An intermediate-conductance Ca²⁺-activated K⁺ channel is important for secretion in pancreatic duct cells

DEFF Research Database (Denmark)

Hayashi, Mikio; Wang, Jing; Hede, Susanne Edeling

2012-01-01

2; Slack; Slick; and an intermediate-conductance Ca(2+)-activated K(+) (IK) channel (K(Ca)3.1). The following functional studies were focused on the IK channel. 5,6-Dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DC-EBIO), an activator of IK channel, increased equivalent short-circuit current...

Electric field control of the small-polaron hopping conduction in spatial confined Pr0.7(Ca0.6Sr0.40.3MnO3/PMN-PT heterostructure

Directory of Open Access Journals (Sweden)

Hao Kuang

2017-05-01

Full Text Available The electric field dependent high-temperature small-polaron hopping conduction was investigated in patterned Pr0.7(Ca0.6Sr0.40.3MnO3 strips. The small-polaronic activation energy EA and the carrier localization were found to decrease with the reduction of the strip size. Meanwhile, a similar dependence on the strip size was also obtained for the calculated small-polaron coupling constants, which could be related to the strain relaxation in strips. These results indicate that the spatial confinement prefers to delocalize the carrier and reduce the electron-phonon interaction. Furthermore, opposite variation trends of EA under negative and positive electric field were found in the strips with small size, which could be attributed to the enhancement of polarization effect induced by the reduction of strip size.

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro.

Science.gov (United States)

Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

2017-02-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca 2+ -activated K + channel (BK Ca ) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca 2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca 2+ and preventing neuronal apoptosis, and this is mediated by BK Ca channel activation.

Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

DEFF Research Database (Denmark)

Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke

2009-01-01

PURPOSE: Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK...

Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes.

Science.gov (United States)

Vandorpe, David H; Xu, Chang; Shmukler, Boris E; Otterbein, Leo E; Trudel, Marie; Sachs, Frederick; Gottlieb, Philip A; Brugnara, Carlo; Alper, Seth L

2010-01-15

Deoxygenation of sickle erythrocytes activates a cation permeability of unknown molecular identity (Psickle), leading to elevated intracellular [Ca(2+)] ([Ca(2+)](i)) and subsequent activation of K(Ca) 3.1. The resulting erythrocyte volume decrease elevates intracellular hemoglobin S (HbSS) concentration, accelerates deoxygenation-induced HbSS polymerization, and increases the likelihood of cell sickling. Deoxygenation-induced currents sharing some properties of Psickle have been recorded from sickle erythrocytes in whole cell configuration. We now show by cell-attached and nystatin-permeabilized patch clamp recording from sickle erythrocytes of mouse and human that deoxygenation reversibly activates a Ca(2+)- and cation-permeable conductance sensitive to inhibition by Grammastola spatulata mechanotoxin-4 (GsMTx-4; 1 microM), dipyridamole (100 microM), DIDS (100 microM), and carbon monoxide (25 ppm pretreatment). Deoxygenation also elevates sickle erythrocyte [Ca(2+)](i), in a manner similarly inhibited by GsMTx-4 and by carbon monoxide. Normal human and mouse erythrocytes do not exhibit these responses to deoxygenation. Deoxygenation-induced elevation of [Ca(2+)](i) in mouse sickle erythrocytes did not require KCa3.1 activity. The electrophysiological and fluorimetric data provide compelling evidence in sickle erythrocytes of mouse and human for a deoxygenation-induced, reversible, Ca(2+)-permeable cation conductance blocked by inhibition of HbSS polymerization and by an inhibitor of strctch-activated cation channels. This cation permeability pathway is likely an important source of intracellular Ca(2+) for pathologic activation of KCa3.1 in sickle erythrocytes. Blockade of this pathway represents a novel therapeutic approach for treatment of sickle disease.

Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes.

Directory of Open Access Journals (Sweden)

David H Vandorpe

2010-01-01

Full Text Available Deoxygenation of sickle erythrocytes activates a cation permeability of unknown molecular identity (Psickle, leading to elevated intracellular [Ca(2+] ([Ca(2+](i and subsequent activation of K(Ca 3.1. The resulting erythrocyte volume decrease elevates intracellular hemoglobin S (HbSS concentration, accelerates deoxygenation-induced HbSS polymerization, and increases the likelihood of cell sickling. Deoxygenation-induced currents sharing some properties of Psickle have been recorded from sickle erythrocytes in whole cell configuration.We now show by cell-attached and nystatin-permeabilized patch clamp recording from sickle erythrocytes of mouse and human that deoxygenation reversibly activates a Ca(2+- and cation-permeable conductance sensitive to inhibition by Grammastola spatulata mechanotoxin-4 (GsMTx-4; 1 microM, dipyridamole (100 microM, DIDS (100 microM, and carbon monoxide (25 ppm pretreatment. Deoxygenation also elevates sickle erythrocyte [Ca(2+](i, in a manner similarly inhibited by GsMTx-4 and by carbon monoxide. Normal human and mouse erythrocytes do not exhibit these responses to deoxygenation. Deoxygenation-induced elevation of [Ca(2+](i in mouse sickle erythrocytes did not require KCa3.1 activity.The electrophysiological and fluorimetric data provide compelling evidence in sickle erythrocytes of mouse and human for a deoxygenation-induced, reversible, Ca(2+-permeable cation conductance blocked by inhibition of HbSS polymerization and by an inhibitor of strctch-activated cation channels. This cation permeability pathway is likely an important source of intracellular Ca(2+ for pathologic activation of KCa3.1 in sickle erythrocytes. Blockade of this pathway represents a novel therapeutic approach for treatment of sickle disease.

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

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Yuan Hung Lo

2013-01-01

Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain

DEFF Research Database (Denmark)

Grunnet, Morten; Kaufmann, Walter A

2004-01-01

Based on electrophysiological studies, Ca(2+)-activated K(+) channels and voltage-gated Ca(2+) channels appear to be located in close proximity in neurons. Such colocalization would ensure selective and rapid activation of K(+) channels by local increases in the cytosolic calcium concentration...

Effects on atrial fibrillation in aged hypertensive rats by Ca(2+)-activated K(+) channel inhibition

DEFF Research Database (Denmark)

Diness, Jonas Goldin; Skibsbye, Lasse; Jespersen, Thomas

2011-01-01

We have shown previously that inhibition of small conductance Ca(2+)-activated K(+) (SK) channels is antiarrhythmic in models of acutely induced atrial fibrillation (AF). These models, however, do not take into account that AF derives from a wide range of predisposing factors, the most prevalent ...

Cell swelling activates cloned Ca(2+)-activated K(+) channels: a role for the F-actin cytoskeleton

DEFF Research Database (Denmark)

Jorgensen, Nanna K; Pedersen, Stine F; Rasmussen, Hanne B

2003-01-01

Cloned Ca(2+)-activated K(+) channels of intermediate (hIK) or small (rSK3) conductance were expressed in HEK 293 cells, and channel activity was monitored using whole-cell patch clamp. hIK and rSK3 currents already activated by intracellular calcium were further increased by 95% and 125......%, respectively, upon exposure of the cells to a 33% decrease in extracellular osmolarity. hIK and rSK3 currents were inhibited by 46% and 32%, respectively, by a 50% increase in extracellular osmolarity. Cell swelling and channel activation were not associated with detectable increases in [Ca(2+)](i), evidenced...... by population and single-cell measurements. In addition, inhibitors of IK and SK channels significantly reduced the rate of regulatory volume decrease (RVD) in cells expressing these channels. Cell swelling induced a decrease, and cell shrinkage an increase, in net cellular F-actin content. The swelling...

Structure and electrical conduction of the system La sub(1-x)Ca sub(x)FeO sub(3-α)

International Nuclear Information System (INIS)

Hombo, Jukichi; Urabe, Noriake; Hiroshige, Gota; Hamada, Kotaro.

1982-01-01

Perovskite phases in the system, La sub(1-x)Ca sub(x)FeO sub(3-α) were prepared with La 2 O 3 , CaCO 3 , and Fe 2 O 3 by firing in air and in vacuo. The compositions of samples fired in vacuo and in air are represented as La sub(1-x)Ca sub(x)FeO sub(3-x 2) and La sub(1-x)Ca sub(x)Fe sub(1-y)sup(3+)Fe sub(y)sup(4+)O sub(3-x/2+y/2), respectively. That is, samples fired in vacuo contain some oxygen vacancies and no tetravalent iron; in contrast, samples fired in air contain both oxygen vacancies and tetravalent iron in the structures. The electrical conductivities of these synthesized oxides depended extensively upon the content of tetravalent iron. For instance, the conductivity of the sample x = 0.6 fired in air was larger by 10 6 than that of the sample fired in vacuo. In this system, except for the two terminal compositions of x = 0 and x = 1.0, the values of activation energy for conduction are considerably small, and from the results of thermo-electromotive force measurement, the charge carrier was positive. Furthermore, the conductivity increased somewhat with time during the conductivity measurement by the direct-current method. These facts suggest that the electrical conducted would not be ionic but electronic. The electrical conduction would then be carried out by the so-called hopping mechanism by which the positive charge is transferred. (author)

Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive

Science.gov (United States)

Garver, Hannah; Galligan, James J.; Fink, Gregory D.

2011-01-01

Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. PMID:21131476

Structure and electrical conduction of the system La sub(1-x)Ca sub(x)FeO sub(3-. cap alpha. )

Energy Technology Data Exchange (ETDEWEB)

Hombo, Jukichi; Urabe, Noriake [Kumamoto Univ. (Japan). Faculty of Engineering; Hiroshige, Gota; Hamada, Kotaro

1982-08-01

Perovskite phases in the system, La sub(1-x)Ca sub(x)FeO sub(3-..cap alpha..) were prepared with La/sub 2/O/sub 3/, CaCO/sub 3/, and Fe/sub 2/O/sub 3/ by firing in air and in vacuo. The compositions of samples fired in vacuo and in air are represented as La sub(1-x)Ca sub(x)FeO sub(3-x 2) and La sub(1-x)Ca sub(x)Fe sub(1-y)sup(3+)Fe sub(y)sup(4+)O sub(3-x/2+y/2), respectively. That is, samples fired in vacuo contain some oxygen vacancies and no tetravalent iron; in contrast, samples fired in air contain both oxygen vacancies and tetravalent iron in the structures. The electrical conductivities of these synthesized oxides depended extensively upon the content of tetravalent iron. For instance, the conductivity of the sample x = 0.6 fired in air was larger by 10/sup 6/ than that of the sample fired in vacuo. In this system, except for the two terminal compositions of x = 0 and x = 1.0, the values of activation energy for conduction are considerably small, and from the results of thermo-electromotive force measurement, the charge carrier was positive. Furthermore, the conductivity increased somewhat with time during the conductivity measurement by the direct-current method. These facts suggest that the electric conduction would not be ionic but electronic. The electrical conduction would then be carried out by the so-called hopping mechanism by which the positive charge is transferred.

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro

Institute of Scientific and Technical Information of China (English)

Fang Su; An-Chen Guo; Wei-Wei Li; Yi-Long Zhao; Zheng-Yi Qu; Yong-Jun Wang; Qun Wang; Yu-Lan Zhu

2017-01-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion;however,the underlying mechanism has not been elucidated.In the present study,we showed that expression of the neuronal large-conductance,Ca2+-activated K+ channel (BKCa) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivatior/reoxygenation (OGD/R) compared with controls.Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R,attenuated the OGD/R-induced elevation of cytosolic Ca2+ levels,and reduced the number of apoptotic neurons.Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax.The protective effect of ethanol preconditioning was antagonized by a BKCa channel inhibitor,paxilline.Inside-out patches in primary neurons also demonstrated the direct activation of the BKCa channel by 10 mmol/L ethanol.The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca2+ and preventing neuronal apoptosis,and this is mediated by BKCa channel activation.

Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum

NARCIS (Netherlands)

Chen, Mao Xiang; Gorman, Shelby A.; Benson, Bill; Singh, Kuljit; Hieble, J. Paul; Michel, Martin C.; Tate, Simon N.; Trezise, Derek J.

2004-01-01

The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in

Mg,Ca-ATPase activity under irradiation

International Nuclear Information System (INIS)

Ladutin, V.V.; Orlova, V.V.; Lob, P.A.; Gerasiminko, I.V.; Mack, E.I.

2003-01-01

Full text: The influence of different doses irradiation at the Mg,Ca-ATPase activity at the rat brain has been investigated. The analyses were made at the apparatus of LKB and Carl-Ceis-Jena firm with help of reagents of Sigma and Boehringer firm. Rats decapitated after 1, 3, 6, 24 and 48 h after action of irradiation. Dose 0.206 C/kg. Erythrocytes. 1 and 3h after irradiation influence- decrease of Mg,Ca-ATPase activity to 86-87% relatively control level, 24 and 48 h - increase of activity to the control level. Dose 0.312 C/kg. Large hemispheres. 1h - decrease of ATPase activity to 90% relatively control, 3h - increase to control level, 24h - fall to 86%, after 48h small increase to 93% relatively control. Dose 9.287 C/kg. Large hemispheres. 1h - sharp fall of Mg, Ca-ATPase activity to 67 % relatively control, increase of activity to 96% after 3h and sharp fall of activity to 64% 6h after action of irradiation. Dose 9.287 C/kg. Cerebellum. 1h - sharp decrease of ATPase activity to 80%. After 3h -sharp increase to 160% relatively control level and sharp fall of ATPase activity to 47% relatively control after 6h. The mechanism of radiation pathology of active ion transport has been discussed

Consequences of Ca multisite occupation for the conducting properties of BaTiO{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Zulueta, Y.A., E-mail: yohandysalexis.zuluetaleyva@student.kuleuven.be [Departamento de Física, Facultad de Ciencias Naturales, Universidad de Oriente, CP-90500 Santiago de Cuba (Cuba); Department of Chemistry, KU Leuven, B-3001 Leuven (Belgium); Dawson, J.A. [Department of Engineering, University of Cambridge, Cambridge CB2 1PZ (United Kingdom); Leyet, Y. [Departamento de Engenharia de Materiais, Universidade Federal do Amazonas, Av. General Rodrigo Otávio, 6200 – Coroado I, 69077-000 Manaus (Brazil); Departamento de Física, Universidade Federal do Amazonas, Av. General Rodrigo Otávio, 6200 – Coroado I, 69077-000 Manaus, Amazonas (Brazil); Anglada-Rivera, J. [Instituto Federal de Educação Ciência e Tecnologia do Amazonas, Av. 7de Setembro, 1975, 69020-120 Manaus (Brazil); Guerrero, F. [Departamento de Física, Universidade Federal do Amazonas, Av. General Rodrigo Otávio, 6200 – Coroado I, 69077-000 Manaus, Amazonas (Brazil); Silva, R.S. [Departamento de Física, Universidade Federal de Sergipe, 49100-000 São Cristóvão, SE (Brazil); Nguyen, Minh Tho [Department of Chemistry, KU Leuven, B-3001 Leuven (Belgium)

2016-11-15

In combination with the dielectric modulus formalism and theoretical calculations, a newly developed defect incorporation mode, which is a combination of the standard A- and B-site doping mechanisms, is used to explain the conducting properties in 5 mol% Ca-doped BaTiO{sub 3}. Simulation results for Ca solution energies in the BaTiO{sub 3} lattice show that the new oxygen vacancy inducing mixed mode exhibits low defect energies. A reduction in dc conductivity compared with undoped BaTiO{sub 3} is witnessed for the incorporation of Ca. The conducting properties of 5 mol% Ca-doped BaTiO{sub 3} are analyzed using molecular dynamics and impedance spectroscopy. The ionic conductivity activation energies for each incorporation mode are calculated and good agreement with experimental data for oxygen migration is observed. The likely existence of the proposed defect configuration is also analyzed on the basis of these methods. - Graphical abstract: Oxygen vacancy formation as a result of self-compensation in Ca-doped BaTiO{sub 3}.

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

Science.gov (United States)

Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

2017-03-01

Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

Information in small neuronal ensemble activity in the hippocampal CA1 during delayed non-matching to sample performance in rats

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Takahashi Susumu

2009-09-01

Full Text Available Abstract Background The matrix-like organization of the hippocampus, with its several inputs and outputs, has given rise to several theories related to hippocampal information processing. Single-cell electrophysiological studies and studies of lesions or genetically altered animals using recognition memory tasks such as delayed non-matching-to-sample (DNMS tasks support the theories. However, a complete understanding of hippocampal function necessitates knowledge of the encoding of information by multiple neurons in a single trial. The role of neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed quantitatively in this study using multi-neuronal recordings and an artificial neural network classifier as a decoder. Results The activity of small neuronal ensembles (6-18 cells over brief time intervals (2-50 ms contains accurate information specifically related to the matching/non-matching of continuously presented stimuli (stimulus comparison. The accuracy of the combination of neurons pooled over all the ensembles was markedly lower than those of the ensembles over all examined time intervals. Conclusion The results show that the spatiotemporal patterns of spiking activity among cells in the small neuronal ensemble contain much information that is specifically useful for the stimulus comparison. Small neuronal networks in the hippocampal CA1 might therefore act as a comparator during recognition memory tasks.

Quantification and distribution of big conductance Ca2+-activated K+ channels in kidney epithelia

DEFF Research Database (Denmark)

Grunnet, Morten; Hay-Schmidt, Anders; Klaerke, Dan A

2005-01-01

and immunohistochemical studies. In cortical collecting ducts, BK channels were exclusively located in principal cells while no channels could be found in intercalated cells. The abundant and distinct distribution in kidney epithelia talks in favor for BK channels being important contributors in maintaining salt......Big conductance Ca2+ activated K+ channels (BK channels) is an abundant channel present in almost all kind of tissue. The accurate quantity and especially the precise distribution of this channel in kidney epithelia are, however, still debated. The aim of the present study has therefore been...... to examine the presence of BK channels in kidney epithelia and determine the actual number and distribution of these channels. For this purpose, a selective peptidyl ligand for BK channels called iberiotoxin or the radiolabeled double mutant analog 125I-IbTX-D19Y/Y36F has been employed. The presence of BK...

Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium

DEFF Research Database (Denmark)

Rosenbaum, Sofia T; Svalø, Julie; Nielsen, Karsten

2012-01-01

Small-conductance calcium-activated potassium (SK3) channels have been detected in human myometrium and we have previously shown a functional role of SK channels in human myometrium in vitro. The aims of this study were to identify the precise localization of SK3 channels and to quantify SK3 m....... This is the first report to provide evidence for a possible role of SK3 channels in human uterine telocytes....

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

Science.gov (United States)

Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

2015-01-01

Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

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Qijing Chen

Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease

DEFF Research Database (Denmark)

Vanderwinden, Jean-Marie; Rumessen, Jüri J; de Kerchove d'Exaerde, Alban

2002-01-01

The apamin-sensitive component of the inhibitory response of the gastrointestinal musculature involves the small conductance Ca(2+)-activated K(+) channel SK3. Kit-immunoreactive (ir) interstitial cells of Cajal appear to be involved in nitrergic inhibition while the role of the recently describe...

Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

Science.gov (United States)

Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

2015-06-09

Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission.

Apelin-13 inhibits large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism.

Directory of Open Access Journals (Sweden)

Amit Modgil

Full Text Available Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca(2+-activated K(+ (BKCa channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BK(Ca channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 (0.001-1 μM caused concentration-dependent inhibition of BK(Ca in VSM cells. Apelin-13 (0.1 µM significantly decreased BK(Ca current density from 71.25 ± 8.14 pA/pF to 44.52 ± 7.10 pA/pF (n=14 cells, P<0.05. This inhibitory effect of apelin-13 was confirmed by single channel recording in cell-attached patches, in which extracellular application of apelin-13 (0.1 µM decreased the open-state probability (NPo of BK(Ca channels in freshly isolated VSM cells. However, in inside-out patches, extracellular application of apelin-13 (0.1 µM did not alter the NPo of BK(Ca channels, suggesting that the inhibitory effect of apelin-13 on BKCa is not mediated by a direct action on BK(Ca. In whole cell patches, pretreatment of VSM cells with LY-294002, a PI3-kinase inhibitor, markedly attenuated the apelin-13-induced decrease in BK(Ca current density. In addition, treatment of arteries with apelin-13 (0.1 µM significantly increased the ratio of phosphorylated-Akt/total Akt, indicating that apelin-13 significantly increases PI3-kinase activity. Taken together, the data suggest that apelin-13 inhibits BK(Ca channel via a PI3-kinase-dependent signaling pathway in cerebral artery VSM cells, which may contribute to its regulatory action in the control of vascular tone.

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

DEFF Research Database (Denmark)

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

2008-01-01

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

Novel phenolic inhibitors of small/intermediate-conductance Ca²⁺-activated K⁺ channels, KCa3.1 and KCa2.3.

Directory of Open Access Journals (Sweden)

Aida Oliván-Viguera

Full Text Available BACKGROUND: KCa3.1 channels are calcium/calmodulin-regulated voltage-independent K(+ channels that produce membrane hyperpolarization and shape Ca(2+-signaling and thereby physiological functions in epithelia, blood vessels, and white and red blood cells. Up-regulation of KCa3.1 is evident in fibrotic and inflamed tissues and some tumors rendering the channel a potential drug target. In the present study, we searched for novel potent small molecule inhibitors of KCa3.1 by testing a series of 20 selected natural and synthetic (polyphenols, synthetic benzoic acids, and non-steroidal anti-inflammatory drugs (NSAIDs, with known cytoprotective, anti-inflammatory, and/or cytostatic activities. METHODOLOGY/PRINCIPAL FINDINGS: In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM and resveratrol (EC50 10 µM as KCa3.1 inhibitors with moderate potency. The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM, followed by mesalamine (EC50≥10 µM. The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyloxymethyl]phenyl]methyl 3-fluoro-4-hydroxy-benzoate, was identified as a potent mixed KCa2/3 channel inhibitor with an EC50 of 19 nM for KCa3.1 and 360 pM for KCa2.3, which affected KCa1.1 and Kv channels only at micromolar concentrations. The KCa3.1/KCa2-activator SKA-31 antagonized the 13b-blockade. In proliferation assays, 13b was not cytotoxic and reduced proliferation of 3T3 fibroblasts as well as caffeic acid. In isometric vessel myography, 13b increased contractions of porcine coronary arteries to serotonin and antagonized endothelium-derived hyperpolarization-mediated vasorelaxation to pharmacological KCa3.1/KCa2.3 activation. CONCLUSIONS/SIGNIFICANCE: We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel

Activation of a Ca-bentonite as buffer material

Science.gov (United States)

Huang, Wei-Hsing; Chen, Wen-Chuan

2016-04-01

Swelling behavior is an important criterion in achieving the low-permeability sealing function of buffer material. A potential buffer material may be used for radioactive waste repository in Taiwan is a locally available clayey material known as Zhisin clay, which has been identified as a Ca-bentonite. Due to its Ca-based origin, Zhisin was found to exhibit swelling capacity much lower than that of Na-bentonite. To enhance the swelling potential of Zhisin clay, a cation exchange process by addition of Na2CO3 powder was introduced in this paper. The addition of Na2CO3 reagent to Zhisin clay, in a liquid phase, caused the precipitation of CaCO3 and thereby induced a replacement of Ca2+ ions by Na+ ions on the surface of bentonite. Characterization test conducted on Zhisin clay includes chemical analysis, cation exchange capacity, X-ray diffraction, and thermogravimetry (TG). Free-swelling test apparatus was developed according to International Society of Rock Mechanics recommendations. A series of free-swelling tests were conducted on untreated and activated specimens to characterize the effect of activation on the swelling capacity of Zhisin clay. Efforts were made to determine an optimum dosage for the activation, and to evaluate the aging effect. Also, the activated material was evaluated for its stability in various hydrothermal conditions for potential applications as buffer material in a repository. Experimental results show that Na2CO3-activated Zhisin clay is superior in swelling potential to untreated Zhisin clay. Also, there exists an optimum amount of activator in terms of improvements in the swelling capacity. A distinct time-swell relationship was discovered for activated Zhisin clay. The corresponding mechanism refers to exchange of cations and breakdown of quasi-crystal, which results in ion exchange hysteresis of Ca-bentonite. Due to the ion exchange hysteresis, activated bentonite shows a post-rise time-swell relationship different than the sigmoid

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi

2010-11-18

A family of peptide signaling molecules (AtPeps) and their plasma membrane receptor AtPepR1 are known to act in pathogendefense signaling cascades in plants. Little is currently known about the molecular mechanisms that link these signaling peptides and their receptor, a leucine-rich repeat receptor-like kinase, to downstream pathogen-defense responses. We identify some cellular activities of these molecules that provide the context for a model for their action in signaling cascades. AtPeps activate plasma membrane inwardly conducting Ca 2+ permeable channels in mesophyll cells, resulting in cytosolic Ca 2+ elevation. This activity is dependent on their receptor as well as a cyclic nucleotide-gated channel (CNGC2). We also show that the leucine-rich repeat receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33) is mediated by the Ca 2+ signaling pathway associated with AtPep peptides and their receptor. The work presented here indicates that extracellular AtPeps, which can act as danger-associated molecular patterns, signal by interaction with their receptor, AtPepR1, a plasma membrane protein that can generate cGMP. Downstream from AtPep and AtPepR1 in a signaling cascade, the cGMP-activated channel CNGC2 is involved in AtPep- and AtPepR1-dependent inward Ca 2+ conductance and resulting cytosolic Ca 2+ elevation. The signaling cascade initiated by AtPeps leads to expression of pathogen- defense genes in a Ca 2+-dependent manner.

Theorizing Small Children’s Conduct of Everyday Life

DEFF Research Database (Denmark)

Røn Larsen, Maja; Stanek, Anja Hvidtfeldt

The aim of this paper is to relate the concept conduct of everyday life to small children (ages 0 to 3 years). The paper will contribute to the understanding of small children’s common and shared lives in day care or public nursery, as well as their developmental and social learning processes......, 2011). We thus approach the empirical and theoretical challenge related to the study of small children’s every day life through analysis of the dialectic relation of the small child as a subject with agency, participating in societal contexts in which the child develops and learns. Accordingly, we...... argue that children develop their conduct of everyday life though play and learning in interconnected social practices among peers, parents and professionals. These activities take place in- and across various societal settings, such as home and institutional arrangements, e.g. nursery or day care. We...

Electrical conductivity of cobalt–titanium substituted SrCaM hexaferrites

International Nuclear Information System (INIS)

Eraky, M.R.

2012-01-01

A series of polycrystalline M-type hexagonal ferrites with the composition Sr 0.5 Ca 0.5 Co x Ti x Fe 12−2x O 19 (where x=0.0–0.8) were prepared by the conventional ceramic technique. The electrical conductivity has been measured from 300 to 590 K. The dc conductivity, σ dc , exhibited a semiconductor behavior. The negative sign of thermoelectric power coefficient S reveals that all samples are n-type semiconductors. Both σ dc and mobility, μ d , increases with the substitution of Co 2+ and Ti 4+ ions, reach maximum at x=0.4 and start decreasing at x>0.4. Many conduction mechanisms were discussed to explain the electric conduction in the system. It was found that the hopping conduction is the predominant conduction mechanism. For samples with compositional parameter x=0.0 and 0.8, the band conduction mechanism shares in electric conduction beside the hopping process. - Highlights: ► SrCaCoTiM hexaferrites have been prepared by conventional ceramic technique. ► The electrical conductivity exhibited a semiconductor behavior. There is an increase in conductivity up to x=0.4 for Co and Ti substitution. ► The hopping conduction is the predominant conduction mechanism.

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Endothelial Small- and Intermediate-Conductance KCa Channels

DEFF Research Database (Denmark)

Wulff, Heike; Köhler, Ralf

2013-01-01

ABSTRACT:: Most cardiovascular researchers are familiar with intermediate-conductance KCa3.1 and small-conductance KCa2.3 channels because of their contribution to endothelium-derived hyperpolarization (EDH). However, to immunologists and neuroscientists these channels are primarily known...... for their role in lymphocyte activation and neuronal excitability. KCa3.1 is involved in the proliferation and migration of T cells, B cell, mast cells, macrophages, fibroblasts and dedifferentiated vascular smooth muscle cells and is, therefore, being pursued as a potential target for use in asthma...

Novel electrical conductivity properties in Ca-doped BiFeO3 nanoparticles

International Nuclear Information System (INIS)

Wang, X.; Wang, S. Y.; Liu, W. F.; Xi, X. J.; Zhang, H.; Guo, F.; Xu, X. L.; Li, M.; Liu, L.; Zhang, C.; Li, X.; Yang, J. B.

2015-01-01

The charge defective structure in Bi 1−x Ca x FeO 3 (CBFO, x = 0, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3) nanoparticles (NPs) ranging from 140 to 25 nm as well as their relations to band gap and leakage current behavior are investigated. It is demonstrated that Ca doping effectively narrows the band gap from ∼2.16 to ∼2.02 eV, due to the appearance and accumulation of oxygen vacancy. Subsequently, enhanced electrical conductivity was obtained in these CBFO NPs, which leads to the appearance of a distinct threshold switching behavior in Ca-doped BFO NPs with higher conductivity at room temperature. Possible mechanisms for Ca doping effects on the electric conduction were discussed upon the interplay of NPs’ size effect and mobile charged defects on the basis of reduced particle size and the increased density of oxygen vacancy analyzed through X-ray photoelectron spectrum

Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

Science.gov (United States)

Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

2015-01-01

Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

Twenty-four-hour exposure to altered blood flow modifies endothelial Ca2+-activated K+ channels in rat mesenteric arteries

DEFF Research Database (Denmark)

Hilgers, Rob H P; Janssen, Ger M J; Fazzi, Gregorio E

2010-01-01

We tested the hypothesis that changes in arterial blood flow modify the function of endothelial Ca2+-activated K+ channels [calcium-activated K+ channel (K(Ca)), small-conductance calcium-activated K+ channel (SK3), and intermediate calcium-activated K+ channel (IK1)] before arterial structural...... remodeling. In rats, mesenteric arteries were exposed to increased [+90%, high flow (HF)] or reduced blood flow [-90%, low flow (LF)] and analyzed 24 h later. There were no detectable changes in arterial structure or in expression level of endothelial nitric-oxide synthase, SK3, or IK1. Arterial relaxing...... arteries, the balance between the NO/prostanoid versus EDHF response was unaltered. However, the contribution of IK1 to the EDHF response was enhanced, as indicated by a larger effect of TRAM-34 and a larger residual NS309-induced relaxation in the presence of UCL 1684. Reduction of blood flow selectively...

Molecular and functional expression of high conductance Ca 2+ activated K+ channels in the eel intestinal epithelium

DEFF Research Database (Denmark)

Lionetto, Maria G; Rizzello, Antonia; Giordano, Maria E

2008-01-01

Several types of K(+) channels have been identified in epithelial cells. Among them high conductance Ca(2+)-activated K(+) channels (BK channels) are of relevant importance for their involvement in regulatory volume decrease (RVD) response following hypotonic stress. The aim of the present work...... was to investigate the functional and molecular expression of BK in the eel intestine, which is a useful experimental model for cell volume regulation research. In the present paper using rat BK channel-specific primer, a RT-PCR signal of 696 pb cDNA was detected in eel intestine, whole nucleotide sequence showed...... high similarity (83%) to the alpha subunit of BK channel family. BK channel protein expression was verified by immunoblotting and confocal microscopy, while the functional role of BK channels in epithelial ion transport mechanisms and cell volume regulation was examined by electrophysiological...

Metallic and semi-conducting resistivity behaviour of La0.7Ca0.3- x K x MnO3 ( x = 0.05, 0.1) manganites

Science.gov (United States)

Varshney, Dinesh; Dodiya, Neha

2015-12-01

The temperature dependence of electrical resistivity, ρ, of ceramic La0.7Ca0.3- x K x MnO3 ( x = 0.05, 0.1) is investigated in metallic and semi-conducting phase. The metallic resistivity is attributed to be caused by electron-phonon, electron-electron and electron-magnon scattering. Substitutions affect average mass and ionic radii of A-site resulting in an increase in Debye temperature θ D attributed to hardening of lattice with K doping. The optical phonon modes shift gradually to lower mode frequencies leading to phonon softening. Estimated resistivity compared with reported metallic resistivity, accordingly ρ diff. = [ ρ exp. - { ρ 0 + ρ e-ph (= ρ ac + ρ op)}], infers electron-electron and electron-magnon dependence over most of the temperature range. Semi-conducting nature is discussed with variable range hopping and small polaron conduction model. The decrease in activation energies and increase in density of states at the Fermi level with enhanced Ca doping is consistently explained by cationic disorder and Mn valence.

Ionic conductivity and the formation of cubic CaH2 in the LiBH4-Ca(BH4)2 composite

DEFF Research Database (Denmark)

Sveinbjörnsson, Dadi Þorsteinn; Blanchard, Didier; Mýrdal, Jón Steinar Garðarsson

2014-01-01

LiBH4–Ca(BH4)2 composites were prepared by ball milling. Their crystal structures and phase composition were investigated using synchrotron X-ray diffraction and Rietveld refinement, and their ionic conductivity was measured using impedance spectroscopy. The materials were found to form a physical...... treatment. Concurrent formation of elemental boron may also occur. The ionic conductivity of the composites was measured using impedance spectroscopy, and was found to be lower than that of ball milled LiBH4. Electronic band structure calculations indicate that cubic CaH2 with hydrogen defects...... is electronically conducting. Its formation along with the possible precipitation of boron therefore has an effect on the measured conductivity of the LiBH4–Ca(BH4)2 composites and may increase the risk of an internal short-circuit in the cells....

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

NARCIS (Netherlands)

Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner

Enhanced K+-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE−/− mice

Science.gov (United States)

Beleznai, Timea; Takano, Hiromichi; Hamill, Claire; Yarova, Polina; Douglas, Gillian; Channon, Keith; Dora, Kim

2011-01-01

Aims Agonists that evoke smooth muscle cell hyperpolarization have the potential to stimulate both local and conducted dilation. We investigated whether the endothelium-dependent vasodilators acetylcholine (ACh) and SLIGRL stimulated conducted dilation and whether this was altered by deficiency in apolipoprotein E (ApoE−/−). Methods and results Isolated mesenteric arteries were cannulated, pressurized, and precontracted with phenylephrine. Agonists were either added to the bath to study local dilation or were restricted to one end of arteries to study conducted dilation. An enhanced sensitivity to both ACh and SLIGRL was observed in mesenteric arteries from ApoE−/− mice compared with wild-type controls. Inhibition of nitric oxide (NO) synthase blocked ACh responses, but had no effect on maximum dilation to SLIGRL. SLIGRL increased endothelial cell Ca2+, hyperpolarized smooth muscle cells, and fully dilated arteries. The NO-independent dilation to SLIGRL was blocked with high [KCl] or Ca2+-activated K+-channel blockers. The hyperpolarization and dilation to SLIGRL passed through the artery to at least 2.5 mm upstream. The conducted dilation was not affected by a deficit in ApoE and could also be stimulated by ACh, suggesting NO itself could stimulate conducted dilation. Conclusion In small mesenteric arteries of ApoE−/− mice, NO-independent dilation is enhanced. Since both NO-dependent and -independent pathways can stimulate local and conducted dilation, the potential for reducing vascular resistance is improved in these vessels. PMID:21690174

Novel electrical conductivity properties in Ca-doped BiFeO{sub 3} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Wang, X.; Wang, S. Y., E-mail: shouyu.wang@yahoo.com [Tianjin Normal University, College of Physics and Materials Science (China); Liu, W. F., E-mail: wfliu@tju.edu.cn [Tianjin University, Department of Applied Physics, Institute of Advanced Materials Physics, Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Faculty of Science (China); Xi, X. J. [Tianjin Normal University, College of Physics and Materials Science (China); Zhang, H. [Tianjin University, Department of Applied Physics, Institute of Advanced Materials Physics, Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Faculty of Science (China); Guo, F. [Tianjin Normal University, College of Physics and Materials Science (China); Xu, X. L. [Tianjin University, Department of Applied Physics, Institute of Advanced Materials Physics, Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Faculty of Science (China); Li, M.; Liu, L.; Zhang, C.; Li, X.; Yang, J. B. [Tianjin Normal University, College of Physics and Materials Science (China)

2015-05-15

The charge defective structure in Bi{sub 1−x}Ca{sub x}FeO{sub 3} (CBFO, x = 0, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3) nanoparticles (NPs) ranging from 140 to 25 nm as well as their relations to band gap and leakage current behavior are investigated. It is demonstrated that Ca doping effectively narrows the band gap from ∼2.16 to ∼2.02 eV, due to the appearance and accumulation of oxygen vacancy. Subsequently, enhanced electrical conductivity was obtained in these CBFO NPs, which leads to the appearance of a distinct threshold switching behavior in Ca-doped BFO NPs with higher conductivity at room temperature. Possible mechanisms for Ca doping effects on the electric conduction were discussed upon the interplay of NPs’ size effect and mobile charged defects on the basis of reduced particle size and the increased density of oxygen vacancy analyzed through X-ray photoelectron spectrum.

The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.

Science.gov (United States)

Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2014-05-01

Voltage-gated Ca(2+) channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca(2+) channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca(2+) channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca(2+) channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3(-/-) mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca(2+) influx into RTN neurons can trigger small-conductance Ca(2+)-activated K(+)-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca(2+) channels in rodent sleep. The role of CaV2.3 Ca(2+) channels was analyzed in CaV2.3(-/-) mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3(-/-) mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca(2+) channel expression. The detailed mechanisms of SWS increase in CaV2.3(-/-) mice remain to be determined. Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra

Thermal conductivity of Ca3Co2O6 single crystals

Science.gov (United States)

Che, H. L.; Shi, J.; Wu, J. C.; Rao, X.; Liu, X. G.; Zhao, X.; Sun, X. F.

2018-05-01

Ca3Co2O6 is a rare example of one-dimensional Ising spin-chain material with the moments preferentially aligned along the c axis. In this work, we study the c-axis thermal conductivity (κc) of Ca3Co2O6 single crystal at low temperatures down to 0.3 K and in magnetic fields up to 14 T. The zero-field κc(T) shows a large phonon peak and can be well fitted by using the classical Debye model, which indicates that the heat transport is purely phononic. Moreover, the low-T κc(H) isotherms with H || c display a field-independent behavior. These results indicate that there is no contribution of magnetic excitations to the thermal conductivity in Ca3Co2O6, neither carrying heat nor scattering phonons, which can be attributed to the Ising-like spin anisotropy.

MiRNA-135a regulates the expression of small conductance calcium-activated potassium (SK3) channels in epilepsy-like conditions

NARCIS (Netherlands)

Honrath, Birgit; Norwood, Braxton; Tanrioever, Gaye; Kuter, Katarzyna; Henshall, David C; Aksel-Aksoy, Ayla; Schratt, Gerhard; Pasterkamp, Jeroen; Dencher, Norbert A.; Nieweg, Katja; Culmsee, Carsten; Dolga, Amalia Mihalea

2017-01-01

Background Excessive and hypersynchronous neuronal discharges are key characteristics in the pathophysiology of neurological disorders such as epilepsy. Owing to their ability of regulating neuronal excitability, small conductance calcium-activated potassium (SK) channels have been implicated in

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake.

Science.gov (United States)

Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

2017-05-01

Mitochondrial calcium ([Ca 2+ ] m ) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca 2+ ] m uptake upon SK channel activation as detected by time lapse mitochondrial Ca 2+ measurements with the Ca 2+ -binding mitochondria-targeted aequorin and FRET-based [Ca 2+ ] m probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca 2+ ] m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.

Conduction and transport numbers in metacomposites MeWO4 · WO3 (Me = Ca, Sr, Ba)

International Nuclear Information System (INIS)

Nejman, A.Ya.; Pestereva, N.N.; Sharafutdinov, A.R.; Kostikov, Yu.P.

2005-01-01

The conductivity and transfer numbers of charge carriers for composites in the MeWO 4 -WO 3 (Me = Ca, Sr, Ba) systems are studied as a function of the temperature and the activity of oxygen in a gas phase. The transfer numbers are determined by the emf method and are estimated from dependences of conductivity on the activity of oxygen in a gas phase. The deficiencies of the given procedure as applied to investigation of properties of composite phases are analyzed. The materials under study are classified as metacomposites. The concentration intervals of the ionic, mixed, and electronic conductivities are determined. The conductivity of (100-x)MeWO 4 · xWO 3 composites is predominantly ionic at x ≤ 10 (Me = Ca), x ≤ 60 (Me = Sr), and x ≤ 45 (Me = Ba). The obtained data are explained in the framework of a model that represents a composite as a distributed matrix system where a film of surface phase MeW-s with a high mobility of oxygen ions plays the role of a connected matrix. It is presumed that the surface phase MeW-s possesses double-sided surface activity (α MeW-s ≤ α WO 3 , α MeWO 4 ) and a higher mobility with respect to MeWO 4 and WO 3 . The discovered anomalies of dependences σ O 2- (T) and partial conductivities σ O 2- , σ el (T) are explained by a change in the stoichiometry, morphology, and the degree of tie-up of surface phase MeW-s caused by a change in the temperature and composition of composites [ru

Ionic conductivity of Ca and Mg doped NdGdZr1.95Sc0.05O7

International Nuclear Information System (INIS)

Anithakumari, P.; Mandal, B.P.; Grover, V.; Tyagi, A.K.; Mishra, A.K.

2014-01-01

The ionic conductivity of pyrochlore based materials makes them promising candidates for fuel-cell applications where high ionic conductivity and low activation energy are desired. Earlier it has been reported that 5%Sc doped GdNdZr 2 O 7 shows highest ionic conductivity. In this present work, an attempt has been made to further increase the oxygen vacancy concentration by the incorporation of Ca 2+ and Mg 2+ ions at A site of NdGdZr 1.95 Sc 0.05 O 7 (NGZS)

A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle.

Science.gov (United States)

Bao, Rongfeng; Lifshitz, Lawrence M; Tuft, Richard A; Bellvé, Karl; Fogarty, Kevin E; ZhuGe, Ronghua

2008-07-01

Ca(2+) sparks are highly localized, transient releases of Ca(2+) from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca(2+) sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca(2+)-activated K(+) channels, and also gate Ca(2+)-activated Cl(-) (Cl((Ca))) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca(2+) sparks is well understood, little information is available on how Ca(2+) sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl((Ca)) channels in spark sites in airway myocytes from mouse. Ca(2+) sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca(2+) current underlying a Ca(2+) spark (I(Ca(spark))), with an appropriate correction for endogenous fixed Ca(2+) buffer, which was characterized by flash photolysis of NPEGTA. We found that I(Ca(spark)) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca(2+) sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the I(Ca(spark)) by less than 3 ms, and its rising phase matches the duration of the I(Ca(spark)). We further determined that Cl((Ca)) channels on average are exposed to a [Ca(2+)] of 2.4 microM or greater during Ca(2+) sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca(2+)] produced by a reaction-diffusion simulation with measured I(Ca(spark)). Finally we estimated that the number of Cl((Ca)) channels localized in Ca(2+) spark sites could account for all the Cl((Ca)) channels in the entire cell. Taken together these results lead us to propose a model in which

Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine

Science.gov (United States)

Baker, Salah A.; Drumm, Bernard T.; Saur, Dieter; Hennig, Grant W.; Ward, Sean M.

2016-01-01

Key points Interstitial cells of Cajal at the level of the deep muscular plexus (ICC‐DMP) in the small intestine generate spontaneous Ca2+ transients that consist of localized Ca2+ events and limited propagating Ca2+ waves.Ca2+ transients in ICC‐DMP display variable characteristics: from discrete, highly localized Ca2+ transients to regionalized Ca2+ waves with variable rates of occurrence, amplitude, duration and spatial spread.Ca2+ transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells.Ca2+ transients in ICC‐DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s).Functional intracellular Ca2+ stores are essential for spontaneous Ca2+ transients, and the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump is necessary for maintenance of spontaneity.Ca2+ release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3Rs). Release from these channels is interdependent.ICC express transcripts of multiple RyRs and InsP3Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Abstract Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC‐DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC‐DMP are mediated by activation of Ca2+‐activated Cl− channels; thus, Ca2+ signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca2+ transients in ICC‐DMP within intact jejunal muscles expressing a genetically encoded Ca2+ indicator (GCaMP3) selectively in ICC. ICC‐DMP displayed spontaneous Ca2+ transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca2+ transients was highly variable, and it was

Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine.

Science.gov (United States)

Baker, Salah A; Drumm, Bernard T; Saur, Dieter; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

2016-06-15

Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) -activated K(+) channels.

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Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-06-01

Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). At a concentration without direct effect on vascular tone, kaempferol (3 × 10(-6) M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by N(ω)-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10(-4) M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10(-6) M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10(-3) M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa 1.1; 10(-7) M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa 1.1 channels. © 2015 The British Pharmacological Society.

A Close Association of RyRs with Highly Dense Clusters of Ca2+-activated Cl− Channels Underlies the Activation of STICs by Ca2+ Sparks in Mouse Airway Smooth Muscle

Science.gov (United States)

Bao, Rongfeng; Lifshitz, Lawrence M.; Tuft, Richard A.; Bellvé, Karl; Fogarty, Kevin E.; ZhuGe, Ronghua

2008-01-01

Ca2+ sparks are highly localized, transient releases of Ca2+ from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca2+ sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca2+-activated K+ channels, and also gate Ca2+-activated Cl− (Cl(Ca)) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca2+ sparks is well understood, little information is available on how Ca2+ sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl(Ca) channels in spark sites in airway myocytes from mouse. Ca2+ sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca2+ current underlying a Ca2+ spark (ICa(spark)), with an appropriate correction for endogenous fixed Ca2+ buffer, which was characterized by flash photolysis of NPEGTA. We found that ICa(spark) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca2+ sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the ICa(spark) by less than 3 ms, and its rising phase matches the duration of the ICa(spark). We further determined that Cl(Ca) channels on average are exposed to a [Ca2+] of 2.4 μM or greater during Ca2+ sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca2+] produced by a reaction-diffusion simulation with measured ICa(spark). Finally we estimated that the number of Cl(Ca) channels localized in Ca2+ spark sites could account for all the Cl(Ca) channels in the entire cell. Taken together these results lead us to propose a model in which RyRs and Cl(Ca) channels in Ca2+ spark sites localize

Mechanism of small-polaron formation in the biferroic YCrO{sub 3} doped with calcium

Energy Technology Data Exchange (ETDEWEB)

Duran, A., E-mail: dural@cnyn.unam.mx [Universidad Nacional Autonoma de Mexico, Centro de Nanociencias y Nanotecnologia, Apartado Postal 41, C.P. 22800, Ensenada, B.C. (Mexico); Verdin, E. [Universidad de Sonora, Departamento de Fisica, Apartado Postal 1626, Hermosillo, Sonora C.P. 8300 (Mexico); Escamilla, R.; Morales, F.; Escudero, R. [Universidad Nacional Autonoma de Mexico, Instituto de Investigaciones en Materiales, Apartado Postal 70-360, Mexico D.F. 04510 (Mexico)

2012-04-16

Highlights: Black-Right-Pointing-Pointer The Ca doped in the YCrO3 matrix was analyzed by means of complete structural, magnetic and electric properties. Black-Right-Pointing-Pointer E{sub act} deduced by Arrhenius' Law suggests small-polarons as conduction mechanisms in pristine and doped sample. Black-Right-Pointing-Pointer Local non-centrosymmetry in pristine sample is proposed as responsible of small polarons formation. Black-Right-Pointing-Pointer A mechanism of formation of small polarons is proposed supported by experimental evidence. Black-Right-Pointing-Pointer The structural distortion caused by the Ca doped in the YCrO3 matrix is harmful to the Ferroic properties. - Abstract: The effects of Ca substitutions on the structure, magnetism and electrical properties of YCrO{sub 3} ceramics are investigated by X-ray diffraction, magnetic susceptibility and electrical conductivity measurements. The cell volume decrease occurs through the change from Cr(III) to Cr(IV) as a result of the charge compensation of the Ca doping. No changes are observed in the antiferromagnetic transition temperature while strong changes are observed in the transport measurements due to Ca content. The increase of the electrical conductivity as well as the decrease of the activation energy is caused by the formation of the small-polarons localized in the O-Cr-O lattice distortion. The origin of small-polarons in the undoped sample is different in nature from the calcium doped. 'Local non-centrosymmetry' is the source of the small-polaron formation in undoped sample, while the change from Cr(III) to Cr(IV) through the charge compensation of Ca(II) in the Y(III) site is the source of small-polarons formations. The decrease of the average bond length Cr-O as well as effective moments in the paramagnetic state and the increase of the electrical conductivity are clear evidence that the Ca doping induces localized polarons, which in turn, these quasiparticles move from site to

[β-estradiol activates BK(Ca) in mesenteric artery smooth muscle cells of post-menopause women].

Science.gov (United States)

Cheng, Jun; Zeng, Xiao-Rong; Li, Peng-Yun; Lu, Ting-Ting; Tan, Xiao-Qiu; Wen, Jing; Yang, Yan

2012-04-25

The aim of the present study was to study the effect of β-estradiol (β-E(2)) on the large-conductance Ca(2+)-activated potassium (BK(Ca)) channel in mesenteric artery smooth muscle cells (SMCs). The mesenteric arteries were obtained from post-menopause female patients with abdominal surgery, and the SMCs were isolated from the arteries using an enzymatic disassociation. According to the sources, the SMCs were divided into non-hypertension (NH) and essential hypertension (EH) groups. Single channel patch clamp technique was used to investigate the effect of β-E(2) and ICI 182780 (a specific blocker of estrogen receptor) on BK(Ca) in the SMCs. The results showed the opening of BK(Ca) in the SMCs was voltage and calcium dependent, and could be blocked by IbTX. β-E(2) (100 μmol/L) significantly increased open probability (Po) of BK(Ca) in both NH and EH groups. After β-E(2) treatment, NH group showed higher Po of BK(Ca) compared with EH group. ICI 182780 could inhibit the activating effect of β-E(2) on BK(Ca) in no matter NH or EH groups. These results suggest β-E(2) activates BK(Ca) in mesenteric artery SMCs from post-menopause women via estrogen receptor, but hypertension may decline the activating effect of β-E(2) on BK(Ca).

Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

Directory of Open Access Journals (Sweden)

Peter Rellos

2010-07-01

Full Text Available Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.

Science.gov (United States)

Zhang, Xiao-Dong; Coulibaly, Zana A; Chen, Wei Chun; Ledford, Hannah A; Lee, Jeong Han; Sirish, Padmini; Dai, Gu; Jian, Zhong; Chuang, Frank; Brust-Mascher, Ingrid; Yamoah, Ebenezer N; Chen-Izu, Ye; Izu, Leighton T; Chiamvimonvat, Nipavan

2018-03-16

Small-conductance Ca 2+ -activated K + (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca 2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca 2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca 2+ microdomains necessary for SK channel activation. SK currents coupled with Ca 2+ influx via L-type Ca 2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Ca v 1.2 Ca 2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Ca v 1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca 2+ signaling.

Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII

Science.gov (United States)

Li, Lu; Stefan, Melanie I.; Le Novère, Nicolas

2012-01-01

NMDA receptor dependent long-term potentiation (LTP) and long-term depression (LTD) are two prominent forms of synaptic plasticity, both of which are triggered by post-synaptic calcium elevation. To understand how calcium selectively stimulates two opposing processes, we developed a detailed computational model and performed simulations with different calcium input frequencies, amplitudes, and durations. We show that with a total amount of calcium ions kept constant, high frequencies of calcium pulses stimulate calmodulin more efficiently. Calcium input activates both calcineurin and Ca2+/calmodulin-dependent protein kinase II (CaMKII) at all frequencies, but increased frequencies shift the relative activation from calcineurin to CaMKII. Irrespective of amplitude and duration of the inputs, the total amount of calcium ions injected adjusts the sensitivity of the system to calcium input frequencies. At a given frequency, the quantity of CaMKII activated is proportional to the total amount of calcium. Thus, an input of a small amount of calcium at high frequencies can induce the same activation of CaMKII as a larger amount, at lower frequencies. Finally, the extent of activation of CaMKII signals with high calcium frequency is further controlled by other factors, including the availability of calmodulin, and by the potency of phosphatase inhibitors. PMID:22962589

Significance of CaV3.2 T-type Ca2+ channels for pressure- and flow-dependent vasomotor responses in rat and mouse mesenteric small arteries

DEFF Research Database (Denmark)

Jensen, Lars Jørn; Björling, K.; Hansen, Pernille B. Lærkegaard

RNA was similar in WT vs. CaV3.2-/- mice. CONCLUSION: FMVD responses appear to rely on an endothelium-dependent hyperpolarization in rat small mesenteric arteries. CaV3.2 channels are negative feedback modulators of myogenic tone in small mesenteric artery in young mice. The age-dependent decline in CaV3...... in young CaV3.2-/- mice (8-15 weeks) vs. age-matched WT mice (Pyoung WT mice, the CaV3.2 blocker NiCl2 (30 µM) significantly enhanced myogenic tone (P... was not seen (N=4). In young and old CaV3.2-/- mice no effects of NiCl2 were observed. The FMVD response in rat mesenteric arteries was not blocked by L-NAME, but was almost abolished by the SKCa/IKCa channel blockers apamin/TRAM-34 (50 nM/1 µM) (P

Burst activity and ultrafast activation kinetics of CaV1.3 Ca²⁺ channels support presynaptic activity in adult gerbil hair cell ribbon synapses.

Science.gov (United States)

Zampini, Valeria; Johnson, Stuart L; Franz, Christoph; Knipper, Marlies; Holley, Matthew C; Magistretti, Jacopo; Masetto, Sergio; Marcotti, Walter

2013-08-15

Auditory information transfer to afferent neurons relies on precise triggering of neurotransmitter release at the inner hair cell (IHC) ribbon synapses by Ca²⁺ entry through CaV1.3 Ca²⁺ channels. Despite the crucial role of CaV1.3 Ca²⁺ channels in governing synaptic vesicle fusion, their elementary properties in adult mammals remain unknown. Using near-physiological recording conditions we investigated Ca²⁺ channel activity in adult gerbil IHCs. We found that Ca²⁺ channels are partially active at the IHC resting membrane potential (-60 mV). At -20 mV, the large majority (>70%) of Ca²⁺ channel first openings occurred with an estimated delay of about 50 μs in physiological conditions, with a mean open time of 0.5 ms. Similar to other ribbon synapses, Ca²⁺ channels in IHCs showed a low mean open probability (0.21 at -20 mV), but this increased significantly (up to 0.91) when Ca²⁺ channel activity switched to a bursting modality. We propose that IHC Ca²⁺ channels are sufficiently rapid to transmit fast signals of sound onset and support phase-locking. Short-latency Ca²⁺ channel opening coupled to multivesicular release would ensure precise and reliable signal transmission at the IHC ribbon synapse.

Inhibitory Neural Regulation of the Ca2+ Transients in Intramuscular Interstitial Cells of Cajal in the Small Intestine

Directory of Open Access Journals (Sweden)

Salah A. Baker

2018-04-01

Full Text Available Gastrointestinal motility is coordinated by enteric neurons. Both inhibitory and excitatory motor neurons innervate the syncytium consisting of smooth muscle cells (SMCs interstitial cells of Cajal (ICC and PDGFRα+ cells (SIP syncytium. Confocal imaging of mouse small intestines from animals expressing GCaMP3 in ICC were used to investigate inhibitory neural regulation of ICC in the deep muscular plexus (ICC-DMP. We hypothesized that Ca2+ signaling in ICC-DMP can be modulated by inhibitory enteric neural input. ICC-DMP lie in close proximity to the varicosities of motor neurons and generate ongoing Ca2+ transients that underlie activation of Ca2+-dependent Cl− channels and regulate the excitability of SMCs in the SIP syncytium. Electrical field stimulation (EFS caused inhibition of Ca2+ for the first 2–3 s of stimulation, and then Ca2+ transients escaped from inhibition. The NO donor (DEA-NONOate inhibited Ca2+ transients and Nω-Nitro-L-arginine (L-NNA or a guanylate cyclase inhibitor (ODQ blocked inhibition induced by EFS. Purinergic neurotransmission did not affect Ca2+ transients in ICC-DMP. Purinergic neurotransmission elicits hyperpolarization of the SIP syncytium by activation of K+ channels in PDGFRα+ cells. Generalized hyperpolarization of SIP cells by pinacidil (KATP agonist or MRS2365 (P2Y1 agonist also had no effect on Ca2+ transients in ICC-DMP. Peptidergic transmitter receptors (VIP and PACAP are expressed in ICC and can modulate ICC-DMP Ca2+ transients. In summary Ca2+ transients in ICC-DMP are blocked by enteric inhibitory neurotransmission. ICC-DMP lack a voltage-dependent mechanism for regulating Ca2+ release, and this protects Ca2+ handling in ICC-DMP from membrane potential changes in other SIP cells.

Study of heat conductivity, electric conductivity and thermo-emf of BiSrCaCu2Ox and Bi1.82Sr1.73Ca1.73Ca1.25Cu2.2Ox systems

International Nuclear Information System (INIS)

Zhukova, T.B.; Parfen'eva, L.S.; Popov, V.V.; Melekh, B.T.; Smirnov, I.A.; Khalmedov, Kh.M.

1991-01-01

Phase compositions are determined and temperature dependences are measured of x-heat conductivity, ρ-electric resistance and α-thermo-emf of polycrystal, monophase, highly textured HTSC samples of BiSrCaCu 2 O x and Bi 1.82 Sr 1.73 Ca 1.25 Cu 2.2 O x produced through method of direct induction melting in the air in a cold container. Sample 'aging' after storage in the air and vacuum, leading to decrease in the number of foring phases and increase in the basic phase content as well as to change of x, ρ and α coefficients is identified

Renovascular BK(Ca) channels are not activated in vivo under resting conditions and during agonist stimulation

DEFF Research Database (Denmark)

Magnusson, Linda; Sørensen, Charlotte Mehlin; Braunstein, Thomas Hartig

2006-01-01

We investigated the role of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by BK(Ca) of the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation.......3 nmol/min) did not have any effect. Renal injection of ANG II (1-4 ng) or NE (10-40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the BK(Ca) opener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE......, there is no indication for a major role for BK(Ca) channels in the control of basal renal tone in vivo. Furthermore, BK(Ca) channels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular BK(Ca) channels...

Milrinone-Induced Postconditioning Requires Activation of Mitochondrial Ca2+-sensitive Potassium (mBKCa) Channels

NARCIS (Netherlands)

Behmenburg, Friederike; Trefz, Lara; Dorsch, Marianne; Ströthoff, Martin; Mathes, Alexander; Raupach, Annika; Heinen, André; Hollmann, Markus W.; Berger, Marc M.; Huhn, Ragnar

2017-01-01

Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced

Activation analysis with small mobile reactors

International Nuclear Information System (INIS)

Chung, C.

1990-01-01

A small nuclear reactor (a low-power reactor without heat removal devices) usually has thermal power output under 100 W and an average in-core thermal neutron flux below 10 9 n/cm 2 s. Conventional activation analysis is restricted to determination of specific elements with large neutron capture cross sections in sizable samples. In-vivo prompt gamma activation analysis (IVPGAA) can be used for diagnosis of elemental composition of the human body, particularly the essential elements Ca, Cl, N, and P in the whole body, and toxic Cd and Hg in contaminated organs. In this chapter, activation analysis using an external neutron beam from the Tsing Hua Mobile Educational Reactor (THMER) for in vivo activation is described. Characteristics of the mobile reactor, in-vivo medical diagnosis, and radiation safety are emphasized. 17 refs, 12 figs, 3 tabs

Transport and ordering of polarons in CER manganites PrCaMnO

International Nuclear Information System (INIS)

Schramm, S; Hoffmann, J; Jooss, Ch

2008-01-01

The temperature-dependent resistivity and the colossal resistance effect induced by strong electric fields of the small-band Pr 1-x Ca x MnO 3 (PCMO) manganites are analysed with respect to the influence of the Ca doping, post-annealing, the prehistory of the electric stimulation, and the physical dimensions of the sample. Despite the phase separation between charge and orbital ordered and disordered phases, PCMO reveals the properties of a homogeneous medium with a conductivity governed by the hopping of small polarons if the electric field is not too strong. In contrast, high electric fields induce a structural transition which gives rise to a glassy behaviour in the transient regime. In the low resistance state the small activation energy of charge carrier hopping implies a transition to large polaron hopping

Biophysical characterization of inwardly rectifying potassium currents (I(K1) I(K,ACh), I(K,Ca)) using sinus rhythm or atrial fibrillation action potential waveforms

DEFF Research Database (Denmark)

Tang, Chuyi; Skibsbye, Lasse; Yuan, Lei

2015-01-01

Although several physiological, pathophysiological and regulatory properties of classical inward rectifier K+ current I(K1), G-protein coupled inwardly-rectifying K+ current I(K,ACh) and the small-conductance Ca2+ activated K+ current I(K,Ca) have been identified, quantitative biophysical details...

Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes.

OpenAIRE

David H Vandorpe; Chang Xu; Boris E Shmukler; Leo E Otterbein; Marie Trudel; Frederick Sachs; Philip A Gottlieb; Carlo Brugnara; Seth L Alper

2010-01-01

Background: Deoxygenation of sickle erythrocytes activates a cation permeability of unknown molecular identity (Psickle), leading to elevated intracellular [Ca2+] ([Ca2+]i) and subsequent activation of KCa 3.1. The resulting erythrocyte volume decrease elevates intracellular hemoglobin S (HbSS) concentration, accelerates deoxygenation-induced HbSS polymerization, and increases the likelihood of cell sickling. Deoxygenation-induced currents sharing some properties of Psickle have been recorded...

Identification and characterization of Ca2+-activated K+ channels in granulosa cells of the human ovary

Directory of Open Access Journals (Sweden)

Berg Ulrike

2009-04-01

Full Text Available Abstract Background Granulosa cells (GCs represent a major endocrine compartment of the ovary producing sex steroid hormones. Recently, we identified in human GCs a Ca2+-activated K+ channel (KCa of big conductance (BKCa, which is involved in steroidogenesis. This channel is activated by intraovarian signalling molecules (e.g. acetylcholine via raised intracellular Ca2+ levels. In this study, we aimed at characterizing 1. expression and functions of KCa channels (including BKCa beta-subunits, and 2. biophysical properties of BKCa channels. Methods GCs were obtained from in vitro-fertilization patients and cultured. Expression of mRNA was determined by standard RT-PCR and protein expression in human ovarian slices was detected by immunohistochemistry. Progesterone production was measured in cell culture supernatants using ELISAs. Single channels were recorded in the inside-out configuration of the patch-clamp technique. Results We identified two KCa types in human GCs, the intermediate- (IK and the small-conductance KCa (SK. Their functionality was concluded from attenuation of human chorionic gonadotropin-stimulated progesterone production by KCa blockers (TRAM-34, apamin. Functional IK channels were also demonstrated by electrophysiological recording of single KCa channels with distinctive features. Both, IK and BKCa channels were found to be simultaneously active in individual GCs. In agreement with functional data, we identified mRNAs encoding IK, SK1, SK2 and SK3 in human GCs and proteins of IK and SK2 in corresponding human ovarian cells. Molecular characterization of the BKCa channel revealed the presence of mRNAs encoding several BKCa beta-subunits (beta2, beta3, beta4 in human GCs. The multitude of beta-subunits detected might contribute to variations in Ca2+ dependence of individual BKCa channels which we observed in electrophysiological recordings. Conclusion Functional and molecular studies indicate the presence of active IK and SK

Endothelial Ca+-activated K+ channels in normal and impaired EDHF-dilator responses--relevance to cardiovascular pathologies and drug discovery.

Science.gov (United States)

Grgic, Ivica; Kaistha, Brajesh P; Hoyer, Joachim; Köhler, Ralf

2009-06-01

The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels (K(Ca)) has been suggested to play a critical role in initializing EDHF-dilator responses in conduit and resistance-sized arteries of many species including humans. Endothelial K(Ca) currents are mediated by the two K(Ca) subtypes, intermediate-conductance K(Ca) (KCa3.1) (also known as, a.k.a. IK(Ca)) and small-conductance K(Ca) type 3 (KCa2.3) (a.k.a. SK(Ca)). In this review, we summarize current knowledge about endothelial KCa3.1 and KCa2.3 channels, their molecular and pharmacological properties and their specific roles in endothelial function and, particularly, in the EDHF-dilator response. In addition we focus on recent experimental evidences derived from KCa3.1- and/or KCa2.3-deficient mice that exhibit severe defects in EDHF signalling and elevated blood pressures, thus highlighting the importance of the KCa3.1/KCa2.3-EDHF-dilator system for blood pressure control. Moreover, we outline differential and overlapping roles of KCa3.1 and KCa2.3 for EDHF signalling as well as for nitric oxide synthesis and discuss recent evidence for a heterogeneous (sub) cellular distribution of KCa3.1 (at endothelial projections towards the smooth muscle) and KCa2.3 (at inter-endothelial borders and caveolae), which may explain their distinct roles for endothelial function. Finally, we summarize the interrelations of altered KCa3.1/KCa2.3 and EDHF system impairments with cardiovascular disease states such as hypertension, diabetes, dyslipidemia and atherosclerosis and discuss the therapeutic potential of KCa3.1/KCa2.3 openers as novel types of blood pressure-lowering drugs.

Activation of a Ca2+-dependent cation conductance with properties of TRPM2 by reactive oxygen species in lens epithelial cells.

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Keckeis, Susanne; Wernecke, Laura; Salchow, Daniel J; Reichhart, Nadine; Strauß, Olaf

2017-08-01

Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca 2+ -dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca 2+ - and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca 2+ -activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells. Using whole-cell patch-clamp technique, ionomycin evoked non-selective cation currents with linear current-voltage relationship in both cell types. The current was decreased by flufenamic acid (FFA), 2-APB, 9-phenanthrol and miconazole, but insensitive to DIDS, ruthenium red, and intracellularly applied spermine. H 2 O 2 evoked a comparable current, abolished by FFA. TRPM2 protein expression in HLE-B3 cells was confirmed by means of immunocytochemistry and western blot. In summary, we conclude that lens epithelial cells functionally express Ca 2+ - and H 2 O 2 -activated non-selective cation channels with properties of TRPM2. Copyright © 2017. Published by Elsevier Ltd.

Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock.

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Whitt, Joshua P; McNally, Beth A; Meredith, Andrea L

2018-02-05

Large conductance K + (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca 2+ (Ca 2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca 2+ channels (VGCCs) and channels mediating Ca 2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca 2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca 2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca 2+ i are reduced. Here, to determine whether diurnal regulation of Ca 2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca 2+ channels (LTCCs) are the primary daytime Ca 2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)-mediated Ca 2+ i release. The N- and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca 2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. © 2018 Whitt et al.

Ca2+ signals, cell membrane disintegration, and activation of TMEM16F during necroptosis.

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Ousingsawat, Jiraporn; Cabrita, Inês; Wanitchakool, Podchanart; Sirianant, Lalida; Krautwald, Stefan; Linkermann, Andreas; Schreiber, Rainer; Kunzelmann, Karl

2017-01-01

Activated receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like (MLKL) are essential components of the necroptotic pathway. Phosphorylated MLKL (pMLKL) is thought to induce membrane leakage, leading to cell swelling and disintegration of the cell membrane. However, the molecular identity of the necroptotic membrane pore remains unclear, and the role of pMLKL for membrane permeabilization is currently disputed. We observed earlier that the phospholipid scramblase and ion channel TMEM16F/anoctamin 6 cause large membrane currents, cell swelling, and cell death when activated by a strong increase in intracellular Ca 2+ . We, therefore, asked whether TMEM16F is also central to necroptotic cell death and other cellular events during necroptosis. Necroptosis was induced by TNFα, smac mimetic, and Z-VAD (TSZ) in NIH3T3 fibroblasts and the four additional cell lines HT 29 , 16HBE, H441, and L929. Time-dependent changes in intracellular Ca 2+ , cell morphology, and membrane currents were recorded. TSZ induced a small and only transient oscillatory rise in intracellular Ca 2+ , which was paralleled by the activation of outwardly rectifying Cl - currents, which were typical for TMEM16F/ANO6. Ca 2+ oscillations were due to Ca 2+ release from endoplasmic reticulum, and were independent of extracellular Ca 2+ . The initial TSZ-induced cell swelling was followed by cell shrinkage. Using typical channel blockers and siRNA-knockdown, the Cl - currents were shown to be due to the activation of ANO6. However, the knockdown of ANO6 or inhibitors of ANO6 did not inhibit necroptotic cell death. The present data demonstrate the activation of ANO6 during necroptosis, which, however, is not essential for cell death.

Blockade of Ca2+-activated K+ channels in T cells: an option for the treatment of multiple sclerosis?

DEFF Research Database (Denmark)

Madsen, Lars Siim; Christophersen, Palle; Olesen, Søren-Peter

2005-01-01

Voltage- and Ca(2+)-dependent K(+) channels in the membrane of both T and B lymphocytes are important for the cellular immune response. In the current issue of the European Journal of Immunology, Reich et al. demonstrate that selective blockade of the intermediate-conductance Ca(2+)-activated K(+...

Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells

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Martín, Pedro; Enrique, Nicolás; Palomo, Ana R. Roldán; Rebolledo, Alejandro; Milesi, Veronica

2012-01-01

Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 µM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 µM) can also block whole-cell K+ currents (~45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account. PMID:22688134

Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?

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Jensen, Lars Jørn; Holstein-Rathlou, Niels-Henrik

2009-01-01

The largest peripheral blood pressure drop occurs in terminal arterioles (microm lumen diameter). L-type voltage-dependent Ca2+ channels (VDCCs) are considered the primary pathway for Ca2+ influx during physiologic activation of vascular smooth muscle cells (VSMC). Recent evidence suggests...... was predominantly expressed in endothelial cells. Voltage-dependent Ca2+ entry was inhibited by the new specific T-type blockers R(-)-efonidipine and NNC 55-0396. The effect of NNC 55-0396 persisted in depolarized arterioles, suggesting an unusually high activation threshold of mesenteric T-type channels. T...... that T-type VDCCs are expressed in renal afferent and efferent arterioles, mesenteric arterioles, and skeletal muscle arterioles. T-type channels are small-conductance, low voltage-activated, fast-inactivating channels. Thus, their role in supplying Ca2+ for contraction of VSMC has been disputed. However...

The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

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González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

2014-01-01

An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p calcareum Ca was greater (p calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly absorbed before the duodenum, but Ca from L. calcareum Ca is mostly absorbed in the jejunum and ileum.

Recording of the Neural Activity Induced by the Electrical Subthalamic Stimulation Using Ca2+ Imaging

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Tamura, Atsushi; Yagi, Tetsuya; Osanai, Makoto

The basal ganglia (BG) have important roles in some kind of motor control and learning. Parkinson's disease is one of the motor impairment disease. Recently, to recover a motor severity in patients of Parkinsonism, the stimulus electrode is implanted to the subthalamic nucleus, which is a part of the basal ganglia, and the deep brain stimulation (DBS) is often conducted. However, the effects of the DBS on the subthalamic neurons have not been elucidated. Thus, to analyze the effects of the electrical stimulation on the subthalamic neurons, we conducted the calcium imaging at the mouse subthalamic nucleus. When the single stimulus was applied to the subthalamic nucleus, the intracellular calcium ([Ca2+]i) transients were observed. In the case of application of the single electrical stimulation, the [Ca2+]i arose near the stimulus position. When 100 Hz 10-100 times tetanic stimulations were applied, the responded area and the amplitudes of [Ca2+]i transients were increased. The [Ca2+]i transients were disappeared almost completely on the action potential blockade, but blockade of the excitatory and the inhibitory synaptic transmission had little effects on the responded area and the amplitudes of the [Ca2+]i transients. These results suggested that the electrical stimulation to the subthalamic neurons led to activate the subthalamic neurons directly but not via synaptic transmissions. Thus, DBS may change the activity of the subthalamic neurons, hence, may alter the input-output relationship of the subthalamic neurons

Intracellular Ca(2+) release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal.

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Zhu, Mei Hong; Sung, Tae Sik; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

2015-04-15

Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca(2+)-activated Cl(-) channels. We investigated the hypothesis that the Ca(2+) responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca(2+) stores. ICC, obtained from the small intestine of Kit(+/copGFP) mice, were studied under voltage and current clamp to determine the effects of blocking Ca(2+) uptake into stores and release of Ca(2+) via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca(2+) concentration, suggesting that pacemaker activity depends on Ca(2+) dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca(2+) from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC. Copyright © 2015 the American Physiological Society.

Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal

Science.gov (United States)

Zhu, Mei Hong; Sung, Tae Sik; O'Driscoll, Kate; Koh, Sang Don

2015-01-01

Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca2+-activated Cl− channels. We investigated the hypothesis that the Ca2+ responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca2+ stores. ICC, obtained from the small intestine of Kit+/copGFP mice, were studied under voltage and current clamp to determine the effects of blocking Ca2+ uptake into stores and release of Ca2+ via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca2+ concentration, suggesting that pacemaker activity depends on Ca2+ dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca2+ from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC. PMID:25631870

The potent activation of Ca(2+)-activated K(+) current by NVP-AUY922 in the human pancreatic duct cell line (PANC-1) possibly independent of heat shock protein 90 inhibition.

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Chiang, Nai-Jung; Wu, Sheng-Nan; Chen, Li-Tzong

2015-04-01

NVP-AUY922 (AUY) is a potent inhibitor of heat shock protein 90 (HSP90). Whether this compound can exert additional effects on membrane ion channels remains elusive. We investigated the effect of AUY on ion currents in human pancreatic duct epithelial cells (PDECs), including PANC-1 and MIA PaCa-2. AUY increased the amplitude of the K(+) current (IK) in PANC-1 cells shown by whole-cell configuration. Single-channel recordings revealed a large-conductance Ca(2+)-activated K(+) (BKCa) channel in PANC-1, but not in MIA PaCa-2. In cell-attached mode, AUY increased the probability of BKCa channel opening and also potentiated the activity of stretch-induced channels. However, other HSP inhibitors, 17-AAG or BIIB021 only slightly increased the activity of BKCa channels. In inside-out recordings, sodium hydrosulphide or caffeic acid phenethyl ester increased the activity of BKCa channels, but AUY did not. We further evaluated whether conductance of Ca(2+)-activated K(+) channels (IK(Ca)) influenced secretion of HCO3(-) and fluid in PDECs by using a modified Whitcomb-Ermentrout model. Simulation studies showed that an increase in IK(Ca) resulted in additional secretion of HCO3(-) and fluid by mimicking the effect of AUY in PDECs. Collectively, AUY can interact with the BKCa channel to largely increase IK(Ca) in PDECs. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Positive Feedback Regulation of Agonist-Stimulated Endothelial Ca2+ Dynamics by KCa3.1 Channels in Mouse Mesenteric Arteries

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Qian, Xun; Francis, Michael; Köhler, Ralf

2014-01-01

Intermediate and small conductance KCa channels IK1 (KCa3.1) and SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, and their ablation results in increased arterial tone and hypertension. Activation of IK1 channels by local Ca(2+) transients from internal ...... stores or plasma membrane channels promotes arterial hyperpolarization and vasodilation. Here, we assess arteries from genetically altered IK1 knockout mice (IK1(-/-)) to determine whether IK1 channels exert a positive feedback influence on endothelial Ca(2+) dynamics....

Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

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Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

2016-11-01

Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells

DEFF Research Database (Denmark)

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

2008-01-01

have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously...... known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP......-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small...

Oxidized calmodulin kinase II regulates conduction following myocardial infarction: a computational analysis.

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Matthew D Christensen

2009-12-01

Full Text Available Calmodulin kinase II (CaMKII mediates critical signaling pathways responsible for divergent functions in the heart including calcium cycling, hypertrophy and apoptosis. Dysfunction in the CaMKII signaling pathway occurs in heart disease and is associated with increased susceptibility to life-threatening arrhythmia. Furthermore, CaMKII inhibition prevents cardiac arrhythmia and improves heart function following myocardial infarction. Recently, a novel mechanism for oxidative CaMKII activation was discovered in the heart. Here, we provide the first report of CaMKII oxidation state in a well-validated, large-animal model of heart disease. Specifically, we observe increased levels of oxidized CaMKII in the infarct border zone (BZ. These unexpected new data identify an alternative activation pathway for CaMKII in common cardiovascular disease. To study the role of oxidation-dependent CaMKII activation in creating a pro-arrhythmia substrate following myocardial infarction, we developed a new mathematical model of CaMKII activity including both oxidative and autophosphorylation activation pathways. Computer simulations using a multicellular mathematical model of the cardiac fiber demonstrate that enhanced CaMKII activity in the infarct BZ, due primarily to increased oxidation, is associated with reduced conduction velocity, increased effective refractory period, and increased susceptibility to formation of conduction block at the BZ margin, a prerequisite for reentry. Furthermore, our model predicts that CaMKII inhibition improves conduction and reduces refractoriness in the BZ, thereby reducing vulnerability to conduction block and reentry. These results identify a novel oxidation-dependent pathway for CaMKII activation in the infarct BZ that may be an effective therapeutic target for improving conduction and reducing heterogeneity in the infarcted heart.

Electric modulation of conduction in multiferroic Ca-doped BiFeO3 films

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Yang, C.-H.; Seidel, J.; Kim, S. Y.; Rossen, P. B.; Yu, P.; Gajek, M.; Chu, Y. H.; Martin, L. W.; Holcomb, M. B.; He, Q.; Maksymovych, P.; Balke, N.; Kalinin, S. V.; Baddorf, A. P.; Basu, S. R.; Scullin, M. L.; Ramesh, R.

2009-06-01

Many interesting materials phenomena such as the emergence of high-Tc superconductivity in the cuprates and colossal magnetoresistance in the manganites arise out of a doping-driven competition between energetically similar ground states. Doped multiferroics present a tantalizing evolution of this generic concept of phase competition. Here, we present the observation of an electronic conductor-insulator transition by control of band-filling in the model antiferromagnetic ferroelectric BiFeO3 through Ca doping. Application of electric field enables us to control and manipulate this electronic transition to the extent that a p-n junction can be created, erased and inverted in this material. A `dome-like' feature in the doping dependence of the ferroelectric transition is observed around a Ca concentration of ~1/8, where a new pseudo-tetragonal phase appears and the electric modulation of conduction is optimized. Possible mechanisms for the observed effects are discussed on the basis of the interplay of ionic and electronic conduction. This observation opens the door to merging magnetoelectrics and magnetoelectronics at room temperature by combining electronic conduction with electric and magnetic degrees of freedom already present in the multiferroic BiFeO3.

Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP-Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions.

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Nguyen, Thi Mong Diep; Combarnous, Yves; Praud, Christophe; Duittoz, Anne; Blesbois, Elisabeth

2016-01-01

Sperm require high levels of energy to ensure motility and acrosome reaction (AR) accomplishment. The AMP-activated protein kinase (AMPK) has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+), or of CaMKKs inhibitor (STO-609). Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and β), CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKβ was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+) but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+) than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+). Our results show for the first time the presence of CaMKKs (α and β) and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+) entry in sperm through the Ca(2+)/CaM/CaMKKs/CaMKI pathway. The Ca(2+)/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2+) entry

Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs Effects on AMP-Activated Protein Kinase (AMPK Regulation of Chicken Sperm Functions.

Directory of Open Access Journals (Sweden)

Thi Mong Diep Nguyen

Full Text Available Sperm require high levels of energy to ensure motility and acrosome reaction (AR accomplishment. The AMP-activated protein kinase (AMPK has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+/calmodulin-dependent protein kinase kinases (CaMKKs mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+, or of CaMKKs inhibitor (STO-609. Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and β, CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKβ was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+ but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+ than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+. Our results show for the first time the presence of CaMKKs (α and β and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+ entry in sperm through the Ca(2+/CaM/CaMKKs/CaMKI pathway. The Ca(2+/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2

Interaction between Na+/K+-pump and Na+/Ca2+-exchanger modulates intercellular communication.

Science.gov (United States)

Matchkov, Vladimir V; Gustafsson, Helena; Rahman, Awahan; Briggs Boedtkjer, Donna M; Gorintin, Sarah; Hansen, Anne Kirstine; Bouzinova, Elena V; Praetorius, Helle A; Aalkjaer, Christian; Nilsson, Holger

2007-04-13

Ouabain, a specific inhibitor of the Na(+)/K(+)-pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells is regulated through an interaction between the Na(+)/K(+)-pump and the Na(+)/Ca(2+)-exchanger leading to an increase in the intracellular calcium concentration ([Ca(2+)](i)) in discrete areas near the plasma membrane. [Ca(2+)](i) in smooth muscle cells was imaged in cultured rat aortic smooth muscle cell pairs (A7r5) and in rat mesenteric small artery segments simultaneously with force. In A7r5 coupling between cells was estimated by measuring membrane capacitance. Smooth muscle cells were uncoupled when the Na(+)/K(+)-pump was inhibited either by a low concentration of ouabain, which also caused a localized increase of [Ca(2+)](i) near the membrane, or by ATP depletion. Reduction of Na(+)/K(+)-pump activity by removal of extracellular potassium ([K(+)](o)) also uncoupled cells, but only after inhibition of K(ATP) channels. Inhibition of the Na(+)/Ca(2+)-exchange activity by SEA0400 or by a reduction of the equilibrium potential (making it more negative) also uncoupled the cells. Depletion of intracellular Na(+) and clamping of [Ca(2+)](i) at low concentrations prevented the uncoupling. The experiments suggest that the Na(+)/K(+)-pump may affect gap junction conductivity via localized changes in [Ca(2+)](i) through modulation of Na(+)/Ca(2+)-exchanger activity.

[Effects of desulfurization waste on calcium distribution, Ca(2+)-ATPase activity, and antioxidant characteristics of rice leaf under alkali stress].

Science.gov (United States)

Mao, Gui-Lian; Xu, Xing; Zeng, Jin; Yue, Zi-Hui; Yang, Shu-Juan

2012-02-01

To approach the action mechanisms of desulfurization waste on alleviating alkali stress-induced injury of rice, a pot experiment was conducted to study the variations of leaf total calcium content, calcium distribution, plasma membrane Ca(2+)-ATPase activity, and reactive oxygen content of rice seedlings under alkali stress after the application of desulfurization waste. In the control, a few calcium particulates scattered in the cell wall and chloroplasts, while applying desulfurization waste or CaSO4 increased the calcium particulates in the plasma membrane, intercellular space, cell wall, and vacuole significantly. With the increasing application rate of desulfurization waste or CaSO4, the leaf total calcium content increased, Ca(2+)-ATPase activity in plasma membrane and tonoplast presented an increasing trend, plasma membrane relative permeability, MDA content, and O2 production rate decreased, and SOD and POD activities increased. The desulfurization waste could relieve the alkali stress to rice in some extent, and the main reactive compound in the waste could be CaSO4.

Anti-tumor activity of self-charged (Eu,Ca):WO3 and Eu:CaWO4 nanoparticles

International Nuclear Information System (INIS)

Lin, Cao; Cong, Wang; De'An, Pan; Jiexin, Cao; Ping, Che; Volinsky, Alex A.

2012-01-01

Non-stoichiometric (Eu,Ca):WO 3 and Eu:CaWO 4 nanoparticles with anti-tumor activity are synthesized in a sol-gel method by adding excessive Eu 3+ and Ca 2+ ions to tungsten oxide crystal structure. Colorimetric assay shows that 10 nm (Eu,Ca):WO 3 and Eu:CaWO 4 nanoparticles can effectively inhibit growth of mammary cancer cells without any harm to normal cells. Nanoparticles are characterized by X-ray diffraction, high resolution transmission electron microscopy and fluorescence optical spectrometry. Nanomaterials, insoluble in synthesized water, have complicated self-charging surfaces that trap mammary cancer cells. Surface self-charging effect is suggested as the inhibition mechanism. (author)

Functional role of the Ca2+-activated Cl− channel DOG1/TMEM16A in gastrointestinal stromal tumor cells

International Nuclear Information System (INIS)

Berglund, Erik; Akcakaya, Pinar; Berglund, David; Karlsson, Fredrik; Vukojević, Vladana; Lee, Linkiat; Bogdanović, Darko; Lui, Weng-Onn; Larsson, Catharina; Zedenius, Jan; Fröbom, Robin; Bränström, Robert

2014-01-01

DOG1, a Ca 2+ -activated Cl − channel (CaCC), was identified in 2004 to be robustly expressed in gastrointestinal stromal tumors (GIST). It was rapidly included as a tumor marker in routine diagnostics, but the functional role remained unknown. CaCCs are important regulators of normal physiological functions, but also implicated in tumorigenesis, cancer progression, metastasis, cell migration, apoptosis, proliferation and viability in several malignancies. We therefore investigated whether DOG1 plays a role in the three latter in GIST by utilizing in vitro cell model systems. Confocal microscopy identified different subcellular localizations of DOG1 in imatinib-sensitive and imatinib-resistant cells. Electrophysiological studies confirmed that DOG1-specific pharmacological agents possess potent activating and inhibiting properties. Proliferation assays showed small effects up to 72 h, and flow cytometric analysis of adherent cells with 7-AAD/Annexin V detected no pharmacological effects on viable GIST cells. However, inhibition of DOG1 conveyed pro-apoptotic effects among early apoptotic imatinib-resistant cells. In conclusion, DOG1 generates Cl − currents in GIST that can be regulated pharmacologically, with small effects on cell viability and proliferation in vitro. Inhibition of DOG1 might act pro-apoptotic on some early apoptotic GIST cell populations. Further studies are warranted to fully illuminate the function of DOG1 and its potential as therapeutic target. - Highlights: • Subcellular DOG1 localization varies between GIST cells. • DOG1 in GIST is voltage- and Ca 2+ -activated. • Known TMEM16A modulators, like A01 and Eact, modulate DOG1. • DOG1 has small effects on cell viability and proliferation in vitro. • DOG1 impact early apoptotic GIST cells to undergo late apoptosis

Unraveling the Role of Structural Order in the Transformation of Electrical Conductivity in Ca2FeCoO6-δ, CaSrFeCoO6-δ, and Sr2FeCoO6-δ.

Science.gov (United States)

Hona, Ram Krishna; Huq, Ashfia; Ramezanipour, Farshid

2017-12-04

The ability to control the electrical conductivity of solid-state oxides using structural parameters has been demonstrated. A correlation has been established between the electrical conductivity and structural order in a series of oxygen-deficient perovskites using X-ray and neutron diffraction, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and electrical conductivity studies at a wide temperature range, 25-800 °C. The crystal structure of CaSrFeCoO 6-δ has been determined, and its stark contrast to Ca 2 FeCoO 6-δ and Sr 2 FeCoO 6-δ has been demonstrated. The Fe/Co distribution over tetrahedral and octahedral sites has been determined using neutron diffraction. There is a systematic increase in the structural order in progression from Sr 2 FeCoO 6-δ (δ = 0.5) to CaSrFeCoO 6-δ (δ = 0.8) and Ca 2 FeCoO 6-δ (δ = 0.9) . The oxygen contents of these materials were determined using iodometric titration and TGA. At room temperature, there is an inverse correlation between the electrical conductivity and structural order. The ordered Ca 2 and CaSr compounds are semiconductors, while the disordered Sr 2 compund shows metallic behavior. The metallic nature of the Sr 2 material persists up to 1073 K (800 °C), while the Ca 2 and CaSr compounds undergo a semiconductor-to-metal transition above 500 and 300 °C, respectively, highlighting another important impact of the structural order. At high temperature, the CaSr compound has the highest conductivity compared to the Ca 2 and Sr 2 materials. There appears to be an optimum degree of structural order that leads to the highest conductivity at high temperature. Another consequence of the structural order is the observation of mixed ionic-electronic conductivity in CaSr and Ca 2 compounds, as is evident from the hysteresis in the conductivity data obtained during heating and cooling cycles. The average ionic radius required for each structural transition was

Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

Science.gov (United States)

Wang, Qian; Huang, Lihong; Yue, Jianbo

2017-06-01

High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

Slope instability caused by small variations in hydraulic conductivity

Science.gov (United States)

Reid, M.E.

1997-01-01

Variations in hydraulic conductivity can greatly modify hillslope ground-water flow fields, effective-stress fields, and slope stability. In materials with uniform texture, hydraulic conductivities can vary over one to two orders of magnitude, yet small variations can be difficult to determine. The destabilizing effects caused by small (one order of magnitude or less) hydraulic conductivity variations using ground-water flow modeling, finite-element deformation analysis, and limit-equilibrium analysis are examined here. Low hydraulic conductivity materials that impede downslope ground-water flow can create unstable areas with locally elevated pore-water pressures. The destabilizing effects of small hydraulic heterogeneities can be as great as those induced by typical variations in the frictional strength (approximately 4??-8??) of texturally similar materials. Common "worst-case" assumptions about ground-water flow, such as a completely saturated "hydrostatic" pore-pressure distribution, do not account for locally elevated pore-water pressures and may not provide a conservative slope stability analysis. In site characterization, special attention should be paid to any materials that might impede downslope ground-water flow and create unstable regions.

A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX Regulation

Science.gov (United States)

Giladi, Moshe; Sasson, Yehezkel; Fang, Xianyang; Hiller, Reuben; Buki, Tal; Wang, Yun-Xing; Hirsch, Joel A.; Khananshvili, Daniel

2012-01-01

Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of “occluded” Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants. PMID:22768191

Immunomodulatory Activity of Ganoderma atrum Polysaccharide on Purified T Lymphocytes through Ca2+/CaN and Mitogen-Activated Protein Kinase Pathway Based on RNA Sequencing.

Science.gov (United States)

Xiang, Quan-Dan; Yu, Qiang; Wang, Hui; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

2017-07-05

Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes and further elucidate the underlying mechanism based on RNA sequencing (RNA-seq). Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ, and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes. KEGG pathway analysis identified 20 significant canonical pathways and seven biological functions. Furthermore, PSG-1 elevated intracellular Ca 2+ concentration and calcineurin (CaN) activity and raised the p-ERK, p-JNK, and p-p38 expression levels. T lymphocytes proliferation and the production of IL-2, IFN-γ, and IL-12 were decreased by the inhibitors of calcium channel and mitogen-activated protein kinases (MAPKs). These results indicated that PSG-1 possesses immunomodulatory activity on purified T lymphocytes, in which Ca 2+ /CaN and MAPK pathways play essential roles.

[Endoplasmic-mitochondrial Ca(2+)-functional unit: dependence of respiration of secretory cells on activity of ryanodine- and IP3 - sensitive Ca(2+)-channels].

Science.gov (United States)

Velykopols'ka, O Iu; Man'ko, B O; Man'ko, V V

2012-01-01

Using Clark oxygen electrode, dependence of mitochondrial functions on Ca(2+)-release channels activity of Chironomus plumosus L. larvae salivary glands suspension was investigated. Cells were ATP-permeabilized in order to enable penetration of exogenous oxidative substrates. Activation of plasmalemmal P2X-receptors (as well as P2Y-receptors) per se does not modify the endogenous respiration of salivary gland suspension. That is, Ca(2+)-influx from extracellular medium does not influence functional activity of mitochondria, although they are located along the basal part of the plasma membrane. Activation of RyRs intensifies endogenous respiration and pyruvate-malate-stimulated respiration, but not succinate-stimulated respiration. Neither activation of IP3Rs (via P2Y-receptors activation), nor their inhibition alters endogenous respiration. Nevertheless, IP3Rs inhibition by 2-APB intensifies succinate-stimulated respiration. All abovementioned facts testify that Ca2+, released from stores via channels, alters functional activity of mitochondria, and undoubtedly confirm the existence of endoplasmic-mitochondrial Ca(2+)-functional unit in Ch. plumosus larvae salivary glands secretory cells. In steady state of endoplasmic-mitochondrial Ca(2+)-functional unit the spontaneous activity of IP3Rs is observed; released through IP3Rs, Ca2+ is accumulated in mitochondria via uniporter and modulates oxidative processes. Activation of RyRs induces the transition of endoplasmic-mitochondrial Ca(2+)-functional unit to the active state, which is required to intensify cell respiration and oxidative phosphorylation. As expected, the transition of endoplasmic-mitochondrial Ca(2+)-functional unit to inactivated state (i. e. inhibition of Ca(2+)-release channels at excessive [Ca2+]i) limits the duration of signal transduction, has protective nature and prevents apoptosis.

Method for Measuring Thermal Conductivity of Small Samples Having Very Low Thermal Conductivity

Science.gov (United States)

Miller, Robert A.; Kuczmarski, Maria a.

2009-01-01

This paper describes the development of a hot plate method capable of using air as a standard reference material for the steady-state measurement of the thermal conductivity of very small test samples having thermal conductivity on the order of air. As with other approaches, care is taken to ensure that the heat flow through the test sample is essentially one-dimensional. However, unlike other approaches, no attempt is made to use heated guards to block the flow of heat from the hot plate to the surroundings. It is argued that since large correction factors must be applied to account for guard imperfections when sample dimensions are small, it may be preferable to simply measure and correct for the heat that flows from the heater disc to directions other than into the sample. Experimental measurements taken in a prototype apparatus, combined with extensive computational modeling of the heat transfer in the apparatus, show that sufficiently accurate measurements can be obtained to allow determination of the thermal conductivity of low thermal conductivity materials. Suggestions are made for further improvements in the method based on results from regression analyses of the generated data.

Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive Ca(2+) channels

DEFF Research Database (Denmark)

Gustafsson, F; Andreasen, D; Salomonsson, Max

2001-01-01

The aim of this study was to evaluate the role of voltage-operated Ca(2+) channels in the initiation and conduction of vasoconstrictor responses to local micropipette electrical stimulation of rat mesenteric arterioles (28 +/- 1 microm, n = 79) in vivo. Local and conducted (600 microm upstream from...... the pipette) vasoconstriction was not blocked by TTX (1 micromol/l, n = 5), nifedipine, or nimodipine (10 micromol/l, n = 9). Increasing the K(+) concentration of the superfusate to 75 mmol/l did not evoke vasoconstriction, but this depolarizing stimulus reversibly abolished vasoconstrictor responses...

Mobilisation of store Ca2+ activates tyrosine hydroxylase in bovine adrenal chromaffin cells

International Nuclear Information System (INIS)

McKenzie, S.; Marley, P.D.

2001-01-01

Full text: Many receptor agonists are able to activate tyrosine hydroxylase (TOH) in bovine adrenal chromaffin cells. The majority of these are dependent on extracellular Ca 2+ for this action. Entry of extracellular Ca 2+ through voltage-operated Ca 2+ channels is very effective at activating TOH. The contribution of the intracellular Ca 2+ stores to TOH activation however is not known. Previous studies have shown that mobilisation of intracellular Ca 2+ stores is effective at increasing phosphorylation of TOH, but its effect on TOH activity has not been studied. Therefore, in the present study, the effect of mobilisation of store Ca 2+ on TOH activity was investigated using primary cultures of bovine adrenal chromaffin cells. Cells were prepared from abattoir tissue and cultured for 3-6 days. TOH activity was determined over 10 minutes, measuring the 14 CO 2 produced following the hydroxylation and rapid decarboxylation of 14 C-tyrosine offered to intact cells. Caffeine increased TOH activity in a concentration-dependent manner with a maximum response of 100% increase at 20mM. This effect was not due to osmolarity since 20mM sucrose had no effect.Nor was it due to inhibition of phosphodiesterases, since the effect of caffeine was still seen in the presence of 1mM IBMX. However,caffeine-induced TOH activation was substantially reduced in the absence of extracellular Ca 2+ . The results suggest that TOH activity can be increased by mobilising intracellular Ca 2+ stores, but that this effect involves extracellular Ca 2+ influx, possibly through store-operated channels. Copyright (2001) Australian Neuroscience Society

Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.

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Brenda L Bloodgood

2009-09-01

Full Text Available Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines, which consist of a bulbous head separated from the parent dendrite by a thin neck. Although activation of voltage-gated channels in the spine and stimulus-evoked constriction of the spine neck can influence synaptic signals, the contribution of electrical filtering by the spine neck to basal synaptic transmission is largely unknown. Here we use spine and dendrite calcium (Ca imaging combined with 2-photon laser photolysis of caged glutamate to assess the impact of electrical filtering imposed by the spine morphology on synaptic Ca transients. We find that in apical spines of CA1 hippocampal neurons, the spine neck creates a barrier to the propagation of current, which causes a voltage drop and results in spatially inhomogeneous activation of voltage-gated Ca channels (VGCCs on a micron length scale. Furthermore, AMPA and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively that are colocalized on individual spine heads interact to produce two kinetically and mechanistically distinct phases of synaptically evoked Ca influx. Rapid depolarization of the spine triggers a brief and large Ca current whose amplitude is regulated in a graded manner by the number of open AMPARs and whose duration is terminated by the opening of small conductance Ca-activated potassium (SK channels. A slower phase of Ca influx is independent of AMPAR opening and is determined by the number of open NMDARs and the post-stimulus potential in the spine. Biphasic synaptic Ca influx only occurs when AMPARs and NMDARs are coactive within an individual spine. These results demonstrate that the morphology of dendritic spines endows associated synapses with specialized modes of signaling and permits the graded and independent control of multiple phases of synaptic Ca influx.

Predominant constitutive CFTR conductance in small airways

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Lytle Christian

2005-01-01

Full Text Available Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD are inflammation of the small airways (bronchiolitis and destruction of lung parenchyma (emphysema. These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. Methods We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25, but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25 were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM+IBMX (100 μM, ATP (100 μM, or adenosine (100 μM, but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM, GlyH-101* (5–50 μM, and CFTRInh-172* (5 μM. RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.

Fusion-activated Ca(2+ entry: an "active zone" of elevated Ca(2+ during the postfusion stage of lamellar body exocytosis in rat type II pneumocytes.

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Pika Miklavc

2010-06-01

Full Text Available Ca(2+ is essential for vesicle fusion with the plasma membrane in virtually all types of regulated exocytoses. However, in contrast to the well-known effects of a high cytoplasmic Ca(2+ concentration ([Ca(2+](c in the prefusion phase, the occurrence and significance of Ca(2+ signals in the postfusion phase have not been described before.We studied isolated rat alveolar type II cells using previously developed imaging techniques. These cells release pulmonary surfactant, a complex of lipids and proteins, from secretory vesicles (lamellar bodies in an exceptionally slow, Ca(2+- and actin-dependent process. Measurements of fusion pore formation by darkfield scattered light intensity decrease or FM 1-43 fluorescence intensity increase were combined with analysis of [Ca(2+](c by ratiometric Fura-2 or Fluo-4 fluorescence measurements. We found that the majority of single lamellar body fusion events were followed by a transient (t(1/2 of decay = 3.2 s rise of localized [Ca(2+](c originating at the site of lamellar body fusion. [Ca(2+](c increase followed with a delay of approximately 0.2-0.5 s (method-dependent and in the majority of cases this signal propagated throughout the cell (at approximately 10 microm/s. Removal of Ca(2+ from, or addition of Ni(2+ to the extracellular solution, strongly inhibited these [Ca(2+](c transients, whereas Ca(2+ store depletion with thapsigargin had no effect. Actin-GFP fluorescence around fused LBs increased several seconds after the rise of [Ca(2+](c. Both effects were reduced by the non-specific Ca(2+ channel blocker SKF96365.Fusion-activated Ca(2+entry (FACE is a new mechanism that leads to [Ca(2+](c transients at the site of vesicle fusion. Substantial evidence from this and previous studies indicates that fusion-activated Ca(2+ entry enhances localized surfactant release from type II cells, but it may also play a role for compensatory endocytosis and other cellular functions.

Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

Science.gov (United States)

Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

2017-10-20

Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

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

DEFF Research Database (Denmark)

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

2010-01-01

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

Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity.

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Shubha Murthy

Full Text Available The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions.

Photocatalytic activity of Fe-doped CaTiO₃ under UV-visible light.

Science.gov (United States)

Yang, He; Han, Chong; Xue, Xiangxin

2014-07-01

The photocatalytic degradation of methylene blue (MB) over Fe-doped CaTiO₃ under UV-visible light was investigated. The as-prepared samples were characterized using X-ray diffraction (XRD), scanning electron microscope (SEM) equipped with an energy dispersive spectrometer (EDS) system, Fourier transform infrared spectra (FT-IR), and UV-visible diffuse reflectance spectroscopy (DRS). The results show that the doping with Fe significantly promoted the light absorption ability of CaTiO₃ in the visible light region. The Fe-doped CaTiO₃ exhibited higher photocatalytic activity than CaTiO₃ for the degradation of MB. However, the photocatalytic activity of the Fe-doped CaTiO₃ was greatly influenced by the calcination temperature during the preparation process. The Fe-doped CaTiO₃ prepared at 500°C exhibited the best photocatalytic activity, with degradation of almost 100% MB (10ppm) under UV-visible light for 180 min. Copyright © 2014. Published by Elsevier B.V.

Novel Phenolic Inhibitors of Small/Intermediate-Conductance Ca(2+)-Activated K(+) Channels, KCa3.1 and KCa2.3

DEFF Research Database (Denmark)

Olivan-Viguera, Aida; Valero, Marta Sofía; Murillo, María Divina

2013-01-01

-inflammatory drugs (NSAIDs), with known cytoprotective, anti-inflammatory, and/or cytostatic activities. METHODOLOGYPRINCIPAL FINDINGS: In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM) and resveratrol (EC50 10 µM) as KCa3.1 inhibitors with moderate potency....... The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM), followed by mesalamine (EC50≥10 µM). The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyl)oxymethyl]phenyl]methyl 3.......3 activation. CONCLUSIONSSIGNIFICANCE: We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel KCa3.1 inhibitors. The high potency of 13b with pan-activity on KCa3.1/KCa2 channels makes 13b a new pharmacological tool to manipulate...

Effect of small quantity of chromium on the electrical, magnetic and magnetocaloric properties of Pr{sub 0.7}Ca{sub 0.3}Mn{sub 0.98}Cr{sub 0.02}O{sub 3} manganite

Energy Technology Data Exchange (ETDEWEB)

Bettaibi, A.; Rahmouni, H. [Universite de Gabes, Laboratoire de Physique des Materiaux et des Nanomateriaux appliquee a l' Environnement, Faculte des Sciences de Gabes cite Erriadh, Gabes (Tunisia); M' nassri, R. [Kairouan University, Higher Institute of Applied Sciences and Technology of Kasserine, Kasserine (Tunisia); Universite de Monastir, Laboratoire de Physico-Chimie des Materiaux, Departement de Physique, Faculte des Sciences de Monastir, Monastir (Tunisia); Selmi, A.; Cheikhrouhou, A. [Sfax University, Laboratory of Physics of Materials, Faculty of Sciences of Sfax, Sfax (Tunisia); Khirouni, K. [Kairouan University, Higher Institute of Applied Sciences and Technology of Kasserine, Kasserine (Tunisia); Chniba Boudjada, N. [Institut NEEL, Grenoble Cedex 09 (France)

2016-03-15

Structural, electrical and thermomagnetic properties of Pr{sub 0.7}Ca{sub 0.3}Mn{sub 0.98}Cr{sub 0.02}O{sub 3} were investigated. Sample was prepared by solid-state reaction method. X-ray diffraction revealed that the sample crystallizes in the orthorhombic system with Pnma space group. Electrical conductivity and complex impedance studies of Pr{sub 0.7}Ca{sub 0.3}Mn{sub 0.98}Cr{sub 0.02}O{sub 3} system are analyzed. The investigated compound exhibits a semiconductor behavior in the whole explored temperature range. From 100 to 206 K, the increase in DC conductance is more than two decade. At higher temperatures, the conductance varies slowly and a saturation region appears. The conduction mechanism is found to be governed by small polaron hopping process which is explained by the short range thermally activated energy. Conductance spectrum is well described by Jonsher law, and the temperature dependence of the frequency exponent confirms that conduction mechanism is governed by hopping process of the localized carriers. Using complex impedance analysis, the compound is modeled by an electrical equivalent circuit. Also, such analysis confirms the contribution of grain boundary to the transport properties. The substitution of Mn by 2 % Cr destroyed the charge order state observed in the parent compound and induced a ferromagnetic phase at low temperatures. For a magnetic field change of 5 T, the material shows a maximum magnetic entropy change ∇S {sup max} = 2.69 J kg{sup -1} K{sup -1} with a full width at half maximum δ {sub TFWHM} = 145 K, and a relative cooling power RCP = 389 J kg{sup -1}. Pr{sub 0.7}Ca{sub 0.3}Mn{sub 0.98}Cr{sub 0.02}O{sub 3} material demonstrates potential proprieties to be used in electronic and thermal devices and as magnetic refrigerant. (orig.)

Safety activities in small businesses

Science.gov (United States)

Sinclair, Raymond C.; Cunningham, Thomas R.

2015-01-01

Background Workplace injuries occur at higher rates in smaller firms than in larger firms, and the number of workplace safety activities appear to be inversely associated with those rates. Predictors of safety activities are rarely studied. Methods This study uses data from a national random survey of firms (n = 722) with less than 250 employees conducted in 2002. Results We found that, regardless of firm size or industry, safety activities were more common in 2002 than they were in a similar 1983 study. Having had an OSHA inspection in the last five years and firm size were stronger predictors of safety activities than industry hazardousness and manager’s perceptions of hazardousness. All four variables were significant predictors (β range .19 to .28; R2 = .27). Conclusions Further progress in the prevention of injuries in small firms will require attention to factors likely subsumed within the firm size variable, especially the relative lack of slack resources that might be devoted to safety activities. PMID:26339124

Synergistic pretreatment of waste activated sludge using CaO_2 in combination with microwave irradiation to enhance methane production during anaerobic digestion

International Nuclear Information System (INIS)

Wang, Jie; Li, Yongmei

2016-01-01

Highlights: • CaO_2/MW pretreatment synergistically enhanced WAS solubilization and CH_4 production. • MW irradiation facilitated more "·OH generation from CaO_2. • The optimal pretreatment condition for methane production was determined. • The growths of both hydrogenotrophic and acetate-utilizing methanogens were promoted. • The dewaterability of WAS was improved considerably by CaO_2/MW treatment. - Abstract: To investigate the effects of combined calcium peroxide (CaO_2) and microwave pretreatment on anaerobic digestion of waste activated sludge, lab-scale experiments were conducted to measure the solubilization, biodegradation, and dewaterability of the waste activated sludge. Additionally, the synergistic effects between CaO_2 and microwave were studied, and the microbial activity and methanogenic archaea community structure were analyzed. Combined pretreatment considerably facilitated the solubilization and subsequent anaerobic digestion of the waste activated sludge. The optimal pretreatment condition was CaO_2 (0.1 g/gVSS)/microwave (480 W, 2 min) for methane production during the subsequent anaerobic digestion process. Under this condition, 80.2% higher CH_4 accumulation yield was achieved after 16 d of anaerobic digestion when compared with the control. The synergistic effects of CaO_2/microwave pretreatment resulted from the different mechanisms of CaO_2 and microwave treatments. Further, microwave irradiation increased "·OH generation from CaO_2 and significantly alleviated the inhibitory effect of CaO_2 on methanogens. The activities of hydrolytic enzymes and acid-forming enzymes in the waste activated sludge were improved after CaO_2 (0.1 g/gVSS)/microwave (480 W, 2 min) pretreatment. Methanogenesis enzyme activity was also higher after CaO_2 treatment (0.1 g/gVSS)/microwave (480 W, 2 min) following a lag period. Illumina MiSeq sequencing analysis indicated that acetate-utilizing methanogen (Methanosaeta sp.) and H_2/CO_2-utilizing

Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.

Science.gov (United States)

Chen, Mao Xiang; Gorman, Shelby A; Benson, Bill; Singh, Kuljit; Hieble, J Paul; Michel, Martin C; Tate, Simon N; Trezise, Derek J

2004-06-01

The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

A dynamic model of interactions of Ca2+, calmodulin, and catalytic subunits of Ca2+/calmodulin-dependent protein kinase II.

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Shirley Pepke

2010-02-01

Full Text Available During the acquisition of memories, influx of Ca2+ into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca2+influx during the first few seconds of activity is interpreted within the Ca2+-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity,including Ca2+/calmodulin-dependent protein kinase II (CaMKII, are regulated by calmodulin, a small protein that can bindup to 4 Ca2+ ions. As a first step toward clarifying how the Ca2+-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca2+, calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca2+ play a significant role in activation of CaMKII in the physiological regime,supporting the notion that processing of Ca2+ signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca2+ is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca2+ transients arises from the kinetics of interaction of fluctuating Ca2+with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic

Functional role of the Ca{sup 2+}-activated Cl{sup −} channel DOG1/TMEM16A in gastrointestinal stromal tumor cells

Energy Technology Data Exchange (ETDEWEB)

Berglund, Erik, E-mail: erik.berglund@ki.se [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden); Akcakaya, Pinar [Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm (Sweden); Berglund, David [Section for Transplantation Surgery, Department of Surgical Sciences, Uppsala University Hospital, Uppsala (Sweden); Karlsson, Fredrik [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden); Vukojević, Vladana [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Lee, Linkiat [Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm (Sweden); Bogdanović, Darko [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Lui, Weng-Onn; Larsson, Catharina [Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm (Sweden); Zedenius, Jan [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden); Fröbom, Robin [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Bränström, Robert [Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm (Sweden)

2014-08-15

DOG1, a Ca{sup 2+}-activated Cl{sup −} channel (CaCC), was identified in 2004 to be robustly expressed in gastrointestinal stromal tumors (GIST). It was rapidly included as a tumor marker in routine diagnostics, but the functional role remained unknown. CaCCs are important regulators of normal physiological functions, but also implicated in tumorigenesis, cancer progression, metastasis, cell migration, apoptosis, proliferation and viability in several malignancies. We therefore investigated whether DOG1 plays a role in the three latter in GIST by utilizing in vitro cell model systems. Confocal microscopy identified different subcellular localizations of DOG1 in imatinib-sensitive and imatinib-resistant cells. Electrophysiological studies confirmed that DOG1-specific pharmacological agents possess potent activating and inhibiting properties. Proliferation assays showed small effects up to 72 h, and flow cytometric analysis of adherent cells with 7-AAD/Annexin V detected no pharmacological effects on viable GIST cells. However, inhibition of DOG1 conveyed pro-apoptotic effects among early apoptotic imatinib-resistant cells. In conclusion, DOG1 generates Cl{sup −} currents in GIST that can be regulated pharmacologically, with small effects on cell viability and proliferation in vitro. Inhibition of DOG1 might act pro-apoptotic on some early apoptotic GIST cell populations. Further studies are warranted to fully illuminate the function of DOG1 and its potential as therapeutic target. - Highlights: • Subcellular DOG1 localization varies between GIST cells. • DOG1 in GIST is voltage- and Ca{sup 2+}-activated. • Known TMEM16A modulators, like A01 and Eact, modulate DOG1. • DOG1 has small effects on cell viability and proliferation in vitro. • DOG1 impact early apoptotic GIST cells to undergo late apoptosis.

Lithium-induced inhibition of Na-K ATPase and Ca ATPase activities in rat brain synaptosome.

Science.gov (United States)

Cho, Y. W.

1995-01-01

To explore the action mechanism of lithium in the brain, the author investigated the effects of lithium on Na-K ATPase and Ca ATPase in rat brain synaptosomes prepared from forebrains by the method of Booth and Clark. The activities of Na-K ATPase and Ca ATPase were assayed by the level of inorganic phosphate liberated from the hydrolysis of ATP. Lithium at the optimum therapeutic concentration of 1 mM decreased the activity of Na-K ATPase from the control value of 19.08 +/- 0.29 to 18.27 +/- 0.10 micromoles Pi/mg protein/h and also reduced the activity of Ca ATPase from 6.38 +/- 0.12 to 5.64 +/- 0.12 micromoles Pi/mg protein/h. The decreased activity of Na-K ATPase will decrease the rate of Ca2+ efflux, probably via an Na-Ca exchange mechanism and will increase the rate of Ca2+ entry by the depolarization of nerve terminals. The reduced activity of Ca ATPase will result in the decreased efflux of Ca2+. As a Conclusion, it can be speculated that lithium elevates the intrasynaptosomal Ca2+ concentration via inhibition of the activities of Na-K ATPase and Ca ATPase, and this increased [Ca2+]i will cause the release of neurotransmitters and neurological effects of lithium. PMID:7598829

Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

Directory of Open Access Journals (Sweden)

Kiril L Hristov

Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

Effect of sulfation on the surface activity of CaO for N2O decomposition

International Nuclear Information System (INIS)

Wu, Lingnan; Hu, Xiaoying; Qin, Wu; Dong, Changqing; Yang, Yongping

2015-01-01

Graphical abstract: - Highlights: • Sulfation of CaO (1 0 0) surface greatly deactivates its surface activity for N 2 O decomposition. • An increase of sulfation degree leads to a decrease of CaO surface activity for N 2 O decomposition. • Sulfation from CaSO 3 into CaSO 4 is the crucial step for deactivating the surface activity for N 2 O decomposition. • The electronic interaction CaO (1 0 0)/CaSO 4 (0 0 1) interface is limited to the bottom layer of CaSO 4 (0 0 1) and the top layer of CaO (1 0 0). • CaSO 4 (0 0 1) and (0 1 0) surfaces show negligible catalytic ability for N 2 O decomposition. - Abstract: Limestone addition to circulating fluidized bed boilers for sulfur removal affects nitrous oxide (N 2 O) emission at the same time, but mechanism of how sulfation process influences the surface activity of CaO for N 2 O decomposition remains unclear. In this paper, we investigated the effect of sulfation on the surface properties and catalytic activity of CaO for N 2 O decomposition using density functional theory calculations. Sulfation of CaO (1 0 0) surface by the adsorption of a single gaseous SO 2 or SO 3 molecule forms stable local CaSO 3 or CaSO 4 on the CaO (1 0 0) surface with strong hybridization between the S atom of SO x and the surface O anion. The formed local CaSO 3 increases the barrier energy of N 2 O decomposition from 0.989 eV (on the CaO (1 0 0) surface) to 1.340 eV, and further sulfation into local CaSO 4 remarkably increases the barrier energy to 2.967 eV. Sulfation from CaSO 3 into CaSO 4 is therefore the crucial step for deactivating the surface activity for N 2 O decomposition. Completely sulfated CaSO 4 (0 0 1) and (0 1 0) surfaces further validate the negligible catalytic ability of CaSO 4 for N 2 O decomposition.

Highly active and durable Ca-doped Ce-SBA-15 catalyst for biodiesel production

International Nuclear Information System (INIS)

Thitsartarn, Warintorn; Maneerung, Thawatchai; Kawi, Sibudjing

2015-01-01

In this work, Ca-doped Ce-incorporated SBA-15 (Ca/CeS) catalyst was successfully synthesized by using direct synthesis of Ce-incorporated SBA-15 followed by impregnation of CaO (calcium oxide). The maximum Si/Ce molar ratio that Ce atoms can be incorporated successfully into the mesoporous framework was found to be 5 (CeS-5). After the impregnation of 30 wt. % Ca, the obtained 30Ca/CeS-5 catalysts showed the superior catalytic performance for transesterification reaction of palm oil with methanol and also the higher catalytic activity as compared to other supported catalysts, i.e. CaO/CeO 2 and CaO–CeO 2 /SBA-15. This can be attributed to the well-dispersion of CaO on the CeS-5 support surface. Furthermore, it was found that the leaching of Si, Ce and Ca from the catalyst into biodiesel produced was negligible (i.e. <1 ppm after 7 cycles), indicating the strong interaction between CaO and CeS-5 support. As a result, the 30Ca/CeS-5 catalyst can be reused at least 15 cycles with insignificant decrease in catalytic activity, offering the efficient CaO-based catalyst for biodiesel production. - Highlights: • Mesoporous Ca-based catalyst was successfully developed for biodiesel production. • Catalyst exhibited high activity towards transesterification (FAME yield > 98%). • Catalyst can be effectively re-used at least 15 cycles. • Extremely low catalyst contaminant (<1 ppm) was presented

Molecular cloning of the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease

International Nuclear Information System (INIS)

Imajoh, Shinobu; Aoki, Kazumasa; Ohno, Shigeo; Emori, Yasufumi; Kawasaki, Hiroshi; Sugihara, Hidemitsu; Suzuki, Koichi

1988-01-01

A nearly full-length cDNA clone for the large subunit of high-Ca 2+ -requiring Ca 2+ -activated neutral protease (mCANP) from human tissues has been isolated. The deduced protein, determined for the first time as an mCANP, has essentially the same structural features as those revealed previously for the large subunits of the low-Ca 2+ -requiring form (μCANP). Namely, the protein, comprising 700 amino acid residues, is characterized by four domains, containing a cysteine protease like domain and a Ca 2+ -binding domain. The overall amino acid sequence similarities of the mCANP large subunit with those of human μCANP and chicken CANP are 62% and 66%, respectively. These values are slightly lower than that observed between μCANP and chicken CANP (70%). Local sequence similarities vary with the domain, 73-78% in the cysteine protease like domain and 48-65% in the Ca 2+ -binding domain. These results suggest that CANPs with different Ca 2+ sensitivities share a common evolutionary origin and that their regulatory mechanisms are similar except for the Ca 2+ concentrations required for activation

Activation of Ca(OH){sub 2} using different siliceous materials

Energy Technology Data Exchange (ETDEWEB)

Karatepe, N.; Ersoy-Mericboyu, A.; Kucukbayrak, S. [Istanbul Technical University, Istanbul (Turkey)

1999-04-01

Siliceous materials such as silica fume, bentonite and diatomite were mixed with Ca(OH){sub 2} and hydrated at different conditions to produce reactive SO{sub 2} sorbents. Two different hydration methods were used, namely atmospheric and pressure hydration. The effects of the hydration temperature, time and siliceous material/Ca(OH){sub 2} weight ratio on the physical properties of the activated sorbents wereinvestigated. A statistical design technique was applied by use of a two-level factorial design matrix to interpret experimental results. In atmospheric hydration, it was found that increasing the temperature and hydration time caused an increase in the total surface area of the sorbents. But, increasing the siliceous material/Ca(OH){sub 2} weight ratio caused a decrease in the total surface area of the sorbents. In pressure hydration, mathematical analysis showed that the surface area of the activated sorbents was positively affected by the hydration variables. Thermogravimetric measurements showed that increasing the amount of reacted Ca(OH){sub 2} during hydration caused an increase in the surface area of the sorbent. X-ray diffraction studies also indicated that calcium silicate hydrates were the principal Ca-containing species formed during hydration.

Automated patch-clamp technique: increased throughput in functional characterization and in pharmacological screening of small-conductance Ca2+ release-activated Ca2+ channels

DEFF Research Database (Denmark)

Schrøder, Rikke L; Friis, Søren; Sunesen, Morten

2008-01-01

require high signal-to-noise ratios obtained by high seal resistances. Automated whole-cell establishment resulted in membrane resistances of 1728 +/- 226 MOmega (n = 44). CRAC channels were activated by a number of methods that raise intracellular calcium concentration, including EGTA, ionomycin, Ins(1......, and the current could be reactivated by subsequent addition of thapsigargin. I(CRAC) was blocked by SKF-96365 and 2-APB with IC50 values of 4.7 +/- 1.1 microM (n = 9) and 7.5 +/- 0.7 (n = 9) microM, respectively. The potencies of these blockers were similar to values reported for I(CRAC) in similar conventional...

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons.

Science.gov (United States)

Sasaki, Takuya; Piatti, Verónica C; Hwaun, Ernie; Ahmadi, Siavash; Lisman, John E; Leutgeb, Stefan; Leutgeb, Jill K

2018-02-01

Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.

Novel method of generation of Ca(HCO32 and CaCO3 aerosols and first determination of hygroscopic and cloud condensation nuclei activation properties

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A. Trimborn

2010-09-01

Full Text Available Atmospheric mineral aerosols contain CaCO3 as a reactive component. A novel method to produce CaCO3 aerosol was developed by spraying Ca(HCO32 solution, which was generated from a CaCO3 suspension and CO2. By aerosol mass spectrometry the freshly sprayed and dried aerosol was characterized to consist of pure Ca(HCO32 which under annealing in a tube furnace transformed into CaCO3. Transmission Electron Microscopy demonstrated that the particles produced were spherical. The method was able to generate aerosol of sufficient concentration and proper size for the study of physiochemical properties and investigations of heterogeneous reactions of mineral aerosol. The dried Ca(HCO32 particles were somewhat more hygroscopic than CaCO3 particles. However, during humidification a restructuring took place and ∼2/3 of the Ca(HCO32 was transformed to CaCO3. The mixed Ca(HCO32/CaCO3(s particles were insoluble with a growth factor of 1.03 at 95% (hygroscopicity parameter κ=0.011±0.007 relative humidity. This compares to a corresponding growth factor of 1.01 for CaCO3(s (κ=0.0016±0.0004. Mass spectrometric composition analysis, restructuring, and insolubility of the mixed particles suggested that solid Ca(HCO32(s was observed. This would be in contrast to the current belief that Ca(HCO32(s is thermodynamically instable. The CCN activity of Ca(HCO32(s aerosol (κ≈0.15 is remarkably higher than that of CaCO3 aerosol (κ=0.0019±0.0007 and less than that of Ca(NO32. The noticeable but limited solubility of Ca(HCO32 of ≈0.01 mol/l explains limited hygroscopic growth and good CCN activity. Experiments in the Large Jülich Aerosol Chamber indicated that Ca(HCO32(s could exist for several hours under dry atmospheric conditions. However, it was likely buried in a protective layer of CaCO3(s. We conclude that Ca(HCO32 may be formed in the atmosphere in cloud droplets of activated mineral dust by reaction of CaCO3 with CO2 and H2O. The presence of Ca(HCO32 and

[Properties and localization of Mg- and Ca-ATpase activities in wheat embryo cell nuclei].

Science.gov (United States)

Vasil'eva, N A; Belkina, G G; Stepanenko, S Y; Atalykova, F I; Oparin, A I

1978-05-01

The isolated nuclei of wheat embryo possess the ATPase activity. The addition of Mg2+ and Ca2+ significantly increases the activities of nuclear ATPases, whereas Hg2+, Cu2+ and Mn2+ inhibit the activity. The activating effect of Mg2+ is enhanced by an addition of Na and K ions. The activity of wheat embryo nuclear Mg-ATPase is higher than its Ca-ATPase activity; both ATPases also differ in their pH optima. Separation of total nuclear protein according to the solubility of its individual protein components in wheat and strong salt solutions, using the detergents, as well as ammonium sulfate precipitation and dialysis do not result in separation of Mg-activated and Ca-activated ATPases, although their levels of activities and ratios change in the course of fractionation. The Mg- and Ca-ATPase activities of the wheat embryo nuclei were found in the nuclear fraction of albumin, in nonhistone proteins and nuclear membranes. In the albumin nuclear fraction and subfractions of non-histone proteins the higher level of activity is observed in Ca-ATPase, whereas in the nuclei and soluble fractions of residual proteins in Mg-ATPase.

Support for Natural Small-Molecule Phenols as Anxiolytics

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Xiaohong Wang

2017-12-01

Full Text Available Natural small-molecule phenols (NSMPs share some bioactivities. The anxiolytic activity of NSMPs is attracting attention in the scientific community. This paper provides data supporting the hypothesis that NSMPs are generally anxiolytic. The anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol, protocatechuic aldehyde, vanillin, thymol, ferulic acid, and caffeic acid, were assayed with the elevated plus maze (EPM test in mice. The oral doses were 5, 10 and 20 mg/kg, except for phloroglucinol for which the doses were 2.5, 5 and 10 mg/kg. All tested phenols had anxiolytic activity in mice. The phenolic hydroxyl group in 4-hydroxycinnamic acid (4-OH CA was essential for the anxiolytic activity in the EPM test in mice and rats compared to 4-chlorocinnamic acid (4-Cl CA. The in vivo spike recording of rats’ hippocampal neurons also showed significant differences between 4-OH CA and 4-Cl CA. Behavioral and neuronal spike recording results converged to indicate the hippocampal CA1 region might be a part of the anxiolytic pathways of 4-OH CA. Therefore, our study provides further experimental data supporting NSMPs sharing anxiolytic activity, which may have general implications for phytotherapy because small phenols occur extensively in herbal medicines.

Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase.

Science.gov (United States)

Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi

2016-11-01

Inward rectifier K + channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP 2 ). Stimulation of the Ca 2+ -sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both G q/11 , which decreases PIP 2 , and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP 2 . How membrane PIP 2 levels are regulated by CaR activation and whether these changes modulate inward rectifier K + are unknown. In this study, we found that activation of CaR by the allosteric agonist, NPSR568, increased inward rectifier K + current (I K1 ) in guinea pig ventricular myocytes and currents mediated by Kir2.1 channels exogenously expressed in HEK293T cells with a similar sensitivity. Moreover, using the fluorescent PIP 2 reporter tubby-R332H-cYFP to monitor PIP 2 levels, we found that CaR activation in HEK293T cells increased membrane PIP 2 concentrations. Pharmacological studies showed that both phospholipase C (PLC) and PI-4-K are activated by CaR stimulation with the latter played a dominant role in regulating membrane PIP 2 and, thus, Kir currents. These results provide the first direct evidence that CaR activation upregulates currents through inward rectifier K + channels by accelerating PIP 2 synthesis. The regulation of I K1 plays a critical role in the stability of the electrical properties of many excitable cells, including cardiac myocytes and neurons. Further, synthetic allosteric modulators that increase CaR activity have been used to treat hyperparathyroidism, and negative CaR modulators are of potential importance in the treatment of osteoporosis. Thus, our results provide further insight into the roles played by CaR in the cardiovascular system and are potentially valuable for heart disease treatment and drug safety.

Small polaron hopping conduction in samples of ceramic La1.4Sr1.6Mn2O7.06

International Nuclear Information System (INIS)

Nakatsugawa, H.; Iguchi, E.; Jung, W.H.; Munakata, F.

1999-01-01

The ceramic sample of La 1.4 Sr 1.6 Mn 2 O 7.06 exhibits the metal-insulator transition and a negative magnetoresistance in the vicinity of the Curie temperature (T C ∼ 100 K). The dc magnetic susceptibility between 100 K and 280 K is nearly constant and decreases gradually with increasing temperature above 280 K. The measurements of dc resistivity and the thermoelectric power indicate that small polaron hopping conduction takes place at T > 280 K. The spin ordering due to the two-dimensional d x 2 -y 2 state occurring at T > 280 K is directly related to the hopping conduction above 280 K, although the spin ordering due to the one-dimensional d 3z 2 -r 2 state takes place at T > T C . The two-dimensional d x 2 -y 2 state extending within the MnO 2 sheets starts to narrow and leads to the carrier localisation at 280 K. The effective number of holes in this sample estimated from the thermoelectric power is considerably smaller than the nominal value. This indicates that the small polaron hopping conduction takes place predominantly within the in-plane MnO 2 sheets. A discussion is given of the experimental results of the ceramic sample of La 2/3 Ca 1/3 MnO 2.98 . Copyright (1999) CSIRO Australia

Structure-function relation of phospholamban: modulation of channel activity as a potential regulator of SERCA activity.

Directory of Open Access Journals (Sweden)

Serena Smeazzetto

Full Text Available Phospholamban (PLN is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+-ATPase (SERCA in the sarcoplasmic reticulum. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a low unitary conductance. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 Å for this channel. This value is similar to that reported for the central pore in the structure of the PLN pentamer. Hence the PLN pentamer, which is in equilibrium with the monomer, is the most likely channel forming structure. Reconstituted PLN mutants, which either stabilize (K27A and R9C or destabilize (I47A the PLN pentamer and also phosphorylated PLN still generate the same unitary conductance of the wt/non-phosphorylated PLN. However the open probability of the phosphorylated PLN and of the R9C mutant is significantly lower than that of the respective wt/non-phosphorylated control. In the context of data on PLN/SERCA interaction and on Ca(2+ accumulation in the sarcoplasmic reticulum the present results are consistent with the view that PLN channel activity could participate in the balancing of charge during Ca(2+ uptake. A reduced total conductance of the K(+ transporting PLN by phosphorylation or by the R9C mutation may stimulate Ca(2+ uptake in the same way as an inhibition of K(+ channels in the SR membrane. The R9C-PLN mutation, a putative cause of dilated cardiomyopathy, might hence affect SERCA activity also via its inherent low open probability.

Sphingosine inhibits the sarco(endo)plasmic reticulum Ca"2"+-ATPase (SERCA) activity

International Nuclear Information System (INIS)

Benaim, Gustavo; Pimentel, Adriana A.; Felibertt, Pimali; Mayora, Adriana; Colman, Laura; Sojo, Felipe; Rojas, Héctor; De Sanctis, Juan B.

2016-01-01

The increase in the intracellular Ca"2"+ concentration ([Ca"2"+]_i) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca"2"+]_i by inhibiting the sarco(endo)plasmic reticulum Ca"2"+-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca"2"+ pump. The results showed that addition of sphingosine produced a release of Ca"2"+ from the endoplasmic reticulum followed by a Ca"2"+ entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca"2"+]_I in mammalian cells.

Dechlorination of hexachlorobenzene using ultrafine Ca-Fe composite oxides

International Nuclear Information System (INIS)

Ma Xiaodong; Zheng Minghui; Liu Wenbin; Qian Yong; Zhang Bing; Liu Wenxia

2005-01-01

Ca-Fe composite oxides with different Ca/Fe atomic ratios were synthesized by co-precipitation method and characterized by X-ray diffraction (XRD), scanning electron microscopy with elemental X-ray analysis (SEM-EDX) and inductively coupled plasma optical emission spectrometer (ICP-OES). Their dechlorination activities were evaluated using hexachlorobenzene (HCB) as a model compound. The results indicate that the dechlorination activity is related to the composition of metal oxides. Different compositions lead to the formation of different phases of Ca-Fe composite oxides. When Ca/Fe atomic ratio was 3.4, the dechlorination activity reached 97%, which was the highest in the dechlorination of HCB at 300 deg. C for 0.5 h. This may be related to the formation of Ca 2 Fe 2 O 5 phase and small agglomerate size of oxide crystal of about 1 μm. The effect of reaction time on HCB dechlorination and the pathway of dechlorination were investigated using the Ca-Fe composite oxide with the highest activity. It was found that hydrodechlorination took place in the destruction of HCB, the dechlorination efficiency is almost 100% after 2 h reaction. After reaction, quantitative measurement of chloride ion and qualitative analysis of CaCO 3 indicate besides hydrodechlorination, other degradation routes may be present. The mechanism of synergic dechlorination using Ca-Fe composite oxides was discussed

Ionic conductivity in new perovskite type oxides: NaAZrMO6 (A = Ca or Sr; M = Nb or Ta)

International Nuclear Information System (INIS)

Rajendran, Deepthi N.; Ravindran Nair, K.; Prabhakar Rao, P.; Sibi, K.S.; Koshy, Peter; Vaidyan, V.K.

2008-01-01

New oxides of the type, NaAZrMO 6 (M = Ca or Sr; M = Nb or Ta), have been prepared by the solid-state reaction technique. Phase identification by powder X-ray diffraction (XRD) shows that NaCaZrMO 6 has orthorhombic perovskite type structure (Pnma) and NaSrZrMO 6 has cubic perovskite type structure (Pm3m). The grain morphology observation by scanning electron microscope (SEM) shows well-sintered grains. ac impedance spectra and electrical conductivity measurements in air, oxygen and nitrogen atmospheres indicate that they are probable oxide ion conductors with ionic conductivities of the order of 10 -3 S cm -1 at 750 deg. C

Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

International Nuclear Information System (INIS)

Chen, Jie-Ying; Cheng, Ya-Nan; Han, Lei; Wei, Feng; Yu, Wen-Wen; Zhang, Xin-Wei; Cao, Shui; Yu, Jin-Pu

2015-01-01

A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients. Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated. Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs. K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment

Effect of Ca{sup 2+} substitution on impedance and electrical conduction mechanism of Ba{sub 1−x}Ca{sub x}Zr{sub 0.1}Ti{sub 0.9}O{sub 3} (0.00≤x≤0.20) ceramics

Energy Technology Data Exchange (ETDEWEB)

Mondal, Tanusree [Functional Ceramics Laboratory, Department of Applied Physics, Indian Institute of Technology (ISM), Dhanbad 826004 (India); Das, Sayantani [Department of Physics, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700009 (India); Badapanda, T. [Department of Physics, C.V. Raman College of Engineering, Bhubaneswar, Odisha 7520544 (India); Sinha, T.P. [Department of Physics, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009 (India); Sarun, P.M., E-mail: sarun.res@gmail.com [Functional Ceramics Laboratory, Department of Applied Physics, Indian Institute of Technology (ISM), Dhanbad 826004 (India)

2017-03-01

The Ca modified Ba{sub 1−x}Ca{sub x}Zr{sub 0.1}Ti{sub 0.9}O{sub 3} (BCZT) system for x=0.00–0.20 is synthesized by the high-temperature conventional solid state reaction method. The morphotropic phase boundary (MPB) between the tetragonal and cubic structure is obtained at room temperature for the composition x=0.15. The doping of Ca facilitates the enhancement of the homogeneity of microstructure and growth of the grain size. The phase transition is also confirmed by Raman spectroscopy. In order to explore the effect of Ca concentration variation on the conduction mechanism of BaZr{sub 0.1}Ti{sub 0.9}O{sub 3} (BZT) ceramic, the frequency dependent ac impedance spectroscopy technique is used at various temperatures. The effect of Ca doping on the electrical properties of BZT is clearly noticeable. The resistance of the grain (bulk) and the grain boundary is increased as a consequence of the increase in the activation energy of Ca substituted BZT samples. The enhanced resistivity of the Ca substituted BZT ceramics is explained in terms of the decrease in the mobility of the charge carriers associated with the lattice distortion. The electric modulus analysis reveals the enhanced capacitance of BCZT ceramics which is in good agreement with the results obtained from complex impedance analysis.

Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task.

Science.gov (United States)

Martig, Adria K; Mizumori, Sheri J Y

2011-02-01

Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle Ca(V)1.1 calcium channel splice variants.

Science.gov (United States)

Tuluc, Petronel; Flucher, Bernhard E

2011-12-01

Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel Ca(V)1.1 is the exception. The classical splice variant Ca(V)1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel Ca(V)1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. Ca(V)1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting Ca(V)1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical Ca(V)1.1a channel.

Mechanochemical synthesis of CaO•ZnO.K2CO3 catalyst: Characterization and activity for methanolysis of sunflower oil

Directory of Open Access Journals (Sweden)

Kesić Željka

2015-01-01

Full Text Available The goal of this study was to prepare CaO.ZnO catalyst which contain small amount of K2CO3 and analyze its activity for biodiesel synthesis. Catalyst was prepared using the following procedure: CaO and ZnO (molar ratio of 1:2, water and K2CO3 (in various amounts were mechanochemically treated and after milling heated at 700 oC in air atmosphere for obtaining mixed CaO•ZnO/xK2CO3 oxides (x = 0, 1, 2 and 4; mole of K2CO3 per 10 mole of CaO. All the samples were characterized by X-ray diffraction (XRD, inductively coupled plasma (ICP, X-ray photoelectron spectroscopy (XPS, thermogravimetric analysis (TGA, infrared spectroscopy (FTIR, scanning electron microscopy/energy-dispersive spectroscopy (SEM/EDS, particle size laser diffraction (PSLD distribution, solubility measurement of Ca, Zn and K ions in methanol as well as by determination of their alkalinity (Hammett indicator method. Prepared CaO•ZnO/xK2CO3 composite powders were tested as catalysts for methanolysis of sunflower oil at 70ºC using molar ratio of sunflower oil to methanol of 1:10 and with 2 mas% of catalyst based on oil weight. The presence of K2CO3 in prepared samples was found to increase the activity of catalyst, and that such effect is caused by homogeneous-heterogeneous catalysis of biodiesel synthesis. [Projekat Ministarstva nauke Republike Srbije, br. 45001

Effect of sulfation on the surface activity of CaO for N{sub 2}O decomposition

Energy Technology Data Exchange (ETDEWEB)

Wu, Lingnan, E-mail: wulingnan@126.com [School of Energy, Power and Mechanical Engineering, North China Electric Power University, 102206 Beijing (China); National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Hu, Xiaoying, E-mail: huxy@ncepu.edu.cn [National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Qin, Wu, E-mail: qinwugx@126.com [National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Dong, Changqing, E-mail: cqdong1@163.com [National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Yang, Yongping, E-mail: yypncepu@163.com [School of Energy, Power and Mechanical Engineering, North China Electric Power University, 102206 Beijing (China)

2015-12-01

Graphical abstract: - Highlights: • Sulfation of CaO (1 0 0) surface greatly deactivates its surface activity for N{sub 2}O decomposition. • An increase of sulfation degree leads to a decrease of CaO surface activity for N{sub 2}O decomposition. • Sulfation from CaSO{sub 3} into CaSO{sub 4} is the crucial step for deactivating the surface activity for N{sub 2}O decomposition. • The electronic interaction CaO (1 0 0)/CaSO{sub 4} (0 0 1) interface is limited to the bottom layer of CaSO{sub 4} (0 0 1) and the top layer of CaO (1 0 0). • CaSO{sub 4} (0 0 1) and (0 1 0) surfaces show negligible catalytic ability for N{sub 2}O decomposition. - Abstract: Limestone addition to circulating fluidized bed boilers for sulfur removal affects nitrous oxide (N{sub 2}O) emission at the same time, but mechanism of how sulfation process influences the surface activity of CaO for N{sub 2}O decomposition remains unclear. In this paper, we investigated the effect of sulfation on the surface properties and catalytic activity of CaO for N{sub 2}O decomposition using density functional theory calculations. Sulfation of CaO (1 0 0) surface by the adsorption of a single gaseous SO{sub 2} or SO{sub 3} molecule forms stable local CaSO{sub 3} or CaSO{sub 4} on the CaO (1 0 0) surface with strong hybridization between the S atom of SO{sub x} and the surface O anion. The formed local CaSO{sub 3} increases the barrier energy of N{sub 2}O decomposition from 0.989 eV (on the CaO (1 0 0) surface) to 1.340 eV, and further sulfation into local CaSO{sub 4} remarkably increases the barrier energy to 2.967 eV. Sulfation from CaSO{sub 3} into CaSO{sub 4} is therefore the crucial step for deactivating the surface activity for N{sub 2}O decomposition. Completely sulfated CaSO{sub 4} (0 0 1) and (0 1 0) surfaces further validate the negligible catalytic ability of CaSO{sub 4} for N{sub 2}O decomposition.

Measurements of Small Exposures of Gamma Radiation with CaSO{sub 4}:Mn Radiothermoluminescence

Energy Technology Data Exchange (ETDEWEB)

Bjaerngard, Bengt

1963-08-15

A system for measurements of small exposures of gamma radiation using CaSO{sub 4}:Mn thermoluminescence has been developed. The construction and performance of a read-out apparatus is described as well as the construction and characteristics of a simple dosimeter. The reproducibility of the method at various exposures is estimated. 20 {mu}R of 1 MeV gamma radiation can be measured with a reproducibility within {+-} 50 % (standard deviation)

Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus

International Nuclear Information System (INIS)

Heyliger, C.E.; Prakash, A.; McNeill, J.

1987-01-01

Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca 2+ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca 2+ transport, little appears to be known about its Ca 2+ transporting capability in the diabetic myocardium. In this regard, the authors have examined the status of the cardiac sarcolemmal Ca 2+ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection. Ca 2+ pump activity assessed by measuring its Ca 2+ -stimulated adenosine triphosphatase and Ca 2+ -uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca 2+ pump is defective in the diabetic myocardium and may be involved in the altered Ca 2+ transport of the heart during diabetes mellitus

Fabrication and analysis of small-scale thermal energy storage with conductivity enhancement

International Nuclear Information System (INIS)

Thapa, Suvhashis; Chukwu, Sam; Khaliq, Abdul; Weiss, Leland

2014-01-01

Highlights: • Useful thermal conductivity envelope established for small scale TES. • Paraffin conductivity enhanced from .5 to 3.8 W/m K via low-cost copper insert. • Conductivity increase beyond 5 W/m K shows diminished returns. • Storage with increased conductivity lengthened thermoelectric output up to 247 s. - Abstract: The operation and useful operating parameters of a small-scale Thermal Energy Storage (TES) device that collects and stores heat in a Phase Change Material (PCM) is explored. The PCM utilized is an icosane wax. A physical device is constructed on the millimeter scale to examine specific effects of low-cost thermal conductivity enhancements that include copper foams and other metallic inserts. Numerical methods are utilized to establish useful operating range of small-scale TES devices in general, and the limits of thermal conductivity enhancement on thermoelectric operation specifically. Specific attention is paid to the manufacturability of the various constructs as well as the resulting thermal conductivity enhancement. A maximum thermal conductivity of 3.8 W/m K is achieved in experimental testing via copper foam enhancement. A simplified copper matrix achieves conductivity of 3.7 W/m K and allows significantly reduced fabrication effort. These results compare favorably to baseline wax conductivity of .5 W/m K. Power absorption is recorded of about 900 W/m 2 . Modeling reveals diminishing returns beyond 4–6 W/m K for devices on this scale. Results show the system capable of extending thermoelectric operation several minutes through the use of thermal energy storage techniques within the effective conductivity ranges

Solid electrolytes based on {1 − (x + y}ZrO2-(xMgO-(yCaO ternary system: Preparation, characterization, ionic conductivity, and dielectric properties

Directory of Open Access Journals (Sweden)

Nazli Zeeshan

2018-01-01

Full Text Available Different composition of composite material of zirconium dioxide co-doped with magnesium oxide [MgO(x] and calcium oxide [CaO(y] according to the general molecular formula {1 − (x + y}ZrO2-(xMgO-(yCaO were prepared by co-precipitation method and characterized by different techniques, such as XRD, FTIR, TG-DTA, and SEM. Co-doping was conducted to enhance the ionic conductivity, as mixed system show higher conductivity than the single doped one. Arrhenius plots of the conductance revealed that the co-doped composition “6Mg3Ca” has a higher conductivity with a minimum activation energy of 0.003 eV in temperature range of 50–190 °C. With increasing temperature, dielectric constant value increased; however, with increasing frequency it shows opposite trend. Co-doped composition C2 exhibit higher conductivity compared to C3, owing to the concentration of Mg content (0–6%; the conductivity decreases thereafter. Zirconium oxide was firstly used for medical purpose in orthopaedics, but currently different type of zirconia-ceramic materials has been successfully introduced into the clinic to fix the dental prostheses.

(Patho)physiological implications of the novel epithelial Ca2+ channels TRPV5 and TRPV6.

NARCIS (Netherlands)

Nijenhuis, T.; Hoenderop, J.G.J.; Nilius, B.; Bindels, R.J.M.

2003-01-01

The epithelial Ca(2+) channels TRPV5 and TRPV6 constitute the apical Ca(2+) entry mechanism in active Ca(2+) (re)absorption. These two members of the superfamily of transient receptor potential (TRP) channels were cloned from the vitamin-D-responsive epithelia of kidney and small intestine and

Active pore space utilization in nanoporous carbon-based supercapacitors: Effects of conductivity and pore accessibility

Science.gov (United States)

Seredych, Mykola; Koscinski, Mikolaj; Sliwinska-Bartkowiak, Malgorzata; Bandosz, Teresa J.

2012-12-01

Composites of commercial graphene and nanoporous sodium-salt-polymer-derived carbons were prepared with 5 or 20 weight% graphene. The materials were characterized using the adsorption of nitrogen, SEM/EDX, thermal analysis, Raman spectroscopy and potentiometric titration. The samples' conductivity was also measured. The performance of the carbon composites in energy storage was linked to their porosity and electronic conductivity. The small pores (<0.7) were found as very active for double layer capacitance. It was demonstrated that when double layer capacitance is a predominant mechanism of charge storage, the degree of the pore space utilization for that storage can be increased by increasing the conductivity of the carbons. That active pore space utilization is defined as gravimetric capacitance per unit pore volume in pores smaller than 0.7 nm. Its magnitude is affected by conductivity of the carbon materials. The functional groups, besides pseudocapacitive contribution, increased the wettability and thus the degree of the pore space utilization. Graphene phase, owing to its conductivity, also took part in an insitu increase of the small pore accessibility and thus the capacitance of the composites via enhancing an electron transfer to small pores and thus imposing the reduction of groups blocking the pores for electrolyte ions.

Ca2+-dependent K+ Channels in Exocrine Salivary Glands

Science.gov (United States)

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

2014-01-01

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

Recovery of rhythmic activity in a central pattern generator: analysis of the role of neuromodulator and activity-dependent mechanisms.

Science.gov (United States)

Zhang, Yili; Golowasch, Jorge

2011-11-01

The pyloric network of decapods crustaceans can undergo dramatic rhythmic activity changes. Under normal conditions the network generates low frequency rhythmic activity that depends obligatorily on the presence of neuromodulatory input from the central nervous system. When this input is removed (decentralization) the rhythmic activity ceases. In the continued absence of this input, periodic activity resumes after a few hours in the form of episodic bursting across the entire network that later turns into stable rhythmic activity that is nearly indistinguishable from control (recovery). It has been proposed that an activity-dependent modification of ionic conductance levels in the pyloric pacemaker neuron drives the process of recovery of activity. Previous modeling attempts have captured some aspects of the temporal changes observed experimentally, but key features could not be reproduced. Here we examined a model in which slow activity-dependent regulation of ionic conductances and slower neuromodulator-dependent regulation of intracellular Ca(2+) concentration reproduce all the temporal features of this recovery. Key aspects of these two regulatory mechanisms are their independence and their different kinetics. We also examined the role of variability (noise) in the activity-dependent regulation pathway and observe that it can help to reduce unrealistic constraints that were otherwise required on the neuromodulator-dependent pathway. We conclude that small variations in intracellular Ca(2+) concentration, a Ca(2+) uptake regulation mechanism that is directly targeted by neuromodulator-activated signaling pathways, and variability in the Ca(2+) concentration sensing signaling pathway can account for the observed changes in neuronal activity. Our conclusions are all amenable to experimental analysis.

Preparation, structural characterization, and in vitro cell studies of three-dimensional SiO2-CaO binary glass scaffolds built ofultra-small nanofibers.

Science.gov (United States)

Luo, Honglin; Li, Wei; Ao, Haiyong; Li, Gen; Tu, Junpin; Xiong, Guangyao; Zhu, Yong; Wan, Yizao

2017-07-01

Three-dimensional (3D) nanofibrous scaffolds hold great promises in tissue engineering and regenerative medicine. In this work, for the first time, 3D SiO 2 -CaO binary glass nanofibrous scaffolds have been fabricated via a combined method of template-assisted sol-gel and calcination by using bacterial cellulose as the template. SEM with EDS, TEM, and AFM confirm that the molar ratio of Ca to Si and fiber diameter of the resultant SiO 2 -CaO nanofibers can be controlled by immersion time in the solution of tetraethyl orthosilicate and ethanol. The optimal immersion time was 6h which produced the SiO 2 -CaO binary glass containing 60at.% Si and 40at.% Ca (named 60S40C). The fiber diameter of 60S40C scaffold is as small as 29nm. In addition, the scaffold has highly porous 3D nanostructure with dominant mesopores at 10.6nm and macropores at 20μm as well as a large BET surface area (240.9m 2 g -1 ), which endow the 60S40C scaffold excellent biocompatibility and high ALP activity as revealed by cell studies using osteoblast cells. These results suggest that the 60S40C scaffold has great potential in bone tissue regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning.

Science.gov (United States)

Farley, J; Auerbach, S

Phosphorylation of ion channels has been suggested as one molecular mechanism responsible for learning-produced long-term changes in neuronal excitability. Persistent training-produced changes in two distinct K+ currents (IA (ref. 2), IK-Ca (refs 3,4)) and a voltage-dependent calcium current (ICa; refs 3,4) have previously been shown to occur in type B photoreceptors of Hermissenda, as a result of associative learning. But the identity of the phosphorylation pathway(s) responsible for these changes has not as yet been determined. Injections of cyclic AMP-dependent protein kinase reduce a K+ current (IK) in B cells which is different from those changed by training, but fails to reduce IA and IK-Ca. Phosphorylase b kinase (an exogenous calcium/calmodulin-dependent kinase) reduces IA, but whether IK-Ca and ICa are changed in the manner of associative training is not yet known. Another protein kinase present in high concentrations in both mammalian brain and molluscan nervous systems is protein kinase C, which is both calcium- and phospholipid-sensitive. We now present evidence that activation of protein kinase C by the tumour promoter phorbol ester (PDB) and intracellular injection of the enzyme induce conductance changes similar to those caused by associative training in Hermissenda B cells (that is a reduction of IA and IK-Ca, and enhancement of ICa). These results represent the first direct demonstration that protein kinase C affects membrane K+ ion conductance mechanisms.

The C-terminal random coil region tunes the Ca²⁺-binding affinity of S100A4 through conformational activation.

Directory of Open Access Journals (Sweden)

Annette Duelli

Full Text Available S100A4 interacts with many binding partners upon Ca2+ activation and is strongly associated with increased metastasis formation. In order to understand the role of the C-terminal random coil for the protein function we examined how small angle X-ray scattering of the wild-type S100A4 and its C-terminal deletion mutant (residues 1-88, Δ13 changes upon Ca2+ binding. We found that the scattering intensity of wild-type S100A4 changes substantially in the 0.15-0.25 Å-1 q-range whereas a similar change is not visible in the C-terminus deleted mutant. Ensemble optimization SAXS modeling indicates that the entire C-terminus is extended when Ca2+ is bound. Pulsed field gradient NMR measurements provide further support as the hydrodynamic radius in the wild-type protein increases upon Ca2+ binding while the radius of Δ13 mutant does not change. Molecular dynamics simulations provide a rational explanation of the structural transition: the positively charged C-terminal residues associate with the negatively charged residues of the Ca2+-free EF-hands and these interactions loosen up considerably upon Ca2+-binding. As a consequence the Δ13 mutant has increased Ca2+ affinity and is constantly loaded at Ca2+ concentration ranges typically present in cells. The activation of the entire C-terminal random coil may play a role in mediating interaction with selected partner proteins of S100A4.

In vivo behaviors of Ca(OH){sub 2} activated nano SiO{sub 2} (n{sub Ca}/n{sub Si} = 3) cement in rabbit model

Energy Technology Data Exchange (ETDEWEB)

Lin, Qing, E-mail: lnqing@yahoo.com [School of Material Engineering, Jinling Institute of Technology, Nanjing 211169 (China); Zhang, Xiaojuan [School of Material Engineering, Jinling Institute of Technology, Nanjing 211169 (China); Lu, Chunhua; Lan, Xianghui [State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology, Nanjing 210009 (China); Hou, Guihua [Key Laboratory for Advanced Technology in Environmental Protection of Jiangsu Province, Yancheng Institute of Technology, Yancheng 224051 (China); Xu, Zhongzi [State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology, Nanjing 210009 (China)

2016-01-01

In vivo behaviors of Ca(OH){sub 2} activated nano SiO{sub 2} (n{sub Ca}/n{sub Si} = 3, TCS) cement were investigated in the rabbit femoral defects using the poly(methyl methacrylate) (PMMA) as control. The deposited apatite and CaCO{sub 3} layers round TCS paste surfaces were completely used to construct the new bone tissue. TCS paste could stimulate the formation of new bone tissue in marrow tissue. The osteostimulation was mainly attributed to the proliferation and differentiation effects of Ca and Si ions released from TCS paste on the osteoprogenitor cells. However, Calcium–Silicate–Hydrate (C–S–H) gel in TCS paste was harder to degradate than Ca(OH){sub 2}. TCS paste kept the original shape during implantation, and could not provide the pores or spaces for further formation of bone tissue. Osteolytic defects induced by wear particles from TCS paste surface could not be completely avoided, because of the interfacial strain and the extensive micromotion between TCS paste surface and new bone tissue. Overall, our results indicated that Ca(OH){sub 2} activated nano SiO{sub 2} cement was bioactivity and osteostimulation. The further improvements of Ca(OH){sub 2} activated nano SiO{sub 2} cement should be done by achieving a balance between biological properties and mechanical performances. - Highlights: • Ca(OH){sub 2} activated nano SiO{sub 2} (n{sub Ca}/n{sub Si} = 3, TCS) cement was in vivo bioactivity. • Deposited apatite and CaCO{sub 3} particles round TCS paste were utilized to restructure new bone tissue. • TCS paste was able to induce osteogenesis in marrow tissue. • Wear particle could induced osteolytic defect between TCS paste and bone tissue.

Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.

Science.gov (United States)

Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi; Jacquemond, Vincent

2015-04-01

Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca(2+) homeostasis and excitation-contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein-tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca(2+) transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca(2+) release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP-expressing fibers showed a reversible depression of Ca(2+) release during trains, with the peak Ca(2+) transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP-expressing fibers. Cav1.1 Ca(2+) channel-mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule-bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

Cry64Ba and Cry64Ca, Two ETX/MTX2-Type Bacillus thuringiensis Insecticidal Proteins Active against Hemipteran Pests.

Science.gov (United States)

Liu, Yonglei; Wang, Yinglong; Shu, Changlong; Lin, Kejian; Song, Fuping; Bravo, Alejandra; Soberón, Mario; Zhang, Jie

2018-02-01

Genetically modified crops that express insecticidal Bacillus thuringiensis (Bt) proteins have become a primary approach for control of lepidopteran (moth) and coleopteran (beetle) pests that feed by chewing the plants. However, the sap-sucking insects (Hemiptera) are not particularly susceptible to Bt toxins. In this study, we describe two Cry toxins (Cry64Ba and Cry64Ca) from Bt strain 1012 that showed toxicity against two important hemipteran rice pests, Laodelphax striatellus and Sogatella furcifera Both of these proteins contain an ETX/MTX2 domain and share common sequence features with the β-pore-forming toxins. Coexpression of cry64Ba and cry64Ca genes in the acrystalliferous Bt strain HD73 - resulted in high insecticidal activity against both hemipteran pests. No toxicity was observed on other pests such as Ostrinia furnacalis , Plutella xylostella , or Colaphellus bowringi Also, no hemolytic activity or toxicity against cancer cells was detected. Binding assays showed specific binding of the Cry64Ba/Cry64Ca toxin complex to brush border membrane vesicles isolated from L. striatellus Cry64Ba and Cry64Ca are Bt Cry toxins highly effective against hemipteran pests and could provide a novel strategy for the environmentally friendly biological control of rice planthoppers in transgenic plants. IMPORTANCE In Asia, rice is an important staple food, whose production is threatened by rice planthoppers. To date, no effective Bacillus thuringiensis (Bt) protein has been shown to have activity against rice planthoppers. We cloned two Bt toxin genes from Bt strain 1012 that showed toxicity against small brown planthoppers ( Laodelphax striatellus ) and white-backed planthoppers ( Sogatella furcifera ). To our knowledge, the proteins encoded by the cry64Ba and cry64Ca genes are the most efficient insecticidal Bt Cry proteins with activity against hemipteran insects reported so far. Cry64Ba and Cry64Ca showed no toxicity against some lepidopteran or coleopteran pests

Ion microprobe assessment of the heterogeneity of Mg/Ca, Sr/Ca and Mn/Ca ratios in Pecten maximus and Mytilus edulis (bivalvia shell calcite precipitated at constant temperature

Directory of Open Access Journals (Sweden)

P. S. Freitas

2009-07-01

Full Text Available Small-scale heterogeneity of biogenic carbonate elemental composition can be a significant source of error in the accurate use of element/Ca ratios as geochemical proxies. In this study ion microprobe (SIMS profiles showed significant small-scale variability of Mg/Ca, Sr/Ca and Mn/Ca ratios in new shell calcite of the marine bivalves Pecten maximus and Mytilus edulis that was precipitated during a constant-temperature culturing experiment. Elevated Mg/Ca, Sr/Ca and Mn/Ca ratios were found to be associated with the deposition of elaborate shell features, i.e. a shell surface stria in P. maximus and surface shell disturbance marks in both species, the latter a common occurrence in bivalve shells. In both species the observed small-scale elemental heterogeneity most likely was not controlled by variable transport of ions to the extra-pallial fluid, but by factors such as the influence of shell organic content and/or crystal size and orientation, the latter reflecting conditions at the shell crystal-solution interface. In the mid and innermost regions of the P. maximus shell the lack of significant small-scale variation of Mg/Ca ratios, which is consistent with growth at constant temperature, suggest a potential application as a palaeotemperature proxy. Cross-growth band element/Ca ratio profiles in the interior of bivalve shells may provide more promising palaeo-environmental tools than sampling from the outer region of bivalve shells.

A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome

Science.gov (United States)

Wilson, Dan; Ermentrout, Bard; Němec, Jan; Salama, Guy

2017-09-01

Abnormal Ca2+ handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca2+ release from Ca2+-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca2+-channel window current. In bradycardia and long QT type 2 (LQT2), a second, non-voltage triggered cytosolic Ca2+ elevation increases gradually in amplitude, occurs before overt voltage instability, and then precedes the rise of EADs. Here, we used a modified Shannon-Puglisi-Bers model of rabbit ventricular myocytes to reproduce experimental Ca2+ dynamics in bradycardia and LQT2. Abnormal systolic Ca2+-oscillations and EADs caused by SR Ca2+-release are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance. Two gates control RyR2 activation and inactivation and sense cytosolic Ca2+ while a third gate senses luminal junctional SR Ca2+. The model predicts EADs in bradycardia and low extracellular [K+] and cessation of SR Ca2+-release terminate salvos of EADs. Ca2+-waves, systolic cell-synchronous Ca2+-release, and multifocal diastolic Ca2+ release seen in subcellular Ca2+-mapping experiments are observed in the 2-dimensional version of the model. These results support the role of SR Ca2+-overload, abnormal SR Ca2+-release, and the subsequent activation of the electrogenic Na+/Ca2+-exchanger as the mechanism of TdP. The model offers new insights into the genesis of cardiac arrhythmia and new therapeutic strategies.

Ionic conductivity in new perovskite type oxides: NaAZrMO{sub 6} (A = Ca or Sr; M = Nb or Ta)

Energy Technology Data Exchange (ETDEWEB)

Rajendran, Deepthi N.; Ravindran Nair, K. [Regional Research Laboratory (CSIR), Trivandrum 695019 (India); Prabhakar Rao, P. [Regional Research Laboratory (CSIR), Trivandrum 695019 (India)], E-mail: padala_rao@yahoo.com; Sibi, K.S.; Koshy, Peter [Regional Research Laboratory (CSIR), Trivandrum 695019 (India); Vaidyan, V.K. [Department of Physics, University of Kerala, Trivandrum 695581 (India)

2008-06-15

New oxides of the type, NaAZrMO{sub 6} (M = Ca or Sr; M = Nb or Ta), have been prepared by the solid-state reaction technique. Phase identification by powder X-ray diffraction (XRD) shows that NaCaZrMO{sub 6} has orthorhombic perovskite type structure (Pnma) and NaSrZrMO{sub 6} has cubic perovskite type structure (Pm3m). The grain morphology observation by scanning electron microscope (SEM) shows well-sintered grains. ac impedance spectra and electrical conductivity measurements in air, oxygen and nitrogen atmospheres indicate that they are probable oxide ion conductors with ionic conductivities of the order of 10{sup -3} S cm{sup -1} at 750 deg. C.

The empirical relationship between the managerial conduct and internal control activities in South African small, medium and micro enterprises

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Juan-Pierre Bruwer

2017-07-01

Aim: Since a system of internal control comprises five inter-related elements, while also taking into consideration that management is ultimately responsible for the internal control in their respective business entities, which is greatly influenced by their managerial conduct, this research study placed focus on determining the relationship which exist between the managerial conduct and the internal control activities evident in South African SMMEs. Setting: This study was conducted in the Cape Metropole, South Africa by obtaining responses from 240 stakeholders of SMMEs: 120 members of management and 120 employees. Methods: In order to achieve the latter, quantitative data were collected through a questionnaire and analysed accordingly through both descriptive statistics and inferential statistics. Results: From the results, a very weak negative statistically significant relationship was identified between the managerial conduct and the internal control activities evident in South African SMMEs. Conclusion: Essentially, management and employees should revisit the internal control activities evident in their respective SMMEs through placing emphasis on those internal control activities which can be built on their control environment.

Catalytic properties of inositol trisphosphate kinase: activation by Ca2+ and calmodulin

International Nuclear Information System (INIS)

Ryu, S.H.; Lee, S.Y.; Lee, K.Y.; Rhee, S.G.

1987-01-01

Inositol 1,4,5-triphosphate (Ins-1,4,5-P 3 ) is an important second-messenger molecule that mobilizes Ca 2+ from intracellular stores in response to the occupancy of receptor by various Ca 2+ -mobilizing agonists. The fate of Ins-1,4,5-P 3 is determined by two enzymes, a 3-kinase and a 5-phosphomonoesterase. The first enzyme converts Ins-1,4,5-P 3 to Ins-1,3,4,5-P 4 , whereas the latter forms Ins-1,4-P 2 . Recent studies suggest that Ins-1,3,4,5-P 4 might modulate the entry of Ca 2+ from an extracellular source. In the current report, the authors describe the partial purification of the 3-kinase from the cytosolic fraction of bovine brain and studies of its catalytic properties. They found that the 3-kinase activity is significantly activated by the Ca 2+ /calmodulin complex. Therefore, they propose that Ca 2+ mobilized from endoplasmic reticulum by the action of Ins-1,4,5-P 3 forms a complex with calmodulin, and that the Ca 2+ /calmodulin complex stimulates the conversion of Ins-1,4,5-P 3 , and intracellular Ca 2+ mobilizer, to Ins-1,3,4,5-P 4 , an extracellular Ca 2+ mobilizer. A rapid assay method for the 3-kinase was developed that is based on the separation of [3- 32 P]Ins-1,3,4,5-P 4 and [γ- 32 P]ATP by thin-layer chromatography. Using this new assay method, they evaluated kinetic parameters (K/sub m/ for ATP = 40 μM, K/sub m/ for Ins-1,4,5-P 3 = 0.7 μM, K/sub i/ for ADP = 12 μM) and divalent cation specificity (Mg 2+ > > Mn 2+ > Ca 2+ ) for the 3-kinase

Sphingosine inhibits the sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA) activity

Energy Technology Data Exchange (ETDEWEB)

Benaim, Gustavo, E-mail: gbenaim@idea.gob.ve [Instituto de Estudios Avanzados (IDEA), Caracas (Venezuela, Bolivarian Republic of); Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Pimentel, Adriana A., E-mail: adriana.pimentel@ucv.ve [Facultad de Farmacia, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Felibertt, Pimali [Facultad de Ciencias, Universidad de Carabobo, Valencia (Venezuela, Bolivarian Republic of); Mayora, Adriana [Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Colman, Laura [Instituto Pasteur de Montevideo, Montevideo (Uruguay); Sojo, Felipe [Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Rojas, Héctor [Instituto de Inmunología, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of); Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas (Venezuela, Bolivarian Republic of); De Sanctis, Juan B. [Instituto de Inmunología, Universidad Central de Venezuela (UCV), Caracas (Venezuela, Bolivarian Republic of)

2016-04-29

The increase in the intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca{sup 2+}]{sub i} by inhibiting the sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca{sup 2+} pump. The results showed that addition of sphingosine produced a release of Ca{sup 2+} from the endoplasmic reticulum followed by a Ca{sup 2+} entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca{sup 2+}]{sub I} in mammalian cells.

Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity

DEFF Research Database (Denmark)

Bjelke, Jais R; Olsen, Ole H; Fodje, Michel

2008-01-01

between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity. Moreover, mutation of the Lys(161)-interactive residue Asp(217) or Asp(219) to Ala reduced the amidolytic...... activity by 40-50%, whereas the K161A mutation resulted in 80% reduction. Hence one of these Asp residues in the Ca(2+)-binding loop appears to suffice for some residual interaction with Lys(161), whereas the more severe effect upon replacement of Lys(161) is due to abrogation of the interaction with the N......-terminal tail. However, Ca(2+) attenuation of the repulsion between Asp(212) and Glu(296) keeps the activity above that of apoFVIIa. Altogether, our data suggest that repulsion involving Asp(212) in the Ca(2+)-binding loop suppresses FVIIa activity and that optimal activity requires a favorable interaction...

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

Directory of Open Access Journals (Sweden)

Krishna Samanta

2015-07-01

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

Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

Directory of Open Access Journals (Sweden)

Sylvain J Le Marchand

Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase

OpenAIRE

Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi

2016-01-01

Inward rectifier K+ channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP2). Stimulation of the Ca2+-sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both Gq/11, which decreases PIP2, and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP2. How membrane PIP2 levels are regulated by CaR activation and wheth...

Robust random telegraph conductivity noise in single crystals of the ferromagnetic insulating manganite La0.86Ca0.14MnO3

Science.gov (United States)

Przybytek, J.; Fink-Finowicki, J.; Puźniak, R.; Shames, A.; Markovich, V.; Mogilyansky, D.; Jung, G.

2017-03-01

Robust random telegraph conductivity fluctuations have been observed in La0.86Ca0.14MnO3 manganite single crystals. At room temperatures, the spectra of conductivity fluctuations are featureless and follow a 1 /f shape in the entire experimental frequency and bias range. Upon lowering the temperature, clear Lorentzian bias-dependent excess noise appears on the 1 /f background and eventually dominates the spectral behavior. In the time domain, fully developed Lorentzian noise appears as pronounced two-level random telegraph noise with a thermally activated switching rate, which does not depend on bias current and applied magnetic field. The telegraph noise is very robust and persists in the exceptionally wide temperature range of more than 50 K. The amplitude of the telegraph noise decreases exponentially with increasing bias current in exactly the same manner as the sample resistance increases with the current, pointing out the dynamic current redistribution between percolation paths dominated by phase-separated clusters with different conductivity as a possible origin of two-level conductivity fluctuations.

Energetic performance is improved by specific activation of K+ fluxes through K(Ca) channels in heart mitochondria

DEFF Research Database (Denmark)

Aon, Miguel A; Cortassa, Sonia; Wei, An-Chi

2009-01-01

Mitochondrial volume regulation depends on K+ movement across the inner membrane and a mitochondrial Ca2+-dependent K+ channel (mitoK(Ca)) reportedly contributes to mitochondrial K+ uniporter activity. Here we utilize a novel K(Ca) channel activator, NS11021, to examine the role of mito...... similar nonspecific (toxin-insensitive) effects at high concentrations. The results indicate that activating K+ flux through mitoK(Ca) mediates a beneficial effect on energetics that depends on mitochondrial swelling with maintained DeltaPsi(m)....

Regulation of the epithelial Ca2+ channels in small intestine as studied by quantitative mRNA detection.

NARCIS (Netherlands)

Abel, M. van; Hoenderop, J.G.J.; Kemp, J.W.C.M. van der; Leeuwen, J.P.P.M. van; Bindels, R.J.M.

2003-01-01

The epithelial Ca2+ channels TRPV5 and TRPV6 are localized to the brush border membrane of intestinal cells and constitute the postulated rate-limiting entry step of active Ca2+ absorption. The aim of the present study was to investigate the hormonal regulation of these channels. To this end, the

Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

Science.gov (United States)

Bonanni, Laura; Chachar, Mushtaque; Jover-Mengual, Teresa; Li, Hongmei; Jones, Adrienne; Yokota, Hidenori; Ofengeim, Dimitry; Flannery, Richard J; Miyawaki, Takahiro; Cho, Chang-Hoon; Polster, Brian M; Pypaert, Marc; Hardwick, J Marie; Sensi, Stefano L; Zukin, R Suzanne; Jonas, Elizabeth A

2006-06-21

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

Intra-Abdominal Desmoplastic Small Round Cell Tumor with Elevated Serum CA 125: A Case Report

Directory of Open Access Journals (Sweden)

Sheau-Fang Yang

2003-10-01

Full Text Available Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive tumor usually involving the peritoneum. It occurs more commonly in young males and is characterized by distinctive clinical, histologic, and immunophenotypic features. The histogenesis of DSRCT remains unknown. Coexpression of epithelial, mesenchymal, and neural antigens in the same cell provides evidence that DSRCT may arise from a primitive pluripotent stem cell with divergent differentiation. Recently, according to cytogenetic studies, some authors have proposed that the divergent differentiation of DSRCT may be the result of the fusion of Ewing's sarcoma gene and Wilms' tumor suppressor gene. Clinically, an elevated serum CA 125 concentration is found in some patients with DSRCT. We present the case of a 29-year-old man with diffuse intra-abdominal DSRCT and elevated serum CA 125 concentration and briefly review the relevant literature.

Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells

DEFF Research Database (Denmark)

Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle

2007-01-01

Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Ji, Meiju; Guan, Haixia; Gao, Cuixia; Shi, Bingyin; Hou, Peng

2011-01-01

Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood. We determined the promoter methylation of 6 genes and PIK3CA amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with PIK3CA amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC). Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of CALCA, CDH1, DAPK1, and EVX2 was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of RASSF1A methylation in ADC than SCC. In addition, PIK3CA amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with PIK3CA amplification. Our data showed highly frequent promoter methylation and PIK3CA amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with PIK3CA amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway

Appearance of small polaron hopping conduction in iron modified cobalt lithium bismuth borate glasses

Energy Technology Data Exchange (ETDEWEB)

Dahiya, M. S.; Khasa, S., E-mail: skhasa@yahoo.com; Yadav, Arti [Physics Department, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, India-131039 (India); Agarwal, A. [Applied Physics Department, Guru Jambheshwara University of Science and Technology, Hisar, India-125001 (India)

2016-05-23

Lithium bismuth borate glasses containing different amounts of cobalt and iron oxides having chemical composition xFe{sub 2}O{sub 3}•(20-x)CoO•30Li{sub 2}O•10Bi{sub 2}O{sub 3}•40B{sub 2}O{sub 3} (x = 0, 5, 10, 15 and 20 mol% abbreviated as CFLBB1-5 respectively) prepared via melt quench technique have been investigated for their dc electrical conductivity. The amorphous nature of prepared glasses has been confirmed through X-ray diffraction measurements. The dc electrical conductivity has been analyzed by applying Mott’s small polaron hopping model. Activation energies corresponding to lower and higher temperature region have been evaluated. The iron ion concentration (N), mean spacing between iron ions (R) and polaron radius (R{sub p}) has been evaluated using the values of phonon radius (R{sub ph}) and Debye temperature (θ{sub D}). The glass sample without iron (CFLBB1) shows ionic conductivity but the incorporation of iron in the glass matrix results in the appearance of electronic conductivity.

Activity-dependent intracellular Ca2+ transients in unmyelinated nerve fibres of the isolated adult rat vagus nerve.

Science.gov (United States)

Wächtler, J; Mayer, C; Grafe, P

1998-04-01

Confocal laser scanning microscopy was used to follow changes in the free intracellular calcium concentration ([Ca2+]i) in nerve fibres and adjacent Schwann cells in isolated rat vagus nerves. [Ca2+]i was monitored by the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during repetitive (1-50 Hz) supramaximal electrical stimulation or by bath application of ATP. Trains of action potentials were more effective at elongated, fibre-like structures of the vagus nerves, whereas ATP-induced Ca2+ transients were found predominantly in regions of Schwann cell bodies. Activity-induced Ca2+ signals were unaffected by pharmacological manipulation of intracellular Ca2+ stores, during long-lasting application of purinergic receptor agonists, or by substitution of extracellular Na+ with Li+. However, they were abolished in the presence of Ca2+-free bathing solution or after the blocking of Ca2+ channels with Cd2+. Ca2+ transients were also observed during Ca2+ action potentials. Such "Ca2+ spikes" were elicited by electrical stimulation in the presence of a combination of tetrodotoxin and K+ channel blockers. These data suggest that voltage-dependent Ca2+ channels, activated during short trains of Na+ action potentials, produce an increase in intra-axonal [Ca2+] of rat vagus nerves. We did not find evidence for activity-dependent Ca2+ transients in the Schwann cells surrounding the unmyelinated axons.

Age-dependent impact of Ca_V3.2 T-type calcium channel deletion on myogenic tone and flow-mediated vasodilatation in small arteries

DEFF Research Database (Denmark)

Mikkelsen, Miriam F.; Björling, Karl; Jensen, Lars Jørn

2016-01-01

, structural remodeling, and mRNA + protein expression in small mesenteric arteries from CaV3.2 knock-out vs. wild-type mice at young vs. mature adult age. In young mice, only, deletion of CaV3.2 led to enhanced myogenic response and ∼50 % reduction of flow-mediated vasodilatation. Ni(2+) had both CaV3...

Activity-Dependent IGF-1 Exocytosis is Controlled by the Ca2+-Sensor Synaptotagmin-10

Science.gov (United States)

Cao, Peng; Maximov, Anton; Südhof, Thomas C.

2011-01-01

Synaptotagmins Syt1, Syt2, Syt7, and Syt9 act as Ca2+-sensors for synaptic and neuroendocrine exocytosis, but the function of other synaptotagmins remains unknown. Here, we show that olfactory bulb neurons secrete IGF-1 by an activity-dependent pathway of exocytosis, and that Syt10 functions as the Ca2+-sensor that triggers IGF-1 exocytosis in these neurons. Deletion of Syt10 impaired activity-dependent IGF-1 secretion in olfactory bulb neurons, resulting in smaller neurons and an overall decrease in synapse numbers. Exogenous IGF-1 completely reversed the Syt10 knockout phenotype. Syt10 co-localized with IGF-1 in somatodendritic vesicles of olfactory bulb neurons, and Ca2+-binding to Syt10 caused these vesicles to undergo exocytosis, thereby secreting IGF-1. Thus, Syt10 controls a previously unrecognized pathway of Ca2+-dependent exocytosis that is spatially and temporally distinct from Ca2+-dependent synaptic vesicle exocytosis controlled by Syt1 in the same neurons, and two different synaptotagmins regulate distinct Ca2+-dependent membrane fusion reactions during exocytosis in the same neuron. PMID:21496647

PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus.

Science.gov (United States)

Guo, Xiaoguang; Kashihara, Toshihide; Nakada, Tsutomu; Aoyama, Toshifumi; Yamada, Mitsuhiko

2018-06-01

In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, molecular mechanism underlying the PDGF-induced migration of VSMCs remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a Ca V 1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase (SFK)/Abl inhibitor, bosutinib, in a less-than-additive manner. PDGF significantly increased Ca V 1.2 channel currents without altering Ca V 1.2 protein expression levels in A7r5 cells. This reaction was inhibited by C-terminal Src kinase, a selective inhibitor of SFKs. In contractile VSMCs, the C-terminus of Ca V 1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length Ca V 1.2 (Ca V 1.2FL) is expressed much more abundantly than truncated Ca V 1.2. In a heterologous expression system, c-Src activated Ca V 1.2 channels composed of Ca V 1.2FL but not truncated Ca V 1.2 (Ca V 1.2Δ1763) or Ca V 1.2Δ1763 plus clipped DCT. Further, c-Src enhanced the coupling efficiency between the voltage-sensing domain and activation gate of Ca V 1.2FL channels by phosphorylating Tyr1709 and Tyr1758 in PCT. Compared with Ca V 1.2Δ1763, c-Src could more efficiently bind to and phosphorylate Ca V 1.2FL irrespective of the presence or absence of clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational Ca V 1.2 modifications.

Modulation of intracellular calcium waves and triggered activities by mitochondrial ca flux in mouse cardiomyocytes.

Directory of Open Access Journals (Sweden)

Zhenghang Zhao

Full Text Available Recent studies have suggested that mitochondria may play important roles in the Ca(2+ homeostasis of cardiac myocytes. However, it is still unclear if mitochondrial Ca(2+ flux can regulate the generation of Ca(2+ waves (CaWs and triggered activities in cardiac myocytes. In the present study, intracellular/cytosolic Ca(2+ (Cai (2+ was imaged in Fluo-4-AM loaded mouse ventricular myocytes. Spontaneous sarcoplasmic reticulum (SR Ca(2+ release and CaWs were induced in the presence of high (4 mM external Ca(2+ (Cao (2+. The protonophore carbonyl cyanide p-(trifluoromethoxyphenylhydrazone (FCCP reversibly raised basal Cai (2+ levels even after depletion of SR Ca(2+ in the absence of Cao (2+ , suggesting Ca(2+ release from mitochondria. FCCP at 0.01 - 0.1 µM partially depolarized the mitochondrial membrane potential (Δψ m and increased the frequency and amplitude of CaWs in a dose-dependent manner. Simultaneous recording of cell membrane potentials showed the augmentation of delayed afterdepolarization amplitudes and frequencies, and induction of triggered action potentials. The effect of FCCP on CaWs was mimicked by antimycin A (an electron transport chain inhibitor disrupting Δψ m or Ru360 (a mitochondrial Ca(2+ uniporter inhibitor, but not by oligomycin (an ATP synthase inhibitor or iodoacetic acid (a glycolytic inhibitor, excluding the contribution of intracellular ATP levels. The effects of FCCP on CaWs were counteracted by the mitochondrial permeability transition pore blocker cyclosporine A, or the mitochondrial Ca(2+ uniporter activator kaempferol. Our results suggest that mitochondrial Ca(2+ release and uptake exquisitely control the local Ca(2+ level in the micro-domain near SR ryanodine receptors and play an important role in regulation of intracellular CaWs and arrhythmogenesis.

Proximate, mineral composition and antioxidant activity of traditional small millets cultivated and consumed in Rayalaseema region of south India.

Science.gov (United States)

Vali Pasha, Kotwal; Ratnavathi, Chamarthy Venkata; Ajani, Jayanna; Raju, Dugyala; Manoj Kumar, Sriramoju; Beedu, Sashidhar Rao

2018-01-01

Millets are a diverse group of small seeded grasses, widely grown around the world as cereal foods. This communication details the proximate, mineral profile and antioxidant activity of six different small millets (Finger, Foxtail, Proso, Little, Barnyard and Kodo millets) and their 21 cultivars that are traditionally cultivated and consumed in the region of Ralayaseema, south India. The proximate analysis revealed that these millets are rich in protein, fat, ash (mineral), total dietary fibre and total phenols with appreciable antioxidant activity. However, starch and amylose content was comparatively lower as compared to major millet sorghum. ICP-MS analysis of small millets demonstrated that they are rich in minerals such as Ca, P, K, Mg, Fe, Cu, Zn, Mn, Cr, Mo and Se. Finger and kodo millets were found to be nutritionally superior over other small millets. The results suggest that small millets have a potential to provide food security and can combat micronutrient malnutrition. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Ca2+-induced uncoupling of Aplysia bag cell neurons.

Science.gov (United States)

Dargaei, Zahra; Standage, Dominic; Groten, Christopher J; Blohm, Gunnar; Magoski, Neil S

2015-02-01

Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons of Aplysia are a group of electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during a prolonged period of synchronous firing called the afterdischarge. Accompanying the afterdischarge is an increase in intracellular Ca2+ and the activation of protein kinase C (PKC). We used whole cell recording from paired cultured bag cell neurons to demonstrate that electrical coupling is regulated by both Ca2+ and PKC. Elevating Ca2+ with a train of voltage steps, mimicking the onset of the afterdischarge, decreased junctional current for up to 30 min. Inhibition was most effective when Ca2+ entry occurred in both neurons. Depletion of Ca2+ from the mitochondria, but not the endoplasmic reticulum, also attenuated the electrical synapse. Buffering Ca2+ with high intracellular EGTA or inhibiting calmodulin kinase prevented uncoupling. Furthermore, activating PKC produced a small but clear decrease in junctional current, while triggering both Ca2+ influx and PKC inhibited the electrical synapse to a greater extent than Ca2+ alone. Finally, the amplitude and time course of the postsynaptic electrotonic response were attenuated after Ca2+ influx. A mathematical model of electrically connected neurons showed that excessive coupling reduced recruitment of the cells to fire, whereas less coupling led to spiking of essentially all neurons. Thus a decrease in electrical synapses could promote the afterdischarge by ensuring prompt recovery of electrotonic potentials or making the neurons more responsive to current spreading through the network. Copyright © 2015 the American Physiological Society.

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

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Cooper, Jacob C; Phadnis, Nitin

2017-07-01

Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Active generation and propagation of Ca2+ signals within tunneling membrane nanotubes.

Science.gov (United States)

Smith, Ian F; Shuai, Jianwei; Parker, Ian

2011-04-20

A new mechanism of cell-cell communication was recently proposed after the discovery of tunneling nanotubes (TNTs) between cells. TNTs are membrane protrusions with lengths of tens of microns and diameters of a few hundred nanometers that permit the exchange of membrane and cytoplasmic constituents between neighboring cells. TNTs have been reported to mediate intercellular Ca(2+) signaling; however, our simulations indicate that passive diffusion of Ca(2+) ions alone would be inadequate for efficient transmission between cells. Instead, we observed spontaneous and inositol trisphosphate (IP(3))-evoked Ca(2+) signals within TNTs between cultured mammalian cells, which sometimes remained localized and in other instances propagated as saltatory waves to evoke Ca(2+) signals in a connected cell. Consistent with this, immunostaining showed the presence of both endoplasmic reticulum and IP(3) receptors along the TNT. We propose that IP(3) receptors may actively propagate intercellular Ca(2+) signals along TNTs via Ca(2+)-induced Ca(2+) release, acting as amplification sites to overcome the limitations of passive diffusion in a chemical analog of electrical transmission of action potentials. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.

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Shun Liang

Full Text Available The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE is largely unclear.Using the Müllerian inhibiting substance type II receptor (MISIIR promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.

Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct cells in primary culture.

Science.gov (United States)

Valencia, L; Bidet, M; Martial, S; Sanchez, E; Melendez, E; Tauc, M; Poujeol, C; Martin, D; Namorado, M D; Reyes, J L; Poujeol, P

2001-05-01

To characterize Ca(2+) transport in newborn rat cortical collecting duct (CCD) cells, we used nifedipine, which in adult rat distal tubules inhibits the intracellular Ca(2+) concentration ([Ca(2+)](i)) increase in response to hormonal activation. We found that the dihydropyridine (DHP) nifedipine (20 microM) produced an increase in [Ca(2+)](i) from 87.6 +/- 3.3 nM to 389.9 +/- 29.0 nM in 65% of the cells. Similar effects of other DHP (BAY K 8644, isradipine) were also observed. Conversely, DHPs did not induce any increase in [Ca(2+)](i) in cells obtained from proximal convoluted tubule. In CCD cells, neither verapamil nor diltiazem induced any rise in [Ca(2+)](i). Experiments in the presence of EGTA showed that external Ca(2+) was required for the nifedipine effect, while lanthanum (20 microM), gadolinium (100 microM), and diltiazem (20 microM) inhibited the effect. Experiments done in the presence of valinomycin resulted in the same nifedipine effect, showing that K(+) channels were not involved in the nifedipine-induced [Ca(2+)](i) rise. H(2)O(2) also triggered [Ca(2+)](i) rise. However, nifedipine-induced [Ca(2+)](i) increase was not affected by protamine. In conclusion, the present results indicate that 1) primary cultures of cells from terminal nephron of newborn rats are a useful tool for investigating Ca(2+) transport mechanisms during growth, and 2) newborn rat CCD cells in primary culture exhibit a new apical nifedipine-activated Ca(2+) channel of capacitive type (either transient receptor potential or leak channel).

Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle.

Science.gov (United States)

Zhuge, Ronghua; Bao, Rongfeng; Fogarty, Kevin E; Lifshitz, Lawrence M

2010-01-15

Ca2+ sparks are short lived and localized Ca2+ transients resulting from the opening of ryanodine receptors in sarcoplasmic reticulum. These events relax certain types of smooth muscle by activating big conductance Ca2+-activated K+ channels to produce spontaneous transient outward currents (STOCs) and the resultant closure of voltage-dependent Ca2+ channels. But in many smooth muscles from a variety of organs, Ca2+ sparks can additionally activate Ca2+-activated Cl(-) channels to generate spontaneous transient inward current (STICs). To date, the physiological roles of Ca2+ sparks in this latter group of smooth muscle remain elusive. Here, we show that in airway smooth muscle, Ca2+ sparks under physiological conditions, activating STOCs and STICs, induce biphasic membrane potential transients (BiMPTs), leading to membrane potential oscillations. Paradoxically, BiMPTs stabilize the membrane potential by clamping it within a negative range and prevent the generation of action potentials. Moreover, blocking either Ca2+ sparks or hyperpolarization components of BiMPTs activates voltage-dependent Ca2+ channels, resulting in an increase in global [Ca2+](i) and cell contraction. Therefore, Ca2+ sparks in smooth muscle presenting both STICs and STOCs act as a stabilizer of membrane potential, and altering the balance can profoundly alter the status of excitability and contractility. These results reveal a novel mechanism underlying the control of excitability and contractility in smooth muscle.

Thermal neutron detection by activation of CaSO4:Dy + KBr thermoluminescent phosphors

International Nuclear Information System (INIS)

Gordon, A.M.P.L.; Muccillo, R.

1979-01-01

Thermoluminescence (TL) studies to detect thermal neutrons were performed in cold-pressed CaSO 4 :0,1%Dy + KBr samples. The detection is based on the self-irradiation of the CaSO 4 :Dy TL phosphor by the Br isotopes activated by exposure to a mixed neutron-gamma field. (Author) [pt

Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

Science.gov (United States)

Liu, Yu-Zhang; Wang, Yao; Shen, Weida; Wang, Zhiru

2017-08-01

Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear

Ca(2+-dependent regulation of the Ca(2+ concentration in the myometrium mitochondria. II. Ca(2+ effects on mitochondria membranes polarization and [Ca(2+](m

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L. G. Babich

2017-06-01

Full Text Available It is known that Ca2+ accumulation in the mitochondria undergoes complex regulation by Ca2+ itself. But the mechanisms of such regulation are still discussed. In this paper we have shown that Ca ions directly or indirectly regulate the level of myometrium mitochondria membranes polarization. The additions of 100 µM Ca2+ were accompanied by depolarization of the mitochondria membranes. The following experiments were designed to study the impact of Ca2+ on the myometrium mitochondria [Ca2+]m. Isolated myometrium mitochondria were preincubated without or with 10 μM Са2+ followed by 100 μM Са2+ addition. Experiments were conducted in three mediums: without ATP and Mg2+ (0-medium, in the presence of 3 mM Mg2+ (Mg-medium and 3 mM Mg2+ + 3 mM ATP (Mg,ATP-medium. It was shown that the effects of 10 μM Са2+ addition were different in different mediums, namely in 0- and Mg-medium the [Ca2+]m values increased, whereas in Mg,ATP-medium statistically reliable changes were not registered. Preincubation of mitochondria with 10 μM Са2+ did not affect the [Ca2+]m value after the addition of 100 μM Са2+. The [Ca2+]m values after 100 μM Са2+ addition were the same in 0- and Mg,ATP-mediums and somewhat lower in Mg-medium. Preliminary incubation of mitochondria with 10 μM Са2+ in 0- and Mg-mediums reduced changes of Fluo 4 normalized fluorescence values that were induced by 100 μM Са2+ additions, but in Mg,ATP-medium such differences were not recorded. It is concluded that Са2+ exchange in myometrium mitochondria is regulated by the concentration of Ca ions as in the external medium, so in the matrix of mitochondria. The medium composition had a significant impact on the [Са2+]m values in the absence of exogenous cation. It is suggested that light increase of [Са2+]m before the addition of 100 μM Са2+ may have a positive effect on the functional activity of the mitochondria.

Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

Science.gov (United States)

Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

2012-01-01

Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

Magnetoresistance and magnetothermopower properties of Bi/Ca/Co/O and Bi(Pb)/Ca/Co/O misfit layer cobaltites

CERN Document Server

Maignan, A; Hervieu, M; Michel, C; Pelloquin, D; Khomskii, D

2003-01-01

Two new compounds of the Bi/Ca/Co/O and Bi(Pb)/Ca/Co/O systems have been prepared. Their structure is built up from the intergrowth of four rock-salt-type layers and one [CoO sub 2 ] hexagonal layer. Both cobaltites exhibit large thermopower values (S sub 3 sub 0 sub 0 sub K approx 140 mu V K sup - sup 1), low resistivity values (rho sub 3 sub 0 sub 0 sub K = 40-60 m OMEGA cm) and small thermal conductivities (kappa sub 3 sub 0 sub 0 sub K approx 1 W K sup - sup 1 m sup - sup 1). Furthermore, these compounds exhibit a negative magnetoresistance, (MR = rho sub H - rho sub H sub sub 0 /rho sub H sub = sub 0), reaching, at 2.5 K, - 85% in 7 T for the Bi/Ca/Co/O misfit cobaltite. A large negative magnetothermopower is also found for these cobaltites in the same temperature range. A qualitative explanation of the observed behaviour is proposed.

Repeating Spatial-Temporal Motifs of CA3 Activity Dependent on Engineered Inputs from Dentate Gyrus Neurons in Live Hippocampal Networks.

Science.gov (United States)

Bhattacharya, Aparajita; Desai, Harsh; DeMarse, Thomas B; Wheeler, Bruce C; Brewer, Gregory J

2016-01-01

Anatomical and behavioral studies, and in vivo and slice electrophysiology of the hippocampus suggest specific functions of the dentate gyrus (DG) and the CA3 subregions, but the underlying activity dynamics and repeatability of information processing remains poorly understood. To approach this problem, we engineered separate living networks of the DG and CA3 neurons that develop connections through 51 tunnels for axonal communication. Growing these networks on top of an electrode array enabled us to determine whether the subregion dynamics were separable and repeatable. We found spontaneous development of polarized propagation of 80% of the activity in the native direction from DG to CA3 and different spike and burst dynamics for these subregions. Spatial-temporal differences emerged when the relationships of target CA3 activity were categorized with to the number and timing of inputs from the apposing network. Compared to times of CA3 activity when there was no recorded tunnel input, DG input led to CA3 activity bursts that were 7× more frequent, increased in amplitude and extended in temporal envelope. Logistic regression indicated that a high number of tunnel inputs predict CA3 activity with 90% sensitivity and 70% specificity. Compared to no tunnel input, patterns of >80% tunnel inputs from DG specified different patterns of first-to-fire neurons in the CA3 target well. Clustering dendrograms revealed repeating motifs of three or more patterns at up to 17 sites in CA3 that were importantly associated with specific spatial-temporal patterns of tunnel activity. The number of these motifs recorded in 3 min was significantly higher than shuffled spike activity and not seen above chance in control networks in which CA3 was apposed to CA3 or DG to DG. Together, these results demonstrate spontaneous input-dependent repeatable coding of distributed activity in CA3 networks driven by engineered inputs from DG networks. These functional configurations at measured times

Failed fuel diagnosis during WWER reactor operation using the RTOP-CA code

International Nuclear Information System (INIS)

Likhanskii, V.; Afanasieva, E.; Sorokin, A.; Evdokimov, I.; Kanukova, V.; Khromov, A.

2006-01-01

The mechanistic code RTOP-CA is developed for objectives of failed fuel diagnosis during WWER reactor operation. The RTOP-CA code enables to solve a direct problem: modelling the failed fuel behavior and prediction of primary coolant activity if characteristics of failures in the reactor core are known. Results of verification of the RTOP-CA code are presented. Separate physical models were verified on small-scale in-pile and out-of-pile experiments. Integral verification cases included data obtained at research reactors and at nuclear power plants. The RTOP-CA code is used for development of a neural-network approach to the inverse problem: detection of failure characteristics on the base of data on primary coolant activity during reactor operation. Preliminary results of application of the neural-network approach for evaluation of fuel failure characteristics are presented. (authors)

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

Science.gov (United States)

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

2014-06-01

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

Synthesis, Structural Characterization, and Antitumor Activity of a Ca(II Coordination Polymer Based on 1,6-Naphthalenedisulfonate and 4,4′-Bipyridyl

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Xishi Tai

2013-08-01

Full Text Available A novel Ca(II coordination polymer, [CaL(4,4′-bipyridyl(H2O4]n (L = 1,6-naphthalenedisulfonate, was synthesized by reaction of calcium perchlorate with 1,6-naphthalenedisulfonic acid disodium salt and 4,4′-bipyridyl in CH3CH2OH/H2O. It was characterized by elemental analysis, IR, molar conductivity and thermogravimetric analysis. X-ray crystallography reveals that the Ca(II coordination polymer belongs to the orthorhombic system, with space group P212121. The geometry of the Ca(II ion is a distorted CaNO6 pengonal bipyramid, arising from its coordination by four water molecules, one nitrogen atom of 4,4′-bipyridyl molecule, and two oxygen atoms from two L ligands. The complex molecules form a helical chain by self-assembly. The antitumor activity of 1,6-naphthalenedisulfonic acid disodium salt and the Ca(II coordination polymer against human hepatoma smmc-7721 cell line and human lung adenocarcinoma A549 cell line reveals that the Ca(II coordination polymer inhibits cell growth of human lung adenocarcinoma A549 cell line with IC50 value of 27 μg/mL, and is more resistive to human lung adenocarcinoma A549 cell line as compared to 1,6-naphthalenedisulfonic acid disodium salt.

Electrochemical properties of mixed conducting (La,M)(CoFe) oxide perovskites (M=3DSr, Ca, and Ba)

Energy Technology Data Exchange (ETDEWEB)

Stevenson, J.W.; Armstrong, T.R.; Bates, J.L. [and others

1996-04-01

Electrical properties and oxygen permeation properties of solid mixed-conducting electrolytes (La,M)(CoFe) oxide perovskites (M=3DSr, Ca, and Ba) have been characterized. These materials are potentially useful as passive membranes to separate high purity oxygen from air and as the cathode in a fuel cell. Dilatometric linear expansion measurements were performed as a function of temperature and oxygen partial pressure to evaluate the stability.

Zn2+, not Ca2+, is the most effective cation for activation of dolichol kinase of mammalian brain.

Science.gov (United States)

Sakakihara, Y; Volpe, J J

1985-12-15

The cation specificity of dolichol kinase of mammalian brain and the potential involvement of a Ca2+-calmodulin system in regulation of this enzyme have been studied. Among 10 divalent cations examined, Zn2+ was found to be most effective for the activation of dolichol kinase of rat and calf brain and cultured C-6 glial cells. The activations with Ca2+, Co2+, and Mg2+ were 53%, 32%, and 18% of the full activation with Zn2+, respectively. No combinations of the cations could activate the enzyme as much as Zn2+ alone. A role for a Ca2+-calmodulin system in the regulation of brain dolichol kinase was not supported by our data. First, the concentration of free Ca2+ required for the maximum activation of dolichol kinase was two to three orders of magnitude greater than the concentration required by typical calmodulin-dependent enzymes. Second, neither the depletion of calmodulin from the microsomal fraction nor the addition of exogenous calmodulin caused an alteration in the activation of dolichol kinase by Ca2+ (or Zn2+). Third, antagonists of calmodulin failed to suppress the activation of the enzyme by Ca2+ (or Zn2+). The data raise the possibility that Zn2+ is involved in the regulation of dolichol kinase in brain.

Characterization of Bacillus subtilis YfkE (ChaA): a calcium-specific Ca2+/H+ antiporter of the CaCA family.

Science.gov (United States)

Fujisawa, Makoto; Wada, Yuko; Tsuchiya, Takahiro; Ito, Masahiro

2009-08-01

YfkE, a protein from Bacillus subtilis, exhibits homology to the Ca(2+):Cation Antiporter (CaCA) Family. In a fluorescence-based assay of everted membrane vesicles prepared from Na(+)(Ca(2+))/H(+) antiporter-defective mutant Escherichia coli KNabc, YfkE exhibited robust Ca(2+)/H(+) antiport activity, with a K (m) for Ca(2+) estimated at 12.5 muM at pH 8.5 and 113 muM at pH 7.5. Neither Na(+) nor K(+) served as a substrate. Mg(2+) also did not serve as a substrate, but inhibited the Ca(2+)/H(+) antiporter activity. The Ca(2+) transport capability of YfkE was also observed directly by transport assays in everted membrane vesicles using radiolabeled (45)Ca(2+). Transcriptional analysis from the putative yfkED operon using beta-garactosidase activity as a reporter revealed that both of the yfkE and yfkD genes are regulated by forespore-specific sigma factor, SigG, and the general stress response regulator, SigB. These results suggest that YfkE may be needed for Ca(2+) signaling in the sporulation or germination process in B. subtilis. ChaA is proposed as the designation for YfkE of B. subtilis.

Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

Science.gov (United States)

Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

2015-01-01

Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways. Copyright © 2015 Elsevier Ltd

Hydrothermal synthesis of Ca3Bi8O15 rods and their visible light photocatalytic properties

International Nuclear Information System (INIS)

Li, Wenjuan; Kong, Desheng; Cui, Xiaoli; Du, Dandan; Yan, Tingjiang; You, Jinmao

2014-01-01

Graphical abstract: The novel Ca 3 Bi 8 O 15 rods can utilize the sunlight efficiently with the small band-gap. Using methyl orange (MO) as a model organic pollutant, the photocatalysts exhibited good photocatalytic activity, with the photodegradation conversion ratio of MO being up to 90% after 2 h of visible light (420 nm < λ < 800 nm) irradiation. - Highlights: • Ca 3 Bi 8 O 15 rods were synthesized by a hydrothermal method. • They can utilize the sunlight efficiently with the small band-gap. • They showed good photocatalytic activities in the degradation of MO, RhB and 4-CP. • The conversion ratio of MO was up to 90% after 2 h of visible light irradiation. - Abstract: High efficient visible light Ca 3 Bi 8 O 15 photocatalysts were synthesized by a hydrothermal method. Characterized by X-ray diffractometer, transmission electron microscopy, and the UV–vis diffuse reflectance spectroscopy, the results showed that the novel Ca 3 Bi 8 O 15 rods can utilize the sunlight efficiently with the small band-gap. Using methyl orange (MO) as a model organic pollutant, the photocatalysts exhibited good photocatalytic activity, with the photodegradation conversion ratio of MO being up to 90% after 2 h of visible light (420 nm < λ < 800 nm) irradiation. Furthermore, they also showed good photocatalytic activities in the degradation of rhodamine B and p-chlorophenol. Through the investigation of the degraded mechanism, the main active species played important roles in the degradation process were holes, O 2 · − and ·OH

ß-Adrenergic Stimulation Increases RyR2 Activity via Intracellular Ca2+ and Mg2+ Regulation

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Li, Jiao; Imtiaz, Mohammad S.; Beard, Nicole A.; Dulhunty, Angela F.; Thorne, Rick; vanHelden, Dirk F.; Laver, Derek R.

2013-01-01

Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs) by intracellular Ca2+ and Mg2+ and the role of these changes in SR Ca2+ release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control) and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca2+] adrenergic stimulation increased luminal Ca2+ activation of single RyR channels, decreased luminal Mg2+ inhibition and decreased inhibition of RyRs by mM cytoplasmic Mg2+. At cytoplasmic [Ca2+] >1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg2+ and Ca2+ inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca2+ activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1) increasing the activating potency of Ca2+ binding to the luminal Ca2+ site and decreasing its affinity for luminal Mg2+ and 2) decreasing affinity of the low-affinity Ca2+/Mg2+ cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter. PMID:23533585

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi; Verma, Rajeev K.; Gehring, Christoph A; Yamaguchi, Yube; Zhao, Yichen; Ryan, Clarence A.; Berkowitz, Gerald A.

2010-01-01

receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

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Paolo Cossu-Rocca

Full Text Available Triple Negative Breast Cancer (TNBC accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

Science.gov (United States)

Cossu-Rocca, Paolo; Orrù, Sandra; Muroni, Maria Rosaria; Sanges, Francesca; Sotgiu, Giovanni; Ena, Sara; Pira, Giovanna; Murgia, Luciano; Manca, Alessandra; Uras, Maria Gabriela; Sarobba, Maria Giuseppina; Urru, Silvana; De Miglio, Maria Rosaria

2015-01-01

Triple Negative Breast Cancer (TNBC) accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

The manifestation of spin-phonon coupling in CaMnO{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Goian, V., E-mail: goian@fzu.cz; Kamba, S.; Borodavka, F.; Nuzhnyy, D.; Savinov, M. [Institute of Physics, The Czech Academy of Sciences, Na Slovance 2, 182 21 Prague (Czech Republic); Belik, A. A. [International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)

2015-04-28

Recently predicted presence of spin-phonon coupling in the CaMnO{sub 3} is experimentally confirmed in infrared (IR), Raman and time-domain THz spectra. Most of phonon frequencies seen below 350 cm{sup −1} exhibit significant shifts on cooling below antiferromagnetic phase transition at T{sub N} ≅ 120 K. Moreover, several new modes activate in the IR and Raman spectra on cooling below T{sub N}. Sum of phonon contributions to static permittivity exhibits small but reliable anomaly at T{sub N}. On the other hand, the spin-phonon coupling is not manifested in temperature dependence of radio-frequency permittivity, because intrinsic permittivity is screened by extrinsic contribution from conductivity, which enhances the permittivity to giant values.

Superionic conductors with the fluorite structure: a) Measurement of the ionic conductivity of SrF2 at high temperatures, b) Study of the thermodynamic properties at CaF2 by numerical simulation

International Nuclear Information System (INIS)

Evangelakis, Georges

1989-01-01

In this work we present the results of an experimental study concerning the superionic conductivity of SrF 2 and those obtained by an investigation of the thermodynamical properties of CaF 2 using molecular dynamics simulation in the superionic region. The conductivity measurements in SrF 2 have been performed at high temperatures (700-1350 K) and various frequencies (10 Hz-10 MHz). At each temperature a frequency dependence of the conductivity has been detected. The analysis of the results using complex impedance diagrams revealed that this dependence is not an intrinsic property of the material but is related to electrodes effects. The apparent activation energies associated to the different parts of the intrinsic and extrinsic conductivity regions have been determined. Unfortunately no clear conclusion relative to the conduction mechanism can be made there from. Computer simulations by molecular dynamics have been performed in CaF 2 modeled using a rigid ion potential. The diffusion coefficient, the specific heat, structure factors, mean square displacements of both anions and cations, as well as the temperature dependence of these quantities have been calculated. The good agreement found between calculated quantities and experimental results justified us in using the crude approximation of a rigid on potential. A direct computation of the superionic conductivity has been obtained for the first time using non-equilibrium molecular dynamics in the linear response regime. From the independent calculation of the diffusion coefficient and the conductivity, the Havens ratio has been deduced, Hr 0.34, in the superionic region. Its value suggests that the superionic conductivity of CaF 2 is due to a collective and correlated mechanism, a fact which has been confirmed by the MD trajectory analysis. (author) [fr

Thermal conductivity in Pr{sub 1-x}Ca{sub x}MnO{sub 3} and SrTiO{sub 3} thin film systems

Energy Technology Data Exchange (ETDEWEB)

Wiedigen, Stefanie; Kramer, Thilo; Mangipudi, Kodanda R.; Hoffmann, Joerg; Volkert, Cynthia A.; Jooss, Christian [Institute for Materials Physics, University of Goettingen (Germany); Feuchter, Manuel; Kamlah, Marc [Institute for Applied Materials, Karlsruhe Institute of Technology (Germany)

2012-07-01

Epitaxial multilayers and superlattices are one recent approach for the design of efficient thermoelectrics. To study the effect of phonon blocking and scattering on thermal conductivity of oxide multilayers, a combination of two perovskites with promising thermoelectric properties is selected: the orthorhombic Pr{sub 1-x}Ca{sub x}MnO{sub 3} and the cubic SrTiO{sub 3}. In order to investigate the effect of microstructure, interfaces and acoustic impedance mismatch on thermal conductivity {kappa} high preparation quality is needed. Our thin films were prepared by ion-beam and magnetron sputtering. Structural analysis is done by XRD and TEM and is presented in combination with thermal conductivity measurements using the 3{omega} method. Single layers of Pr{sub 1-x}Ca{sub x}MnO{sub 3} show low {kappa} values and no significant increase of thermal conductivity with increasing doping. In homoepitaxial single layers of SrTiO{sub 3} preparation conditions have a high impact on {kappa}, most probably due to different concentrations of point defects. Pr{sub 1-x}Ca{sub x}MnO{sub 3}/SrTiO{sub 3} multilayers show a {kappa} decreases systematically with increasing number of double layers. The results are discussed in the light of the theoretically calculated phonon dispersion and the experimentally observed microstructure.

Acetylcholine release and inhibitory interneuron activity in hippocampal CA1

Directory of Open Access Journals (Sweden)

A. Rory McQuiston

2014-09-01

Full Text Available Acetylcholine release in the central nervous system (CNS has an important role in attention, recall and memory formation. One region influenced by acetylcholine is the hippocampus, which receives inputs from the medial septum and diagonal band of Broca complex (MS/DBB. Release of acetylcholine from the MS/DBB can directly affect several elements of the hippocampus including glutamatergic and GABAergic neurons, presynaptic terminals, postsynaptic receptors and astrocytes. A significant portion of acetylcholine’s effect likely results from the modulation of GABAergic inhibitory interneurons, which have crucial roles in controlling excitatory inputs, synaptic integration, rhythmic coordination of principal neurons and outputs in the hippocampus. Acetylcholine affects interneuron function in large part by altering their membrane potential via muscarinic and nicotinic receptor activation. This minireview describes recent data from mouse hippocampus that investigated changes in CA1 interneuron membrane potentials following acetylcholine release. The interneuron subtypes affected, the receptor subtypes activated, and the potential outcome on hippocampal CA1 network function is discussed.

Ozone (O{sub 3}) elicits neurotoxicity in spinal cord neurons (SCNs) by inducing ER Ca{sup 2+} release and activating the CaMKII/MAPK signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Li, Yun; Lin, Xiaowen; Zhao, XueJun; Xie, Juntian; JunNan, Wang; Sun, Tao; Fu, Zhijian, E-mail: zhijian_fu@163.com

2014-11-01

Ozone (O{sub 3}) is widely used in the treatment of spinal cord related diseases. Excess or accumulation of this photochemical air can however be neurotoxic. In this study, in vitro cultured Wister rat spinal cord neurons (SCNs) were used to investigate the detrimental effects and underlying mechanisms of O{sub 3}. Ozone in a dose-dependent manner inhibited cell viability at a range of 20 to 500 μg/ml, with the dose at 40 μg/ml resulting in a decrease of cell viability to 75%. The cell death after O{sub 3} exposure was related to endoplasmic reticulum (ER) calcium (Ca{sup 2+}) release. Intracellular Ca{sup 2+} chelator, ER stabilizer (inositol 1,4,5-trisphosphate receptor (IP3R) antagonist and ryanodine receptor (RyR) antagonist) and calcium/calmodulin-dependent protein kinase II (CaMKII) antagonist could effectively block Ca{sup 2+} mobilization and inhibit cell death following 40 μg/ml O{sub 3} exposure. In addition, ER Ca{sup 2+} release due to O{sub 3} exposure enhanced phospho-p38 and phospho-JNK levels and apoptosis of SCNs through activating CaMKII. Based on these results, we confirm that ozone elicits neurotoxicity in SCNs via inducing ER Ca{sup 2+} release and activating CaMKII/MAPK signaling pathway. Therefore, physicians should get attention to the selection of treatment concentrations of oxygen/ozone. And, approaches, such as chelating intracellular Ca{sup 2+} and stabilizing neuronal Ca{sup 2+} homeostasis could effectively ameliorate the neurotoxicity of O{sub 3}. - Highlights: • Exposure to O{sub 3} can reduce the viability of SCNs and cause the cell death. • Exposure to O{sub 3} can trigger RyR and IP3R dependent intracellular Ca{sup 2+} release. • Exposure to O{sub 3} can enhance the phospho-CaMKII, phospho-JNK and phospho-p38 levels.

The hippocampal CA2 ensemble is sensitive to contextual change.

Science.gov (United States)

Wintzer, Marie E; Boehringer, Roman; Polygalov, Denis; McHugh, Thomas J

2014-02-19

Contextual learning involves associating cues with an environment and relating them to past experience. Previous data indicate functional specialization within the hippocampal circuit: the dentate gyrus (DG) is crucial for discriminating similar contexts, whereas CA3 is required for associative encoding and recall. Here, we used Arc/H1a catFISH imaging to address the contribution of the largely overlooked CA2 region to contextual learning by comparing ensemble codes across CA3, CA2, and CA1 in mice exposed to familiar, altered, and novel contexts. Further, to manipulate the quality of information arriving in CA2 we used two hippocampal mutant mouse lines, CA3-NR1 KOs and DG-NR1 KOs, that result in hippocampal CA3 neuronal activity that is uncoupled from the animal's sensory environment. Our data reveal largely coherent responses across the CA axis in control mice in purely novel or familiar contexts; however, in the mutant mice subject to these protocols the CA2 response becomes uncoupled from CA1 and CA3. Moreover, we show in wild-type mice that the CA2 ensemble is more sensitive than CA1 and CA3 to small changes in overall context. Our data suggest that CA2 may be tuned to remap in response to any conflict between stored and current experience.

Defect structure, nonstoichiometry, and phase stability of Ca-doped YCrO3

International Nuclear Information System (INIS)

Carini, G.F. II; Anderson, H.U.; Nasrallah, M.M.; Sparlin, D.M.

1991-01-01

The dependence of the defect structure of Ca-doped YCrO 3 on oxygen activity and temperature was investigated by high temperature thermogravimetric measurements. Defect models developed from electrical conductivity data obtained in a previous study were used to interpret the thermogravimetric data. A correlation was found between the electrical conductivity and the thermogravimetric data which suggested that these data were concomitantly dependent on the acceptor dopant and oxygen vacancy dependence of the thermodynamic parameters. Kroeger-Vink type diagrams showing the regions of stability with respect to oxygen activity and temperature were constructed. The TGA data show that Ca-doped YCrO 3 is even more stable toward reduction than doped LaCrO 3

CC genotype of anti-apoptotic gene BCL-2 (-938 C/A) is an independent prognostic marker of unfavorable clinical outcome in patients with non-small-cell lung cancer.

Science.gov (United States)

Javid, J; Mir, R; Mirza, M; Imtiyaz, A; Prasant, Y; Mariyam, Z; Julka, P K; Mohan, A; Lone, M; Ray, P C; Saxena, A

2015-04-01

B cell lymphoma 2 (BCL-2) gene is a well-known regulator of apoptosis and a key element in cancer development and progression. A regulatory (-938C>A, rs2279115) single-nucleotide polymorphism in the inhibitory P2 BCL-2 gene promoter generates significantly different BCL-2 promoter activities and has been associated with different clinical outcomes in various malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on the risk and survival of Indian patients suffering from NSCLC. A hospital-based case-control study of 155 age- and sex-matched patients diagnosed with NSCLC and 155 cancer-free controls was conducted and genotyped by performing PIRA-PCR to elucidate the putative association between clinical outcome and genotypes of BCL-2 (-938C>A, rs2279115). The association of the polymorphism with the survival of NSCLC patients was analyzed by Kaplan-Meier curves. In Indian NSCLC, patients increased risk of developing NSCLC was found to be associated with BCL-2 (-938) CC genotype, [OR 3.68 (1.92-6.79), RR 1.87 (1.35-2.57) and RD 31.03 (16.79-45.27) p 0.00006 for CC and OR 2.08 (1.18-3.66), RR 1.36 (1.08-1.71) and RD 17.74 (4.68-30.81) p 0.01 for AC genotype]. Patients homozygous for C allele exhibited a significant poor overall survival compared with patients displaying AC + CC or AC or AA genotype [median survival (months) 8 vs. 11 vs. 14 vs. 35.5 (p A) polymorphism. Genetic polymorphism in the inhibitory P2 promoter region of anti-apoptotic BCL-2 genes contributes to the risk of developing non-small-cell lung cancer in Indian population. BCL-2 (-938CC) genotype was an independent adverse prognostic factor for patients with NSCLC.

Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

Science.gov (United States)

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal Soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

2014-09-01

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Llorens, Franc; Thüne, Katrin; Sikorska, Beata; Schmitz, Matthias; Tahir, Waqas; Fernández-Borges, Natalia; Cramm, Maria; Gotzmann, Nadine; Carmona, Margarita; Streichenberger, Nathalie; Michel, Uwe; Zafar, Saima; Schuetz, Anna-Lena; Rajput, Ashish; Andréoletti, Olivier; Bonn, Stefan; Fischer, Andre; Liberski, Pawel P; Torres, Juan Maria; Ferrer, Isidre; Zerr, Inga

2017-04-27

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP Sc ). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca 2+ ) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca 2+ responsive genes in sCJD brain tissue, accompanied by two Ca 2+ -dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrP Sc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca 2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention.

Method and Apparatus for Measuring Thermal Conductivity of Small, Highly Insulating Specimens

Science.gov (United States)

Miller, Robert A (Inventor); Kuczmarski, Maria A (Inventor)

2013-01-01

A method and apparatus for the measurement of thermal conductivity combines the following capabilities: 1) measurements of very small specimens; 2) measurements of specimens with thermal conductivity on the same order of that as air; and, 3) the ability to use air as a reference material. Care is taken to ensure that the heat flow through the test specimen is essentially one-dimensional. No attempt is made to use heated guards to minimize the flow of heat from the hot plate to the surroundings. Results indicate that since large correction factors must be applied to account for guard imperfections when specimen dimensions are small, simply measuring and correcting for heat from the heater disc that does not flow into the specimen is preferable.

Hose instability at arbitrary conductivity

International Nuclear Information System (INIS)

Lee, E.P.

1975-01-01

A model is developed for studying the dynamics of a low-current, highly relativistic beam propagating in a conducting medium. Here the conductivity (sigma) is of arbitrary magnitude, the usual assumption being that the scale beam radius (a) is small compared with the magnetic skin length (4 π sigma a 2 /c). A dispersion formula for the hose instability is derived for the case of uniform sigma and Bennett current profile J/sub b/(r) varies as (a 2 + r 2 ) -2 . The peak growth rate at fixed laboratory position, maximized with respect to sigma as well as driver frequency, is approximately 0.465 c/a. This growth rate is realized when 4 π sigma a/c = √12/5. (U.S.)

Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin

Directory of Open Access Journals (Sweden)

Alice Sheehan

2018-03-01

filaments. Many of these compounds were either pure re-couplers or pure desensitizers, indicating these properties are independent; moreover, re-coupling ability could be lost with small changes of compound structure, indicating the possibility of specificity. Small molecules that can re-couple may have therapeutic potential.HIGHLIGHTS- Inherited cardiomyopathies are common diseases that are currently untreatable at a fundamental level and therefore finding a small molecule treatment is highly desirable.- We have identified a molecular level dysfunction common to nearly all mutations: uncoupling of the relationship between troponin I phosphorylation and modulation of myofilament Ca2+-sensitivity, essential for normal responses to adrenaline.- We have identified a new class of drugs that are capable of both reducing Ca2+-sensitivity and/or recouping the relationship between troponin I phosphorylation and Ca2+-sensitivity.- The re-coupling phenomenon can be explained on the basis of a single mechanism that is testable.- Measurements with a wide range of small molecules of varying structures can indicate the critical molecular features required for recoupling and allows the prediction of other potential re-couplers.

Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin.

Science.gov (United States)

Sheehan, Alice; Messer, Andrew E; Papadaki, Maria; Choudhry, Afnan; Kren, Vladimír; Biedermann, David; Blagg, Brian; Khandelwal, Anuj; Marston, Steven B

2018-01-01

. Many of these compounds were either pure re-couplers or pure desensitizers, indicating these properties are independent; moreover, re-coupling ability could be lost with small changes of compound structure, indicating the possibility of specificity. Small molecules that can re-couple may have therapeutic potential. HIGHLIGHTS - Inherited cardiomyopathies are common diseases that are currently untreatable at a fundamental level and therefore finding a small molecule treatment is highly desirable.- We have identified a molecular level dysfunction common to nearly all mutations: uncoupling of the relationship between troponin I phosphorylation and modulation of myofilament Ca 2+ -sensitivity, essential for normal responses to adrenaline.- We have identified a new class of drugs that are capable of both reducing Ca 2+ -sensitivity and/or recouping the relationship between troponin I phosphorylation and Ca 2+ -sensitivity.- The re-coupling phenomenon can be explained on the basis of a single mechanism that is testable.- Measurements with a wide range of small molecules of varying structures can indicate the critical molecular features required for recoupling and allows the prediction of other potential re-couplers.

The optimal period of Ca-EDTA treatment for parthenogenetic activation of porcine oocytes during maturation culture

OpenAIRE

MORITA, Yasuhiro; TANIGUCHI, Masayasu; TANIHARA, Fuminori; ITO, Aya; NAMULA, Zhao; DO, Lanh Thi Kim; TAKAGI, Mitsuhiro; TAKEMOTO, Tatsuya; OTOI, Takeshige

2016-01-01

The changes triggered by sperm-induced activation of oocytes, which are required for normal oocyte development, can be mediated by other agents, thereby inducing the parthenogenesis. In this study, we exposed porcine oocytes to 1 mM Ca-EDTA, a metal-ion chelator, at various intervals during 48 hr of in vitro maturation to determine the optimum period of Ca-EDTA treatment for parthenogenetic activation. When the oocytes were cultured with or without Ca-EDTA from 36 hr (post-12), 24 hr (post-24...

Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

Science.gov (United States)

Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

2014-01-01

Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is

Sr/Ca mass ratio determination in bones using fast neutron activation analysis

International Nuclear Information System (INIS)

Hult, Mikael; Fessler, Andreas

1998-01-01

The Sr/Ca mass ratio in human bones reveals information regarding the diet which is of interest in archaeology. By using fast neutron activation analysis this ratio can be measured in a non-destructive manner, which is important when bones are considered too precious to allow for destructive analysis. Simulations and measurements showed that the nuclear reactions 88 Sr(n, 2n) 87m Sr and 44 Ca(n, p) 44 K are highly useful for the purpose

Conducting everyday life

DEFF Research Database (Denmark)

Juhl, Pernille

, they are involved in preventive interventions. I conducted participatory observations with the children in their everyday life. Overall, the study stresses that even small children must be perceived as active participants who act upon and struggle with different conditions and meaning making processes across......In the paper I discuss how small children (0-4 year) develop through ‘conducting everyday life’ across contexts (Holzkamp 2013). I discuss how this process of conducting everyday life is essential when discussing the ‘good life for children’ from a child perspective. These issues are addressed...... contexts (home, day care, part-time foster family) and in relation to other co-participants....

Meiosis, egg activation, and nuclear envelope breakdown are differentially reliant on Ca2+, whereas germinal vesicle breakdown is Ca2+ independent in the mouse oocyte

Science.gov (United States)

Tombes, R. M.; Simerly, C.; Borisy, G. G.; Schatten, G.

1992-01-01

During early development, intracellular Ca2+ mobilization is not only essential for fertilization, but has also been implicated during other meiotic and mitotic events, such as germinal vesicle breakdown (GVBD) and nuclear envelope breakdown (NEBD). In this study, the roles of intracellular and extracellular Ca2+ were examined during meiotic maturation and reinitiation at parthenogenetic activation and during first mitosis in a single species using the same methodologies. Cumulus-free metaphase II mouse oocytes immediately resumed anaphase upon the induction of a large, transient Ca2+ elevation. This resumption of meiosis and associated events, such as cortical granule discharge, were not sensitive to extracellular Ca2+ removal, but were blocked by intracellular Ca2+ chelators. In contrast, meiosis I was dependent on external Ca2+; in its absence, the formation and function of the first meiotic spindle was delayed, the first polar body did not form and an interphase-like state was induced. GVBD was not dependent on external Ca2+ and showed no associated Ca2+ changes. NEBD at first mitosis in fertilized eggs, on the other hand, was frequently, but not always associated with a brief Ca2+ transient and was dependent on Ca2+ mobilization. We conclude that GVBD is Ca2+ independent, but that the dependence of NEBD on Ca2+ suggests regulation by more than one pathway. As cells develop from Ca(2+)-independent germinal vesicle oocytes to internal Ca(2+)-dependent pronuclear eggs, internal Ca2+ pools increase by approximately fourfold.

Small polaron conduction in lead modified lanthanum ferrite ceramics

Energy Technology Data Exchange (ETDEWEB)

Bhargav, K.K.; Ram, S.; Majumder, S.B., E-mail: subhasish@matsc.iitkgp.ernet.in

2015-07-25

Highlights: • La{sub 0.8}Pb{sub 0.2}FeO{sub 3} (ε{sub r} ∼ 30,000) shows higher dielectric constant than LaFeO{sub 3} (∼14,000). • Lower A-site dopant content, the dielectric maxima shift to higher temperature. • The frequency dependence of ε{sub r} and tan δ vs. temperature exhibit CDC like behavior. • R{sub g} and R{sub gb} of Pb modified LaFeO{sub 3} follow small polaron hopping conduction model. - Abstract: In the present work we have illustrated the physics of the electrical characteristics of nanocrystalline La{sub 1−x}Pb{sub x}FeO{sub 3,} (0 ⩽ x ⩽ 0.2) powder prepared using auto-combustion synthesis. The effect of lead doping on the dielectric, impedance and ac conductivity characteristics of lanthanum ferrite has systematically been investigated. The synthesized powders were phase pure and crystallized into centro-symmetric Pnma space group. As compared to pure LaFeO{sub 3} ceramics (dielectric constant ∼ 14,000), the dielectric constant is grossly increased (∼30,000) in Pb doped LaFeO{sub 3}. The temperature dependence of dielectric constant of 10.0 at.% Pb doped LaFeO{sub 3} exhibits dielectric maxima similar to that observed in ferroelectric ceramics with non-centrosymmetric point group. For La{sub 0.8}Pb{sub 0.2}FeO{sub 3} ceramics, the frequency dependence of the dielectric constant and loss tangent at various temperatures (300–450 K) exhibit typical colossal dielectric constant (CDC) like behavior. From the impedance spectroscopy we have estimated the grain and grain boundary resistance and capacitance of Pb doped LaFeO{sub 3} that follow a small polaron hopping conduction model. Long range movement of the charge carriers govern the CDC behavior.

Influence of nickel doping on oxygen-ionic conductivity of the n = 1 Ruddlesden-Popper Phases La{sub 1.85}Ca{sub 0.15}(Cu{sub 1−x}Ni{sub x})O{sub 4−δ} (δ = 0.0905)

Energy Technology Data Exchange (ETDEWEB)

Midouni, Adnene [Useful Materials Valorization Laboratory, National Centre of Research in Materials Science, Technologic Park of Borj Cedria, B.P. 73, 8027 Soliman (Tunisia); Université de Tunis El Manar, Campus Universitaire Farhat Hached, B.P. No 94- Rommana, 1068 Tunis (Tunisia); Houchati, Mohamed Ikbal, E-mail: ikb_med@yahoo.fr [Useful Materials Valorization Laboratory, National Centre of Research in Materials Science, Technologic Park of Borj Cedria, B.P. 73, 8027 Soliman (Tunisia); Unité de Recherche Catalyse et Matériaux pour l’Environnement et les Procédés URCMEP (UR11ES85), Faculté des Sciences de Gabès/Université de Gabès, Campus Universitaire Cité Erriadh, Gabès 6072 (Tunisia); Othman, Walid Belhaj [Laboratoire de Physico-Chimie des Matériaux Minéraux et leurs Applications, CNRSM, Technopole de Borj Cedria, B.P. 95, Hammam-Lif 2050 (Tunisia); Chniba-Boudjada, Nassira [Laboratoire de Cristallographie, CNRS, 25 Avenue des Martyrs, BP 166, 3804 Grenoble Cedex 9 (France); Ceretti, Monica; Paulus, Werner [Institut de Chimie Moléculaire et des Matériaux – UMR 5253 – ICG C2M: Chimie et Cristallochimie des Matériaux, Université de Montpellier 2, Case courrier 01504 Place Eugène Bataillon, Bat 15, F-34095 Montpellier cedex 5 (France); and others

2016-08-15

The results of the synthesis and characterization of the optimally doped La{sub 1.85}Ca{sub 0.15}(Cu{sub 1−x}Ni{sub x})O{sub 4-δ} solid solution with x = 0, 0.1, 0.2 and 0.3 are reported. The versatility of these La{sub 1.85}Ca{sub 0.15}(Cu{sub 1−x}Ni{sub x})O{sub 4−δ} materials is explained on the basis of structural features and the ability to accommodate oxygen nonstoichiometry. According to powder X-ray and neutron diffraction data, La{sub 1.85}Ca{sub 0.15}(Cu{sub 1−x}Ni{sub x})O{sub 4−δ} adopts the tetragonal structure with oxygen vacancies occurring preferentially at the O{sub ap} sites within the {(La/Ca)O} layers of the perovskite blocks and the oxygen deviation from stoichiometry δ was found to be δ=0.0905(6). The bulk conductivity indicated an Arrhenius-type thermally activated process and oxygen vacancies are the possible ionic charge carriers at T=270 °C. An increase of the conductivity was detected when Ni was introduced. With nickel ratio variation, a strong correlation was observed between the Cu(Ni)-O{sub ap} apical bond length variation and the conductivity variation through controlling the O{sup 2−} ion migration. - Highlights: • We report the synthesis and structure of the La{sub 1.85}Ca{sub 0.15}(Cu{sub 1−x}Ni{sub x})O{sub 4−δ} (0≤x≤0.3; δ=0.0905) compounds. • La{sub 1.85}Ca{sub 0.15}(Cu{sub 1−x}Ni{sub x})O{sub 4−δ} (x=0.0, 0.2, 0.3) doped with Ni{sup 2+} have a higher conductivity than undoped La{sub 1.85}Ca{sub 0.15}CuO{sub 4−δ}. • At T=270 °C, sample x=0.3 has the highest conductivity (0.2915 sm{sup −1}).

Radioimmunoassay studies of intestinal calcium-binding protein in the pig. 2. The distribution of intestinal CaBP in pig tissues

International Nuclear Information System (INIS)

Arnold, B.M.; Kuttner, M.; Willis, D.M.; Hitchman, A.J.W.; Harrison, J.E.; Murray, T.M.

1975-01-01

Using a specific radioimmunoassay for porcine intestinal calcium-binding protein (CaBP), we have measured the concentration of CaBP in the various tissues and organs of normal pigs. Intestinal CaBP was present in highest concentration in the upper small intestine, with lower concentrations in the distal small intestine. Intestinal CaBP was also found, in lower concentrations, in kidney, liver, thyroid, pancreas, and blood. In all other tissues, including parathyroid, bone, skeletal muscle, and brain, CaBP immunoreactivity was undetectable or less than in blood. The elution profile of calcium-binding activity and immunoreactivity from gel filtration analysis of kidney and parathyroid extracts suggest that the calcium-binding protein in the parathyroid gland, and the major calcium-binding protein(s) in the kidney, are chemically and immunochemically different from intestinal CaBP. (author)

Radioimmunoassay studies of intestinal calcium-binding protein in the pig. II. The distribution of intestinal CaBP in pig tissues

Energy Technology Data Exchange (ETDEWEB)

Arnold, B M; Kuttner, M; Willis, D M; Hitchman, A J.W.; Harrison, J E; Murray, T M [Toronto Univ., Ontario (Canada). Dept. of Medicine

1975-12-01

Using a specific radioimmunoassay for porcine intestinal calcium-binding protein (CaBP), we have measured the concentration of CaBP in the various tissues and organs of normal pigs. Intestinal CaBP was present in highest concentration in the upper small intestine, with lower concentrations in the distal small intestine. Intestinal CaBP was also found, in lower concentrations, in kidney, liver, thyroid, pancreas, and blood. In all other tissues, including parathyroid, bone, skeletal muscle, and brain, CaBP immunoreactivity was undetectable or less than in blood. The elution profile of calcium-binding activity and immunoreactivity from gel filtration analysis of kidney and parathyroid extracts suggest that the calcium-binding protein in the parathyroid gland, and the major calcium-binding protein(s) in the kidney, are chemically and immunochemically different from intestinal CaBP.

Evidence for a modulation of neutral trehalase activity by Ca2+ and cAMP signaling pathways in Saccharomyces cerevisiae

Directory of Open Access Journals (Sweden)

Souza A.C.

2002-01-01

Full Text Available Saccharomyces cerevisiae neutral trehalase (encoded by NTH1 is regulated by cAMP-dependent protein kinase (PKA and by an endogenous modulator protein. A yeast strain with knockouts of CMK1 and CMK2 genes (cmk1cmk2 and its isogenic control (CMK1CMK2 were used to investigate the role of CaM kinase II in the in vitro activation of neutral trehalase during growth on glucose. In the exponential growth phase, cmk1cmk2 cells exhibited basal trehalase activity and an activation ratio by PKA very similar to that found in CMK1CMK2 cells. At diauxie, even though both cells presented comparable basal trehalase activities, cmk1cmk2 cells showed reduced activation by PKA and lower total trehalase activity when compared to CMK1CMK2 cells. To determine if CaM kinase II regulates NTH1 expression or is involved in post-translational modulation of neutral trehalase activity, NTH1 promoter activity was evaluated using an NTH1-lacZ reporter gene. Similar ß-galactosidase activities were found for CMK1CMK2 and cmk1cmk2 cells, ruling out the role of CaM kinase II in NTH1 expression. Thus, CaM kinase II should act in concert with PKA on the activation of the cryptic form of neutral trehalase. A model for trehalase regulation by CaM kinase II is proposed whereby the target protein for Ca2+/CaM-dependent kinase II phosphorylation is not the neutral trehalase itself. The possible identity of this target protein with the recently identified trehalase-associated protein YLR270Wp is discussed.

Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

International Nuclear Information System (INIS)

Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

1982-01-01

The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings.

Science.gov (United States)

Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Faber, Cornelius; Stroh, Albrecht

2016-11-01

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca 2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca 2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca 2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca 2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. © The Author(s) 2015.

Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings

Science.gov (United States)

Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Stroh, Albrecht

2015-01-01

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. PMID:26661247

AM fungal exudates activate MAP kinases in plant cells in dependence from cytosolic Ca(2+) increase.

Science.gov (United States)

Francia, Doriana; Chiltz, Annick; Lo Schiavo, Fiorella; Pugin, Alain; Bonfante, Paola; Cardinale, Francesca

2011-09-01

The molecular dialogue occurring prior to direct contact between the fungal and plant partners of arbuscular-mycorrhizal (AM) symbioses begins with the release of fungal elicitors, so far only partially identified chemically, which can activate specific signaling pathways in the host plant. We show here that the activation of MAPK is also induced by exudates of germinating spores of Gigaspora margarita in cultured cells of the non-leguminous species tobacco (Nicotiana tabacum), as well as in those of the model legume Lotus japonicus. MAPK activity peaked about 15 min after the exposure of the host cells to the fungal exudates (FE). FE were also responsible for a rapid and transient increase in free cytosolic Ca(2+) in Nicotiana plumbaginifolia and tobacco cells, and pre-treatment with a Ca(2+)-channel blocker (La(3+)) showed that in these cells, MAPK activation was dependent on the cytosolic Ca(2+) increase. A partial dependence of MAPK activity on the common Sym pathway could be demonstrated for a cell line of L. japonicus defective for LjSym4 and hence unable to establish an AM symbiosis. Our results show that MAPK activation is triggered by an FE-induced cytosolic Ca(2+) transient, and that a Sym genetic determinant acts to modulate the intensity and duration of this activity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Preparation, characterization and activity evaluation of CaZrTi2O7 photocatalyst

International Nuclear Information System (INIS)

Chen Shifu; Ji Mingsong; Yuang Yunguang; Liu Wei

2012-01-01

CaZrTi 2 O 7 photocatalyst sample was prepared by a polymerizable complex method. The photocatalyst was characterized by X-ray powder diffraction, scanning electron microscopy, UV–Vis diffuse reflectance spectroscopy, photoluminescence emission spectroscopy, Brunauer–Emmett–Teller analysis, N 2 adsorption measurements, and terephthalic acid probed fluorescence technique. The photocatalytic activity of the sample was evaluated by photocatalytic oxidation of methyl orange and photocatalytic reduction of Cr 2 O 7 2− and nitrobenzene. The results showed that when the reaction solution was illuminated by UV light for 50 min, the photooxidation efficiency of methyl orange and the photoreduction efficiency of Cr 2 O 7 2− were 83.1% and 87.9%, respectively. When methanol was used as the holes scavengers and the illumination time was 10 h in the photocatalytic reduction experiment of nitrobenzene, the production efficiency of aniline was 70.3%. The effect of the heat treatment conditions on the photocatalytic activity was also investigated. The optimum preparation condition for CaZrTi 2 O 7 sample is 800 °C for 12 h. The mechanisms of influence on the photocatalytic activity of the sample were also discussed with the valance band theory. - Highlights: ► CaZrTi 2 O 7 photocatalyst was prepared by a polymerizable complex method. ► The heat treatment has a significant influence on the photocatalytic activity. ► The optimal heat treatment condition is approximately 800 °C for 12 h. ► The CaZrTi 2 O 7 has the band bap of about 2.89 eV with particle size of about 80 nm.

Thermal conductivity of electron-doped CaMnO3 perovskites: Local lattice distortions and optical phonon thermal excitation

International Nuclear Information System (INIS)

Wang Yang; Sui Yu; Wang Xianjie; Su Wenhui; Liu Xiaoyang; Fan, Hong Jin

2010-01-01

The thermal transport properties of a series of electron-doped CaMnO 3 perovskites have been investigated. Throughout the temperature range 5-300 K, phonon thermal conductivity is dominant, and both electron and spin wave contributions are negligible. The short phonon mean free paths in this system result in the relatively low thermal conductivities. The strong phonon scatterings stem from the A-site mismatch and bond-length fluctuations induced by local distortions of MnO 6 octahedra. The thermal conductivity in the magnetically ordered state is enhanced as a result of the decrease in spin-phonon scattering. The results also indicate that above the magnetic ordering temperature, observable thermal excitation of optical phonons occurs. The contribution of optical phonons to thermal conductivity becomes non-negligible and is proposed to play an important role in the glass-like thermal transport behavior (i.e. positive temperature dependence of the thermal conductivity) in the paramagnetic state. These features can be understood in terms of an expression of thermal conductivity that includes both acoustic and optical phonon terms.

CaMKII Regulates Synaptic NMDA Receptor Activity of Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension.

Science.gov (United States)

Li, De-Pei; Zhou, Jing-Jing; Zhang, Jixiang; Pan, Hui-Lin

2017-11-01

NMDAR activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Calcium/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated EPSCs and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats. The basal amplitude of evoked NMDAR-EPSCs and puff NMDA currents in retrogradely labeled PVN neurons were significantly higher in SHRs than in WKY rats. The CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP) normalized the increased amplitude of NMDAR-EPSCs and puff NMDA currents in labeled PVN neurons in SHRs but had no effect in WKY rats. Treatment with AIP also normalized the higher frequency of NMDAR-mediated miniature EPSCs of PVN neurons in SHRs. CaMKII-mediated phosphorylation level of GluN2B serine 1303 (S1303) in the PVN, but not in the hippocampus and frontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased level of phosphorylated GluN2B S1303 in the PVN. In addition, microinjection of AIP into the PVN significantly reduced arterial blood pressure and lumbar sympathetic nerve discharges in SHRs. Our findings suggest that CaMKII activity is increased in the PVN and contributes to potentiated presynaptic and postsynaptic NMDAR activity to elevate sympathetic vasomotor tone in hypertension. SIGNIFICANCE STATEMENT Heightened sympathetic vasomotor tone is a major contributor to the development of hypertension. Although glutamate NMDA receptor (NMDAR)-mediated excitatory drive in the hypothalamus plays a critical role in increased sympathetic output in hypertension, the molecular mechanism involved in

Effects of Al2O3 and/or CaO on properties of yttria stabilized zirconia electrolyte doped with multi-elements

International Nuclear Information System (INIS)

Lv Zhengang; Guo Ruisong; Yao Pei; Dai Fengying

2007-01-01

Yttria stabilized zirconia (YSZ) has a high oxide ion conductivity at high temperatures. Some rare earth elements (e.g., Yb, Sc, Dy) with similar cation radii to Zr 4+ can dissolve into ZrO 2 , increasing its vacancy concentration and crystal lattice distortion, and therefore enhancing its conductivity and lowering the activation energy. It is expected this material could be used as intermediate temperature electrolyte. In the present work, YSZ electrolyte materials doped by multi-elements (Sc 2 O 3 or Dy 2 O 3 and Yb 2 O 3 ) were prepared by high temperature solid-state method. The high temperature conductivity was improved obviously, reaching 0.18 S/cm at 1000 deg. C, but the density and mechanical properties of sintered materials were not sufficiently high. It is found that sinterability and mechanical properties could be improved by inclusion of a small amount of Al 2 O 3 and/or CaO into the multi-elements doped YSZ materials and our results proved it. The results showed density and bending strength of sintered bodies were enhanced by Al 2 O 3 addition by 4.6% and 30%, respectively, while the conductivity did not degrade remarkably. But the degradation in bending strength and conductivity resulting from the CaO addition happened due to the second phase formed at the grain boundary. XRD patterns showed that all samples had cubic fluorite structure and crystalline lattice parameter was increased. SEM photographs obviously revealed the grain growth for the samples with CaO inclusion

Gliadin peptides induce tissue transglutaminase activation and ER-stress through Ca2+ mobilization in Caco-2 cells.

Directory of Open Access Journals (Sweden)

Ivana Caputo

Full Text Available BACKGROUND: Celiac disease (CD is an intestinal inflammatory condition that develops in genetically susceptible individuals after exposure to dietary wheat gliadin. The role of post-translational modifications of gliadin catalyzed by tissue transglutaminase (tTG seems to play a crucial role in CD. However, it remains to be established how and where tTG is activated in vivo. We have investigated whether gliadin peptides modulate intracellular Ca(2+ homeostasis and tTG activity. METHODS/PRINCIPAL FINDINGS: We studied Ca(2+ homeostasis in Caco-2 cells by single cell microfluorimetry. Under our conditions, A-gliadin peptides 31-43 and 57-68 rapidly mobilized Ca(2+ from intracellular stores. Specifically, peptide 31-43 mobilized Ca(2+ from the endoplasmic reticulum (ER and mitochondria, whereas peptide 57-68 mobilized Ca(2+ only from mitochondria. We also found that gliadin peptide-induced Ca(2+ mobilization activates the enzymatic function of intracellular tTG as revealed by in situ tTG activity using the tTG substrate pentylamine-biotin. Moreover, we demonstrate that peptide 31-43, but not peptide 57-68, induces an increase of tTG expression. Finally, we monitored the expression of glucose-regulated protein-78 and of CCAAT/enhancer binding protein-homologous protein, which are two biochemical markers of ER-stress, by real-time RT-PCR and western blot. We found that chronic administration of peptide 31-43, but not of peptide 57-68, induces the expression of both genes. CONCLUSIONS: By inducing Ca(2+ mobilization from the ER, peptide 31-43 could promote an ER-stress pathway that may be relevant in CD pathogenesis. Furthermore, peptides 31-43 and 57-68, by activating intracellular tTG, could alter inflammatory key regulators, and induce deamidation of immunogenic peptides and gliadin-tTG crosslinking in enterocytes and specialized antigen-presenting cells.

CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells

Directory of Open Access Journals (Sweden)

M.A. Mudado

2004-06-01

Full Text Available T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 ± 1.87 ms (N = 16. The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 ± 2.4 and 6.7 ± 0.3 mV (pre-pulse of -120 mV, N = 15, and -27.0 ± 0.97 and 7.5 ± 0.7 mV (pre-pulse of -40 mV, N = 9. The 8-mV shift in the activation mid-point was statistically significant (P < 0.05. The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of a1G (CaV3.1 and a1I (CaV3.3 T-type Ca2+ channel mRNA transcripts.

ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.

Directory of Open Access Journals (Sweden)

Jiao Li

Full Text Available Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs by intracellular Ca(2+ and Mg(2+ and the role of these changes in SR Ca(2+ release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca(2+] 1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg(2+ and Ca(2+ inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca(2+ activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1 increasing the activating potency of Ca(2+ binding to the luminal Ca(2+ site and decreasing its affinity for luminal Mg(2+ and 2 decreasing affinity of the low-affinity Ca(2+/Mg(2+ cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter.

Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

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H. M. N. Iqbal

2015-09-01

Full Text Available We have developed novel composites by grafting caffeic acid (CA onto the P(3HB-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB-EC i.e., P(3HB-EC (control, 5CA-g-P(3HB-EC, 10CA-g-P(3HB-EC, 15CA-g-P(3HB-EC and 20CA-g-P(3HB-EC. FT-IR (Fourier-transform infrared spectroscopy was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics.

Trace Elements in the Conductive Tissue of Beef Heart Determined by Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Wester, P O

1965-08-15

By means of neutron activation analysis, samples of four beef hearts taken from the bundle of His and adjacent ventricular muscle, the AV node and adjacent atrial muscle are investigated with respect to the concentration of 23 trace elements. The bulk elements K, Na and P are also determined. A recently developed ion-exchange technique, combined with subsequent {gamma}-spectrometry, is used. The following trace elements are determined: Ag, As, Au, Ba, Br, .Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Rb, Sb, Sc, Se, Sm, W and Zn. In the conductive tissue compared to adjacent muscle tissue, calculations on a wet weight basis show a lower concentration of Cs, Cu, Fe, K, P, Rb and Zn in the former, and a higher concentration of Ag, Au, Br, Ca and Na. The mean differences ({mu}g/g wet tissue), as well as their degree of significance, between the bundle of His and adjacent tissue from the ventricular septum, between the AV node and adjacent atrial muscle, between the ventricular septum and the right atrium, and between the bundle of His and the AV node are given for the elements Cu, Fe, K, Na, P and Zn.

Trace Elements in the Conductive Tissue of Beef Heart Determined by Neutron Activation Analysis

International Nuclear Information System (INIS)

Wester, P.O.

1965-08-01

By means of neutron activation analysis, samples of four beef hearts taken from the bundle of His and adjacent ventricular muscle, the AV node and adjacent atrial muscle are investigated with respect to the concentration of 23 trace elements. The bulk elements K, Na and P are also determined. A recently developed ion-exchange technique, combined with subsequent γ-spectrometry, is used. The following trace elements are determined: Ag, As, Au, Ba, Br, .Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Rb, Sb, Sc, Se, Sm, W and Zn. In the conductive tissue compared to adjacent muscle tissue, calculations on a wet weight basis show a lower concentration of Cs, Cu, Fe, K, P, Rb and Zn in the former, and a higher concentration of Ag, Au, Br, Ca and Na. The mean differences (μg/g wet tissue), as well as their degree of significance, between the bundle of His and adjacent tissue from the ventricular septum, between the AV node and adjacent atrial muscle, between the ventricular septum and the right atrium, and between the bundle of His and the AV node are given for the elements Cu, Fe, K, Na, P and Zn

Activity of RE/sub 2/O/sub 3/ in liquid La/sub 2/O/sub 3/-Al/sub 2/O/sub 3/-CaF/sub 2/ and Ce/sub 2/O/sub 3/-CaO-CaF/sub 2/ slags

International Nuclear Information System (INIS)

Changzhen, W.; Shuqing, Y.; Qieng, D.

1985-01-01

In the course of electro-slag refining, if the slag contains rare earth oxides, the amount of rare earth introduced to the steel depends on the composition of the slag and other conditions. The main aim of this investigation is to study the activity of RE/sub 2/O/sub 3/ in the electro-slags of various compositions. One is the La/sub 2/O/sub 3/-CaO-CaF/sub 2/ ternary slag system and the other is the Ce/sub 2/O/sub 3/-CaO-CaF/sub 2/ slag system. The iso-activity diagram for RE/sub 2/O/sub 3/ and the liquid boundary for slags system were estimated

Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

Science.gov (United States)

Namer, Barbara; Ørstavik, Kirstin; Schmidt, Roland; Mair, Norbert; Kleggetveit, Inge Petter; Zeidler, Maximillian; Martha, Theresa; Jorum, Ellen; Schmelz, Martin; Kalpachidou, Theodora; Kress, Michaela; Langeslag, Michiel

2017-01-01

The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. PMID:28769867

Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

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Barbara Namer

2017-07-01

Full Text Available The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0. The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.

Direct detection of SERCA calcium transport and small-molecule inhibition in giant unilamellar vesicles

International Nuclear Information System (INIS)

Bian, Tengfei; Autry, Joseph M.; Casemore, Denise; Li, Ji; Thomas, David D.; He, Gaohong; Xing, Chengguo

2016-01-01

We have developed a charge-mediated fusion method to reconstitute the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA) in giant unilamellar vesicles (GUV). Intracellular Ca 2+ transport by SERCA controls key processes in human cells such as proliferation, signaling, and contraction. Small-molecule effectors of SERCA are urgently needed as therapeutics for Ca 2+ dysregulation in human diseases including cancer, diabetes, and heart failure. Here we report the development of a method for efficiently reconstituting SERCA in GUV, and we describe a streamlined protocol based on optimized parameters (e.g., lipid components, SERCA preparation, and activity assay requirements). ATP-dependent Ca 2+ transport by SERCA in single GUV was detected directly using confocal fluorescence microscopy with the Ca 2+ indicator Fluo-5F. The GUV reconstitution system was validated for functional screening of Ca 2+ transport using thapsigargin (TG), a small-molecule inhibitor of SERCA currently in clinical trials as a prostate cancer prodrug. The GUV system overcomes the problem of inhibitory Ca 2+ accumulation for SERCA in native and reconstituted small unilamellar vesicles (SUV). We propose that charge-mediated fusion provides a widely-applicable method for GUV reconstitution of clinically-important membrane transport proteins. We conclude that GUV reconstitution is a technological advancement for evaluating small-molecule effectors of SERCA.

High conductive and long-term phase stable anode materials for SOFCs: A2FeMoO6 (A = Ca, Sr, Ba)

Science.gov (United States)

Huan, Yu; Li, Yining; Yin, Baoyi; Ding, Dong; Wei, Tao

2017-08-01

In this work, the mixed oxide-ion/electron conductor (MIEC) double-perovskite compounds A2FeMoO6 (AFMO, A = Ca, Sr, Ba) are investigated as anode materials for O2--ion conducting solid-oxide fuel cells (SOFCs). Several advantages are outlined here; 1) under H2 atmosphere, the conductivities of Ba2FeMoO6 (BFMO), Sr2FeMoO6 (SFMO) and Ca2FeMoO6 (CFMO) reach as high as 243, 302 and 561 S cm-1, respectively, which can be comparable with the commercial NiO-electrolyte anode; 2) excellent structure and phase stability at high temperature and in H2 atmosphere; 3) matched thermodynamic compatibility (such as TECs) with electrolyte materials; 4) fast oxidization for fuel with O2- ions accepted by oxygen vacancies from the electrolyte. Moreover, with H2 as fuel gas, the cell power output, cell's long-term stabilities and the structural parameter are also been examined to evaluate the AFMO anode.

Electric conductivity of solid solutions the Cs3-2xMxPO4 (M=Ba, Sr, Ca, Mg) systems

International Nuclear Information System (INIS)

Burmakin, E.I.; Stroev, S.S.; Shekhtman, G.Sh.; Antonov, B.D.

2003-01-01

The solid solutions in the Cs 3-2x M x PO 4 (M=Ba, Sr, Ca, Mg) system are synthesized and their thermal behavior and electric conductivity are studied. The introduction of the alkaline earth metal cations into cesium orthophosphates is accompanied by the shift of the phase transition occurring in the pure Cs 3 PO 4 at 450-620 Deg C into the low-temperature area as well as by increase in the cesium-cation conductivity at low temperatures. The electric conductivity in the area of existence of the Cs 3 PO 4 high-temperature modification slightly depends on the availability and concentration of the modifying additions, which make it possible to suppose the calcium sublattice structural disordering [ru

The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries.

Science.gov (United States)

Kloza, Monika; Baranowska-Kuczko, Marta; Malinowska, Barbara; Karpińska, Olga; Harasim-Symbor, Ewa; Kasacka, Irena; Kozłowska, Hanna

2017-12-01

The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (K Ca 2.3/K Ca 3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type response was investigated, in endothelium-intact sMAs using a wire myograph, by examining acetylcholine-evoked vasorelaxation in the presence of N ω -nitro-L-arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and cyclooxygenase, respectively). In normo- and hypertension the efficacy of EDH-type relaxation was similar and inhibition of K Ca 2.3 and K Ca 3.1 by UCL1684 and TRAM-34, respectively, given alone or in combination, attenuated EDH-mediated vasorelaxation. K Ca 3.1 expression and NS309 (K Ca 2.3/K Ca 3.1 activator)-induced relaxation was reduced in sMAs of DOCA-salt rats. Endothelium denudation and incubation with UCL1684 and TRAM-34 attenuated the maximal NS309-evoked vasorelaxation in both groups. URB597 had no effect in functional studies, but increased the expression of K Ca 3.1 in the sMAs. K Ca 2.3/K Ca 3.1-EDH-mediated relaxation was maintained in the sMAs of DOCA-salt rats despite endothelial dysfunction and down-regulation of K Ca 3.1. Furthermore, K Ca 3.1 played a key role in the EDH-type dilator response of sMAs in normo- and hypertension. The hypotensive effect of URB597 is independent of K Ca 2.3/K Ca 3.1-EDH-type relaxation. Copyright © 2017 Elsevier Inc. All rights reserved.

Luminescence Properties of CaF2 Nanostructure Activated by Different Elements

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Numan Salah

2015-01-01

Full Text Available Nanostructures of calcium fluoride (CaF2 doped with Eu, Tb, Dy, Cu, and Ag were synthesized by the coprecipitation method and studied for their thermoluminescence (TL and photoluminescence (PL properties. The PL emission spectrum of pure CaF2 nanostructure has a broad band in the 370–550 nm range. Similar spectra were observed in case of doped samples, beside extra bands related to these impurities. The maximum PL intensity was observed in Eu doped sample. The TL results of Eu, Cu, Ag, and Tb doped samples show weak glow peaks below 125°C, whereas Dy doped one is found to be highly sensitive with a prominent peak at 165°C. This sample was further exposed to a wide range of gamma rays exposures from 137Cs source. The response curve is linear in the 100 Gy-10 kGy range. It is also observed that the particle size of CaF2 nanostructure was significantly reduced by increasing Dy concentration. These results showed that Dy is a proper activator in the host of CaF2 nanostructure, providing a highly sensitive dosimeter in a wide range of exposures and also plays a role as a controlling agent for particle size growth.

Nucleoporin 62 and Ca(2+)/calmodulin dependent kinase kinase 2 regulate androgen receptor activity in castrate resistant prostate cancer cells.

Science.gov (United States)

Karacosta, Loukia G; Kuroski, Laura A; Hofmann, Wilma A; Azabdaftari, Gissou; Mastri, Michalis; Gocher, Angela M; Dai, Shuhang; Hoste, Allen J; Edelman, Arthur M

2016-02-15

Re-activation of the transcriptional activity of the androgen receptor (AR) is an important factor mediating progression from androgen-responsive to castrate-resistant prostate cancer (CRPC). However, the mechanisms regulating AR activity in CRPC remain incompletely understood. Ca(2+) /calmodulin-dependent kinase kinase (CaMKK) 2 was previously shown to regulate AR activity in androgen-responsive prostate cancer cells. Our objective was to further explore the basis of this regulation in CRPC cells. The abundance of CaMKK2 in nuclear fractions of androgen-responsive prostate cancer and CRPC, cells were determined by subcellular fractionation and Western blotting. CaMKK2 association with nuclear pore complexes (NPCs) and nucleoporins (Nups) including Nup62, were imaged by structured illumination and super-resolution fluorescence microscopy and co-immunoprecipitation, respectively. The abundance and subcellular localization of CaMKK2 and Nup62 in human clinical specimens of prostate cancer was visualized by immunohistochemistry. The role of Nups in the growth and viability of CRPC cells was assessed by RNA interference and cell counting. The involvement of CaMKK2 and Nup62 in regulating AR transcriptional activity was addressed by RNA interference, chromatin immunoprecipitation, androgen response element reporter assay, and Western blotting. CaMKK2 was expressed at higher levels in the nuclear fraction of CPRC C4-2 cells, than in that of androgen-responsive LNCaP cells. In C4-2 cells, CaMKK2 associated with NPCs of the nuclear envelope and physically interacted with Nup62. CaMKK2 and Nup62 demonstrated pronounced, and similar increases in both expression and perinuclear/nuclear localization in human clinical specimens of advanced prostate cancer relative to normal prostate. Knockdown of Nup62, but not of Nups, 98 or 88, reduced growth and viability of C4-2 cells. Knockdown of Nup62 produced a greater reduction of the growth and viability of C4-2 cells than of non

Fabrication of CaFe2O4 nanofibers via electrospinning method with enhanced visible light photocatalytic activity

Science.gov (United States)

Wang, Jianmin; Wang, Yunan; Liu, Yinglei; Li, Song; Cao, Feng; Qin, Gaowu

CaFe2O4 nanofibers with diameters of about 130nm have been fabricated via a facile electrospinning method. The structures, morphologies and optical properties of the obtained CaF2O4 nanofibers have been investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Visible UV-Vis diffuse reflectance spectrum. The photocatalytic activities of the CaFe2O4 nanofibers are evaluated by the photo-degradation of Methyl orange (MO). The results show that the CaFe2O4 nanofibers (72%) exhibit much higher photocatalytic performance than the CaFe2O4 powders (27%) prepared by conventional method under visible light irradiation. The enhanced photocatalytic performance of CaFe2O4 nanofibers could be attributed to the large surface area, high photogenerated charge carriers density and low charge transfer resistance, as revealed by photoelectrochemical measurement. And fundamentally, it could be attributed to the decreased particle size and the fibrous nanostructure. This work not only provides an efficient way to improve the photocatalytic activity of CaFe2O4, but also provides a new method for preparing materials with nanofibrous structure.

Electrical conduction in (Na0⋅ 125Bi0⋅ 125 Ba0⋅ 65Ca0⋅)(Nd0 ...

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science; Volume 29; Issue 1. Electrical conduction in (Na0.125Bi0.125Ba0.65Ca0.1)(Nd0.065Ti0.87Nb0.065)O3 ceramic. Syed Mahboob G Prasad G S Kumar. Ceramics and Glasses Volume 29 Issue 1 February 2006 pp 35-41 ...

Hydrolysis of molten CaCl2-CaF2 with additions of CaO

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Espen Olsen

2017-10-01

Full Text Available Calcium halide based molten salts have recently attracted interest for a number of applications such as direct reduction of oxides for metal production and as liquefying agent in cyclic sorption processes for CO2 by CaO from dilute flue gases (Ca-looping. A fundamental aspect of these melts is the possible hydrolysis reaction upon exposure to gaseous H2O forming corrosive and poisonous hydrogen halides. In this work experiments have been performed investigating the formation of HCl and HF from a molten salt consisting of a 13.8 wt% CaF2 in CaCl2 eutectic exposed to a flowing gas consisting of 10 vol% H2O in N2. Hydrolysis has been investigated as function of content of CaO and temperature. HCl and HF are shown to be formed at elevated temperatures; HCl forms to a substantially larger extent than HF. Addition of CaO has a marked, limiting effect on the hydrolysis. Thermodynamic modeling of the reaction indicates activity coefficients for CaO above unity in the system. For cyclic CO2-capture based on thermal swing, it is advisable to keep the temperature in the carbonation (absorption reactor well below 850 ℃ while maintaining a high CaO content if molten CaCl2 is employed. Similar conclusions can be drawn with regards to CaF2.

Ca isotopes in refractory inclusions

International Nuclear Information System (INIS)

Niederer, F.R.; Papanastassiou, D.A.

1984-01-01

We report measurements of the absolute isotope abundance of Ca in Ca-Al-rich inclusions from the Allende and Leoville meteorites. Improved high precision measurements are reported also for 46 Ca. We find that nonlinear isotope effects in Ca are extremely rare in these inclusions. The absence of nonlinear effects in Ca, except for the effects in FUN inclusions, is in sharp contrast to the endemic effects in Ti. One fine-grained inclusion shows an excess of 46 Ca of (7 +- 1) per mille, which is consistent with addition of only 46 Ca or of an exotic (*) component with 46 Ca* approx. 48 Ca*. FUN inclusion EK-1-4-1 shows a small 46 Ca excess of (3.3 +- 1.0) per mille; this confirms that the exotic Ca components in EK-1-4-1 were even more deficient in 46 Ca relative to 48 Ca than is the case for normal Ca. The Ca in the Ca-Al-rich inclusions shows mass dependent isotope fractionation effects which have a range from -3.8 to +6.7 per mille per mass unit difference. This range is a factor of 20 wider than the range previously established for bulk meteorites and for terrestrial and lunar samples. Ca and Mg isotope fractionation effects in the Ca-Al-rich inclusions are common and attributed to kinetic isotope effects. (author)

Arabidopsis calmodulin-like protein CML36 is a calcium (Ca2+) sensor that interacts with the plasma membrane Ca2+-ATPase isoform ACA8 and stimulates its activity.

Science.gov (United States)

Astegno, Alessandra; Bonza, Maria Cristina; Vallone, Rosario; La Verde, Valentina; D'Onofrio, Mariapina; Luoni, Laura; Molesini, Barbara; Dominici, Paola

2017-09-08

Calmodulin-like (CML) proteins are major EF-hand-containing, calcium (Ca 2+ )-binding proteins with crucial roles in plant development and in coordinating plant stress tolerance. Given their abundance in plants, the properties of Ca 2+ sensors and identification of novel target proteins of CMLs deserve special attention. To this end, we recombinantly produced and biochemically characterized CML36 from Arabidopsis thaliana We analyzed Ca 2+ and Mg 2+ binding to the individual EF-hands, observed metal-induced conformational changes, and identified a physiologically relevant target. CML36 possesses two high-affinity Ca 2+ /Mg 2+ mixed binding sites and two low-affinity Ca 2+ -specific sites. Binding of Ca 2+ induced an increase in the α-helical content and a conformational change that lead to the exposure of hydrophobic regions responsible for target protein recognition. Cation binding, either Ca 2+ or Mg 2+ , stabilized the secondary and tertiary structures of CML36, guiding a large structural transition from a molten globule apo-state to a compact holoconformation. Importantly, through in vitro binding and activity assays, we showed that CML36 interacts directly with the regulative N terminus of the Arabidopsis plasma membrane Ca 2+ -ATPase isoform 8 (ACA8) and that this interaction stimulates ACA8 activity. Gene expression analysis revealed that CML36 and ACA8 are co-expressed mainly in inflorescences. Collectively, our results support a role for CML36 as a Ca 2+ sensor that binds to and modulates ACA8, uncovering a possible involvement of the CML protein family in the modulation of plant-autoinhibited Ca 2+ pumps. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Environmental Education and Small Business Environmental Activity

Science.gov (United States)

Redmond, Janice; Walker, Beth

2011-01-01

Environmental education is seen as a key driver of small business environmental management, yet little is known about the activities small business owner-managers are undertaking to reduce their environmental impact or in what areas they may need education. Therefore, research that can identify environmental management activities being undertaken…

A New Negative Allosteric Modulator AP14145 for the Study of Small Conductance Calcium-Activated Potassium Channels

DEFF Research Database (Denmark)

Simo Vicens, Rafel; Kirchhoff, Jeppe Egedal; Dolce, Bernardo

2017-01-01

) prolongation in anaesthetised rats and a beam walk test was performed in mice to determine acute CNS related effects of the drug. Key results: AP14145 was found to be an equipotent negative allosteric modulator of KCa2.2 and KCa2.3 channels (IC50 = 1.1 ± 0.3 μM L-1). The presence of AP14145 (10 μM L-1......) increased the EC50 of Ca2+ on KCa2.3 from 0.36 ± 0.02 μM L-1 to 1.2 ± 0.1 μM L-1. The inhibitory effect strongly depended on two amino acids, S508 and A533. AP14145 concentration-dependently prolonged AERP in rats. Moreover, AP14145 (10 mg kg-1) did not trigger any apparent CNS effects in mice. Conclusion...... and implications: AP14145 is a negative allosteric modulator of KCa2.2 and KCa2.3 that shifts the calcium dependence of channel activation, an effect strongly dependent on two identified amino acids. AP14145 prolongs AERP in rats and does not trigger any acute CNS effects in mice. The understanding of how KCa2...

The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Nardi, Antonio; Calloe, Kirstine

2007-01-01

, a mitochondrial K(+) channel with KCa1.1-resembling properties has been found in the heart, where it may be involved in regulation of energy consumption. In the present study, the effect of a novel NeuroSearch compound, 1-(3,5-bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea (NS11021...

Fishing activity in Northern Rio de Janeiro State (Brazil and its relation with small cetaceans

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Ana Paula Madeira Di Beneditto

1998-01-01

Full Text Available Research on fishing activity at Atafona village, in Northern Rio de Janeiro, Brazil (21°35'S, was carried out between 1987-96 for the purpose of relating it to the accidental capture of small cetaceans and of estimating the relationship between fishing activity and the diet of small cetaceans. Data on fishing operations were obtained at the cold storage plants management, from interviews with fishermen and personal observations. The most representative fishing resources were Xyphopenaeus kroyeri, Micropogonias furnieri, Carcharhinus plumbeus, C. acronotus,and Rhizoprionodon porosus. Gillnets are responsible for the accidental capture of small cetaceans in the region, mainly Pontoporia blainvillei and Sotalia fluviatilis (marine form. Four types of gillnets that are used on the region ("minjuada", "sarda", "caçoá" and "pescadinha" were dangerous to these species because they are placed in their preferred habitat. There is no competition between fishermen and small cetaceans due to the selection in the capture of commercialized fishesInvestigação sobre a atividade pesqueira na localidade de Atafona, Norte do Rio de Janeiro, Brasil (21º25`S, foi conduzida entre 1987-96 com o objetivo de relacioná-la com a captura acidental e a dieta dos pequenos cetáceos. Dados sobre as operações pesqueiras foram obtidos na administração dos entrepostos de pesca, através de entrevistas com pescadores e observações pessoais. Os recursos pesqueiros mais representativos foram Xyphopenaeus kroyeri, Micropogonias furnieri, Carcharhinus plumbeus, C. acronotus, and Rhizoprionodon porosus. As redes de espera são responsáveis pela captura acidental de pequenos cetáceos na região, principalmente de Pontoporia blainvillei e Sotalia fluviatilis (forma marinha. Quatro tipos de redes de espera que são usadas na região ("minjuada", "sarda", "caçoá" and "pescadinha" foram mais perigosas para essas espécies pois são colocadas no seu hábitat preferencial

Activated carbon supported CaO for conversion of palm oil to ...

African Journals Online (AJOL)

In this study, activated carbon supported CaO catalyst was used for the transesterification reaction of palm oil. The catalyst was prepared according to the conventional incipient witness impregnation method. Kinetic experiment was performed in a batch reactor in the presence of heterogeneous catalyst for a wide range of ...

Use of CaO as an activator for producing a price-competitive non-cement structural binder using ground granulated blast furnace slag

Energy Technology Data Exchange (ETDEWEB)

Kim, Min Sik; Jun, Yubin; Lee, Changha, E-mail: clee@unist.ac.kr; Oh, Jae Eun, E-mail: ohjaeeun@unist.ac.kr

2013-12-15

The use of calcium oxide (CaO) demonstrates a superior potential for the activation of ground granulated blast furnace slag (GGBFS), and it produces a higher mechanical strength than calcium hydroxide [Ca(OH){sub 2}]. The mechanical strength differences between CaO- and Ca(OH){sub 2}-activated GGBFS binders are explored using isothermal calorimetry, powder X-ray diffraction, thermogravimetric and differential thermal analysis (TGA and DTA) as well as compressive strength testing. Calcium silicate hydrate (C–S–H), Ca(OH){sub 2} and a hydrotalcite-like phase are found as reaction products in all samples. The TGA and DTA results indicate that the use of CaO produces more C–S–H, although this is not likely to be the primary cause of higher strength development in the CaO-activated GGBFS. Rather, other factors such as porosity may govern the strength at a higher order of magnitude. Significant reduction of Ca(OH){sub 2} occurs only with the use of Ca(OH){sub 2}, followed by the formation of carbonate (CaCO{sub 3}), indicating carbonation. -- Highlights: •CaO showed a better potential for the activation of GGBFS than Ca(OH){sub 2}. •Strength test, XRD, TGA/DTA and isothermal calorimetry are used. •C-S-H, Ca(OH){sub 2}, and a hydrotalcite-like phase are found in all samples. •The use of Ca(OH){sub 2} causes some degree of carbonation.

The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD.

Science.gov (United States)

Nesci, Salvatore; Trombetti, Fabiana; Ventrella, Vittoria; Pirini, Maurizio; Pagliarani, Alessandra

2018-01-26

The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Moreover, the addition of acetyl-CoA or palmitate, which would favor the enzyme ac(et)ylation, does not affect the F1FO-ATPase activity. Consistently, NAD+ may play a new role, not associated with redox and non-redox enzymatic reactions, in the Ca2+-dependent regulation of the F1FO-ATPase activity.

INTRACELLULAR Ca2+ HOMEOSTASIS

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Shahdevi Nandar Kurniawan

2015-01-01

Full Text Available Ca2+ signaling functions to regulate many cellular processes. Dynamics of Ca2+ signaling or homeostasis is regulated by the interaction between ON and OFF reactions that control Ca2+ flux in both the plasma membrane and internal organelles such as the endoplasmic reticulum (ER and mitochondria. External stimuli activate the ON reactions, which include Ca2+ into the cytoplasm either through channels in the plasma membrane or from internal storage like in ER. Most of the cells utilize both channels/sources, butthere area few cells using an external or internal source to control certain processes. Most of the Ca2+ entering the cytoplasm adsorbed to the buffer, while a smaller part activate effect or to stimulate cellular processes. Reaction OFF is pumping of cytoplasmic Ca2+ using a combination mechanism of mitochondrial and others. Changes in Ca2+ signal has been detected in various tissues isolated from animals induced into diabetes as well as patients with diabetes. Ca2+ signal interference is also found in sensory neurons of experimental animals with diabetes. Ca2+ signaling is one of the main signaling systems in the cell.

Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

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Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

2010-08-01

Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

Intracellular alkalinization induces cytosolic Ca2+ increases by inhibiting sarco/endoplasmic reticulum Ca2+-ATPase (SERCA.

Directory of Open Access Journals (Sweden)

Sen Li

Full Text Available Intracellular pH (pHi and Ca(2+ regulate essentially all aspects of cellular activities. Their inter-relationship has not been mechanistically explored. In this study, we used bases and acetic acid to manipulate the pHi. We found that transient pHi rise induced by both organic and inorganic bases, but not acidification induced by acid, produced elevation of cytosolic Ca(2+. The sources of the Ca(2+ increase are from the endoplasmic reticulum (ER Ca(2+ pools as well as from Ca(2+ influx. The store-mobilization component of the Ca(2+ increase induced by the pHi rise was not sensitive to antagonists for either IP(3-receptors or ryanodine receptors, but was due to inhibition of the sarco/endoplasmic reticulum Ca(2+-ATPase (SERCA, leading to depletion of the ER Ca(2+ store. We further showed that the physiological consequence of depletion of the ER Ca(2+ store by pHi rise is the activation of store-operated channels (SOCs of Orai1 and Stim1, leading to increased Ca(2+ influx. Taken together, our results indicate that intracellular alkalinization inhibits SERCA activity, similar to thapsigargin, thereby resulting in Ca(2+ leak from ER pools followed by Ca(2+ influx via SOCs.

Nanomolar Bifenthrin Alters Synchronous Ca2+ Oscillations and Cortical Neuron Development Independent of Sodium Channel Activity

OpenAIRE

Cao, Zhengyu; Cui, Yanjun; Nguyen, Hai M.; Jenkins, David Paul; Wulff, Heike; Pessah, Isaac N.

2014-01-01

Bifenthrin, a relatively stable type I pyrethroid that causes tremors and impairs motor activity in rodents, is broadly used. We investigated whether nanomolar bifenthrin alters synchronous Ca 2+ oscillations (SCOs) necessary for activity-dependent dendritic development. Primary mouse cortical neurons were cultured 8 or 9 days in vitro (DIV), loaded with the Ca2+ indicator Fluo-4, and imaged using a Fluorescence Imaging Plate Reader Tetra. Acute exposure to bifenthrin rapidly increased the fr...

Interplay of activation kinetics and the derivative conductance determines resonance properties of neurons

Science.gov (United States)

Pena, Rodrigo F. O.; Ceballos, Cesar C.; Lima, Vinicius; Roque, Antonio C.

2018-04-01

In a neuron with hyperpolarization activated current (Ih), the correct input frequency leads to an enhancement of the output response. This behavior is known as resonance and is well described by the neuronal impedance. In a simple neuron model we derive equations for the neuron's resonance and we link its frequency and existence with the biophysical properties of Ih. For a small voltage change, the component of the ratio of current change to voltage change (d I /d V ) due to the voltage-dependent conductance change (d g /d V ) is known as derivative conductance (GhDer). We show that both GhDer and the current activation kinetics (characterized by the activation time constant τh) are mainly responsible for controlling the frequency and existence of resonance. The increment of both factors (GhDer and τh) greatly contributes to the appearance of resonance. We also demonstrate that resonance is voltage dependent due to the voltage dependence of GhDer. Our results have important implications and can be used to predict and explain resonance properties of neurons with the Ih current.

Stochastic simulation of a single inositol 1,4,5-trisphosphate-sensitive Ca2+ channel reveals repetitive openings during 'blip-like' Ca2+ transients.

Science.gov (United States)

Swillens, S; Champeil, P; Combettes, L; Dupont, G

1998-05-01

Confocal microscope studies with fluorescent dyes of inositol 1,4,5-trisphosphate (InsP3)-induced intracellular Ca2+ mobilization recently established the existence of 'elementary' events, dependent on the activity of individual InsP3-sensitive Ca2+ channels. In the present work, we try by theoretical stochastic simulation to explain the smallest signals observed in those studies, which were referred to as Ca2+ 'blips' [Parker I., Yao Y. Ca2+ transients associated with openings of inositol trisphosphate-gated channels in Xenopus oocytes. J Physiol Lond 1996; 491: 663-668]. For this purpose, we assumed a simple molecular model for the InsP3-sensitive Ca2+ channel and defined a set of parameter values accounting for the results obtained in electrophysiological bilayer experiments [Bezprozvanny I., Watras J., Ehrlich B.E. Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature 1991; 351: 751-754; Bezprozvanny I., Ehrlich B.E. Inositol (1,4,5)-trisphosphate (InsP3)-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium. J Gen Physiol 1994; 104: 821-856]. With a stochastic procedure which considered cytosolic Ca2+ diffusion explicitly, we then simulated the behaviour of a single channel, placed in a realistic physiological environment. An attractive result was that the simulated channel exhibited bursts of activity, arising from repetitive channel openings, which were responsible for transient rises in Ca2+ concentration and were reminiscent of the relatively long-duration experimental Ca2+ blips. The influence of the values chosen for the various parameters (affinity and diffusion coefficient of the buffers, luminal Ca2+ concentration) on the kinetic characteristics of these theoretical blips is analyzed.

Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

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Lin, C S; Boltz, R C; Blake, J T; Nguyen, M; Talento, A; Fischer, P A; Springer, M S; Sigal, N H; Slaughter, R S; Garcia, M L

1993-03-01

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by Ca2+ Sensitizers and a Ca2+ Sensitivity Blunting Phosphomimic, cTnT(T204E).

Science.gov (United States)

Schlecht, William; Dong, Wen-Ji

2017-10-18

Several studies have suggested that conformational dynamics are important in the regulation of thin filament activation in cardiac troponin C (cTnC); however, little direct evidence has been offered to support these claims. In this study, a dye homodimerization approach is developed and implemented that allows the determination of the dynamic equilibrium between open and closed conformations in cTnC's hydrophobic cleft. Modulation of this equilibrium by Ca 2+ , cardiac troponin I (cTnI), cardiac troponin T (cTnT), Ca 2+ -sensitizers, and a Ca 2+ -desensitizing phosphomimic of cTnT (cTnT(T204E) is characterized. Isolated cTnC contained a small open conformation population in the absence of Ca 2+ that increased significantly upon the addition of saturating levels of Ca 2+ . This suggests that the Ca 2+ -induced activation of thin filament arises from an increase in the probability of hydrophobic cleft opening. The inclusion of cTnI increased the population of open cTnC, and the inclusion of cTnT had the opposite effect. Samples containing Ca 2+ -desensitizing cTnT(T204E) showed a slight but insignificant decrease in open conformation probability compared to samples with cardiac troponin T, wild type [cTnT(wt)], while Ca 2+ sensitizer treated samples generally increased open conformation probability. These findings show that an equilibrium between the open and closed conformations of cTnC's hydrophobic cleft play a significant role in tuning the Ca 2+ sensitivity of the heart.

How Did Ca. 300 Years of Explosive Activity at Kilauea End?

Science.gov (United States)

Swanson, D. A.

2013-12-01

Kilauea experienced ~300 years of frequent explosive eruptions following caldera collapse in about 1500 CE, producing the Keanakāko';i Tephra. The first 200 years were dominated by juvenile-rich phreatomagmatic eruptions, and the next 100 years by lithic-rich phreatomagmatic and phreatic explosive events. For most of this time, the caldera was deep enough (≥600 m) to allow magma and hot rock to interact with external water at and below the water table. This situation changed after the deadly 1790 eruption. The first eruption was magmatic, involving high fountaining that deposited pumice across >25 km2 south of the caldera. The pumice is hard to find today; it was mostly eroded away soon after deposition and is found only in protected areas along drainages and next to obstacles. The deposit has a consistent internal stratigraphy regardless of its thickness (maximum of 12 cm): lower third mostly achneliths (Pele's hair and tears), upper two- thirds pumice bombs and lapilli. The fountaining, the first purely magmatic event since reticulite erupted in ca. 1500, probably signifies a rising magma column and early filling of the caldera. The next eruption was phreatic, depositing fine lithic ash a few millimeters thick across >45 km2 south of the caldera. It may record withdrawal of the magma column and collapse of part of the caldera floor to or below the water table. The magma column rose soon thereafter, and its free surface was above the water table for some time. This event is recorded by Pele's hair deposited on the lithic ash across >30 km2 south of the caldera. The hair forms a jackstraw mat Pele's hair that blows kilometers downwind, forming a paper-thin deposit that glistens in the sun like golden grain. Phreatic activity followed, depositing small lapilli now embedded in the hair and lithic ash. This was perhaps a vent-opening event for a dominantly phreatomagmatic eruption. The deposit of this eruption, mostly lithic but with scattered fluidal lapilli, is 0

Photoluminescence properties of Eu2+-activated Ca2Y2Si2O9 phosphor

NARCIS (Netherlands)

Zhang, Zhijun; Delsing, A.C.A.; Notten, P.H.L.; Zhao, Jingtai; Hintzen, H.T.J.M.

2012-01-01

Eu2+-activated Ca2Y2Si2O9 phosphors with different Eu2+ concentrations have been prepared by a solid-state reaction method at high temperature and their photoluminescence (PL) properties were investigated. Photoluminescence results show that Eu2+-doped Ca2Y2Si2O9 can be efficiently excited by

Stimulation of Na+-alanine cotransport activates a voltage-dependent conductance in single proximal tubule cells isolated from frog kidney

Science.gov (United States)

Robson, L; Hunter, M

1999-01-01

The swelling induced by Na+-alanine cotransport in proximal tubule cells of the frog kidney is followed by regulatory volume decrease (RVD). This RVD is inhibited by gadolinium (Gd3+), an inhibitor of stretch-activated channels, but is independent of extracellular Ca2+. In this study, the whole cell patch clamp technique was utilized to examine the effect of Na+-alanine cotransport on two previously identified volume- and Gd3+-sensitive conductances. One conductance is voltage dependent and anion selective (GVD) whilst the other is voltage independent and cation selective (GVI). Addition of 5 mM L-alanine to the bathing solution increased the whole cell conductance and gave a positive (depolarizing) shift in the reversal potential (Vrev, equivalent to the membrane potential in current-clamped cells) consistent with activation of Na+-alanine cotransport. Vrev shifted from -36 ± 4·9 to +12·9 ± 4·2 mV (n= 15). In the presence of alanine, the total whole cell conductance had several components including the cotransporter conductance and GVD and GVI. These conductances were separated using Gd3+, which inhibits both GVD and GVI, and the time dependency of GVD. Of these two volume-sensitive conductances, L-alanine elicited a specific increase in GVD, whereas GVI was unaffected. The L-alanine-induced activation of GVD was significantly reduced when cells were incubated in a hypertonic bathing solution. In summary, in single proximal tubule cells isolated from frog kidney, on stimulation of Na+-alanine cotransport GVD is activated, while GVI is unaffected. Taken with other evidence, this suggests that GVD is activated by cell swelling, consequent upon alanine entry, and may play a role as an anion efflux pathway during alanine-induced volume regulation. PMID:10226159

Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

Science.gov (United States)

Brock, Stephanie E; Rendon, Beatriz E; Yaddanapudi, Kavitha; Mitchell, Robert A

2012-11-02

AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.

Combined Evaluation of AFP, CA15-3, CA125, CA19-9, and CEA Tumor Markers in Patients with Hepatitis B and C.

Science.gov (United States)

Assmar, Mehdi; Yeganeh, Sara; Mansourghanaei, Fariborz; Amirmozafari, Nour

2016-12-01

This study aimed to determine the role of tumor markers AFP, CA15-3, CA125, CA19-9 and CEA in patients with hepatitis B and C. This descriptive cross-sectional study was performed from Oct 2012 to Oct 2014. Serum samples of 129 patients with hepatitis B and C referred to Guilan Liver and Digestive Disease Research Center in Rasht, Iran were collected and checked for the existence of the listed tumor markers by ELISA. No increase in serum levels of tumor marker CA19-9, CEA and CA15-3 were seen in patients with hepatitis ( P >0.05). In patients with hepatitis B, increase in CA125 were observed ( P =0.03). In hepatitis C patients, there was an increase in AFP levels ( P =0.03). The levels of AFP and CA125 markers were high in hepatitis C and hepatitis B, respectively. However, the increased levels were not seen is malignancy. Due to the small sample size, further study is necessary to find the reasons of the increase.

Slender Ca ii H Fibrils Mapping Magnetic Fields in the Low Solar Chromosphere

Energy Technology Data Exchange (ETDEWEB)

Jafarzadeh, S.; Rutten, R. J.; Szydlarski, M. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Solanki, S. K.; Wiegelmann, T.; Riethmüller, T. L.; Noort, M. van; Barthol, P.; Gandorfer, A.; Gizon, L.; Hirzberger, J. [Max Planck Institute for Solar System Research, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Rodríguez, J. Blanco [Grupo de Astronomía y Ciencias del Espacio, Universidad de Valencia, E-46980 Paterna, Valencia (Spain); Iniesta, J. C. del Toro; Suárez, D. Orozco [Instituto de Astrofísica de Andalucía (CSIC), Apartado de Correos 3004, E-18080 Granada (Spain); Knölker, M. [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307-3000 (United States); Pillet, V. Martínez [National Solar Observatory, 3665 Discovery Drive, Boulder, CO 80303 (United States); Schmidt, W., E-mail: shahin.jafarzadeh@astro.uio.no [Kiepenheuer-Institut für Sonnenphysik, Schöneckstr. 6, D-79104 Freiburg (Germany)

2017-04-01

A dense forest of slender bright fibrils near a small solar active region is seen in high-quality narrowband Ca ii H images from the SuFI instrument onboard the Sunrise balloon-borne solar observatory. The orientation of these slender Ca ii H fibrils (SCF) overlaps with the magnetic field configuration in the low solar chromosphere derived by magnetostatic extrapolation of the photospheric field observed with Sunrise/IMaX and SDO/HMI. In addition, many observed SCFs are qualitatively aligned with small-scale loops computed from a novel inversion approach based on best-fit numerical MHD simulation. Such loops are organized in canopy-like arches over quiet areas that differ in height depending on the field strength near their roots.

A novel core–shell nanocomposite Ni–Ca@mSiO_2 for benzophenone selective hydrogenation

International Nuclear Information System (INIS)

Han, Xue; Feng, Wenhui; Chu, Xiaoning; Chu, Hailong; Niu, Libo; Bai, Guoyi

2017-01-01

A novel core–shell nanocomposite Ni–Ca@mSiO_2 was first prepared by a modified Stöber method in this paper. It has a core–shell structure with Ni (about 8 nm in diameter) and Ca as the cores and mesoporous silica as the outer shell, as proven by the transmission electron microscopy. This nanocomposite exhibited good catalytic performance in the selective hydrogenation of benzophenone, with 96.1% conversion and 94.9% selectivity for benzhydrol under relatively mild reaction conditions. It was demonstrated that addition of small amounts of alkaline Ca can not only markedly improve the dispersion of the active species but also tune the acid–base property of this nanocomposite, resulting in the efficient suppression of benzhydrol dehydration to achieve a high selectivity. Furthermore, the core–shell nanocomposite Ni–Ca@mSiO_2 can be recycled four runs without appreciable loss of its initial activity, more stable than the traditional supported nanocatalyst Ni–Ca/mSiO_2. It was suggested that the outer mesoporous silica shell of Ni–Ca@mSiO_2 can prevent both the aggregation and the leaching of the active Ni species, accounting for its relatively good stability.

Glu¹⁰⁶ in the Orai1 pore contributes to fast Ca²⁺-dependent inactivation and pH dependence of Ca²⁺ release-activated Ca²⁺ (CRAC) current.

Science.gov (United States)

Scrimgeour, Nathan R; Wilson, David P; Rychkov, Grigori Y

2012-01-15

FCDI (fast Ca²⁺-dependent inactivation) is a mechanism that limits Ca²⁺ entry through Ca²⁺ channels, including CRAC (Ca²⁺ release-activated Ca²⁺) channels. This phenomenon occurs when the Ca²⁺ concentration rises beyond a certain level in the vicinity of the intracellular mouth of the channel pore. In CRAC channels, several regions of the pore-forming protein Orai1, and STIM1 (stromal interaction molecule 1), the sarcoplasmic/endoplasmic reticulum Ca²⁺ sensor that communicates the Ca²⁺ load of the intracellular stores to Orai1, have been shown to regulate fast Ca²⁺-dependent inactivation. Although significant advances in unravelling the mechanisms of CRAC channel gating have occurred, the mechanisms regulating fast Ca²⁺-dependent inactivation in this channel are not well understood. We have identified that a pore mutation, E106D Orai1, changes the kinetics and voltage dependence of the ICRAC (CRAC current), and the selectivity of the Ca²⁺-binding site that regulates fast Ca²⁺-dependent inactivation, whereas the V102I and E190Q mutants when expressed at appropriate ratios with STIM1 have fast Ca²⁺-dependent inactivation similar to that of WT (wild-type) Orai1. Unexpectedly, the E106D mutation also changes the pH dependence of ICRAC. Unlike WT ICRAC, E106D-mediated current is not inhibited at low pH, but instead the block of Na⁺ permeation through the E106D Orai1 pore by Ca²⁺ is diminished. These results suggest that Glu¹⁰⁶ inside the CRAC channel pore is involved in co-ordinating the Ca²⁺-binding site that mediates fast Ca²⁺-dependent inactivation.

Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

Science.gov (United States)

Kay, A R; Wong, R K

1987-11-01

1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

Anoxia increases potassium conductance in hippocampal nerve cells.

Science.gov (United States)

Hansen, A J; Hounsgaard, J; Jahnsen, H

1982-07-01

The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

Nanomolar bifenthrin alters synchronous Ca2+ oscillations and cortical neuron development independent of sodium channel activity.

Science.gov (United States)

Cao, Zhengyu; Cui, Yanjun; Nguyen, Hai M; Jenkins, David Paul; Wulff, Heike; Pessah, Isaac N

2014-04-01

Bifenthrin, a relatively stable type I pyrethroid that causes tremors and impairs motor activity in rodents, is broadly used. We investigated whether nanomolar bifenthrin alters synchronous Ca(2+) oscillations (SCOs) necessary for activity-dependent dendritic development. Primary mouse cortical neurons were cultured 8 or 9 days in vitro (DIV), loaded with the Ca(2+) indicator Fluo-4, and imaged using a Fluorescence Imaging Plate Reader Tetra. Acute exposure to bifenthrin rapidly increased the frequency of SCOs by 2.7-fold (EC50 = 58 nM) and decreased SCO amplitude by 36%. Changes in SCO properties were independent of modifications in voltage-gated sodium channels since 100 nM bifenthrin had no effect on the whole-cell Na(+) current, nor did it influence neuronal resting membrane potential. The L-type Ca(2+) channel blocker nifedipine failed to ameliorate bifenthrin-triggered SCO activity. By contrast, the metabotropic glutamate receptor (mGluR)5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine] normalized bifenthrin-triggered increase in SCO frequency without altering baseline SCO activity, indicating that bifenthrin amplifies mGluR5 signaling independent of Na(+) channel modification. Competitive [AP-5; (-)-2-amino-5-phosphonopentanoic acid] and noncompetitive (dizocilpine, or MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate]) N-methyl-d-aspartate antagonists partially decreased both basal and bifenthrin-triggered SCO frequency increase. Bifenthrin-modified SCO rapidly enhanced the phosphorylation of cAMP response element-binding protein (CREB). Subacute (48 hours) exposure to bifenthrin commencing 2 DIV-enhanced neurite outgrowth and persistently increased SCO frequency and reduced SCO amplitude. Bifenthrin-stimulated neurite outgrowth and CREB phosphorylation were dependent on mGluR5 activity since MPEP normalized both responses. Collectively these data identify a new mechanism by which bifenthrin potently alters Ca(2

Enhanced Expression of WD Repeat-Containing Protein 35 via CaMKK/AMPK Activation in Bupivacaine-Treated Neuro2a Cells

Science.gov (United States)

Huang, Lei; Kondo, Fumio; Gosho, Masahiko; Feng, Guo-Gang; Harato, Misako; Xia, Zhong-yuan; Ishikawa, Naohisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

We previously reported that bupivacaine induces reactive oxygen species (ROS) generation, p38 mitogen-activated protein kinase (MAPK) activation and nuclear factor-kappa B activation, resulting in an increase in expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. However, the identity of signaling upstream of p38 MAPK pathways to WDR35 expression remains unclear. It has been shown that AMP-activated protein kinase (AMPK) can activate p38 MAPK through diverse mechanisms. In addition, several kinases acting upstream of AMPK have been identified including Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Recent studies reported that AMPK may be involved in bupivacaine-induced cytotoxicity in Schwann cells and in human neuroblastoma SH-SY5Y cells. The present study was undertaken to test whether CaMKK and AMPK are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Our results showed that bupivacaine induced activation of AMPK and p38 MAPK in Neuro2a cells. The AMPK inhibitors, compound C and iodotubercidin, attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. Treatment with the CaMKK inhibitor STO-609 also attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. These results suggest that bupivacaine activates AMPK and p38 MAPK via CaMKK in Neuro2a cells, and that the CaMKK/AMPK/p38 MAPK pathway is involved in regulating WDR35 expression. PMID:24859235

Coded Aperture Nuclear Scintigraphy: A Novel Small Animal Imaging Technique

Directory of Open Access Journals (Sweden)

Dawid Schellingerhout

2002-10-01

Full Text Available We introduce and demonstrate the utility of coded aperture (CA nuclear scintigraphy for imaging small animals. CA imaging uses multiple pinholes in a carefully designed mask pattern, mounted on a conventional gamma camera. System performance was assessed using point sources and phantoms, while several animal experiments were performed to test the usefulness of the imaging system in vivo, with commonly used radiopharmaceuticals. The sensitivity of the CA system for 99mTc was 4.2 × 103 cps/Bq (9400 cpm/μCi, compared to 4.4 × 104 cps/Bq (990 cpm/μCi for a conventional collimator system. The system resolution was 1.7 mm, as compared to 4–6 mm for the conventional imaging system (using a high-sensitivity low-energy collimator. Animal imaging demonstrated artifact-free imaging with superior resolution and image quality compared to conventional collimator images in several mouse and rat models. We conclude that: (a CA imaging is a useful nuclear imaging technique for small animal imaging. The advantage in signal-to-noise can be traded to achieve higher resolution, decreased dose or reduced imaging time. (b CA imaging works best for images where activity is concentrated in small volumes; a low count outline may be better demonstrated using conventional collimator imaging. Thus, CA imaging should be viewed as a technique to complement rather than replace traditional nuclear imaging methods. (c CA hardware and software can be readily adapted to existing gamma cameras, making their implementation a relatively inexpensive retrofit to most systems.

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

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...

Electrical Properties of Ba3Ca1.18Nb1.82O9-  Proton-Conducting Electrolyte Prepared by a Combustion Method

KAUST Repository

Bi, Lei

2013-10-07

Ba3Ca1.18Nb1.82O9-δ (BCN18), regarded as a promising proton-conducting electrolyte material for solid oxide fuel cells, is usually synthesized by a solid-state reaction because of the limited choice of Nb precursors. This study presents a wet chemical route for preparing BCN18 powders that were then sintered into pellets. Electrochemical impedance spectroscopy studies indicated that BCN18 pellets show proton conductivity, since their total conductivity in wet air was significantly larger than that in dry air. However, a detailed analysis showed that only the BCN18 bulk behaves as a proton conductor, while its grain boundary conductivity did not increase in wet air.

Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

Directory of Open Access Journals (Sweden)

Bopanna I Kalappa

2010-11-01

Full Text Available The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596.An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the entire pyramidal neuron and occasionally

Studies on the Protective Effects of Scutellarein against Neuronal Injury by Ischemia through the Analysis of Endogenous Amino Acids and Ca2+ Concentration Together with Ca2+-ATPase Activity

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Hao Tang

2015-01-01

Full Text Available Scutellarin, which is extracted from the dried plant of Erigeron breviscapus, has been reported to protect the neural injury against excitotoxicity induced by ischemia. However, there are a few studies on the protective effects of scutellarein, which is the main metabolite of scutellarin in vivo. Thus, this study investigated the neuroprotective effects of scutellarein on cerebral ischemia/reperfusion in rats by bilateral common carotid artery occlusion (BCCAO model, through the analysis of endogenous amino acids using HILIC-MS/MS, and evaluation of Ca2+ concentration together with Ca2+-ATPase activity. The results showed that scutellarein having good protective effects on cerebral ischemia/reperfusion might by decreasing the excitatory amino acids, increasing the inhibitory amino acids, lowing intracellular Ca2+ level, and improving Ca2+-ATPase activity, which suggested that scutellarein might be a promising potent agent for the therapy of ischemic cerebrovascular disease.

L-Type Voltage-Gated Ca2+ Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites

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Brian G. Hiester

2017-11-01

Full Text Available The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface. Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely, potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered surface expression of key synaptic proteins by gating the mode of RE fusion.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

Science.gov (United States)

Cannady, Reginald; Fisher, Kristen R; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W

2017-05-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use

A quantitative description of tubular system Ca2+ handling in fast‐ and slow‐twitch muscle fibres

Science.gov (United States)

Cully, Tanya R.; Edwards, Joshua N.; Murphy, Robyn M.

2016-01-01

Key points Current methods do not allow a quantitative description of Ca2+ movements across the tubular (t‐) system membrane without isolating the membranes from their native skeletal muscle fibre.Here we present a fluorescence‐based method that allows determination of the t‐system [Ca2+] transients and derivation of t‐system Ca2+ fluxes in mechanically skinned skeletal muscle fibres. Differences in t‐system Ca2+‐handling properties between fast‐ and slow‐twitch fibres from rat muscle are resolved for the first time using this new technique.The method can be used to study Ca2+ handling of the t‐system and allows direct comparisons of t‐system Ca2+ transients and Ca2+ fluxes between groups of fibres and fibres from different strains of animals. Abstract The tubular (t‐) system of skeletal muscle is an internalization of the plasma membrane that maintains a large Ca2+ gradient and exchanges Ca2+ between the extracellular and intracellular environments. Little is known of the Ca2+‐handling properties of the t‐system as the small Ca2+ fluxes conducted are difficult to resolve with conventional methods. To advance knowledge in this area we calibrated t‐system‐trapped rhod‐5N inside skinned fibres from rat and [Ca2+]t‐sys, allowing confocal measurements of Ca2+‐dependent changes in rhod‐5N fluorescence during rapid changes in the intracellular ionic environment to be converted to [Ca2+] transients in the t‐system ([Ca2+]t‐sys (t)). Furthermore, t‐system Ca2+‐buffering power was determined so that t‐system Ca2+ fluxes could be derived from [Ca2+]t‐sys (t). With this new approach, we show that rapid depletion of sarcoplasmic reticulum (SR) Ca2+ induced a robust store‐operated Ca2+ entry (SOCE) in fast‐ and slow‐twitch fibres, reducing [Ca2+]t‐sys to fibre types. Abruptly introducing internal solutions with 1 mm Mg2+ and [Ca2+]cyto (28 nm–1.3 μm) to Ca2+‐depleted fibres generated t‐system Ca2+ uptake rates

A quantitative description of tubular system Ca(2+) handling in fast- and slow-twitch muscle fibres.

Science.gov (United States)

Cully, Tanya R; Edwards, Joshua N; Murphy, Robyn M; Launikonis, Bradley S

2016-06-01

Current methods do not allow a quantitative description of Ca(2+) movements across the tubular (t-) system membrane without isolating the membranes from their native skeletal muscle fibre. Here we present a fluorescence-based method that allows determination of the t-system [Ca(2+) ] transients and derivation of t-system Ca(2+) fluxes in mechanically skinned skeletal muscle fibres. Differences in t-system Ca(2+) -handling properties between fast- and slow-twitch fibres from rat muscle are resolved for the first time using this new technique. The method can be used to study Ca(2+) handling of the t-system and allows direct comparisons of t-system Ca(2+) transients and Ca(2+) fluxes between groups of fibres and fibres from different strains of animals. The tubular (t-) system of skeletal muscle is an internalization of the plasma membrane that maintains a large Ca(2+) gradient and exchanges Ca(2+) between the extracellular and intracellular environments. Little is known of the Ca(2+) -handling properties of the t-system as the small Ca(2+) fluxes conducted are difficult to resolve with conventional methods. To advance knowledge in this area we calibrated t-system-trapped rhod-5N inside skinned fibres from rat and [Ca(2+) ]t-sys , allowing confocal measurements of Ca(2+) -dependent changes in rhod-5N fluorescence during rapid changes in the intracellular ionic environment to be converted to [Ca(2+) ] transients in the t-system ([Ca(2+) ]t-sys (t)). Furthermore, t-system Ca(2+) -buffering power was determined so that t-system Ca(2+) fluxes could be derived from [Ca(2+) ]t-sys (t). With this new approach, we show that rapid depletion of sarcoplasmic reticulum (SR) Ca(2+) induced a robust store-operated Ca(2+) entry (SOCE) in fast- and slow-twitch fibres, reducing [Ca(2+) ]t-sys to fibre types. Abruptly introducing internal solutions with 1 mm Mg(2+) and [Ca(2+) ]cyto (28 nm-1.3 μm) to Ca(2+) -depleted fibres generated t-system Ca(2+) uptake rates dependent on [Ca(2

KChIP2 regulates the cardiac Ca2+ transient and myocyte contractility by targeting ryanodine receptor activity.

Directory of Open Access Journals (Sweden)

Drew M Nassal

Full Text Available Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss. Therefore, KChIP2 was acutely silenced in isolated guinea pig myocytes, which led to significant reductions in the Ca2+ transient amplitude and prolongation of the transient duration. This change was reinforced by a decline in sarcomeric shortening. Notably, these results were unexpected when considering previous observations showing enhanced ICa,L and prolonged action potential duration following KChIP2 loss, suggesting a disruption of fundamental Ca2+ handling proteins. Evaluation of SERCA2a, phospholamban, RyR, and sodium calcium exchanger identified no change in protein expression. However, assessment of Ca2+ spark activity showed reduced spark frequency and prolonged Ca2+ decay following KChIP2 loss, suggesting an altered state of RyR activity. These changes were associated with a delocalization of the ryanodine receptor activator, presenilin, away from sarcomeric banding to more diffuse distribution, suggesting that RyR open probability are a target of KChIP2 loss mediated by a dissociation of presenilin. Typically, prolonged action potential duration and enhanced Ca2+ entry would augment cardiac contractility, but here we see KChIP2 fundamentally disrupts Ca2+ release events and compromises myocyte contraction. This novel role targeting presenilin localization and RyR activity reveals a significance for KChIP2 loss that reflects adverse remodeling observed in cardiac disease settings.

Functional role of voltage gated Ca2+ channels in heart automaticity

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Pietro eMesirca

2015-02-01

Full Text Available Pacemaker activity of automatic cardiac myocytes controls the heartbeat in everyday life. Cardiac automaticity is under the control of several neurotransmitters and hormones and is constantly regulated by the autonomic nervous system to match the physiological needs of the organism. Several classes of ion channels and proteins involved in intracellular Ca2+ dynamics contribute to pacemaker activity. The functional role of voltage-gated calcium channels (VGCCs in heart automaticity and impulse conduction has been matter of debate for 30 years. However, growing evidence shows that VGCCs are important regulators of the pacemaker mechanisms and play also a major role in atrio-ventricular impulse conduction. Incidentally, studies performed in genetically modified mice lacking L-type Cav1.3 (Cav1.3-/- or T-type Cav3.1 (Cav3.1-/- channels show that genetic inactivation of these channels strongly impacts pacemaking. In cardiac pacemaker cells, VGCCs activate at negative voltages at the beginning of the diastolic depolarization and importantly contribute to this phase by supplying inward current. Loss-of-function of these channels also impairs atrio-ventricular conduction. Furthermore, inactivation of Cav1.3 channels promotes also atrial fibrillation and flutter in knockout mice suggesting that these channels can play a role in stabilizing atrial rhythm. Genomic analysis demonstrated that Cav1.3 and Cav3.1 channels are widely expressed in pacemaker tissue of mice, rabbits and humans. Importantly, human diseases of pacemaker activity such as congenital bradycardia and heart block have been attributed to loss-of-function of Cav1.3 and Cav3.1 channels. In this article, we will review the current knowledge on the role of VGCCs in the generation and regulation of heart rate and rhythm. We will discuss also how loss of Ca2+ entry through VGCCs could influence intracellular Ca2+ handling and promote atrial arrhythmias.

Electrical Conductivity of Cancrinite-Type Na8 - 2 x Ca x [Al6Si6O24][CO3] · 2H2O ( x ≤ 0.03) Crystals

Science.gov (United States)

Sorokin, N. I.

2018-05-01

The electrical conductivity of crystals of artificial cancrinite Na8 - 2 x Ca x [Al6Si6O24][CO3] · 2H2O ( x ≤ 0.03) has been studied in the temperature range of 498-604 K. These crystals were grown by hydrothermal synthesis on a seed in the Na2O-Al2O3-SiO2-H2O system ( t = 380-420°C, P = 3 × 107-9 × 107 Pa). The ionic conductivity of a single-crystal sample (sp. gr. P63), measured along the crystallographic axis c, is low: σ = 8 × 10-7 S/cm at 300°C. The electric transport activation energy is E a = 0.81 ± 0.05 eV. The relationship between the ionic conductivity and specific features of the atomic structure of cancrinites is discussed.

High level of CA 125 due to large endometrioma.

Science.gov (United States)

Phupong, Vorapong; Chen, Orawan; Ultchaswadi, Pornthip

2004-09-01

CA 125 is a tumor-associated antigen. Its high levels are usually associated with ovarian malignancies, whereas smaller increases in the levels were associated with benign gynecologic conditions. The authors report a high level of CA 125 in a case of large ovarian endometrioma. A 45-year-old nulliparous Thai woman, presented with an increase of her abdominal girth for 7 months. Transabdominal ultrasonogram demonstrated a large ovarian cyst and multiple small leiomyoma uteri, and serum CA 125 level was 1,006 U/ml. The preoperative diagnosis was ovarian cancer with leiomyoma uteri. Exploratory laparotomy was performed. There were a large right ovarian endometrioma, small left ovarian endometrioma and multiple small leiomyoma. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed and histopathology confirmed the diagnosis of endometrioma and leiomyoma. The serum CA 125 level declined to non-detectable at the 4th week. She was well at discharge and throughout her 4th week follow-up period Although a very high level of CA 125 is associated with a malignant process, it can also be found in benign conditions such as a large endometrioma. The case emphasizes the association of high levels of CA 125 with benign gynecologic conditions.

Graben structure in the Las Cañadas edifice (Tenerife, Canary Islands): implications for active degassing and insights on the caldera formation

Science.gov (United States)

Galindo, Inés; Soriano, Carles; Martí, Joan; Pérez, Nemesio

2005-06-01

A graben structure has been identified at the western area of the Las Cañadas caldera wall, here referred as the Los Azulejos Graben. This graben is 1 km wide and is bounded by two major normal faults trending NE-SW, the Los Azulejos Fault and the Ucanca Fault. The graben was active for at least 0.5 Ma, from the end of the Ucanca Fm to the end of the Guajara Fm, and before the collapse of the Las Cañadas edifice that formed the western caldera. A right-lateral transtension regime operated in the graben as suggested by small fault orientations and kinematics. The prolongation of the NE rift zone of Tenerife to the Cañadas edifice is the most likely volcano-tectonic scenario for the graben. In this context, inflation of phonolitic shallow magma chambers may have produced reverse faults and reactivation of normal faults. An intense and widespread hydrothermal alteration, here called Azulejos-type, occurred mainly before the graben formation, while a fault-related hydrothermal alteration occurred during and after the graben. Diffuse carbon dioxide and hydrogen degassing in and around the Las Cañadas caldera show relatively enriched values along a NE-SW trend suggesting that faults in the Los Azulejos Graben act as a pathway for deep-seated gases to the surface. Diffuse degassing and hydrothermalism indicate that the graben area has been a zone of intense fluid circulation during the evolution of the Las Cañadas edifice.

Dysregulation of Neuronal Ca2+ Channel Linked to Heightened Sympathetic Phenotype in Prohypertensive States

OpenAIRE

Larsen, Hege E.; Bardsley, Emma N.; Lefkimmiatis, Konstantinos; Paterson, David J.

2016-01-01

Hypertension is associated with impaired nitric oxide (NO)–cyclic nucleotide (CN)-coupled intracellular calcium (Ca2+) homeostasis that enhances cardiac sympathetic neurotransmission. Because neuronal membrane Ca2+ currents are reduced by NO-activated S-nitrosylation, we tested whether CNs affect membrane channel conductance directly in neurons isolated from the stellate ganglia of spontaneously hypertensive rats (SHRs) and their normotensive controls. Using voltage-clamp and cAMP–protein kin...

Calibration-free electrical conductivity measurements for highly conductive slags

International Nuclear Information System (INIS)

Macdonald, Christopher J.; Gao, Huang; Pal, Uday B.; Van den Avyle, James A.; Melgaard, David K.

2000-01-01

This research involves the measurement of the electrical conductivity (K) for the ESR (electroslag remelting) slag (60 wt.% CaF 2 - 20 wt.% CaO - 20 wt.% Al 2 O 3 ) used in the decontamination of radioactive stainless steel. The electrical conductivity is measured with an improved high-accuracy-height-differential technique that requires no calibration. This method consists of making continuous AC impedance measurements over several successive depth increments of the coaxial cylindrical electrodes in the ESR slag. The electrical conductivity is then calculated from the slope of the plot of inverse impedance versus the depth of the electrodes in the slag. The improvements on the existing technique include an increased electrochemical cell geometry and the capability of measuring high precision depth increments and the associated impedances. These improvements allow this technique to be used for measuring the electrical conductivity of highly conductive slags such as the ESR slag. The volatilization rate and the volatile species of the ESR slag measured through thermogravimetric (TG) and mass spectroscopy analysis, respectively, reveal that the ESR slag composition essentially remains the same throughout the electrical conductivity experiments

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

Science.gov (United States)

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

2014-01-01

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

Ca2+-dependent proteolytic activity in crab claw muscle: effects of inhibitors and specificity for myofibrillar proteins

International Nuclear Information System (INIS)

Mykles, D.L.; Skinner, D.M.

1983-01-01

The claw closer muscle of the Bermuda land crab, Gecarcinus lateralis, undergoes a sequential atrophy and restoration during each molting cycle. The role of Ca 2+ -dependent proteinases in the turn-over of myofibrillar protein in normal anecdysial (intermolt) claw muscle is described. Crab Ca 2+ -dependent proteinase degrades the myofibrillar proteins actin, myosin heavy and light chains, paramyosin, tropomyosin, and troponin-T and -I. Ca 2+ -dependent proteinase activity in whole homogenates and 90,000 x g supernatant fractions from muscle homogenates has been characterized with respect to Ca 2+ requirement, substrate specificity, and effects of proteinase inhibitors. The enzyme is inhibited by antipain, leupeptin, E-64, and iodoacetamide; it is insensitive to pepstatin A. The specificity of crab Ca 2+ -dependent proteinase was examined with native myosin with normal ATPase activity as well as with radioiodinated myosin and radioiodinated hemolymph proteins. Hydrolysis of 125 I-myosin occurs in two phases, both Ca 2+ -dependent: (1) heavy chain (M/sub r/ = 200,000) is cleaved into four large fragments (M/sub r/ = 160,000, 110,000, 73,000, 60,000) and numerous smaller fragments; light chain (M/sub r/ = 18,000) is cleaved to a 15,000-Da fragment; (2) the fragments produced in the first phase are hydrolyzed to acid-soluble material. Although radioiodinated native hemolymph proteins are not susceptible to the Ca 2+ -dependent proteinase, those denatured by carboxymethylation are degraded. These data suggest that crab Ca 2+ -dependent proteinase is involved in turnover of myofibrillar protein in normal muscle and muscle undergoing proecdysial atrophy

Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

Science.gov (United States)

Bernal-Martínez, Juan; Ortega Soto, Arturo

2004-09-01

Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

A novel core–shell nanocomposite Ni–Ca@mSiO{sub 2} for benzophenone selective hydrogenation

Energy Technology Data Exchange (ETDEWEB)

Han, Xue; Feng, Wenhui; Chu, Xiaoning; Chu, Hailong; Niu, Libo; Bai, Guoyi, E-mail: baiguoyi@hotmail.com [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science (China)

2017-02-15

A novel core–shell nanocomposite Ni–Ca@mSiO{sub 2} was first prepared by a modified Stöber method in this paper. It has a core–shell structure with Ni (about 8 nm in diameter) and Ca as the cores and mesoporous silica as the outer shell, as proven by the transmission electron microscopy. This nanocomposite exhibited good catalytic performance in the selective hydrogenation of benzophenone, with 96.1% conversion and 94.9% selectivity for benzhydrol under relatively mild reaction conditions. It was demonstrated that addition of small amounts of alkaline Ca can not only markedly improve the dispersion of the active species but also tune the acid–base property of this nanocomposite, resulting in the efficient suppression of benzhydrol dehydration to achieve a high selectivity. Furthermore, the core–shell nanocomposite Ni–Ca@mSiO{sub 2} can be recycled four runs without appreciable loss of its initial activity, more stable than the traditional supported nanocatalyst Ni–Ca/mSiO{sub 2}. It was suggested that the outer mesoporous silica shell of Ni–Ca@mSiO{sub 2} can prevent both the aggregation and the leaching of the active Ni species, accounting for its relatively good stability.

Optimization of thermal conductivity lightweight brick type AAC (Autoclaved Aerated Concrete) effect of Si & Ca composition by using Artificial Neural Network (ANN)

Science.gov (United States)

Zulkifli; Wiryawan, G. P.

2018-03-01

Lightweight brick is the most important component of building construction, therefore it is necessary to have lightweight thermal, mechanical and aqustic thermal properties that meet the standard, in this paper which is discussed is the domain of light brick thermal conductivity properties. The advantage of lightweight brick has a low density (500-650 kg/m3), more economical, can reduce the load 30-40% compared to conventional brick (clay brick). In this research, Artificial Neural Network (ANN) is used to predict the thermal conductivity of lightweight brick type Autoclaved Aerated Concrete (AAC). Based on the training and evaluation that have been done on 10 model of ANN with number of hidden node 1 to 10, obtained that ANN with 3 hidden node have the best performance. It is known from the mean value of MSE (Mean Square Error) validation for three training times of 0.003269. This ANN was further used to predict the thermal conductivity of four light brick samples. The predicted results for each of the AAC1, AAC2, AAC3 and AAC4 light brick samples were 0.243 W/m.K, respectively; 0.29 W/m.K; 0.32 W/m.K; and 0.32 W/m.K. Furthermore, ANN is used to determine the effect of silicon composition (Si), Calcium (Ca), to light brick thermal conductivity. ANN simulation results show that the thermal conductivity increases with increasing Si composition. Si content is allowed maximum of 26.57%, while the Ca content in the range 20.32% - 30.35%.

Formation of CaB6 in the thermal decomposition of the hydrogen storage material Ca(BH4)2.

Science.gov (United States)

Sahle, Christoph J; Sternemann, Christian; Giacobbe, Carlotta; Yan, Yigang; Weis, Christopher; Harder, Manuel; Forov, Yury; Spiekermann, Georg; Tolan, Metin; Krisch, Michael; Remhof, Arndt

2016-07-20

Using a combination of high resolution X-ray powder diffraction and X-ray Raman scattering spectroscopy at the B K- and Ca L2,3-edges, we analyzed the reaction products of Ca(BH4)2 after annealing at 350 °C and 400 °C under vacuum conditions. We observed the formation of nanocrystalline/amorphous CaB6 mainly and found only small contributions from amorphous B for annealing times larger than 2 h. For short annealing times of 0.5 h at 400 °C we observed neither CaB12H12 nor CaB6. The results indicate a reaction pathway in which Ca(BH4)2 decomposes to B and CaH2 and finally reacts to form CaB6. These findings confirm the potential of using Ca(BH4)2 as a hydrogen storage medium and imply the desired cycling capabilities for achieving high-density hydrogen storage materials.

Preparation of a highly concentrated, completely monomeric, active sarcoplasmic reticulum Ca2+-ATPase.

Science.gov (United States)

Lüdi, H; Hasselbach, W

1985-11-21

Sarcoplasmic reticulum vesicles from fast skeletal muscle were partially delipidated with sodium cholate at high ionic strength and sedimented in a discontinuous sucrose gradient. Phospholipid content was reduced from 0.777 mumol/mg protein to 0.242 mumol/mg protein. As judged from gel electrophoresis and high pressure liquid gel chromatography, accessory proteins were removed during centrifugation and the Ca2+-ATPase was obtained in an almost pure form. Addition of myristoylglycerophosphocholine (1 mg/mg protein) reactivates ATPase and dinitrophenylphosphatase activity to the same degree obtained with native vesicles. Using the analytical ultracentrifuge it could be demonstrated that the reactivated Ca2+-ATPase was present exclusively in a monomeric state. These results were obtained at high and low ionic strength and up to a protein concentration of 10 mg/ml. Therefore this preparation should be very useful to investigate differences between oligomeric and monomeric Ca2+-ATPase.

Conotoxins as Tools to Understand the Physiological Function of Voltage-Gated Calcium (CaV Channels

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David Ramírez

2017-10-01

Full Text Available Voltage-gated calcium (CaV channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1–1.4; CaV2.1–2.3 and Low-voltage activated (LVA, CaV3.1–3.3. HVA channels are highly expressed in brain (neurons, heart, and adrenal medulla (chromaffin cells, among others, and are also classified into subtypes which can be distinguished using pharmacological approaches. Cone snails are marine gastropods that capture their prey by injecting venom, “conopeptides”, which cause paralysis in a few seconds. A subset of conopeptides called conotoxins are relatively small polypeptides, rich in disulfide bonds, that target ion channels, transporters and receptors localized at the neuromuscular system of the animal target. In this review, we describe the structure and properties of conotoxins that selectively block HVA calcium channels. We compare their potency on several HVA channel subtypes, emphasizing neuronal calcium channels. Lastly, we analyze recent advances in the therapeutic use of conotoxins for medical treatments.

Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

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Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

2016-01-01

Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the

Activity coefficients of CaCl{sub 2} in (serine or proline + water) mixtures at T = 298.15 K

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Ma Jingjing [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); Zhang Xinkuan [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); School of Chemistry and Chemical Engineering, Xinxiang University, Xinxiang, Henan 453003 (China); Zhuo Kelei, E-mail: lchow@mail.ucf.ed [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); Liu Hongxun; Wang Jianji [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China)

2010-05-15

Activity coefficients for the (CaCl{sub 2} + amino acid + water) system were determined at a temperature of 298.15 K using ion-selective electrodes. The range of molalities of CaCl{sub 2} is (0.01 to 0.20) mol . kg{sup -1}, and that of amino acids is (0.10 to 0.40) mol . kg{sup -1}. The activity coefficients obtained from the Debye-Hueckel extended equation and the Pitzer equation are in good agreement with each other. Results show that the interactions between CaCl{sub 2} and amino acid are controlled mainly by the electrostatic interactions (attraction). Gibbs free energy interaction parameters (g{sub EA}) and salting constants (k{sub S}) are positive, indicating that these amino acids are salted out by CaCl{sub 2}. These results are discussed based on group additivity model.

Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE.

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Molina, Rafael; Auge, Jose Maria; Escudero, Jose Miguel; Marrades, Ramon; Viñolas, Nuria; Carcereny, Emilio; Ramirez, Jose; Filella, Xavier

2008-01-01

Tumor marker serum levels were prospectively studied in 289 patients with suspected, but unconfirmed, lung cancer and in 513 patients with lung cancer [417 non-small cell lung cancer (NSCLC) patients and 96 small cell lung cancer (SCLC) patients]. In patients with benign disease, abnormal serum levels were found for the following tumor markers: CEA (in 6.6% of patients); CA 19.9 (6.2%); CA 125 (28.7%); NSE (0.7%); CYFRA (8.7%); TAG-72.3 (4.2%); SCC (3.5%), and CA 15.3 (3.5%). Excluding patients with renal failure or liver diseases, tumor marker specificity improved with abnormal levels in 0.5% for NSE, 0.9% for SCC, 2.8% for CEA, CA 15.3 and TAG-72.3, 3.8% for CA 19.9, 4.2% for CYFRA and 21.4% for CA 125. Excluding CA 125, one of the markers was abnormal in 15% of patients without malignancy. Tumor marker sensitivity was related to cancer histology and tumor extension. NSE had the highest sensitivity in SCLC and CYFRA and CEA in NSCLC. Significantly higher concentrations of CEA, SCC, CA 125, CA 15.3 and TAG-72.3 were found in NSCLC than in SCLC. Likewise, significantly higher CEA (p tumors. Using a combination of 3 tumor markers (CEA, CYFRA 21-1 in all histologies, SCC in squamous tumors and CA 15.3 in adenocarcinomas), a high sensitivity may be achieved in all histological types. Tumor markers may be useful in the histological differentiation of NSCLC and SCLC. Using specific criteria for the differentiation of SCLC and NSCLC, the sensitivity was 84.2 and 68.8%, the specificity was 93.8 and 99.7%, the positive predictive value was 98.3 and 98.5% and the negative predictive value was 57.7 and 93.3%, respectively. Copyright 2008 S. Karger AG, Basel.

Differential Activity of Voltage- and Ca2+-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case

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Salvador Valle-Reyes

2018-05-01

Full Text Available Activation of resting T cells relies on sustained Ca2+ influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca2+- or voltage-activated K+ channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3. Voltage dependence of activation and inactivation of Kv1.3 current were shifted up to by 15 mV to more negative potentials upon a prolonged incubation in the whole cell mode and displayed little difference at a stable state in all cell lines but CEM, where the activation curve was biphasic, with a high and low potential components. In Jurkat, KCa currents were dominated by apamine-sensitive KCa2.2 channels, whereas only KCa3.1 current was detected in healthy T and leukemic CEM and MOLT-3 cells. Despite a high proliferation potential of Jurkat cells, Kv and KCa currents were unexpectedly small, more than 10-fold lesser as compared to activated healthy human T cells, CEM and MOLT-3, which displayed characteristic Kv1.3high:KCa3.1high phenotype. Our results suggest that Jurkat cells represent perhaps a singular case and call for more extensive studies on primary leukemic T cell lines as well as a verification of the therapeutic potential of specific KCa3.1 blockers to combat acute lymphoblastic T leukemias.

Controls of Ca/Mg/Fe activity ratios in pore water chemistry models of the Callovian-Oxfordian clay formation

International Nuclear Information System (INIS)

Lerouge, C.; Grangeon, S.; Wille, G.; Flehoc, C.; Gailhanou, H.; Gaucher, E.C.; Tournassat, C.; Vinsot, A.; Made, B.; Altmann, S.

2013-01-01

In the pore water chemistry model of the Callovian-Oxfordian clay formation, the divalent cations Ca, Mg, and Fe are controlled by equilibrium reactions with pure carbonates: calcite for Ca, dolomite for Mg, and siderite for Fe. Results of a petrological study and computing of the Ca/Mg and Ca/Fe activity ratios based on natural pore water chemistry provide evidence that equilibrium with pure calcite and pure dolomite is a reasonable assumption for undisturbed pore waters; on the other hand, siderite cannot be considered at equilibrium with pore waters at the formation scale. (authors)

Controls of Ca/Mg/Fe activity ratios in pore water chemistry models of the Callovian-Oxfordian clay formation

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Lerouge, C.; Grangeon, S.; Wille, G.; Flehoc, C.; Gailhanou, H.; Gaucher, E.C.; Tournassat, C. [BRGM av. Claude Guillemin BP6009 45060 Orleans cedex 2 (France); Vinsot, A. [ANDRA Meuse/Haute-Marne Underground research Laboratory (URL), RD 960, 55290 Bure (France); Made, B.; Altmann, S. [ANDRA - Parc de la Croix Blanche, 1-7 rue Jean Monnet, 92298 Chatenay-Malabry Cedex (France)

2013-07-01

In the pore water chemistry model of the Callovian-Oxfordian clay formation, the divalent cations Ca, Mg, and Fe are controlled by equilibrium reactions with pure carbonates: calcite for Ca, dolomite for Mg, and siderite for Fe. Results of a petrological study and computing of the Ca/Mg and Ca/Fe activity ratios based on natural pore water chemistry provide evidence that equilibrium with pure calcite and pure dolomite is a reasonable assumption for undisturbed pore waters; on the other hand, siderite cannot be considered at equilibrium with pore waters at the formation scale. (authors)

Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells

DEFF Research Database (Denmark)

Dyrda, Agnieszka; Cytlak, Urszula; Ciuraszkiewicz, Anna

2010-01-01

-activated transient PCa observed here under local membrane deformation is a likely contributor to the Ca(2+)-mediated effects observed during the normal aging process of red blood cells, and to the increased Ca(2+) content of red cells in certain hereditary anemias such as thalassemia and sickle cell anemia....

Anomalous size effect in conductivity of Bi films of small thickness

International Nuclear Information System (INIS)

Anopchenko, A.S.; Kashirin, V.Yu.; Komnik, Yu.F.

1995-01-01

Experimental data are obtained at helium temperature, which describe the kinetic properties (conductivity, magnetoresistance and Hall coefficient) of Bi films whose thicknesses are within 100-500 A. The small-thickness Bi films display an anomalous size effect- the growing conductivity at decreasing thickness, and pronounced quantum interference effects - weak electron localization and enhancing electron-electron interaction in a disordered system. The information derived on the kinetic properties of the films is used to identify the character of the changes in the electron and hole concentrations and mobilities with a decreasing thickness. The isotropy of the properties in the films plane due to the axial texture has permitted us to use the equations for a conductor with two types of charge carriers. The used kinetic characteristics correctly take into account the contribution of the quantum corrections related to quantum interference. It is found that the concentration of the charge carries increases appreciably (by about two orders of magnitude) as the film thickness decreases to 100 A, which determines the anomalous size effect in the conductivity of the films

Morphology determination of small particles by electron microscopy and electrical conduction measurements

International Nuclear Information System (INIS)

Robrieux, B.; Desrousseaux, G.; Renou, A.; Gillet, M.

1989-01-01

In this paper, we show that it is possible to deduce the actual morphology of small particle condensed onto an insulator by combining the granularity analysis from electron micrographs and the electrical sheet conductance of the deposit on its substrate. Assuming the particles are truncated ellipsoids, we determine the excentricity and the contact angle with the substrate for Au on amorphous carbon and MgO substrates. (orig.)

Adeno-associated virus (AAV-mediated suppression of Ca2+/calmodulin kinase IV activity in the nucleus accumbens modulates emotional behaviour in mice

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Bading Hilmar

2007-12-01

Full Text Available Abstract Background Calcium/calmodulin-dependent protein kinase IV (CaMKIV controls activity-dependent gene transcription by regulating the activity of the cyclic AMP response element binding protein (CREB. This signaling pathway is involved in gating emotional responses in the CNS but previous studies did not address the potential roles of CaMKIV in discrete brain regions. In the present study, we aimed at specifically dissecting the role of CaMKIV in the nucleus accumbens of adult mice. Results We used recombinant adeno-associated virus (rAAV-mediated gene transfer of a dominant-negative CaMKIV variant (rAAV-dnCaMKIV to inhibit endogenous CaMKIV in the nucleus accumbens. rAAV-dnCaMKIV treated animals were subjected to a battery of tests including, prepulse inhibition of the acoustic startle response, open field, social interaction and anxiety-related behaviour. We found that basal locomotor activity in the open field, and prepulse inhibition or startle performance were unaltered in mice infected with rAAV-dnCaMKIV in the nucleus accumbens. However, anxiogenic effects were revealed in social interaction testing and the light/dark emergence test. Conclusion Our findings suggest a modulatory role of CaMKIV in the nucleus accumbens in anxiety-like behaviour but not sensorimotor gating.

Inhibiting the Activity of CA1 Hippocampal Neurons Prevents the Recall of Contextual Fear Memory in Inducible ArchT Transgenic Mice.

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Masanori Sakaguchi

Full Text Available The optogenetic manipulation of light-activated ion-channels/pumps (i.e., opsins can reversibly activate or suppress neuronal activity with precise temporal control. Therefore, optogenetic techniques hold great potential to establish causal relationships between specific neuronal circuits and their function in freely moving animals. Due to the critical role of the hippocampal CA1 region in memory function, we explored the possibility of targeting an inhibitory opsin, ArchT, to CA1 pyramidal neurons in mice. We established a transgenic mouse line in which tetracycline trans-activator induces ArchT expression. By crossing this line with a CaMKIIα-tTA transgenic line, the delivery of light via an implanted optrode inhibits the activity of excitatory CA1 neurons. We found that light delivery to the hippocampus inhibited the recall of a contextual fear memory. Our results demonstrate that this optogenetic mouse line can be used to investigate the neuronal circuits underlying behavior.

Hydrogen peroxide modulates Ca2+-activation of single permeabilized fibres from fast- and slow-twitch skeletal muscles of rats.

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Plant, D R; Lynch, G S; Williams, D A

2000-01-01

We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H2O2. The effects of H2O2 on maximum Ca2+-activated force were dose-dependent with 30 min exposure to 5 mM H2O2 causing a progressive decrease by 22+/-3 and 13+/-2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H2O2 (100 microM and 1 mM) had no effect on maximum Ca2+-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H2O2-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca2+-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca2+ (pCa50) was not altered by exposure to any concentration of exogenous H2O2. However, all concentrations of H2O2 diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca2+ binding to troponin is altered. H2O2 (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H2O2 may reduce the maximum Ca2+ activated force production in skinned muscle fibres by decreasing the force per crossbridge.

Distribution of rSlo Ca2+-activated K+ channels in rat astrocyte perivascular endfeet.

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Price, Diana L; Ludwig, Jeffrey W; Mi, Huaiyu; Schwarz, Thomas L; Ellisman, Mark H

2002-11-29

Evidence that Ca(2+)-activated K(+) (K(Ca)) channels play a role in cell volume changes and K(+) homeostasis led to a prediction that astrocytes would have K(Ca) channels near blood vessels in order to maintain K(+) homeostasis. Consistent with this thinking the present study demonstrates that rSlo K(Ca) channels are in glial cells of the adult rat central nervous system (CNS) and highly localized to specializations of astrocytes associated with the brain vasculature. Using confocal and thin-section electron microscopic immunolabeling methods the distribution of rSlo was examined in adult rat brain. Strong rSlo immunolabeling was present around the vasculature of most brain regions. Examination of dye-filled hippocampal astrocytes revealed rSlo immunolabeling polarized in astrocytic endfeet. Ultrastructural analysis confirmed that the rSlo staining was concentrated in astrocytic endfeet ensheathing capillaries as well as abutting the pia mater. Immunostaining within the endfeet was predominantly distributed at the plasma membrane directly adjacent to either the vascular basal lamina or the pial surface. The distribution of the aquaporin-4 (AQP-4) water channel was also examined using dye-filled hippocampal astrocytes. In confirmation of earlier reports, intense AQP-4 immunolabeling was generally observed at the perimeter of blood vessels, and coincided with perivascular endfeet and rSlo labeling. We propose that rSlo K(Ca) channels, with their sensitivity to membrane depolarization and intracellular calcium, play a role in the K(+) modulation of cerebral blood flow. Additional knowledge of the molecular and cellular machinery present at perivascular endfeet may provide insight into the structural and functional molecular elements responsible for the neuronal activity-dependent regulation of cerebral blood flow. Copyright 2002 Elsevier Science B.V.

Study on Ca2+ antagonistic effect and mechanism of Chinese herbal drugs using 45Ca

International Nuclear Information System (INIS)

Yang Yuanyou; Liu Ning; Mo Shangwu; Qiu Mingfeng; Jin Jiannan; Liao Jiali

2002-01-01

The Ca 2+ antagonistic effect and mechanism of Chinese herbal drugs are studied by using 45 Ca. The results indicate that potential-dependent Ca 2+ channel (PDC) and receptor-operated Ca 2+ channel (ROC) in cell membranes of smooth muscle can be blocked by several Chinese herbal drugs, including as Crocus sativus L., Carthamus L., Di-ao-xin-xue-kang (DAXXG) and Ginkgo biloba L. leaves. Among them Crocus sativus L. has the strongest antagonistic effect on Ca 2+ channel, while Ginkgo biloba L. leaves has no obvious effect. The whole prescription and the other functional drugs have significant effect on ROC and PDC. The compositions extracted by hexane have the strongest antagonistic. The wrinkled giant hyssop have five active compositions and Pei-lan have two active compositions

Tax Support of Small Enterprises Activity in Ukraine

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Pronoza Pavlo V

2015-03-01

Full Text Available The purpose of the article is to evaluate the importance of small enterprises for the economic development of Ukraine and determine priorities of their stimulation. The analysis of quantitative indicators of small businesses and their comparison with the average level of all enterprises in Ukraine as a whole allowed evaluating their importance in the development of the country. There has been identified a special role of small enterprises in Ukraine’s economy and confirmed the expediency of using tax regulation instruments aimed at their development. There was identified an insufficient efficiency level of tax regulation of small businesses in Ukraine due to using a simplified system of taxation, accounting and reporting. The basic tools used in the framework of tax regulation of small enterprises activities in international practice have been determined. Additional analysis of performance of small enterprises by types of economic activity on the basis of an integrated assessment permitted to identify priorities of using tax regulation instruments in Ukraine.

Mechanically stiff, electrically conductive composites of polymers and carbon nanotubes

Science.gov (United States)

Worsley, Marcus A.; Kucheyev, Sergei O.; Baumann, Theodore F.; Kuntz, Joshua D.; Satcher, Jr., Joe H.; Hamza, Alex V.

2015-07-21

Using SWNT-CA as scaffolds to fabricate stiff, highly conductive polymer (PDMS) composites. The SWNT-CA is immersing in a polymer resin to produce a SWNT-CA infiltrated with a polymer resin. The SWNT-CA infiltrated with a polymer resin is cured to produce the stiff and electrically conductive composite of carbon nanotube aerogel and polymer.

Mechanically stiff, electrically conductive composites of polymers and carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Worsley, Marcus A.; Kucheyev, Sergei O.; Baumann, Theodore F.; Kuntz, Joshua D.; Satcher, Jr., Joe H.; Hamza, Alex V.

2017-10-17

Using SWNT-CA as scaffolds to fabricate stiff, highly conductive polymer (PDMS) composites. The SWNT-CA is immersing in a polymer resin to produce a SWNT-CA infiltrated with a polymer resin. The SWNT-CA infiltrated with a polymer resin is cured to produce the stiff and electrically conductive composite of carbon nanotube aerogel and polymer.

Vapor pressures and isopiestic molalities of concentrated CaCl2(aq), CaBr2(aq), and NaCl(aq) to T = 523 K

International Nuclear Information System (INIS)

Gruszkiewicz, Miroslaw S.; Simonson, John M.

2005-01-01

The Oak Ridge National Laboratory high-temperature isopiestic apparatus was outfitted with precise pressure gauges to allow for direct vapor pressure measurements. Vapor pressures over concentrated solutions of CaCl 2 (aq), and CaBr 2 (aq) were measured at temperatures between (380.15 and 523.15) K in the range of water activities between 0.2 and 0.85. Isopiestic molalities were used to determine osmotic coefficients at the conditions where NaCl reference standard solutions remained undersaturated. The main goal of this work was to improve the accuracy of isopiestic comparisons based on the calcium chloride reference standard. Osmotic coefficients for CaCl 2 (aq) and CaBr 2 (aq) calculated from both isopiestic and direct vapor pressure results were combined with the literature data and used to build general thermodynamic models based on a variant of extended Pitzer ion-interaction equations and valid at the saturation pressure of water. While these empirical models approach the accuracy of the experimental data in a wider range of concentrations and temperatures than any previously published equations, considerable amounts of accurate data and a substantial effort are required in order to obtain a satisfactory representation using power series-based virial equations. The effect of experimental uncertainties on the accuracy of the direct vapor pressure results is discussed, including in particular the error caused by the presence in the apparatus of a small amount of CO 2 . The substantial decrease of the solubility product of CaCO 3 in concentrated chloride solutions at temperatures above 423 K is a serious defect of calcium chloride as a water activity reference standard

Effects of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in Wistar rats.

Science.gov (United States)

Olatunji, Lawrence A; Usman, Taofeek O; Adebayo, Joseph O; Olatunji, Victoria A

2012-09-01

To investigate the effects of oral administration of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in rats. The 25 and 50 mg/(kg·d) of aqueous extracts of H. sabdariffa were respectively given to rats in the experimental groups for 28 d, and rats in the control group received an appropriate volume of distilled water as vehicle. Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in the kidney were assayed by spectrophotometric method. Administrations of 25 and 50 mg/(kg·d) of aqueous extract of H. sabdariffa significantly decreased the Ca(2+)-Mg(2+)-ATPase activity in the kidney of rats (Psabdariffa may preserve the renal function despite a decreased renal Ca(2+)-Mg(2+)-ATPase activity.