthir, Moncef; Drobinski, Philippe; Lebeaupin-Brossier, Cindy; Mairech, Hanen

    2016-01-01

    We investigate the sensitivity of the sea surface circulation in the Sicily Channel to surface winds, using a 15-year long (1994-2008) air-sea coupled numerical simulation. Analysis is based on the clustering of six main wind regimes over the Sicily Channel domain. The analysis of the corresponding sea current clusters shows that sea circulation in this area is sensitive to surface wind patterns. This wind modulates the strength of the two main branches of the sea circulation in the Sicily Channel (i.e. the Atlantic Tunisian Current and the Atlantic Ionian Stream). The modulation of these two currents depends on the wind regime, and displays a strong seasonal variability. It is also shown that the sea circulation in the Sicily Channel is strongly controlled by the thermohaline circulation and the bathymetry (geostrophic current). However, the contribution to the total current of its ageostrophic component forced by the surface winds is significant, with a correlation coefficient varying from 0.3 to 0.7.

  9. Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue

    OpenAIRE

    1996-01-01

    The role of amiloride-sensitive Na+ channels (ASSCs) in the transduction of salty taste stimuli in rat fungiform taste buds has been well established. Evidence for the involvement of ASSCs in salt transduction in circumvallate and foliate taste buds is, at best, contradictory. In an attempt to resolve this apparent controversy, we have begun to look for functional ASSCs in taste buds isolated from fungiform, foliate, and circumvallate papillae of male Sprague-Dawley rats. By use of a combinat...

  10. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation

    OpenAIRE

    Di, Anke; Gao, Xiao-Pei; Qian, Feng; Kawamura, Takeshi; Han, Jin; Hecquet, Claudie; Ye, Richard D; Vogel, Stephen M.; Malik, Asrar B.

    2011-01-01

    The NADPH oxidase activity of phagocytes and its generation of reactive oxygen species (ROS) is critical for host-defense, but ROS overproduction can also lead to inflammation and tissue injury. Here we report that TRPM2, a non-selective and redox-sensitive cation channel, inhibits ROS production in phagocytic cells and prevents endotoxin-induced lung inflammation in mice. TRPM2-deficient mice challenged with endotoxin (lipopolysaccharide) showed an increased inflammatory signature and decrea...

  11. Natriuretic peptides modulate ATP-sensitive K+ channels in rat ventricular cardiomyocytes

    OpenAIRE

    Burley, Dwaine S.; Charles D Cox; Zhang, Jin; Wann, Kenneth T.; Baxter, Gary F.

    2014-01-01

    B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and (Cys-18)-atrial natriuretic factor (4–23) amide (C-ANF), are cytoprotective under conditions of ischemia–reperfusion, limiting infarct size. ATP-sensitive K+ channel (KATP) opening is also cardioprotective, and although the KATP activation is implicated in the regulation of cardiac natriuretic peptide release, no studies have directly examined the effects of natriuretic peptides on cardiac KATP activity. Normoxic cardi...

  12. Temperature sensitivity of surface channel effects on high-purity germanium detectors

    International Nuclear Information System (INIS)

    The temperature sensitivity of surface channel effects on planar high-purity germanium detectors was measured using 60-keV gamma-ray scanning techniques, as part of a radiation damage study. When measured in this manner, the surface effects on most detectors showed extreme temperature sensitivity in the 72-95 K region. The effect of the surface channel increased with increasing temperature to such an extent that the efficiency, as measured by the count rate in the 1332-keV peak from a 60Co source, decreased by a factor of over two in some cases. Since the peak efficiency for the 1332-keV gamma ray decreased as the temperature increased throughout the operating range (72-120 K) the effect of the surface channel must continue to increase beyond the temperature (95 K) at which the 60-keV scan loses its sensitivity because of the strong attenuation of these much lower energy gamma rays. Radiation damage had no measurable effect on the surface characteristics. No correlation between the surface effects and the resolution changes of the 1332-keV peak was observed. (orig.)

  13. Temperature sensitivity of surface channel effects on high-purity germanium detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hull, E.L. [Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Pehl, R.H. [Lawrence Berkeley Laboratory, Berkeley, CA 94720 (United States); Madden, N.W. [Lawrence Berkeley Laboratory, Berkeley, CA 94720 (United States); Luke, P.N. [Lawrence Berkeley Laboratory, Berkeley, CA 94720 (United States); Cork, C.P. [Lawrence Berkeley Laboratory, Berkeley, CA 94720 (United States); Malone, D.L. [Lawrence Berkeley Laboratory, Berkeley, CA 94720 (United States); Xing, J.S. [Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Komisarcik, K. [Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Vanderwerp, J.D. [Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Friesel, D.L. [Indiana Univ., Bloomington, IN (United States). Cyclotron Facility

    1995-10-15

    The temperature sensitivity of surface channel effects on planar high-purity germanium detectors was measured using 60-keV gamma-ray scanning techniques, as part of a radiation damage study. When measured in this manner, the surface effects on most detectors showed extreme temperature sensitivity in the 72-95 K region. The effect of the surface channel increased with increasing temperature to such an extent that the efficiency, as measured by the count rate in the 1332-keV peak from a {sup 60}Co source, decreased by a factor of over two in some cases. Since the peak efficiency for the 1332-keV gamma ray decreased as the temperature increased throughout the operating range (72-120 K) the effect of the surface channel must continue to increase beyond the temperature (95 K) at which the 60-keV scan loses its sensitivity because of the strong attenuation of these much lower energy gamma rays. Radiation damage had no measurable effect on the surface characteristics. No correlation between the surface effects and the resolution changes of the 1332-keV peak was observed. (orig.).

  14. Temperature sensitivity of surface channel effects on high-purity germanium detectors

    Science.gov (United States)

    Hull, E. L.; Pehl, R. H.; Madden, N. W.; Luke, P. N.; Cork, C. P.; Malone, D. L.; Xing, J. S.; Komisarcik, K.; Vanderwerp, J. D.; Friesel, D. L.

    1995-02-01

    The temperature sensitivity of surface channel effects on planar high-purity germanium detectors was measured using 60-keV gamma-ray scanning techniques, as part of a radiation damage study. When measured in this manner, the surface effects on most detectors showed extreme temperature sensitivity in the 72-95 K region. The effect of the surface channel increased with increasing temperature to such an extent that the efficiency, as measured by the count rate in the 1332-keV peak from a 60Co source, decreased by a factor of over two in some cases. Since the peak efficiency for the 1332-keV gamma ray decreased as the temperature increased throughout the operating range (72-120 K) the effect of the surface channel must continue to increase beyond the temperature (95 K) at which the 60-keV scan loses its sensitivity because of the strong attenuation of these much lower energy gamma rays. Radiation damage had no measurable effect on the surface characteristics. No correlation between the surface effects and the resolution changes of the 1332-keV peak was observed.

  15. New Conotoxin SO-3 Targeting N-type Voltage-Sensitive Calcium Channels

    Directory of Open Access Journals (Sweden)

    Lei Wen

    2006-04-01

    Full Text Available Selective blockers of the N-type voltage-sensitive calcium (CaV channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to ω-conotoxin MVIIA (MVIIA, a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.

  16. Iptakalim protects against hypoxic brain injury through multiple pathways associated with ATP-sensitive potassium channels.

    Science.gov (United States)

    Zhu, H-L; Luo, W-Q; Wang, H

    2008-12-10

    The rapid and irreversible brain injury produced by anoxia when stroke occurs is well known. Cumulative evidence suggests that the activation of neuronal ATP-sensitive potassium (KATP) channels may have inherent protective effects during cerebral hypoxia, yet little information regarding the therapeutic effects of KATP channel openers is available. We hypothesized that pretreatment with a KATP channel opener might protect against brain injury induced by cerebral hypoxia. In this study, adult Wistar rats were treated with iptakalim, a new KATP channel opener, which is selective for SUR2 type KATP channels, by intragastric administration at doses of 2, 4, or 8 mg/kg/day for 7 days before being exposed to simulated high altitude equivalent to 8000 m in a decompression chamber for 8 h leading to hypoxic brain injury. By light and electron microscopic images, we observed that hypobaric hypoxia-induced brain injury could be prevented by pretreatment with iptakalim. It was also observed that the permeability of the blood-brain barrier, water content, Na+ and Ca2+ concentration, and activities of Na+,K+-ATPase, Ca2+-ATPase and Mg2+-ATPase in rat cerebral cortex were increased and the gene expression of the occludin or aquaporin-4 was down- or upregulated respectively, which could also be prevented by the pretreatment with iptakalim at doses of 2, 4, or 8 mg/kg in a dose-dependent manner. Furthermore, we found that in an oxygen-and-glucose-deprived model in ECV304 cells and rat cortical astrocytes, pretreatment with iptakalim significantly increased survived cell rates and decreased lactate dehydrogenate release, which were significantly antagonized by glibenclamide, a K(ATP) channel blocker. We conclude that iptakalim is a promising drug that may protect against brain injury induced by acute hypobaric hypoxia through multiple pathways associated with SUR2-type K(ATP) channels, suggesting a new therapeutic strategy for stroke treatment. PMID:18951957

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

    Directory of Open Access Journals (Sweden)

    Kummer Wolfgang

    2006-07-01

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

  18. ATP-sensitive K+ channel knockout induces cardiac proteome remodeling predictive of heart disease susceptibility.

    Science.gov (United States)

    Arrell, D Kent; Zlatkovic, Jelena; Kane, Garvan C; Yamada, Satsuki; Terzic, Andre

    2009-10-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (K(ATP)) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode consequences of Kir6.2 K(ATP) channel pore deletion. Differential two-dimensional gel electrophoresis reproducibly resolved >800 protein species from hearts of asymptomatic wild-type and Kir6.2-knockout counterparts. K(ATP) channel ablation remodeled the cardiac proteome, significantly altering 71 protein spots, from which 102 unique identities were assigned following hybrid linear ion trap quadrupole-Orbitrap tandem mass spectrometry. Ontological annotation stratified the K(ATP) channel-dependent protein cohort into a predominant bioenergetic module (63 resolved identities), with additional focused sets representing signaling molecules (6), oxidoreductases (8), chaperones (6), and proteins involved in catabolism (6), cytostructure (8), and transcription and translation (5). Protein interaction mapping, in conjunction with expression level changes, localized a K(ATP) channel-associated subproteome within a nonstochastic scale-free network. Global assessment of the K(ATP) channel deficient environment verified the primary impact on metabolic pathways and revealed overrepresentation of markers associated with cardiovascular disease. Experimental imposition of graded stress precipitated exaggerated structural and functional myocardial defects in the Kir6.2-knockout, decreasing survivorship and validating the forecast of disease susceptibility. Proteomic cartography thus provides an integral view of molecular remodeling in the heart induced by K(ATP) channel deletion, establishing a

  19. Expression of ATP sensitive K+ channel subunit Kir6.1 in rat kidney

    Directory of Open Access Journals (Sweden)

    M Zhou

    2009-06-01

    Full Text Available ATP-sensitive K+ (KATP channels in kidney are considered to play roles in regulating membrane potential during the change in intracellular ATP concentration. They are composed of channel subunits (Kir6.1, Kir6.2, which are members of the inwardly rectifying K+ channel family, and sulphonylurea receptors (SUR1, SUR2A and SUR2B, which belong to the ATP-binding cassette superfamily. In the present study, we have investigated the expression and localization of Kir6.1 in rat kidney with Western blot analysis, immunohistochemistry, in situ hybridization histochemistry, and immunoelectron microscopy. Western blot analysis showed that Kir6.1 was expressed in the mitochondria and microsome fractions of rat kidney and very weakly in the membrane fractions. Immunohistochemistry revealed that Kir6.1 was widely distributed in renal tubular epithelial cells, glomerular mesangial cells, and smooth muscles of blood vessels. In immunoelectron microscopy, Kir6.1 is mainly localized in the mitochondria, endoplasmic reticulum (ER, and very weakly in cell membranes. Thus, Kir6.1 is contained in the kidney and may be a candidate of mitochondrial KATP channels.

  20. Critical channel power calculation for nominal operation in the CNE (Embalse nuclear power plant): sensitivity study

    International Nuclear Information System (INIS)

    In the Embalse nuclear power plant (CNE), the Regional Overpower Protection System acting on the Shutdown Systems number 1 and number 2 protects the reactor against overpowers in the reactor field for a localized peaking or a power increase in the reactor as a whole. This report summarizes the results of the critical channel power calculation for the time average powers configuration for the 380 reactor field channels. The final purpose of this work is to analyze and eventually modify the detector set points. Other reactor configurations are being analyzed. The report also presents a sensitivity analysis in order to evaluate potential sources of error and uncertainties which could affect the ROP performance. (author)

  1. A Theoretical Model for Calculating Voltage Sensitivity of Ion Channels and the Application on Kv1.2 Potassium Channel

    Science.gov (United States)

    Yang, Huaiyu; Gao, Zhaobing; Li, Ping; Yu, Kunqian; Yu, Ye; Xu, Tian-Le; Li, Min; Jiang, Hualiang

    2012-01-01

    Voltage sensing confers conversion of a change in membrane potential to signaling activities underlying the physiological processes. For an ion channel, voltage sensitivity is usually experimentally measured by fitting electrophysiological data to Boltzmann distributions. In our study, a two-state model of the ion channel and equilibrium statistical mechanics principle were used to test the hypothesis of empirically calculating the overall voltage sensitivity of an ion channel on the basis of its closed and open conformations, and determine the contribution of individual residues to the voltage sensing. We examined the theoretical paradigm by performing experimental measurements with Kv1.2 channel and a series of mutants. The correlation between the calculated values and the experimental values is at respective level, R2 = 0.73. Our report therefore provides in silico prediction of key conformations and has identified additional residues critical for voltage sensing. PMID:22768937

  2. Intracellular signalling mechanism responsible for modulation of sarcolemmal ATP-sensitive potassium channels by nitric oxide in ventricular cardiomyocytes

    OpenAIRE

    Zhang, DM; Chai, Y.; Erickson, JR; Brown, JH; Bers, DM; Lin, YF

    2014-01-01

    Key points: Both the ATP-sensitive potassium (KATP) channel and the gaseous messenger nitric oxide (NO) play fundamental roles in protecting the heart from injuries related to ischaemia. NO has previously been suggested to modulate cardiac KATP channels; however, the underlying mechanism remains largely unknown. In this study, by performing electrophysiological and biochemical assays, we demonstrate that NO potentiation of KATP channel activity in ventricular cardiomyocytes is prevented by ph...

  3. Is gliclazide a sulfonylurea with difference? A review in 2016.

    Science.gov (United States)

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-06-01

    Sulfonylureas (SUs) remain the most commonly prescribed drug after metformin in the treatment of type 2 diabetes (T2DM), despite the availability of several newer agents. The primary reason of SUs being most popular is their quick glycemic response, time-tested experience and least cost. Although SUs are one amongst the several other second line agents after metformin in all major guidelines, the new Dutch type 2 guidelines specifically advise gliclazide as the preferred second line drug instead of SUs as a class. The World Health Organization (WHO) has also included gliclazide in their Model List of Essential Medicines 2013 motivated by its safety data in elderly patients. Specifically advising gliclazide may have been based on emerging evidence suggesting cardiovascular neutrality of gliclazide over other SUs. This prompted us to do a literature review of gliclazide efficacy and safety data compared to other SUs as well as oral anti-diabetic drugs. PMID:26924475

  4. S-glutathionylation of an auxiliary subunit confers redox sensitivity to Kv4 channel inactivation.

    Directory of Open Access Journals (Sweden)

    Henry H Jerng

    Full Text Available Reactive oxygen species (ROS regulate ion channels, modulate neuronal excitability, and contribute to the etiology of neurodegenerative disorders. ROS differentially suppress fast "ball-and-chain" N-type inactivation of cloned Kv1 and Kv3 potassium channels but not of Kv4 channels, likely due to a lack of reactive cysteines in Kv4 N-termini. Recently, we discovered that N-type inactivation of Kv4 channel complexes can be independently conferred by certain N-terminal variants of Kv4 auxiliary subunits (DPP6a, DPP10a. Here, we report that both DPP6a and DPP10a, like Kv subunits with redox-sensitive N-type inactivation, contain a highly conserved cysteine in their N-termini (Cys-13. To test if N-type inactivation mediated by DPP6a or DPP10a is redox sensitive, Xenopus oocyte recordings were performed to examine the effects of two common oxidants, tert-butyl hydroperoxide (tBHP and diamide. Both oxidants markedly modulate DPP6a- or DPP10a-conferred N-type inactivation of Kv4 channels, slowing the overall inactivation and increasing the peak current. These functional effects are fully reversed by the reducing agent dithiothreitol (DTT and appear to be due to a selective modulation of the N-type inactivation mediated by these auxiliary subunits. Mutation of DPP6a Cys-13 to serine eliminated the tBHP or diamide effects, confirming the importance of Cys-13 to the oxidative regulation. Biochemical studies designed to elucidate the underlying molecular mechanism show no evidence of protein-protein disulfide linkage formation following cysteine oxidation. Instead, using a biotinylated glutathione (BioGEE reagent, we discovered that oxidation by tBHP or diamide leads to S-glutathionylation of Cys-13, suggesting that S-glutathionylation underlies the regulation of fast N-type inactivation by redox. In conclusion, our studies suggest that Kv4-based A-type current in neurons may show differential redox sensitivity depending on whether DPP6a or DPP10a is highly

  5. S-glutathionylation of an auxiliary subunit confers redox sensitivity to Kv4 channel inactivation.

    Science.gov (United States)

    Jerng, Henry H; Pfaffinger, Paul J

    2014-01-01

    Reactive oxygen species (ROS) regulate ion channels, modulate neuronal excitability, and contribute to the etiology of neurodegenerative disorders. ROS differentially suppress fast "ball-and-chain" N-type inactivation of cloned Kv1 and Kv3 potassium channels but not of Kv4 channels, likely due to a lack of reactive cysteines in Kv4 N-termini. Recently, we discovered that N-type inactivation of Kv4 channel complexes can be independently conferred by certain N-terminal variants of Kv4 auxiliary subunits (DPP6a, DPP10a). Here, we report that both DPP6a and DPP10a, like Kv subunits with redox-sensitive N-type inactivation, contain a highly conserved cysteine in their N-termini (Cys-13). To test if N-type inactivation mediated by DPP6a or DPP10a is redox sensitive, Xenopus oocyte recordings were performed to examine the effects of two common oxidants, tert-butyl hydroperoxide (tBHP) and diamide. Both oxidants markedly modulate DPP6a- or DPP10a-conferred N-type inactivation of Kv4 channels, slowing the overall inactivation and increasing the peak current. These functional effects are fully reversed by the reducing agent dithiothreitol (DTT) and appear to be due to a selective modulation of the N-type inactivation mediated by these auxiliary subunits. Mutation of DPP6a Cys-13 to serine eliminated the tBHP or diamide effects, confirming the importance of Cys-13 to the oxidative regulation. Biochemical studies designed to elucidate the underlying molecular mechanism show no evidence of protein-protein disulfide linkage formation following cysteine oxidation. Instead, using a biotinylated glutathione (BioGEE) reagent, we discovered that oxidation by tBHP or diamide leads to S-glutathionylation of Cys-13, suggesting that S-glutathionylation underlies the regulation of fast N-type inactivation by redox. In conclusion, our studies suggest that Kv4-based A-type current in neurons may show differential redox sensitivity depending on whether DPP6a or DPP10a is highly expressed

  6. Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35)

    Institute of Scientific and Technical Information of China (English)

    Min Kong; Maowen Ba; Hui Liang; Peng Shao; Tianxia Yu; Ying Wang

    2013-01-01

    In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nω-nitro-L-arginine, also protected PC12 cells from intracellular reactive oxygen species levels. However, the H2O2-degrading enzyme catalase could that the increases in both mitochondrial membrane potential and reactive oxygen species levels adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β

  7. Synthesis and herbicidal activities of pyridyl sulfonylureas:More convenient preparation process of phenyl pyrimidylcarbamates

    Institute of Scientific and Technical Information of China (English)

    Ning Ma; Zhi Jin Fan; Bao Lei Wang; Yong Hong Li; Zheng Ming Li

    2008-01-01

    Four 4-monosubstituted pyrimidine pyridyl sulfonylureas were synthesized from pyridinesulfonamide and phenyl pyrimidyl-carbamate and screened for herbicidal activities.We also reported a convenient preparation process of phenyl pyrimidylcarbamates from pyrimidineamine and phenyl chloroformate.

  8. Cyclic AMP-dependent phosphorylation of voltage-sensitive sodium channels in primary cultures of rat brain cells

    Energy Technology Data Exchange (ETDEWEB)

    Rossie, S.; Catterall, W.A.

    1986-03-05

    The ..cap alpha.. subunit of the voltage-sensitive Na channel from rat brain is phosphorylated by cAMP-dependent protein kinase in purified preparations and in synaptosomes. The authors have begun to study cAMP-dependent phosphorylation of Na channels in intact cells. Rat brain cells collected at embryonic day 15 and maintained in culture for approximately 21 days were subjected to treatments designed to increase intracellular cAMP. Cells were solubilized and Na channels were isolated by immunoprecipitation, then rephosphorylated with the catalytic subunit of cAMP-dependent protein kinase and /sup 32/P-ATP, to allow incorporation of /sup 32/P into available cAMP-dependent phosphorylation sites of Na channels. The amount of /sup 32/P incorporated into channel is inversely proportional to the extent of endogenous phosphorylation. Treatment of cells with forskolin inhibited rephosphorylation of Na channels, indicating that enhanced endogenous phosphorylation of channels had occurred. The effect of forskolin on cell surface Na channels occurred rapidly, was sustained over 30 min., and was half-maximal at 6..mu..M. 8-Br-cAMP, (EC/sub 50/-5mM) and isobutylmethylxanthine (EC/sub 50/-60..mu..M) also caused inhibition of /sup 32/P incorporation into Na channels. These results indicate that the extent of cAMP-dependent phosphorylation of voltage-sensitive Na channels in intact brain neurons is modified by changes in intracellular levels of cAMP.

  9. Pharmacoeconomic aspects of the use of sulfonylurea drugs in type 2 diabetes mellitus

    OpenAIRE

    Alla Vsevolodovna Rudakova

    2011-01-01

    In Russia, sulfonylurea drugs are extensively prescribed to patients with type 2 diabetes mellitus. This work was designed to study pharmacoeconomic aspects of application of 2nd generation sulfonylureas based on the results of the GUIDE study comparing effects of therapy with gliclazide modified release (diabeton MV) and glimepiride (amaryl). The two drugs are known to be equally effective, but gliclazide creates a much smaller risk of hypoglycemia than glymepiride. Cost-effectivene...

  10. Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model

    OpenAIRE

    Sharma, Naveen; Sim, Yun-Beom; Park, Soo-hyun; Lim, Su-Min; Kim, Sung-Su; Jung, Jun-Sub; Hong, Jae-Seung; Suh, Hong-Won

    2015-01-01

    Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepir...

  11. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation.

    Science.gov (United States)

    Di, Anke; Gao, Xiao-Pei; Qian, Feng; Kawamura, Takeshi; Han, Jin; Hecquet, Claudie; Ye, Richard D; Vogel, Stephen M; Malik, Asrar B

    2012-01-01

    The NADPH oxidase activity of phagocytes and its generation of reactive oxygen species (ROS) is critical for host defense, but ROS overproduction can also lead to inflammation and tissue injury. Here we report that TRPM2, a nonselective and redox-sensitive cation channel, inhibited ROS production in phagocytic cells and prevented endotoxin-induced lung inflammation in mice. TRPM2-deficient mice challenged with endotoxin (lipopolysaccharide) had an enhanced inflammatory response and diminished survival relative to that of wild-type mice challenged with endotoxin. TRPM2 functioned by dampening NADPH oxidase-mediated ROS production through depolarization of the plasma membrane in phagocytes. As ROS also activate TRPM2, our findings establish a negative feedback mechanism for the inactivation of ROS production through inhibition of the membrane potential-sensitive NADPH oxidase. PMID:22101731

  12. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation

    Science.gov (United States)

    Di, Anke; Gao, Xiao-Pei; Qian, Feng; Kawamura, Takeshi; Han, Jin; Hecquet, Claudie; Ye, Richard D.; Vogel, Stephen M.; Malik, Asrar B.

    2011-01-01

    The NADPH oxidase activity of phagocytes and its generation of reactive oxygen species (ROS) is critical for host-defense, but ROS overproduction can also lead to inflammation and tissue injury. Here we report that TRPM2, a non-selective and redox-sensitive cation channel, inhibits ROS production in phagocytic cells and prevents endotoxin-induced lung inflammation in mice. TRPM2-deficient mice challenged with endotoxin (lipopolysaccharide) showed an increased inflammatory signature and decreased survival compared to controls. TRPM2 functions by dampening NADPH oxidase-mediated ROS production through depolarization of the plasma membrane in phagocytes. Since ROS also activates TRPM2, our findings establish a negative feedback mechanism inactivating ROS production through inhibition of the membrane potential-sensitive NADPH oxidase. PMID:22101731

  13. Sensitivity of P-Channel MOSFET to X- and Gamma-Ray Irradiation

    Directory of Open Access Journals (Sweden)

    Milić Pejović

    2013-01-01

    Full Text Available Investigation of Al-gate p-channel MOSFETs sensitivity following irradiation using 200 and 280 kV X-ray beams as well as gamma-ray irradiation of 60Co in the dose range from 1 to 5 Gy was performed in this paper. The response followed on the basis of threshold voltage shift and was studied as a function of absorbed dose. It was shown that the most significant change in threshold voltage was in the case of MOSFET irradiation in X-ray fields of 200 kV and when the gate voltage was +5 V. For practical applications in dosimetry, the sensitivity of the investigated MOSFETs was also satisfactory for X-ray tube voltage of 280 kV and for gamma rays. Possible processes in gate oxide caused by radiation and its impact on the response of MOSFETs were also analyzed in this paper.

  14. O2-sensitive K+ channels: role of the Kv1.2 α-subunit in mediating the hypoxic response

    Science.gov (United States)

    Conforti, Laura; Bodi, Ilona; Nisbet, John W; Millhorn, David E

    2000-01-01

    One of the early events in O2 chemoreception is inhibition of O2-sensitive K+ (KO2) channels. Characterization of the molecular composition of the native KO2 channels in chemosensitive cells is important to understand the mechanism(s) that couple O2 to the KO2 channels. The rat phaeochromocytoma PC12 clonal cell line expresses an O2-sensitive voltage-dependent K+ channel similar to that recorded in other chemosensitive cells. Here we examine the possibility that the Kv1.2 α-subunit comprises the KO2 channel in PC12 cells. Whole-cell voltage-clamp experiments showed that the KO2 current in PC12 cells is inhibited by charybdotoxin, a blocker of Kv1.2 channels. PC12 cells express the Kv1.2 α-subunit of K+ channels: Western blot analysis with affinity-purified anti-Kv1.2 antibody revealed a band at ≈80 kDa. Specificity of this antibody was established in Western blot and immunohystochemical studies. Anti-Kv1.2 antibody selectively blocked Kv1.2 current expressed in the Xenopus oocyte, but had no effect on Kv2.1 current. Anti-Kv1.2 antibody dialysed through the patch pipette completely blocked the KO2 current, while the anti-Kv2.1 and irrelevant antibodies had no effect. The O2 sensitivity of recombinant Kv1.2 and Kv2.1 channels was studied in Xenopus oocytes. Hypoxia inhibited the Kv1.2 current only. These findings show that the KO2 channel in PC12 cells belongs to the Kv1 subfamily of K+ channels and that the Kv1.2 α-subunit is important in conferring O2 sensitivity to this channel. PMID:10790158

  15. O2-sensitive K+ channels: role of the Kv1.2 -subunit in mediating the hypoxic response.

    Science.gov (United States)

    Conforti, L; Bodi, I; Nisbet, J W; Millhorn, D E

    2000-05-01

    One of the early events in O2 chemoreception is inhibition of O2-sensitive K+ (KO2) channels. Characterization of the molecular composition of the native KO2 channels in chemosensitive cells is important to understand the mechanism(s) that couple O2 to the KO2 channels. The rat phaeochromocytoma PC12 clonal cell line expresses an O2-sensitive voltage-dependent K+ channel similar to that recorded in other chemosensitive cells. Here we examine the possibility that the Kv1.2 alpha-subunit comprises the KO2 channel in PC12 cells. Whole-cell voltage-clamp experiments showed that the KO2 current in PC12 cells is inhibited by charybdotoxin, a blocker of Kv1.2 channels. PC12 cells express the Kv1.2 alpha-subunit of K+ channels: Western blot analysis with affinity-purified anti-Kv1.2 antibody revealed a band at approximately 80 kDa. Specificity of this antibody was established in Western blot and immunohystochemical studies. Anti-Kv1.2 antibody selectively blocked Kv1.2 current expressed in the Xenopus oocyte, but had no effect on Kv2.1 current. Anti-Kv1.2 antibody dialysed through the patch pipette completely blocked the KO2 current, while the anti-Kv2.1 and irrelevant antibodies had no effect. The O2 sensitivity of recombinant Kv1.2 and Kv2.1 channels was studied in Xenopus oocytes. Hypoxia inhibited the Kv1.2 current only. These findings show that the KO2 channel in PC12 cells belongs to the Kv1 subfamily of K+ channels and that the Kv1.2 alpha-subunit is important in conferring O2 sensitivity to this channel. PMID:10790158

  16. [Simultaneous determination of ten sulfonylurea herbicide residues in soybeans by high performance liquid chromatography].

    Science.gov (United States)

    Qi, Yan; Zhan, Chunrui; Zhang, Xinzhong; Chu, Xiaogang

    2004-11-01

    A reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of ten sulfonylurea herbicide (oxasulfuron, thifensulfuron-methyl, metsulfuron-methyl, triasulfuron, chlorsulfuron, bensulfuron-methyl, prosulfuron, pyrazosulfuron-methyl, chlorimuron-ethyl and primisufuron-methyl) residues in soybeans. Sulfonylurea herbicides were extracted with acetonitrile, followed by hexane partitioning. After the extract was cleaned up with a Florisil column, sulfonylurea herbicides were analyzed by HPLC-photo diode array detector (DAD) and quantified by external standard method. The pre-treatment method of the samples and the chromatographic conditions of the analysis were critically examined. The linear ranges of 10 sulfonylureas were 0.1 - 10.0 mg/L, and the correlation coefficients were 0.999 6 - 0.999 7. The average recoveries of ten sulfonylurea herbicides in spiked soybeans ranged from 69.8% to 100.7%, and the relative standard deviations were between 1.89% and 10.43%. The limit of detection was 20 microg/kg. The results have indicated that the method developed is easier, faster, and has better purification effect. It has also demonstrated that this multiresidue analytical method can meet the requirements for the simultaneous determination of many sulfonylurea herbicides in import and export inspection for soybeans. PMID:15807119

  17. Role of the epithelial sodium channel in salt-sensitive hypertension

    Institute of Scientific and Technical Information of China (English)

    Yan SUN; Jia-ning ZHANG; Dan ZHAO; Qiu-shi WANG; Yu-chun GU; He-ping MA; Zhi-ren ZHANG

    2011-01-01

    The epithelial sodium channel (ENaC) is a heteromeric channel composed of three similar but distinct subunits, a, β and Y. This channel is an end-effector in the rennin-angiotensin-aldosterone system and resides in the apical plasma membrane of the renal cortical collecting ducts, where reabsorption of Na+ through ENaC is the final renal adjustment step for Na+ balance. Because of its regulation and function, the ENaC plays a critical role in modulating the homeostasis of Na+ and thus chronic blood pressure. The development of most forms of hypertension requires an increase in Na+ and water retention. The role of ENaC in developing high blood pressure is exemplified in the gain-of-function mutations in ENaC that cause Liddle's syndrome, a severe but rare form of inheritable hypertension.The evidence obtained from studies using animal models and in human patients indicates that improper Na+ retention by the kidney elevates blood pressure and induces salt-sensitive hypertension.

  18. Macroform and microform-induced change in redox-sensitive chemistries of river channel surface sediments

    Science.gov (United States)

    Byrne, P.; Zhang, H.; Heathwaite, A. L.; Binley, A.; Ullah, S.; Kaeser, D.; Heppell, C. M.; Lansdown, K.; Trimmer, M.

    2012-04-01

    In-stream geomorphological features such as riffle-pool sequences (macroforms) can produce steep hydraulic gradients which induce flow in and out of the riverbed - hyporheic exchange flow (HEF). The acceleration of flow over channel obstacles such as large cobbles and boulders (microforms) can create variation in surface-subsurface pressure gradients and generation of HEF. HEF in shallow surface sediments affect the transformation of redox-sensitive chemical forms and, therefore, the attenuation or release of nutrients in river systems. Here, we examine the relationship between stream geomorphological environment (microform and macroform) and concentration profiles of redox-sensitive species (nitrate, sulphate, iron, manganese) in shallow (15cm) subsurface sediments. In-situ passive samplers (diffusive equilibrium in thin films - DET) are used to obtain biogeochemical data from armoured environments at fine scale (cm) depth resolution where there is strong upwelling. The probes were deployed in a 50m reach of the River Eden, Cumbria, UK, during baseflow conditions. The experimental setup allowed for the assessment of differences in redox-sensitive chemistries between a riffle and pool environment and between smooth and rough bed surfaces in the pool. The passive sensing basis of the DET methodology provided a means for investigating how HEF systems generated at two different geomorphological scales influence the concentration and spatial patterns of redox-sensitive species. DET's capability of measuring at high spatial resolution allowed the extent of hyporheic mixing to be targeted, even though it is often limited to the top few centimetres of sediment.

  19. GABA transmission via ATP-dependent K+ channels regulates α-synuclein secretion in mouse striatum.

    Science.gov (United States)

    Emmanouilidou, Evangelia; Minakaki, Georgia; Keramioti, Maria V; Xylaki, Mary; Balafas, Evangelos; Chrysanthou-Piterou, Margarita; Kloukina, Ismini; Vekrellis, Kostas

    2016-03-01

    α-Synuclein is readily released in human and mouse brain parenchyma, even though the normal function of the secreted protein has not been yet elucidated. Under pathological conditions, such as in Parkinson's disease, pathologically relevant species of α-synuclein have been shown to propagate between neurons in a prion-like manner, although the mechanism by which α-synuclein transfer induces degeneration remains to be identified. Due to this evidence extracellular α-synuclein is now considered a critical target to hinder disease progression in Parkinson's disease. Given the importance of extracellular α-synuclein levels, we have now investigated the molecular pathway of α-synuclein secretion in mouse brain. To this end, we have identified a novel synaptic network that regulates α-synuclein release in mouse striatum. In this brain area, the majority of α-synuclein is localized in corticostriatal glutamatergic terminals. Absence of α-synuclein from the lumen of brain-isolated synaptic vesicles suggested that they are unlikely to mediate its release. To dissect the mechanism of α-synuclein release, we have used reverse microdialysis to locally administer reagents that locally target specific cellular pathways. Using this approach, we show that α-synuclein secretion in vivo is a calcium-regulated process that depends on the activation of sulfonylurea receptor 1-sensitive ATP-regulated potassium channels. Sulfonylurea receptor 1 is distributed in the cytoplasm of GABAergic neurons from where the ATP-dependent channel regulates GABA release. Using a combination of specific agonists and antagonists, we were able to show that, in the striatum, modulation of GABA release through the sulfonylurea receptor 1-regulated ATP-dependent potassium channels located on GABAergic neurons controls α-synuclein release from the glutamatergic terminals through activation of the presynaptic GABAB receptors. Considering that sulfonylurea receptors can be selectively targeted, our

  20. Binding of [125I]iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    International Nuclear Information System (INIS)

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with [125I] iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for [125I] iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited [125I] iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes

  1. Strain differences in pH-sensitive K+ channel-expressing cells in chemosensory and nonchemosensory brain stem nuclei

    OpenAIRE

    Martino, Paul F.; Olesiak, S.; Batuuka, D.; Riley, D; Neumueller, S.; Forster, H. V.; Hodges, M. R.

    2014-01-01

    The ventilatory CO2 chemoreflex is inherently low in inbred Brown Norway (BN) rats compared with other strains, including inbred Dahl salt-sensitive (SS) rats. Since the brain stem expression of various pH-sensitive ion channels may be determinants of the CO2 chemoreflex, we tested the hypothesis that there would be fewer pH-sensitive K+ channel-expressing cells in BN relative to SS rats within brain stem sites associated with respiratory chemoreception, such as the nucleus tractus solitarius...

  2. Crystal Structure of the Human K2P TRAAK, a Lipid- and Mechano-Sensitive K[superscript +] Ion Channel

    Energy Technology Data Exchange (ETDEWEB)

    Brohawn, Stephen G.; del Mármol, Josefina; MacKinnon, Roderick (Rockefeller)

    2012-03-01

    TRAAK channels, members of the two-pore domain K{sup +} (potassium ion) channel family K2P, are expressed almost exclusively in the nervous system and control the resting membrane potential. Their gating is sensitive to polyunsaturated fatty acids, mechanical deformation of the membrane, and temperature changes. Physiologically, these channels appear to control the noxious input threshold for temperature and pressure sensitivity in dorsal root ganglia neurons. We present the crystal structure of human TRAAK at a resolution of 3.8 angstroms. The channel comprises two protomers, each containing two distinct pore domains, which create a two-fold symmetric K{sup +} channel. The extracellular surface features a helical cap, 35 angstroms tall, that creates a bifurcated pore entry way and accounts for the insensitivity of two-pore domain K{sup +} channels to inhibitory toxins. Two diagonally opposed gate-forming inner helices form membrane-interacting structures that may underlie this channel's sensitivity to chemical and mechanical properties of the cell membrane.

  3. A fully integrated, monolithic, cryogenic charge sensitive preamplifier using N-channel JFETs and polysilicon resistors

    International Nuclear Information System (INIS)

    In this paper, an integrated charge preamplifier to be used with small (10--30 mm2) Si(Li) and Ge(Li) X-ray detectors is described. The preamplifier is designed to operate at cryogenic temperatures (∼100 K to 160 K) for the best performance. An N-channel JFET process technology for integrated charge sensitive preamplifiers has been developed. The process integrates multiple pinch-off voltage JFETs fabricated in an n-type epitaxial layer on a low resistivity p-type substrate. The process also incorporates polysilicon resistors integrated on the same die as the JFETs. The optimized polysilicon resistors exhibit 1/f noise nearly as good as metal film resistors at the same current. Results for integrated amplifier are discussed

  4. Effect of sulfonylureas on hepatic fatty acid oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Patel, T.B.

    1986-08-01

    In isolated rat livers perfused with oleic acid (0.1 mM), infusion of tolbutamide or glyburide decreased the rate of ketogenesis in a dose-dependent manner. The inhibition of fatty acid oxidation was maximal at 2.0 mM and 10 M concentrations of tolbutamide and glyburide, respectively. Neither tolbutamide nor glyburide inhibited ketogenesis in livers perfused with octanoate. The inhibition of hepatic ketogenesis by sulfonylureas was independent of perfusate oleic acid concentration. Additionally, in rat livers perfused with oleic acid in the presence of L-(-)-carnitine (10 mM), submaximal concentrations of tolbutamide and glyburide did not inhibit hepatic ketogenesis. Finally, glyburide infusion into livers perfused with (U- $C)oleic acid (0.1 mM) increased the rate of UC label incorporation into hepatic triglycerides by 2.5-fold. These data suggest that both tolbutamide and glyburide inhibit long-chain fatty acid oxidation by inhibition the key regulatory enzyme, carnitine palmitoyltransferase I, most probably by competing with L-(-)-carnitine.

  5. Effect of sulfonylureas on hepatic fatty acid oxidation

    International Nuclear Information System (INIS)

    In isolated rat livers perfused with oleic acid (0.1 mM), infusion of tolbutamide or glyburide decreased the rate of ketogenesis in a dose-dependent manner. The inhibition of fatty acid oxidation was maximal at 2.0 mM and 10 μM concentrations of tolbutamide and glyburide, respectively. Neither tolbutamide nor glyburide inhibited ketogenesis in livers perfused with octanoate. The inhibition of hepatic ketogenesis by sulfonylureas was independent of perfusate oleic acid concentration. Additionally, in rat livers perfused with oleic acid in the presence of L-(-)-carnitine (10 mM), submaximal concentrations of tolbutamide and glyburide did not inhibit hepatic ketogenesis. Finally, glyburide infusion into livers perfused with [U-1$C]oleic acid (0.1 mM) increased the rate of 14C label incorporation into hepatic triglycerides by 2.5-fold. These data suggest that both tolbutamide and glyburide inhibit long-chain fatty acid oxidation by inhibition the key regulatory enzyme, carnitine palmitoyltransferase I, most probably by competing with L-(-)-carnitine

  6. Diabetes mellitus in the young: Gliptins or sulfonylurea after metformin?

    Directory of Open Access Journals (Sweden)

    J Muthukrishnan

    2012-01-01

    Full Text Available Introduction: Diagnosis and initial management of diabetes mellitus (DM in the young are clinical dilemma. Gliptins may be a safer and more effective option than sulfonylureas. Few Indian studies have addressed this issue of clinical relevance. Aim: To compare the use of sitagliptin and glimepiride as early add-on drugs along with metformin in young patients with DM to achieve optimum glycemic targets. Methods: This was a prospective, open-label, cohort study set in a tertiary care hospital in North India. Newly diagnosed patients of DM ≤35 year of age were initially treated to pre-defined glycemic goals (Fasting plasma glucose (FPG 70-130, post prandial glucose (PPG 180, PPG > 250 mg/dl with/without catabolic symptoms/ketosis were withdrawn. Results: Sitagliptin with metfromin and metfromin alone group fared better than the glimepiride group for glycemic control, lesser treatment failures, and less weight gain. Conclusion : In this limited study, we found that sitagliptin is a safer and more effective option in young, newly diagnosed patients with DM. Findings of this study are relevant for clinical practice in Indian setting.

  7. Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

    Energy Technology Data Exchange (ETDEWEB)

    Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.; Ertel, P.J.; Bemis, K.G.; Robertson, D.W. (Eli Lilly and Company, Indianapolis, IN (USA))

    1991-01-01

    Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09 microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas.

  8. Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

    International Nuclear Information System (INIS)

    Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09 microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas

  9. Computational identification of residues that modulate voltage sensitivity of voltage-gated potassium channels

    Directory of Open Access Journals (Sweden)

    Li Bin

    2005-08-01

    Full Text Available Abstract Background Studies of the structure-function relationship in proteins for which no 3D structure is available are often based on inspection of multiple sequence alignments. Many functionally important residues of proteins can be identified because they are conserved during evolution. However, residues that vary can also be critically important if their variation is responsible for diversity of protein function and improved phenotypes. If too few sequences are studied, the support for hypotheses on the role of a given residue will be weak, but analysis of large multiple alignments is too complex for simple inspection. When a large body of sequence and functional data are available for a protein family, mature data mining tools, such as machine learning, can be applied to extract information more easily, sensitively and reliably. We have undertaken such an analysis of voltage-gated potassium channels, a transmembrane protein family whose members play indispensable roles in electrically excitable cells. Results We applied different learning algorithms, combined in various implementations, to obtain a model that predicts the half activation voltage of a voltage-gated potassium channel based on its amino acid sequence. The best result was obtained with a k-nearest neighbor classifier combined with a wrapper algorithm for feature selection, producing a mean absolute error of prediction of 7.0 mV. The predictor was validated by permutation test and evaluation of independent experimental data. Feature selection identified a number of residues that are predicted to be involved in the voltage sensitive conformation changes; these residues are good target candidates for mutagenesis analysis. Conclusion Machine learning analysis can identify new testable hypotheses about the structure/function relationship in the voltage-gated potassium channel family. This approach should be applicable to any protein family if the number of training examples and

  10. Amiloride-sensitive channels in type I fungiform taste cells in mouse

    Directory of Open Access Journals (Sweden)

    Clapp Tod R

    2008-01-01

    Full Text Available Abstract Background Taste buds are the sensory organs of taste perception. Three types of taste cells have been described. Type I cells have voltage-gated outward currents, but lack voltage-gated inward currents. These cells have been presumed to play only a support role in the taste bud. Type II cells have voltage-gated Na+ and K+ current, and the receptors and transduction machinery for bitter, sweet, and umami taste stimuli. Type III cells have voltage-gated Na+, K+, and Ca2+ currents, and make prominent synapses with afferent nerve fibers. Na+ salt transduction in part involves amiloride-sensitive epithelial sodium channels (ENaCs. In rodents, these channels are located in taste cells of fungiform papillae on the anterior part of the tongue innervated by the chorda tympani nerve. However, the taste cell type that expresses ENaCs is not known. This study used whole cell recordings of single fungiform taste cells of transgenic mice expressing GFP in Type II taste cells to identify the taste cells responding to amiloride. We also used immunocytochemistry to further define and compare cell types in fungiform and circumvallate taste buds of these mice. Results Taste cell types were identified by their response to depolarizing voltage steps and their presence or absence of GFP fluorescence. TRPM5-GFP taste cells expressed large voltage-gated Na+ and K+ currents, but lacked voltage-gated Ca2+ currents, as expected from previous studies. Approximately half of the unlabeled cells had similar membrane properties, suggesting they comprise a separate population of Type II cells. The other half expressed voltage-gated outward currents only, typical of Type I cells. A single taste cell had voltage-gated Ca2+ current characteristic of Type III cells. Responses to amiloride occurred only in cells that lacked voltage-gated inward currents. Immunocytochemistry showed that fungiform taste buds have significantly fewer Type II cells expressing PLC signalling

  11. Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

    OpenAIRE

    Wang, Shuying; Davis, Brian M.; Zwick, Melissa; Waxman, Stephen G.; Albers, Kathryn M.

    2005-01-01

    Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify proteins that might contribute to this loss of sensation. We first show using behavioral testing that thermal sensitivity in aged male and female mice is reduced. Expression of sodium channel (Nav1.8 and Nav1.9) and transient receptor potential vanilloid (TRPV) channels in DRG and peripheral nerves...

  12. Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor

    OpenAIRE

    Tricarico, Domenico; Barbieri, Mariagrazia; Camerino, Diana Conte

    2000-01-01

    Taurine is a sulphonic aminoacid present in high amounts in various tissues including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and anti-schaemic effects. The cellular mechanism of action of taurine is under investigation and appears to involve the interaction of the sulphonic aminoacid with several ion channels.Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K+ channel (KATP) ...

  13. Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats

    OpenAIRE

    Behmenburg, Friederike; Dorsch, Marianne; Huhn, Ragnar; Mally, David; Heinen, André; Hollmann, Markus W.; Berger, Marc M

    2015-01-01

    Background Mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBKCa channels in the rat heart in vitro. Methods Male Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system...

  14. ATP-sensitive potassium channels in capillaries isolated from guinea-pig heart

    Science.gov (United States)

    Schnitzler, Michael Mederos y; Derst, Christian; Daut, Jürgen; Preisig-Müller, Regina

    2000-01-01

    The full-length cDNAs of two different α-subunits (Kir6.1 and Kir6.2) and partial cDNAs of three different β-subunits (SUR1, SUR2A and SUR2B) of ATP-sensitive potassium (KATP) channels of the guinea-pig (gp) were obtained by screening a cDNA library from the ventricle of guinea-pig heart. Cell-specific reverse-transcriptase PCR with gene-specific intron-spanning primers showed that gpKir6.1, gpKir6.2 and gpSUR2B were expressed in a purified fraction of capillary endothelial cells. In cardiomyocytes, gpKir6.1, gpKir6.2, gpSUR1 and gpSUR2A were detected. Patch-clamp measurements were carried out in isolated capillary fragments consisting of 3–15 endothelial cells. The membrane capacitance measured in the whole-cell mode was 19.9 ± 1.0 pF and was independent of the length of the capillary fragment, which suggests that the endothelial cells were not electrically coupled under our experimental conditions. The perforated-patch technique was used to measure the steady-state current-voltage relation of capillary endothelial cells. Application of K+ channel openers (rilmakalim or diazoxide) or metabolic inhibition (250 μm 2,4-dinitrophenol plus 10 mM deoxyglucose) induced a current that reversed near the calculated K+ equilibrium potential. Rilmakalim (1 μm), diazoxide (300 μm) and metabolic inhibition increased the slope conductance measured at −55 mV by a factor of 9.0 (±1.8), 2.5 (±0.2) and 3.9 (±1.7), respectively. The effects were reversed by glibenclamide (1 μm). Our results suggest that capillary endothelial cells from guinea-pig heart express KATP channels composed of SUR2B and Kir6.1 and/or Kir6.2 subunits. The hyperpolarization elicited by the opening of KATP channels may lead to an increase in free cytosolic Ca2+, and thus modulate the synthesis of NO and the permeability of the capillary wall. PMID:10835035

  15. Transformation kinetics and mechanism of the sulfonylurea herbicides pyrazosulfuron ethyl and halosulfuron methyl in aqueous solutions.

    Science.gov (United States)

    Zheng, Wei; Yates, Scott R; Papiernik, Sharon K

    2008-08-27

    Pyrazosulfuron ethyl (PE) and halosulfuron methyl (HM) are two new highly active sulfonylurea herbicides that have been widely used for weed control in a variety of vegetables and other crops. These two herbicides have similar molecular structures, differing only in the substitutions on the pyrazole ring. Chemical hydrolysis is a primary process affecting the environmental fate of sulfonylurea pesticides. The hydrolytic transformation kinetics of PE and HM were investigated as a function of pH and temperature. For both herbicides, the hydrolysis rate was pH-dependent and increased with increasing temperature. The hydrolysis of both sulfonylureas was much faster in acidic or basic media than under neutral conditions. Identification of hydrolytic products by liquid chromatography-mass spectrometry (LC-MS) suggested that both PE and HM were subject to cleavage and contraction of the sulfonylurea bridge. The hydrolysis rate of HM was significantly higher than that of PE in alkaline solutions, despite their structural similarity. A chlorine substitution on HM's pyrazole ring makes HM more susceptible to bridge contraction than PE under basic conditions. The hydrolysis of HM and PE was relatively unaffected by the presence of cyclic oligosaccharides (cyclodextrins), indicating that natural OH-containing organic compounds occurring in aquatic environments may have little impact on the transformation of these sulfonylurea herbicides. PMID:18651743

  16. Effect of ionizing radiation on voltage-sensitive sodium channels in the brain

    International Nuclear Information System (INIS)

    It has generally been assumed that the mature central nervous system is not sensitive to ionizing radiation because cell division of neurons no longer occurs. In general, rather large doses have been required in order to observe changes in morphological, physiological, biochemical, and behavioral endpoints. In order to focus on one of the most fundamental mechanisms in the generation and propagation of action potentials, experiments were undertaken to determine whether ionizing radiation could alter the ability of the neurotoxins, veratridine and batrachotoxin, to stimulate /sup 22/Na uptake into synaptosomes. Synaptosomal preparations were irradiated with varying doses of high-energy electrons or gamma photons. Both qualities of radiation reduced /sup 22/Na uptake stimulated by either toxin after doses as low as 100 rad in a concentration-dependent manner. When concentration-response curves for the neurotoxins were derived at increasing doses of radiation, the maximum effectiveness of the toxins was progressively diminished. The data suggest that the central nervous system may be more sensitive to the effects of ionizing radiation than previously believed and that the effects observed may reflect a loss of viable sodium channels. Such effects may have biological significance

  17. Evolution of vertebrate transient receptor potential vanilloid 3 channels: opposite temperature sensitivity between mammals and western clawed frogs.

    Directory of Open Access Journals (Sweden)

    Shigeru Saito

    2011-04-01

    Full Text Available Transient Receptor Potential (TRP channels serve as temperature receptors in a wide variety of animals and must have played crucial roles in thermal adaptation. The TRP vanilloid (TRPV subfamily contains several temperature receptors with different temperature sensitivities. The TRPV3 channel is known to be highly expressed in skin, where it is activated by warm temperatures and serves as a sensor to detect ambient temperatures near the body temperature of homeothermic animals such as mammals. Here we performed comprehensive comparative analyses of the TRPV subfamily in order to understand the evolutionary process; we identified novel TRPV genes and also characterized the evolutionary flexibility of TRPV3 during vertebrate evolution. We cloned the TRPV3 channel from the western clawed frog Xenopus tropicalis to understand the functional evolution of the TRPV3 channel. The amino acid sequences of the N- and C-terminal regions of the TRPV3 channel were highly diversified from those of other terrestrial vertebrate TRPV3 channels, although central portions were well conserved. In a heterologous expression system, several mammalian TRPV3 agonists did not activate the TRPV3 channel of the western clawed frog. Moreover, the frog TRPV3 channel did not respond to heat stimuli, instead it was activated by cold temperatures. Temperature thresholds for activation were about 16 °C, slightly below the lower temperature limit for the western clawed frog. Given that the TRPV3 channel is expressed in skin, its likely role is to detect noxious cold temperatures. Thus, the western clawed frog and mammals acquired opposite temperature sensitivity of the TRPV3 channel in order to detect environmental temperatures suitable for their respective species, indicating that temperature receptors can dynamically change properties to adapt to different thermal environments during evolution.

  18. Effects of mitochondrial ATP-sensitive potassium channels on the proliferation and secretion of human airway smooth muscle cells.

    OpenAIRE

    2014-01-01

    Bronchial asthma is the common chronic inflammatory disease and is characterized by chronic airway inflammation, airway remodeling, and airway hyperreactivity (AHR). Aim of this study was to investigate the effects of mitochondrial ATP-sensitive potassium channels (MitoKATP) on the proliferation and secretion of human airway smooth muscle cells (HASMCs). HASMCs were treated with the serum from asthmatic patients to establish HASMCs asthma model of passive sensitization. Rhodamine 123 (R-123) ...

  19. Cross-resistance pattern and alternative herbicides for Cyperus difformis resistant to sulfonylurea herbicides in Korea.

    Science.gov (United States)

    Kuk, Yong In; Kim, Kyung Hyun; Kwon, Oh Do; Lee, Do Jin; Burgos, Nilda R; Jung, Sunyo; Guh, Ja Ock

    2004-01-01

    A Cyperus difformis L accession from Chonnam province, Korea was tested for resistance to the sulfonylurea herbicide, imazosulfuron. The accession was confirmed to be resistant (R) and was cross-resistant to other sulfonylurea herbicides, bensulfuron-methyl, cyclosulfamuron and pyrazosulfuron-ethyl, the pyrimidinyl thiobenzoate herbicide, bispyribac-sodium, and the imidazolinone herbicide imazapyr, but not to imazaquin. Multiple resistance was tested using twelve herbicides with target sites other than acetolactate synthase (ALS). The R biotype could be controlled by other herbicides with different modes of action such as butachlor, carfentrazone-ethyl, clomeprop, dithiopyr, esprocarb, mefenacet, oxadiazon, pretilachlor, pyrazolate and thiobencarb, applied to soil at recommended rates. Several sulfonylurea herbicide-based mixtures can control both the R and S biotypes of C difformis, except sulfonylurea plus dimepiperate, molinate or pyriftalid, and pyrazolate plus butachlor. Although mixtures of sulfonylurea herbicides might be more effective, they should be avoided and used only in special cases. In terms of in vitro ALS activity, the R biotype was 1139-, 3583-, 1482-, 416-, 5- and 9-fold more resistant to bensulfuron-methyl, cyclosulfamuron, imazosulfuron, pyrazosulfuron-ethyl, bispyribac-sodium and imazapyr, respectively, than the S biotype. The in vivo ALS activity of the R biotype was also less affected by the sulfonylurea herbicides, imazosulfuron and pyrazosulfuron-ethyl, than the S biotype. Results of in vitro and in vivo ALS assays indicated that the resistance mechanism of C difformis to ALS inhibitor herbicides was primarily due to an alteration in the target enzyme, ALS. Greenhouse experiments showed delayed flowering and reduced seed production of the R biotype, which could possibly result in reduced fitness. This unusual observation needs to be confirmed in field situations. PMID:14727745

  20. Empagliflozin as Add-on to Metformin Plus Sulfonylurea in Patients With Type 2 Diabetes

    OpenAIRE

    Häring, Hans-Ulrich; Merker, Ludwig; Seewaldt-Becker, Elke; WEIMER Marc; Meinicke, Thomas; Woerle, Hans J.; Broedl, Uli C.; ,

    2013-01-01

    OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients inadequately controlled on metformin and sulfonylurea (HbA1c ≥7 to ≤10%) were randomized and treated with once-daily empagliflozin 10 mg (n = 225), empagliflozin 25 mg (n = 216), or placebo (n = 225) for 24 weeks. The primary end point was change from baseline in HbA1c at week 24. Key secondary end points were ch...

  1. Selective potentiation of insulin-mediated glucose disposal in normal dogs by the sulfonylurea glipizide.

    OpenAIRE

    Putnam, W S; Andersen, D K; Jones, R S; Lebovitz, H E

    1981-01-01

    Investigative data have suggested that the extrapancreatic actions of the sulfonylureas may be paramount in their chronic antidiabetic action. The present study examines the effects of chronic sulfonylurea treatment on in vivo insulin action. Peripheral insulin levels, hepatic glucose production (Ra), and overall glucose disposal (Rd) were studied in six awake, normal dogs given both 0.5 and 1.0 mU/kg per min pork insulin for 2.5 h. This produces stable hyperinsulinemia from 15 to 150 min. Fa...

  2. L—type calcium channel blockers inhibit the development but not the expression of sensitization to morphine in mice

    Institute of Scientific and Technical Information of China (English)

    ZhanQ; ZhenJW

    2002-01-01

    The relationship between opioid actions and L-type calcium channel blockers has been well documented.However,there is no report relevant to L-type calcium channel blockers and morphinesensitization,which is suggested to be an analog of behaviors that are the characteristics of drug addiction.Here the effects of three L-type calcium channel blockers,nimodipine,nifedipine and verapamil,on morphine-induced locomotor activity,the development and the expression of sensitization to morphine were studied systematically.The results showed that both nimodipine and verapamil attenuated,while nifedipine had only a tendency to decrease morphine-induced locomotor activity.All the three drugs inhibited the development of sensitization to morphine.However,none of them showed any effects on the expression of morphine sensitization.These results indicate that blocking L-tpye calcium channel attenuates the locomotor stimulating effects of morphine and inhibits the development but not the expression of morphine-sensitization.

  3. First direct electron microscopic visualization of a tight spatial coupling between GABAA-receptors and voltage-sensitive calcium channels

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Belhage, B; Schousboe, A

    1992-01-01

    Using cerebellar granule neurons in culture it was demonstrated that exposure of the cells to the GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) leads to an increase in the number of voltage-gated calcium channels as revealed by quantitative preembedding indirect...... immunogold labelling using a monoclonal antibody specific for phenylalkylamine and dihydropyridine sensitive Ca2+ channels. Using the same technique and a monoclonal antibody (bd-17) to the beta 2/beta 3-subunit of the GABAA-receptor, double labelling of Ca2+ channels and GABAA-receptors with gold particles...... of different and well defined sizes were performed. This showed that in THIP-treated cultures 20% of GABAA-receptors in cell processes were located in close proximity (i.e. within 40 nm) of Ca2+ channels in the plasma membrane. This was not observed in non-treated cultures nor was it observed in cell...

  4. Tx1, from Phoneutria nigriventer spider venom, interacts with dihydropyridine sensitive-calcium channels in GH3 cells

    International Nuclear Information System (INIS)

    The aim of this work was to use the binding assay of tritiated-dihydropyridine and radioiodinated Tx1, isolated from the Phoneutria nigriventer venom, in order to show the presence of Cav1 calcium channels on pituitary tumour cell (GH3). We showed that GH3 cells have specific sites for 125I-Tx1, which are sensitive to nifedipine (∼20%). Reverse competition assay with 3H-PN200-110 (40% inhibition) and electrophysiological data (50% inhibition) suggest that Cav1 calcium channels are target sites for this toxin. To summarize, Tx1 binds to specific sites on GH3 cells and this interaction results in Cav1 calcium channel blockade. 3H-PN200-110 and 125I-Tx1 binding assays proved to be useful tools to show the presence of calcium channels on GH3 cells. (author)

  5. Surface-sensitive two-dimensional magneto-fingerprint in mesoscopic Bi2Se3 channels.

    Science.gov (United States)

    Kandala, Abhinav; Richardella, Anthony; Zhang, Duming; Flanagan, Thomas C; Samarth, Nitin

    2013-06-12

    Periodic Aharonov–Bohm and Altshuler–Aronov–Spivak oscillations have traditionally been observed in lateral transport through patterned mesoscopic loops of diffusive conductors. However, our studies of perpendicular-to-plane magnetotransport in straight-channel, diffusive devices of epitaxial Bi2Se3 surprisingly reveal signatures of Aharonov–Bohm orbits, periodic conductance fluctuation magneto-fingerprints, even though the devices are not explicitly patterned into loops. We show that the length scale of these orbits corresponds to the typical perimeter of triangular terraces found on the surface of these thin film devices, strongly suggesting that the periodic magneto-fingerprint arises from coherent scattering of electron waves from the step-edges. Our interpretation is bolstered by control measurements in devices without such surface morphology that only show a conventional, aperiodic magneto-fingerprint. These results show that lithographically patterned Bi2Se3 devices provide a novel class of mesoscopic physical systems for systematic studies of coherent surface sensitive transport. PMID:23642037

  6. Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution

    Science.gov (United States)

    Majhi, Rakesh Kumar; Saha, Somdatta; Kumar, Ashutosh; Ghosh, Arijit; Swain, Nirlipta; Goswami, Luna; Mohapatra, Pratyush; Maity, Apratim; Kumar Sahoo, Vivek

    2015-01-01

    Transient Receptor Potential cation channel, subfamily Melastatin, member 8 (TRPM8) is involved in detection of cold temperature, different noxious compounds and in execution of thermo- as well as chemo-sensitive responses at cellular levels. Here we explored the molecular evolution of TRPM8 by analyzing sequences from various species. We elucidate that several regions of TRPM8 had different levels of selection pressure but the 4th–5th transmembrane regions remain highly conserved. Analysis of synteny suggests that since vertebrate origin, TRPM8 gene is linked with SPP2, a bone morphogen. TRPM8, especially the N-terminal region of it, seems to be highly variable in human population. We found 16,656 TRPM8 variants in 1092 human genomes with top variations being SNPs, insertions and deletions. A total of 692 missense mutations are also mapped to human TRPM8 protein of which 509 seem to be delateroiours in nature as supported by Polyphen V2, SIFT and Grantham deviation score. Using a highly specific antibody, we demonstrate that TRPM8 is expressed endogenously in the testis of rat and sperm cells of different vertebrates ranging from fish to higher mammals. We hypothesize that TRPM8 had emerged during vertebrate evolution (ca 450 MYA). We propose that expression of TRPM8 in sperm cell and its role in regulating sperm function are important factors that have guided its molecular evolution, and that these understandings may have medical importance. PMID:26500819

  7. SPAK Sensitive Regulation of the Epithelial Na+ Channel ENaC

    Directory of Open Access Journals (Sweden)

    Musaab Ahmed

    2015-06-01

    Full Text Available Background/Aims: The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na+,K+,2Cl- cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na+ channel (ENaC. Methods: ENaC was expressed in Xenopus oocytes with or without additional expression of wild type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK or catalytically inactive D212ASPAK, and ENaC activity estimated from amiloride (50 µM sensitive current (Iamil in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine Iamil in colonic tissue from wild type mice (spakwt/wt and from gene targeted mice carrying WNK insensitive SPAK (spaktg/tg. Results: Iamil was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes Iamil was significantly increased following coexpression of wild-type SPAK and T233ESPAK, but not following coexpression of T233ASPAK or D212ASPAK. Colonic Iamil was significantly higher in spakwt/wt than in spaktg/tg mice. Conclusion: SPAK has the potential to up-regulate ENaC.

  8. Influence of Thromboxane A2 on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

    Science.gov (United States)

    Jeong, In Seok; Cho, Hwa Jin; Cho, Jeong Gwan; Kim, Sang Hyung; Na, Kook Joo

    2016-01-01

    Background and Objectives Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. Subjects and Methods Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. Results In the excised inside-out patches, the thromboxane A2 analog, U46619, decreased the KATP channel activity in a dose-dependent manner; however, the thromboxane A2 receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced KATP channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced KATP channel activity. Conclusion Thromboxane A2 may inhibit KATP channel activity, and may have a harmful effect on ischemic myocardium. PMID:27482267

  9. TMEM16F is a component of a Ca2+-activated Cl- channel but not a volume-sensitive outwardly rectifying Cl- channel.

    Science.gov (United States)

    Shimizu, Takahiro; Iehara, Takahiro; Sato, Kaori; Fujii, Takuto; Sakai, Hideki; Okada, Yasunobu

    2013-04-15

    TMEM16 (transmembrane protein 16) proteins, which possess eight putative transmembrane domains with intracellular NH2- and COOH-terminal tails, are thought to comprise a Cl(-) channel family. The function of TMEM16F, a member of the TMEM16 family, has been greatly controversial. In the present study, we performed whole cell patch-clamp recordings to investigate the function of human TMEM16F. In TMEM16F-transfected HEK293T cells but not TMEM16K- and mock-transfected cells, activation of membrane currents with strong outward rectification was found to be induced by application of a Ca(2+) ionophore, ionomycin, or by an increase in the intracellular free Ca(2+) concentration. The free Ca(2+) concentration for half-maximal activation of TMEM16F currents was 9.6 μM, which is distinctly higher than that for TMEM16A/B currents. The outwardly rectifying current-voltage relationship for TMEM16F currents was not changed by an increase in the intracellular Ca(2+) level, in contrast to TMEM16A/B currents. The Ca(2+)-activated TMEM16F currents were anion selective, because replacing Cl(-) with aspartate(-) in the bathing solution without changing cation concentrations caused a positive shift of the reversal potential. The anion selectivity sequence of the TMEM16F channel was I(-) > Br(-) > Cl(-) > F(-) > aspartate(-). Niflumic acid, a Ca(2+)-activated Cl(-) channel blocker, inhibited the TMEM16F-dependent Cl(-) currents. Neither overexpression nor knockdown of TMEM16F affected volume-sensitive outwardly rectifying Cl(-) channel (VSOR) currents activated by osmotic swelling or apoptotic stimulation. These results demonstrate that human TMEM16F is an essential component of a Ca(2+)-activated Cl(-) channel with a Ca(2+) sensitivity that is distinct from that of TMEM16A/B and that it is not related to VSOR activity. PMID:23426967

  10. Sensitivity of a hydraulic model to changes in channel erosion during extreme flooding

    OpenAIRE

    Wong, Jefferson S.; Freer, Jim E; Bates, Paul D.; Stephens, Elisabeth M.

    2014-01-01

    Recent research into flood modelling has primarily concentrated on the simulation of inundation flow without considering the influences of channel morphology. River channels are often represented by a simplified geometry that is implicitly assumed to remain unchanged during flood simulations. However, field evidence demonstrates that significant morphological changes can occur during floods to mobilise the boundary sediments. Despite this, the effect of channel morphology on model results has...

  11. Inhibition of the ATP-sensitive potassium channel from mouse pancreatic β-cells by surfactants

    OpenAIRE

    Smith, Paul A.; Proks, Peter

    1998-01-01

    We have used patch-clamp methods to study the effects of the detergents, Cremophor, Tween 80 and Triton X100 on the KATP channel in the pancreatic β-cell from mouse.All three detergents blocked KATP channel activity with the following order of potency: Tween 80 (KiTriton X100 (Ki=350 nM)>Cremophor. In all cases the block was poorly reversible.Single-channel studies suggested that at low doses, the detergents act as slow blockers of the KATP channel.Unlike the block produced by tolbutamide, th...

  12. Mass spectrometry of the photolysis of sulfonylurea herbicides in Prairie waters.

    Science.gov (United States)

    Headley, John V; Du, Jing-Long; Peru, Kerry M; McMartin, Dena W

    2010-01-01

    This review of mass spectrometry of sulfonylurea herbicides includes a focus on studies relevant to Canadian Prairie waters. Emphasis is given to data gaps in the literature for the rates of photolysis of selected sulfonylurea herbicides in different water matrices. Specifically, results are evaluated for positive ion electrospray tandem mass spectrometry with liquid chromatography separation for the study of the photolysis of chlorsulfuron, tribenuron-methyl, thifensulfuron-methyl, metsulfuron-methyl, and ethametsulfuron-methyl. LC-MS/MS is shown to be the method of choice for the quantification of sulfonylurea herbicides with instrumental detection limits ranging from 1.3 to 7.2 pg (on-column). Tandem mass spectrometry coupled with the use of authentic standards likewise has proven to be well suited for the identification of transformation products. To date, however, the power of time-of-flight MS and ultrahigh resolution MS has not been exploited fully for the identification of unknown photolysis products. Dissipation of the herbicides under natural sunlight fit pseudo-first-order kinetics with half-life values ranging from 4.4 to 99 days. For simulated sunlight, radiation wavelengths shorter than 400 nm are required to induce significant photolytic reactions. The correlation between field dissipation studies and laboratory photolysis experiments suggests that photolysis is a major pathway for the dissipation of some sulfonylurea herbicides in natural Prairie waters. PMID:19890978

  13. Highly Sensitive Multi-Channel IDC Sensor Array for Low Concentration Taste Detection

    Directory of Open Access Journals (Sweden)

    Md. Rajibur Rahaman Khan

    2015-06-01

    Full Text Available In this study, we designed and developed an interdigitated capacitor (IDC-based taste sensor array to detect different taste substances. The designed taste sensing array has four IDC sensing elements. The four IDC taste sensing elements of the array are fabricated by incorporating four different types of lipids into the polymer, dioctyl phenylphosphonate (DOPP and tetrahydrofuran (THF to make the respective dielectric materials that are individually placed onto an interdigitated electrode (IDE via spin coating. When the dielectric material of an IDC sensing element comes into contact with a taste substance, its dielectric properties change with the capacitance of the IDC sensing element; this, in turn, changes the voltage across the IDC, as well as the output voltage of each channel of the system. In order to assess the effectiveness of the sensing system, four taste substances, namely sourness (HCl, saltiness (NaCl, sweetness (glucose and bitterness (quinine-HCl, were tested. The IDC taste sensor array had rapid response and recovery times of about 12.9 s and 13.39 s, respectively, with highly stable response properties. The response property of the proposed IDC taste sensor array was linear, and its correlation coefficient R2 was about 0.9958 over the dynamic range of the taste sensor array as the taste substance concentration was varied from 1 μM to 1 M. The proposed IDC taste sensor array has several other advantages, such as real-time monitoring capabilities, high sensitivity 45.78 mV/decade, good reproducibility with a standard deviation of about 0.029 and compactness, and the circuitry is based on readily available and inexpensive electronic components. The proposed IDC taste sensor array was compared with the potentiometric taste sensor with respect to sensitivity, dynamic range width, linearity and response time. We found that the proposed IDC sensor array has better performance. Finally, principal component analysis (PCA was applied

  14. Reach-scale channel sensitivity to multiple human activities and natural events: Lower Santa Clara River, California, USA

    Science.gov (United States)

    Downs, Peter W.; Dusterhoff, Scott R.; Sears, William A.

    2013-05-01

    Understanding the cumulative impact of natural and human influences on the sensitivity of channel morphodynamics, a relative measure between the drivers for change and the magnitude of channel response, requires an approach that accommodates spatial and temporal variability in the suite of primary stressors. Multiple historical data sources were assembled to provide a reach-scale analysis of the lower Santa Clara River (LSCR) in Ventura County, California, USA. Sediment supply is naturally high due to tectonic activity, earthquake-generated landslides, wildfires, and high magnitude flow events during El Niño years. Somewhat typically for the region, the catchment has been subject to four reasonably distinct land use and resource management combinations since European-American settlement. When combined with analysis of channel morphological response (quantifiable since ca. 1930), reach-scale and temporal differences in channel sensitivity become apparent. Downstream reaches have incised on average 2.4 m and become narrower by almost 50% with changes focused in a period of highly sensitive response after about 1950 followed by forced insensitivity caused by structural flood embankments and a significant grade control structure. In contrast, the middle reaches have been responsive but are morphologically resilient, and the upstream reaches show a mildly sensitive aggradational trend. Superimposing the natural and human drivers for change reveals that large scale stressors (related to ranching and irrigation) have been replaced over time by a suite of stressors operating at multiple spatial scales. Lower reaches have been sensitive primarily to 'local' scale impacts (urban growth, flood control, and aggregate mining) whereas, upstream, catchment-scale influences still prevail (including flow regulation and climate-driven sediment supply factors). These factors illustrate the complexity inherent to cumulative impact assessment in fluvial systems, provide evidence for a

  15. Regulation of substantia nigra pars reticulata GABAergic neuron activity by hydrogen peroxide via flufenamic acid-sensitive channels and KATP channels

    Directory of Open Access Journals (Sweden)

    Christian R Lee

    2011-04-01

    Full Text Available Substantia nigra pars reticulata (SNr GABAergic neurons are key output neurons of the basal ganglia. Given the role of these neurons in motor control, it is important to understand factors that regulate their firing rate and pattern. One potential regulator is hydrogen peroxide (H2O2, a reactive oxygen species that is increasingly recognized as a neuromodulator. We used whole-cell current clamp recordings of SNr GABAergic neurons in guinea-pig midbrain slices to determine how H2O2 affects the activity of these neurons and to explore the classes of ion channels underlying those effects. Elevation of H2O2 levels caused an increase in the spontaneous firing rate of SNr GABAergic neurons, whether by application of exogenous H2O2 or amplification of endogenous H2O2 through inhibition of glutathione peroxidase with mercaptosuccinate. This effect was reversed by flufenamic acid, implicating transient receptor potential (TRP channels. Conversely, depletion of endogenous H2O2 by catalase, a peroxidase enzyme, decreased spontaneous firing rate and firing precision of SNr neurons, demonstrating tonic control of firing rate by H2O2. Elevation of H2O2 in the presence of flufenamic acid revealed an inhibition of tonic firing that was prevented by blockade of ATP-sensitive K+ (KATP channels with glibenclamide. In contrast to guinea-pig SNr neurons, the dominant effect of H2O2 elevation in mouse SNr GABAergic neurons was hyperpolarization, indicating a species difference in H2O2-dependent regulation. Thus, H2O2 is an endogenous modulator of SNr GABAergic neurons, acting primarily through presumed TRP channels in guinea pig, with additional modulation via KATP channels to regulate SNr output.

  16. Differential regulation of proton-sensitive ion channels by phospholipids: a comparative study between ASICs and TRPV1.

    Directory of Open Access Journals (Sweden)

    Hae-Jin Kweon

    Full Text Available Protons are released in pain-generating pathological conditions such as inflammation, ischemic stroke, infection, and cancer. During normal synaptic activities, protons are thought to play a role in neurotransmission processes. Acid-sensing ion channels (ASICs are typical proton sensors in the central nervous system (CNS and the peripheral nervous system (PNS. In addition to ASICs, capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1 channels can also mediate proton-mediated pain signaling. In spite of their importance in perception of pH fluctuations, the regulatory mechanisms of these proton-sensitive ion channels still need to be further investigated. Here, we compared regulation of ASICs and TRPV1 by membrane phosphoinositides, which are general cofactors of many receptors and ion channels. We observed that ASICs do not require membrane phosphatidylinositol 4-phosphate (PI(4P or phosphatidylinositol 4,5-bisphosphate (PI(4,5P2 for their function. However, TRPV1 currents were inhibited by simultaneous breakdown of PI(4P and PI(4,5P2. By using a novel chimeric protein, CF-PTEN, that can specifically dephosphorylate at the D3 position of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5P3, we also observed that neither ASICs nor TRPV1 activities were altered by depletion of PI(3,4,5P3 in intact cells. Finally, we compared the effects of arachidonic acid (AA on two proton-sensitive ion channels. We observed that AA potentiates the currents of both ASICs and TRPV1, but that they have different recovery aspects. In conclusion, ASICs and TRPV1 have different sensitivities toward membrane phospholipids, such as PI(4P, PI(4,5P2, and AA, although they have common roles as proton sensors. Further investigation about the complementary roles and respective contributions of ASICs and TRPV1 in proton-mediated signaling is necessary.

  17. Temperature-sensitive gating of TRPV1 channel as probed by atomistic simulations of its trans- and juxtamembrane domains.

    Science.gov (United States)

    Chugunov, Anton O; Volynsky, Pavel E; Krylov, Nikolay A; Nolde, Dmitry E; Efremov, Roman G

    2016-01-01

    Heat-activated transient receptor potential channel TRPV1 is one of the most studied eukaryotic proteins involved in temperature sensation. Upon heating, it exhibits rapid reversible pore gating, which depolarizes neurons and generates action potentials. Underlying molecular details of such effects in the pore region of TRPV1 is of a crucial importance to control temperature responses of the organism. Despite the spatial structure of the channel in both open (O) and closed (C) states is known, microscopic nature of channel gating and mechanism of thermal sensitivity are still poorly understood. In this work, we used unrestrained atomistic molecular dynamics simulations of TRPV1 (without N- and C-terminal cytoplasmic domains) embedded into explicit lipid bilayer in its O- and C-states. We found that the pore domain with its neighboring loops undergoes large temperature-dependent conformational transitions in an asymmetric way, when fragments of only one monomer move with large amplitude, freeing the pore upon heating. Such an asymmetrical gating looks rather biologically relevant because it is faster and more reliable than traditionally proposed "iris-like" symmetric scheme of channel opening. Analysis of structural, dynamic, and hydrophobic organization of the pore domain revealed entropy growth upon TRPV1 gating, which is in line with current concepts of thermal sensitivity. PMID:27612191

  18. Studies of the voltage-sensitive calcium channels in smooth muscle, neuronal, and cardiac tissues using 1,4-dihydropyridine calcium channel antagonists and activators

    International Nuclear Information System (INIS)

    This study describes the investigation of the voltage-sensitive Ca+ channels in vascular and intestinal smooth muscle, chick neural retina cells and neonatal rat cardiac myocytes using 1,4-dihydropyridine Ca2+ channel antagonists and activators. In rat aorta, the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) produced Ca2+-dependent contractile responses. The responses to TPA were blocked by the Ca2+ channel antagonists. The effects of the enantiomers of Bay K 8644 and 202-791 were characterized in both rat tail artery and guinea pig ileal longitudinal smooth muscle preparations using pharmacologic and radioligand binding assays. The (S)-enantiomers induced contraction and potentiated the responses to K+ depolarization. The (R)-enantiomers inhibited the tension responses to K+. All the enantiomers inhibited specific [3H]nitrendipine binding. The pharmacologic activities of both activator and antagonist ligands correlated on a 1:1 basis with the binding affinities. In chick neural retina cells the (S)-enantiomers of Bay K 8644 and 202-791 enhanced Ca2+ influx. In contrast, the (R)-enantiomers inhibited Ca2+ influx. The enantiomers of Bay K 8644 and 202-791 inhibited specific [3H]PN 200-110 binding competitively. Binding of 1,4-dihydropyridines was characterized in neonatal rat heart cells

  19. Rapid determination of sixteen sulfonylurea herbicides in surface water by solid phase extraction cleanup and ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry.

    Science.gov (United States)

    Yan, Cuimin; Zhang, Beibei; Liu, Wenyuan; Feng, Feng; Zhao, Yonggang; Du, Hui

    2011-11-15

    A sensitive and very fast analytical method has been developed for the simultaneous quantification of sixteen sulfonylurea herbicides in surface water. An ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry method with solid phase extraction for sample cleanup has been developed for screening sixteen sulfonylurea herbicides (oxasulfuron, thifensulfuron-methyl, cinosulfuron, metsulfuron methyl, sulfometuron methyl, triasulfuron, rimsulfuron, ethametsulfuron methyl, sulfosulfuron, tribenuron methyl, bensulfuron methyl, iodosulfuron methyl, pyrazosulfuron ethyl, prosulfuron, chlorimuron ethyl, ethoxysulfuron) in water samples simultaneously within 12 min. Water samples were acidified, and the target herbicides were extracted by passing through ProElut C18 extraction cartridges. After drying by nitrogen flow, the cartridges were eluted with elution solvents, and the eluate was then evaporated to dryness, redissolved and analyzed. The mobile phase composed of 0.02% formic acid and acetonitrile using gradient elution. A triple quadrupole mass spectrometer equipped with an electrospray ionization source operated in the positive ion with selective reaction monitoring mode. Each of the analytes in all the samples was monitored using protonated molecule and its two characteristic fragment ions for confirmation. The limits of detection for all analytes were below 1.0 ng/mL, except for sulfosulfuron and prosulfuron, and limits of quantitation were between 1 and 8 ng/mL for this method. Three water types were used for the validation of the method. PMID:21983197

  20. Numerical sensitivity analysis of passive EHF and SMMW channels to tropospheric water vapor, clouds, and precipitation

    Science.gov (United States)

    Gasiewski, A. J.

    1992-01-01

    Potential uses of specific extremely High Frequency (EHF) and Sub-Millimeter-Wave (SMMW) channels at 90, 166, 183, 220, 325, 340, and 410 GHz for passive spaceborne remote sensing of the troposphere and lower stratosphere are investigated using an iterative numerical radiative transfer model. Collectively, these channels offer potential for high spatial resolution imaging using diffraction-limited apertures of practical size, along with the ability to profile water vapor, map precipitation beneath optically opaque cloud cover, and to measure nonprecipitating cloud (e.g., cirrus) parameters. A widely-spaced set of EHF and SMMW channels can yield observable degrees of freedom related to clouds and precipitation not available by exclusively using the more thoroughly studied microwave channels below 183 GHz. A new passive airborne imaging instrument for tropospheric meteorological sensing is described.

  1. Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels

    Science.gov (United States)

    Yu, Haibo; Lin, Zhihong; Mattmann, Margrith E.; Zou, Beiyan; Terrenoire, Cecile; Zhang, Hongkang; Wu, Meng; McManus, Owen B.; Kass, Robert S.; Lindsley, Craig W.; Hopkins, Corey R.; Li, Min

    2013-01-01

    Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1–KCNEx complexes. Mutations in either KCNQ1 or KCNE1 genes result in diseases in brain, heart, and the respiratory system. In addition to complexities arising from existence of five KCNE subunits, KCNE1 to KCNE5, recent studies in heterologous systems suggest unorthodox stoichiometric dynamics in subunit assembly is dependent on KCNE expression levels. The resultant KCNQ1–KCNE channel complexes may have a range of zero to two or even up to four KCNE subunits coassembling per KCNQ1 tetramer. These findings underscore the need to assess the selectivity of small-molecule KCNQ1 modulators on these different assemblies. Here we report a unique small-molecule gating modulator, ML277, that potentiates both homomultimeric KCNQ1 channels and unsaturated heteromultimeric (KCNQ1)4(KCNE1)n (n < 4) channels. Progressive increase of KCNE1 or KCNE3 expression reduces efficacy of ML277 and eventually abolishes ML277-mediated augmentation. In cardiomyocytes, the slowly activating delayed rectifier potassium current, or IKs, is believed to be a heteromultimeric combination of KCNQ1 and KCNE1, but it is not entirely clear whether IKs is mediated by KCNE-saturated KCNQ1 channels or by channels with intermediate stoichiometries. We found ML277 effectively augments IKs current of cultured human cardiomyocytes and shortens action potential duration. These data indicate that unsaturated heteromultimeric (KCNQ1)4(KCNE1)n channels are present as components of IKs and are pharmacologically distinct from KCNE-saturated KCNQ1–KCNE1 channels. PMID:23650380

  2. Intracellular signalling mechanism responsible for modulation of sarcolemmal ATP-sensitive potassium channels by nitric oxide in ventricular cardiomyocytes.

    Science.gov (United States)

    Zhang, Dai-Min; Chai, Yongping; Erickson, Jeffrey R; Brown, Joan Heller; Bers, Donald M; Lin, Yu-Fung

    2014-03-01

    The ATP-sensitive potassium (KATP) channels are crucial for stress adaptation in the heart. It has previously been suggested that the function of KATP channels is modulated by nitric oxide (NO), a gaseous messenger known to be cytoprotective; however, the underlying mechanism remains poorly understood. Here we sought to delineate the intracellular signalling mechanism responsible for NO modulation of sarcolemmal KATP (sarcKATP) channels in ventricular cardiomyocytes. Cell-attached patch recordings were performed in transfected human embryonic kidney (HEK) 293 cells and ventricular cardiomyocytes freshly isolated from adult rabbits or genetically modified mice, in combination with pharmacological and biochemical approaches. Bath application of the NO donor NOC-18 increased the single-channel activity of Kir6.2/SUR2A (i.e., the principal ventricular-type KATP) channels in HEK293 cells, whereas the increase was abated by KT5823 [a selective cGMP-dependent protein kinase (PKG) inhibitor], mercaptopropionyl glycine [MPG; a reactive oxygen species (ROS) scavenger], catalase (an H2O2-degrading enzyme), myristoylated autocamtide-2 related inhibitory peptide (mAIP) selective for Ca2+ / calmodulin-dependent protein kinase II (CaMKII) and U0126 [an extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor], respectively. The NO donors NOC-18 and N-(2-deoxy-α,β-d-glucopyranose-2-)-N2-acetyl-S-nitroso-d,l-penicillaminamide (glycol-SNAP-2) were also capable of stimulating native sarcKATP channels preactivated by the channel opener pinacidil in rabbit ventricular myocytes, through reducing the occurrence and the dwelling time of the long closed states whilst increasing the frequency of channel opening; in contrast, all these changes were reversed in the presence of inhibitors selective for soluble guanylyl cyclase (sGC), PKG, calmodulin, CaMKII or ERK1/2. Mimicking the action of NO donors, exogenous H2O2 potentiated pinacidil-preactivated sarcKATP channel activity in

  3. Application of perturbation theory to sensitivity calculations of PWR type reactor cores using the two-channel model

    International Nuclear Information System (INIS)

    Sensitivity calculations are very important in design and safety of nuclear reactor cores. Large codes with a great number of physical considerations have been used to perform sensitivity studies. However, these codes need long computation time involving high costs. The perturbation theory has constituted an efficient and economical method to perform sensitivity analysis. The present work is an application of the perturbation theory (matricial formalism) to a simplified model of DNB (Departure from Nucleate Boiling) analysis to perform sensitivity calculations in PWR cores. Expressions to calculate the sensitivity coefficients of enthalpy and coolant velocity with respect to coolant density and hot channel area were developed from the proposed model. The CASNUR.FOR code to evaluate these sensitivity coefficients was written in Fortran. The comparison between results obtained from the matricial formalism of perturbation theory with those obtained directly from the proposed model makes evident the efficiency and potentiality of this perturbation method for nuclear reactor cores sensitivity calculations (author). 23 refs, 4 figs, 7 tabs

  4. Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats

    OpenAIRE

    Mario I. Ortiz

    2013-01-01

    BACKGROUND: There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA) in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA.OBJECTIVE: To determine whether metformin-sulfonylurea combinations affect DIA during the formalin test.METHODS: Rats received the appropriate vehicle or diclofenac before 1% formaldehyde was injected into the paw. Rats were also pretreated with vehicle, glibenclamide, glipiz...

  5. Role of Epac2A/Rap1 signaling in interplay between incretin and sulfonylurea in insulin secretion.

    Science.gov (United States)

    Takahashi, Harumi; Shibasaki, Tadao; Park, Jae-Hyung; Hidaka, Shihomi; Takahashi, Toshimasa; Ono, Aika; Song, Dae-Kyu; Seino, Susumu

    2015-04-01

    Incretin-related drugs and sulfonylureas are currently used worldwide for the treatment of type 2 diabetes. We recently found that Epac2A, a cAMP binding protein having guanine nucleotide exchange activity toward Rap, is a target of both incretin and sulfonylurea. This suggests the possibility of interplay between incretin and sulfonylurea through Epac2A/Rap1 signaling in insulin secretion. In this study, we examined the combinatorial effects of incretin and various sulfonylureas on insulin secretion and activation of Epac2A/Rap1 signaling. A strong augmentation of insulin secretion by combination of GLP-1 and glibenclamide or glimepiride, which was found in Epac2A(+/+) mice, was markedly reduced in Epac2A(-/-) mice. In contrast, the combinatorial effect of GLP-1 and gliclazide was rather mild, and the effect was not altered by Epac2A ablation. Activation of Rap1 was enhanced by the combination of an Epac-selective cAMP analog with glibenclamide or glimepiride but not gliclazide. In diet-induced obese mice, ablation of Epac2A reduced the insulin secretory response to coadministration of the GLP-1 receptor agonist liraglutide and glimepiride. These findings clarify the critical role of Epac2A/Rap1 signaling in the augmenting effect of incretin and sulfonylurea on insulin secretion and provide the basis for the effects of combination therapies of incretin-related drugs and sulfonylureas. PMID:25315008

  6. [Sulfonylureas in today's blood glucose lowering therapy. New data on advantages and potential barriers of an "old" antidiabetic group].

    Science.gov (United States)

    Winkler, Gábor

    2015-03-29

    Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today's therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs - first of all dipeptidyl peptidase-4 inhibitors - and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect. PMID:25796278

  7. Quinidine-sensitive K+ channels in the basolateral membrane of embryonic coprodeum epithelium: regulation by aldosterone and thyroxine.

    Science.gov (United States)

    Illek, B; Fischer, H; Clauss, W

    1993-01-01

    Basolateral K+ channels and their regulation during aldosterone- and thyroxine-stimulated Na+ transport were studied in the lower intestinal epithelium (coprodeum) of embryonic chicken in vitro. Isolated tissues of the coprodeum were mounted in Ussing chambers and investigated under voltage-clamped conditions. Simultaneous stimulation with aldosterone (1 mumol.l-1) and thyroxine (1 mumol.l-1) raised short-circuit current after a 1- to 2-h latent period. Maximal values were reached after 6-7 h of hormonal treatment, at which time transepithelial Na+ absorption was more than tripled (77 +/- 11 microA.cm-2) compared to control (24 +/- 8 microA.cm-2). K+ currents across the basolateral membrane were investigated after permeabilizing the apical membrane with the pore-forming antibiotic amphotericin B and application of a mucosal-to-serosal K+ gradient. This K+ current could be dose dependently depressed by the K+ channel blocker quinidine. Fluctuation analysis of the short-circuit current revealed a spontaneous and a blocker-induced Lorentzian noise component in the power density spectra. The Lorentzian corner frequencies increased linearly with the applied blocker concentration. This enabled the calculation of single K+ channel current and K+ channel density. Single K+ channel current was not affected by stimulation, whereas the number of quinidine-sensitive K+ channels in the basolateral membrane increased from 11 to 26.10(6).cm-2 in parallel to the hormonal stimulation transepithelial Na+ transport. This suggests that the basolateral membrane is a physiological target during synergistic aldosterone and thyroxine regulation of transepithelial Na+ transport for maintaining intracellular K+ homeostasis. PMID:8151014

  8. Rational design and validation of a vanilloid-sensitive TRPV2 ion channel.

    Science.gov (United States)

    Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

    2016-06-28

    Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S-S498F-L505T-Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular "glue" that bridges the S4-S5 linker to the S1-S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor. PMID:27298359

  9. Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

    Science.gov (United States)

    Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S; Minor, Daniel L

    2016-02-25

    Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNa(V)) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNa(V) CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNa(V) CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNa(V) voltage dependencies, and demonstrate that a discrete domain can encode the temperature-dependent response of a channel. PMID:26919429

  10. Cooperation between cAMP signalling and sulfonylurea in insulin secretion.

    Science.gov (United States)

    Shibasaki, T; Takahashi, T; Takahashi, H; Seino, S

    2014-09-01

    Although glucose is physiologically the most important regulator of insulin secretion, glucose-induced insulin secretion is modulated by hormonal and neural inputs to pancreatic β-cells. Most of the hormones and neurotransmitters evoke intracellular signals such as cAMP, Ca²⁺ , and phospholipid-derived molecules by activating G protein-coupled receptors (GPCRs). In particular, cAMP is a key second messenger that amplifies insulin secretion in a glucose concentration-dependent manner. The action of cAMP on insulin secretion is mediated by both protein kinase A (PKA)-dependent and Epac2A-dependent mechanisms. Many of the proteins expressed in β-cells are phosphorylated by PKA in vitro, but only a few proteins in which PKA phosphorylation directly affects insulin secretion have been identified. On the other hand, Epac2A activates the Ras-like small G protein Rap in a cAMP-dependent manner. Epac2A is also directly activated by various sulfonylureas, except for gliclazide. 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analogue, and glibenclamide, a sulfonylurea, synergistically activate Epac2A and Rap1, whereas adrenaline, which suppresses cAMP production in pancreatic β-cells, blocks activation of Epac2A and Rap1 by glibenclamide. Thus, cAMP signalling and sulfonylurea cooperatively activate Epac2A and Rap1. This interaction could account, at least in part, for the synergistic effects of incretin-related drugs and sulfonylureas in insulin secretion. Accordingly, clarification of the mechanism of Epac2A activation may provide therapeutic strategies to improve insulin secretion in diabetes. PMID:25200305

  11. Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis

    OpenAIRE

    Romley, John A.; Gong, Cynthia; Jena, Anupam B.; Goldman, Dana P.; Williams, Bradley; Peters, Anne

    2015-01-01

    Study question Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride? Methods: This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465 918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4 355 418 person quarters)...

  12. Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis

    OpenAIRE

    Romley, John A.; Gong, Cynthia; Jena, Anupam B.; Goldman, Dana P.; Williams, Bradley; Peters, Anne

    2015-01-01

    Study question Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride? Methods This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465 918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4 355 418 person quarters);...

  13. Core-shell magnetic molecularly imprinted polymers as sorbent for sulfonylurea herbicide residues.

    Science.gov (United States)

    Miao, Shan Shan; Wu, Mei Sheng; Zuo, Hai Gen; Jiang, Chen; Jin, She Feng; Lu, Yi Chen; Yang, Hong

    2015-04-15

    Sulfonylurea herbicides are widely used at lower dosage for controlling broad-leaf weeds and some grasses in cereals and economic crops. It is important to develop a highly efficient and selective pretreatment method for analyzing sulfonylurea herbicide residues in environments and samples from agricultural products based on magnetic molecularly imprinted polymers (MIPs). The MIPs were prepared by a surface molecular imprinting technique especially using the vinyl-modified Fe3O4@SiO2 nanoparticle as the supporting matrix, bensulfuron-methyl (BSM) as the template molecule, methacrylic acid (MAA) as a functional monomer, trimethylolpropane trimethacrylate (TRIM) as a cross-linker, and azodiisobutyronitrile (AIBN) as an initiator. The MIPs show high affinity, recognition specificity, fast mass transfer rate, and efficient adsorption performance toward BSM with the adsorption capacity reaching up to 37.32 mg g(-1). Furthermore, the MIPs also showed cross-selectivity for herbicides triasulfuron (TS), prosulfuron (PS), and pyrazosulfuron-ethyl (PSE). The MIP solid phase extraction (SPE) column was easier to operate, regenerate, and retrieve compared to those of C18 SPE column. The developed method showed highly selective separation and enrichment of sulfonylurea herbicide residues, which enable its application in the pretreatment of multisulfonylurea herbicide residues. PMID:25797565

  14. A novel high-throughput screening assay for HCN channel blocker using membrane potential-sensitive dye and FLIPR.

    Science.gov (United States)

    Vasilyev, Dmitry V; Shan, Qin J; Lee, Yan T; Soloveva, Veronica; Nawoschik, Stanley P; Kaftan, Edward J; Dunlop, John; Mayer, Scott C; Bowlby, Mark R

    2009-10-01

    Hyperpolarization-activated cation nonselective (HCN) channels represent an interesting group of targets for drug development. In this study, the authors report the development of a novel membrane potential-sensitive dye (MPSD) assay for HCN channel modulators that has been miniaturized into 384-well fluorescent imaging plate reader (FLIPR) high-throughput screening (HTS) format. When optimized (by cell plating density, plate type, cell recovery from cryopreservation), the well-to-well signal variability was low, with a Z' = 0.73 and coefficient of variation = 6.4%, whereas the MPSD fluorescence signal amplitude was -23,700 +/- 1500 FLIPR(3) relative fluorescence units (a linear relationship was found between HCN1 MPSD fluorescence signal and the cell plating density) and was completely blocked by 30 microM ZD7288. The assay tolerated up to 1% DMSO, inclusion of which did not significantly change the signal kinetics or amplitude. A single-concentration screening of an ion channel-focused library composed of 4855 compounds resulted in 89 HCN1 blocker hits, 51 of which were subsequently analyzed with an 8-point concentration-response analysis on the IonWorks HT electrophysiology platform. The correlation between MPSD and the electrophysiology assay was moderate, as shown by the linear regression analysis (r(2) = 0.56) between the respective IC(50)s obtained using these 2 assays. The reported HTS-compatible HCN channel blocker assay can serve as a tool in drug discovery in the pursuit of HCN channel isoform-selective small molecules that could be used in the development of clinically relevant compounds. PMID:19773585

  15. A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene

    DEFF Research Database (Denmark)

    Gregersen, Noomi; Dahl, Hans A.; Buttenschön, Henriette N.;

    2012-01-01

    Panic disorder (PD) is a mental disorder with recurrent panic attacks that occur spontaneously and are not associated to any particular object or situation. There is no consensus on what causes PD. However, it is recognized that PD is influenced by environmental factors, as well as genetic factors...... the Faroe Islands. Subsequently, we conducted a fine mapping, which revealed the amiloride-sensitive cation channel 1 (ACCN1) located on chromosome 17q11.2-q12 as a potential candidate gene for PD. The further analyses of the ACCN1 gene using single-nucleotide polymorphisms (SNPs) revealed significant...

  16. A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1

    OpenAIRE

    Zhang, Ning; Inan, Sadeet; Cowan, Alan; Sun, Ronghua; Wang, Ji Ming; Rogers, Thomas J.; Caterina, Michael; Oppenheim, Joost J.

    2005-01-01

    Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca2+ influx mediated by TRPV1. When CCR1:TRPV1...

  17. Transient neonatal diabetes due to a missense mutation (E227K) in the gene encoding the ATP-sensitive potassium channel (KCNJ11).

    Science.gov (United States)

    Martins, Luísa; Lourenço, Rita; Maia, Ana Lúcia; Maciel, Paula; Monteiro, Maria Isabel; Pacheco, Lucinda; Anselmo, João; César, Rui; Gomes, Maria Fernanda

    2015-10-01

    Neonatal diabetes is a monogenic form of diabetes. Herein, we report on a newborn presenting diabetic ketoacidosis at 17 days of life. A KCNJ11 mutation was identified. In such cases, insulin can be replaced by sulfonylurea with a successful metabolic control, as an example of how molecular diagnosis may influence the clinical management of the disorder. PMID:26509005

  18. pH-sensitive K(+) channel TREK-1 is a novel target in pancreatic cancer.

    Science.gov (United States)

    Sauter, Daniel R P; Sørensen, Christiane E; Rapedius, Markus; Brüggemann, Andrea; Novak, Ivana

    2016-10-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and new therapeutic targets are urgently needed. One of the hallmarks of cancer is changed pH-homeostasis and potentially pH-sensors may play an important role in cancer cell behavior. Two-pore potassium channels (K2P) are pH-regulated channels that conduct a background K(+) current, which is involved in setting the plasma membrane potential (Vm). Some members of the K2P superfamily were reported as crucial players in driving tumor progression. The aim of this study was to investigate pH-regulated K(+) currents in PDAC cells and determine possible effects on their pathological phenotype. Using a planar high-throughput patch-clamp system (SyncroPatch 384PE) we identified a pH-regulated K(+) current in the PDAC cell line BxPC-3. The current was inhibited by extracellular acidification and intracellular alkalization. Exposure to a set of different K(+) channel inhibitors, and the TREK-1 (K2P2.1)-specific activator BL1249, TREK-1 was identified as the main component of pH-regulated current. A voltage-sensor dye (VF2.1.Cl) was used to monitor effects of pH and BL1249 on Vm in more physiological conditions and TREK-1-mediated current was found as critical player in setting Vm. We assessed a possible role of TREK-1 in PDAC progression using cell proliferation and migration assays and observed similar trends with attenuated proliferation/migration rates in acidic (pH7.4) conditions. Notably, BL1249 inhibited both PDAC cell proliferation and migration indicating that hyperpolarization of Vm attenuates cancer cell behavior. TREK-1 may therefore be a promising novel target for PDAC therapy. PMID:27443495

  19. Improving the sensitivity of Higgs boson searches in the golden channel

    CERN Document Server

    Gainer, James S; Low, Ian; Vega-Morales, Roberto

    2011-01-01

    Leptonic decays of the Higgs boson in the ZZ* channel yield what is known as the golden channel due to its clean signature and good total invariant mass resolution. In addition, the full kinematic distribution of the decay products can be reconstructed, which, nonetheless, is not taken into account in traditional search strategy relying only on measurements of the total invariant mass. In this work we implement a type of multivariate analysis known as the matrix element method, which exploits differences in the full production and decay matrix elements between the Higgs boson and the dominant irreducible background from q bar{q} -> ZZ*. Analytic expressions of the differential distributions for both the signal and the background are also presented. We perform a study for the Large Hadron Collider at sqrt{s}=7 TeV for Higgs masses between 175 and 350 GeV. We find that, with an integrated luminosity of 2.5 fb^-1 or higher, improvements in the order of 10 - 20 % could be obtained for both discovery significance ...

  20. Baclofen and adenosine inhibition of synaptic transmission at CA3-CA1 synapses display differential sensitivity to K+ channel blockade.

    Science.gov (United States)

    Skov, Jane; Andreasen, Mogens; Hablitz, John J; Nedergaard, Steen

    2011-05-01

    The metabotropic GABA(B) and adenosine A(1) receptors mediate presynaptic inhibition through regulation of voltage-dependent Ca(2+) channels, whereas K(+) channel regulation is believed to have no role at the CA3-CA1 synapse. We show here that the inhibitory effect of baclofen (20 μM) and adenosine (300 μM) on field EPSPs are differentially sensitive to Cs(+) (3.5 mM) and Ba(2+) (200 μM), but not 4-aminopyridine (100 μM). Barium had no effect on paired-pulse facilitation (PPF) in itself, but gave significant reduction (14 ± 5%) when applied in the presence of baclofen, but not adenosine, suggesting that the effect is presynaptic and selective on the GABA(B) receptor-mediated response. The effect of Ba(2+) on PPF was not mimicked by tertiapin (30 nM), indicating that the underlying mechanism does not involve GIRK channels. Barium did not affect PPF in slices from young rats (P7-P8), suggesting developmental regulation. The above effects of Ba(2+) on adult tissue were reproduced when measuring evoked whole-cell EPSCs from CA1 pyramidal neurons: PPF was reduced by 22 ± 3% in the presence of baclofen and unaltered in adenosine. In contrast, Ba(2+) caused no significant change in frequency or amplitude of miniature EPSCs. The Ba(2+)-induced reduction of PPF was antagonized by LY341495, suggesting metabotropic glutamate receptor involvement. We propose that these novel effects of Ba(2+) and Cs(+) are exerted through blockade of inwardly rectifying K(+) channels in glial cells, which are functionally interacting with the GABA(B) receptor-dependent glutamate release that generates heterosynaptic depression. PMID:21274618

  1. The Sensitivity of Sediment Path-Lengths to Channel Morphology: Results from Physical Models of Braided Rivers

    Science.gov (United States)

    Kasprak, A.; Ashmore, P.; Peirce, S.; Wheaton, J. M.

    2013-12-01

    The travel distances of coarse sediment in gravel-bed rivers during floods, or their path-lengths, exhibit strong dependencies on the arrangement of geomorphic units they are sourced from, routed through or around, and finally deposited on. Despite previous research on both braiding and single-thread meandering streams, a coherent rule set which relates particle path lengths to morphology remains elusive; such a rule set has the potential to vastly simplify models which seek to predict sediment transport or morphodynamics in these channels. Here we seek to understand the sensitivity of particle path-length distributions to morphology via a physical model of a braided stream, by using fluorescent tracer particles to track sediment path-lengths. These flume experiments provide a rich dataset composed of before-and-after bed photogrammetry, along with high-resolution photography and high-speed video documentation of particle deposition and mobility. Initial analyses indicate a strong coupling between particle path-length and the spatial arrangement of in-channel geomorphic units, with bar heads and point bars frequently acting as sink locations for tracer particles. This is interesting as it suggests that morphodynamics are in part contingent on morphology with strong positive feedbacks on hydraulics, deposition and negative feedbacks on path-length. Several mechanisms of braiding were captured in the simulations as erosional source processes for the tracers, including chute cutoff of point bars, bank erosion, channel incision, and bar edge trimming. These results may help inform the development of morphodynamic models for braided rivers which rely on particle path-lengths to simplify sediment transport algorithms, and such relations between channel morphology and path-length hold the potential to benefit numerous other modeling efforts, as well as provide a heuristic framework with which to understand fluvial morphodynamics.

  2. Photoaffinity labeling of components of the apamin-sensitive K+ channel in neuronal membranes

    International Nuclear Information System (INIS)

    An azidonitrophenylaminoacetyl mono[125I]iodoapamin derivative was prepared which showed specific binding to rat neuronal membranes. UV photolysis lead to the irreversible occupation of binding sites. Photo- labeling of intact primary cultured rat neurons followed by membrane solubilization, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography revealed the covalent incorporation of radioactivity into 3 main components with Mr = 86,000, 30,000, and 23, 000. Labeling was completely prevented by a competing excess of native apamin. Similar studies on purified synaptic membranes from the rat brain showed another labeling pattern with major bands corresponding to Mr = 86,000 and 59,000. Although the reasons for the partial discrepancy between cultured embryonic neurons and an adult brain membrane fraction are not yet clear, the authors conclude that these proteins are intimately associated with the apamin binding site and are probably components of a type of Ca2+-activated K+ channel

  3. Photoaffinity labeling of components of the apamin-sensitive K+ channel in neuronal membranes

    Energy Technology Data Exchange (ETDEWEB)

    Seagar, M.J.; Labbe-Jullie, C.; Granier, C.; Van Rietschoten, J.; Couraud, F.

    1985-04-10

    An azidonitrophenylaminoacetyl mono(/sup 125/I)iodoapamin derivative was prepared which showed specific binding to rat neuronal membranes. UV photolysis lead to the irreversible occupation of binding sites. Photo- labeling of intact primary cultured rat neurons followed by membrane solubilization, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography revealed the covalent incorporation of radioactivity into 3 main components with Mr = 86,000, 30,000, and 23, 000. Labeling was completely prevented by a competing excess of native apamin. Similar studies on purified synaptic membranes from the rat brain showed another labeling pattern with major bands corresponding to Mr = 86,000 and 59,000. Although the reasons for the partial discrepancy between cultured embryonic neurons and an adult brain membrane fraction are not yet clear, the authors conclude that these proteins are intimately associated with the apamin binding site and are probably components of a type of Ca2+-activated K+ channel.

  4. The pore region of the Kv1.2alpha subunit is an important component of recombinant Kv1.2 channel oxygen sensitivity.

    Science.gov (United States)

    Conforti, Laura; Takimoto, Koichi; Petrovic, Milan; Pongs, Olaf; Millhorn, David

    2003-06-27

    Oxygen-sensitive K(+) channels are important elements in the cellular response to hypoxia. Although much progress has been made in identifying their molecular composition, the structural components associated to their O(2)-sensitivity are not yet understood. Recombinant Kv1.2 currents expressed in Xenopus oocytes are inhibited by a decrease in O(2) availability. On the contrary, heterologous Kv2.1 channels are O(2)-insensitive. To elucidate the protein segment responsible for the O(2)-sensitivity of Kv1.2 channels, we analyzed the response to anoxia of Kv1.2/Kv2.1 chimeric channels. Expression of chimeric Kv2.1 channels each containing the S4, the S1-S3 or the S6-COOH segments of Kv1.2 polypeptide resulted in a K(+) current insensitive to anoxia. In contrast, transferring the S5-S6 segment of Kv1.2 into Kv2.1 produced an O(2)-sensitive K(+) current. Finally, mutating a redox-sensitive methionine residue (M380) of Kv1.2 polypeptide did not affect O(2)-sensitivity. Thus, the pore and its surrounding regions of Kv1.2 polypeptide confer its hypoxic inhibition. This response is independent on the redox modulation of methionine residues in this protein segment. PMID:12804584

  5. ATP-Sensitive K+ Channel Knockout Induces Cardiac Proteome Remodeling Predictive of Heart Disease Susceptibility

    OpenAIRE

    Arrell, D. Kent; Zlatkovic, Jelena; Kane, Garvan C; Yamada, Satsuki; Terzic, Andre

    2009-01-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (KATP) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode conse...

  6. Silver/titania nanocable as fast electron transport channel for dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Highlights: ► We report a novel path for high-performance dye sensitized solar cells. ► Nanocables of Ag/TiO2 hetero-structure are applied in photo-anode of DSSCs. ► The hetero-structure favors electron extraction and transportation. ► A DSSC performance enhancement is received with nanocable loaded photo-anodes. - Abstract: Nanocables of silver nanowire/titania sheath hetero-structure are synthesized and applied in photo-anode of dye-sensitized solar cells. The metal/semiconductor hetero-structure builds Schottky barrier which favors the extraction and transportation of photo-generated electrons. The short circuit current is improved from 5.70 mA to 8.91 mA aided by 1 wt% nanocables with a conversion efficiency enhancement of 37.9% on 1 cm × 1 cm cells. Electrochemical impedance spectroscopy studies suggest that the boost of short circuit current is ascribed to the reduce resistance in the TiO2/dye/electrolyte. The present results pave a novel path for high-performance dye sensitized solar cells.

  7. Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels.

    Science.gov (United States)

    Sepúlveda, Francisco V; Pablo Cid, L; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K(+) channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K(+) channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K(+) homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K(+)-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

  8. Can water sensitive urban design systems help to preserve natural channel-forming flow regimes in an urbanised catchment?

    Science.gov (United States)

    Wella-Hewage, Chathurika Subhashini; Alankarage Hewa, Guna; Pezzaniti, David

    2016-01-01

    Increased stormwater runoff and pollutant loads due to catchment urbanisation bring inevitable impacts on the physical and ecological conditions of environmentally sensitive urban streams. Water sensitive urban design (WSUD) has been recognised as a possible means to minimise these negative impacts. This paper reports on a study that investigated the ability of infiltration-based WSUD systems to replicate the predevelopment channel-forming flow (CFF) regime in urban catchments. Catchment models were developed for the 'pre-urban', 'urban' and 'managed' conditions of a case study catchment and the hydrological effect on CFF regime was investigated using a number of flow indices. The results clearly show that changes to flow regime are apparent under urban catchment conditions and are even more severe under highly urbanised conditions. The use of WSUD systems was found to result in the replication of predevelopment flow regimes, particularly at low levels of urbanisation. Under highly urbanised conditions (of managed catchments) overcontrol of the CFF indices was observed as indicated by flow statistics below their pre-urban values. The overall results suggest that WSUD systems are highly effective in replicating the predevelopment CFF regime in urban streams and could be used as a means to protect environmentally sensitive urban streams. PMID:26744937

  9. Confidence limits with multiple channels and arbitrary probability distributions for sensitivity and expected background

    CERN Document Server

    Perrotta, A

    2002-01-01

    A MC method is proposed to compute upper limits, in a pure Bayesian approach, when the errors associated with the experimental sensitivity and expected background content are not Gaussian distributed or not small enough to apply usual approximations. It is relatively easy to extend the procedure to the multichannel case (for instance when different decay branching, luminosities or experiments have to be combined). Some of the searches for supersymmetric particles performed in the DELPHI experiment at the LEP electron- positron collider use such a procedure to propagate systematics into the calculation of cross-section upper limits. One of these searches is described as an example. (6 refs).

  10. Channeling of electron transport to improve collection efficiency in mesoporous titanium dioxide dye sensitized solar cell stacks

    Energy Technology Data Exchange (ETDEWEB)

    Fakharuddin, Azhar; Ahmed, Irfan; Yusoff, Mashitah M.; Jose, Rajan, E-mail: rjose@ump.edu.my, E-mail: joserajan@gmail.com [Nanostructured Renewable Energy Materials Laboratory, Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, 26300 Pahang (Malaysia); Khalidin, Zulkeflee [Faculty of Electrical and Electronics Engineering, Universiti Malaysia Pahang, 26300 Pahang (Malaysia)

    2014-02-03

    Dye-sensitized solar cell (DSC) modules are generally made by interconnecting large photoelectrode strips with optimized thickness (∼14 μm) and show lower current density (J{sub SC}) compared with their single cells. We found out that the key to achieving higher J{sub SC} in large area devices is optimized photoelectrode volume (V{sub D}), viz., thickness and area which facilitate the electron channeling towards working electrode. By imposing constraints on electronic path in a DSC stack, we achieved >50% increased J{sub SC} and ∼60% increment in photoelectric conversion efficiency in photoelectrodes of similar V{sub D} (∼3.36 × 10{sup −4} cm{sup 3}) without using any metallic grid or a special interconnections.

  11. Channeling of electron transport to improve collection efficiency in mesoporous titanium dioxide dye sensitized solar cell stacks

    International Nuclear Information System (INIS)

    Dye-sensitized solar cell (DSC) modules are generally made by interconnecting large photoelectrode strips with optimized thickness (∼14 μm) and show lower current density (JSC) compared with their single cells. We found out that the key to achieving higher JSC in large area devices is optimized photoelectrode volume (VD), viz., thickness and area which facilitate the electron channeling towards working electrode. By imposing constraints on electronic path in a DSC stack, we achieved >50% increased JSC and ∼60% increment in photoelectric conversion efficiency in photoelectrodes of similar VD (∼3.36 × 10−4 cm3) without using any metallic grid or a special interconnections

  12. Comparable long-term mortality risk associated with individual sulfonylureas in diabetes patients with heart failure

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Gislason, Gunnar H; Jørgensen, Casper H;

    2011-01-01

    pancreatic specificity, i.e., with tolbutamide, glipizide, and gliclazide as specific, and glibenclamide, and glimepiride as non-specific agents, no differential prognosis was found between the two groups (HR 1.04 [0.96–1.14], for non-specific, compared to pancreas specific agents). The prognosis was not...... dependent on prior acute myocardial infarction or ischemic heart disease (p for interactions >0.3). Conclusions In current clinical practice, it is unlikely that there are considerable differences in risk of mortality associated with individual sulfonylureas in patients with heart failure....

  13. The influence of selected spraying parameters on two formulation of sulfonylurea herbicides effect

    OpenAIRE

    KIELOCH, Renata; Krzysztof DOMARADZKI

    2013-01-01

    The objective of this study was the evaluation of spray volume and nozzle type effect on different formulation (water dispersible granules - WG and oil dispersion - OD) of two sulfonylurea herbicides: the mixture iodosulfuron methyl sodium + amidosulfuron and iodosulfuron methyl sodium + mesosulfuron methyl efficacy. There were investigated three levels of spray volume (125 l*ha-1, 250 l*ha-1 and 350 l*ha-1) and two types of nozzle (extended range flat nozzle TeeJet XR 11003-VS and drift guar...

  14. Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing 1,2,4-Triazolinone Moiety

    Institute of Scientific and Technical Information of China (English)

    LIU Zhuo; PAN Li; LI Yong-hong; WANG Su-hua; LI Zheng-ming

    2013-01-01

    A series of new sulfonylureas incorporating 1,2,4-triazolinone moiety was synthesized,which were further bio-assayed for the herbicidal activity against four herbs,representative of monocotyledons and dicotyledons.Some of them exhibited high potency to inhibit the growth of dicotyledons(Bassica napus and Amaranthus retroflexus) in the pot experiment.Compounds 9a and 9b also displayed an excellent herbicidal activity against Bassica napus at a concentration of 15 g/hectare,which were comparable with commercial triasulfuron.

  15. Polysaccharide isolated from Triticum aestivum stimulates insulin release from pancreatic cells via the ATP-sensitive K+ channel.

    Science.gov (United States)

    Lee, Sun-Hee; Lim, Sung-Won; Lee, Young-Mi; Lee, Hoi-Seon; Kim, Dae-Ki

    2012-05-01

    Traditional natural plants have been used throughout the world for their antidiabetic effects. The aim of the present study was to investigate the stimulating activity of a polysaccharide extract derived from T. aestivum sprout (TASP) on insulin secretion in vitro using the RIN-5F pancreatic β-cell line and rat pancreatic islets. In these experiments, TASP (0.1 to 2 mg/ml) augmented glucose-stimulated insulin secretion in a dose-dependent manner in the presence of a stimulatory glucose concentration (16.7 mM), but not of a basal concentration (1.1 mM). Although TASP failed to enhance the high K+-induced insulin secretion, the insulinotropic effect of TASP was significantly inhibited by diazoxide, an opener of ATP-sensitive K+ channel blocking insulin release. TASP potentiated the insulin secretion induced by other secretagogues, such as IBMX and tolbutamide. Moreover, glucose-derived blood insulin levels were significantly elevated by oral administration of TASP to mice, similarly to antidiabetic drugs. We also demonstrated that TASP significantly increased glucose-induced 45Ca2+ uptake and proinsulin mRNA expression in rat islets. Overall, our results suggest that TASP has a stimulating effect on insulin secretion and production in pancreatic β-cells via K+ channel closure and calcium influx. These results suggest that TASP may be useful as a candidate for the therapy of diabetes mellitus. PMID:22322245

  16. Delay-Sensitive Distributed Power and Transmission Threshold Control for S-ALOHA Network with Finite State Markov Fading Channels

    CERN Document Server

    Huang, Huang

    2009-01-01

    In this paper, we consider the delay-sensitive power and transmission threshold control design in S-ALOHA network with FSMC fading channels. The random access system consists of an access point with K competing users, each has access to the local channel state information (CSI) and queue state information (QSI) as well as the common feedback (ACK/NAK/Collision) from the access point. We seek to derive the delay-optimal control policy (composed of threshold and power control). The optimization problem belongs to the memoryless policy K-agent infinite horizon decentralized Markov decision process (DEC-MDP), and finding the optimal policy is shown to be computationally intractable. To obtain a feasible and low complexity solution, we recast the optimization problem into two subproblems, namely the power control and the threshold control problem. For a given threshold control policy, the power control problem is decomposed into a reduced state MDP for single user so that the overall complexity is O(NJ), where N a...

  17. [Determination of 32 sulfonylurea herbicide residues in sweet corns and green soybeans by QuEChERS-liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Wang, Lianzhu; Huang, Xiaoyan; Wang, Dengfei; Chen, Yong; Xu, Dunming; Zhou, Yu

    2015-05-01

    A fast method based on QuEChERS methodology for the simultaneous determination of 32 sulfonylurea herbicide residues in sweet corns and green soybeans was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clean-up effects of three dispersive sorbents were evaluated in terms of the residue mass for extracts after evaporation and recoveries. The three sorbents were C18, a mixture of two sorbents--silica coated with zirconium dioxide (Z-Sep) and C18, a bonded C18 zirconia-coated silica (Z-Sep+). As a result, the best effects were obtained from using Z-Sep/C18 sorbents. The samples were extracted with acetonitrile, and salted out with anhydrous magnesium sulphate and sodium chloride. The extracts were cleaned up with dispersive solid phase extraction using Z-Sep/C18 sorbents. Chromatographic analysis was carried out using a CSH C18 column with gradient elution. The pesticides were analyzed by negative electrospray ionization tandem mass spectrometry under scheduled multiple reaction monitoring mode. The quantification was achieved using matrix-matched standard calibrations as the external standard. The recoveries at fortification levels of 10, 20, 100 µg/kg in sweet corns and green beans ranged from 80.0% to 108.2% with the relative standard deviations of 1.2%-13.0%. The limits of quantification (S/N ≥ 10) were 0.2-5.0 µg/kg. The method has been proven to be simple, sensitive, environmental, and thus suitable for the determination of the 32 sulfonylurea herbicide residues in sweet corns and green soy- beans. PMID:26387208

  18. Effects of mitochondrial ATP-sensitive potassium channels on the proliferation and secretion of human airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Changbiao Chen

    2014-12-01

    Full Text Available Bronchial asthma is the common chronic inflammatory disease and is characterized by chronic airway inflammation, airway remodeling, and airway hyperreactivity (AHR. Aim of this study was to investigate the effects of mitochondrial ATP-sensitive potassium channels (MitoKATP on the proliferation and secretion of human airway smooth muscle cells (HASMCs. HASMCs were treated with the serum from asthmatic patients to establish HASMCs asthma model of passive sensitization. Rhodamine 123 (R-123 and 2,7-dichloro-dihydrofluorescein diacetate (DCFH-DA fluorescence staining were used to detect mitochondrial membrane potential (Δψm and the content of reactive oxygen species (ROS in the cells, respectively. The cell counting was used to detect cell proliferation, and RT-PCR was used to detect the expression of TGF-β1 mRNA. In the normal + Diazoxide group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-β1 expression were enhanced, compared with the normal control group (p<0.05. There were no significant differences between the normal + 5-hydroxydecanoate (5-HD group and the normal control group. In the asthma model control group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-β1 expression were enhanced, compared with normal control group, (p<0.05. The aforementioned indices were enhanced in the asthma model + Diazoxide group, when compared with the asthma model control group, whereas these indices were attenuated in the asthma model + 5-HD group, when compared with the asthma model control group (p<0.05. In conclusion, asthma could activate MitoKATP channels in HASMCs, promote HASMC proliferation and TGF-β1 expression.

  19. AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels

    International Nuclear Information System (INIS)

    In vivo and in vitro methods were used to characterize AHR-16303B, a novel compound with antagonistic action at 5-HT2 receptors and voltage-sensitive calcium channels. The 5-HT2 receptor-antagonistic properties of AHR-16303B were demonstrated by inhibition of (a) [3H]ketanserin binding to rat cerebral cortical membranes (IC50 = 165 nM); (b) 5-hydroxytryptamine (5-HT)-induced foot edema in rats (minimum effective dose, (MED) = 0.32 mg/kg orally, p.o.); (c) 5-HT-induced vasopressor responses in spontaneously hypertensive rats (SHR) (ID50 = 0.18 mg/kg intravenously (i.v.), 1.8 mg/kg p.o.), (d) 5-HT-induced antidiuresis in rats (MED = 1 mg/kg p.o.), and (e) platelet aggregation induced by 5-HT + ADP (IC50 = 1.5 mM). The calcium antagonist properties of AHR-16303B were demonstrated by inhibition of (a) [3H]nimodipine binding to voltage-sensitive calcium channels on rabbit skeletal muscle membranes (IC50 = 15 nM), (b) KCl-stimulated calcium flux into cultured PC12 cells (IC50 = 81 nM), and (c) CaCl2-induced contractions of rabbit thoracic aortic strips (pA2 = 8.84). AHR-16303B had little or no effect on binding of radioligands to dopamine2 (DA2) alpha 1, alpha 2, H1, 5-HT1 alpha, beta 2, muscarinic M1, or sigma opioid receptors; had no effect on 5-HT3 receptor-mediated vagal bradycardia; and had only minor negative inotropic, chronotropic, and dromotropic effects on isolated guinea pig atria. In conscious SHR, 30 mg/kg p.o. AHR-16303B completely prevented the vasopressor responses to i.v. 5-HT, and decreased blood pressure (BP) by 24% 3 h after dosing

  20. Radionuclide transport in running waters, sensitivity analysis of bed-load, channel geometry and model discretisation

    International Nuclear Information System (INIS)

    In this report, further investigations of the model concept for radionuclide transport in stream, developed in the SKB report TR-05-03 is presented. Especially three issues have been the focus of the model investigations. The first issue was to investigate the influence of assumed channel geometry on the simulation results. The second issue was to reconsider the applicability of the equation for the bed-load transport in the stream model, and finally the last issue was to investigate how the model discretisation will influence the simulation results. The simulations showed that there were relatively small differences in results when applying different cross-sections in the model. The inclusion of the exact shape of the cross-section in the model is therefore not crucial, however, if cross-sectional data exist, the overall shape of the cross-section should be used in the model formulation. This could e.g. be accomplished by using measured values of the stream width and depth in the middle of the stream and by assuming a triangular shape. The bed-load transport was in this study determined for different sediment characteristics which can be used as an order of magnitude estimation if no exact determinations of the bed-load are available. The difference in the calculated bed-load transport for the different materials was, however, found to be limited. The investigation of model discretisation showed that a fine model discretisation to account for numerical effects is probably not important for the performed simulations. However, it can be necessary for being able to account for different conditions along a stream. For example, the application of mean slopes instead of individual values in the different stream reaches can result in very different predicted concentrations

  1. Confidence Limits with Multiple Channels and Arbitrary Probability Distributions for Sensitivity and Expected Background

    Science.gov (United States)

    Perrotta, Andrea

    A MC method is proposed to compute upper limits, in a pure Bayesian approach, when the errors associated to the experimental sensitivity and to the expected background content are not Gaussian distributed or not small enough to apply the usual approximations. It is relatively easy to extend the procedure to the multichannel case (for instance when different decay branchings, or luminosities or experiments have to be combined). Some of the searches for supersymmetric particles performed in the DELPHI experiment at the LEP electron-positron collider use such a procedure to propagate the systematics into the calculation of the cross-section upper limits. One of these searches will be described as an example.

  2. The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1: contributions of the pore domains

    OpenAIRE

    Yuill, KH; Stansfeld, PJ; Ashmole, I; Sutcliffe, MJ; Stanfield, PR

    2007-01-01

    We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ repla...

  3. Acid sensitive background potassium channels K2P3.1 and K2P9.1 undergo rapid dynamin-dependent endocytosis

    OpenAIRE

    Mant, Alexandra; Williams, Sarah; O'Kelly, Ita

    2013-01-01

    Acid-sensitive, two-pore domain potassium channels, K2p3.1 and K2p9.1, are implicated in cardiac and nervous tissue responses to hormones, neurotransmitters and drugs. K2p3.1 and K2p9.1 leak potassium from the cell at rest and directly impact membrane potential. Hence altering channel number on the cell surface drives changes in cellular electrical properties. The rate of K2p3.1 and K2p9.1 delivery to and recovery from the plasma membrane determines both channel number at the cell surface and...

  4. Cross-resistance to short residual sulfonylurea herbicides in transgenic tobacco plants.

    Science.gov (United States)

    Gabard, J M; Charest, P J; Iyer, V N; Miki, B L

    1989-10-01

    Transgenic Nicotiana tabacum plants, produced by Agrobacterium tumefaciens-mediated transformation with a mutant gene (csr1-1) coding for acetohydroxyacid synthase (AHAS) from a chlorsulfuron resistant Arabidopsis thaliana line GH50 (GW Haughn et al. [1988] Mol Gen Genet 211: 266-271; GW Haughn, C Somerville [1986] Mol Gen Genet 204: 430-434), were selected directly on 80 micrograms per liter (225 nanomolar) chlorsulfuron. The expression of csr-1 in two separate transgenic lines CHL-1 and CHL-2 was confirmed by biochemical and genetic analyses. The AHAS activity of GH50 and the equivalent component of AHAS activity in CHL-2 was resistant to three short residual sulfonylurea herbicides, DPX-M6316, DPX-A7881, and DPX-L5300, in addition to chlorsulfuron but not to the sulfonylurea CGA 131'036. Cross-resistance to the imidazolinones AC 263, 499, AC 252, 214, and AC 243,997 was not observed. Parallel observations were made on the inhibition of seedling growth in soil or on culture medium. The relevance of these findings for the application of transgenic plants in agriculture is discussed. PMID:16667071

  5. Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels were Negatively Regulated by Captopril in Volume-Overload Heart Failure Rats.

    Science.gov (United States)

    Hongyuan, Bai; Xin, Dong; Jingwen, Zhang; Li, Gao; Yajuan, Ni

    2016-08-01

    In heart failure (HF), the malignant arrhythmias occur frequently; a study demonstrated that upregulation of I KAS resulted in recurrent spontaneous ventricular fibrillation in HF. However, the regulation of SK channels was poorly understood. The activation of SK channels depended on [Ca(2+)]i and PP2A; studies suggested that angiotensin II can regulate them. So, we hypothesized that in HF, the excess of angiotensin may regulate the SK channels and result in the remodeling of SK channels. To test the hypothesis, we used volume-overload-induced HF rat model, treated with captopril, performed whole-cell patch clamp to record apamin-sensitive currents (I KAS), and I-V curve was studied. The sensitivity of I KAS to [Ca(2+)]i was also explored by setting various [Ca(2+)]i (10, 100, 500, 900, 1000, and 10,000 nM), and the steady-state Ca(2+) response of I KAS was attained and performed Hill fitting with the equation (y = 1/[1 + (EC50/x) (n) ]). Immunofluorescent staining, real-time PCR, Western blot were also carried out to furtherly investigate the underlying molecular mechanisms of the regulation. Captopril significantly decreased the mean density of I KAS when [Ca(2+)]i was 500, 900, 1000, and 10000 nM. The Hill fitting showed significantly different EC50 values and the Hill coefficients and showed captopril significantly shifted rightward the steady-state Ca(2+) response of I KAS. The results of real-time PCR and Western blot demonstrated captopril decreased the mRNA and protein expression of SK3 channels. Captopril significantly downregulated the sensitivity of SK channels to [Ca(2+)]i and the SK3 channels expression in HF, and reversed the SK channels remodeling. PMID:26924798

  6. Tunable sensitivity phase detection of transmitted-type dual-channel guided-mode resonance sensor based on phase-shift interferometry.

    Science.gov (United States)

    Kuo, Wen-Kai; Syu, Siang-He; Lin, Peng-Zhi; Yu, Hsin Her

    2016-02-01

    This paper reports on a transmitted-type dual-channel guided-mode resonance (GMR) sensor system that uses phase-shifting interferometry (PSI) to achieve tunable phase detection sensitivity. Five interference images are captured for the PSI phase calculation within ∼15  s by using a liquid crystal retarder and a USB web camera. The GMR sensor structure is formed by a nanoimprinting process, and the dual-channel sensor device structure for molding is fabricated using a 3D printer. By changing the rotation angle of the analyzer in front of the camera in the PSI system, the sensor detection sensitivity can be tuned. The proposed system may achieve high throughput as well as high sensitivity. The experimental results show that an optimal detection sensitivity of 6.82×10-4  RIU can be achieved. PMID:26836099

  7. Functionally distinct sodium channels in ventricular epicardial and endocardial cells contribute to a greater sensitivity of the epicardium to electrical depression

    OpenAIRE

    Cordeiro, J. M.; Mazza, M.; Goodrow, R.; Ulahannan, N.; Antzelevitch, C; DI DIEGO, J.M.

    2008-01-01

    A greater depression of the action potential (AP) of the ventricular epicardium (Epi) versus endocardium (Endo) is readily observed in experimental models of acute ischemia and Brugada syndrome. Endo and Epi differences in transient outward K+ current and/or ATP-sensitive K+ channel current are believed to contribute to the differential response. The present study tested the hypothesis that the greater sensitivity of Epi is due in part to its functionally distinct early fast Na+ current (INa)...

  8. Differential mechanisms of Cantú syndrome-associated gain of function mutations in the ABCC9 (SUR2) subunit of the KATP channel.

    Science.gov (United States)

    Cooper, Paige E; Sala-Rabanal, Monica; Lee, Sun Joo; Nichols, Colin G

    2015-12-01

    Cantú syndrome (CS) is a rare disease characterized by congenital hypertrichosis, distinct facial features, osteochondrodysplasia, and cardiac defects. Recent genetic analysis has revealed that the majority of CS patients carry a missense mutation in ABCC9, which codes for the sulfonylurea receptor SUR2. SUR2 subunits couple with Kir6.x, inwardly rectifying potassium pore-forming subunits, to form adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels, which link cell metabolism to membrane excitability in a variety of tissues including vascular smooth muscle, skeletal muscle, and the heart. The functional consequences of multiple uncharacterized CS mutations remain unclear. Here, we have focused on determining the functional consequences of three documented human CS-associated ABCC9 mutations: human P432L, A478V, and C1043Y. The mutations were engineered in the equivalent position in rat SUR2A (P429L, A475V, and C1039Y), and each was coexpressed with mouse Kir6.2. Using macroscopic rubidium ((86)Rb(+)) efflux assays, we show that K(ATP) channels formed with P429L, A475V, or C1039Y mutants enhance K(ATP) activity compared with wild-type (WT) channels. We used inside-out patch-clamp electrophysiology to measure channel sensitivity to ATP inhibition and to MgADP activation. For P429L and A475V mutants, sensitivity to ATP inhibition was comparable to WT channels, but activation by MgADP was significantly greater. C1039Y-dependent channels were significantly less sensitive to inhibition by ATP or by glibenclamide, but MgADP activation was comparable to WT. The results indicate that these three CS mutations all lead to overactive K(ATP) channels, but at least two mechanisms underlie the observed gain of function: decreased ATP inhibition and enhanced MgADP activation. PMID:26621776

  9. Hypoglycemia Secondary to Sulfonylurea Ingestion in a Patient with End Stage Renal Disease: Results from a 72-Hour Fast

    Directory of Open Access Journals (Sweden)

    Alice Abraham

    2015-01-01

    Full Text Available Insulin, proinsulin, and C-peptide levels increase with sulfonylurea exposure but the acuity of increase has not been described in dialysis patients. We present a case of a dialysis patient who presented with hypoglycemia and was found to have accidental sulfonylurea ingestion. This is a 73-year-old man with ESRD on peritoneal dialysis, without history of diabetes, who presented with hypoglycemia. Past medical history includes multiple myeloma, congestive heart failure, and hypertension. At initial presentation, his blood glucose was 47 mg/dL, with concomitant elevations in the following: C-peptide 30.5 (nl: 0.8–3.5 ng/mL, insulin 76 (nl: 3–19 μIU/mL, and proinsulin 83.3 (nl: ≤8.0 pmol/L. During the 72-hour fast, which he completed without hypoglycemia, insulin declined to be within normal limits (to 12 μIU/mL; proinsulin (to 12.1 pmol/L and C-peptide (to 7.2 ng/mL levels decreased but remained elevated. The sulfonylurea screen ultimately returned positive for glipizide, clinching the diagnosis. This is the first reported case which characterizes the chronic elevation of proinsulin in a patient with ESRD, as well as its dramatic increase after a presumed solitary exposure to sulfonylurea. The 72-hour fast conducted gives insight into the clearance of insulin, proinsulin, and C-peptide after sulfonylurea ingestion in ESRD.

  10. EFFECTS OF PYRETHROIDS ON VOLTAGE-SENSITIVE CALCIUM CHANNELS: A CRITICAL EVALUATION OF STRENGTHS, WEAKNESSES, DATA NEEDS, AND RELATIONSHIP TO ASSESSMENT OF CUMULATIVE NEUROTOXICITY.

    Science.gov (United States)

    A recently published review (Soderlund et al., 2002, Toxicology 171, 3-59.) of the mechanisms of acute neurotoxicity of pyrethroid compounds postulated that voltage-sensitive calcium channels (VSCC) may be a target of some pyrethroid compounds and that effects on VSCC may contrib...

  11. Contribution of K+ channels and ouabain-sensitive mechanisms to the endothelium-dependent relaxations of horse penile small arteries

    Science.gov (United States)

    Prieto, Dolores; Simonsen, Ulf; Hernández, Medardo; García-Sacristán, Albino

    1998-01-01

    Penile small arteries (effective internal lumen diameter of 300–600 μm) were isolated from the horse corpus cavernosum and mounted in microvascular myographs in order to investigate the mechanisms underlying the endothelium-dependent relaxations to acetylcholine (ACh) and bradykinin (BK).In arteries preconstricted with the thromboxane analogue U46619 (3–30 nM), ACh and BK elicited concentration-dependent relaxations, pD2 and maximal responses being 7.71±0.09 and 91±1% (n=23), and 8.80±0.07 and 89±2% (n=24) for ACh and BK, respectively. These relaxations were abolished by mechanical endothelial cell removal, attenuated by the nitric oxide (NO) synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NOARG, 100 μM) and unchanged by indomethacin (3 μM). However, raising extracellular K+ to concentrations of 20–30 mM significantly inhibited the ACh and BK relaxant responses to 63±4% (P<0.01, n=7) and to 59±4% (P<0.01, n=6), respectively. ACh- and BK-elicited relaxations were abolished in arteries preconstricted with K+ in the presence of 100 μM L-NOARG.In contrast to the inhibitor of ATP-sensitive K+ channels, the blockers of Ca2+-activated K+ (KCa) channels, charybdotoxin (30 nM) and apamin (0.3 μM), each induced slight but significant rightward shifts of the relaxations to ACh and BK without affecting the maximal responses. Combination of charybdotoxin and apamin did not cause further inhibition of the relaxations compared to either toxin alone. In the presence of L-NOARG (100 μM), combined application of the two toxins resulted in the most effective inhibition of the relaxations to both ACh and BK. Thus, pD2 and maximal responses for ACh and BK were 7.65±0.08 and 98±1%, and 9.17±0.09 and 100±0%, respectively, in controls, and 5.87±0.09 (P<0.05, n=6) and 38±11% (P<0.05, n=6), and 8.09±0.14 (P<0.01, n=6) and 98±1% (n=6), respectively, after combined application of charybdotoxin plus apamin and L-NOARG.The selective inhibitor of

  12. Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon

    Institute of Scientific and Technical Information of China (English)

    Yu JIN; Wei-ping XIE; Hong WANG

    2012-01-01

    Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries.The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance,reverse pulmonary vascular remodeling,and thereby improving right ventricular function.Iptakalim,a lipophilic para-amino compound with a low molecular weight,has been demonstrated to be a new selective ATP-sensitive potassium (KATP) channel opener via pharmacological,electrophysiological,biochemical studies,and receptor binding tests.In hypoxia-induced animal models,iptakalim decreases the elevated mean pressure in pulmonary arteries,and attenuates remodeling in the right ventricle,pulmonary arteries and airways.Furthermore,iptakalim has selective antihypertensive effects,selective vasorelaxation effects on smaller arteries,and protective effects on endothelial cells,but no effects on the central nervous,respiratory,digestive or endocrine systems at therapeutic dose.Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1,reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells.Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials,it can be a potential candidate of HPH in the future.

  13. Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

    Science.gov (United States)

    Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

    2016-02-01

    Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

  14. Channelized debris flow hazard mitigation through the use of flexible barriers: a simplified computational approach for a sensitivity analysis.

    Science.gov (United States)

    Segalini, Andrea; Ferrero, Anna Maria; Brighenti, Roberto

    2013-04-01

    A channelized debris flow is usually represented by a mixture of solid particles of various sizes and water, flowing along a laterally confined inclined channel-shaped region up to an unconfined area where it slow down its motion and spreads out into a flat-shaped mass. The study of these phenomena is very difficult due to their short duration and unpredictability, lack of historical data for a given basin and complexity of the involved mechanical phenomena. The post event surveys allow for the identification of some depositional features and provide indication about the maximum flow height; however they lack information about development of the phenomena with time. For this purpose the monitoring of recursive events has been carried out by several Authors. Most of the studies, aimed at the determination of the characteristic features of a debris flow, were carried out in artificial channels, where the main involved variables were measured and other where controlled during the tests; however, some uncertainties remained and other scaled models where developed to simulate the deposition mechanics as well as to analyze the transportation mechanics and the energy dissipation. The assessment of the mechanical behavior of the protection structures upon impact with the flow as well as the energy associated to it are necessary for the proper design of such structures that, in densely populated area, can avoid victims and limit the destructive effects of such a phenomenon. In this work a simplified structural model, developed by the Authors for the safety assessment of retention barrier against channelized debris flow, is presented and some parametric cases are interpreted through the proposed approach; this model is developed as a simplified and efficient tool to be used for the verification of the supporting cables and foundations of a flexible debris flow barrier. The present analytical and numerical-based approach has a different aim of a FEM model. The computational

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

    International Nuclear Information System (INIS)

    Dielectrophoresis (DEP)-the motion of particles in non-uniform AC fields-has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K+ and Ca2+ levels were extremely similar between sensitive and resistant lines, levels of Cl- were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function. (note)

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

    Science.gov (United States)

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

    2008-01-01

    Dielectrophoresis (DEP)—the motion of particles in non-uniform AC fields—has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K+ and Ca2+ levels were extremely similar between sensitive and resistant lines, levels of Cl- were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function.

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

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, L [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Shelmerdine, H [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Hughes, M P [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Coley, H M [Postgraduate Medical School, University of Surrey, Guildford GU27XH (United Kingdom); Huebner, Y [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Labeed, F H [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom)

    2008-01-21

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

  18. T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants.

    Science.gov (United States)

    Gangarossa, Giuseppe; Laffray, Sophie; Bourinet, Emmanuel; Valjent, Emmanuel

    2014-01-01

    The fine-tuning of neuronal excitability relies on a tight control of Ca(2+) homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type channel Cav3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca(2+) channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations. PMID:24672455

  19. T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants.

    Directory of Open Access Journals (Sweden)

    Giuseppe Gangarossa

    2014-03-01

    Full Text Available The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type channel Cav3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca2+ channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations.

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

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Aalkjær, Christian; Nilsson, Holger; Matchkov, Vladimir V; Freiberg, Jacob; Holstein-Rathlou, N.-H.

    2007-01-01

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

  1. Development of a method for the simultaneous determination of six sulfonylurea herbicides in wheat, rice, and corn by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kang, Shu; Chang, Na; Zhao, Yang; Pan, Canping

    2011-09-28

    A sensitive and reliable method was developed and validated for trace determination of sulfonylurea herbicides residues in cereals (wheat, rice, and corn) by liquid chromatography-tandem mass spectrometry. The selected analytes were ethoxysulfuron, ethametsulfuron-methyl, bensulfuron-methyl, chlorimuron-ethyl, pyrazosulfuron-ethyl, and cyclosulfamuron. In this work, the extraction procedure was performed by using a mixture solvent of phosphate buffer (pH 9.5)/acetonitrile (8:2, v/v) as the extraction solvent and then was cleaned up by using Spe-ed C18/18% SPE cartridges, providing good recoveries for all of the tested analytes and with no matrix effects affecting method accuracy. The limits of detection for the studied analytes in cereal samples were between 0.043 and 0.23 μg kg(-1), and the limits of quantification were between 0.14 and 0.77 μg kg(-1), lower in all cases than the maximum residue limits permitted by the European Union for this kind of food. The developed methodology has demonstrated its suitability for the monitoring of these residues in cereal samples with high sensitivity, precision, and satisfactory recoveries. PMID:21800900

  2. Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

    Czech Academy of Sciences Publication Activity Database

    Armstrong, C. T.; Mason, Philip E.; Anderson, J. L. R.; Dempsey, Ch. E.

    2016-01-01

    Roč. 6, Feb 22 (2016), 21759/1-21759/10. ISSN 2045-2322 Institutional support: RVO:61388963 Keywords : K+ channel * potassium channels * sensing domain Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.578, year: 2014 http://www.nature.com/articles/srep21759

  3. Loss of ATP-Sensitive Potassium Channel Surface Expression in Heart Failure Underlies Dysregulation of Action Potential Duration and Myocardial Vulnerability to Injury.

    Directory of Open Access Journals (Sweden)

    Zhan Gao

    Full Text Available The search for new approaches to treatment and prevention of heart failure is a major challenge in medicine. The adenosine triphosphate-sensitive potassium (KATP channel has been long associated with the ability to preserve myocardial function and viability under stress. High surface expression of membrane KATP channels ensures a rapid energy-sparing reduction in action potential duration (APD in response to metabolic challenges, while cellular signaling that reduces surface KATP channel expression blunts APD shortening, thus sacrificing energetic efficiency in exchange for greater cellular calcium entry and increased contractile force. In healthy hearts, calcium/calmodulin-dependent protein kinase II (CaMKII phosphorylates the Kir6.2 KATP channel subunit initiating a cascade responsible for KATP channel endocytosis. Here, activation of CaMKII in a transaortic banding (TAB model of heart failure is coupled with a 35-40% reduction in surface expression of KATP channels compared to hearts from sham-operated mice. Linkage between KATP channel expression and CaMKII is verified in isolated cardiomyocytes in which activation of CaMKII results in downregulation of KATP channel current. Accordingly, shortening of monophasic APD is slowed in response to hypoxia or heart rate acceleration in failing compared to non-failing hearts, a phenomenon previously shown to result in significant increases in oxygen consumption. Even in the absence of coronary artery disease, failing myocardium can be further injured by ischemia due to a mismatch between metabolic supply and demand. Ischemia-reperfusion injury, following ischemic preconditioning, is diminished in hearts with CaMKII inhibition compared to wild-type hearts and this advantage is largely eliminated when myocardial KATP channel expression is absent, supporting that the myocardial protective benefit of CaMKII inhibition in heart failure may be substantially mediated by KATP channels. Recognition of Ca

  4. Multiple resistance to sulfonylureas and imidazolinones conferred by an acetohydroxyacid synthase gene with separate mutations for selective resistance.

    Science.gov (United States)

    Hattori, J; Rutledge, R; Labbé, H; Brown, D; Sunohara, G; Miki, B

    1992-03-01

    The acetohydroxyacid synthase (AHAS) gene from the Arabidopsis thaliana mutant line GH90 carrying the imidazolinone resistance allele imr1 was cloned. Expression of the AHAS gene under the control of the CaMV 35S promoter in transgenic tobacco resulted in selective imidazolinone resistance, confirming that the single base-pair change found near the 3' end of the coding region of this gene is responsible for imidazolinone resistance. A chimeric AHAS gene containing both the imr1 mutation and the csr1 mutation, responsible for selective resistance to sulfonylurea herbicides, was constructed. It conferred on transgenic tobacco plants resistance to both sulfonylurea and imidazolinone herbicides. The data illustrate that a multiple-resistance phenotype can be achieved in an AHAS gene through combinations of separate mutations, each of which individually confers resistance to only one class of herbicides. PMID:1557022

  5. Kir6.2△C26 Channel Traffics to Plasma Membrane by Constitutive Exocytosis

    Institute of Scientific and Technical Information of China (English)

    Ping ZHAO; Wei LI; Yong-Ming DONG; Dan ZHU; An-Lian QU; Tao XU; Zheng-Xing WU

    2006-01-01

    Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels regulate many cellular functions by coupling the metabolic state of the cell to the changes in membrane potential. Truncation of C-terminal 26 amino acid residues of Kir6.2 protein (Kir6.2△C26) deletes its endoplasmic reticulum retention signal, allowing functional expression of Kir6.2 in the absence of sulfonylurea receptor subunit. pEGFP-Kir6.2△C26 and pKir6.2△C26-IRES2-EGFP expression plasmids were constructed and transfected into HEK293 cells. We identified that Kir6.2△C26 was localized on the plasma membrane and trafficked to the plasmalemma by means of constitutive exocytosis of Kir6.2△C26 transport vesicles, using epi-fluorescence and total internal reflection fluorescence microscopy. Our electrophysiological data showed that Kir6.2△C26 alone expressed KATP currents, whereas EGFP-Kir6.2△C26 fusion protein displayed no KATP channel activity.

  6. Effects of the Number of Active Receiver Channels on the Sensitivity of a Reflector Antenna System with a Multi-Beam Wideband Phased Array Feed

    CERN Document Server

    Iupikov, O

    2016-01-01

    A method for accurate modeling of a reflector antenna system with a wideband phased array feed is presented and used to study the effects of the number of active antenna elements and associated receiving channels on the receiving sensitivity of the antenna system. Numerical results are shown for a practical design named APERTIF that is currently under developed at The Netherlands Institute for Radio Astronomy (ASTRON).

  7. Association between Genetic Polymorphisms in Cav2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery

    OpenAIRE

    Soichiro Ide; Daisuke Nishizawa; Ken-ichi Fukuda; Shinya Kasai; Junko Hasegawa; Masakazu Hayashida; Masabumi Minami; Kazutaka Ikeda

    2013-01-01

    Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca(2+) channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Ca(v)2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide po...

  8. Quantitative autoradiography of the binding sites for ( sup 125 I) iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Gehlert, D.R.; Gackenheimer, S.L.; Mais, D.E.; Robertson, D.W. (Eli Lilly and Co., Indianapolis, IN (USA))

    1991-05-01

    We have developed a high specific activity ligand for localization of ATP-sensitive potassium channels in the brain. When brain sections were incubated with ({sup 125}I)iodoglyburide (N-(2-((((cyclohexylamino)carbonyl)amino)sulfonyl)ethyl)-5-{sup 125}I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific ({sup 125}I)iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of ({sup 125}I)iodoglyburide binding indicated a broad distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels.

  9. Quantitative autoradiography of the binding sites for [125I] iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain

    International Nuclear Information System (INIS)

    We have developed a high specific activity ligand for localization of ATP-sensitive potassium channels in the brain. When brain sections were incubated with [125I]iodoglyburide (N-[2-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]ethyl]-5-125I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific [125I]iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of [125I]iodoglyburide binding indicated a broad distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels

  10. Association between Genetic Polymorphisms in Cav2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery

    OpenAIRE

    Ide, Soichiro; Nishizawa, Daisuke; Fukuda, Ken-ichi; Kasai, Shinya; Hasegawa, Junko; Hayashida, Masakazu; Minami, Masabumi; Ikeda, Kazutaka

    2013-01-01

    Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca2+ channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Cav2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymo...

  11. A Patient Suffering from Hypokalemic Periodic Paralysis Is Deficient in Skeletal Muscle ATP-sensitive K+ channels

    OpenAIRE

    Jovanović, Sofija; Du, Qingyou; Mukhopadhyay, Somnath; Swingler, Robert; Buckley, Richard; McEachen, Jane; Jovanović, Aleksandar

    2008-01-01

    Hypokalemic periodic paralysis (HOPP) is a rare disease associated with attacks of muscle weakness and hypokalemia. In the present study, immunoprecipitation/Western blotting has shown that a HOPP patient was deficient in sarcolemmal KATP channels. Real-time RT-PCR has revealed that HOPP has decreased mRNA levels of Kir6.2, a pore-forming KATP channel subunit, without affecting the expression of other KATP channel-forming proteins. Based on these findings, we conclude that HOPP could be assoc...

  12. Effects of ethanol on voltage-sensitive Na-channels in cultured skeletal muscle: Up-regulation as a result of chronic treatment

    International Nuclear Information System (INIS)

    The effects of acute and chronic treatment with ethanol were studied on the number and activity of tetrodotoxin-sensitive Na-channels in cultured rat skeletal muscle. The number of channels was determined by measurements of specific binding of [3H] saxitoxin (STX) in whole cell preparations. Measurements were also made of the frequency and rate of rise of spontaneously occurring action potentials, which are the physiologic expression of Na-channel density. Acute ethanol (37.5-150 mM), while causing depolarization of membrane potential and blockade of electrical activity, was without effect on specific STX binding. Neither methanol, acetaldehyde nor ethylene glycol had significant effects on these properties when given acutely in the same concentrations as ethanol. Chronic ethanol caused dose-related increases in STX binding and action potential properties with maximal levels being attained after 3 days of treatment at a concentration of 150 mM. On removal of ethanol from the culture medium all properties returned to control levels after 48 hr. Both increased external K+ and tetrodotoxin, which up-regulate Na-channels by reducing cytosolic Ca++, potentiated the ethanol-induced increase in Na-channel density. The increase in STX binding was not associated with changes in affinity of the binding sites for the ligand but was completely prevented by treatment with cycloheximide and actinomycin D. The results demonstrate that ethanol interacts with the cell membrane to induce synthesis of STX-binding sites

  13. Blockade of presynaptic 4-aminopyridine-sensitive potassium channels increases initial neurotransmitter release probability, reinstates synaptic transmission altered by GABAB receptor activation in rat midbrain periaqueductal gray.

    Science.gov (United States)

    Li, Guangying; Liu, Zhi-Liang; Zhang, Wei-Ning; Yang, Kun

    2016-01-01

    The activation of γ-aminobutyric acid receptor subtype B (GABAB) receptors in the midbrain ventrolateral periaqueductal gray (vlPAG) induces both postsynaptic and presynaptic inhibition. Whereas the postsynaptic inhibition is mediated by G protein-coupled inwardly rectifying K channels, the presynaptic inhibition of neurotransmitter release is primarily mediated by voltage-gated calcium channels. Using whole-cell recordings from acute rat PAG slices, we report here that the bath application of 4-aminopyridine, a voltage-gated K channel blocker, increases the initial GABA and glutamate release probability (P) and reinstates P depressed by presynaptic GABAB receptor activation at inhibitory and excitatory synapses, respectively. However, Ba, which blocks G protein-coupled inwardly rectifying K channels, does not produce similar effects. Our data suggest that the blockade of presynaptic 4-aminopyridine-sensitive K channels in vlPAG facilitates neurotransmitter release and reinstates synaptic transmission that has been altered by presynaptic GABAB receptor activation. Because vlPAG is involved in the descending pain control system, the present results may have potential therapeutic applications. PMID:26575285

  14. Identification of a Binding Motif in the S5 Helix That Confers Cholesterol Sensitivity to the TRPV1 Ion Channel*

    OpenAIRE

    Picazo-Juárez, Giovanni; Romero-Suárez, Silvina; Nieto-Posadas, Andrés; Llorente, Itzel; Jara-Oseguera, Andrés; Briggs, Margaret; McIntosh, Thomas J.; Simon, Sidney A.; Ladrón-de-Guevara, Ernesto; Islas, León D.; Rosenbaum, Tamara

    2011-01-01

    The TRPV1 ion channel serves as an integrator of noxious stimuli with its activation linked to pain and neurogenic inflammation. Cholesterol, a major component of cell membranes, modifies the function of several types of ion channels. Here, using measurements of capsaicin-activated currents in excised patches from TRPV1-expressing HEK cells, we show that enrichment with cholesterol, but not its diastereoisomer epicholesterol, markedly decreased wild-type rat TRPV1 currents. Substitutions in t...

  15. Abnormal activation of potassium channels in aortic smooth muscle of rats with peritonitis-induced septic shock.

    Science.gov (United States)

    Kuo, Jiunn-Horng; Chen, Shiu-Jen; Shih, Chih-Chin; Lue, Wei-Ming; Wu, Chin-Chen

    2009-07-01

    This study was conducted to examine the role of membrane hyperpolarization in mediating vascular hyporeactivity induced by cecal ligation and puncture (CLP) in endothelial-denuded strips of rat thoracic aorta ex vivo. The CLP for 18 h elicited a significant fall of blood pressure and a severe vascular hyporeactivity to norepinephrine as seen in severe sepsis. At the end of the in vivo experiments, thoracic aortas were removed from both CLP-treated and control rats. After removal of the endothelium, aortic segments were mounted in myographs for the recording of isometric tension and smooth muscle membrane potential. The membrane potential recording showed that a hyperpolarization was observed in the CLP-treated rats when compared with the control rats. This hyperpolarization was reversed by iberiotoxin (a large-conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), barium (an inward rectifier K+ channels blocker), N-(1-adamantyl)-N'-cyclohexyl-4-morpholinecarboxamidine hydrochloride (a pore-forming blocker of adenosine triphosphate (ATP)-sensitive K+ channels [KATP]), or methylene blue (a nonspecific guanylyl cyclase [GC] inhibitor). However, this hyperpolarization was not significantly affected by apamin (a small-conductance Ca2+-activated K+ channel blocker), glibenclamide (a sulfonylurea blocker of KATP), N(omega)-nitro-L-arginine methyl ester (a NOS inhibitor), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an NO-sensitive GC inhibitor). In addition, the basal tension of the tissues obtained from CLP rats was increased simultaneously, whereas membrane potential was reversed. In contrast, none of these inhibitors had significant effects on the membrane potential or the basal tension in control tissues. Thus, we provide electrophysiological and functional evidence demonstrating that an abnormal activation of K+ channels in vascular smooth muscle in animals with septic shock induced by CLP. Our observations

  16. The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials

    Science.gov (United States)

    Varvaki Rados, Dimitris; Catani Pinto, Lana; Reck Remonti, Luciana; Bauermann Leitão, Cristiane; Gross, Jorge Luiz

    2016-01-01

    Background Sulfonylureas are an effective and inexpensive treatment for type 2 diabetes. There is conflicting data about the safety of these drugs regarding mortality and cardiovascular outcomes. The objective of the present study was to evaluate the safety of the sulfonylureas most frequently used and to use trial sequential analysis (TSA) to analyze whether the available sample was powered enough to support the results. Methods and Findings Electronic databases were reviewed from 1946 (Embase) or 1966 (MEDLINE) up to 31 December 2014. Randomized clinical trials (RCTs) of at least 52 wk in duration evaluating second- or third-generation sulfonylureas in the treatment of adults with type 2 diabetes and reporting outcomes of interest were included. Primary outcomes were all-cause and cardiovascular mortality. Additionally, myocardial infarction and stroke events were evaluated. Data were summarized with Peto odds ratios (ORs), and the reliability of the results was evaluated with TSA. Forty-seven RCTs with 37,650 patients and 890 deaths in total were included. Sulfonylureas were not associated with all-cause (OR 1.12 [95% CI 0.96 to 1.30]) or cardiovascular mortality (OR 1.12 [95% CI 0.87 to 1.42]). Sulfonylureas were also not associated with increased risk of myocardial infarction (OR 0.92 [95% CI 0.76 to 1.12]) or stroke (OR 1.16 [95% CI 0.81 to 1.66]). TSA could discard an absolute difference of 0.5% between the treatments, which was considered the minimal clinically significant difference. The major limitation of this review was the inclusion of studies not designed to evaluate safety outcomes. Conclusions Sulfonylureas are not associated with increased risk for all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke. Current evidence supports the safety of sulfonylureas; an absolute risk of 0.5% could be firmly discarded. Review registration PROSPERO CRD42014004330 PMID:27071029

  17. Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes

    Science.gov (United States)

    Fan, Zhuo; Wen, Ting; Chen, Yaoxu; Huang, Lijie; Lin, Wei; Yin, Chunxia; Tan, Wen

    2016-01-01

    KATP channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of KATP channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcKATP channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcKATP channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria. PMID:26949448

  18. Magnetic molecular imprint-based extraction of sulfonylurea herbicides and their determination by capillary liquid chromatography

    International Nuclear Information System (INIS)

    We have developed a simple method for the extraction of sulfonylurea herbicides (SUHs) from environmental water samples. It is based on a magnetic molecular imprint (MMIP) as a sorbent. The MMIP was prepared using metsulfuron-methyl as the template molecule, methacrylic acid as the functional monomer, trimethylolpropane trimethacrylate as the cross-linking agent, and magnetite as the magnetic component. Extraction can be carried out by blending and stirring water sample, extraction solvent and MMIP. Once the extraction is completed, the MMIP containing the SUHs can be separated from the sample matrix with a magnet. The SUHs desorbed from the polymers were then quantified by capillary liquid chromatography with diode array detection. The limits of quantification are in the range of 0.08 to 0.1 ng mL-1. Repeatabilities of peak areas and retention times range from 2.9 % to 4.0 % and from 0.1 % to 0.3 %, respectively. The method was successfully applied to the determination of the SUHs bensulfuron-methyl, metsulfuronmethyl, pyrazosulfuron-methyl, thifensulfuron-methyl, and triasulfuron in waste water samples. Recoveries range from 94.3 % to 102.3 %. (author)

  19. The influence of selected spraying parameters on two formulation of sulfonylurea herbicides effect

    Directory of Open Access Journals (Sweden)

    Renata KIELOCH

    2013-03-01

    Full Text Available The objective of this study was the evaluation of spray volume and nozzle type effect on different formulation (water dispersible granules - WG and oil dispersion - OD of two sulfonylurea herbicides: the mixture iodosulfuron methyl sodium + amidosulfuron and iodosulfuron methyl sodium + mesosulfuron methyl efficacy. There were investigated three levels of spray volume (125 l*ha-1, 250 l*ha-1 and 350 l*ha-1 and two types of nozzle (extended range flat nozzle TeeJet XR 11003-VS and drift guard flat nozzle TeeJet DG 11003-VS. Each herbicide was used at recommended dose and reduced by half. Spray volume and nozzle type did not affect activity of the mixture iodosulfuron methyl sodium + amidosulfuron, but differentiated the efficacy of OD formulation of iodosulfuron methyl sodium + mesosulfuron methyl, when it was applied at lowered dose. As spray volume rose, herbicide efficacy decreased. Nozzle type influenced OD formulation of the mixture iodosulfuron methyl sodium + mesosulfuron methyl, independently on dose. Significantly weaker efficacy was obtained when drift guard nozzle was used.

  20. Isoform-specific modulation of the chemical sensitivity of conserved TRPA1 channel in the major honeybee ectoparasitic mite, Tropilaelaps mercedesae.

    Science.gov (United States)

    Dong, Xiaofeng; Kashio, Makiko; Peng, Guangda; Wang, Xinyue; Tominaga, Makoto; Kadowaki, Tatsuhiko

    2016-06-01

    We identified and characterized the TRPA1 channel of Tropilaelaps mercedesae (TmTRPA1), one of two major species of honeybee ectoparasitic mite. Three TmTRPA1 isoforms with unique N-terminal sequences were activated by heat, and the isoform highly expressed in the mite's front legs, TmTRPA1b, was also activated by 27 plant-derived compounds including electrophiles. This suggests that the heat- and electrophile-dependent gating mechanisms as nocisensitive TRPA1 channel are well conserved between arthropod species. Intriguingly, one TmTRPA1 isoform, TmTRPA1a, was activated by only six compounds compared with two other isoforms, demonstrating that the N-terminal sequences are critical determinants for the chemical sensitivity. This is the first example of isoform-specific modulation of chemical sensitivity of TRPA1 channel in one species. α-terpineol showed repellent activity towards T. mercedesae in a laboratory assay and repressed T. mercedesae entry for reproduction into the brood cells with fifth instar larvae in hives. Thus, α-terpineol could be used as the potential compound to control two major honeybee ectoparasitic mites, T. mercedesae and Varroa destructor, in the apiculture industry. PMID:27307515

  1. Sensitivity and specificity of simultaneously acquired (dual channel) radiogallium and Tc-99m-HDP in painful hip and knee prosthetic joints

    International Nuclear Information System (INIS)

    Differentiation of prosthetic loosening from infection, by use of sequential bone and radiogallium imaging, has been discussed in the literature. The authors investigated simultaneous (2 channel) imaging of Ga-67 and Tc-99m-HDP in multiviews, in order to assess the parameter of Tc-99m-Ga-67 incongruity. Acquisition of data was carried out 2 days after 5 mCi of Ga-67 citrate IV and 2 hours after 8 mCi of Tc-99m-HDP. Dual data channels were used to insure perfect superimposition of the images and to reduce total imaging time. Normalized bone images were taken, then subtracted from those of Ga-67, by means of progressive weighting factors. A total of 68 studies were carried out on 43 patients. Exams involved both knee and hip prostheses, in population with 63% of the patients over age 60 years. Time from placement of the prosthesis to the dual radionuclide exam was within 2 years in 48% and within 5 years in 78%. Sensitivity was 0.88 and specificity 0.89. Using information on the follow-up dual channel studies, 40/43 cases were correctly identified (93%). Dual channel radionuclide imaging offers a readily available and accurate means of differentiating infection from loosening of hip or knee prostheses

  2. Role of ATP-sensitive K+-channels in antiarrhythmic and cardioprotective action of adaptation to intermittent hypobaric hypoxia

    Czech Academy of Sciences Publication Activity Database

    Kolář, František; Neckář, Jan; Ošťádal, Bohuslav; Maslov, L. N.; Stakheev, D. L.; Tayurskaya, A. S.; Lishmanov, Yu. B.

    2008-01-01

    Roč. 145, č. 4 (2008), s. 418-421. ISSN 0007-4888 R&D Projects: GA ČR(CZ) GA305/07/0875 Institutional research plan: CEZ:AV0Z50110509 Keywords : arrhythmias * myocardial infarction * K(ATP) channels Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 0.258, year: 2008

  3. First direct electron microscopic visualization of a tight spatial coupling between GABAA-receptors and voltage-sensitive calcium channels

    DEFF Research Database (Denmark)

    Hansen, G H; Belhage, B; Schousboe, A

    1992-01-01

    of different and well defined sizes were performed. This showed that in THIP-treated cultures 20% of GABAA-receptors in cell processes were located in close proximity (i.e. within 40 nm) of Ca2+ channels in the plasma membrane. This was not observed in non-treated cultures nor was it observed in cell...

  4. Α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve.

    Science.gov (United States)

    Wang, Xiu-Chao; Wang, Shan; Zhang, Ming; Gao, Fang; Yin, Chun; Li, Hao; Zhang, Ying; Hu, San-Jue; Duan, Jian-Hong

    2016-02-01

    It is known that some patients with diabetic neuropathy are usually accompanied by abnormal painful sensations. Evidence has accumulated that diabetic neuropathic pain is associated with the hyperexcitability of peripheral nociceptors. Previously, we demonstrated that reduced conduction failure of polymodal nociceptive C-fibers and enhanced voltage-dependent sodium currents of small dorsal root ganglion (DRG) neurons contribute to diabetic hyperalgesia. To further investigate whether and how potassium channels are involved in the conduction failure, α-dendrotoxin (α-DTX), a selective blocker of the low-threshold sustained Kv1 channel, was chosen to examine its functional capability in modulating the conduction properties of polymodal nociceptive C-fibers and the excitability of sensory neurons. We found that α-DTX reduced the conduction failure of C-fibers from coccygeal nerve in vivo accompanied by an increased initial conduction velocity but a decreased activity-dependent slowing of conduction velocity. In addition, the number of APs evoked by step currents was significantly enhanced after the treatment with α-DTX in small-diameter sensory neurons. Further study of the mechanism indicates α-DTX-sensitive K(+) current significantly reduced and the activation of this current in peak and steady state shifted to depolarization for diabetic neurons. Expression of Kv channel subunits Kv1.2 and Kv1.6 was downregulated in both small dorsal root ganglion neurons and peripheral C-fibers. Taken together, these results suggest that α-DTX-sensitive Kv1 channels might play an important role in regulating the conduction properties of polymodal nociceptive C-fibers and firing properties of sensory neurons. PMID:26609114

  5. Inhibition of T-Type Voltage Sensitive Calcium Channel Reduces Load-Induced OA in Mice and Suppresses the Catabolic Effect of Bone Mechanical Stress on Chondrocytes

    OpenAIRE

    Srinivasan, Padma P.; Parajuli, Ashutosh; Price, Christopher; Wang, Liyun; Duncan, Randall L.; Kirn-Safran, Catherine B.

    2015-01-01

    Voltage-sensitive calcium channels (VSCC) regulate cellular calcium influx, one of the earliest responses to mechanical stimulation in osteoblasts. Here, we postulate that T-type VSCCs play an essential role in bone mechanical response to load and participate in events leading to the pathology of load-induced OA. Repetitive mechanical insult was used to induce OA in Cav3.2 T-VSCC null and wild-type control mouse knees. Osteoblasts (MC3T3-E1) and chondrocytes were treated with a selective T-VS...

  6. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries.

    Science.gov (United States)

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C

    2015-10-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment. PMID:26362752

  7. Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

    OpenAIRE

    Hu, Ji; Song, Zhen-Yuan; Zhang, Hong-Hong; Qin, Xin; Hu, Shufen; Jiang, Xinghong; Xu, Guang-Yin

    2016-01-01

    Background/Aims Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. Methods Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the...

  8. pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer

    DEFF Research Database (Denmark)

    Sauter, Daniel Rafael Peter; Sørensen, Christiane Elisabeth; Rapedius, Markus;

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and new therapeutic targets are urgently needed. One of the hallmarks of cancer is changed pH-homeostasis and potentially pH-sensors may play an important role in cancer cell behavior. Two-pore potassium channels (K2P) are p...... both PDAC cell proliferation and migration indicating that hyperpolarization of Vm attenuates cancer cell behavior. TREK-1 may therefore be a promising novel target for PDAC therapy....

  9. Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway

    OpenAIRE

    Lazar, Alexandra; Lenkey, Nora; Pesti, Krisztina; Fodor, Laszlo; Mike, Arpad

    2015-01-01

    The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their...

  10. Study on Phytotoxicity of Sulfonylurea Herbicides%磺酰脲类除草剂药害规律的研究

    Institute of Scientific and Technical Information of China (English)

    赵建庄

    2001-01-01

    采用作物主根长法测定了常用两种磺酰脲类除草剂对玉米(Zea mays L.)农大1 236和豌豆(Pisum sativum L.)中碗6号的相对毒力,玉米试验结果表明,以IC 50值比较,氯磺 隆、胺苯磺隆对玉米的毒力较高,容易造成药害。豌豆试验结果表明,豌豆对氯磺隆和胺苯 磺隆比玉米更敏感。离体玉米和豌豆ALS酶的研究表明,豌豆的ALS对两种磺酰脲类除草剂较 玉米更敏感,氯磺隆对两种作物的ALS抑制作用也较胺苯磺隆强。%The relative toxicity of two commonly used sulfonylurea herbici des were tested by main root length using maize CAU1236 (Zea mays L. ) and pea (Pisum sativum L.)No.6CB. IC50 values for maize indi cated that, chlorsulfuron, ethametsulfuron-methyl had high toxicity to maize, m aize had photo toxicity to these herbicide easily. Study on pea indicated that, pea was more sensitive to chlorsulfuron and ethametsulfuron-methyl. Study on in vitro ALS of maize and pea indicated that, ALS from pea was more sensitive than ALS from maize, chlorsulfuron had stronger inhibition to ALS of two crops than e thametsulfuron-methyl did.

  11. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis.

    Science.gov (United States)

    Schopman, J E; Simon, A C R; Hoefnagel, S J M; Hoekstra, J B L; Scholten, R J P M; Holleman, F

    2014-01-01

    Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experience hypoglycaemia when treated with sulfonylurea or insulin. We searched MEDLINE and EMBASE for randomized controlled trials that compared incretin-based drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the latter therapies. Subgroup and meta-regression analyses were performed to study possible associations with potential risk factors for hypoglycaemia. Data of 25 studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with glucose ≤3.1 mmol/L or ≤2.8 mmol/L was experienced by 10.1% [95% confidence interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5-1.3%) of patients. Hypoglycaemia with glucose ≤3.1 mmol/L and severe hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8-2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk factors were significant in a stepwise multivariate meta-regression analysis. Too few studies had insulin as comparator, so these data could not be meta-analysed. The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in clinical trials remain free of any relevant hypoglycaemia. Gliclazide was associated with the lowest risk of hypoglycaemia. Because participants in randomized controlled trials differ from the general population, care should be taken when translating these data into clinical practice. PMID:24030920

  12. Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

    OpenAIRE

    Chazan A.C.S.; Gomes M.B.

    2001-01-01

    To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 ± 8.3 years, with a duration of diabetes of 10.6 ± 6.6 years, fasting plasma glucose of 277.3 ± 64.6 mg/dl and a body mass index of 27.4 ± 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedti...

  13. Function of Transient Receptor Potential Cation Channel Subfamily V Member 4 (TRPV4) as a Mechanical Transducer in Flow-sensitive Segments of Renal Collecting Duct System*

    Science.gov (United States)

    Berrout, Jonathan; Jin, Min; Mamenko, Mykola; Zaika, Oleg; Pochynyuk, Oleh; O'Neil, Roger G.

    2012-01-01

    The TRPV4 Ca2+-permeable channel is sensitive to mechanical stimuli. In the current study we have employed immunocytochemical staining in kidney slices and functional assessments (Ca2+ imaging) in isolated, split-opened, tubule segments to define TRPV4 sites of expression and flow-dependent function in the collecting duct system. Staining patterns revealed strong expression of TRPV4 along the entire collecting duct system with highest levels at the apical (luminal)/subapical region of the principal cells (PCs), the dominant cell type, with more diffuse staining in intercalated cells (ICs). Using fluorescence Ca2+ imaging and the selective TRPV4 agonist, GSK1016790A, we demonstrated functional TRPV4 channels in PCs and ICs of split-opened cortical collecting ducts and connecting tubules. The agonist was ineffective in inducing a rise in [Ca2+]i in the absence of extracellular Ca2+ or in tubules from TRPV4-deficient animals. Most importantly, a 10-fold elevation in luminal (apical) fluid flow induced a rapid and sustained influx of Ca2+ that was abolished by the TRPV channel inhibitor, ruthenium red, or in tubules isolated from TRPV4 deficient animals. We concluded that TRPV4 is highly expressed along the entire collecting duct system where it appears to function as a sensor/transducer of flow-induce mechanical stresses. PMID:22298783

  14. σ-1 Receptor Inhibition of ASIC1a Channels is Dependent on a Pertussis Toxin-Sensitive G-Protein and an AKAP150/Calcineurin Complex.

    Science.gov (United States)

    Mari, Yelenis; Katnik, Christopher; Cuevas, Javier

    2015-10-01

    ASIC1a channels play a major role in various pathophysiological conditions including depression, anxiety, epilepsy, and neurodegeneration following ischemic stroke. Sigma-1 (σ-1) receptor stimulation depresses the activity of ASIC1a channels in cortical neurons, but the mechanism(s) by which σ-1 receptors exert their influence on ASIC1a remains unknown. Experiments were undertaken to elucidate the signaling cascade linking σ-1 receptors to ASIC1a channels. Immunohistochemical studies showed that σ-1 receptors, ASIC1a and A-kinase anchoring peptide 150 colocalize in the plasma membrane of the cell body and processes of cortical neurons. Fluorometric Ca(2+) imaging experiments showed that disruption of the macromolecular complexes containing AKAP150 diminished the effects of the σ-1 on ASIC1a, as did application of the calcineurin inhibitors, cyclosporin A and FK-506. Moreover, whole-cell patch clamp experiments showed that σ-1 receptors were less effective at decreasing ASIC1a-mediated currents in the presence of the VIVIT peptide, which binds to calcineurin and prevents cellular effects dependent on AKAP150/calcineurin interaction. The coupling of σ-1 to ASIC1a was also disrupted by preincubation of the neurons in the G-protein inhibitor, pertussis toxin (PTX). Taken together, our data reveal that σ-1 receptor block of ASIC1a function is dependent on activation of a PTX-sensitive G-protein and stimulation of AKAP150 bound calcineurin. PMID:24925261

  15. The opening of maitotoxin-sensitive calcium channels induces the acrosome reaction in human spermatozoa: differences from the zona pellucida

    Institute of Scientific and Technical Information of China (English)

    Julio C Chávez; Claudia L Trevi(n)o; Gerardo A de Blas; José L de la Vega-Beltrán; Takuya Nishigaki; Mayel Chirinos; María Elena González-González; Fernando Larrea; Alejandra Solís; Alberto Darszon

    2011-01-01

    The acrosome reaction(AR),an absolute requirement for spermatozoa and egg fusion,requires the influx of Ca2+into the spermatozoa through voltage-dependent Ca2+channels and store-operated channels.Maitotoxin(MTx),a Ca2+-mobilizing agent,has been shown to be a potent inducer of the mouse sperm AR,with a pharmacology similar to that of the zona pellucida(ZP),possibly suggesting a common pathway for both inducers.Using recombinant human ZP3(rhZP3),mouse ZP and two MTx channel blockers(U73122 and U73343),we investigated and compared the MTx-and ZP-induced ARs in human and mouse spermatozoa.Herein,we report that MTx induced AR and elevated intracellular Ca2+([Ca2+]1)in human spermatozoa,both of which were blocked by U73122 and U73343.These two compounds also inhibited the MTx-induced AR in mouse spermatozoa.In disagreement with our previous proposal,the AR triggered by rhZP3 or mouse ZP was not blocked by U73343,indicating that in human and mouse spermatozoa,the AR induction by the physiologicalligands or by MTx occurred through distinct pathways.U73122,but not U73343(inactive analogue),can block phospholipase C(PLC).Another PLC inhibitor,edelfosine,also blocked the rhZP3-and ZP-induced ARs.These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR.Notably,edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human,suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.

  16. Influence of calcium channel antagonist on the pharmacodynamics of a second-generation sulfonylurea in rats and rabbits

    Directory of Open Access Journals (Sweden)

    Gopala Krishna Murthy T

    2008-01-01

    Full Text Available Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose concentration known as hyperglycemia. Diabetes mellitus covers a wide range of heterogeneous diseases and involves management of its associated acute and chronic complications; thus, there is every possibility of administering other drugs along with the primary anti-diabetic agent, which may be the cause for a drug-drug interaction to occur. In the present study, the possible pharmacodynamic interaction was studied with amlodipine besylate and gliclazide in diabetic rats and healthy rabbits. The animals were divided into three groups. Gliclazide was studied at a dose of 1.44 mg/200 g and 5.6 mg/1.5 kg body weight in rats and rabbits respectively. Amlodipine besylate at a dose of 0.090 mg/200 g and 0.350 mg/1.5 kg body weight was used for the interaction study in rats and rabbits respectively. The drugs were administered orally and the blood samples were collected before and after administration of drug for a period of 16 h in rats and 24 h in rabbits. The serum samples were then subjected to glucose estimation by glucose peroxides method. The percentage reduction in blood glucose levels were calculated with respect to initial levels. Gliclazide showed a significant reduction of elevated and normal blood glucose levels. The extent of blood glucose reduction was comparatively reduced in the case of combination therapy of amlodipine besylate and gliclazide. The study also suggests the necessity to readjust the dose of gliclazide when co-administered with amlodipine besylate.

  17. Influence of calcium channel antagonist on the pharmacodynamics of a second-generation sulfonylurea in rats and rabbits

    OpenAIRE

    Gopala Krishna Murthy T; Mayuren C

    2008-01-01

    Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose concentration known as hyperglycemia. Diabetes mellitus covers a wide range of heterogeneous diseases and involves management of its associated acute and chronic complications; thus, there is every possibility of administering other drugs along with the primary anti-diabetic agent, which may be the cause for a drug-drug interaction to occur. In the present study, the possible pharmacodynamic interaction ...

  18. A highly sensitive flow-through amperometric immunosensor based on the Peroxidase chip and enzyme-channeling principle.

    Science.gov (United States)

    Zeravik, J; Ruzgas, T; Fránek, M

    2003-10-01

    A concept based on the Peroxidase-chip (P-chip), antibody co-immobilization, competitive and enzyme-channeling principle was exploited to develop an integrated flow-through amperometric biosensor for detection of environmental pollutants such as s-triazine herbicides. In this concept, recombinant peroxidase is immobilized on the gold electrode (P-chip) in such a way that direct electron transfer is achieved. The recognition and quantitation the target analyte is realized through the competition between the simazine-glucose oxidase (GOD) conjugate and free simazine for the binding sites of the monoclonal antibody co-immobilized with peroxidase on the gold electrode. The arrangement allows to generate a specific signal in the presence of glucose through the channeling of H2O2 produced by GOD conjugate bound to the antibody. The immunosensor exhibited 50% signal decrease (IC50 value) at approximately 0.02 microg l(-1). A concentration of 0.1 ng l(-1) gave a signal clearly distinguishable from the blank whereas the ELISA using the same antibody had a typical detection limit of about 1 microg l(-1), which is four orders of magnitude higher compared to the presented biosensor system. The results demonstrated that gene engineering biomolecules, in this case recombinant peroxidase, might be attractive reagents for the development of electrochemical immunosensors. PMID:12896832

  19. Multiple saxitoxin-binding sites in bullfrog muscle: tetrodotoxin-sensitive sodium channels and tetrodotoxin-insensitive sites of unknown function

    International Nuclear Information System (INIS)

    The possible presence of multiple sodium channel subtypes in bullfrog skeletal muscle was investigated in binding experiments with [3H]saxitoxin and in single-channel studies using planar lipid bilayers. Two classes of [3H]saxitoxin-binding sites were identified in membrane preparations. One class displayed a toxin specificity characteristic of voltage-dependent sodium channels: high affinity for saxitoxin (KD approximately equal to 0.5 nM), neosaxitoxin (KD approximately equal to 0.1 nM), and tetrodotoxin (KD approximately equal to 1.3 nM). A second class of membrane-associated binding sites exhibited high affinity for saxitoxin (KD approximately equal to 0.1 nM), lower affinity for neosaxitoxin (KD approximately equal to 25 nM), and complete insensitivity to tetrodotoxin at concentrations up to 32 microM. The first class corresponded to functional tetrodotoxin-sensitive sodium channels that could be incorporated and observed in planar bilayers in the presence of batrachotoxin. The unusual, tetrodotoxin-insensitive binding activity for [3H]saxitoxin was also found at nM levels in the high speed supernatant of homogenized skeletal muscle without the addition of detergents. This soluble class of sites exhibited low affinity for neosaxitoxin (KD approximately equal to 60 nM) and a very slow dissociation rate of [3H]saxitoxin (t0.5 approximately equal to 90 min), properties nearly identical to those of the tetrodotoxin-insensitive sites in membranes. The soluble saxitoxin-binding activity is also characterized by a more basic pH dependence and a complete lack of binding competition between saxitoxin and alkali cations. Bullfrog muscle appears to be a good tissue source for the purification of this soluble saxitoxin-binding protein

  20. Multi-channel Wiener Filter for Speech Dereverberation in Hearing Aids - Sensitivity to DoA Errors

    DEFF Research Database (Denmark)

    Kuklasinski, Adam; Doclo, Simon; Jensen, Søren Holdt;

    2016-01-01

    In this paper we study the robustness of a recently proposed Multi-channel Wiener Filter-based speech dereverberation algorithm to errors in the assumed direction of arrival (DoA) of the target speech. Different subsets of microphones of a pair of behind-the-ear hearing aids are used to construct...... various monaural and binaural configurations of the algorithm. Via a simulation experiment with frontally positioned target it is shown, that when correct DoA is assumed binaural configurations of the algorithm almost double the improvement of PESQ measure over monaural configurations. However, in...... conditions where the assumed DoA is increasingly incorrect, the performance of the binaural configurations is shown to deteriorate more quickly than that of the monaural configurations. In effect, for large DoA errors it is the simpler, monaural configurations that perform better....

  1. Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway.

    Science.gov (United States)

    Lazar, Alexandra; Lenkey, Nora; Pesti, Krisztina; Fodor, Laszlo; Mike, Arpad

    2015-01-01

    The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their interaction with the membrane. In this electrophysiology study we used three different pH values: 6.0, 7.3, and 8.6 to test the significance of the protonation-deprotonation equilibrium in drug access and affinity. We investigated drugs of several different indications: carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine, flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone, silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine, sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline, nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone, and trazodone. We recorded the pH-dependence of potency, reversibility, as well as onset/offset kinetics. As expected, we observed a strong correlation between the acidic dissociation constant (pKa) of drugs and the pH-dependence of their potency. Unexpectedly, however, the pH-dependence of reversibility or kinetics showed diverse patterns, not simple correlation. Our data are best explained by a model where drug molecules can be trapped in at least two chemically different environments: A hydrophilic trap (which may be the aqueous cavity within the inner vestibule), which favors polar and less lipophilic compounds, and a lipophilic trap (which may be the membrane phase itself, and/or lipophilic binding sites on the channel). Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic and acidic extracellular pH, respectively. PMID:26441665

  2. Ionic-liquid-functionalized magnetic particles as an adsorbent for the magnetic SPE of sulfonylurea herbicides in environmental water samples.

    Science.gov (United States)

    He, Zeying; Liu, Donghui; Zhou, Zhiqiang; Wang, Peng

    2013-10-01

    In this paper, a new ionic-liquid-functionalized magnetic material was prepared based on the immobilization of an ionic liquid on silica magnetic particles that could be successfully used as an adsorbent for the magnetic SPE of five sulfonylurea herbicides (bensulfuron-methyl, prosulfuron, pyrazosulfuron-ethyl, chlorimuron-ethyl and triflusulfuron-methyl) from environmental water samples. The main parameters affecting the extraction efficiency such as desorption conditions, sample pH, extraction time and so on, were optimized using the Taguchi method. Good linearities were obtained with correlation coefficients ranging from 0.9992 to 0.9999 in the concentration range of 0.1-50 μg L(-1) and the LODs were 0.053-0.091 μg L(-1). Under the optimum conditions, the enrichment factors of the method were 1155-1380 and the recoveries ranged from 77.8 to 104.4%. The proposed method was reliable and could be applied to the residue analysis of sulfonylurea herbicides in environmental water samples (tap, reservoir and river). PMID:23894051

  3. Sulfonylurea Receptor 1 Contributes to the Astrocyte Swelling and Brain Edema in Acute Liver Failure

    OpenAIRE

    Jayakumar, A.R.; Valdes, V.; Tong, X. Y.; Shamaladevi, N.; W Gonzalez; Norenberg, M.D.

    2014-01-01

    Astrocyte swelling (cytotoxic brain edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/brain edema in other neurological disorders is the ATP-dependent, non-selective cation channel (NCCa-ATP ch...

  4. Magnetic solid-phase extraction of sulfonylurea herbicides in environmental water samples by Fe3O4@dioctadecyl dimethyl ammonium chloride@silica magnetic particles.

    Science.gov (United States)

    He, Zeying; Liu, Donghui; Li, Ranhong; Zhou, Zhiqiang; Wang, Peng

    2012-10-17

    A magnetic solid phase extraction (MSPE) method coupled with high-performance liquid chromatography (HPLC) was proposed for the determination of five sulfonylurea herbicides (bensulfuron-methyl, prosulfuron, pyrazosulfuron-ethyl, chlorimuron-ethyl and triflusulfuron-methyl) in environmental water samples. The magnetic adsorbent was prepared by incorporating Fe(3)O(4) nanoparticles and surfactant into a silica matrix according to a sol-gel procedure, which can provide surfactant free extracts during the eluting step to avoid chromatographic interference. The prepared adsorbent was used to extract the sulfonylurea herbicides in several kinds of water samples. The main factors affecting the extraction efficiency, including desorption conditions, extraction time, sample volume, and sample solution pH were optimized. Under the optimum conditions, good linearity was obtained within the range of 0.2-50.0 μg L(-1) for all analytes, with correlation coefficients ranging from 0.9993 to 0.9999. The enrichment factors were between 1200 and 1410, and the limits of detection were between 0.078 and 0.10 μg L(-1). The proposed method was successfully applied in the analysis of sulfonylurea herbicides in environmental samples (tap, reservoir, river, and rice field). The recoveries of the method ranged between 80.4% and 107.1%. This study reported for the first time the use of MSPE procedure in the preconcentration of sulfonylurea herbicides in environmental samples. The procedure proved to be efficient, environmentally friendly, and fast. PMID:22986132

  5. Development and utilization of a fluorescence-based receptor-binding assay for the site 5 voltage-sensitive sodium channel ligands brevetoxin and ciguatoxin.

    Science.gov (United States)

    McCall, Jennifer R; Jacocks, Henry M; Niven, Susan C; Poli, Mark A; Baden, Daniel G; Bourdelais, Andrea J

    2014-01-01

    Brevetoxins are a family of ladder-frame polyether toxins produced during blooms of the marine dinoflagellate Karenia brevis. Consumption of fish exposed to K. brevis blooms can lead to the development of neurotoxic shellfish poisoning. The toxic effects of brevetoxins are due to activation of voltage-sensitive sodium channels (VSSCs) in cell membranes. Binding of toxins has historically been measured using a radioligand competition assay that is fraught with difficulty. In this study, we developed a novel fluorescence-based binding assay for the brevetoxin receptor. Several fluorophores were conjugated to polyether brevetoxin-2 and used as the labeled ligand. Brevetoxin analogs were able to compete for binding with the fluorescent ligands. This assay was qualified against the standard radioligand receptor assay for the brevetoxin receptor. Furthermore, the fluorescence-based assay was used to determine relative concentrations of toxins in raw extracts of K. brevis culture, and to determine ciguatoxin affinity to site 5 of VSSCs. The fluorescence-based assay was quicker, safer, and far less expensive. As such, this assay can be used to replace the current radioligand assay and will be a vital tool for future experiments examining the binding affinity of various ligands for site 5 on sodium channels. PMID:24830141

  6. Protein kinase C regulates the activity of voltage-sensitive calcium channels of the rat chromaffin cells

    International Nuclear Information System (INIS)

    Phorbol dibutyrate (PB), an activator of protein kinase C was used as a tool to study the role of protein kinase C in the secretion of catecholamines (CA) from the perfused adrenal gland of rat. Secretion of CA evoked by splanchnic nerve stimulation, nicotine (N), carbamylcholine (C) and 35 mM K (K) was enhanced (about 2-fold) by 30 nM PB, but that evoked by muscarine (M) was not. In Ca-free and 1 mM EGTA Krebs solution, N and M did not evoke secretion, and PB also had no effect. If Ca concentration of the perfusion medium was maintained at 0.1 mM, N-evoked secretion was reduced over 80% but M-evoked secretion was still about 60% of the control value. Addition of PB to this medium did not modify secretion evoked by M, but N-evoked secretion was facilitated by 3-fold. Ca45 flux data showed that N-, C-, and K-evoked secretion of CA was associated with 2- to 3-fold increase in Ca45 uptake. However, M-evoked secretion did not cause Ca45 uptake. These results suggest that N utilizes extracellular whereas M utilizes mostly intracellular Ca ions for the secretion of CA. PB alone did not affect Ca45 uptake, but after stimulation with N, C and K, Ca45 uptake was further enhanced by PB. It is concluded that protein kinase C phosphorylates membrane proteins that control opening and closing of Ca channels regulated by nicotine receptors and changes in membrane potentials

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  8. Association between genetic polymorphisms in Ca(v2.3 (R-type Ca2+ channels and fentanyl sensitivity in patients undergoing painful cosmetic surgery.

    Directory of Open Access Journals (Sweden)

    Soichiro Ide

    Full Text Available Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca(2+ channels (VACCs play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Ca(v2.3 (R-type VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymorphisms (SNPs of the human CACNA1E (calcium channel, voltage-dependent, R type, alpha 1E subunit gene that encodes Cav2.3 VACCs influence the analgesic effects of opioids. Thus, the present study examined associations between fentanyl sensitivity and SNPs in the human CACNA1E gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. We first conducted linkage disequilibrium (LD analyses of 223 SNPs in a region that contains the CACNA1E gene using genomic samples from 100 patients, and a total of 13 LD blocks with 42 Tag SNPs were observed within and around the CACNA1E gene region. In the preliminary study using the same 100 genomic samples, only the rs3845446 A/G SNP was significantly associated with perioperative fentanyl use among these 42 Tag SNPs. In a confirmatory study using the other 255 genomic samples, this SNP was also significantly associated with perioperative fentanyl use. Thus, we further analyzed associations between genotypes of this SNP and all of the clinical data using a total of 355 samples. The rs3845446 A/G SNP was associated with intraoperative fentanyl use, 24 h postoperative fentanyl requirements, and perioperative fentanyl use. Subjects who carried the minor G allele required significantly less fentanyl for pain control compared with subjects who did not carry this allele. Although further validation is needed, the present findings show the possibility of the involvement of CACNA1E

  9. Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

    OpenAIRE

    Sepúlveda, Francisco V.; L Pablo Cid; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique...

  10. Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis

    Science.gov (United States)

    Romley, John A; Gong, Cynthia; Jena, Anupam B; Goldman, Dana P; Williams, Bradley

    2015-01-01

    Study question Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride? Methods This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465 918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4 355 418 person quarters); 71 895 (15.4%) patients also filled a prescription for warfarin (416 479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status. Summary answer and limitations In quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416 479 v 1903/3 938 939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416 479 v 20 759/3 938 939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416 479 v 14 414/3 938 939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and

  11. Influence of pH, light cycle, and temperature on ecotoxicity of four sulfonylurea herbicides towards Lemna gibba

    DEFF Research Database (Denmark)

    Rosenkrantz, Rikke Tjørnhøj; Cedergreen, Nina; Baun, Anders;

    2013-01-01

    In chemical regulation, e.g. the EU Water Framework Directive, REACH, or the Pesticide Directive, standardized ecotoxicological tests are applied to evaluate and rank the hazard of compounds and for deriving environmental quality standards (EQS). Standardized test methods prescribe fixed testing...... conditions e.g. specific temperature, pH, light intensity etc. However, environmental conditions under which the organisms live are rarely identical to the standard conditions. Thus, the ecotoxicity of compounds found in standard test is not only a function of the compounds inherent physico...... test conditions on the toxicity of four sulfonylurea herbicides (SUs). The toxicity of the four SUs towards Lemna gibba was investigated at three pH levels (6, 7.5 and 9), at two temperatures (15 and 24 °C) and two light regimes (continuous and 12:12 h light:dark cycle) The EC50 increased twofold to...

  12. Equal sensitivity of Cav1.2 and Cav1.3 channels to the opposing modulations of PKA and PKG in mouse chromaffin cells.

    Science.gov (United States)

    Mahapatra, Satyajit; Marcantoni, Andrea; Zuccotti, Annalisa; Carabelli, Valentina; Carbone, Emilio

    2012-10-15

    Mouse chromaffin cells (MCCs) express high densities of L-type Ca2+ channels (LTCCs), which control pacemaking activity and catecholamine secretion proportionally to their density of expression. In vivo phosphorylation of LTCCs by cAMP-PKA and cGMP–PKG, regulate LTCC gating in two opposing ways: the cAMP-PKA pathway potentiates while the cGMP–PKG cascade inhibits LTCCs. Despite this, no attempts have been made to answer three key questions related to the two Cav1 isoforms expressed in MCCs (Cav1.2 and Cav1.3): (i) how much are the two Cav1 channels basally modulated by PKA and PKG?, (ii) to what extent can Cav1.2 and Cav1.3 be further regulated by PKA or PKG activation?, and (iii) are the effects of both kinases cumulative when simultaneously active? Here, by comparing the size of L-type currents of wild-type (WT; Cav1.2+Cav1.3) and Cav1.3−/− KO (Cav1.2) MCCs, we provide new evidence that both PKA and PKG pathways affect Cav1.2 and Cav1.3 to the same extent either under basal conditions or induced stimulation. Inhibition of PKA by H89 (5 μM) reduced the L-type current in WT and KO MCCs by∼60%,while inhibition of PKG by KT 5823 (1 μM) increased by∼40% the same current in both cell types. Given that Cav1.2 and Cav1.3 carry the same quantity of Ca2+ currents, this suggests equal sensitivity of Cav1.2 and Cav1.3 to the two basal modulatory pathways. Maximal stimulation of cAMP–PKA by forskolin (100 μM) and activation of cGMP–PKG by pCPT-cGMP (1mM) uncovered a∼25% increase of L-type currents in the first case and∼65% inhibition in the second case in both WT and KO MCCs, suggesting equal sensitivity of Cav1.2 and Cav1.3 during maximal PKA or PKG stimulation. The effects of PKA and PKG were cumulative and most evident when one pathway was activated and the other was inhibited. The two extreme combinations(PKA activation–PKG inhibition vs. PKG activation-PKA inhibition) varied the size of L-type currents by one order of magnitude (from 180% to 18

  13. Dihydropyridine-sensitive calcium channel activity related to prolactin, growth hormone, and luteinizing hormone release from anterior pituitary cells in culture: interactions with somatostatin, dopamine, and estrogens

    International Nuclear Information System (INIS)

    In the present work, we determined the activity of voltage-dependent dihydropyridine (DHP)-sensitive Ca2+ channels related to PRL, GH, and LH secretion in primary cultures of pituitary cells from male or female rats. We investigated their modulation by 17 beta-estradiol (E2) and their involvement in dopamine (DA) and somatostatin (SRIF) inhibition of PRL and GH release. BAY-K-8644 (BAYK), a DHP agonist which increases the opening time of already activated channels, stimulated PRL and GH secretion in a dose-dependent manner. The effect was more pronounced on PRL than on GH release. BAYK-evoked hormone secretion was further amplified by simultaneous application of K+ (30 or 56 mM) to the cell cultures; in parallel, BAYK-induced 45Ca uptake by the cells was potentiated in the presence of depolarizing stimuli. In contrast, BAYK was unable to stimulate LH secretion from male pituitary cells, but it potentiated LHRH- as well as K+-induced LH release; it had only a weak effect on LH secretion from female cell cultures. Basal and BAYK-induced pituitary hormone release were blocked by the Ca2+ channel antagonist nitrendipine. Under no condition did BAYK affect the hydrolysis of phosphoinositides or cAMP formation. Pretreatment of female pituitary cell cultures with E2 (10(-9) M) for 72 h enhanced LH and PRL responses to BAYK, but was ineffective on GH secretion. DA (10(-7) M) inhibited basal and BAYK-induced PRL release from male or female pituitary cells treated or not treated with E2 (10(-9) M). SRIF (10(-9) and 10(-8) M) reversed BAYK-evoked GH release to the same extent in cell cultures derived from male or female animals. It was ineffective on BAYK-induced PRL secretion in the absence of E2, but antagonized it after E2 pretreatment. The effect was dependent upon the time of steroid treatment and was specific, since 17 alpha-estradiol was inactive

  14. Gastroprotective effects of thymol on acute and chronic ulcers in rats: The role of prostaglandins, ATP-sensitive K(+) channels, and gastric mucus secretion.

    Science.gov (United States)

    Ribeiro, Ana Roseli S; Diniz, Polyana B F; Pinheiro, Malone S; Albuquerque-Júnior, Ricardo L C; Thomazzi, Sara M

    2016-01-25

    Thymol, a monoterpene phenol derivative of cymene, is found in abundance in the essential oils of Thymus, Origanum, and Lippia species. The present study investigated the gastroprotective actions of thymol (10, 30, and 100 mg/kg, p.o.) in the acute (ethanol- and nonsteroidal anti-inflammatory drug-induced ulcers) and chronic (acetic acid-induced ulcers) ulcer models in rats. Some of the mechanisms underlying to the gastroprotective effect of thymol were investigated in the ethanol-induced ulcer model. Gastric secretion parameters (volume, pH, and total acidity) were also evaluated by the pylorus ligature model, and the mucus in the gastric content was determined. The anti-Helicobacter pylori activity of thymol was performed using the agar-well diffusion method. Thymol (10, 30, and 100 mg/kg) produced dose dependent reduction (P < 0.01) on the total lesion area in the ethanol-induced ulcer model. The gastroprotective response caused by thymol (30 mg/kg) was significantly attenuated (P < 0.001) by intraperitoneal treatment of rats with indomethacin (a non-selective inhibitor of cyclo-oxygenase, 10 mg/kg) and glibenclamide (ATP-sensitive K(+) channel blocker, 10 mg/kg), but not by DL-Propargylglycine (PAG, a cystathionine-γ-lyase inhibitor, 25 mg/kg) and Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME, a non-selective inhibitor of nitric oxide synthase, 70 mg/kg). Thymol (30 and 100 mg/kg) also reduced the ulcer index (P < 0.05) and the total lesion area (P < 0.001) in the indomethacin- and acetic-acid-induced ulcer models, respectively. In the model pylorus ligature, the treatment with thymol failed to significantly change the gastric secretion parameters. However, after treatment with thymol (30 and 100 mg/kg), there was a significant increase (P < 0.01) in mucus production. Thymol no showed anti-H. pylori activity in vitro. Collectively, the present results provide convincing evidence that thymol displays gastroprotective actions on the acute and chronic

  15. Sensitivity of Satellite-Based Skin Temperature to Different Surface Emissivity and NWP Reanalysis Sources Demonstrated Using a Single-Channel, Viewing-Angle-Corrected Retrieval Algorithm

    Science.gov (United States)

    Scarino, B. R.; Minnis, P.; Yost, C. R.; Chee, T.; Palikonda, R.

    2015-12-01

    Single-channel algorithms for satellite thermal-infrared- (TIR-) derived land and sea surface skin temperature (LST and SST) are advantageous in that they can be easily applied to a variety of satellite sensors. They can also accommodate decade-spanning instrument series, particularly for periods when split-window capabilities are not available. However, the benefit of one unified retrieval methodology for all sensors comes at the cost of critical sensitivity to surface emissivity (ɛs) and atmospheric transmittance estimation. It has been demonstrated that as little as 0.01 variance in ɛs can amount to more than a 0.5-K adjustment in retrieved LST values. Atmospheric transmittance requires calculations that employ vertical profiles of temperature and humidity from numerical weather prediction (NWP) models. Selection of a given NWP model can significantly affect LST and SST agreement relative to their respective validation sources. Thus, it is necessary to understand the accuracies of the retrievals for various NWP models to ensure the best LST/SST retrievals. The sensitivities of the single-channel retrievals to surface emittance and NWP profiles are investigated using NASA Langley historic land and ocean clear-sky skin temperature (Ts) values derived from high-resolution 11-μm TIR brightness temperature measured from geostationary satellites (GEOSat) and Advanced Very High Resolution Radiometers (AVHRR). It is shown that mean GEOSat-derived, anisotropy-corrected LST can vary by up to ±0.8 K depending on whether CERES or MODIS ɛs sources are used. Furthermore, the use of either NOAA Global Forecast System (GFS) or NASA Goddard Modern-Era Retrospective Analysis for Research and Applications (MERRA) for the radiative transfer model initial atmospheric state can account for more than 0.5-K variation in mean Ts. The results are compared to measurements from the Surface Radiation Budget Network (SURFRAD), an Atmospheric Radiation Measurement (ARM) Program ground

  16. Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide

    OpenAIRE

    Martin Javorský; Eva Babjaková; Lucia Klimčáková; Zbynek Schroner; Jozef Židzik; Mária Štolfová; Ján Šalagovič; Ivan Tkáč

    2013-01-01

    Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the ...

  17. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells.

    NARCIS (Netherlands)

    Thebault, S.C.; Lemonnier, L.; Bidaux, G.; Flourakis, M.; Bavencoffe, A.; Gordienko, D.; Roudbaraki, M.; Delcourt, P.; Panchin, Y.; Shuba, Y.; Skryma, R.; Prevarskaya, N.

    2005-01-01

    Recent cloning of a cold/menthol-sensitive TRPM8 channel (transient receptor potential melastatine family member 8) from rodent sensory neurons has provided the molecular basis for the cold sensation. Surprisingly, the human orthologue of rodent TRPM8 also appears to be strongly expressed in the pro

  18. Determination of four sulfonylurea herbicides in tea by matrix solid-phase dispersion cleanup followed by dispersive liquid-liquid microextraction.

    Science.gov (United States)

    Liang, Pei; Wang, Jinjin; Liu, Guojiao; Guan, Jinyan

    2014-09-01

    Matrix solid-phase dispersion combined with dispersive liquid-liquid microextraction has been developed as a new sample pretreatment method for the determination of four sulfonylurea herbicides (chlorsulfuron, bensulfuron-methyl, chlorimuron-ethyl, and pyrazosulfuron) in tea by high-performance liquid chromatography with diode array detection. The extraction and cleanup by matrix solid-phase dispersion was carried out by using CN-silica as dispersant and carbon nanotubes as cleanup sorbent eluted with acidified dichloromethane. The eluent of matrix solid-phase dispersion was evaporated and redissolved in 0.5 mL methanol, and used as the dispersive solvent of the following dispersive liquid-liquid microextraction procedure for further purification and enrichment of the target analytes before high-performance liquid chromatography analysis. Under the optimum conditions, the method yielded a linear calibration curve in the concentration range from 5.0 to 10 000 ng/g for target analytes with a correlation coefficients (r(2)) ranging from 0.9959 to 0.9998. The limits of detection for the analytes were in the range of 1.31-2.81 ng/g. Recoveries of the four sulfonylurea herbicides at two fortification levels were between 72.8 and 110.6% with relative standard deviations lower than 6.95%. The method was successfully applied to the analysis of four sulfonylurea herbicides in several tea samples. PMID:24956010

  19. Metsulfuron-methyl Molecularly Imprinted Stir Bar Sorptive Extraction Coupled with High Performance Liquid Chromatography for Trace Sulfonylurea Herbicides Analysis in Complex Samples

    Institute of Scientific and Technical Information of China (English)

    XU Zhi-gang; DU Zhuo; LIAN Hai-xian; HU Yu-ling; LI Gong-ke

    2012-01-01

    Metsulfuron-methyl molecularly imprinted polymer(MIP)-coated stir bar was prepared for sorptive extraction of sulfonylurea herbicides in complex samples.The MIP-coating was about 21.3 μm thickness with the relative standard deviation(RSD) of 4.4%(n=10).It was homogeneous and porous with good thermal stability and chemical stability.The extraction capability of the MIP-coating was 2.8 timcs over that of the non-imprinted polymer (NIP)-coating in hexane.The MIP-coating exhibited selective adsorption ability to the template and its analogues.The extraction conditions,including extraction solvent,desorption solvent,extraction time,desorption time and stirring speed,were optimized.A method for the determination of six sulfonylurea herbicides by MIP-coated stir bar sorptive extraction coupled with high performance liquid chromatography(HPLC) was developed.The linear range was 10-200 μg/L and the detection limits were within a range of 2.0-3.3 μg/L.It was also applied to the analysis of sulfonylurea herbicides in spiked river water,soil and rice samples.

  20. Di-photon cross section measurement and sensitivity study for Higgs search in the H → γγ channel with the ATLAS detector

    International Nuclear Information System (INIS)

    This work is done with the ATLAS collaboration. Three independent methods are proposed to measure the photon trigger efficiency. They are first evaluated using Monte Carlo simulation and then applied on 2010 data. The two photon-based methods show consistent results, with efficiency discrepancy at a few % level. For the method based on electron sample, the statistics is too low to draw conclusion. A detailed QCD di-photon cross-section measurement is performed on a data sample corresponding to a luminosity of (37.2 ± 1.2) pb-1, in which a 2D fit method is introduced to extract the signal yields. The differential distributions of the observables Mγγ, pTγγ and Δφγγ are derived and compared with the predictions from the DIPHOX and RESBOS generators. A good agreement is found for the Mγγ distribution, whereas discrepancies are observed in the pTγγ and Δφγγ distributions. In the study of the H → γγ channel based on a simulated sample, a deterioration of 4% in the exclusion limit is observed after incorporating the systematic uncertainty arising from the resolution of the di-photon invariant mass. In the real data analysis, the 2D fit method is also applied to decompose the backgrounds in the di-photon candidate invariant mass range [100, 150] GeV. The sensitivity of the Higgs boson search in the two photon final state is then reappraised. 3.2-4.2 times the standard model predicted cross-section in the 110-140 GeV mass range is expected to be excluded with 1 fb-1 of data at √(s)=7 TeV. (author)

  1. Inhibition of T-Type Voltage Sensitive Calcium Channel Reduces Load-Induced OA in Mice and Suppresses the Catabolic Effect of Bone Mechanical Stress on Chondrocytes.

    Directory of Open Access Journals (Sweden)

    Padma P Srinivasan

    Full Text Available Voltage-sensitive calcium channels (VSCC regulate cellular calcium influx, one of the earliest responses to mechanical stimulation in osteoblasts. Here, we postulate that T-type VSCCs play an essential role in bone mechanical response to load and participate in events leading to the pathology of load-induced OA. Repetitive mechanical insult was used to induce OA in Cav3.2 T-VSCC null and wild-type control mouse knees. Osteoblasts (MC3T3-E1 and chondrocytes were treated with a selective T-VSCC inhibitor and subjected to fluid shear stress to determine how blocking of T-VSCCs alters the expression profile of each cell type upon mechanical stimulation. Conditioned-media (CM obtained from static and sheared MC3T3-E1 was used to assess the effect of osteoblast-derived factors on the chondrocyte phenotype. T-VSCC null knees exhibited significantly lower focal articular cartilage damage than age-matched controls. In vitro inhibition of T-VSCC significantly reduced the expression of both early and late mechanoresponsive genes in osteoblasts but had no effect on gene expression in chondrocytes. Furthermore, treatment of chondrocytes with CM obtained from sheared osteoblasts induced expression of markers of hypertrophy in chondrocytes and this was nearly abolished when osteoblasts were pre-treated with the T-VSCC-specific inhibitor. These results indicate that T-VSCC plays a role in signaling events associated with induction of OA and is essential to the release of osteoblast-derived factors that promote an early OA phenotype in chondrocytes. Further, these findings suggest that local inhibition of T-VSCC may serve as a therapy for blocking load-induced bone formation that results in cartilage degeneration.

  2. Protective effects of iptakalim, a novel ATP-sensitive potassium channel opener, on global cerebral ischemia-evoked insult in gerbils

    Institute of Scientific and Technical Information of China (English)

    Hua CHEN; Yong YANG; Hong-hong YAO; Xing-chun TANG; Jian-hua DING; Hai WANG; Gang HU

    2006-01-01

    Aim: To investigate the protective role of iptakalim, a novel ATP sensitive potassium channel opener, on global cerebral ischemia-evoked insult in gerbils and glutamate-induced PC 12 cell injury. Methods: Global cerebral ischemia was induced by occluding the bilateral common carotid arteries in gerbils for 5 min. The open field maze and T-maze were employed to investigate the experimental therapeutic value of iptakalim on ischemic brain insult (n=8). The pyramidal cells in the hippocampal CA1 regions were counted to assess the protective effects of iptakalim. Glutamate released from the gerbil hippocampus and PC 12 cells were determined by HPLC. Intracellular calcium was measured by Fluo-3 AM with A Bio-Rad Radiance 2100TM confocal system in conjunction with a Nikon TE300 microscope. Astrocyte glutamate uptake measurements were determined by liquid scintillation counting. Results: Iptakalim (0.5-4.0 mg/kg per day, ip) could reduce the high locomotor activity evoked by ischemia and improve global cerebral ischemia-induced working memory impairments. Histological studies revealed that iptakalim could increase the survival neuron in the hippocampus CA1 zone in a dose-dependent manner. Moreover, iptakalim could reverse ischemia-evoked increases of glutamate in the hippocampus of gerbils. In an in vitro study, iptakalim protected PC 12 cells against glutamate-induced excitotoxicity, reduced the [Ca2+]; increases, and enhanced the glutamate uptake activity of primary cultured astrocytes. Conclusions: Iptakalim plays a key role in preventing global cerebral ischemia-evoked insults in gerbils and glutamate-induced PC12 cell injury by anti-excitotoxicity. Iptakalim might be a promising novel candidate for the prevention and/or treatment of stroke.

  3. Effect of antihistaminic agents on the ATP-sensitive potassium channel activity in isolated mouse ventricular cardiomyocytes%组胺拮抗剂对小鼠ATP-敏感性钾离子通道的影响

    Institute of Scientific and Technical Information of China (English)

    朴伶华; 姜圣男; 柳贤德

    2013-01-01

    Objective The purpose of this study was to clarify the effect of the first generation histamine H1 receptor antagonists on adenosine triphosphate-sensitive potassium (KATP) channel in isolated mouse ventricular cardiomyocytes using excised inside-out and cell-attached patch clamp techniques. Methods Mouse heart ventricular cardiomyocytes were isolated, and excised inside-out and cell-attached patch clamp techniques were used to determine the effect of the antihistamines on the KATP channel activity. Results In the excised inside-out patch configuration, H1-antihistaminic agents (chlorpheniramine, pyrilamine and diphenhydramine), in a dose ranging from 1 to 100 μmol/L, inhibited KATP channel activity in a dose-dependent manner. The potency order reducing the channel activity was pyrilamine>diphenhydramine>chlorpheniramine. All the three antihistamines (100 μmol/L) also inhibited pinacidil-induced KATP channel activity in the cell-attached patch configuration. The potency order of the three antihistamines inhibiting KATP channel activity was pyrilamine>chlorpheniramine>diphenhydramine in the cell-attached configurations. Histamine did not affect the pinacidil-induced KATP channel activity by itself, in addition, did not influence the effects elicited by the three antihistamines on pinacidil-induced KATP channel activity in the cell-attached patches. Conclusions It is concluded that the first generation histamine H1 receptor antagonists are involved in the regulation of ATP-sensitive potassium channel activity in the mouse cardiac ventricular myocytes, and that the inhibitory action of the antihistaminic agents on the channel is not dependent on H1-receptors.%目的 观察比较3种组胺拮抗剂对缺血性心肌细胞的ATP-敏感性钾离子通道中的影响.方法 利用急性酶解法分离小鼠心室肌细胞.结果 组胺拮抗剂pyrilamine、chlorpheniramine及diphenhydramine均可抑制ATP-敏感性钾离子通道的活性,抑制程度为pyrilamine

  4. Quantitative Evaluation of Compliance with Recommendation for Sulfonylurea Dose Co-Administered with DPP-4 Inhibitors in Japan

    Directory of Open Access Journals (Sweden)

    Motonobu Sakaguchi

    2012-09-01

    Full Text Available After the launch of dipeptidyl peptidase-4 (DPP-4, a new oral hypoglycemic drug (OHD, in December 2009, severe hypoglycemia cases were reported in Japan. Although the definite cause was unknown, co-administration with sulfonylureas (SU was suspected as one of the potential risk factors. The Japan Association for Diabetes Education and Care (JADEC released a recommendation in April 2010 to lower the dose of three major SUs (glimepiride, glibenclamide, and gliclazide when adding a DPP-4 inhibitor. To evaluate the effectiveness of this risk minimization action along with labeling changes, dispensing records for 114,263 patients prescribed OHDs between December 2008 and December 2010 were identified in the Nihon-Chouzai pharmacy claims database. The adherence to the recommended dosing of SU co-prescribed with DPP-4 inhibitors increased from 46.3% before to 63.8% after the JADEC recommendation (p < 0.01 by time-series analysis, while no change was found in those for SU monotherapy and SU with other OHD co-prescriptions. The adherence was significantly worse for those receiving a glibenclamide prescription. The JADEC recommendation, along with labeling changes, appeared to have a favorable effect on the risk minimization action in Japan. In these instances, a pharmacy claims database can be a useful tool to evaluate risk minimization actions.

  5. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement.

    Science.gov (United States)

    Kalra, Sanjay; Aamir, A H; Raza, Abbas; Das, A K; Azad Khan, A K; Shrestha, Dina; Qureshi, Md Faisal; Md Fariduddin; Pathan, Md Faruque; Jawad, Fatema; Bhattarai, Jyoti; Tandon, Nikhil; Somasundaram, Noel; Katulanda, Prasad; Sahay, Rakesh; Dhungel, Sanjib; Bajaj, Sarita; Chowdhury, Subhankar; Ghosh, Sujoy; Madhu, S V; Ahmed, Tofail; Bulughapitiya, Uditha

    2015-01-01

    Since their introduction in clinical practice in the 1950's, Sulfonylureas (SUs) have remained the main-stay of pharmacotherapy in the management of type 2 diabetes. Despite their well-established benefits, their place in therapy is inappropriately being overshadowed by newer therapies. Many of the clinical issues associated with the use of SUs are agent-specific, and do not pertain to the class as such. Modern SUs (glimepiride, gliclazide MR) are backed by a large body of evidence, experience, and most importantly, outcome data, which supports their role in managing patients with diabetes. Person-centred care, i.e., careful choice of SU, appropriate dosage, timing of administration, and adequate patient counseling, will ensure that deserving patients are not deprived of the advantages of this well-established class of anti-diabetic agents. Considering their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs should be considered as recommended therapy for the treatment of diabetes in South Asia. This initiative by SAFES aims to encourage rational, safe and smart prescription of SUs, and includes appropriate medication counseling. PMID:26425465

  6. TIVMETIX OD – A Sulfonylurea-based Herbicide with improved efficacy through novel oil dispersion (OD formulation technology

    Directory of Open Access Journals (Sweden)

    Gimeno, Barbara

    2016-02-01

    Full Text Available TIVMETIX OD is a novel oil dispersion (OD post-emergence herbicide for the spring application (BBCH 13-39 against broad-leafed weeds in all varieties of winter and spring wheat, winter and spring barley, winter rye and triticale. With the new GAT-developed and patented OD technology the sulfonylureas thifensulfuron-methyl (190 g/L and metsulfuron-methyl (19 g/L could be combined in a liquid OD formulation. This guarantees a high level of safety and increased user friendliness and simplified dosing. Dust formation is avoided and problems of electrostatic charging of granulates and powders, or the transportation by wind do not occur. In TIVMETIX OD, the enhancing ingredients as oil, agents and adjuvants constitute part of its formulation. Excellent film forming properties on the leaf surface of the weeds result in their direct and enhanced interaction, thus leading to increased uptake of the active substances. Therefore, the amount of active substance per hectare could be reduced by up to 36 % while efficacy is maintained at a level which is at least equivalent to reference products. Furthermore, TIVMETIX OD can be used in mixture or sequence with a variety of other herbicides and does not show an effect on succeeding crops.

  7. Exploitation of sulfonylurea resistance marker and non-homologous end joining mutants for functional analysis in Zymoseptoria tritici.

    Science.gov (United States)

    Sidhu, Y S; Cairns, T C; Chaudhari, Y K; Usher, J; Talbot, N J; Studholme, D J; Csukai, M; Haynes, K

    2015-06-01

    The lack of techniques for rapid assembly of gene deletion vectors, paucity of selectable marker genes available for genetic manipulation and low frequency of homologous recombination are major constraints in construction of gene deletion mutants in Zymoseptoria tritici. To address these issues, we have constructed ternary vectors for Agrobacterium tumefaciens mediated transformation of Z. tritici, which enable the single step assembly of multiple fragments via yeast recombinational cloning. The sulfonylurea resistance gene, which is a mutated allele of the Magnaporthe oryzae ILV2 gene, was established as a new dominant selectable marker for Z. tritici. To increase the frequency of homologous recombination, we have constructed Z. tritici strains deficient in the non-homologous end joining pathway of DNA double stranded break repair by inactivating the KU70 and KU80 genes. Targeted gene deletion frequency increased to more than 85% in both Z. tritici ku70 and ku80 null strains, compared to ⩽10% seen in the wild type parental strain IPO323. The in vitro growth and in planta pathogenicity of the Z. tritici ku70 and ku80 null strains were comparable to strain IPO323. Together these molecular tools add significantly to the platform available for genomic analysis through targeted gene deletion or promoter replacements and will facilitate large-scale functional characterization projects in Z. tritici. PMID:26092796

  8. A Sulfonylurea Herbicide Resistance Gene from Arabidopsis thaliana as a New Selectable Marker for Production of Fertile Transgenic Rice Plants.

    Science.gov (United States)

    Li, Z; Hayashimoto, A; Murai, N

    1992-10-01

    A mutant acetolactate synthase (ALS) gene, csr1-1, isolated from sulfonylurea herbicide-resistant Arabidopsis thaliana, was placed under control of a cauliflower mosaic virus 35S promoter (35S). Rice protoplasts were transformed with the 35S/ALS chimeric gene and regenerated into fertile transgenic rice (Oryza sativa) plants. The 35S/ALS gene was expressed effectively as demonstrated by northern blot hybridization analysis, and conferred to transformed calli at least 200-fold greater chlorsulfuron resistance than nontransformed control calli. Effective selection of 35S/ALS-transformed protoplasts was achieved at extremely low chlorsulfuron concentrations of 10 nm. The results demonstrated that the 35S/ALS gene is an alternative selectable marker for rice protoplast transformation and fertile transgenic rice production. The results also suggest that the mutant form of Arabidopsis ALS enzyme operates normally in rice cells. Thus, the mechanism of protein transport to chloroplast and ALS inhibition by chlorsulfuron is apparently conserved among plant species as diverse as Arabidopsis (dicotyledon) and rice (monocotyledon). PMID:16653044

  9. Separation and concentration of sulfonylurea herbicides in milk by ionic-liquid-based foam flotation solid-phase extraction.

    Science.gov (United States)

    Zhang, Liyuan; Cao, Bocheng; Yao, Di; Yu, Runzhong; Yu, Changqing; Zhang, Hanqi; Yu, Aimin

    2015-05-01

    The ultrasound-assisted ionic liquid foam flotation solid-phase extraction of sulfonylurea herbicides in milk was developed and validated. The proteins and lipids were isolated from the sample matrix by adding salt and adjusting the pH value. The target analytes eluted from the solid-phase extraction cartridge were determined by high-performance liquid chromatography. Some experimental parameters, including the pH value of sample solution, amount of NaCl, ionic liquid type, extraction time, flow rate of carrier gas, flotation time, and solid-phase extraction cartridge type were investigated and optimized. Under the optimized experimental conditions, the limits of detection for metsulfuron, pyrazosulfuron, chlorimuron-ethyl, and nicosulfuron were 1.3, 0.6, 0.7, and 1.1 μg/L, respectively. When the present method was applied to the analysis of milk samples the recoveries of the analytes ranged from 84.3 to 105.2% and relative standard deviations were >5.7%. PMID:25727190

  10. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Since their introduction in clinical practice in the 1950′s, Sulfonylureas (SUs have remained the main-stay of pharmacotherapy in the management of type 2 diabetes. Despite their well-established benefits, their place in therapy is inappropriately being overshadowed by newer therapies. Many of the clinical issues associated with the use of SUs are agent-specific, and do not pertain to the class as such. Modern SUs (glimepiride, gliclazide MR are backed by a large body of evidence, experience, and most importantly, outcome data, which supports their role in managing patients with diabetes. Person-centred care, i.e., careful choice of SU, appropriate dosage, timing of administration, and adequate patient counseling, will ensure that deserving patients are not deprived of the advantages of this well-established class of anti-diabetic agents. Considering their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs should be considered as recommended therapy for the treatment of diabetes in South Asia. This initiative by SAFES aims to encourage rational, safe and smart prescription of SUs, and includes appropriate medication counseling.

  11. Down Regulated Expression of the β1 Subunit of the Big-conductance Ca2+ Sensitive K+ Channel in Sphincter of Oddi Cells from Rabbits Fed with a High Cholesterol Diet

    Institute of Scientific and Technical Information of China (English)

    Pang DU; Guang-Bin CUI; Ya-Rong WANG; Xiao-Yong ZHANG; Ke-Jun MA; Jing-Guo WEI

    2006-01-01

    Hypercholesterolemia, which is closely related to gallbladder bile stasis, can cause sphincter of Oddi dysfunction (SOD) by increasing the tension of sphincter of Oddi (SO). Intracellular calcium ion concentration ([Ca2+]i) could influence the tension of SO. The β1 subunit of the big-conductance Ca2+sensitive K+ channel (BKCa) can enhance the sensitivity of the BKCa channel to [Ca2+]i. Absence and decline of the BKCa channel subunit β1 could lead to many diseases. However, the relationship between hypercholesterolemia and the expression of β1 subunit is not well understood. In this study, we successfully expressed and purified the rabbit BKCa β1 subunit protein and prepared its polyclonal antibody. The specificity of the prepared antibody was determined by western blotting. A SOD rabbit model induced by a high cholesterol diet was established and the expression of the β1 subunit of SO was determined by immunohistochemical staining and western blotting. Compared with the controls, our results demonstrated that hypercholesterolemia could decrease the expression of the β1 subunit in the SO cells from rabbits. This indicates that lower expression of BKCa channel β1 subunit might induce SOD.

  12. 运动与ATP-敏感型钾离子通道%Exercise and adenosine triphosphate-sensitive potassium channel

    Institute of Scientific and Technical Information of China (English)

    张如江; 宋永晶

    2014-01-01

    背景:在运动生理状态下,KATP 在调节冠状动脉张力、运动诱导心肌保护效应和延缓骨骼肌疲劳等多个方面具有重要作用。目的:对KATP在运动中的作用进行了综述和探讨,以期为深入了解运动调节机体代谢提供理论参考。方法:检索1991年1月至2014年6月 PubMed数据库及维普中文科技数据库文献。英文检索词为“KATP Channels;Adenosine Triphosphate;Sports;Myocardium;Ion Channels”,中文检索词为“KATP通道;三磷酸腺苷;运动;心肌;离子通道”。选择与KATP分子结构、生物学功能及调控相关,以及KATP与冠状动脉、心肌、骨骼肌疲劳及运动能力相关的文献42篇文献进行探讨。结果与结论:ATP敏感性钾离子通道可以偶联细胞内能量代谢和细胞膜兴奋性,在应对各种生理和病理应激时是保护心肌的效应器之一。长期的耐力训练则会增加骨骼肌和心肌KATP的表达,可能是心肌和骨骼肌对运动应激产生的一种适应性表现。KATP 可能参与冠状动脉血流量的调节。在运动诱导的减轻心肌缺血再灌注损伤的保护效应中,心肌KATP具有重要作用。当骨骼肌疲劳发生时,KATP的激活有利于防止ATP的过度消耗而造成肌纤维损伤和细胞死亡,有利于疲劳的快速恢复。关于KATP与运动能力的关系仍需进一步的研究。%BACKGROUND:In the condition of exercise physiology, adenosine triphosphate-sensitive potassium (KATP) channel plays an important role in many aspects, such as regulation of coronary artery tension, exercise-induced myocardial protection effect and delay of skeletal muscle fatigue. OBJECTIVE:To review and investigate the role of KATP in exercise in order to provide theoretical reference for understanding mechanism underlying exercise regulation of body’s metabolism. METHODS: A computer-based online search of PubMed and VIP databases was performed for articles

  13. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

    DEFF Research Database (Denmark)

    Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter;

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1......, patients uncontrolled on sulfonylurea monotherapy were divided into two HbA(1c) (A1C) arms: > or =8 to < or =9.5% (moderately high) and >9.5 to < or =12% (very high). Patients were randomized to adjunctive premeal INH (n = 225) or metformin (n = 202). The primary efficacy end point was change in A1C from...... patients with type 2 diabetes poorly controlled on a sulfonylurea (A1C >9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated....

  14. Contamination of rice field water with sulfonylurea and phenoxy herbicides in the Muda Irrigation Scheme, Kedah, Malaysia.

    Science.gov (United States)

    Ismail, B S; Prayitno, S; Tayeb, M A

    2015-07-01

    The purpose of the present study was to investigate the potential risk of herbicide contamination (2,4-dichlorophenoxy (2,4-D), 2-methyl-4-chlorophenoxyacetic acid (MCPA), metsulfuron, bensulfuron, and pyrazosulfuron) in the rice fields of the Muda Irrigation Scheme, Kedah, Malaysia. The study included two areas with different irrigation water sources namely non-recycled (N-RCL) and recycled (RCL) water. Periodic water sampling was carried out from the drainage canals during the planting period of the wet season 2006/2007 and dry season 2007. The HPLC-UV was used to detect herbicide residues in the water samples collected from the rice fields. The results showed that the concentration of sulfonylurea herbicides such as bensulfuron and metsulfuron in the rice field was 0.55 and 0.51 μg/L, respectively. The potential risk of contamination depended on the actual dosage of each herbicide applied by farmers to their rice fields. The potential risk of water pollution by the five herbicides studied in the area with RCL water tended to be more widespread compared to the area with N-RCL water due to surface water runoff with higher levels of weedicides to the surrounding areas. During the two seasons, 50-73% of the water samples collected from the area receiving RCL water contained the five herbicides studied at concentrations of more than 0.05 μg/L, and this percentage was higher than that from the areas receiving N-RCL water (45-69%). During the wet season, the overall total mean concentration of the eight herbicides found in the samples collected from the area with RCL water (6.27 μg/L) was significantly higher (P  0.05) in the herbicide concentrations between the areas receiving RCL (6.16 μg/L) and N-RCL water (7.43 μg/L) water. PMID:26045037

  15. Sulfonylurea herbicides in an agricultural catchment basin and its adjacent wetland in the St. Lawrence River basin.

    Science.gov (United States)

    de Lafontaine, Yves; Beauvais, Conrad; Cessna, Allan J; Gagnon, Pierre; Hudon, Christiane; Poissant, Laurier

    2014-05-01

    The use of sulfonylurea herbicides (SU) has increased greater than 100 times over the past 30 years in both Europe and North America. Applied at low rates, their presence, persistence and potential impacts on aquatic ecosystems remain poorly studied. During late-spring to early fall in 2009-2011, concentrations of 9 SU were assessed in two agricultural streams and their receiving wetland, an enlargement of the St. Lawrence River (Canada). Six SU in concentrations >LOQ (10 ng L(-1)) were detected in 10% or less of surface water samples. Rimsulfuron was detected each year, sulfosulfuron and nicosulfuron in two years and the others in one year only, suggesting that application of specific herbicides varied locally between years. Detection frequency and concentrations of SU were not significantly associated with total precipitation which occurred 1 to 5d before sampling. Concentrations and fate of SU differed among sites due to differences in stream dynamics and water quality characteristics. The persistence of SU in catchment basin streams reflected the dissipation effects associated with stream discharge. Maximum concentrations of some SU (223 and 148 ng L(-1)) were occasionally above the baseline level (100 ng L(-1)) for aquatic plant toxicity, implying potential toxic stress to flora in the streams. Substantially lower concentrations (max 55 ng L(-1)) of SU were noted at the downstream wetland site, likely as a result from dilution and mixing with St. Lawrence River water, and represent less toxicological risk to the wetland flora. Sporadic occurrence of SU at low concentrations in air and rain samples indicated that atmospheric deposition was not an important source of herbicides to the study area. PMID:24534695

  16. Nomenclature for Ion channel Subunits

    OpenAIRE

    Bradley, Jonathan; Frings, Stephan; Yau, King-Wai; Reed, Randall

    2001-01-01

    Presents the nomenclature for ion channel subunits. Role of ion channels in the mediation of visual and olfactory signal transduction; Expression of ion channels in cell types and tissues; Assessment on the nucleotide sensitivity, ion conductance and calcium modulation in heteromers.

  17. Micro-channel plate detector

    Energy Technology Data Exchange (ETDEWEB)

    Elam, Jeffrey W.; Lee, Seon W.; Wang, Hsien -Hau; Pellin, Michael J.; Byrum, Karen; Frisch, Henry J.

    2015-09-22

    A method and system for providing a micro-channel plate detector. An anodized aluminum oxide membrane is provided and includes a plurality of nanopores which have an Al coating and a thin layer of an emissive oxide material responsive to incident radiation, thereby providing a plurality of radiation sensitive channels for the micro-channel plate detector.

  18. ATP敏感钾通道调节血管张力的分子机制%KATP channel action in vascular tone regulation: from genetics to diseases

    Institute of Scientific and Technical Information of China (English)

    施巍巍; 杨洋; 石云; 姜淳

    2012-01-01

    ATP敏感钾通道(ATP-sensitive potassium channel,KATP通道)广泛分布在血管系统,并在血管张力调节中发挥重要作用.KATp通道由4个孔道形成的内向整流钾离子通道(inward rectifier K+ channels,Kir)亚基和4个磺脲受体调节亚基(sulfonylurea receptor,SUR)组成.尽管其它一些亚基在血管中也存在,Kir6.1/SUR2B是主要的血管亚型KATP通道.KATP通道转基因小鼠的研究以及人群中KATP通道基因突变的发现,都强烈支持KATP通道对于心血管系统的动态平衡调控是不可缺少的.大量的血管活性物质通过调节KATP通道活性来改变血管平滑肌细胞的膜电位,从而调节血管张力.多数内源性血管收缩物质,例如血管加压素,激活蛋白激酶C (protein kinase C,PKC),磷酸化KAP通道并抑制其活性;而血管扩张物质,如血管活性肠肽,通过增加cAMP的形成和提高蛋白激酶A(protein kinase A,PKA)的活性来增加KATP通道的活性.PKC作用于Kir6.1亚基C-末端,磷酸化4个保守的丝氨酸,而PKA磷酸化SUR2B亚基第2核苷酸结合域的Ser1387位点.血管KATP通道也受活性氧的调节,其中Kir6.1的Cys176是一个重要的过氧化物调节位点.此外,KATP通道功能可被一些慢性的病理生理条件上调,如感染性休克.核因子-κB依赖的基因转录是脂多糖诱导的血管KATP通道激活的一个机制.本综述将概括性描述血管KATP通道在生理和病理情况下受到的调节,以期阐明血管KATP通道在治疗和预防心血管疾病方面可能是一个有用的靶点.%ATP-sensitive potassium (KATP) channels are widely distributed in vasculatures,and play an important role in the vascular tone regulation.The KATP channels consist of 4 pore-forming inward rectifier K+ channel (Kir) subunits and 4 regulatory sulfonylurea receptors (SUR).The major vascular isoform of KATP channels is composed of Kir6.1/SUR2B,although low levels of other subunits are also present in vascular beds

  19. Gender-specific Effects of Treatment with Lifestyle, Metformin or Sulfonylurea on Glycemic Control and Body Weight: A German Multicenter Analysis on 9 108 Patients.

    Science.gov (United States)

    Schütt, M; Zimmermann, A; Hood, R; Hummel, M; Seufert, J; Siegel, E; Tytko, A; Holl, R W

    2015-11-01

    Effects of diabetes treatment are strongly connected to individual factors, but the relevant role of gender has not been addressed so far. This observational study evaluates whether monotherapy with lifestyle, metformin or sulfonylurea has gender-specific effects on glycemic control and/or body weight. Data of 9 108 patients with type 2 diabetes from 129 German diabetes centers were assessed by a standardized, prospective, computer-based diabetes care and outcome documentation system (DPV-Wiss-database; age 63.1±12.8 years, diabetes duration 5.7±7.4 years, HbA1c 55±17.7 mmol/mol [7.2±1.6%], BMI 30.6±6.1 kg/m(2), 49.3% female patients). Antidiabetic concepts included lifestyle intervention (n=5,787), metformin (n=2,180), sulfonylurea (n=943) or other antidiabetic drugs (n=198), respectively. HbA1c and body weight were compared before and after a stable monotherapeutical period of 0.8±0.4 years. Women had a significantly higher reduction of body weight after treatment with lifestyle (women-0.8±0.1 vs. men-0.2±0.1 kg; pdiabetes. PMID:26285070

  20. Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

    Directory of Open Access Journals (Sweden)

    Chazan A.C.S.

    2001-01-01

    Full Text Available To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 ± 8.3 years, with a duration of diabetes of 10.6 ± 6.6 years, fasting plasma glucose of 277.3 ± 64.6 mg/dl and a body mass index of 27.4 ± 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1, 320 mg gliclazide and bedtime NPH insulin (phase 2, and insulin (phase 3. At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01. Twelve patients (48% reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8 vs 66.7 kg (42.8-101.4 (P<0.05, with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose score (C-peptide/glucose x 100 increased from 0.9 (0.2-2.1 to 1.3 (0.2-4.7 during combined therapy (P<0.01. Despite a 50% increase in insulin doses in phase 3 (12 U (9-30 vs 18 U (11-60; P<0.01 only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02. A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5 vs 0.6 (0-2.15; P = 0.08 and C-peptide incremental area (2.47 (0.22-6.2 vs 1.2 (0-3.35; P = 0.07 was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response.

  1. Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with 99mTc-DTPA-glipizide

    International Nuclear Information System (INIS)

    This study was aimed to assess pancreas beta cell activity using 99mTc-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated. DTPA dianhydride was conjugated with GLP in the presence of sodium amide, yielding 60%. Biodistribution and planar images were obtained at 30-120 min after injection of 99mTc-DTPA-GLP (1 mg/rat, 0.74 and 11.1 MBq per rat, respectively) in normal female Fischer 344 rats. The control group was given 99mTc-DTPA. To demonstrate pancreas beta cell uptake of 99mTc-DTPA-GLP via a receptor-mediated process, a group of rats was pretreated with streptozotocin (a beta cell toxin, 55 mg/kg, intravenous (i.v.)) and the images were acquired at immediately-65 min on day 5 post-treatment. The effect on the glucose levels after a single administration (ip) of DTPA-GLP was compared to glipizide (GLP) for up to 6 h. The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was >96%. 99mTc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas 99mTc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with 99mTc-DTPA-GLP in normal rat, however, 99mTc-DTPA has poor uptake suggesting the specificity of 99mTc-DTPA-GLP. Pancreas beta cell uptake could be blocked by pre-treatment with streptozotocin. DTPA-GLP showed an equal or better response in lowering the glucose levels compared to the existing GLP drug. It is feasible to use 99mTc-DTPA-GLP to assess pancreas beta cell receptor recognition. 99mTc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors. (author)

  2. Regulación por proteasas del canal de sodio sensible al amiloride (ENaC Amiloride sensitive sodium channels (ENaC and their regulation by proteases

    Directory of Open Access Journals (Sweden)

    Luciano Galizia

    2011-04-01

    Full Text Available El ENaC es un canal que permite el movimiento de Na+ desde el líquido luminal hacia las células en numerosos epitelios reabsortivos y también en otros tejidos como la placenta. ENaC juega un papel crucial en la homeostasis de los electrolitos y volumen de líquido extracelular. Es regulado por numerosas hormonas, incluyendo la aldosterona y bloqueado por el diurético amiloride. El ENaC está formado por tres subunidades homólogas α, β y γ que forman el poro por el cual se mueven los iones Na+. Dos factores regulan la actividad del ENaC. 1 el número de canales insertos en la membrana celular y 2 la probabilidad de apertura o tiempo en que se encuentra abierto el canal. El número de canales es el resultado de un balance entre su síntesis y degradación. La probabilidad de apertura depende de la proteólisis de zonas específicas de las subunidades α y γ por múltiples proteasas dentro de la célula y en el espacio extracelular. Entre las proteasas más estudiadas se encuentran la furina, prostasina, elastasa, plasmina y tripsina. Existen sustancias endógenas que bloquean la actividad de estas proteasas como la aprotinina, la bikunina y la nexina-1 y la expresión de las proteasas y sus inhibidores es regulada a su vez por la aldosterona, la tasa de movimiento de Na y el TFGβ. En este trabajo presentamos algunos ejemplos de esta regulación y su potencial papel en condiciones normales y en ciertas enfermedades como la fibrosis quística, renales e hipertensión.ENaC is a channel that mediates entry of Na+ from the luminal fluid into the cells in many reabsorbing epithelia and it is also expressed in human placenta. ENaC is crucial in the control of electrolyte and extracellular volume homeostasis. ENaC is regulated by several hormones, including aldosterone and blocked by amiloride and its analogs. ENaC channels are composed by three homologous subunits, α, β and γ that form the pore where Na ions are transported. Two factors

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    -frequency waves may transform into high-frequency whole-cell calcium oscillations. Simultaneously, multiple cells synchronize leading to rhythmic generation of tension. We present a mathematical model of vascular smooth muscle cells that aims at characterizing this sudden transition. Simulations show calcium...... onset of oscillations in membrane potential within the individual cell may underlie sudden intercellular synchronization and the appearance of vasomotion. Key words: Vasomotion, Chloride channel, cGMP, Mathematical model, Calcium waves....

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

    Directory of Open Access Journals (Sweden)

    Norbert Babai

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

  5. RFI channels

    Science.gov (United States)

    Mceliece, R. J.

    1980-01-01

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

  6. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

    DEFF Research Database (Denmark)

    Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter;

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1...

  7. 磺脲类药物用于2型糖尿病患者的心血管安全性评价%Evaluation on Cardiovascular Safety of Sulfonylureas for Type 2 Diabetes Treatment

    Institute of Scientific and Technical Information of China (English)

    张舫; 童南伟

    2016-01-01

    磺脲类(sulfonylureas,SUs)药物治疗2型糖尿病已有逾50年历史。自1970年University Group Diabetes Program试验发表以来,有关SUs的心血管安全性一直备受争议。尽管存在一些SUs致心血管不良反应的假说,但无一可提供可靠的证据。目前,某些观察性研究提示,SUs与心血管事件发生风险增加有关,但随机对照试验却得出了相悖结论。在评价SUs心血管安全性时,需根据具体药物、使用剂量和疗程、患者的年龄、体质指数等因素综合考虑。迄今,尚缺乏旨在探索SUs心血管结局的头对头研究数据,但正在进行的大型临床试验有望阐明SUs和心血管疾病的发生是否存在因果关系。%Sulfonylureas have been used for type 2 diabetes treatment over 50 years. Since publication of the University Group Diabetes Program in 1970, the cardiovascular safety of sulfonylureas has been contentious. Although several hypotheses linking sulfonylurea to detrimental cardiovascular events exist, none provide conclusive evidence. Presently, several observational studies suggest that sulfonylureas are associated with increased adverse cardiovascular outcome; however, randomized controlled trials have demonstrated a neutral effect. Evaluating cardiovascular safety of sulfonylureas should be based on comprehensive consideration, such as differential drugs, doses, durations, age of patient, body mass index. To date, there is lack of head-to-head study, which is focused on cardiovascular outcome of sulfonylureas. Fortunately, the current ongoing large clinical trials may clarify the cardiovascular safety of sulfonylureas.

  8. Tuberização de dois cultivares de batata sob aplicação de sulfoniluréias Effect of sulfonylurea herbicides on tuberization of two potato cultivars

    Directory of Open Access Journals (Sweden)

    M.C.S.S. Novo

    2006-01-01

    recommended rate. At harvest, root fresh weight, number and fresh weight of normal and malformed tubers and total yield of tubers were determined. None of the rates applied killed the potato plants.Sulfonylurea application affected tuber development causing anomalies but these also varied with products and rates. 'Atlantic' yield losses were greater than 'Lady Rosetta's yield losses when metsulfuron-methyl was applied. 'Lady Rosetta' tuber yield was more sensitive than that of'Atlantic to nicosulfuron and sulfometuron-methyl.

  9. Channeling in quasicrystals

    Energy Technology Data Exchange (ETDEWEB)

    Du Marchie van Voorthuysen, E.H.; Smulders, P.J.M. (Vakgroep Nucleaire Vaste Stof Fysica, Univ. of Groningen (Netherlands)); Werkman, R.D. (Vakgroep Vaste Stof Fysica, Univ. of Groningen (Netherlands)); Boer, J.L. de; Smaalen, S. van (Lab. of Inorganic Chemistry, Univ. of Groningen (Netherlands))

    1992-02-01

    Ion-beam channeling has been observed in quasicrystals. For 1 MeV {sup 4}He{sup +} ions in icosahedral AlCuFe the maximum effect found is 36%. The full width at half maximum of the observed dips is 1.3deg. The effect persists up to great depths (>200 nm), thus showing a high degree of ordering in this phase. The channeling effect is sensitive to radiation damage. (orig.).

  10. Channeling in quasicrystals

    International Nuclear Information System (INIS)

    Ion-beam channeling has been observed in quasicrystals. For 1 MeV 4He+ ions in icosahedral AlCuFe the maximum effect found is 36%. The full width at half maximum of the observed dips is 1.3deg. The effect persists up to great depths (>200 nm), thus showing a high degree of ordering in this phase. The channeling effect is sensitive to radiation damage. (orig.)

  11. Effect of coriaria lactone on adenosine triphosphate-sensitive potassium channels in pyramidal neurons%马桑内酯对锥体神经元三磷酸腺苷敏感钾通道的作用

    Institute of Scientific and Technical Information of China (English)

    邹晓毅; 周华; 周树舜

    2005-01-01

    BACKGROUND: Abnormal neuronal discharge arose from the activation of cell membrane ion channels and transmembrane ion transport. The electric activity of the cells is associated with cell metabolism fundamentally through adenosine triphosphate (ATP)-sensitive potassium(KATP) channels.Currently the involvement of KATP channels in the pathogenesis of epilepsy and the regulation of KATP channels by coriaria lacton (EL) remain unknown.OBJETCIVE: To investigate the changes of cell membrane KATP channels in rat hippocampal neurons in response to CL as an epilepsy-inducing agent, and explore the role of KATP channels in the pathogenesis of epilepsy.DESIGN: Randomized controlled experiment.SETTING: Department of Neurology, West China Hospital Affiliated to Sichuan University, and Teaching and Research Section of Physiology,West China College of Preclinical Medicine and Forensic Medicine of Sichuan University.MATERIALS: This experiment was carried out at Luzhou Medical College between May and December 2000. Hippocampus pyramidal neurons were obtained from neonatal Wistar rats and randomized into normal control group, tetraethylammonium chloride (TEA) group, DNP group, CL group, and electric conductance and dynamics group.METHODS: The hippocampus of newborn Wistar rats was separated under aseptic condition and cultured for 24 hours prior to treatment with 10 μmol/L cytarabine for selective cell culture for 7-10 days. The cells in good growth exhibiting typical morphology of pyramidal neurons were then selected for patch-clamp experiment. The cells in the normal control group were treated with normal saline, which was replaced by 5 mmol/L TEA in TEA group, by 30 μmol/L DNP then 0.5 mol/L ATP in DNP group, and by 1.0 mL/L CL then 1 μmol/L glibenclamide in CL group. In electric conductance and dynamics group, the clamp voltage was firstly adjusted to investigate the channel opening before CL was added to the cells.MAIN OUTCOME MEASURES: ① Activity and curve of neuronal

  12. Schizophrenia spectrum participants have reduced visual contrast sensitivity to chromatic (red/green and luminance (light/dark stimuli: new insights into information processing, visual channel function and antipsychotic effects

    Directory of Open Access Journals (Sweden)

    Kristin Suzanne Cadenhead

    2013-08-01

    Full Text Available Background: Individuals with schizophrenia spectrum diagnoses have deficient visual information processing as assessed by a variety of paradigms including visual backward masking, motion perception and visual contrast sensitivity (VCS. In the present study, the VCS paradigm was used to investigate potential differences in magnocellular (M versus parvocellular (P channel function that might account for the observed information processing deficits of schizophrenia spectrum patients. Specifically, VCS for near threshold luminance (black/white stimuli is known to be governed primarily by the M channel, while VCS for near threshold chromatic (red/green stimuli is governed by the P channel. Methods: VCS for luminance and chromatic stimuli (counterphase-reversing sinusoidal gratings, 1.22 c/deg, 8.3 Hz was assessed in 53 patients with schizophrenia (including 5 off antipsychotic medication, 22 individuals diagnosed with schizotypal personality disorder and 53 healthy comparison subjects. Results: Schizophrenia spectrum groups demonstrated reduced VCS in both conditions relative to normals, and there was no significant group by condition interaction effect. Post-hoc analyses suggest that it was the patients with schizophrenia on antipsychotic medication as well as SPD participants who accounted for the deficits in the luminance condition. Conclusions: These results demonstrate visual information processing deficits in schizophrenia spectrum populations but do not support the notion of selective abnormalities in the function of subcortical channels as suggested by previous studies. Further work is needed in a longitudinal design to further assess VCS as a vulnerability marker for psychosis as well as the effect of antipsychotic agents on performance in schizophrenia spectrum populations.

  13. Nicosulfuron application in agricultural soils drives the selection towards NS-tolerant microorganisms harboring various levels of sensitivity to nicosulfuron.

    Science.gov (United States)

    Petric, Ines; Karpouzas, Dimitrios G; Bru, David; Udikovic-Kolic, Nikolina; Kandeler, Ellen; Djuric, Simonida; Martin-Laurent, Fabrice

    2016-03-01

    The action mode of sulfonylurea herbicides is the inhibition of the acetohydroxyacid synthase (AHAS) required for the biosynthesis of amino acids valine and isoleucine in plants. However, this enzyme is also present in a range of non-targeted organisms, among which soil microorganisms are known for their pivotal role in ecosystem functioning. In order to assess microbial toxicity of sulfonylurea herbicide nicosulfuron (NS), a tiered microcosm (Tier I) to field (Tier II) experiment was designed. Soil bacteria harboring AHAS enzyme tolerant to the herbicide nicosulfuron were enumerated, isolated, taxonomically identified, and physiologically characterized. Results suggested that application of nicosulfuron drives the selection towards NS-tolerant bacteria, with increasing levels of exposure inducing an increase in their abundance and diversity in soil. Tolerance to nicosulfuron was shown to be widespread among the microbial community with various bacteria belonging to Firmicutes (Bacillus) and Actinobacteria (Arthrobacter) phyla representing most abundant and diverse clusters. While Arthrobacter bacterial population dominated community evolved under lower (Tier II) nicosulfuron selection pressure, it turns out that Bacillus dominated community evolved under higher (Tier I) nicosulfuron selection pressure. Different NS-tolerant bacteria likewise showed different levels of sensitivity to the nicosulfuron estimated by growth kinetics on nicosulfuron. As evident, Tier I exposure allowed selection of populations able to better cope with nicosulfuron. One could propose that sulfonylureas-tolerant bacterial community could constitute a useful bioindicator of exposure to these herbicides for assessing their ecotoxicity towards soil microorganisms. PMID:26517995

  14. Isovector channel of relativistic and non-relativistic energy density functionals and its sensitive influence on the density dependence of symmetry energy

    CERN Document Server

    Wang, X B; Xu, F R

    2010-01-01

    The non-relativistic approximations of relativistic energy density functionals (such as the Relativistic Mean-Field and the Quark-Meson-Coupling models) have been deduced. The formulae are compared with the non-relativistic Skyrme-Hartree-Fock model. These models give quite different descriptions of nuclear matter as well as finite nuclei in the extreme cases of high isospin and high density. In the non-relativistic approximations, it is found that the difference is traced back to the isovector channel of the models and leads to significant effect on the density-dependent behavior of the nuclear symmetry energy. A new Skyrme effective interaction is obtained from the Quark-Meson-Coupling model.

  15. Synthesis and Crystal Structure of a Sodium Monosulfuron-ester (N-[2'-(4-Methyl)pyrimidinyl]-2-carbomethoxy Benzyl Sulfonylurea Sodium)

    Institute of Scientific and Technical Information of China (English)

    KOU Jun-Jie; LI Zheng-Ming; SONG Hai-Bin

    2006-01-01

    Monosulfuron-ester is a novel sulfonylurea herbicide with ultra-low dosage. Herein sodium monosulfuron-ester was synthesized and its crystal structure was determined by X-ray diffraction method. The title compound belongs to monoclinic, space group P21/c with a = 9.335(5), b = 20.632(12), c = 13.853(8) (A), β = 107.193(9)°, Mr = 487.46, Z = 4, Dc = 1.270 g/cm3, μ = 0.293 mm-1, F(000) = 1015, R = 0.0859 and wR = 0.2633. In the title compound, Na coordinates with N(1), O(1) and O(3) from one monosulfuron-ester molecule, N(4A) and O(5A) from the other monosulfuron-ester molecule and one oxygen atom from DMSO to give six coordination bonds.

  16. Correlation between measures of hypoglycemia and glycemic improvement in sulfonylurea treated patients with type 2 diabetes in India: Results from the OBSTACLE hypoglycemia study

    Directory of Open Access Journals (Sweden)

    S Kalra

    2014-01-01

    Full Text Available Background: This study aimed to assess correlation between measures of hypoglycemia and glycemic control in patients with type 2 diabetes mellitus (T2DM treated with sulfonylureas. Materials and Methods: T2DM patients being initiated on a sulfonylurea (SU on background of a failing oral antihyperglycemic regimen were followed up for 12 weeks. (HbA1c was measured at baseline and end of follow-up. Hypoglycemia was assessed using Stanford Hypoglycemia Questionnaire at week 12. Results: Of the total 1069 patients enrolled, 950 were considered evaluable. A weak negative correlation was observed between end of follow-up HbA1c values and hypoglycemia score, using both linear regression analysis (correlation coefficient -0.12; P = 0.0002 and negative binomial regression (β slope -0.09; P = 0.0010. A similar correlation was also observed between change in HbA1c from baseline and hypoglycemia score (β slope -0.07; P = 0.0048. Mean HbA1c reduction was lowest (0.65 ± 2.27% in patients not reporting any hypoglycemia and highest (1.28 ± 2.40% in patients with hypoglycemia score greater than median of 2 (P = 0.0031. There was no correlation between hypoglycemia frequency and end of follow-up HbA1c values (P = 0.4111. Conclusion: With addition of SU on a background of a failing oral anti-hyperglycemic regimen, the extent of glycemic control correlates directly with measures of patient reported hypoglycemia.

  17. Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Institute of Neuroscience, Soochow University, Suzhou (China); Hu, S.M. [Institute of Neuroscience, Soochow University, Suzhou (China); Xie, H.; Qiao, S.G. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Liu, H. [Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Davis, CA (United States); Liu, C.F. [Institute of Neuroscience, Soochow University, Suzhou (China)

    2015-03-27

    This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoK{sub ATP}) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoK{sub ATP} channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoK{sub ATP} channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

  18. L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons.

    Science.gov (United States)

    Hoddah, Hanaa; Marcantoni, Andrea; Comunanza, Valentina; Carabelli, Valentina; Carbone, Emilio

    2009-01-01

    Using immortalized hypothalamic GT1-7 neurons, which express the CB1 cannabinoid receptor (CB1R) and three Ca2+ channel types (T, R and L), we found that the CB1R agonist WIN 55,212-2 inhibited the voltage-gated Ca2+ currents by about 35%. The inhibition by WIN 55,212-2 (10 microM) was reversible and prevented by nifedipine (3 microM), suggesting a selective action on L-type Ca2+ channels (LTCCs). WIN 55,212-2 action exhibited all the features of voltage-independent Ca2+ channel modulation: (1) no changes of the activation kinetics, (2) equal depressive action at all potentials and (3) no facilitation following strong prepulses. At variance with WIN 55,212-2, the CB1R inverse agonist AM-251 (10 microM) caused 20% increase of Ca2+ currents. The inhibition of LTCCs by WIN 55,212-2 was prevented by overnight PTX-incubation and by intracellular perfusion with GDP-beta-S. The latter caused also a 20% Ca2+ current up-regulation. WIN 55,212-2 action was also prevented by application of the PKA-blocker H89 or by loading the neurons with 8-CPT-cAMP. Our results suggest that LTCCs in GT1-7 neurons are partially inhibited at rest due to a constitutive CB1R activity removed by AM-251 and GDP-beta-S. Activation of CB1R via PTX-sensitive G proteins and cAMP/PKA pathway selectively depresses LTCCs that critically control the synchronized spontaneous firing and pulsatile release of gonadotropin-releasing hormone in GT1-7 neurons. PMID:19818494

  19. Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

    International Nuclear Information System (INIS)

    This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion

  20. The pH-sensitive structure of the C-terminal domain of voltage-gated proton channel and the thermodynamic characteristics of Zn2+ binding to this domain

    International Nuclear Information System (INIS)

    Highlights: • The α-helical content of the C-terminus is decreased with a pH increase. • The thermostability of the C-terminus is decreased with a pH increase. • Zn2+ binds to His244 and His266 residues within the C-terminal domain. • The binding of Zn2+ to His244 residue is an endothermic heat reaction. • The binding of Zn2+ to His266 residue is an exothermic heat reaction. - Abstract: The voltage-gated proton channel Hv1 is strongly sensitive to Zn2+. The H+ conduction is decreased at a high concentration of Zn2+ and Hv1 channel closing is slowed by the internal application of Zn2+. Although the recent studies demonstrated that Zn2+ interacts with the intracellular C-terminal domain, the binding sites and details of the interaction remain unknown. Here, we studied the pH-dependent structural stability of the intracellular C-terminal domain of human Hv1 and showed that Zn2+ binds to His244 and His266 residues. The thermodynamics signature of Zn2+ binding to the two sites was investigated by isothermal titration calorimetry. The binding of Zn2+ to His244 (mutant H266A) and His266 (mutant H244A) were an endothermic heat reaction and an exothermic heat reaction, respectively

  1. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    International Nuclear Information System (INIS)

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release

  2. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  3. Ion channel screening.

    Science.gov (United States)

    Dunlop, John; Bowlby, Mark; Peri, Ravikumar; Tawa, Gregory; LaRocque, James; Soloveva, Veronica; Morin, John

    2008-08-01

    Ion channels are attractive targets for drug discovery with recent estimates indicating that voltage and ligand-gated channels account for the third and fourth largest gene families represented in company portfolios after the G protein coupled and nuclear hormone receptor families. A historical limitation on ion channel targeted drug discovery in the form of the extremely low throughput nature of the gold standard assay for assessing functional activity, patch clamp electrophysiology in mammalian cells, has been overcome by the implementation of multi-well plate format cell-based screening strategies for ion channels. These have taken advantage of various approaches to monitor ion flux or membrane potential using radioactive, non-radioactive, spectroscopic and fluorescence measurements and have significantly impacted both high-throughput screening and lead optimization efforts. In addition, major advances have been made in the development of automated electrophysiological platforms to increase capacity for cell-based screening using formats aimed at recapitulating the gold standard assay. This review addresses the options available for cell-based screening of ion channels with examples of their utility and presents case studies on the successful implementation of high-throughput screening campaigns for a ligand-gated ion channel using a fluorescent calcium indicator, and a voltage-gated ion channel using a fluorescent membrane potential sensitive dye. PMID:18694388

  4. Functional Expression of an Arachnid Sodium Channel Reveals Residues Responsible for Tetrodotoxin Resistance in Invertebrate Sodium Channels*

    OpenAIRE

    Du, Yuzhe; Nomura, Yoshiko; Liu, Zhiqi; Huang, Zachary Y.; Dong, Ke

    2009-01-01

    Tetrodotoxin (TTX) is a potent blocker of voltage-gated sodium channels, but not all sodium channels are equally sensitive to inhibition by TTX. The molecular basis of differential TTX sensitivity of mammalian sodium channels has been largely elucidated. In contrast, our knowledge about the sensitivity of invertebrate sodium channels to TTX remains poor, in part because of limited success in functional expression of these channels. In this study, we report the functional characterization in X...

  5. dl-白花前胡甲素对人大脑皮层ATP敏感钾通道的作用%Effect of dl-praeruptorin A on ATP sensitive potassium channels inhuman cortical neurons

    Institute of Scientific and Technical Information of China (English)

    张沈丽; 李金鸣; 肖庆桓; 吴安华; 赵青; 杨国瑞; 张克义

    2001-01-01

    目的:研究白花前胡甲素(Pd-Ia)对人大脑皮层神经元ATP敏感钾通道的作用.方法:应用膜片箝全细胞记录技术,采用累积给药方式.箝制电压-40mV,指令电压-30到+100 mV,时程600 ms.结果:Pd-Ia以浓度依赖方式激活ATP敏感钾通道.当用含不同浓度的(0.001,0.01,0.1和1 μmol/L)Pd-Ia细胞外液灌流时,电流值分别从给药前的(0.9±0.4)nA增大到给药后的(1.0±0.4)nA,(1.1±0.4)nA,(1.2±0.4)nA和(1.3±0.4)nA(P<0.01,n=5).然后用含ATP敏感钾通道的特异抑制剂格列苯脲(10 μmol/L)的细胞外液冲洗,电流减小至(0.90±0.37)nA(P<0.01,n=5). 结论:Pd-Ia可开放ATP敏感钾通道,是一种钾通道开放剂.%AIM: To investigate the effect of dl-praeruptorin A (PdIa) on ATP sensitive potassium channels (KATP channel) in human cortical neurons. METHODS: Using standard whole cell recording method. Cell membranes were held at - 40 mV, commanding potential was - 30 to + 100 mV and duration was 600 ms. RESULTS: PdIa activated KATP channels in human cortical neurons in a concentration-dependent manner. After consecutive perfusion with extemal solution containing Pd-Ia 0.001,0.01, 0.1, and 1 μmol/L, currents increased from control (0.9±0.4) nAto (1.0±0.4) nA, (1.1±0.4) nA, (1.2±0.4) nA, and (1.3±0.4) nA (P<0.05 or P < 0.01, n = 5 ) respectively. Then the current decreased to (0.90±0.37) nA (P<0.01, n=5) after washout with glibenclamide (10 μmol/L ). The increscent part of the currents could nearly be inhibited by specific KATP channel inhibitor. CONCLUSION: Pd-Ia could open KATP channel and it is a kind of potassium channel opener.

  6. Changes in cerebral blood flow during olfactory stimulation in patients with multiple chemical sensitivity: a multi-channel near-infrared spectroscopic study.

    Directory of Open Access Journals (Sweden)

    Kenichi Azuma

    Full Text Available Multiple chemical sensitivity (MCS is characterized by somatic distress upon exposure to odors. Patients with MCS process odors differently from controls. This odor-processing may be associated with activation in the prefrontal area connecting to the anterior cingulate cortex, which has been suggested as an area of odorant-related activation in MCS patients. In this study, activation was defined as a significant increase in regional cerebral blood flow (rCBF because of odorant stimulation. Using the well-designed card-type olfactory test kit, changes in rCBF in the prefrontal cortex (PFC were investigated after olfactory stimulation with several different odorants. Near-infrared spectroscopic (NIRS imaging was performed in 12 MCS patients and 11 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included subjective assessment of physical and psychological status and the perception of irritating and hedonic odors. Significant changes in rCBF were observed in the PFC of MCS patients on both the right and left sides, as distinct from the center of the PFC, compared with controls. MCS patients adequately distinguished the non-odorant in 10 odor repetitions during the early stage of the olfactory stimulation test, but not in the late stage. In comparison to controls, autonomic perception and negative affectivity were poorer in MCS patients. These results suggest that prefrontal information processing associated with odor-processing neuronal circuits and memory and cognition processes from past experience of chemical exposure play significant roles in the pathology of this disorder.

  7. The pH-sensitive structure of the C-terminal domain of voltage-gated proton channel and the thermodynamic characteristics of Zn{sup 2+} binding to this domain

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Qing; Li, Chuanyong; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2015-01-02

    Highlights: • The α-helical content of the C-terminus is decreased with a pH increase. • The thermostability of the C-terminus is decreased with a pH increase. • Zn{sup 2+} binds to His{sup 244} and His{sup 266} residues within the C-terminal domain. • The binding of Zn{sup 2+} to His{sup 244} residue is an endothermic heat reaction. • The binding of Zn{sup 2+} to His{sup 266} residue is an exothermic heat reaction. - Abstract: The voltage-gated proton channel Hv1 is strongly sensitive to Zn{sup 2+}. The H{sup +} conduction is decreased at a high concentration of Zn{sup 2+} and Hv1 channel closing is slowed by the internal application of Zn{sup 2+}. Although the recent studies demonstrated that Zn{sup 2+} interacts with the intracellular C-terminal domain, the binding sites and details of the interaction remain unknown. Here, we studied the pH-dependent structural stability of the intracellular C-terminal domain of human Hv1 and showed that Zn{sup 2+} binds to His{sup 244} and His{sup 266} residues. The thermodynamics signature of Zn{sup 2+} binding to the two sites was investigated by isothermal titration calorimetry. The binding of Zn{sup 2+} to His{sup 244} (mutant H266A) and His{sup 266} (mutant H244A) were an endothermic heat reaction and an exothermic heat reaction, respectively.

  8. Use of gold nanoparticle-coated sorbent materials for the selective preconcentration of sulfonylurea herbicides in water samples and determination by capillary liquid chromatography.

    Science.gov (United States)

    Lerma-García, María Jesús; Simó-Alfonso, Ernesto F; Zougagh, Mohammed; Ríos, Angel

    2013-02-15

    Two new gold nanoparticle (NP) coated materials (silica supported on gold NP with and without ionic liquid) were synthesized for solid phase extraction of sulfonylurea herbicides (SUHs), such as bensulfuron-methyl (BSM), metsulfuron-methyl (MSM), pyrazosulfuron-methyl (PSM), thifensulfuron-methyl (TFM) and triasulfuron (TS), from water samples, followed by capillary liquid chromatography coupled to diode array detection (CLC-DAD). Several factors influencing the preconcentration efficiency of SUHs and its subsequent determination, such as pH of the sample, eluent and reusability of sorbents, have been investigated. Under the optimum conditions, the developed method allowed the determination of BSM, MSM, PSM, TFM and TS in a linear range between 0.05 and 1.00 μg mL(-1), with relative standard deviation values lower than 4.5% (n=10), in all cases. Detection limits within 0.002-0.009 μg mL(-1) range were achieved. The usefulness of the proposed method was demonstrated by the analysis of river water samples, in which recoveries between 83.9 and 105.0% were obtained. The Au-NP-ionic liquid-functionalized silica sorbent showed higher recoveries (selectivity) for the SUHs than the commercially available C18 sorbents. PMID:23598033

  9. N-methylimidazolium ionic liquid-functionalized silica as a sorbent for selective solid-phase extraction of 12 sulfonylurea herbicides in environmental water and soil samples.

    Science.gov (United States)

    Fang, Guozhen; Chen, Jing; Wang, Junping; He, Jinxing; Wang, Shuo

    2010-03-01

    A novel material for solid-phase extraction (SPE) was synthesized by chemical immobilization of a functionalized N-methylimidazolium ionic liquid on silica gel. Cartridges packed with the synthetic material were successfully applied to the pre-concentration of trace-level thifensulfuron-methyl, metsulfuron-methyl, chlorsulfuron, sulfometuron-methyl, rimsulfuron, ethametsulfuron, tribenuron-methyl, bensulfuron-methyl, prosulfuron, pyrazosulfuron, chlorimuron-ethyl and primisulfuron from environmental water and soil samples. The 12 sulfonylurea herbicides (SUs) obtained a good resolution in less than 50 min using HPLC with a UV detector. The recovery studies using the ionic liquid-functionalized silica as a sorbent were performed by three consecutive extractions of water and soil samples at two spiked levels. The average recovery for each analyte was in the range of 53.8-118.2% for the water samples and 60.9-121.3% for the soil sample, with RSDs lower than 11.3% in all cases. The ionic liquid-functionalized silica cartridges showed higher selectivity for the SUs than commercially available C(18) cartridges did. PMID:20116796

  10. Integrated criteria for covert channel auditing

    Institute of Scientific and Technical Information of China (English)

    Chang-da WANG; Shi-guang JU

    2008-01-01

    A new concept, the security level difference of a covert channel, is presented, which means the security level span from the sender to the receiver of the covert channel. Based on this, the integrated criteria for covert channel auditing are given. Whereas TCSEC (Trusted Computer System Evaluation Criteria) or CC (Common Criteria for Information Technology Security Evaluation) only use the bandwidth to evaluate the threat of covert channels, our new criteria integrate the security level difference, the bandwidth sensitive parameter, bandwidth, duration and instantaneous time of covert channels, so as to give a comprehensive evaluation of the threat of covert channels in a multilevel security system.

  11. Sonification of Multi-Channel Image Data

    OpenAIRE

    Hermann, Thomas; Nattkemper, Tim Wilhelm; Schubert, Walter; Ritter, Helge; Falavar, V.

    2000-01-01

    This paper presents a method to inspect multi-channel image data by creating audible em sonifications, which are `sound images', computed from a stack of image data. While visualization of multi-channel image data is limited by the available three color channels, our perception of sound is sensitive to a potentially much larger number of frequency channels or dynamic patterns, that can be perceived simultaneously. Browsing the image stack while listening to the sonifications facilitates the i...

  12. 新型热中子敏感微通道板探测效率的蒙特-卡罗模拟研究∗%Optimal calculation of detection efficiency for thermal neutron sensitive micro channel plate

    Institute of Scientific and Technical Information of China (English)

    王胜; 李航; 曹超; 吴洋; 霍合勇; 唐彬

    2015-01-01

    The traditional digital imaging of neutron radiography is based on neutron scintillation screen cooperated with charge coupled device (CCD) camera, whose spatial resolution and neutron detection efficiency are contradictory. Neutron detection method based on microchannel plates (MCP) could solve the problem appearing in traditional method. It could supply high spatial resolution, high neutron detection efficiency and high time resolution. It is of benefit to high-resolution neutron radiography and neutron energy choice imaging. Tremsin et al. [Tremsin A S, Feller W B, Downing R G, Mildner D R 2004 U. S. Government Work not Protected by U. S. Copyright p340] calculated the detection efficiency of thermal neutron sensitivity MCP in 2004. Then his team fabricated a prototype of neutron detection system based on MCP and carried out the neutron imaging experiments on several neutron sources. The experimental results show that spatial resolution is nearly 15 µm and neutron detection efficiency for cold neutron is more than 70%. In China, Yang Y G et al. [15] from Tsinghua University developed a neutron detection system based on MCP, and preliminary neutron experimental results indicate that spatial resolution is about 200 µm. In order to find the optimal structure of MCP, in this paper we calculate the detection efficiency of thermal neutron sensitive MCP doped (or coated) by boron and gadolinium with Monte-Carlo method. The neutron detection efficiency P is determined by three terms P1, P2 and P3, which are related by P =P1 × P2 × P3. Here, P1 is the possibility that the neutrons are absorbed by MCP solid parts, P2 is the possibility that the secondary particle escapes into MCP channel and generates an electron avalanche, and P3 is the possibility that the electron avalanch is recorded by readout system. Theoretical analysis indicates that more solid parts of MCP can make P1 higher and increase the difficulty for secondary particle to escape, and make P2 lower

  13. Role of the membrane for mechanosensing by tethered channels

    CERN Document Server

    Sabass, Benedikt

    2016-01-01

    Biologically important membrane channels are gated by force at attached tethers. Here, we generically characterize the non-trivial interplay of force, membrane tension, and channel deformations that can affect gating. A central finding is that minute conical channel deformation under force leads to significant energy release during opening. We also calculate channel-channel interactions and show that they can amplify force sensitivity of tethered channels.

  14. Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea.

    Science.gov (United States)

    Xiaoyan, Chen; Jing, Wang; Xiaochun, Huang; Yuyu, Tan; Shunyou, Deng; Yingyu, Fu

    2016-06-01

    Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24 hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea. Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N = 73) with T2DM who had inadequate glycemic control (HbA1c 7.0%-10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50 mg twice daily (BID, n = 37) or saxagliptin 5 mg once daily (QD, n = 36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks. Results At baseline, the mean (±SD) age was 62.9 ± 6.55 years, disease duration was 7.0 ± 2.33 years, and HbA1c was 8.4 ± 0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81 ± 1.16 mmol/L to 4.06 ± 0.86 mmol/L (p<0.001) in the vildagliptin group and from 5.66 ± 1.14 mmol/L to 4.79 ± 1.25 mmol/L (p = 0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74 ± 0.48 mmol/L vs. 0.87 ± 0.40 mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22 ± 0.40% and 1.07 ± 0.36%, respectively, with no significant difference between the groups (p = 0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug. Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese

  15. Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP-Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins.

    Science.gov (United States)

    Imani, Alireza; Khansari, Maryam; Azizi, Yaser; Rakhshan, Kamran; Faghihi, Mahdieh

    2015-08-01

    Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others, the mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronary effluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs). PMID:26545994

  16. Association between Three Mutations, F1565C, V1023G and S996P, in the Voltage-Sensitive Sodium Channel Gene and Knockdown Resistance in Aedes aegypti from Yogyakarta, Indonesia

    Directory of Open Access Journals (Sweden)

    Juli Rochmijati Wuliandari

    2015-07-01

    Full Text Available Mutations in the voltage-sensitive sodium channel gene (Vssc have been identified in Aedes aegypti and some have been associated with pyrethroid insecticide resistance. Whether these mutations cause resistance, alone or in combination with other alleles, remains unclear, but must be understood if mutations are to become markers for resistance monitoring. We describe High Resolution Melt (HRM genotyping assays for assessing mutations found in Ae. aegypti in Indonesia (F1565C, V1023G, S996P and use them to test for associations with pyrethroid resistance in mosquitoes from Yogyakarta, a city where insecticide use is widespread. Such knowledge is important because Yogyakarta is a target area for releases of Wolbachia-infected mosquitoes with virus-blocking traits for dengue suppression. We identify three alleles across Yogyakarta putatively linked to resistance in previous research. By comparing resistant and susceptible mosquitoes from bioassays, we show that the 1023G allele is associated with resistance to type I and type II pyrethroids. In contrast, F1565C homozygotes were rare and there was only a weak association between individuals heterozygous for the mutation and resistance to a type I pyrethroid. As the heterozygote is expected to be incompletely recessive, it is likely that this association was due to a different resistance mechanism being present. A resistance advantage conferred to V1023G homozygotes through addition of the S996P allele in the homozygous form was suggested for the Type II pyrethroid, deltamethrin. Screening of V1023G and S996P should assist resistance monitoring in Ae. aegypti from Yogyakarta, and these mutations should be maintained in Wolbachia strains destined for release in this city to ensure that these virus-blocking strains of mosquitoes are not disadvantaged, relative to resident populations.

  17. A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME Study

    Directory of Open Access Journals (Sweden)

    Mitsunori Sugiyama

    2010-01-01

    Full Text Available Background: Morning blood pressure (BP surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS-restoring Ca-channel blocker (CCB azelnidipine (AZ on this age-related morning BP increase. Methods: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%. Results: At baseline, ME-Dif (morning systolic BP [SBP]–evening SBP increased with age, independently of ME-Ave (average of the morning and evening SBPs. This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day, ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of –18.1 ± 15.6 and –2.5 ± 13.2 mmHg, respectively (both p < 0.001. AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. Conclusions: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol.

  18. On-line preconcentration and determination of six sulfonylurea herbicides in cereals by MEKC with large-volume sample stacking and polarity switching.

    Science.gov (United States)

    Yi, Ling-Xiao; Chen, Guan-Hua; Fang, Rou; Zhang, Li; Shao, Yu-Xiu; Chen, Ping; Tao, Xiang-Xiang

    2013-05-01

    A new MEKC method with large-volume sample stacking and polarity switching was developed for on-line preconcentration and detection of sulfonylurea herbicide (SUH) residues in cereals, including nicosulfuron (NS), thifensulfuon (methyl) (TFM), tribenuron-methly (TBM), sulfometuron-methyl (SMM), pyrazosulfuron-ethyl (PSE), and chlorimuron-ethyl (CME). In order to achieve a high resolution and enrichment factor, several parameters were optimized, such as the pH of the running buffer, the concentration of the BGE and the SDS, the separate voltage, the sample size, the pH, and the electrolyte concentration of the sample. The optimal running buffer was composed of 30 mM borate and 80 mM SDS at pH 7.0. The borate concentration in the sample was 30 mM and the pH value of the sample was the same as that of the running buffer. The concentrating voltage and the separating voltage were -15 kV and 15 kV, respectively. The sample size was 1.455 kPa × 780 s (33.11 cm). Under the optimum conditions, for NS, TFM, TBM, SMM, PSE, and CME, the enrichment factors were 613, 642, 835, 570, 709, and 599; the LODs were 0.29-0.50 ng/g, 0.22-0.36 ng/g, 0.60-0.89 ng/g, 0.39-0.72 ng/g, 0.28-0.56 ng/g, and 0.31-0.57 ng/g; the LOQs of six SUHs were all 5 ng/g; the average recoveries of the spiked sample were 86.68-92.99%, 80.73-93.65%, 81.49-94.40%, 82.97-95.1%, 82.96-98.84%, and 80.41-92.94%, respectively. PMID:23436573

  19. Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin

    Directory of Open Access Journals (Sweden)

    Ye An Kim

    2015-12-01

    Full Text Available BackgroundDipeptidyl peptidase-4 (DPP-4 inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU. We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients.MethodsWe included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with ≥25% reduction in glycosylated hemoglobin (HbA1c within 12 weeks.ResultsAt baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4% achieved an HbA1c level ≤7%. Sixty-six patients (8.2%, 47 men were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG, HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of β-cells.ConclusionAn oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.

  20. Effects of Exhaustive Exercise on the ATP-sensitive Potassium Channel in Sinoatrial Node of Rats%力竭运动对大鼠窦房结ATP-敏感型钾离子通道的影响

    Institute of Scientific and Technical Information of China (English)

    薄冰; 常芸

    2012-01-01

    目的:探讨两周力竭运动对大鼠窦房结ATP-敏感型钾离子通道(KATP通道)亚基Kir6.2mRNA表达及通道电流密度的影响.方法:健康雄性SD大鼠180只,8周龄,体重(220±8)g,共分9组,每组20只,包括安静对照组(C组)1组、一次力竭组(O组)4组、反复力竭组(R组)4组.安静对照组不进行任何运动.反复力竭组大鼠尾部负重3%体重,每天进行1次力竭游泳,每次约2小时,每周6天,共运动2周.一次力竭组大鼠在正常喂养2周后进行一次力竭游泳运动,运动方案同反复力竭组.运动组大鼠分别于运动后即刻、4小时、12小时、24小时不同时相取材,一次力竭运动各组大鼠分别以O-0h、O-4h、O-12h、O-24h命名,反复力竭运动各组大鼠分别以R-0h、R-4h、R-12h、R-24h命名,应用实时荧光定量PCR技术测定KATP通道亚基Kir6.2 mRNA表达变化,应用细胞急性分离及全细胞膜片钳技术测定通道电流密度变化,以观察力竭游泳运动对大鼠窦房结细胞膜上KATP通道的影响.结果:反复力竭运动各组Kir6.2 mRNA表达显著高于对照组(P<0.01).反复力竭各时相组KATP通道IK.ATP电流密度显著高于对照组及一次力竭组(P<0.01).结论:反复力竭运动可引起窦房结细胞膜KATP通道亚基Kir6.2 mRNA表达及IK,ATP电流密度增加,这可能引起窦房结细胞舒张期自动除极及自律活动减慢,提示反复力竭运动对于KATP通道的影响可能成为运动引发窦房结功能障碍及运动性心律失常的离子通道机制之一.%Objective This paper discusses the subunit mRNA and current density of ATP-sensitive potassium channel (KAtp channel) in sinoatrial node (SAN) at different time phrases after exhaustive exercise. Methods 180 healthy adult male SD rats were equally assigned into 9 groups ;1 control group (C) ,4 single exhaustive swimming groups (O-0hour,O-4hours,O-12hours,O-24hours) ,and 4 2-week repeated exhaustive swimming groups (R-0hour,R-4hours,R-12

  1. Preparation of a bifunctional pyrazosulfuron-ethyl imprinted polymer with hydrophilic external layers by reversible addition-fragmentation chain transfer polymerization and its application in the sulfonylurea residue analysis.

    Science.gov (United States)

    Yang, Meixian; Zhang, Yingying; Lin, Shen; Yang, Xinlin; Fan, Zhijin; Yang, Lixia; Dong, Xiangchao

    2013-09-30

    A new bifunctional pyrazosulfuron-ethyl imprinted polymer was synthesized by the combination of molecular imprinting technology and living radical polymerization. In the synthesis, the pyrazosulfuron-ethyl imprinted polymer was obtained by the reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization followed by grafting poly(glyceryl monomethacrylate) (pGMMA) by the post-RAFT polymerization. In this research, we used polyethylene glycol (PEG) as the polymeric porogen in order to increase the porosity of the material which is a new porogen application in the precipitation polymerization. The imprinted polymer has selectivity for the template and ability of humic acids exclusion which has shown the merits of molecularly imprinted polymers and restricted access materials. An online solid-phase extraction/HPLC method for the analysis of three sulfonylurea residues in soil samples has been developed and validated. The recovery of 81-99% in the spiked levels of 40-200 μg kg(-1) was obtained and the limit of detection (LOD) and limit of quantification (LOQ) were less than 4.8 and 15.9 μg kg(-1) respectively. The results demonstrated that this bifunctional material can be used for the efficient pyrazosulfuron-ethyl extraction in the sulfonylurea residue analysis from environmental samples. PMID:23953454

  2. Synthesis, Biological Activities of Mono-substituted Pyrimidine-pyridine Sulfonylurea Compounds%单取代嘧啶基吡啶磺酰脲化合物的合成和生物活性

    Institute of Scientific and Technical Information of China (English)

    童军; 郑占英; 李永红; 王素华; 李正名

    2012-01-01

    [方法]以单取代苯磺酰脲除草剂为基础,在分子中以吡啶环代替苯环设计合成了15个新的吡啶磺酰脲化合物,所有合成的化合物经核磁、元素分析确证,并对其生物活性进行了研究.[结论]剂量为300 g a.i./hm2时,大部分化合物对被测4种杂草的抑制活性不明显.%[Methods] Based on the structure of mono-substituted pyrimidine sulfonylurea herbicides developed 15 novel pyridinyl sulfonylurea molecules containing mono-substituted pyrimidine rings were designed and synthesized. The structures of all compounds were confirmed by 1H NMR and elemental analysis. The bioassay was also carried out, [Conclusions] The biological screening results showed that the inhibitory effects of most of synthesized compounds were not obvious at the concentration of 300 g a.i./ha.

  3. Channel Networks

    Science.gov (United States)

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

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

  4. Single Na+ channels activated by veratridine and batrachotoxin

    OpenAIRE

    1987-01-01

    Voltage-sensitive Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers in the presence of either of the alkaloid toxins veratridine (VT) or batrachotoxin (BTX). Both of these toxins are known to cause persistent activation of Na+ channels. With BTX as the channel activator, single channels remain open nearly all the time. Channels activated with VT open and close on a time scale of 1-10 s. Increasing the VT concentration enhances the probabil...

  5. Chromatic effects in long periodic transport channels

    Energy Technology Data Exchange (ETDEWEB)

    Litvinenko V. N.; Hao, Y.; Jing, Y.

    2015-05-03

    Long periodic transport channels are frequently used in accelerator complexes and suggested for using in high-energy ERLs for electron-hadron colliders. Without proper chromaticity compensation, such transport channels exhibit high sensitivity to the random orbit errors causing significant emittance growth. Such emittance growth can come from both the correlated and the uncorrelated energy spread. In this paper we present results of our theoretical and numerical studies of such effects and develop a criteria for acceptable chromaticity in such channels.

  6. Epilepsy-Related Slack Channel Mutants Lead to Channel Over-Activity by Two Different Mechanisms.

    Science.gov (United States)

    Tang, Qiong-Yao; Zhang, Fei-Fei; Xu, Jie; Wang, Ran; Chen, Jian; Logothetis, Diomedes E; Zhang, Zhe

    2016-01-01

    Twelve sodium-activated potassium channel (KCNT1, Slack) genetic mutants have been identified from severe early-onset epilepsy patients. The changes in biophysical properties of these mutants and the underlying mechanisms causing disease remain elusive. Here, we report that seven of the 12 mutations increase, whereas one mutation decreases, the channel's sodium sensitivity. Two of the mutants exhibit channel over-activity only when the intracellular Na(+) ([Na(+)]i) concentration is ∼80 mM. In contrast, single-channel data reveal that all 12 mutants increase the maximal open probability (Po). We conclude that these mutant channels lead to channel over-activity predominantly by increasing the ability of sodium binding to activate the channel, which is indicated by its maximal Po. The sodium sensitivity of these epilepsy causing mutants probably determines the [Na(+)]i concentration at which these mutants exert their pathological effects. PMID:26725113

  7. Channeling experiment

    International Nuclear Information System (INIS)

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

  8. Proadrenomedullin NH2-terminal 20 peptide inhibits the voltage-gated Ca2+ channel current through a pertussis toxin-sensitive G protein in rat pheochromocytoma-derived PC 12 cells.

    OpenAIRE

    Takano, K; Yamashita, N; Fujita, T.

    1996-01-01

    The effect of proadrenomedullin NH2-terminal 20 peptide (PAMP) on the voltage-gated Ca2+ channel current was investigated using the perforated whole-cell clamp technique on NGF-treated PC12 cells. PAMP inhibited the Ba2+ current through N-type Ca2+ channels in a concentration dependent manner. Injection of GDPbetaS into the cell abolished the inhibition while injection of GTPgammaS into the cell made the inhibition irreversible, indicating that the PAMP-induced inhibition of the voltage-gated...

  9. Potassium channels in prostate and colonic cancer

    OpenAIRE

    Ousingsawat, Jiraporn

    2007-01-01

    Large conductance Ca2+-activated K+ channels in human prostate cancer The KCNMA1 gene encoding the alpha-subunit of BK channels is amplified and BK channel expression is enhanced in late-stage, metastatic and hormone-refractory human prostate cancer tissues, whereas benign prostate tissues show only a weak expression of BK channels. PC-3 hormone-insensitive prostate cancer cells, but not hormone-sensitive prostate cancer cells (LNCaP) and benign prostate hyperplasia cells (BPH-1), show an ...

  10. Brownian transport in corrugated channels with inertia

    Science.gov (United States)

    Ghosh, P. K.; Hänggi, P.; Marchesoni, F.; Nori, F.; Schmid, G.

    2012-08-01

    Transport of suspended Brownian particles dc driven along corrugated narrow channels is numerically investigated in the regime of finite damping. We show that inertial corrections cannot be neglected as long as the width of the channel bottlenecks is smaller than an appropriate particle diffusion length, which depends on the the channel corrugation and the drive intensity. With such a diffusion length being inversely proportional to the damping constant, transport through sufficiently narrow obstructions turns out to be always sensitive to the viscosity of the suspension fluid. The inertia corrections to the transport quantifiers, mobility, and diffusivity markedly differ for smoothly and sharply corrugated channels.

  11. Brownian transport in corrugated channels with inertia

    CERN Document Server

    Ghosh, P K; Marchesoni, F; Nori, F; Schmid, G; 10.1103/PhysRevE.86.021112

    2012-01-01

    The transport of suspended Brownian particles dc-driven along corrugated narrow channels is numerically investigated in the regime of finite damping. We show that inertial corrections cannot be neglected as long as the width of the channel bottlenecks is smaller than an appropriate particle diffusion length, which depends on the the channel corrugation and the drive intensity. Being such a diffusion length inversely proportional to the damping constant, transport through sufficiently narrow obstructions turns out to be always sensitive to the viscosity of the suspension fluid. The inertia corrections to the transport quantifiers, mobility and diffusivity, markedly differ for smoothly and sharply corrugated channels.

  12. Microwave Radiometer – 3 Channel (MWR3C) Handbook

    Energy Technology Data Exchange (ETDEWEB)

    Cadeddu, MP

    2012-05-04

    The microwave radiometer 3-channel (MWR3C) provides time-series measurements of brightness temperatures from three channels centered at 23.834, 30, and 89 GHz. These three channels are sensitive to the presence of liquid water and precipitable water vapor.

  13. Behavioral characterization of mice lacking Trek channels

    OpenAIRE

    Mirkovic, Kelsey; Palmersheim, Jaime; Lesage, Florian; Wickman, Kevin

    2012-01-01

    Two-pore domain K+ (K2P) channels are thought to underlie background K+ conductance in many cell types. The Trek subfamily of K2P channels consists of three members, Trek1/Kcnk2, Trek2/Kcnk10, and Traak/Kcnk4, all three of which are expressed in the rodent CNS. Constitutive ablation of the Trek1 gene in mice correlates with enhanced sensitivity to ischemia and epilepsy, decreased sensitivity to the effects of inhaled anesthetics, increased sensitivity to thermal and mechanical pain, and resis...

  14. Behavioral characterization of mice lacking Trek channels

    OpenAIRE

    Kelsey Mirkovic; Florian Lesage

    2012-01-01

    Two-pore domain K+ (K2P) channels are thought to underlie background K+ conductance in many cell types. The Trek subfamily of K2P channels consists of three members, Trek1/Kcnk2, Trek2/Kcnk10, and Traak/Kcnk4, all three of which are expressed in the rodent CNS. Constitutive ablation of the Trek1 gene in mice correlates with enhanced sensitivity to ischemia and epilepsy, decreased sensitivity to the effects of inhaled anesthetics, increased sensitivity to thermal and mechanical pain, and res...

  15. Channel strategy adaptation

    OpenAIRE

    Rangan, V. Kasturi; Nueno, Jose L

    1999-01-01

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

  16. Global sensitivity of aviation NOx effects to the HNO3-forming channel of the HO2 + NO reaction

    OpenAIRE

    K. Gottschaldt; Voigt, C.; Jöckel, P.; M. Righi; Deckert, R.; S. Dietmüller

    2013-01-01

    The impact of a recently proposed HNO3-forming channel of the HO2 + NO reaction on atmospheric ozone, methane and their precursors is assessed with the aim to investigate its effects on aviation NOx induced radiative forcing. The first part of the study addresses the differences in stratospheric and tropospheric HOx-NOx chemistry in general, by comparing a global climate simulation without the above reaction to two simulations with different rate coefficient parameter...

  17. Methods of albedo electron densimetry. 2. Two-channel methods

    Energy Technology Data Exchange (ETDEWEB)

    Sorokin, V.B. (Tomskij Politekhnicheskij Inst. (USSR). Nauchno-Issledovatel' skij Inst. Ehlektronnoj Introskopii)

    1981-12-01

    Two-channel methods of densimetry permitting to realize control over density of materials with fluctuating composition which have been developed on the basis of one-channel albedo electron methods are considered. The two-channel methods permits to decrease the errors as compared with one-channel ones and when central-peripheral method is applied - also to increase the sensitivity to density variation. The methods are intended for control density of porous materials, especially in powder metallurgy, ceramics production, etc.

  18. Sensitivity analysis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  19. Gluten Sensitivity

    Science.gov (United States)

    ... like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different from ... small intestine. Some of the symptoms of gluten sensitivity are similar to celiac disease. They include tiredness ...

  20. Polyunsaturated fatty acids modify the gating of Kv channels

    Directory of Open Access Journals (Sweden)

    Cristina eMoreno

    2012-09-01

    Full Text Available Polyunsaturated fatty acids (PUFAs have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are blocked by n-3 PUFAs of marine (docosahexaenoic and eicosapentaenoic acid, DHA and EPA and plant origin (alpha-linolenic acid, ALA at physiological concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the range of membrane potentials coinciding with those of Kv1.5 channel activation, suggesting that PUFAs-channel binding may derive a significant fraction of its voltage sensitivity through the coupling to channel gating. A similar shift in the activation voltage was noted for the effects of arachidonic acid (AA and DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time-dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5 channel opening is a prerequisite for the PUFA-channel interaction. Similar to the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply increased in the range of membrane potentials that coincided with the range of Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are also coupled to channel gating. Furthermore, AA regulates the inactivation process in other Kv channels, introducing a fast voltage-dependent inactivation in non-inactivating Kv channels. These results have been explained within the framework that AA closes voltage-dependent potassium channels by inducing conformational changes in the selectivity filter, suggesting that Kv channel gating is lipid dependent.

  1. Mobile radio channels

    CERN Document Server

    Pätzold, Matthias

    2011-01-01

    Providing a comprehensive overview of the modelling, analysis and simulation of mobile radio channels, this book gives a detailed understanding of fundamental issues and examines state-of-the-art techniques in mobile radio channel modelling. It analyses several mobile fading channels, including terrestrial and satellite flat-fading channels, various types of wideband channels and advanced MIMO channels, providing a fundamental understanding of the issues currently being investigated in the field. Important classes of narrowband, wideband, and space-time wireless channels are explored in deta

  2. Channel nut tool

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Marvin

    2016-01-12

    A method, system, and apparatus for installing channel nuts includes a shank, a handle formed on a first end of a shank, and an end piece with a threaded shaft configured to receive a channel nut formed on the second end of the shaft. The tool can be used to insert or remove a channel nut in a channel framing system and then removed from the channel nut.

  3. ATP-sensitive potassium channel opener protects PC12 Cells against ischemia/hypoxia-induced apoptosis through PI3K/Akt signaling pathway%ATP敏感性钾通道开放剂通过PI3K/Akt信号通路对缺血缺氧诱导PC12细胞凋亡发挥保护作用

    Institute of Scientific and Technical Information of China (English)

    张鸿; 贾春红; 赵丹阳; 王占强; 鲁阳; 王润玲

    2011-01-01

    目的 研究ATP敏感性钾通道(KATP)开放剂对缺血缺氧诱导PC12细胞凋亡及Akt蛋白和mRNA表达的影响.探讨KATP开放剂的保护作用机制.方法 取传代后3d Pc12细胞,分为对照组,缺血缺氧组,KATP通道开放剂组,KATP通道开放剂+阻断剂组.采用Annexin-v FITC/PI双染流式细胞分析仪检测凋亡率,应用免疫荧光染色和Western-blotting及RT-PCR方法检测P-Akt蛋白及mRNA表达水平.结果 缺血缺氧组细胞凋亡率高于对照组,24h达高峰,KATP开放剂组低于缺血缺氧组,KATP通道开放剂+阻断剂组高于KATP通道开放剂组(0.01).缺血缺氧后p-Akt蛋白及mRNA表达高于对照组,12h达高峰;KATP通道开放剂组高于缺血缺氧组,KATP通道开放剂+阻断剂组低于KATP通道开放剂组(P<0.01).结论 KATP开放剂可能通过激活PI3K/Akt信号通路,对缺血后PC12细胞凋亡发挥保护作用.%Objective To investigate the effect of ATP-sensitive potassium channel (KATP) openers on iscbemia-hypoxia-induced PC12 cell apoptosis and the expression of Akt mRNA and protein.Methods PC12 cells 3 days after passage were divided into control group, ischemia-hypoxia group, KATP channel opener group and KATP channel opener+blocker group.Apoptosis rate was detected using Annexin-v FITC/PI double staining flow cytometry, mRNA and protein levels of p-Akt were measured by immunofluorescent staining, Western-blotting and RT-PCR methods.Results The percentage of apoptotic PC12 cells is higher in iscbemia-hypoxia group than in control, peaked at 24h, lower in KATP channel opener group than in iscbemia-hypoxia 8roup, higher in KATP channel opener+blocker group than in KATP channel opener (P<0.01).The mRNA and protein levels of p-Akt were increased, reached peak at 12h, in ischemia-hypoxia group compared with control, higher in KATP channel opener group than in ischemia-hypoxia group, lower in KATP channel opener+blocker group than in KATP channel opener (P<0.01).Conclusion The

  4. Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund's Adjuvant Models of Pain.

    Directory of Open Access Journals (Sweden)

    David J Matson

    Full Text Available While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported "compound 52" aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund's adjuvant (CFA model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Aδ-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors.

  5. The Earliest Ion Channels

    Science.gov (United States)

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

    2009-12-01

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

  6. Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels.

    Science.gov (United States)

    Du, Yuzhe; Nomura, Yoshiko; Liu, Zhiqi; Huang, Zachary Y; Dong, Ke

    2009-12-01

    Tetrodotoxin (TTX) is a potent blocker of voltage-gated sodium channels, but not all sodium channels are equally sensitive to inhibition by TTX. The molecular basis of differential TTX sensitivity of mammalian sodium channels has been largely elucidated. In contrast, our knowledge about the sensitivity of invertebrate sodium channels to TTX remains poor, in part because of limited success in functional expression of these channels. In this study, we report the functional characterization in Xenopus oocytes of the first non-insect, invertebrate voltage-gated sodium channel from the varroa mite (Varroa destructor), an ecto-parasite of the honeybee. This arachnid sodium channel activates and inactivates rapidly with half-maximal activation at -18 mV and half-maximal fast inactivation at -29 mV. Interestingly, this arachnid channel showed surprising TTX resistance. TTX blocked this channel with an IC(50) of 1 microM. Subsequent site-directed mutagenesis revealed two residues, Thr-1674 and Ser-1967, in the pore-forming region of domains III and IV, respectively, which were responsible for the observed resistance to inhibition by TTX. Furthermore, sequence comparison and additional amino acid substitutions suggested that sequence polymorphisms at these two positions could be a widespread mechanism for modulating TTX sensitivity of sodium channels in diverse invertebrates. PMID:19828457

  7. Gramicidin Channels: Versatile Tools

    Science.gov (United States)

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

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

  8. Multi-Channel Retailing

    Directory of Open Access Journals (Sweden)

    Dirk Morschett, Dr.,

    2005-01-01

    Full Text Available Multi-channel retailing entails the parallel use by retailing enterprises of several sales channels. The results of an online buyer survey which has been conducted to investigate the impact of multi-channel retailing (i.e. the use of several retail channels by one retail company on consumer behaviour show that the frequently expressed concern that the application of multi-channel systems in retailing would be associated with cannibalization effects, has proven unfounded. Indeed, the appropriate degree of similarity, consistency, integration and agreement achieves the exact opposite. Different channels create different advantages for consumers. Therefore the total benefit an enterprise which has a multi-channel system can offer to its consumers is larger, the greater the number of available channels. The use of multi-channel systems is associated with additional purchases in the different channels. Such systems are thus superior to those offering only one sales channel to their customers. Furthermore, multi-channel systems with integrated channels are superior to those in which the channels are essentially autonomous and independent of one another. In integrated systems, consumers can achieve synergy effects in the use of sales-channel systems. Accordingly, when appropriately formulated, multi-channel systems in retailing impact positively on consumers. They use the channels more frequently, buy more from them and there is a positive customer-loyalty impact. Multi-channel systems are strategic options for achieving customer loyalty, exploiting customer potential and for winning new customers. They are thus well suited for approaching differing and varied target groups.

  9. Sensitivity analysis

    International Nuclear Information System (INIS)

    General remarks on sensitivity analysis, the study of changes in a model output produced by varying model inputs, are made first. Sampling methods are discussed, and three sensitivity measures: partial rank correlation, derivative or response surface, and partial variance are described. Some sample results for a 16-input, 13-output hydrodynamics model are given. Both agreement and disagreement were found among the sensitivity measures. 4 figures

  10. Radiation sensitizers

    International Nuclear Information System (INIS)

    The following classes of radiosensitizers are discussed: electron affinic compounds, pyrimidine analogs, and antibiotics. Metronidazole and nitroimidazole are discussed as examples of electron-affinic compounds. Studies on the enhancement ratio for sensitization of x-irradiated hamster cells showed that these drugs sensitize at concentrations much lower than the toxic concentrations. Criteria for a clinically useful hypoxic cell sensitizer are listed and mechanisms of electron-affinic sensitizers are discussed. The radiosensitizing effects of the pyrimidine analogs, BUDR, BCDR, IUDR, CUDR, and FUDR, are examined and the enhancement of radiation effects by the chemotherapeutic agent, 5-fluorouracil, is discussed. Other agents discussed are methotrexate, actinomycin D, bleomycin, and adriamycin

  11. Effects of vildagliptin relative to sulfonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: influence of age and treatment with/without metformin in the VIRTUE study

    Directory of Open Access Journals (Sweden)

    Hassoun AAK

    2016-07-01

    Full Text Available Ahmed AK Hassoun,1 Md Faruque Pathan,2 Rita C Medlej,3,4 Monira Alarouj,5 Inass Shaltout,6 Manoj S Chawla,7 Ditte Knap,8 Julius A Vaz9 1Dubai Diabetes Centre, Dubai, UAE; 2Department of Endocrinology, BIRDEM Hospital, Dhaka, Bangladesh; 3Department of Endocrinology, Hotel Dieu de France Hospital, 4Chronic Care Centre, Saint Joseph University, Beirut, Lebanon; 5Dasman Diabetes Institute, Dasman, Kuwait; 6Faculty of Medicine, Cairo University, Cairo, Egypt; 7Lina Diabetes Care Centre, Mumbai, India; 8Novartis Pharma AG, Basel, Switzerland; 9Novartis Healthcare Private Limited, Hyderabad, India Background: VIRTUE was a prospective, observational study assessing the effectiveness and safety of vildagliptin vs sulfonylureas (SUs (both as monotherapy and in combination with metformin in patients with type 2 diabetes mellitus who fasted during Ramadan. A post hoc analysis was carried out to assess the effect of treatment with/without metformin and age (<65 years or ≥65 years. Patients and methods: Patients were recruited from the Middle East and Asia. The primary end point was proportion of patients with one or more hypoglycemic event (HE during Ramadan. Secondary end points included change from baseline in glycated hemoglobin (HbA1c, body weight, and safety. Results: Overall, 684 patients received vildagliptin and 631 received SUs. Most patients received dual therapy with metformin (n=1,148 and were aged <65 years (n=1,189. A few patients experienced one or more HE with vildagliptin vs SU monotherapy (6.5% vs 14.5% and with vildagliptin + metformin vs SUs + metformin (5.3% vs 20.6%; the latter achieved statistical significance (P<0.001 in both age subgroups (<65 years: 5.5% vs 18.4%, P<0.001; ≥65 years: 2.8% vs 30.9%, P<0.001. Vildagliptin was associated with numerically greater HbA1c and body weight reductions vs SUs, regardless of the therapy type or age. A higher proportion of SU- vs vildagliptin-treated patients experienced adverse events

  12. Pyr3, a TRPC3 channel blocker, potentiates dexamethasone sensitivity and apoptosis in acute lymphoblastic leukemia cells by disturbing Ca(2+) signaling, mitochondrial membrane potential changes and reactive oxygen species production.

    Science.gov (United States)

    Abdoul-Azize, Souleymane; Buquet, Catherine; Vannier, Jean-Pierre; Dubus, Isabelle

    2016-08-01

    Dexamethasone (Dex) is used as a chemotherapeutic drug in the treatment of acute lymphoblastic leukemia (ALL) because of its capacity to induce apoptosis. However, some ALL patients acquire resistance to glucocorticoids (GC). Thus, it is important to explore new agents to overcome GC resistance. The aim of the present work was to assess the ability of Pyr3, a selective inhibitor of transient receptor potential canonical 3 (TRPC3), to sensitize human ALL cells to Dex. We show here, for the first time, that Pyr3 enhances Dex sensitivity through the distraction of Dex-mediated Ca(2+) signaling in ALL cells (in vitro) and primary blasts (ex vivo) associated with mitochondrial-mediated reactive oxygen species production in ALL cells. Pyr3 alone induced Ca(2+) signaling via only endoplasmic reticulum-released Ca(2+) and exerted inhibitory effect on store-operated Ca(2+) entry in dose-dependent manner in ALL cell lines. Pre-incubation of cells with Pyr3 significantly curtailed the thapsigargin- and Dex-evoked Ca(2+) signaling in ALL cell lines. Pyr3 synergistically potentiated Dex lethality, as shown by the induction of cell mortality, G2/M cell cycle arrest and apoptosis in ALL cell lines. Moreover, Pyr3 disrupted Dex-mediated Ca(2+) signaling and increased the sensitivity of Dex-induced cell death in primary blasts from ALL patients. Additional analysis showed that co-treatment with Dex and Pyr3 results in mitochondrial membrane potential depolarization and reactive oxygen species production in ALL cells. Together, Pyr3 exhibited potential therapeutic benefit in combination with Dex to inverse glucocorticoid resistance in human ALL and probably in other lymphoid malignancies. PMID:27179991

  13. Calcium channel blocker overdose

    Science.gov (United States)

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

  14. A point mutation (L1015F) of the voltage-sensitive sodium channel gene associated with lambda-cyhalothrin resistance in Apolygus lucorum (Meyer-Dür) population from the transgenic Bt cotton field of China.

    Science.gov (United States)

    Zhen, Congai; Gao, Xiwu

    2016-02-01

    In China, the green mirid bug, Apolygus lucorum (Meyer-Dür), has caused severe economic damage to many kinds of crops, especially the cotton and jujubes. Pyrethroid insecticides have been widely used for controlling this pest in the transgenic Bt cotton field. Five populations of A. lucorum collected from cotton crops at different locations in China were evaluated for lambda-cyhalothrin resistance. The results showed that only the population collected from Shandong Province exhibited 30-fold of resistance to lambda-cyhalothrin. Neither PBO nor DEF had obvious synergism when compared the synergistic ratio between SS and RR strain which was originated from the Shandong population. Besides, there were no statistically significant differences (p>0.05) in the carboxylesterase, glutathione S-transferase, or 7-ethoxycoumarin O-deethylase activities between the Shandong population and the laboratory susceptible strain (SS). The full-length sodium channel gene named AlVSSC encoding 2028 amino acids was obtained by RT-PCR and rapid amplification of cDNA ends (RACE). One single point mutation L1015F in the AlVSSC was detected only in the Shandong population. Our results revealed that the L1015F mutation associated with pyrethroid resistance was identified in A. lucorum populations in China. These results will be useful for the rational chemical control of A. lucorum in the transgenic Bt cotton field. PMID:26821662

  15. Dynamic channel allocation

    OpenAIRE

    Kaminsky, Andrew D.

    2003-01-01

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

  16. KV7 potassium channels

    DEFF Research Database (Denmark)

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

    2014-01-01

    Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

  17. Quantum Channels With Memory

    International Nuclear Information System (INIS)

    Quantum memory channels represent a very general, yet simple and comprehensible model for causal processes. As such they have attracted considerable research interest, mostly aimed on their transfer capabilities and structure properties. Most notably it was shown that memory channels can be implemented via physically naturally motivated collision models. We also define the concept of repeatable channels and show that only unital channels can be implemented repeat ably with pure memory channels. In the special case of qubit channels we also show that every unital qubit channel has a repeatable implementation. We also briefly explore the possibilities of stroboscopical simulation of channels and show that all random unitary channels can be stroboscopically simulated. Particularly in qubit case, all indivisible qubit channels are also random unitary, hence for qubit all indivisible channels can be stroboscopically simulated. Memory channels also naturally capture the framework of correlated experiments. We develop methods to gather and interpret data obtained in such setting and in detail examine the two qubit case. We also show that for control unitary interactions the measured data will never contradict a simple unitary evolution. Thus no memory effects can be spotted then. (author)

  18. Quantum Multiple Access Channel

    Institute of Scientific and Technical Information of China (English)

    侯广; 黄民信; 张永德

    2002-01-01

    We consider the transmission of classical information over a quantum channel by many senders, which is a generalization of the two-sender case. The channel capacity region is shown to be a convex hull bound by the yon Neumann entropy and the conditional yon Neumann entropies. The result allows a reasonable distribution of channel capacity over the senders.

  19. Desynched channels on IRCnet

    CERN Document Server

    Hansen, Michael

    2008-01-01

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

  20. Single- and Multi-Channel Modulation Detection in Cochlear Implant Users

    OpenAIRE

    John J Galvin; Oba, Sandy; Fu, Qian-Jie; Başkent, Deniz

    2014-01-01

    Single-channel modulation detection thresholds (MDTs) have been shown to predict cochlear implant (CI) users’ speech performance. However, little is known about multi-channel modulation sensitivity. Two factors likely contribute to multichannel modulation sensitivity: multichannel loudness summation and the across-site variance in single-channel MDTs. In this study, single- and multi-channel MDTs were measured in 9 CI users at relatively low and high presentation levels and modulation frequen...

  1. Prediction for the Herbicidal Activities of Sulfonylurea Compounds with QSAR-ANN%QSAR结合人工神经网络预测磺酰脲类除草活性

    Institute of Scientific and Technical Information of China (English)

    何琴; 郭丽丽

    2012-01-01

    采用误差反传前向人工神经网络模型研究了18种磺酰脲类化合物的结构与除草活性之间的关系.以18种磺酰脲类化合物的量子化学参数作为输入,除草活性作为输出,构建网络模型,取得了较好的预测结果.网络的自相容能力和交叉检验结果良好.该方法还可作为QSAR研究及对有机化合物其他性质进行预测的一种有效手段.%The relationship between the structures of 18 sulfonylurea compounds and their herbicidal activi- ties was studied by using the neural network based on the back propagation algorithm. The prediction results were examined by a self-consistency test and a cross-validation test. The self-consistency test and the cross-validation test obtained good results when using the quantum chemical parameters about structure as the inputs of the neural network and their herbicidal activities as the outputs. This method may be helpful for QSAR' s study and may he effective in predicting other important properties of organics.

  2. Capacities of Grassmann channels

    CERN Document Server

    Bradler, Kamil; Jauregui, Rocio

    2010-01-01

    A new class of quantum channels called Grassmann channels is introduced and their classical and quantum capacity is calculated. The channel class appears in a study of the two-mode squeezing operator constructed from operators satisfying the fermionic algebra. We compare Grassmann channels with the channels induced by the bosonic two-mode squeezing operator. Among other results, we challenge the relevance of calculating entanglement measures to assess or compare the ability of bosonic and fermionic states to send quantum information to uniformly accelerated frames.

  3. Allergic sensitization

    DEFF Research Database (Denmark)

    van Ree, Ronald; Hummelshøj, Lone; Plantinga, Maud; Poulsen, Lars K.; Swindle, Emily

    2014-01-01

    Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased...... play a dominant role, B cells switch to IgE-production, a process that is more effective at young age. IgE-producing plasma cells have been shown to be long-lived, hiding in the bone-marrow or inflammatory tissues where they cannot easily be targeted by therapeutic intervention. Allergic sensitization...

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

    OpenAIRE

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

    2008-01-01

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

  5. Gluten Sensitivity

    Science.gov (United States)

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  6. Vibrational Spectra of a Mechanosensitive Channel

    NARCIS (Netherlands)

    Liang, Chungwen; Louhivuori, Martti; Marrink, Siewert J.; Jansen, Thomas L.C.; Knoester, Jasper

    2013-01-01

    We report the simulated vibrational spectra of a mechanosensitive membrane channel in different gating states. Our results show that while linear absorption is insensitive to structural differences, linear dichroism and sum-frequency generation spectroscopies are sensitive to the orientation of the

  7. Radioecological sensitivity

    International Nuclear Information System (INIS)

    After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

  8. Securitization and the Balance Sheet Channel of Monetary Transmission

    OpenAIRE

    Uluc Aysun; Ralf Hepp

    2010-01-01

    This paper shows that the balance sheet channel of monetary transmission works mainly through U.S. bank holding companies that securitize their assets. This finding is different, in spirit, from the widely-found negative relationship between financial development and the strength of the lending channel of monetary transmission. Focusing on the balance sheet channel, and using bank-level observations, we find that securitized banks are more sensitive to borrowers' balance sheets and that monet...

  9. Computer simulation of proton channelling in silicon

    Indian Academy of Sciences (India)

    N K Deepak; K Rajasekharan; K Neelakandan

    2000-06-01

    The channelling of 3 MeV protons in the $\\langle 110\\rangle$ direction of silicon has been simulated using Vineyard model taking into account thermally vibrating nuclei and energy loss due to ionelectron interactions. A beam made up of constant energy particles but with spatial divergence has been simulated for the purpose. The values of the minimum scattering yield and half width of the channelling dip are shown to be depth sensitive and agree well with the measured values. The dependence of yield on the angle of incidence has been found to give information of all three types of channelling. The critical angles for the three types of channelling and wavelength of planar oscillations are consistent with the previous calculations.

  10. Inspection of Candu Nuclear Reactor Fuel Channels

    International Nuclear Information System (INIS)

    The Channel Inspection and Gauging Apparatus of Reactors (CIGAR) is a fully atomated, remotely operated inspection system designed to perform multi-channel, multi-task inspection of CANDU reactor fuel channels. Ultrasonic techniques are used for flaw detection, (with a sensitivity capable of detecting a 0.075 mm deep notch with a signal to noise ratio of 10 dB) and pressure tube wall thickness and diameter measurements. Eddy currrent systems are used to detect the presence of spacers between the coaxial pressure tube and calandria tube, as well as to measure their relative spacing. A servo-accelerometer is used to estimate the sag of the fuel channels. This advanced inspection system was commissioned and declared in service in September 1985. The paper describes the inspection systems themselves and discussed the results achieved to-date. (author)

  11. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Shlomo Shamai (Shitz

    2009-01-01

    Full Text Available This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom (s.d.o.f. are derived for the degraded case with one receiver. Schemes to achieve the s.d.o.f. for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable s.d.o.f. is given for the general case.

  12. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Kramer Gerhard

    2009-01-01

    Full Text Available Abstract This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom ( are derived for the degraded case with one receiver. Schemes to achieve the for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable is given for the general case.

  13. A proposal to search for neutrino oscillations with high sensitivity in the appearance channels νμ → νe and bar νμ → bar νe

    International Nuclear Information System (INIS)

    An experiment is proposed to search concurrently for νμ → νe and bar νμ → bar νe oscillations with high sensitivity at LAMPF. The detector consists of a tank with 200 tons of dilute liquid scintillator with 850 10-in. photomultiplier tubes mounted on the inside tank covering 28% of the surface. Both Cerenkov light and scintillation light will be detected. The tank will reside inside the existing E645 veto shield and the experiment will make use of the present A6 beam-stop neutrino source. After two years of data collection, 90% confidence level limits on bar νmu(νμ) → bar νe(νe) mixing strengths of 2.7(2.7) x 10-4 can be obtained for all Δm2 > 1 eV2. Similarly, for maximal mixing the 90% C.L. limits on Δm2 are 1.7(4.0) x 10-2. This experiment will, therefore, provide the world's best terrestrial limits on νμ → νe oscillations. Other physics to be obtained includes measurements of the charged current reactions νeC → e-N and νμC → μ-N, of the inelastic neutral current reaction νC → νC* (15.11- MeV γ), and a search for the rare decays π0 → ν bar ν and η → ν bar ν

  14. Channel capacity and error exponents of variable rate adaptive channel coding for Rayleigh fading channels

    OpenAIRE

    Lau, KN

    1999-01-01

    We have evaluated the information theoretical performance of variable rate adaptive channel coding for Rayleigh fading channels. The channel states are detected at the receiver and fed back to the transmitter by means of a noiseless feedback link. Based on the channel state informations, the transmitter can adjust the channel coding scheme accordingly. Coherent channel and arbitrary channel symbols with a fixed average transmitted power constraint are assumed. The channel capacity and the err...

  15. Quantum broadcast channels

    CERN Document Server

    Yard, J; Devetak, I; Yard, Jon; Hayden, Patrick; Devetak, Igor

    2006-01-01

    We analyze quantum broadcast channels, which are quantum channels with a single sender and many receivers. Focusing on channels with two receivers for simplicity, we generalize a number of results from the network Shannon theory literature which give the rates at which two senders can receive a common message, while a personalized one is sent to one of them. Our first collection of results applies to channels with a classical input and quantum outputs. The second class of theorems we prove concern sending a common classical message over a quantum broadcast channel, while sending quantum information to one of the receivers. The third group of results we obtain concern communication over an isometry, giving the rates at quantum information can be sent to one receiver, while common quantum information is sent to both, in the sense that tripartite GHZ entanglement is established. For each scenario, we provide an additivity proof for an appropriate class of channels, yielding single-letter characterizations of the...

  16. Open-channel hydraulics

    International Nuclear Information System (INIS)

    This text discusses the following: concepts of fluid flow; the momentum principle; computation of uniform flow; design of channels; and turbulent diffusion and dispersion in steady open-channel flow. Emphasis is concerned only with the flow of water in channels where the water is not transporting significant quantities of air or sediment. The text contains quite a few examples demonstrating the application of the presented principles

  17. Bank Liabilities Channel

    OpenAIRE

    Quadrini, Vincenzo

    2014-01-01

    The financial intermediation sector is important not only for channeling resources from agents in excess of funds to agents in need of funds (lending channel). By issuing liabilities it also creates financial assets held by other sectors of the economy for insurance purpose. When the intermediation sector creates less liabilities or their value falls, agents are less willing to engage in activities that are individually risky but desirable in aggregate (bank liabilities channel). The paper st...

  18. Bank Liabilities Channel

    OpenAIRE

    Vincenzo Quadrini

    2015-01-01

    The financial intermediation sector is important not only for channeling resources from agents in excess of funds to agents in need of funds (lending channel). By issuing liabilities it also creates financial assets held by other sectors of the economy for insurance purpose. When the intermediation sector creates less liabilities or their value falls, agents are less willing to engage in activities that are individually risky but desirable in aggregate (bank liabilities channel). The paper st...

  19. HIPPI and Fibre Channel

    International Nuclear Information System (INIS)

    The High-Performance Parallel Interface (HIPPI) and Fibre Channel are near-gigabit per second data communications interfaces being developed in ANSI standards Task Group X3T9.3. HIPPI is the current interface of choice in the high-end and supercomputer arena, and Fibre Channel is a follow-on effort. HIPPI came from a local area network background, and Fibre Channel came from a mainframe to peripheral interface background

  20. Symmetrization for redundant channels

    Science.gov (United States)

    Tulplue, Bhalchandra R. (Inventor); Collins, Robert E. (Inventor)

    1988-01-01

    A plurality of redundant channels in a system each contain a global image of all the configuration data bases in each of the channels in the system. Each global image is updated periodically from each of the other channels via cross channel data links. The global images of the local configuration data bases in each channel are separately symmetrized using a voting process to generate a system signal configuration data base which is not written into by any other routine and is available for indicating the status of the system within each channel. Equalization may be imposed on a suspect signal and a number of chances for that signal to heal itself are provided before excluding it from future votes. Reconfiguration is accomplished upon detecting a channel which is deemed invalid. A reset function is provided which permits an externally generated reset signal to permit a previously excluded channel to be reincluded within the system. The updating of global images and/or the symmetrization process may be accomplished at substantially the same time within a synchronized time frame common to all channels.

  1. Mechanosensitive ion channels

    Directory of Open Access Journals (Sweden)

    Ken Takahashi

    2016-01-01

    Full Text Available Cell surface receptors are involved in numerous important biological processes including embryogenesis, tissue differentiation, and cellular homeostasis. Among them, mechanosensitive ion channels play an essential role in cellular functions of every cell including neurons, cardiomyocytes, and osteocytes. Here, we discuss types, roles, structures, and biophysical factors that affect the functions of mechanosensitive ion channels.

  2. RFI channels, 2

    Science.gov (United States)

    Mceliece, R. J.

    1981-01-01

    The cutoff parameters for a class of channel models exhibiting burst noise behavior were calculated and the performance of interleaved coding strategies was evaluated. It is concluded that, provided the channel memory is large enough and is properly exploited, interleaved coding is nearly optimal.

  3. Topology optimization of Channel flow problems

    DEFF Research Database (Denmark)

    Gersborg-Hansen, Allan; Sigmund, Ole; Haber, R. B.

    2005-01-01

    ]. Further, the inclusion of inertia effects significantly alters the physics, enabling solutions of new classes of optimization problems, such as velocity--driven switches, that are not addressed by the earlier method. Specifically, we determine optimal layouts of channel flows that extremize a cost...... sensitivities. Our target application is optimal layout design of channels in fluid network systems. Using concepts borrowed from topology optimization of compliant mechanisms in solid mechanics, we introduce a method for the synthesis of fluidic components, such as switches, diodes, etc....

  4. Channelling versus inversion

    DEFF Research Database (Denmark)

    Gale, A.S.; Surlyk, Finn; Anderskouv, Kresten

    2013-01-01

    . Within this channel were smaller erosional structures (<10 m deep) that truncate originally horizontal bedding, are floored by hardgrounds, and locally have a basal fill of granular phosphorite. The entire channel system was progressively infilled by chalk, as demonstrated by the expanded succession of...... the lower Campanian Culver Chalk Formation. The beds of the channel fill are cut by small step faults, resulting from gravitational collapse. Complete burial had taken place by the base of the upper Campanian Portsdown Chalk Formation, which is of even thickness across the region. The structures are......Evidence from regional stratigraphical patterns in Santonian−Campanian chalk is used to infer the presence of a very broad channel system (5 km across) with a depth of at least 50 m, running NNW−SSE across the eastern Isle of Wight; only the western part of the channel wall and fill is exposed...

  5. Incompatibility breaking quantum channels

    International Nuclear Information System (INIS)

    A typical bipartite quantum protocol, such as EPR-steering, relies on two quantum features, entanglement of states and incompatibility of measurements. Noise can delete both of these quantum features. In this work we study the behavior of incompatibility under noisy quantum channels. The starting point for our investigation is the observation that compatible measurements cannot become incompatible by the action of any channel. We focus our attention to channels which completely destroy the incompatibility of various relevant sets of measurements. We call such channels incompatibility breaking, in analogy to the concept of entanglement breaking channels. This notion is relevant especially for the understanding of noise-robustness of the local measurement resources for steering. (paper)

  6. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

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

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that...... they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The...

  7. Athermalized channeled spectropolarimeter enhancement.

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Julia Craven; Way, Brandyn Michael; Mercier, Jeffrey Alan; Hunt, Jeffery P.

    2013-09-01

    Channeled spectropolarimetry can measure the complete polarization state of light as a function of wavelength. Typically, a channeled spectropolarimeter uses high order retarders made of uniaxial crystal to amplitude modulate the measured spectrum with the spectrally-dependent Stokes polarization information. A primary limitation of conventional channeled spectropolarimeters is related to the thermal variability of the retarders. Thermal variation often forces frequent system recalibration, particularly for field deployed systems. However, implementing thermally stable retarders, made of biaxial crystal, results in an athermal channeled spectropolarimeter that relieves the need for frequent recalibration. This report presents experimental results for an anthermalized channeled spectropolarimeter prototype produced using potassium titanyl phosphate. The results of this prototype are compared to the current thermal stabilization state of the art. Finally, the application of the technique to the thermal infrared is studied, and the athermalization concept is applied to an infrared imaging spectropolarimeter design.

  8. Coping with Asymmetric Channel Losses in CSMA/CA

    DEFF Research Database (Denmark)

    Paramanathan, Achuthan; Roetter, Daniel Enrique Lucani; Fitzek, Frank

    2013-01-01

    Inspired by the discrepancy between past theoretical analysis and real measurements for high-load scenarios for intersession network coding, we pinpoint and analyze the source of this discrepancy in wireless networks implementing a CSMA/CA medium access scheme. Our analysis shows that CSMA/CA is ......) confirm the sensitivity of the CSMA/CA scheme in real implementations, and (ii) shows that our adaptive protocol provides a simple, yet potent mechanism to cope with asymmetric channel losses and ultimately to enhance end-to-end throughput in high-load scenarios....... very sensitive to asymmetric channel losses caused by channel conditions. Leveraging this analysis, we present an adaptive channel priority protocol that copes with asymmetric channel losses while being compatible with CSMA/CA. We implement this protocol and perform real-life measurements that (i...

  9. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  10. Activation, Permeability, and Inhibition of Astrocytic and Neuronal Large Pore (Hemi)channels

    DEFF Research Database (Denmark)

    Hansen, Daniel Bloch; Ye, Zu-Cheng; Calloe, Kirstine;

    2014-01-01

    overlapping sensitivity to the inhibitors Brilliant Blue, gadolinium, and carbenoxolone. These results demonstrated isoform-specific characteristics among the large pore membrane channels; an open (hemi)channel is not a nonselective channel. With these isoform-specific properties in mind, we characterized the...

  11. Transmission channels through Na and Al atom wire

    DEFF Research Database (Denmark)

    Kobayashi, N.; Brandbyge, Mads; Tsukada, M.

    First-principles calculations of the transmission channels of single-atom-width Na and Al atom wires bridged between metallic jellium electrodes are presented. For the Na wire, a single channel contributes to the conduction with an almost full quantization value, 2e(2)/h. The conductance is...... insensitive to the geometrical change since the Fermi energy is located above the onset energy of the channel showing the quantization of conductance. On the other hand, for the Al wire. three channels contribute to the conduction. The Fermi energy is placed just at the onset of the second and the third...... channels, and the channel transmissions are very sensitive to the geometrical changes of the wires. (C) 1999 Elsevier Science B.V. All rights reserved....

  12. Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels.

    Science.gov (United States)

    Diaz-Franulic, Ignacio; Poblete, Horacio; Miño-Galaz, Germán; González, Carlos; Latorre, Ramón

    2016-07-01

    The molecular sensors that mediate temperature changes in living organisms are a large family of proteins known as thermosensitive transient receptor potential (TRP) ion channels. These membrane proteins are polymodal receptors that can be activated by cold or hot temperatures, depending on the channel subtype, voltage, and ligands. The stimuli sensors are allosterically coupled to a pore domain, increasing the probability of finding the channel in its ion conductive conformation. In this review we first discuss the allosteric coupling between the temperature and voltage sensor modules and the pore domain, and then discuss the thermodynamic foundations of thermo-TRP channel activation. We provide a structural overview of the molecular determinants of temperature sensing. We also posit an anisotropic thermal diffusion model that may explain the large temperature sensitivity of TRP channels. Additionally, we examine the effect of several ligands on TRP channel function and the evidence regarding their mechanisms of action. PMID:27297398

  13. High throughput electrophysiology: new perspectives for ion channel drug discovery

    DEFF Research Database (Denmark)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter;

    2003-01-01

    Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels. A...... introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery....... cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct...... characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion...

  14. Joint Synchronization and Channel Estimation for OFDM Systems

    Institute of Scientific and Technical Information of China (English)

    CAO Xue-hong

    2005-01-01

    OFDM systems are extremely sensitive to synchronization and channel estimation imperfections. Meanwhile the timing, frequency synchronization and channel estimation may affect each other. This paper investigates a new algorithm of joint estimation utilizing one training signal which can be used in preamble-based OFDM system, such as IEEE 802.11a WLAN system. The scheme includes two stages for performance improvement and simplicity. At the first stage, the coarse timing and frequency offset and channel response are obtained. The fine synchronization and channel estimation based on the coarse stage are obtained at the second stage. The simulation results show that the channel estimation of the proposed joint estimation is quite close to the case with known sync parameters and the BER of the system is quite close to the case with known channel response.

  15. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille

    2015-01-01

    The channel choice branch of e-government studies citizens’ and businesses’ choice of channels for interacting with government, and how government organizations can integrate channels and migrate users towards the most cost-efficient channels. In spite of the valuable contributions offered no sys...... systematic overview exist of channel choice. We present a literature review of channel choice studies in government to citizen context identifying authors, countries, methods, concepts, units of analysis, and theories, and offer suggestionsfor future studies....

  16. Inhibition of T cell proliferation by selective block of Ca(2+)-activated K(+) channels

    DEFF Research Database (Denmark)

    Jensen, B S; Odum, Niels; Jorgensen, N K;

    1999-01-01

    established. The recent cloning of the Ca(2+)-activated, intermediate-conductance K(+) channel (IK channel) has enabled a detailed investigation of the role of this highly Ca(2+)-sensitive K(+) channel in the calcium signaling and subsequent regulation of T cell proliferation. The role IK channels play in T...... cell activation and proliferation has been investigated by using various blockers of IK channels. The Ca(2+)-activated K(+) current in human T cells is shown by the whole-cell voltage-clamp technique to be highly sensitive to clotrimazole, charybdotoxin, and nitrendipine, but not to ketoconazole...... inhibited after block of IK channels by clotrimazole. Clotrimazole and cyclosporin A act synergistically to inhibit T cell proliferation, which confirms that block of IK channels affects the process downstream from T cell receptor activation. We suggest that IK channels constitute another target for immune...

  17. Channelized Streams in Iowa

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — This draft dataset consists of all ditches or channelized pieces of stream that could be identified using three input datasets; namely the1:24,000 National...

  18. TRP channels: an overview

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd

    2005-01-01

    plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.......The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family, the...... TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading to a...

  19. 28-Channel rotary transformer

    Science.gov (United States)

    Mclyman, W. T.

    1981-01-01

    Transformer transmits power and digital data across rotating interface. Array has many parallel data channels, each with potential l megabaud data rate. Ferrite-cored transformers are spaced along rotor; airgap between them reduces crosstalk.

  20. Side-Channel Oscilloscope

    CERN Document Server

    Chaudhuri, Sumanta

    2011-01-01

    Side-Channel Analysis used for codebreaking could be used constructively as a probing tool for internal gates in integrated circuits. This paper outlines basic methods and mathematics for that purpose

  1. CHANNEL ESTIMATION TECHNIQUE

    DEFF Research Database (Denmark)

    2015-01-01

    A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over the communicat......A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over the...... communication channel. The method further includes determining a sequence of second coefficient estimates of the communication channel based on a decomposition of the first coefficient estimates in a dictionary matrix and a sparse vector of the second coefficient estimates, the dictionary matrix including...

  2. TRP channels in disease.

    Science.gov (United States)

    Jordt, S E; Ehrlich, B E

    2007-01-01

    The transient receptor potential (TRP) channels are a large family of proteins with six main subfamilies termed the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin) groups. The sheer number of different TRPs with distinct functions supports the statement that these channels are involved in a wide range of processes ranging from sensing of thermal and chemical signals to reloading intracellular stores after responding to an extracellular stimulus. Mutations in TRPs are linked to pathophysiology and specific diseases. An understanding of the role of TRPs in normal physiology is just beginning; the progression from mutations in TRPs to pathophysiology and disease will follow. In this review, we focus on two distinct aspects of TRP channel physiology, the role of TRP channels in intracellular Ca2+ homeostasis, and their role in the transduction of painful stimuli in sensory neurons. PMID:18193640

  3. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  4. Sensing with Ion Channels

    CERN Document Server

    Martinac, Boris

    2008-01-01

    All living cells are able to detect and translate environmental stimuli into biologically meaningful signals. Sensations of touch, hearing, sight, taste, smell or pain are essential to the survival of all living organisms. The importance of sensory input for the existence of life thus justifies the effort made to understand its molecular origins. Sensing with Ion Channels focuses on ion channels as key molecules enabling biological systems to sense and process the physical and chemical stimuli that act upon cells in their living environment. Its aim is to serve as a reference to ion channel specialists and as a source of new information to non specialists who want to learn about the structural and functional diversity of ion channels and their role in sensory physiology.

  5. Chloride channels in stroke

    Institute of Scientific and Technical Information of China (English)

    Ya-ping ZHANG; Hao ZHANG; Dayue Darrel DUAN

    2013-01-01

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

  6. Identification Via Quantum Channels

    OpenAIRE

    Winter, Andreas

    2012-01-01

    We review the development of the quantum version of Ahlswede and Dueck's theory of identification via channels. As is often the case in quantum probability, there is not just one but several quantizations: we know at least two different concepts of identification of classical information via quantum channels, and three different identification capacities for quantum information. In the present summary overview we concentrate on conceptual points and open problems, referring the reader to the ...

  7. Quantum Feedback Channels

    OpenAIRE

    Bowen, Garry

    2002-01-01

    In Shannon information theory the capacity of a memoryless communication channel cannot be increased by the use of feedback. In quantum information theory the no-cloning theorem means that noiseless copying and feedback of quantum information cannot be achieved. In this paper, quantum feedback is defined as the unlimited use of a noiseless quantum channel from receiver to sender. Given such quantum feedback, it is shown to provide no increase in the entanglement--assisted capacities of a memo...

  8. Physics of Ion Channels

    OpenAIRE

    Kuyucak, Serdar; Bastug, Turgut

    2003-01-01

    We review the basic physics involved in transport of ions across membrane channels in cells. Electrochemical forces that control the diffusion of ions are discussed both from microscopic and macroscopic perspectives. A case is made for use of Brownian dynamics as the minimal phenomenological model that provides a bridge between experiments and more fundamental theoretical approaches. Application of Brownian and molecular dynamics methods to channels with known molecular structures is discussed.

  9. Chaos in quantum channels

    OpenAIRE

    Hosur, Pavan; Qi, Xiao-Liang; Roberts, Daniel; Yoshida, Beni(Institute for Quantum Information & Matter and Walter Burke Institute for Theoretical Physics, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, U.S.A.)

    2016-01-01

    We study chaos and scrambling in unitary channels by considering their entanglement properties as states. Using out-of-time-order correlation functions to diagnose chaos, we characterize the ability of a channel to process quantum information. We show that the generic decay of such correlators implies that any input subsystem must have near vanishing mutual information with almost all partitions of the output. Additionally, we propose the negativity of the tripartite information of the channe...

  10. Hair-bundle friction from transduction channels' gating forces

    Science.gov (United States)

    Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

    2015-12-01

    Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. We have shown recently that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle and thus provide a major source of damping [2]. We develop here a physical theory of passive hair-bundle mechanics that explains the origin of channel friction. We show that channel friction can be understood quantitatively by coupling the dynamics of the conformational change associated with channel gating to tip-link tension. As a result, varying channel properties affects friction, with faster channels producing smaller friction. The analysis emphasizes the dual role of transduction channels' gating forces, which affect both hair-bundle stiffness and drag. Friction originating from gating of ion channels is a general concept that is relevant to all mechanosensitive channels.

  11. Course on Ionic Channels

    CERN Document Server

    1986-01-01

    This book is based on a series of lectures for a course on ionic channels held in Santiago, Chile, on November 17-20, 1984. It is intended as a tutorial guide on the properties, function, modulation, and reconstitution of ionic channels, and it should be accessible to graduate students taking their first steps in this field. In the presentation there has been a deliberate emphasis on the spe­ cific methodologies used toward the understanding of the workings and function of channels. Thus, in the first section, we learn to "read" single­ channel records: how to interpret them in the theoretical frame of kinetic models, which information can be extracted from gating currents in re­ lation to the closing and opening processes, and how ion transport through an open channel can be explained in terms of fluctuating energy barriers. The importance of assessing unequivocally the origin and purity of mem­ brane preparations and the use of membrane vesicles and optical tech­ niques in the stUGY of ionic channels a...

  12. The Correlation Conversion Property of Quantum Channels

    OpenAIRE

    Gyongyosi, Laszlo

    2013-01-01

    Transmission of quantum entanglement will play a crucial role in future networks and long-distance quantum communications. Quantum Key Distribution, the working mechanism of quantum repeaters and the various quantum communication protocols are all based on quantum entanglement. On the other hand, quantum entanglement is extremely fragile and sensitive to the noise of the communication channel over which it has been transmitted. To share entanglement between distant points, high fidelity quant...

  13. Improved Coupled Channels and R-Matrix Models: Predictions to 1 Gev

    OpenAIRE

    LaFrance, P.; Lomon, E. L.; Aw, M.

    1993-01-01

    The $NN$ scattering near inelastic threshold is sensitive to the long-range diagonal interaction in the produced isobar channel. Earlier models included meson exchange potentials in the $NN$ sector and connecting that sector to isobar channels, as well as an $R$-matrix description of short-range quark effects. Including the diagonal pion exchange contributions in the $N\\Delta$ channels coupled to the very inelastic ${}^1D_2$ and ${}^3F_3$ $NN$ channels substantially improves those phase param...

  14. Gluten Sensitivity.

    Science.gov (United States)

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  15. 玉米中9种磺酰脲类除草剂的超高效液相色谱-串联质谱法同时测定%Simultaneous Determination of 9 Sulfonylurea Herbicides in Corn Using Solid-phase Extraction and Ultra Performance Liquid Chromatography with Electrospray Ionization Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    丁菲; 李范珠; 储晓刚; 张峰; 凌云; 孙利; 杨敏莉; 吕泉福; 许成保

    2011-01-01

    采用超高效液相色谱-串联四极杆质谱(UPLC-MS/MS),在多反应监测(MRM )模式下建立了玉米中9种磺酰脲类除草剂残留的定性定量分析方法.样品浸泡后采用甲醇-丙酮(体积比1:1)提取、浓缩,经C18固相萃取柱净化处理.采用UPLC-ESI MS/MS方法测定,外标法定量.9种磺酰脲类除草剂在0.05~2.0 mg·L-1范围内具有较好的线性关系,相关系数均大于0.99,该方法的检出限(LOD,S/N=3)为0.001~0.005 mg·L-1,定量下限(LOQ,S/N=10)为0.062~0.080 mg·kg-1.在1LOQ、2LOQ和5LOQ 3个加标水平下的回收率为60%~85%,相对标准偏差(RSDs)均在10%以内.该方法简便快速,满足玉米中9种磺酰脲类除草剂的快速检测要求.%A new method based on solid phase extraction and ultra performance liquid chromatography -tandem mass spectrometry( UPLC -ESI MS/MS) was developed for the determination of 9 sulfonylurea herbicides(metoxuron, foramsulfuron, cinosulfuron, methabenthiazuron, prosulfuron, linuron, ethoxysulfuron, chloroxuron and cyclosulfamuron) in corn. The corn sample was soared in water, and then extracted with methanol - acetone ( 1: 1, by volume). The extract was cleaned up by C18 solid phase extraction cartridge. The eluent was evaporated to near dryness under a stream of nitregen gas, and redissolved by methanol. The identification and detection of target compounds were achieved under multiple reactions monitoring (MRM) mode with positive electrospray ionization (ESI). 9 sulfonylurea herbcides were quantified by external standard method. The calibration curves of 9 sulfonylurea herbicides were linear in the range of 0. 05 - 2.0 mg · L-1 with correlation coefficients more than O. 99. The limits of detection ( LOD, S/N = 3 ) and the limits of quantitation ( LOQ, S/N= 10) were in the range of 0. 001 -0. 005 mg · L-1 and 0. 062 -0. 080 mg · kg-1, respectively. 1LOQ,2LOQ and 5LOQ were chosen as the three spiked levels of recovery for the method. The recoveries of 9

  16. Morphodynamics of Floodplain Chute Channels

    Science.gov (United States)

    David, S. R.; Edmonds, D. A.

    2015-12-01

    Floodplain chute channel formation is a key process that can enable rivers to transition from single-thread to multi-thread planform geometries. Floodplain chute channels are usually incisional channels connecting topographic lows across point bars and in the floodplain. Surprisingly, it is still not clear what conditions promote chute channel formation and what governs their morphodynamic behavior. Towards this end we have initiated an empirical and theoretical study of floodplain chute channels in Indiana, USA. Using elevation models and satellite imagery we mapped 3064 km2 of floodplain in Indiana, and find that 37.3% of mapped floodplains in Indiana have extensive chute channel networks. These chute channel networks consist of two types of channel segments: meander cutoffs of the main channel and chute channels linking the cutoffs together. To understand how these chute channels link meander cutoffs together and eventually create floodplain channel networks we use Delft3D to explore floodplain morphodynamics. Our first modeling experiment starts from a generic floodplain prepopulated with meander cutoffs to test under what conditions chute channels form.We find that chute channel formation is optimized at an intermediate flood discharge. If the flood discharge is too large the meander cutoffs erosively diffuse, whereas if the floodwave is too small the cutoffs fill with sediment. A moderately sized floodwave reworks the sediment surrounding the topographic lows, enhancing the development of floodplain chute channels. Our second modeling experiments explore how floodplain chute channels evolve on the West Fork of the White River, Indiana, USA. We find that the floodplain chute channels are capable of conveying the entire 10 yr floodwave (Q=1330m3/s) leaving the inter-channel areas dry. Moreover, the chute channels can incise into the floodplain while the margins of channels are aggrading, creating levees. Our results suggest that under the right conditions

  17. Micro-channel plates and vacuum detectors

    Energy Technology Data Exchange (ETDEWEB)

    Gys, T., E-mail: Thierry.Gys@cern.ch

    2015-07-01

    A micro-channel plate is an array of miniature electron multipliers that are each acting as a continuous dynode chain. The compact channel structure results in high spatial and time resolutions and robustness to magnetic fields. Micro-channel plates have been originally developed for night vision applications and integrated as an amplification element in image intensifiers. These devices show single-photon sensitivity with very low noise and have been used as such for scintillating fiber tracker readout in high-energy physics experiments. Given their very short transit time spread, micro-channel plate photomultiplier tubes are also being used in time-of-flight and particle identification detectors. The present paper will cover the history of the micro-channel plate development, basic features, and some of their applications. Emphasis will be put on various new manufacturing processes that have been developed over the last few years, and that result in a significant improvement in terms of efficiency, noise, and lifetime performance.

  18. A Direction Sensitive Fast Neutron Monitor

    International Nuclear Information System (INIS)

    A direction sensitive fast neutron monitor is described and its properties are discussed in some detail. The counter is a modification of the standard long counter of the Hanson and McKibben type. Directional sensitivity is obtained by increasing the shielding of the counter and providing it with a 70 cm long collimator channel. The behaviour of this long counter monitor is compared with that of a standard long counter when both are used in neutron experiments

  19. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

    In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area. PMID:17059356

  20. MEMS in microfluidic channels.

    Energy Technology Data Exchange (ETDEWEB)

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.

    2004-03-01

    Microelectromechanical systems (MEMS) comprise a new class of devices that include various forms of sensors and actuators. Recent studies have shown that microscale cantilever structures are able to detect a wide range of chemicals, biomolecules or even single bacterial cells. In this approach, cantilever deflection replaces optical fluorescence detection thereby eliminating complex chemical tagging steps that are difficult to achieve with chip-based architectures. A key challenge to utilizing this new detection scheme is the incorporation of functionalized MEMS structures within complex microfluidic channel architectures. The ability to accomplish this integration is currently limited by the processing approaches used to seal lids on pre-etched microfluidic channels. This report describes Sandia's first construction of MEMS instrumented microfluidic chips, which were fabricated by combining our leading capabilities in MEMS processing with our low-temperature photolithographic method for fabricating microfluidic channels. We have explored in-situ cantilevers and other similar passive MEMS devices as a new approach to directly sense fluid transport, and have successfully monitored local flow rates and viscosities within microfluidic channels. Actuated MEMS structures have also been incorporated into microfluidic channels, and the electrical requirements for actuation in liquids have been quantified with an elegant theory. Electrostatic actuation in water has been accomplished, and a novel technique for monitoring local electrical conductivities has been invented.

  1. Dequantization Via Quantum Channels

    Science.gov (United States)

    Andersson, Andreas

    2016-08-01

    For a unital completely positive map {Φ} ("quantum channel") governing the time propagation of a quantum system, the Stinespring representation gives an enlarged system evolving unitarily. We argue that the Stinespring representations of each power {Φ^m} of the single map together encode the structure of the original quantum channel and provide an interaction-dependent model for the bath. The same bath model gives a "classical limit" at infinite time {mto∞} in the form of a noncommutative "manifold" determined by the channel. In this way, a simplified analysis of the system can be performed by making the large-m approximation. These constructions are based on a noncommutative generalization of Berezin quantization. The latter is shown to involve very fundamental aspects of quantum-information theory, which are thereby put in a completely new light.

  2. Chaos in quantum channels

    CERN Document Server

    Hosur, Pavan; Roberts, Daniel A; Yoshida, Beni

    2015-01-01

    We study chaos and scrambling in unitary channels by considering their entanglement properties as states. Using out-of-time-order correlation functions to diagnose chaos, we characterize the ability of a channel to process quantum information. We show that the generic decay of such correlators implies that any input subsystem must have near vanishing mutual information with almost all partitions of the output. Additionally, we propose the negativity of the tripartite information of the channel as a general diagnostic of scrambling. This measures the delocalization of information and is closely related to the decay of out-of-time-order correlators. We back up our results with numerics in two non-integrable models and analytic results in a perfect tensor network model of chaotic time evolution. These results show that the butterfly effect in quantum systems implies the information-theoretic definition of scrambling.

  3. Trp channels and itch.

    Science.gov (United States)

    Sun, Shuohao; Dong, Xinzhong

    2016-05-01

    Itch is a unique sensation associated with the scratch reflex. Although the scratch reflex plays a protective role in daily life by removing irritants, chronic itch remains a clinical challenge. Despite urgent clinical need, itch has received relatively little research attention and its mechanisms have remained poorly understood until recently. The goal of the present review is to summarize our current understanding of the mechanisms of acute as well as chronic itch and classifications of the primary itch populations in relationship to transient receptor potential (Trp) channels, which play pivotal roles in multiple somatosensations. The convergent involvement of Trp channels in diverse itch signaling pathways suggests that Trp channels may serve as promising targets for chronic itch treatments. PMID:26385480

  4. QKD Quantum Channel Authentication

    CERN Document Server

    Kosloski, J T

    2006-01-01

    Several simple yet secure protocols to authenticate the quantum channel of various QKD schemes, by coupling the photon sender's knowledge of a shared secret and the QBER Bob observes, are presented. It is shown that Alice can encrypt certain portions of the information needed for the QKD protocols, using a sequence whose security is based on computational-complexity, without compromising all of the sequence's entropy. It is then shown that after a Man-in-the-Middle attack on the quantum and classical channels, there is still enough entropy left in the sequence for Bob to detect the presence of Eve by monitoring the QBER. Finally, it is shown that the principles presented can be implemented to authenticate the quantum channel associated with any type of QKD scheme, and they can also be used for Alice to authenticate Bob.

  5. The neutron channeling phenomenon.

    Science.gov (United States)

    Khanouchi, A; Sabir, A; Boulkheir, M; Ichaoui, R; Ghassoun, J; Jehouani, A

    1997-01-01

    Shields, used for protection against radiation, are often pierced with vacuum channels for passing cables and other instruments for measurements. The neutron transmission through these shields is an unavoidable phenomenon. In this work we study and discuss the effect of channels on neutron transmission through shields. We consider an infinite homogeneous slab, with a fixed thickness (20 lambda, with lambda the mean free path of the neutron in the slab), which contains a vacuum channel. This slab is irradiated with an infinite source of neutrons on the left side and on the other side (right side) many detectors with windows equal to 2 lambda are placed in order to evaluate the neutron transmission probabilities (Khanouchi, A., Aboubekr, A., Ghassoun, J. and Jehouani, A. (1994) Rencontre Nationale des Jeunes Chercheurs en Physique. Casa Blanca Maroc; Khanouchi, A., Sabir, A., Ghassoun, J. and Jehouani, A. (1995) Premier Congré International des Intéractions Rayonnements Matière. Eljadida Maroc). The neutron history within the slab is simulated by the Monte Carlo method (Booth, T. E. and Hendricks, J. S. (1994) Nuclear Technology 5) and using the exponential biasing technique in order to improve the Monte Carlo calculation (Levitt, L. B. (1968) Nuclear Science and Engineering 31, 500-504; Jehouani, A., Ghassoun, J. and Aboubker, A. (1994) In Proceedings of the 6th International Symposium on Radiation Physics, Rabat, Morocco). Then different geometries of the vacuum channel have been studied. For each geometry we have determined the detector response and calculated the neutron transmission probability for different detector positions. This neutron transmission probability presents a peak for the detectors placed in front of the vacuum channel. This study allowed us to clearly identify the neutron channeling phenomenon. One application of our study is to detect vacuum defects in materials. PMID:9463884

  6. Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels

    OpenAIRE

    Yao, Jing; Liu, Beiying; Qin, Feng

    2011-01-01

    The molecular basis of the thermal sensitivity of temperature-sensitive channels appears to arise from a specific protein domain rather than integration of global thermal effects. Using systematic chimeric analysis, we show that the N-terminal region that connects ankyrin repeats to the first transmembrane segment is crucial for temperature sensing in heat-activated vanilloid receptor channels. Changing this region both transformed temperature-insensitive isoforms into temperature-sensitive c...

  7. BLIND CHANNEL ESTIMATION IN DELAY DIVERSITY FOR FREQUENCY SELECTIVE CHANNELS

    Institute of Scientific and Technical Information of China (English)

    Zhao Zheng; Jia Ying; Yin Qinye

    2003-01-01

    Delay diversity is an effective transmit diversity technique to combat adverse ef-fects of fading. Thus far, previous work in delay diversity assumed that perfect estimates ofcurrent channel fading conditions are available at the receiver and training symbols are requiredto estimate the channel from the transmitter to the receiver. However, increasing the number ofthe antennas increases the required training interval and reduces the available time within whichdata may be transmitted. Learning the channel coefficients becomes increasingly difficult for thefrequency selective channels. In this paper, with the subspace method and the delay character ofdelay diversity, a channel estimation method is proposed, which does not use training symbols. Itaddresses the transmit diversity for a frequency selective channel from a single carrier perspectivein the form of a simple equivalent fiat fading model. Monte Carlo simulations give the perfor-mance of channel estimation and the performance comparison of our channel-estimation-baseddetector with decision feedback equalization, which uses the perfect channel information.

  8. Fuel channel refilling

    International Nuclear Information System (INIS)

    Analysis of existing data on fuel channel refilling is presented. The analysis focuses on the data obtained using the Stern Laboratories Cold Water Injection Test (CWIT) Facility. The two-fluid model thermal-hydraulics computer code CATHENA is also used to simulate experimental results on fuel channel refilling from both the CWIT and RD-14 facilities. Conclusions related to single and double break tests, including the effect of non-condensible gases, are presented. A set of recommendations is given for further analysis and separate effect experiments. (67 figs., 5 tabs., 24 refs.)

  9. Ion channels modulating mouse dendritic cell functions.

    Science.gov (United States)

    Matzner, Nicole; Zemtsova, Irina M; Nguyen, Thi Xuan; Duszenko, Michael; Shumilina, Ekaterina; Lang, Florian

    2008-11-15

    Ca(2+)-mediated signal transduction pathways play a central regulatory role in dendritic cell (DC) responses to diverse Ags. However, the mechanisms leading to increased [Ca(2+)](i) upon DC activation remained ill-defined. In the present study, LPS treatment (100 ng/ml) of mouse DCs resulted in a rapid increase in [Ca(2+)](i), which was due to Ca(2+) release from intracellular stores and influx of extracellular Ca(2+) across the cell membrane. In whole-cell voltage-clamp experiments, LPS-induced currents exhibited properties similar to the currents through the Ca(2+) release-activated Ca(2+) channels (CRAC). These currents were highly selective for Ca(2+), exhibited a prominent inward rectification of the current-voltage relationship, and showed an anomalous mole fraction and a fast Ca(2+)-dependent inactivation. In addition, the LPS-induced increase of [Ca(2+)](i) was sensitive to margatoxin and ICAGEN-4, both inhibitors of voltage-gated K(+) (Kv) channels Kv1.3 and Kv1.5, respectively. MHC class II expression, CCL21-dependent migration, and TNF-alpha and IL-6 production decreased, whereas phagocytic capacity increased in LPS-stimulated DCs in the presence of both Kv channel inhibitors as well as the I(CRAC) inhibitor SKF-96365. Taken together, our results demonstrate that Ca(2+) influx in LPS-stimulated DCs occurs via Ca(2+) release-activated Ca(2+) channels, is sensitive to Kv channel activity, and is in turn critically important for DC maturation and functions. PMID:18981098

  10. Tetrodotoxin-resistant sodium channels in neuropathic pain

    OpenAIRE

    Fjell Hjelmström, Jenny

    2000-01-01

    Injury to the peripheral nervous system can cause neuropathic pain. Abnormal sodium channel activity has been implicated as a source of ectopic firing and changes in nociceptive threshold following nerve injury. Primary sensory neurons exhibit at least two types of sodium currents: rapidly inactivating tetrodotoxin-sensitive (TTX-S) and slowly inactivating TTX-resistant (TTX-R) sodium currents. Two TTX-R sodium channels that are expressed in primary sensory neurons have been...

  11. Integration of transient receptor potential canonical channels with lipids

    OpenAIRE

    Beech, D. J.

    2012-01-01

    Transient receptor potential canonical (TRPC) channels are the canonical (C) subset of the TRP proteins, which are widely expressed in mammalian cells. They are thought to be primarily involved in determining calcium and sodium entry and have wide-ranging functions that include regulation of cell proliferation, motility and contraction. The channels are modulated by a multiplicity of factors, putatively existing as integrators in the plasma membrane. This review considers the sensitivities of...

  12. Experimental entanglement restoration on entanglement-breaking channels

    OpenAIRE

    SCIARRINO, Fabio; Nagali, Eleonora; De Martini, Francesco; Gavenda, Miroslav; Filip, Radim

    2008-01-01

    Quantum entanglement, a fundamental property ensuring security of key distribution and efficiency of quantum computing, is extremely sensitive to decoherence. Different procedures have been developed in order to recover entanglement after propagation over a noisy channel. However, besides a certain amount of noise, entanglement is completely lost. In this case the channel is called entanglement breaking and any multi-copy distillation methods cannot help to restore even a bit of entanglement....

  13. Lipid ion channels and the role of proteins

    CERN Document Server

    Mosgaard, Lars D

    2013-01-01

    Synthetic lipid membranes in the absence of proteins can display quantized conduction events for ions that are virtually indistinguishable from those of protein channel. By indistinguishable we mean that one cannot decide based on the current trace alone whether conductance events originate from a membrane, which does or does not contain channel proteins. Additional evidence is required to distinguish between the two cases, and it is not always certain that such evidence can be provided. The phenomenological similarities are striking and span a wide range of phenomena: The typical conductances are of equal order and both lifetime distributions and current histograms are similar. One finds conduction bursts, flickering, and multistep-conductance. Lipid channels can be gated by voltage, and can be blocked by drugs. They respond to changes in lateral membrane tension and temperature. Thus, they behave like voltage-gated, temperature-gated and mechano-sensitive protein channels, or like receptors. Lipid channels ...

  14. The human role in changing river channels

    Science.gov (United States)

    Gregory, K. J.

    2006-09-01

    , because of complex response and contingency. The ways in which changes in cross-section relate to reach and network changes are less clear, despite investigations showing the distribution of changes along segmented channels. When considering the human role in relation to changing river channels, at least five challenges persist. First, because prediction of the nature and amount of likely change at a particular location is not certain, and because the contrasting responses of humid and arid systems needs to be considered, modelling is required to reduce uncertainty, as was first emphasised by Burkham [Burkham, D.E., 1981. Uncertainties resulting from changes in river form. American Society Civil Engineers Proceedings, Journal Hydraulics Division 107, 593-610.]. Second, feedback effects incorporated within the relationship between changes at channel, reach and network scales can have considerable implications, especially because changes now evident may have occurred, or have been initiated, under different environmental conditions. Third, consideration of global climate change is imperative when considering channel sensitivity and responses to threshold conditions. Fourth, channel design involving geomorphology should now be an integral part of restoration procedures. This requires, fifthly, greater awareness of different cultures as a basis for understanding constraints imposed by legislative frameworks. Better understanding of the ways in which the perception of the human role in changing river channels varies with culture as well as varying over time should enhance application of design for river channel landscapes.

  15. Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia.

    Science.gov (United States)

    Conforti, L; Millhorn, D E

    1997-07-15

    1. Electrophysiological (single-channel patch clamp) and molecular biological experiments (reverse transcriptase-polymerase chain reaction) were performed to attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12) cells. 2. Four types of K+ channels were recorded in PC12 cells: a small-conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and two K+ channels with similar conductance (20 pS). These last two channels differed in their time-dependent inactivation: one was a slow-inactivating channel, while the other belonged to the family of fast transient K+ channels. 3. The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to hypoxia produced a 50% reduction in channel activity (number of active channels in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow-inactivating K+ channel that is upregulated by hypoxia. This channel appears to belong to the Shaker subfamily of voltage-gated K+ channels. PMID:9263911

  16. Cell volume and membrane stretch independently control K+ channel activity

    DEFF Research Database (Denmark)

    Bomholtz, Sofia Hammami; Willumsen, Niels J; Olsen, Hervør L; Morera, Francisco J; Latorre, Ramón; Klaerke, Dan A

    . To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK...... current increases with increasing negative hydrostatic pressure (suction) applied to the pipette. Thus, at a pipette pressure of -5.0 +/- 0.1 mmHg the increase amounted to 381 +/- 146% (mean +/- S.E.M., n = 6, P < 0.025). In contrast, in oocytes expressing the strongly volume-sensitive KCNQ1 channel, the...

  17. All channels open

    NARCIS (Netherlands)

    Frank Huysmans; Jos de Haan

    2010-01-01

    Original title: Alle kanalen staan open. The rapid changes taking place in the media landscape in the Netherlands - characterised by digitisation and convergence of media technologies - raise the question of how the Dutch are dealing with the many new opportunities that have opened up. All channels

  18. Chemistry in Microfluidic Channels

    Science.gov (United States)

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

    2011-01-01

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

  19. Generalized tolerance sensitivity and DEA metric sensitivity

    OpenAIRE

    Luka Neralić; Richard E. Wendell

    2015-01-01

    This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  20. A New Covert Channel over Cellular Voice Channel in Smartphones

    OpenAIRE

    Aloraini, Bushra; Johnson, Daryl; Stackpole, Bill; Mishra, Sumita

    2015-01-01

    Investigating network covert channels in smartphones has become increasingly important as smartphones have recently replaced the role of traditional computers. Smartphones are subject to traditional computer network covert channel techniques. Smartphones also introduce new sets of covert channel techniques as they add more capabilities and multiple network connections. This work presents a new network covert channel in smartphones. The research studies the ability to leak information from the...

  1. Improving Virtual Channel Discrimination in a Multi-Channel Context

    OpenAIRE

    Srinivasan, Arthi G.; Shannon, Robert V.; Landsberger, David M.

    2012-01-01

    Improving spectral resolution in cochlear implants is key to improving performance in difficult listening conditions (e.g. speech in noise, music, etc.). Current focusing might reduce channel interaction, thereby increasing spectral resolution. Previous studies have shown that combining current steering and current focusing reduces spread of excitation and improves virtual channel discrimination in a single-channel context. It is unclear whether the single-channel benefits from current focusi...

  2. Consumer channel choice: integrating electronic and conventional service channels

    OpenAIRE

    van Dijk, Geke; Laing, Angus; Minocha, Shailey

    2006-01-01

    When investigating the consumer experience in multi-channel retail service environments, one of the more themes is the decision-making process on channel choice. Most of the literature on channel choice addresses it as a single decision during the consumption process. The study reported in this paper describes how consumers often make several channel choices throughout the consumption process. The described study is an ethnographically inspired, in-depth case study that examined online and of...

  3. Functional reconstitution of skeletal muscle Ca2+ channels: Separation of regulatory and channel components

    International Nuclear Information System (INIS)

    Regulatory properties of a partially purified Ca2+-channel preparation from isolated rabbit skeletal muscle triads were examined in proteoliposomes. By selective reconstitution of protein fractions obtained by wheat germ lectin and ion-exchange chromatography, a separation of Ca2+-channel activity (fraction C) from regulatory component(s) (fraction R) responsible for verapamil sensitivity was achieved. Reconstitution of fraction C alone yielded vesicles that exhibited channel-mediated 45Ca2+ uptake that could be directly inhibited by coreconstitution of G0 in the presence of guanosine 5'-[γ-thio]triphosphate. Coreconstitution of fractions C and R yielded vesicles in which the sensitivity of 45Ca2+ uptake to verapamil was restored. Fraction C included a 180-kDa protein that was phosphorylated by cAMP-dependent protein kinase (PK-A) but not by PK-P and a 145-kDa protein that was not phosphorylated by either kinase. Fraction R contained proteins that did not absorb to wheat germ lectin and included 165-kDa and 55-kDa proteins that were phosphorylated by PK-P but not by PK-A. These results suggest a complex model for Ca2+-channel regulation in skeletal muscle involving a number of distinct, separable protein components

  4. Assessing geomorphic sensitivity in relation to river capacity for adjustment

    Science.gov (United States)

    Reid, H. E.; Brierley, G. J.

    2015-12-01

    River sensitivity describes the nature and rate of channel adjustments. An approach to analysis of geomorphic river sensitivity outlined in this paper relates potential sensitivity based on the expected capacity of adjustment for a river type to the recent history of channel adjustment. This approach was trialled to assess low, moderate and high geomorphic sensitivity for four different types of river (10 reaches in total) along the Lower Tongariro River, North Island, New Zealand. Building upon the River Styles framework, river types were differentiated based upon valley setting (width and confinement), channel planform, geomorphic unit assemblages and bed material size. From this, the behavioural regime and potential for adjustment (type and extent) were determined. Historical maps and aerial photographs were geo-rectified and the channel planform digitised to assess channel adjustments for each reach from 1928 to 2007. Floodplain width controlled by terraces, exerted a strong influence upon reach scale sensitivity for the partly-confined, wandering, cobble-bed river. Although forced boundaries occur infrequently, the width of the active channel zone is constrained. An unconfined braided river reach directly downstream of the terrace-confined section was the most geomorphically sensitive reach. The channel in this reach adjusted recurrently to sediment inputs that were flushed through more confined, better connected upstream reaches. A meandering, sand-bed river in downstream reaches has exhibited negligible rates of channel migration. However, channel narrowing in this reach and the associated delta indicate that the system is approaching a threshold condition, beyond which channel avulsion is likely to occur. As this would trigger more rapid migration, this reach is considered to be more geomorphically sensitive than analysis of its low migration rate alone would indicate. This demonstrates how sensitivity is fashioned both by the behavioural regime of a reach

  5. Creation and dynamical co-evolution of electron and ion channel transport barriers

    International Nuclear Information System (INIS)

    A wide variety of magnetic confinement devices have found transitions to an enhanced confinement regime. Simple dynamical models have been able to capture much of the dynamics of these barriers however an open question has been the disconnected nature of the electron thermal transport channel sometimes observed in the presence of a standard ('ion channel' barrier. By adding to simple barrier model an evolution equation for electron fluctuations we can investigate the interaction between the formation of the standard ion channel barrier and the somewhat less common electron channel barrier. Barrier formation in the electron channel is even more sensitive to the alignment of the various gradients making up the sheared radial electric field than the ion barrier is. Electron channel heat transport is found to significantly increase after the formation of the ion channel barrier but before the electron channel barrier is formed. This increased transport is important in the barrier evolution. (author)

  6. Creation and dynamical co-evolution of electron and ion channel transport barriers

    International Nuclear Information System (INIS)

    A wide variety of magnetic confinement devices have found transitions to an enhanced confinement regime. Simple dynamical models have been able to capture much of the dynamics of these barriers however an open question has been the disconnected nature of the electron thermal transport channel sometimes observed in the presence of a standard ('ion channel') barrier. By adding to simple barrier model an evolution equation for electron fluctuations we can investigate the interaction between the formation of the standard ion channel barrier and the somewhat less common electron channel barrier. Barrier formation in the electron channel is even more sensitive to the alignment of the various gradients making up the sheared radial electric field then the ion barrier is. Electron channel heat transport is found to significantly increase after the formation of the ion channel barrier but before the electron channel barrier is formed. This increased transport is important in the barrier evolution. (author)

  7. Quantum communication under channel uncertainty

    International Nuclear Information System (INIS)

    This work contains results concerning transmission of entanglement and subspaces as well as generation of entanglement in the limit of arbitrary many uses of compound- and arbitrarily varying quantum channels (CQC, AVQC). In both cases, the channel is described by a set of memoryless channels. Only forward communication between one sender and one receiver is allowed. A code is said to be ''good'' only, if it is ''good'' for every channel out of the set. Both settings describe a scenario, in which sender and receiver have only limited channel knowledge. For different amounts of information about the channel available to sender or receiver, coding theorems are proven for the CQC. For the AVQC, both deterministic and randomised coding schemes are considered. Coding theorems are proven, as well as a quantum analogue of the Ahlswede-dichotomy. The connection to zero-error capacities of stationary memoryless quantum channels is investigated. The notion of symmetrisability is defined and used for both classes of channels.

  8. The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes

    OpenAIRE

    Suessbrich, H; Schönherr, R; Heinemann, S H; Attali, B.; Lang, F.; Busch, A.E.

    1997-01-01

    The antipsychotic drug haloperidol can induce a marked QT prolongation and polymorphic ventricular arrhythmias. In this study, we expressed several cloned cardiac K+ channels, including the human ether-a-go-go related gene (HERG) channels, in Xenopus oocytes and tested them for their haloperidol sensitivity.Haloperidol had only little effects on the delayed rectifier channels Kv1.1, Kv1.2, Kv1.5 and IsK, the A-type channel Kv1.4 and the inward rectifier channel Kir2.1 (inhibition

  9. 新除草剂甲硫嘧磺隆的水解动力学与机理研究%Kinetics and Mechanisms of Novel Sulfonylurea Herbicide Methiopyrisulfuron Hydrolysis

    Institute of Scientific and Technical Information of China (English)

    欧晓明; 步海燕; 裴晖; 唐德秀; 黄明智; 付启明; 雷满香; 喻快

    2013-01-01

    甲硫嘧磺隆,试验代号为HNPC-C9908,化学名称为2-(4-甲氧基-6-甲硫基嘧啶-2-基)氨基甲酰基氨基磺酰基苯甲酸甲酯,是我国具有自主知识产权的新型磺酰脲类除草剂品种,主要用于防除麦类作物田各种阔叶杂草和一些禾本科杂草,且对作物安全.采用HPLC和LC-MS等手段研究了甲硫嘧磺隆在水体中的水解动力学及机理,结果表明,甲硫嘧磺隆的水解遵循一级动力学反应,且受溶液pH、温度、粘土矿物和表面活性剂等因素的影响.在pH1~10时,甲硫嘧磺隆的水解速率先随pH值增加而缓慢降低,至pH值为7时达到最低,此后呈显著增加的趋势,至pH10达到最大值.甲硫嘧磺隆在pH5、7、9缓冲溶液中的水解速率随温度升高而明显加快,其水解主要是由反应的活化熵所驱动的.池塘水和稻田水中的微生物对甲硫嘧磺隆的降解无明显影响.表面活性剂0205、EL-40和NP-20对甲硫嘧磺隆的水解速率均有不同程度的影响,其中0205对甲硫嘧磺隆水解表现出明显的促进作用,EL-40对甲硫嘧磺隆的水解有一定的促进作用,而NP-20对甲硫嘧磺隆的水解表现出一定的抑制作用.膨润土对甲硫嘧磺隆的水解具有明显影响,甲硫嘧磺隆在含粘土矿物的水溶液中的水解速率明显低于重蒸水中.甲硫嘧磺隆的水解途径主要涉及到脲桥断裂,其主要降解产物为2-氨基-4-甲氧基-6-甲硫基嘧啶、2-氨基-4-甲氧基-6-甲基亚砜嘧啶,2-氨磺酰基苯甲酸甲酯和2-亚磺酸基苯甲酸甲酯.%Methiopyrisulfuron (test code:HNPC-C9908),chemical name:methyl 2-(4-methoxy-6-methylthio-pyrimidin-2-yl) carbamoylsulfamoyl benzoate,is a novel sulfonylurea herbicide researched and developed by Hunan Research Institute of Chemical Industry,which has been used for weed control in wheat.Hydrolysis kinetics and mechanisms of methiopyrisulfuron in the aqueous solutions were studied in the laboratory using HPLC and LC

  10. Muon cooling channels

    International Nuclear Information System (INIS)

    Parameters of muon cooling channels are discussed that achieve cooling of a muon beam from initial to final emittances in all three degrees of freedom in a given length. Published theories of ionisation cooling yield equilibrium emittances from multiple scattering and energy straggling, and partition numbers. Limits are obtained on the amplitude functions in all three degrees of freedom. Parameters of wedge-shaped absorbers and partition numbers are derived for simultaneous longitudinal and transverse cooling. Limits on length and material of absorbers, and dispersion at the wedge-shaped absorbers are obtained. Parameters are presented for the RF system, e.g. peak voltage, frequency, and stable phase angle. The properties of the magnetic lattice which satisfies the conditions imposed by the longitudinal dynamics are studied. The consequences of changes in the assumed performance of the cooling channel on its parameters are discussed

  11. Boosted Higgs channels

    International Nuclear Information System (INIS)

    In gluon fusion both a modified top Yukawa and new colored particles can alter the cross section. However in a large set of composite Higgs models and in realistic areas of the MSSM parameter space, these two effects can conspire and hide new physics in a Standard Model-like inclusive cross section. We first show that it is possible to break this degeneracy in the couplings by demanding a boosted Higgs recoiling against a high-pT jet. Subsequently we propose an analysis based on this idea in the H→2l+ET channels. This measurement allows an alternative determination of the important top Yukawa besides the t anti tH channel.

  12. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  13. Geysering in boiling channels

    Energy Technology Data Exchange (ETDEWEB)

    Aritomi, Masanori; Takemoto, Takatoshi [Tokyo Institute of Technology, Tokyo (Japan); Chiang, Jing-Hsien [Japan NUS Corp. Ltd., Toyko (Japan)] [and others

    1995-09-01

    A concept of natural circulation BWRs such as the SBWR has been proposed and seems to be promising in that the primary cooling system can be simplified. The authors have been investigating thermo-hydraulic instabilities which may appear during the start-up in natural circulation BWRs. In our previous works, geysering was investigated in parallel boiling channels for both natural and forced circulations, and its driving mechanism and the effect of system pressure on geysering occurrence were made clear. In this paper, geysering is investigated in a vertical column and a U-shaped vertical column heated in the lower parts. It is clarified from the results that the occurrence mechanism of geysering and the dependence of system pressure on geysering occurrence coincide between parallel boiling channels in circulation systems and vertical columns in non-circulation systems.

  14. K-ATP channel expression and pharmacological in vivo and in vitro studies of the K-ATP channel blocker PNU-37883A in rat middle meningeal arteries

    DEFF Research Database (Denmark)

    Ploug, K.B.; Boni, L.J.; Baun, M.;

    2008-01-01

    Background and purpose: Dilatation of cerebral and dural arteries causes a throbbing, migraine-like pain, indicating that these structures are involved in migraine. Clinical trials suggest that adenosine 5'-triphosphate-sensitive K+ (K-ATP) channel opening may cause migraine by dilatating...... intracranial arteries, including the middle meningeal artery (MMA). We studied the K-ATP channel expression profile in rat MMA and examined the potential inhibitory effects of the K-ATP channel blocker PNU-37883A on K-ATP channel opener-induced relaxation of the rat MMA, using the three K-ATP channel openers...... levcromakalim, pinacidil and P-1075. Experimental approach: mRNA and protein expression of K-ATP channel subunits in the rat MMA were studied by quantitative real-time PCR and western blotting, respectively. The in vivo and in vitro effects of the K-ATP channel drugs on rat MMA were studied in the genuine...

  15. Readout of two-dimensional position-sensitive neutron detector

    International Nuclear Information System (INIS)

    The design of readout electronics based on multi-channel charge-sensitive pre-amplifier application specific integrated circuit (ASIC) are introduced, which is to be applied in the two-dimensional position-sensitive thermal neutron detector based on thick gas electron multiplier (THGEM). The ASIC is VA64TA2, a bare chip with 64 channels of charge sensitive pre-amplifier-shaper circuits and every channel with the function of trigger. These chips are packaged with the ceramic pin grid array package CPGA 257, with 257 pints. The readout electronics is controlled by FPGA. The results of single-channel linear performance test and electronics noise performance test are given. The results show that the readout system has good linearity with the dynamic range of 16 fC, and low electronics noise of 1.2 × 10-2 fC. (authors)

  16. Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2.

    Science.gov (United States)

    Liu, Beiying; Qin, Feng

    2016-04-12

    Thermal TRP channels mediate temperature transduction and pain sensation. The vanilloid receptor TRPV2 is involved in detection of noxious heat in a subpopulation of high-threshold nociceptors. It also plays a critical role in development of thermal hyperalgesia, but the underlying mechanism remains uncertain. Here we analyze the heat sensitivity of the TRPV2 channel. Heat activation of the channel exhibits strong use dependence. Prior heat activation can profoundly alter its subsequent temperature responsiveness, causing decreases in both temperature activation threshold and slope sensitivity of temperature dependence while accelerating activation time courses. Notably, heat and agonist activations differ in cross use-dependence. Prior heat stimulation can dramatically sensitize agonist responses, but not conversely. Quantitative analyses indicate that the use dependence in heat sensitivity is pertinent to the process of temperature sensing by the channel. The use dependence of TRPV2 reveals that the channel can have a dynamic temperature sensitivity. The temperature sensing structures within the channel have multiple conformations and the temperature activation pathway is separate from the agonist activation pathway. Physiologically, the use dependence of TRPV2 confers nociceptors with a hypersensitivity to heat and thus provides a mechanism for peripheral thermal hyperalgesia. PMID:27074678

  17. Ion Channels, Natural Nanovalves

    OpenAIRE

    Eisenberg, Bob

    2012-01-01

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

  18. Photon Channelling in Foams

    OpenAIRE

    Schmiedeberg, Michael; Miri, MirFaez; Stark, Holger

    2005-01-01

    Experiments by Gittings, Bandyopadhyay, and Durian [Europhys. Lett.\\ \\textbf{65}, 414 (2004)] demonstrate that light possesses a higher probability to propagate in the liquid phase of a foam due to total reflection. The authors term this observation photon channelling which we investigate in this article theoretically. We first derive a central relation in the work of Gitting {\\em et al.} without any free parameters. It links the photon's path-length fraction $f$ in the liquid phase to the li...

  19. Proton channel models

    OpenAIRE

    Pupo, Amaury; Baez-Nieto, David; Martínez, Agustín; Latorre, Ramón; González, Carlos

    2014-01-01

    Voltage-gated proton channels are integral membrane proteins with the capacity to permeate elementary particles in a voltage and pH dependent manner. These proteins have been found in several species and are involved in various physiological processes. Although their primary topology is known, lack of details regarding their structures in the open conformation has limited analyses toward a deeper understanding of the molecular determinants of their function and regulation. Consequently, the f...

  20. Convolutional Channel Features

    OpenAIRE

    Yang, Bin; Yan, Junjie; Lei, Zhen; Li, Stan Z.

    2015-01-01

    Deep learning methods are powerful tools but often suffer from expensive computation and limited flexibility. An alternative is to combine light-weight models with deep representations. As successful cases exist in several visual problems, a unified framework is absent. In this paper, we revisit two widely used approaches in computer vision, namely filtered channel features and Convolutional Neural Networks (CNN), and absorb merits from both by proposing an integrated method called Convolutio...

  1. Radar channel balancing with commutation

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-02-01

    When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

  2. 高效液相色谱-串联质谱法测定动物源性食品中20种磺酰脲类除草剂残留%Determination of 20 Sulfonylurea Herbicides Residues in Animal Origin Foods by High Performance Liquid Chromatography-Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    刘锦霞; 张莹; 丁利; 刘晓霞; 黄志强; 陈波; 王利兵

    2011-01-01

    建立了动物源性食品中20种磺酰脲类除草剂多残留的分析方法.样品经乙腈均质提取2次,经Waters Oasis HLB固相萃取小柱净化后,在高效液相色谱-电喷雾串联质谱仪多反应监测模式下测定,采用质谱法定性,外标法定量.除草剂采用Eclipse AAA色谱柱,以甲醇和0.1%乙酸溶液为流动相,在梯度洗脱条件下可以得到很好地分离.在6种动物源性食品中分别添加低、中、高3个浓度水平的20种磺酰脲类除草剂,平均回收率为66.07%~112.07%;相对标准偏差为0.7%~19.4%;20种磺酰脲药物在6种动物源性食品中的检出限为0.5~2.5 μg/kg.本方法操作简单、净化效果好、灵敏度高,可应用于动物源性食品中2.种磺酰脲类药物的实际检测分析.%A method was developed for the determination of 20 sulfonylurea herbicides residues in animal origin foods by high performance liquid chromatographytandem mass spectrometry (LC-MS/MS). Sulfonylurea herbicides were extracted with acetonitrile and the extract was cleaned up by Waters OasisHLB solid phase extraction column. Qualitation of the analytes was achieved with multiple reaction monitoring (MRM) and external standard method was used for quantification. The chromatography separation was achieved in gradient mode, on a Eclipse AAA column using methanol and 0.1 % acetic acid aqueous solution. The mean recoveries of 20 sulfonylurea herbicides varied from 66.1% to 112. 1% in pork, fish, chicken, egg, pork liver and milk samples at three spiked levels. The relative standard deviations (RSDs) were in the range of 0. 7% - 19.4%. Depending on each herbicide pesticide, the limits of detection were in the range of 0.5-2.5 μg/kg. The proposed method was successfully applied to the determination of sulfonylurea herbicides residues in animal-derived foods.

  3. The alpha channeling effect

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, N. J.

    2015-12-10

    Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

  4. DMT of weighted Parallel Channels: Application to Broadcast Channel

    CERN Document Server

    Mroueh, Lina; Othman, Ghaya Rekaya-Ben; Belfiore, Jean-Claude

    2008-01-01

    In a broadcast channel with random packet arrival and transmission queues, the stability of the system is achieved by maximizing a weighted sum rate capacity with suitable weights that depend on the queue size. The weighted sum rate capacity using Dirty Paper Coding (DPC) and Zero Forcing (ZF) is asymptotically equivalent to the weighted sum capacity over parallel single-channels. In this paper, we study the Diversity Multiplexing Tradeoff (DMT) of the fading broadcast channel under a fixed weighted sum rate capacity constraint. The DMT of both identical and different parallel weighted MISO channels is first derived. Finally, we deduce the DMT of a broadcast channel using DPC and ZF precoders.

  5. Cell volume changes regulate slick (Slo2.1, but not slack (Slo2.2 K+ channels.

    Directory of Open Access Journals (Sweden)

    Maria A Tejada

    Full Text Available Slick (Slo2.1 and Slack (Slo2.2 channels belong to the family of high-conductance K+ channels and have been found widely distributed in the CNS. Both channels are activated by Na+ and Cl- and, in addition, Slick channels are regulated by ATP. Therefore, the roles of these channels in regulation of cell excitability as well as ion transport processes, like regulation of cell volume, have been hypothesized. It is the aim of this work to evaluate the sensitivity of Slick and Slack channels to small, fast changes in cell volume and to explore mechanisms, which may explain this type of regulation. For this purpose Slick and Slack channels were co-expressed with aquaporin 1 in Xenopus laevis oocytes and cell volume changes of around 5% were induced by exposure to hypotonic or hypertonic media. Whole-cell currents were measured by two electrode voltage clamp. Our results show that Slick channels are dramatically stimulated (196% of control by cell swelling and inhibited (57% of control by a decrease in cell volume. In contrast, Slack channels are totally insensitive to similar cell volume changes. The mechanism underlining the strong volume sensitivity of Slick channels needs to be further explored, however we were able to show that it does not depend on an intact actin cytoskeleton, ATP release or vesicle fusion. In conclusion, Slick channels, in contrast to the similar Slack channels, are the only high-conductance K+ channels strongly sensitive to small changes in cell volume.

  6. On partially entanglement breaking channels

    OpenAIRE

    Chruściński, Dariusz; Kossakowski, Andrzej

    2005-01-01

    Using well known duality between quantum maps and states of composite systems we introduce the notion of Schmidt number of a quantum channel. It enables one to define classes of quantum channels which partially break quantum entanglement. These classes generalize the well known class of entanglement breaking channels.

  7. MIMO Wiretap Channels with Arbitrarily Varying Eavesdropper Channel States

    CERN Document Server

    He, Xiang

    2010-01-01

    In this work, a class of information theoretic secrecy problems is addressed where the eavesdropper channel states are completely unknown to the legitimate parties. In particular, MIMO wiretap channel models are considered where the channel of the eavesdropper is arbitrarily varying over time. Assuming that the number of antennas of the eavesdropper is limited, the secrecy rate of the MIMO wiretap channel in the sense of strong secrecy is derived, and shown to match with the converse in secure degrees of freedom. It is proved that there exists a universal coding scheme that secures the confidential message against any sequence of channel states experienced by the eavesdropper. This yields the conclusion that secure communication is possible regardless of the location or channel states of (potentially infinite number of) eavesdroppers. Additionally, it is observed that, the present setting renders the secrecy capacity problems for multi-terminal wiretap-type channels more tractable as compared the case with fu...

  8. Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users.

    Directory of Open Access Journals (Sweden)

    John J Galvin

    Full Text Available Previous cochlear implant (CI studies have shown that single-channel amplitude modulation frequency discrimination (AMFD can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined.In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure ("which interval is different?". For the reference stimulus, the reference AM (100 Hz was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz was delivered to 1 of 3 channels, and the reference AM (100 Hz delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction.Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2-4 Hz, there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes.Besides the increased loudness, the present results also suggest that multiple

  9. Joint Source-Channel Coding over a Fading Multiple Access Channel with Partial Channel State Information

    CERN Document Server

    Rajesh, R

    2009-01-01

    In this paper we address the problem of transmission of correlated sources over a fast fading multiple access channel (MAC) with partial channel state information available at both the encoders and the decoder. We provide sufficient conditions for transmission with given distortions. Next these conditions are specialized to a Gaussian MAC (GMAC). We provide the optimal power allocation strategy and compare the strategy with various levels of channel state information. Keywords: Fading MAC, Power allocation, Partial channel state information, Correlated sources.

  10. Adaptive evolution of the vertebrate skeletal muscle sodium channel

    Directory of Open Access Journals (Sweden)

    Jian Lu

    2011-01-01

    Full Text Available Tetrodotoxin (TTX is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Na v. The skeletal muscle Na v (Na v1.4 channels in most pufferfish species and certain North American garter snakes are resistant to TTX, whereas in most mammals they are TTX-sensitive. It still remains unclear as to whether the difference in this sensitivity among the various vertebrate species can be associated with adaptive evolution. In this study, we investigated the adaptive evolution of the vertebrate Na v1.4 channels. By means of the CODEML program of the PAML 4.3 package, the lineages of both garter snakes and pufferfishes were denoted to be under positive selection. The positively selected sites identified in the p-loop regions indicated their involvement in Na v1.4 channel sensitivity to TTX. Most of these sites were located in the intracellular regions of the Na v1.4 channel, thereby implying the possible association of these regions with the regulation of voltage-sensor movement.

  11. 外源性硫化氢及KATP通道对大鼠慢性应激结肠高动力的调节%Effect of exogenous H2 S and ATP-sensitive potassium channels on colonic hypermotility in a rat model of chronic stress

    Institute of Scientific and Technical Information of China (English)

    刘颖; 全晓静; 夏虹; 罗和生

    2015-01-01

    目的:研究外源性硫化氢( hydrogen sulfide,H2 S)及ATP敏感性钾通道( ATP-sensitive potassium channels,KATP)在慢性应激结肠高动力中的作用。方法:制作慢性避水应激(water avoidance stress,WAS)和假避水应激( sham water avoidance stress,SWAS)大鼠模型,观察2组大鼠结肠肌条的收缩活性以及硫氢化钠( NaHS)和格列本脲预处理后对2组大鼠结肠肌条收缩影响并计算NaHS的半数抑制浓度( half maximal inhibitory concentration, IC50),使用免疫荧光及Western blotting法观察KATP通道各亚基在结肠中的分布及表达。结果:WAS组结肠肌条收缩活性明显高于SWAS组;NaHS浓度依赖性抑制2组大鼠纵行肌( longitudinal muscle,LM)和环形肌( circular mus-cle,CM)的收缩;WAS组LM和CM的NaHS IC50分别为0.2033 mmol/L和0.1438 mmol/L,均明显低于SWAS组(P<0.01);格列本脲明显增加2组大鼠肌条NaHS IC50(P<0.01);Kir6.1、Kir6.2和SUR-2B在2组大鼠结肠固有肌细胞膜均有分布;WAS组(去除黏膜及黏膜下层后)Kir6.1和SUR2B蛋白表达高于SWAS组(P<0.01)。结论:H2 S外源性供体NaHS对慢性应激结肠高动力具有潜在的治疗作用。 KATP通道亚基Kir6.1/SUR2B表达增加可能是慢性应激结肠动力紊乱的一种适应性反应。%[ ABSTRACT] AIM:To investigate the potential role of exogenous hydrogen sulfide ( H2 S) and ATP-sensitive po-tassium ( KATP ) channels in chronic stress-induced colonic hypermotility.METHODS:Male Wistar rats were divided into water avoidance stress ( WAS) group and sham WAS ( SWAS) group.Organ bath recordings were used to test the contrac-tile activity of colonic strips.The effects of H2 S donor NaHS and pretreatment with glibenclamide on the contractions of co-lonic smooth muscle were studied and the IC50 of NaHS was calculated.The localization and expression of the subunits of KATP channels were determined by

  12. Activation of purified calcium channels by stoichiometric protein phosphorylation

    International Nuclear Information System (INIS)

    Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of 45Ca2+ uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of 45Ca2+ uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd2+, Ni2+, and Mg2+. The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels

  13. Marketing Strategy of Pay Channels

    Directory of Open Access Journals (Sweden)

    Fanbin Zeng

    2012-12-01

    Full Text Available Pay Channels not only need to improve the quality of their content, but also need to focus on marketing strategy. To develop Pay Channels in China, we not only need to improve the content of the TV programs, but also need to focus on the marketing strategy. So far, we have two main approaches of marketing in China. One is being operated by integration platform; the other is by the Channel itself. Pay channels are not developed so well in China. In this paper, we are going to discuss on the existing problems of pay channels in China and try to find out the effective ways to carry out marketing strategy of pay channels. To improve the situation of pay channels in China, we might take the following measures: 1 Pursue different kinds of sales approach. 2 Provide Free Preview to Expand the Scope of Publicity. 3 Lower charging fee. 4 Establish a perfect customer service system.

  14. Wiretap Channel with Action-Dependent Channel State Information

    Directory of Open Access Journals (Sweden)

    Bin Dai

    2013-01-01

    Full Text Available In this paper, we investigate the model of wiretap channel with action-dependent channel state information. Given the message to be communicated, the transmitter chooses an action sequence that affects the formation of the channel states, and then generates the channel input sequence based on the state sequence and the message. The main channel and the wiretap channel are two discrete memoryless channels (DMCs, and they are connected with the legitimate receiver and the wiretapper, respectively. Moreover, the transition probability distribution of the main channel depends on the channel state. Measuring wiretapper’s uncertainty about the message by equivocation, inner and outer bounds on the capacity-equivocation region are provided both for the case where the channel inputs are allowed to depend non-causally on the state sequence and the case where they are restricted to causal dependence. Furthermore, the secrecy capacities for both cases are bounded, which provide the best transmission rate with perfect secrecy. The result is further explained via a binary example.

  15. Lipid-dependent effects of halothane on gramicidin channel kinetics: A new role for lipid packing stress

    OpenAIRE

    Weinrich, Michael; Rostovtseva, Tatiana K.; Bezrukov, Sergey M.

    2009-01-01

    We find that the sensitivity of gramicidin A channels to the anesthetic halothane is highly lipid dependent. Specifically, exposure of membranes made of lamellar DOPC to halothane in concentrations close to clinically relevant reduces channel life-times by an order of magnitude. At the same time, gramicidin channels in membranes of non-lamellar DOPE are little, if at all, affected by halothane. We attribute this difference in channel behavior to a difference in the stress of lipid packing int...

  16. Inhibitory effects of SKF96365 on the activities of K(+) channels in mouse small intestinal smooth muscle cells.

    Science.gov (United States)

    Tanahashi, Yasuyuki; Wang, Ban; Murakami, Yuri; Unno, Toshihiro; Matsuyama, Hayato; Nagano, Hiroshi; Komori, Seiichi

    2016-03-01

    In order to investigate the effects of SKF96365 (SKF), which is a non-selective cationic channel blocker, on K(+) channel currents, we recorded currents through ATP sensitive K(+) (IKATP), voltage-gated K(+) (IKv) and Ca(2+) activated K(+) channels (IBK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 µM) reversibly abolished IKATP that was induced by cromakalim (10 µM), which is a selective ATP sensitive K(+) channel opener. These inhibitory effects were induced in a concentration-dependent and voltage-independent manner. The 50% inhibitory concentration (IC50) was 0.85 µM, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 µM ≈ the IC50 value in IKATP suppression) reversibly inhibited the IKv that was induced by repetitive depolarizing pulses from -80 to 20 mV. However, the extent of the inhibitory effects was only ~30%. In contrast, SKF (1 µM) had no significant effects on spontaneous transient IBK and caffeine-induced IBK. These results indicated that SKF inhibited ATP sensitive K(+) channels and voltage-gated K(+) channels, with the ATP sensitive K(+) channels being more sensitive than the voltage-gated K(+) channels. These inhibitory effects on K(+) channels should be considered when SKF is used as a cationic channel blocker. PMID:26498720

  17. Identifying Calcium Channels and Porters in Plant Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Sze, Heven

    1998-04-01

    The overall objectives of the proposal submitted in 6/90 was to understand how Ca was transported across plant membranes, and how these transport pathways were regulated. Ca participates in many cellular processes, including the transduction of hormonal and environmental signals, secretion, and protein folding. These processes depend on the coordination of passive Ca fluxes via channels and active Ca pumps; however these transport pathways are poorly understood in plants. We had, therefore, proposed to identify and characterize Ca transport proteins, such as the inositol-1 ,4,5-trisphosphate (IP3)-sensitive Ca channels and Ca pumps. We have had difficulties characterizing and cloning the IP3-sensitive Ca channel, but have made considerable progress on the biochemical characterization, and partial purification of a 120 kD Ca-pumping ATPase. We have begun to determine the structure of Ca pumps by molecular cloning and have already obtained a partial cDNA with features characteristic of Ca pumps.

  18. Calibration of the fast 12-channel ECE spectrometer at JET

    International Nuclear Information System (INIS)

    Measurements on the 12-channel ECE grating polychromator at the Joint European Torus are reported. This report describes the performance of the spectrometer in terms of sensitivity and spectral resolution. Measures to improve the systems responsivity and to overcome some characteristic problems of the spectrometer are reported. In addition, a comparison between different methods of absolute calibration of the system is presented. (orig.)

  19. K(ATP) channel openers in the trigeminovascular system

    DEFF Research Database (Denmark)

    Ploug, K B; Amrutkar, D V; Baun, M;

    2012-01-01

    The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involve...

  20. QKD Quantum Channel Authentication

    OpenAIRE

    Kosloski, J. T.

    2006-01-01

    Several simple yet secure protocols to authenticate the quantum channel of various QKD schemes, by coupling the photon sender's knowledge of a shared secret and the QBER Bob observes, are presented. It is shown that Alice can encrypt certain portions of the information needed for the QKD protocols, using a sequence whose security is based on computational-complexity, without compromising all of the sequence's entropy. It is then shown that after a Man-in-the-Middle attack on the quantum and c...

  1. Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging

    OpenAIRE

    Garber, Graham; Smith, Lee Ann; Reenan, Robert A.; Rogina, Blanka

    2012-01-01

    The voltage-gated Na+ channels (VGSC) are complex membrane proteins responsible for generation and propagation of the electrical signals through the brain, the skeletal muscle and the heart. The levels of sodium channels affect behavior and physical activity. This is illustrated by the maleless mutant allele (mlenapts) in Drosophila, where the decreased levels of voltage-gated Na+ channels cause temperature-sensitive paralysis.

  2. Two temporal channels in human V1 identified using fMRI

    OpenAIRE

    Horiguchi, Hiroshi; Nakadomari, Satoshi; Misaki, Masaya; Wandell, Brian A.

    2009-01-01

    Human visual sensitivity to a fairly broad class of dynamic stimuli can be modeled accurately using two temporal channels. Here, we analyze fMRI measurements of the temporal step response to spatially uniform stimuli to estimate these channels in human primary visual cortex (V1). In agreement with the psychophysical literature, the V1 fMRI temporal responses are modeled accurately as a mixture of two (transient and sustained) channels. We derive estimates of the relative contributions from th...

  3. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine

    OpenAIRE

    Vu, Michael T.; Du, Guizhi; Bayliss, Douglas A.; Horner, Richard L.

    2015-01-01

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K+ (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitr...

  4. Emerging approaches to probing ion channel structure and function

    Institute of Scientific and Technical Information of China (English)

    Wei-Guang Li; Tian-Le Xu

    2012-01-01

    Ion channels,as membrane proteins,are the sensors of the cell.They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into unique electrical signals to shape the responses of excitable cells.Because of their importance in cellular communication,ion channels have been intensively studied at the structural and functional levels.Here,we summarize the diverse approaches,including molecular and cellular,chemical,optical,biophysical,and computational,used to probe the structural and functional rearrangements that occur during channel activation (or sensitization),inactivation (or desensitization),and various forms of modulation.The emerging insights into the structure and function of ion channels by multidisciplinary approaches allow the development of new pharmacotherapies as well as new tools useful in controlling cellular activity.

  5. Improving virtual channel discrimination in a multi-channel context.

    Science.gov (United States)

    Srinivasan, Arthi G; Shannon, Robert V; Landsberger, David M

    2012-04-01

    Improving spectral resolution in cochlear implants is key to improving performance in difficult listening conditions (e.g. speech in noise, music, etc.). Current focusing might reduce channel interaction, thereby increasing spectral resolution. Previous studies have shown that combining current steering and current focusing reduces spread of excitation and improves virtual channel discrimination in a single-channel context. It is unclear whether the single-channel benefits from current focusing extend to a multi-channel context, in which the physical and perceptual interference of multiple stimulated channels might overwhelm the benefits of improved spectral resolution. In this study, signal discrimination was measured with and without current focusing, in the presence of competing stimuli on nearby electrodes. Results showed that signal discrimination was consistently better with current focusing than without, regardless of the amplitude of the competing stimuli. Therefore, combining current steering and current focusing may provide more effective spectral cues than are currently available. PMID:22616092

  6. Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

    Directory of Open Access Journals (Sweden)

    Meng Cui

    2014-10-01

    Full Text Available The small- and intermediate-conductance Ca2+-activated potassium (SK/IK channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca2+-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca2+ sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators. © 2014 S. Karger AG, Basel

  7. EFFICIENT UTILIZATION OF CHANNELS USING DYNAMIC GUARD CHANNEL ALLOCATION WITH CHANNEL BORROWING STRATEGY IN HANDOFFS

    Directory of Open Access Journals (Sweden)

    Alagu S

    2012-05-01

    Full Text Available User mobility in wireless data networks is increasing because of technological advances and the desire for voice and multimedia applications. These applications, however, require fast handoffs between base stations to maintain the quality of the connections. In this paper, the authors describe the use of novel and efficient data structure which dynamically allocates guard channel for handoffs and introduces the concept of channel borrowing strategy. The proposed scheme allocates the guard channels for handoff requests dynamically, based on the traffic load for certain time period. A new originating call in the cell coverage area also uses these guard channels if they are unused. Our basic idea is to allow Guard channels to be shared between new calls and handoff calls. This approach maximizes the channel utilization. The simulation results prove that the channel borrowing scheme improves the overall throughput.

  8. Protein complex analysis of native brain potassium channels by proteomics.

    Science.gov (United States)

    Sandoz, Guillaume; Lesage, Florian

    2008-01-01

    TREK potassium channels belong to a family of channel subunits with two-pore domains (K(2P)). TREK1 knockout mice display impaired polyunsaturated fatty acid-mediated protection against brain ischemia, reduced sensitivity to volatile anesthetics, resistance to depression and altered perception of pain. Recently, we isolated native TREK1 channels from mouse brain and identified their specific components by mass spectrometry. Among the identified partners, the A-Kinase Anchoring Protein AKAP150 binds to a regulatory domain of TREK1 and acts as a molecular switch. It transforms low activity, outwardly rectifying TREK1 currents into robust leak conductances resistant to stimulation by arachidonic acid, membrane stretch and acidification. Inhibition of the TREK1/AKAP150 channel by Gs-coupled receptors is as extensive as for TREK1 alone (but faster) whereas inhibition of TREK1/AKAP150 by Gq-coupled receptors is reduced. Furthermore, the association of AKAP150 with TREK1 channels integrates them into postsynaptic scaffolds where G protein-coupled membrane receptors and channels dock simultaneously. This chapter describes the proteomic approach used to study the composition of native TREK1 channels and point out its advantages and limitations over more classical methods (two-hybrid screenings in the yeast and bacteria or GST-pull down). PMID:18998088

  9. K ATP channels in pig and human intracranial arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Sørensen, Mette Aaskov; Strøbech, Lotte Bjørg;

    2008-01-01

    Clinical trials suggest that synthetic ATP-sensitive K(+) (K(ATP)) channel openers may cause headache and migraine by dilating cerebral and meningeal arteries. We studied the mRNA expression profile of K(ATP) channel subunits in the pig and human middle meningeal artery (MMA) and in the pig middle...... cerebral artery (MCA). We determined the order of potency of four K(ATP) channel openers when applied to isolated pig MMA and MCA, and we examined the potential inhibitory effects of the Kir6.1 subunit specific K(ATP) channel blocker PNU-37883A on K(ATP) channel opener-induced relaxation of the isolated...... pig MMA and MCA. Using conventional RT-PCR, we detected the mRNA transcripts of the K(ATP) channel subunits Kir6.1 and SUR2B in all the examined pig and human intracranial arteries. Application of K(ATP) channel openers to isolated pig MMA and MCA in myographs caused a concentration...

  10. Detection, characterization and endovascular therapy planning of intracranial aneurysms with 16-channel multidetector row CT angiography

    Directory of Open Access Journals (Sweden)

    Amr Badry

    2014-03-01

    Conclusion: Sixteen channel Multidetector CT angiography offers high diagnostic accuracy nearly equivalent to that of DSA in the detection of intracranial aneurysms. However, 16 channel- MDCTA still has limited sensitivity in detecting aneurysms of 3 mm or less, despite its technical advances. MDCT can be used as a reliable alternative imaging technique to DSA in selected cases.

  11. DMT of weighted Parallel Channels: Application to Broadcast Channel

    OpenAIRE

    Mroueh, Lina; Rouquette-Léveil, Stéphanie; Othman, Ghaya Rekaya-Ben; Belfiore, Jean-Claude

    2008-01-01

    In a broadcast channel with random packet arrival and transmission queues, the stability of the system is achieved by maximizing a weighted sum rate capacity with suitable weights that depend on the queue size. The weighted sum rate capacity using Dirty Paper Coding (DPC) and Zero Forcing (ZF) is asymptotically equivalent to the weighted sum capacity over parallel single-channels. In this paper, we study the Diversity Multiplexing Tradeoff (DMT) of the fading broadcast channel under a fixed w...

  12. A Micromechanical RF Channelizer

    Science.gov (United States)

    Akgul, Mehmet

    The power consumption of a radio generally goes as the number and strength of the RF signals it must process. In particular, a radio receiver would consume much less power if the signal presented to its electronics contained only the desired signal in a tiny percent bandwidth frequency channel, rather than the typical mix of signals containing unwanted energy outside the desired channel. Unfortunately, a lack of filters capable of selecting single channel bandwidths at RF forces the front-ends of contemporary receivers to accept unwanted signals, and thus, to operate with sub-optimal efficiency. This dissertation focuses on the degree to which capacitive-gap transduced micromechanical resonators can achieve the aforementioned RF channel-selecting filters. It aims to first show theoretically that with appropriate scaling capacitive-gap transducers are strong enough to meet the needed coupling requirements; and second, to fully detail an architecture and design procedure needed to realize said filters. Finally, this dissertation provides an actual experimentally demonstrated RF channel-select filter designed using the developed procedures and confirming theoretical predictions. Specifically, this dissertation introduces four methods that make possible the design and fabrication of RF channel-select filters. The first of these introduces a small-signal equivalent circuit for parallel-plate capacitive-gap transduced micromechanical resonators that employs negative capacitance to model the dependence of resonance frequency on electrical stiffness in a way that facilitates the analysis of micromechanical circuits loaded with arbitrary electrical impedances. The new circuit model not only correctly predicts the dependence of electrical stiffness on the impedances loading the input and output electrodes of parallel-plate capacitive-gap transduced micromechanical device, but does so in a visually intuitive way that identifies current drive as most appropriate for

  13. Acid-sensing ion channels and migraine

    Directory of Open Access Journals (Sweden)

    Yu-qi KANG

    2015-09-01

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

  14. TRPM2 channel regulates endothelial barrier function.

    Science.gov (United States)

    Hecquet, Claudie M; Ahmmed, Gias U; Malik, Asrar B

    2010-01-01

    Oxidative [Au1]stress, through the production of oxygen metabolites such as hydrogen peroxide[Au2] (H(2)O(2)), increases vascular endothelial permeability and plays a crucial role in several lung diseases. The transient receptor potential (melastatin) 2 (TRPM2) is an oxidant-sensitive, nonselective cation channel that is widely expressed in mammalian tissues, including the vascular endothelium. We have demonstrated the involvement of TRPM2 in mediating oxidant-induced calcium entry and endothelial hyperpermeability in cultured pulmonary artery endothelial cells. Here, we provide evidence that neutrophil activation-dependent increase in endothelial permeability and neutrophil extravasation requires TRPM2 in cultured endothelial cells. In addition, protein kinase Calpha (PKCalpha) that rapidly colocalizes with the short (nonconducting) TRPM2 isoform after exposure to hydrogen peroxide positively regulates calcium entry through the functional TRPM2 channel. Thus, increase in lung microvessel permeability and neutrophil sequestration depends on the activation of endothelial TRPM2 by neutrophilic oxidants and on PKCalpha regulation of TRPM2 channel activity. Manipulating TRPM2 function in the endothelium may represent a novel strategy aimed to prevent oxidative stress-related vascular dysfunction. PMID:20204729

  15. Multi-Channel Capacitive Sensor Arrays.

    Science.gov (United States)

    Wang, Bingnan; Long, Jiang; Teo, Koon Hoo

    2016-01-01

    In this paper, multi-channel capacitive sensor arrays based on microstrip band-stop filters are studied. The sensor arrays can be used to detect the proximity of objects at different positions and directions. Each capacitive sensing structure in the array is connected to an inductive element to form resonance at different frequencies. The resonances are designed to be isolated in the frequency spectrum, such that the change in one channel does not affect resonances at other channels. The inductive element associated with each capacitive sensor can be surface-mounted inductors, integrated microstrip inductors or metamaterial-inspired structures. We show that by using metamaterial split-ring structures coupled to a microstrip line, the quality factor of each resonance can be greatly improved compared to conventional surface-mounted or microstrip meander inductors. With such a microstrip-coupled split-ring design, more sensing elements can be integrated in the same frequency spectrum, and the sensitivity can be greatly improved. PMID:26821023

  16. Understanding cell passage through constricted microfluidic channels

    Science.gov (United States)

    Cartas-Ayala, Marco A.; Karnik, Rohit

    2012-11-01

    Recently, several microfluidic platforms have been proposed to characterize cells based on their behaviour during cell passage through constricted channels. Variables like transit time have been analyzed in disease states like sickle cell anemia, malaria and sepsis. Nevertheless, it is hard to make direct comparisons between different platforms and cell types. We present experimental results of the relationship between solid deformable particle properties, i.e. stiffness and relative particle size, and flow properties, i.e. particle's velocity. We measured the hydrodynamic variables during the flow of HL-60 cells, a white myeloid cell type, in narrow microfluidic square channels using a microfluidic differential manometer. We measured the flow force required to move cells of different sizes through microchannels and quantified friction forces opposing cell passage. We determined the non-dimensional parameters that influence the flow of cells and we used them to obtain a non dimensional expression that can be used to predict the forces needed to drive cells through microchannels. We found that the friction force needed to flow HL-60 through a microfluidic channel is the sum of two parts. The first part is a static friction force that is proportional to the force needed to keep the force compressed. The second part is a factor that is proportional to the cell velocity, hence a dynamic term, and slightly sensitive to the compressive force. We thank CONACYT (Mexican Science and Technology Council) for supporting this project, grant 205899.

  17. Secure refinements of communication channels

    OpenAIRE

    Cheval, Vincent; Cortier, Véronique; Le Morvan, Eric

    2015-01-01

    International audience It is a common practice to design a protocol (say Q) assuming some secure channels. Then the secure channels are implemented using any standard protocol, e.g. TLS. In this paper, we study when such a practice is indeed secure. We provide a characterization of both confidential and authenticated channels. As an application, we study several protocols of the literature including TLS and BAC protocols. Thanks to our result, we can consider a larger number of sessions wh...

  18. Gramicidin Channels Are Internally Gated

    OpenAIRE

    Jones, Tyson L.; Fu, Riqiang; Nielson, Frederick; Cross, Timothy A.; Busath, David D

    2010-01-01

    Gramicidin channels are archetypal molecular subjects for solid-state NMR studies and investigations of single-channel or cation conductance. Until now, the transitions between on and off conductance states have been thought, based on multichannel studies, to represent monomer ↔ dimer reactions. Here we use a single-molecule deposition method (vesicle fusion to a planar bilayer) to show that gramicidin dimer channels do not normally dissociate when conductance terminates. Furthermore, the obs...

  19. Determining nitrogen laser channel parameters

    International Nuclear Information System (INIS)

    This paper reports the measurement of the nitrogen laser channel current using a magnetic probe. For a 46 cm laser channel of gap 16 mm operated at 10 kV, 60 torr with foil capacitors of 58 and 28 nF, the channel current, inductance and resistance are found to be 42 kA, l.6 nH and 0.1 Ω respectively. (author)

  20. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to