Investigation of Corner Effect and Identification of Tunneling Regimes in L-Shaped Tunnel Field-Effect-Transistor.

PubMed

Najam, Faraz; Yu, Yun Seop

2018-09-01

Corner-effect existing in L-shaped tunnel field-effect-transistor (LTFET) was investigated using numerical simulations and band diagram analysis. It was found that the corner-effect is caused by the convergence of electric field in the sharp source corner present in an LTFET, thereby increasing the electric field in the sharp source corner region. It was found that in the corner-effect region tunneling starts early, as a function of applied bias, as compared to the rest of the channel not affected by corner-effect. Further, different tunneling regimes as a function of applied bias were identified in the LTFET including source to channel and channel to channel tunneling regimes. Presence of different tunneling regimes in LTFET was analytically justified with a set of equations developed to model source to channel, and channel to channel tunneling currents. Drain-current-gate-voltage (Ids-Vgs) characteristics obtained from the equations is in reasonable qualitative agreement with numerical simulation.

Hall effect mobility for SiC MOSFETs with increasing dose of nitrogen implantation into channel region

NASA Astrophysics Data System (ADS)

Noguchi, Munetaka; Iwamatsu, Toshiaki; Amishiro, Hiroyuki; Watanabe, Hiroshi; Kita, Koji; Yamakawa, Satoshi

2018-04-01

The Hall effect mobility (μHall) of the Si-face 4H-SiC metal–oxide–semiconductor field effect transistor (MOSFET) with a nitrogen (N)-implanted channel region was investigated by increasing the N dose. The μHall in the channel region was systematically examined regarding channel structures, that is, the surface and buried channels. It was experimentally demonstrated that increasing the N dose results in an improvement in μHall in the channel region due to the formation of the buried channel. However, further increase in N dose was found to decrease the μHall in the channel region, owing to the decrease in the electron mobility in the N-implanted bulk region.

Effects of the β1 auxiliary subunit on modification of Rat Na{sub v}1.6 sodium channels expressed in HEK293 cells by the pyrethroid insecticides tefluthrin and deltamethrin

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Bingjun; Soderlund, David M., E-mail: dms6@cornell.edu

We expressed rat Na{sub v}1.6 sodium channels with or without the rat β1 subunit in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on whole-cell sodium currents. In assays with the Na{sub v}1.6 α subunit alone, both pyrethroids prolonged channel inactivation and deactivation and shifted the voltage dependence of channel activation and steady-state inactivation toward hyperpolarization. Maximal shifts in activation were ~ 18 mV for tefluthrin and ~ 24 mV for deltamethrin. These compounds also caused hyperpolarizing shifts of ~ 10–14 mV in the voltage dependence of steady-state inactivation and increased inmore » the fraction of sodium current that was resistant to inactivation. The effects of pyrethroids on the voltage-dependent gating greatly increased the size of sodium window currents compared to unmodified channels; modified channels exhibited increased probability of spontaneous opening at membrane potentials more negative than the normal threshold for channel activation and incomplete channel inactivation. Coexpression of Na{sub v}1.6 with the β1 subunit had no effect on the kinetic behavior of pyrethroid-modified channels but had divergent effects on the voltage-dependent gating of tefluthrin- or deltamethrin-modified channels, increasing the size of tefluthrin-induced window currents but decreasing the size of corresponding deltamethrin-induced currents. Unexpectedly, the β1 subunit did not confer sensitivity to use-dependent channel modification by either tefluthrin or deltamethrin. We conclude from these results that functional reconstitution of channels in vitro requires careful attention to the subunit composition of channel complexes to ensure that channels in vitro are faithful functional and pharmacological models of channels in neurons. - Highlights: • We expressed Na{sub v}1.6 sodium channels with or without β1 subunits in HEK293 cells. • Tefluthrin and deltamethrin shifted channel gating to hyperpolarized potentials. • The β1 subunit had opposite effects on the actions of tefluthrin and deltamethrin. • Auxiliary subunits are required for full reconstitution of channel function. • Channels in HEK293 cells exhibit properties similar to channels in neurons.« less

Polar codes for achieving the classical capacity of a quantum channel

NASA Astrophysics Data System (ADS)

Guha, Saikat; Wilde, Mark

2012-02-01

We construct the first near-explicit, linear, polar codes that achieve the capacity for classical communication over quantum channels. The codes exploit the channel polarization phenomenon observed by Arikan for classical channels. Channel polarization is an effect in which one can synthesize a set of channels, by ``channel combining'' and ``channel splitting,'' in which a fraction of the synthesized channels is perfect for data transmission while the other fraction is completely useless for data transmission, with the good fraction equal to the capacity of the channel. Our main technical contributions are threefold. First, we demonstrate that the channel polarization effect occurs for channels with classical inputs and quantum outputs. We then construct linear polar codes based on this effect, and the encoding complexity is O(N log N), where N is the blocklength of the code. We also demonstrate that a quantum successive cancellation decoder works well, i.e., the word error rate decays exponentially with the blocklength of the code. For a quantum channel with binary pure-state outputs, such as a binary-phase-shift-keyed coherent-state optical communication alphabet, the symmetric Holevo information rate is in fact the ultimate channel capacity, which is achieved by our polar code.

Clofilium inhibits Slick and Slack potassium channels.

PubMed

de Los Angeles Tejada, Maria; Stolpe, Kathleen; Meinild, Anne-Kristine; Klaerke, Dan A

2012-01-01

Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na(+) and Cl(-), and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.

Inhibitory effect of DIDS, NPPB, and phloretin on intracellular chloride channels.

PubMed

Malekova, Lubica; Tomaskova, Jana; Novakova, Marie; Stefanik, Peter; Kopacek, Juraj; Lakatos, Boris; Pastorekova, Silvia; Krizanova, Olga; Breier, Albert; Ondrias, Karol

2007-11-01

We studied the effects of the chloride channel blockers, 5-nitro-2-(phenylpropylamino)-benzoate (NPPB), dihydro-4,4' diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), and phloretin on H2O2-induced primary culture cardiomyocyte apoptosis and activity of intracellular chloride channels obtained from rat heart mitochondrial and lysosomal vesicles. The chloride channel blockers (100 micromol/l) inhibited the H2O2-induced cardiomyocytes apoptosis. We characterized the effect of the blockers on single channel properties of the chloride channels derived from the mitochondrial and lysosomal vesicles incorporated into a bilayer lipid membrane. The single chloride channel currents were measured in 250:50 mmol/l KCl cis/trans solutions. NPPB, DIDS, and phloretin inhibited the chloride channels by decreasing the channel open probability in a concentration-dependent manner with EC50 values of 42, 7, and 20 micromol/l, respectively. NPPB and phloretin inhibited the channel's conductance and open dwell time, indicating that they could affect the chloride selective filter, pore permeability, and gating mechanism of the chloride channels. DIDS and NPPB inhibited the channels from the other side than bongkrekic acid and carboxyatractyloside. The results may contribute to understand a possible involvement of intracellular chloride channels in apoptosis and cardioprotection.

Angiotensin II stimulates basolateral 50-pS K channels in the thick ascending limb.

PubMed

Wang, Mingxiao; Luan, Haiyan; Wu, Peng; Fan, Lili; Wang, Lijun; Duan, Xinpeng; Zhang, Dandan; Wang, Wen-Hui; Gu, Ruimin

2014-03-01

We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.

R- and S-terbutaline activate large conductance and Ca2+ dependent K+ (BKCa) channel through interacting with β2 and M receptor respectively.

PubMed

Fan, Zhuo; Lin, Wei; Lv, Nanying; Ye, Yanrui; Tan, Wen

2016-11-01

This study investigated the effect of the β 2 receptor agonist terbutaline on the single channel activity of BK Ca channel. The effects of racemate and two isomers of terbutaline were all assessed. β 2 adrenoceptors were stably overexpressed on HEK293 cells by lentiviral transduction method and chicken BK Ca channels were transiently expressed on normal HEK293 cell line or HEK293 cells overexpressing β 2 receptors. Data showed that terbutaline significantly increased the single channel open probability of BK Ca channel within 10min. The channel activating effects of terbutaline are stereoselective and mainly stay with the R-enantiomers. The opening probability of BK Ca channel at 10min after drug application normalized to that just before drug application (Po10/Po0s) for R- and S-terbutaline were 7.85±3.20 and 1.06±0.45 respectively at 1μM concentration, corresponding to 28.37±9.96 and 2.68±1.09 at the higher concentration of 10μM. ICI 118551 blocked the effect of R- but not S-terbutaline (10μM), whereas atropine blocked the channel activating effects of S-terbutaline of higher concentration. In addition, the muscarinic receptor agonist carbachol increased the BK Ca channel activity in an atropine-sensitive manner as an positive control experiment, which indicate the involvement of M receptor in the channel activating effect of S-terbutaline. Copyright © 2016. Published by Elsevier B.V.

Effects of channel noise on firing coherence of small-world Hodgkin-Huxley neuronal networks

NASA Astrophysics Data System (ADS)

Sun, X. J.; Lei, J. Z.; Perc, M.; Lu, Q. S.; Lv, S. J.

2011-01-01

We investigate the effects of channel noise on firing coherence of Watts-Strogatz small-world networks consisting of biophysically realistic HH neurons having a fraction of blocked voltage-gated sodium and potassium ion channels embedded in their neuronal membranes. The intensity of channel noise is determined by the number of non-blocked ion channels, which depends on the fraction of working ion channels and the membrane patch size with the assumption of homogeneous ion channel density. We find that firing coherence of the neuronal network can be either enhanced or reduced depending on the source of channel noise. As shown in this paper, sodium channel noise reduces firing coherence of neuronal networks; in contrast, potassium channel noise enhances it. Furthermore, compared with potassium channel noise, sodium channel noise plays a dominant role in affecting firing coherence of the neuronal network. Moreover, we declare that the observed phenomena are independent of the rewiring probability.

Effect of tyrphostin AG879 on Kv4.2 and Kv4.3 potassium channels

PubMed Central

Yu, Haibo; Zou, Beiyan; Wang, Xiaoliang; Li, Min

2015-01-01

Background and Purpose A-type potassium channels (IA) are important proteins for modulating neuronal membrane excitability. The expression and activity of Kv4.2 channels are critical for neurological functions and pharmacological inhibitors of Kv4.2 channels may have therapeutic potential for Fragile X syndrome. While screening various compounds, we identified tyrphostin AG879, a tyrosine kinase inhibitor, as a Kv4.2 inhibitor from. In the present study we characterized the effect of AG879 on cloned Kv4.2/Kv channel-interacting protein 2 (KChIP2) channels. Experimental Approach To screen the library of pharmacologically active compounds, the thallium flux assay was performed on HEK-293 cells transiently-transfected with Kv4.2 cDNA using the Maxcyte transfection system. The effects of AG879 were further examined on CHO-K1 cells expressing Kv4.2/KChIP2 channels using a whole-cell patch-clamp technique. Key Results Tyrphostin AG879 selectively and dose-dependently inhibited Kv4.2 and Kv4.3 channels. In Kv4.2/KChIP2 channels, AG879 induced prominent acceleration of the inactivation rate, use-dependent block and slowed the recovery from inactivation. AG879 induced a hyperpolarizing shift in the voltage-dependence of the steady-state inactivation of Kv4.2 channels without apparent effect on the V1/2 of the voltage-dependent activation. The blocking effect of AG879 was enhanced as channel inactivation increased. Furthermore, AG879 significantly inhibited the A-type potassium currents in the cultured hippocampus neurons. Conclusion and Implications AG879 was identified as a selective and potent inhibitor the Kv4.2 channel. AG879 inhibited Kv4.2 channels by preferentially interacting with the open state and further accelerating their inactivation. PMID:25752739

Effect of tyrphostin AG879 on Kv 4.2 and Kv 4.3 potassium channels.

PubMed

Yu, Haibo; Zou, Beiyan; Wang, Xiaoliang; Li, Min

2015-07-01

A-type potassium channels (IA) are important proteins for modulating neuronal membrane excitability. The expression and activity of Kv 4.2 channels are critical for neurological functions and pharmacological inhibitors of Kv 4.2 channels may have therapeutic potential for Fragile X syndrome. While screening various compounds, we identified tyrphostin AG879, a tyrosine kinase inhibitor, as a Kv 4.2 inhibitor from. In the present study we characterized the effect of AG879 on cloned Kv 4.2/Kv channel-interacting protein 2 (KChIP2) channels. To screen the library of pharmacologically active compounds, the thallium flux assay was performed on HEK-293 cells transiently-transfected with Kv 4.2 cDNA using the Maxcyte transfection system. The effects of AG879 were further examined on CHO-K1 cells expressing Kv 4.2/KChIP2 channels using a whole-cell patch-clamp technique. Tyrphostin AG879 selectively and dose-dependently inhibited Kv 4.2 and Kv 4.3 channels. In Kv 4.2/KChIP2 channels, AG879 induced prominent acceleration of the inactivation rate, use-dependent block and slowed the recovery from inactivation. AG879 induced a hyperpolarizing shift in the voltage-dependence of the steady-state inactivation of Kv 4.2 channels without apparent effect on the V1/2 of the voltage-dependent activation. The blocking effect of AG879 was enhanced as channel inactivation increased. Furthermore, AG879 significantly inhibited the A-type potassium currents in the cultured hippocampus neurons. AG879 was identified as a selective and potent inhibitor the Kv 4.2 channel. AG879 inhibited Kv 4.2 channels by preferentially interacting with the open state and further accelerating their inactivation. © 2015 The British Pharmacological Society.

Graphene nanoribbon field-effect transistors fabricated by etchant-free transfer from Au(788)

NASA Astrophysics Data System (ADS)

Ohtomo, Manabu; Sekine, Yoshiaki; Hibino, Hiroki; Yamamoto, Hideki

2018-01-01

We report etching-free and iodine-free transfer of highly aligned array of armchair-edge graphene nanoribbons (ACGNRs) and their field-effect transistor (FET) characteristics. They were prepared by on-surface polymerization on Au(788) templates. The ACGNRs were mechanically delaminated and transferred onto insulating substrates with the aid of a nano-porous support layer composed of hydrogen silsesquioxane (HSQ). The key process in the mechanical delamination is the intercalation of octanethiol self-assembled monolayers (SAMs), which penetrate the HSQ layer and intercalate between the ACGNRs and Au(788). After the transfer, the octanethiol SAMs were removed with Piranha solution, enabling the reuse of the Au single crystals. The FETs fabricated with the transferred ACGNR array showed ambipolar behavior when the channel length was as long as 60 nm. Quasi-one-dimensional conductivity was observed, which implies a good alignment of GNRs after the transfer. In contrast, short-channel ACGNR FETs (channel length ˜20 nm) suffer from a geometry-dependent short-channel effect. This effect is more severe in the FETs with ACGNRs parallel to the channel, which is an ideal geometry, than in ones perpendicular to the channel. Since the ID-VD curve is well fitted by the power-law model, the short-channel effect likely stems from the space-charge limited current effect, while the wide charge-transfer region in the GNR channel can be another possible cause for the short-channel effect. These results provide us with important insights into the designing short-channel GNR-FETs with improved performance.

Study on effective MOSFET channel length extracted from gate capacitance

NASA Astrophysics Data System (ADS)

Tsuji, Katsuhiro; Terada, Kazuo; Fujisaka, Hisato

2018-01-01

The effective channel length (L GCM) of metal-oxide-semiconductor field-effect transistors (MOSFETs) is extracted from the gate capacitances of actual-size MOSFETs, which are measured by charge-injection-induced-error-free charge-based capacitance measurement (CIEF CBCM). To accurately evaluate the capacitances between the gate and the channel of test MOSFETs, the parasitic capacitances are removed by using test MOSFETs having various channel sizes and a source/drain reference device. A strong linear relationship between the gate-channel capacitance and the design channel length is obtained, from which L GCM is extracted. It is found that L GCM is slightly less than the effective channel length (L CRM) extracted from the measured MOSFET drain current. The reason for this is discussed, and it is found that the capacitance between the gate electrode and the source and drain regions affects this extraction.

Effect of protein tyrosine kinase inhibitors on the current through the Ca(V)3.1 channel.

PubMed

Kurejová, Martina; Lacinová, L'ubica

2006-02-01

In the present study, we have investigated the effects of protein tyrosine kinase (PTK) inhibitors on the Ca(V)3.1 calcium channel stably transfected in HEK293 cells using the whole-cell configuration of the patch-clamp technique. We have tested two different tyrosine kinase inhibitors, genistein and tyrphostin AG213, and their inactive analogs, genistin and tyrphostin AG9. Bath application of genistein, but not genistin, decreased the T-type calcium current amplitude in a concentration-dependent manner with an IC(50) of 24.7+/-2.0 microM. This effect of genistein was accompanied by deceleration of channel activation and acceleration of channel inactivation. Intracellular application of neither genistein nor genistin had a significant effect on the calcium current. Extracellular application of 50 microM tyrphostin AG213 and its inactive analogue, tyrphostin AG9, did not affect the current through the Ca(V)3.1 channel. The effect of genistein on the channel was also not affected by the presence of catalytically active PTK, p60(c-src) inside the cell. We have concluded that genistein directly inhibited the channel. This mechanism does not involve a PTK-dependent pathway. The alteration of the channel kinetics by genistein suggests an interaction with the voltage sensor of the channel together with the channel pore occlusion.

Comparison between the effects of positive noncatastrophic HMB ESD stress in n-channel and p-channel power MOSFET's

NASA Astrophysics Data System (ADS)

Zupac, Dragan; Kosier, Steven L.; Schrimpf, Ronald D.; Galloway, Kenneth F.; Baum, Keith W.

1991-10-01

The effect of noncatastrophic positive human body model (HBM) electrostatic discharge (ESD) stress on n-channel power MOSFETs is radically different from that on p-channel MOSFETs. In n-channel transistors, the stress causes negative shifts of the current-voltage characteristics indicative of positive charge trapping in the gate oxide. In p-channel transistors, the stress increases the drain-to-source leakage current, probably due to localized avalanche electron injection from the p-doped drain.

The effect of Channeling on in-home utilization and subsequent nursing home care: a simultaneous equation perspective.

PubMed Central

Rabiner, D J; Stearns, S C; Mutran, E

1994-01-01

OBJECTIVE. This study explored the relationship between participation in a home/community-based long-term care case management intervention (known as the Channeling demonstration), use of formal in-home care, and subsequent nursing home utilization. STUDY DESIGN. Structural analysis of the randomized Channeling intervention was conducted to decompose the total effects of Channeling on nursing home use into direct and indirect effects. DATA COLLECTION METHOD. Secondary data analysis of the National Long-Term Care Data Set. PRINCIPAL FINDINGS. The use of formal in-home care, which was increased by the Channeling intervention, was positively associated with nursing home utilization at 12 months. However, the negative direct effect of Channeling on nursing home use was of sufficient magnitude to offset this positive indirect effect, so that a small but significant negative total effect of Channeling on subsequent nursing home utilization was found. CONCLUSIONS. This study shows why Channeling did not have a large total impact on nursing home utilization. The analysis did not provide evidence of direct substitution of in-home care for nursing home care because the direct reductions in nursing home utilization due to other aspects of Channeling (including, but not limited to case management) were substantially offset by the indirect increases in nursing home utilization associated with additional home care use. PMID:8002352

Effects of Na(+) and K(+) channel blockade on vulnerability to and termination of fibrillation in simulated normal cardiac tissue.

PubMed

Qu, Zhilin; Weiss, James N

2005-10-01

Na(+) and K(+) channel-blocking drugs have anti- and proarrhythmic effects. Their effects during fibrillation, however, remain poorly understood. We used computer simulation of a two-dimensional (2-D) structurally normal tissue model with phase I of the Luo-Rudy action potential model to study the effects of Na(+) and K(+) channel blockade on vulnerability to and termination of reentry in simulated multiple-wavelet and mother rotor fibrillation. Our main findings are as follows: 1) Na(+) channel blockade decreased, whereas K(+) channel blockade increased, the vulnerable window of reentry in heterogeneous 2-D tissue because of opposing effects on dynamical wave instability. 2) Na(+) channel blockade increased the cycle length of reentry more than it increased refractoriness. In multiple-wavelet fibrillation, Na(+) channel blockade first increased and then decreased the average duration or transient time () of fibrillation. In mother rotor fibrillation, Na(+) channel blockade caused peripheral fibrillatory conduction block to resolve and the mother rotor to drift, leading to self-termination or sustained tachycardia. 3) K(+) channel blockade increased dynamical instability by steepening action potential duration restitution. In multiple-wavelet fibrillation, this effect shortened because of enhanced wave instability. In mother rotor fibrillation, this effect converted mother rotor fibrillation to multiple-wavelet fibrillation, which then could self-terminate. Our findings help illuminate, from a theoretical perspective, the possible underlying mechanisms of termination of different types of fibrillation by antiarrhythmic drugs.

An electrostatic potassium channel opener targeting the final voltage sensor transition

PubMed Central

Börjesson, Sara I.

2011-01-01

Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability. PMID:21624947

Brownian motion and thermophoresis effects on Peristaltic slip flow of a MHD nanofluid in a symmetric/asymmetric channel

NASA Astrophysics Data System (ADS)

Sucharitha, G.; Sreenadh, S.; Lakshminarayana, P.; Sushma, K.

2017-11-01

The slip and heat transfer effects on MHD peristaltic transport of a nanofluid in a non-uniform symmetric/asymmetric channel have studied under the assumptions of elongated wave length and negligible Reynolds number. From the simplified governing equations, the closed form solutions for velocity, stream function, temperature and concentrations are obtained. Also dual solutions are discussed for symmetric and asymmetric channel cases. The effects of important physical parameters are explained graphically. The slip parameter decreases the fluid velocity in middle of the channel whereas it increases the velocity at the channel walls. Temperature and concentration are decreasing and increasing functions of radiation parameter respectively. Moreover, velocity, temperature and concentrations are high in symmetric channel when compared with asymmetric channel.

Minoxidil opens mitochondrial KATP channels and confers cardioprotection

PubMed Central

Sato, Toshiaki; Li, Yulong; Saito, Tomoaki; Nakaya, Haruaki

2003-01-01

ATP-sensitive potassium channel in the mitochondrial inner membrane (mitoKATP channel) rather than in the sarcolemma (sarcKATP channel) appears to play an important role in cardioprotection. We examined the effect of minoxidil, a potent antihypertensive agent and hair growth stimulator, on sarcKATP and mitoKATP channels in guinea-pig ventricular myocytes. Minoxidil activated a glybenclamide-sensitive sarcKATP channel current in the whole-cell recording mode with an EC50 of 182.6 μM. Minoxidil reversibly increased the flavoprotein oxidation, an index of mitoKATP channel activity, in a concentration-dependent manner. The EC50 for mitoKATP channel activation was estimated to be 7.3 μM; this value was notably ≈25-fold lower than that for sarcKATP channel activation. Minoxidil (10 μM) significantly attenuated the ouabain-induced increase of mitochondrial Ca2+ concentration, which was measured by loading cells with rhod-2 fluorescence. Furthermore, pretreatment with minoxidil (10 μM) before 20-min no-flow ischaemia significantly improved the recovery of developed tension measured after 60 min of reperfusion in coronary perfused guinea-pig ventricular muscles. These cardioprotective effects of minoxidil were completely abolished by the mitoKATP channel blocker 5-hydroxydecanoate (500 μM). Our results indicate that minoxidil exerts a direct cardioprotective effect on heart muscle cells, an effect mediated by the selective activation of mitoKATP channels. PMID:14691056

Minoxidil opens mitochondrial K(ATP) channels and confers cardioprotection.

PubMed

Sato, Toshiaki; Li, Yulong; Saito, Tomoaki; Nakaya, Haruaki

2004-01-01

1. ATP-sensitive potassium channel in the mitochondrial inner membrane (mitoK(ATP) channel) rather than in the sarcolemma (sarcK(ATP) channel) appears to play an important role in cardioprotection. We examined the effect of minoxidil, a potent antihypertensive agent and hair growth stimulator, on sarcK(ATP) and mitoK(ATP) channels in guinea-pig ventricular myocytes. 2. Minoxidil activated a glybenclamide-sensitive sarcK(ATP) channel current in the whole-cell recording mode with an EC(50) of 182.6 microm. Minoxidil reversibly increased the flavoprotein oxidation, an index of mitoK(ATP) channel activity, in a concentration-dependent manner. The EC(50) for mitoK(ATP) channel activation was estimated to be 7.3 microm; this value was notably approximately 25-fold lower than that for sarcK(ATP) channel activation. 3. Minoxidil (10 microm) significantly attenuated the ouabain-induced increase of mitochondrial Ca(2+) concentration, which was measured by loading cells with rhod-2 fluorescence. Furthermore, pretreatment with minoxidil (10 microm) before 20-min no-flow ischaemia significantly improved the recovery of developed tension measured after 60 min of reperfusion in coronary perfused guinea-pig ventricular muscles. These cardioprotective effects of minoxidil were completely abolished by the mitoK(ATP) channel blocker 5-hydroxydecanoate (500 microm). 4. Our results indicate that minoxidil exerts a direct cardioprotective effect on heart muscle cells, an effect mediated by the selective activation of mitoK(ATP) channels.

Loperamide: A positive modulator for store-operated calcium channels?

PubMed Central

Harper, Jacquie L.; Shin, Yangmee; Daly, John W.

1997-01-01

The depletion of inositol trisphosphate-sensitive intracellular pools of calcium causes activation of store-operated calcium (SOC) channels. Loperamide at 10–30 μM has no effect on intracellular calcium levels alone, but augments calcium levels in cultured cells when SOC channels have been activated. In HL-60 leukemic cells, the apparent positive modulatory effect of loperamide on SOC channels occurs when these channels have been activated after ATP, thapsigargin, or ionomycin-elicited depletion of calcium from intracellular storage sites. Loperamide has no effect when levels of intracellular calcium are elevated through a mechanism not involving SOC channels by using sphingosine. Loperamide caused augmentation of intracellular calcium levels after activation of SOC channels in NIH 3T3 fibroblasts, astrocytoma 1321N cells, smooth muscle DDT-MF2 cells, RBL-2H3 mast cells, and pituitary GH4C1 cells. Only in astrocytoma cells did loperamide cause an elevation in intracellular calcium in the absence of activation of SOC channels. The augmentation of intracellular calcium elicited by loperamide in cultured cells was dependent on extracellular calcium and was somewhat resistant to agents (SKF 96365, miconazole, clotrimazole, nitrendipine, and trifluoperazine) that in the absence of loperamide effectively blocked SOC channels. It appears that loperamide augments influx of calcium through activated SOC channels. PMID:9405713

Slow and fast visual motion channels have independent binocular-rivalry stages.

PubMed Central

van de Grind, W. A.; van Hof, P.; van der Smagt, M. J.; Verstraten, F. A.

2001-01-01

We have previously reported a transparent motion after-effect indicating that the human visual system comprises separate slow and fast motion channels. Here, we report that the presentation of a fast motion in one eye and a slow motion in the other eye does not result in binocular rivalry but in a clear percept of transparent motion. We call this new visual phenomenon 'dichoptic motion transparency' (DMT). So far only the DMT phenomenon and the two motion after-effects (the 'classical' motion after-effect, seen after motion adaptation on a static test pattern, and the dynamic motion after-effect, seen on a dynamic-noise test pattern) appear to isolate the channels completely. The speed ranges of the slow and fast channels overlap strongly and are observer dependent. A model is presented that links after-effect durations of an observer to the probability of rivalry or DMT as a function of dichoptic velocity combinations. Model results support the assumption of two highly independent channels showing only within-channel rivalry, and no rivalry or after-effect interactions between the channels. The finding of two independent motion vision channels, each with a separate rivalry stage and a private line to conscious perception, might be helpful in visualizing or analysing pathways to consciousness. PMID:11270442

Suppressive effects of diltiazem and verapamil on delayed rectifier K(+)-channel currents in murine thymocytes.

PubMed

Baba, Asuka; Tachi, Masahiro; Maruyama, Yoshio; Kazama, Itsuro

2015-10-01

Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes, and these channels play crucial roles in the lymphocyte activation and proliferation. Since diltiazem and verapamil, which are highly lipophilic Ca(2+) channel blockers (CCBs), exert relatively stronger immunomodulatory effects than the other types of CCBs, they would affect the Kv1.3-channel currents in lymphocytes. Employing the standard patch-clamp whole-cell recording technique in murine thymocytes, we examined the effects of these drugs on the channel currents and the membrane capacitance. Both diltiazem and verapamil significantly suppressed the peak and the pulse-end currents of the channels, although the effects of verapamil were more marked than those of diltiazem. Both drugs significantly lowered the membrane capacitance, indicating the interactions between the drugs and the plasma membranes. This study demonstrated for the first time that CCBs, such as diltiazem and verapamil, exert inhibitory effects on Kv1.3-channels expressed in lymphocytes. The effects of these drugs may be associated with the mechanisms of immunomodulation by which they decrease the production of inflammatory cytokines. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Witnessing effective entanglement over a 2 km fiber channel.

PubMed

Wittmann, Christoffer; Fürst, Josef; Wiechers, Carlos; Elser, Dominique; Häseler, Hauke; Lütkenhaus, Norbert; Leuchs, Gerd

2010-03-01

We present a fiber-based continuous-variable quantum key distribution system. In the scheme, a quantum signal of two non-orthogonal weak optical coherent states is sent through a fiber-based quantum channel. The receiver simultaneously measures conjugate quadratures of the light using two homodyne detectors. From the measured Q-function of the transmitted signal, we estimate the attenuation and the excess noise caused by the channel. The estimated excess noise originating from the channel and the channel attenuation including the quantum efficiency of the detection setup is investigated with respect to the detection of effective entanglement. The local oscillator is considered in the verification. We witness effective entanglement with a channel length of up to 2 km.

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effects of gabapentin in mouse forced swimming test.

PubMed

Ostadhadi, Sattar; Akbarian, Reyhaneh; Norouzi-Javidan, Abbas; Nikoui, Vahid; Zolfaghari, Samira; Chamanara, Mohsen; Dehpour, Ahmad-Reza

2017-07-01

Gabapentin as an anticonvulsant drug also has beneficial effects in treatment of depression. Previously, we showed that acute administration of gabapentin produced an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism that involves the inhibition of nitric oxide (NO). Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of gabapentin. Gabapentin at different doses (5-10 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal route, 60 and 30 min, respectively, before the test. To clarify the probable involvement of K ATP channels, mice were pretreated with K ATP channel inhibitor or opener. Gabapentin at dose 10 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). Co-administration of subeffective dose (1 mg/kg) of glibenclamide (inhibitor of K ATP channels) with gabapentin (3 mg/kg) showed a synergistic antidepressant-like effect. Also, subeffective dose of cromakalim (opener of K ATP channels, 0.1 mg/kg) inhibited the antidepressant-like effect of gabapentin (10 mg/kg). None of the treatments had any impact on the locomotor movement. Our study, for the first time, revealed that antidepressant-like effect of gabapentin in mice is mediated by blocking the K ATP channels.

Large fraction of crystal directions leads to ion channeling

NASA Astrophysics Data System (ADS)

Nordlund, K.; Djurabekova, F.; Hobler, G.

2016-12-01

It is well established that when energetic ions are moving in crystals, they may penetrate much deeper if they happen to be directed in some specific crystal directions. This `channeling' effect is utilized for instance in certain ion beam analysis methods and has been described by analytical theories and atomistic computer simulations. However, there have been very few systematic studies of channeling in directions other than the principal low-index ones. We present here a molecular dynamics-based approach to calculate ion channeling systematically over all crystal directions, providing ion `channeling maps' that easily show in which directions channeling is expected. The results show that channeling effects can be quite significant even at energies below 1 keV, and that in many cases, significant planar channeling occurs also in a wide range of crystal directions between the low-index principal ones. In all of the cases studied, a large fraction (˜20 -60 % ) of all crystal directions show channeling. A practical implication of this is that modern experiments on randomly oriented nanostructures will have a large probability of channeling. It also means that when ion irradiations are carried out on polycrystalline samples, channeling effects on the results cannot a priori be assumed to be negligible. The maps allow for easy selection of good `nonchanneling' directions in experiments or alternatively finding wide channels for beneficial uses of channeling. We implement channeling theory to also give the fraction of channeling directions in a manner directly comparable to the simulations. The comparison shows good qualitative agreement. In particular, channeling theory is very good at predicting which channels are active at a given energy. This is true down to sub-keV energies, provided the penetration depth is not too small.

Electromagnetic fields (UHF) increase voltage sensitivity of membrane ion channels; possible indication of cell phone effect on living cells.

PubMed

Ketabi, N; Mobasheri, H; Faraji-Dana, R

2015-03-01

The effects of ultra high frequency (UHF) nonionizing electromagnetic fields (EMF) on the channel activities of nanopore forming protein, OmpF porin, were investigated. The voltage clamp technique was used to study the single channel activity of the pore in an artificial bilayer in the presence and absence of the electromagnetic fields at 910 to 990 MHz in real time. Channel activity patterns were used to address the effect of EMF on the dynamic, arrangement and dielectric properties of water molecules, as well as on the hydration state and arrangements of side chains lining the channel barrel. Based on the varied voltage sensitivity of the channel at different temperatures in the presence and absence of EMF, the amount of energy transferred to nano-environments of accessible groups was estimated to address the possible thermal effects of EMF. Our results show that the effects of EMF on channel activities are frequency dependent, with a maximum effect at 930 MHz. The frequency of channel gating and the voltage sensitivity is increased when the channel is exposed to EMF, while its conductance remains unchanged at all frequencies applied. We have not identified any changes in the capacitance and permeability of membrane in the presence of EMF. The effect of the EMF irradiated by cell phones is measured by Specific Absorption Rate (SAR) in artificial model of human head, Phantom. Thus, current approach applied to biological molecules and electrolytes might be considered as complement to evaluate safety of irradiating sources on biological matter at molecular level.

Sediment sorting at a side channel bifurcation

NASA Astrophysics Data System (ADS)

van Denderen, Pepijn; Schielen, Ralph; Hulscher, Suzanne

2017-04-01

Side channels have been constructed to reduce the flood risk and to increase the ecological value of the river. In various Dutch side channels large aggradation in these channels occurred after construction. Measurements show that the grain size of the deposited sediment in the side channel is smaller than the grain size found on the bed of the main channel. This suggest that sorting occurs at the bifurcation of the side channel. The objective is to reproduce with a 2D morphological model the fining of the bed in the side channel and to study the effect of the sediment sorting on morphodynamic development of the side channel. We use a 2D Delft3D model with two sediment fractions. The first fraction corresponds with the grain size that can be found on the bed of the main channel and the second fraction corresponds with the grain size found in the side channel. With the numerical model we compute several side channel configurations in which we vary the length and the width of the side channel, and the curvature of the upstream channel. From these computations we can derive the equilibrium state and the time scale of the morphodynamic development of the side channel. Preliminary results show that even when a simple sediment transport relation is used, like Engelund & Hansen, more fine sediment enters the side channel than coarse sediment. This is as expected, and is probably related to the bed slope effects which are a function of the Shields parameter. It is expected that by adding a sill at the entrance of the side channel the slope effect increases. This might reduce the amount of coarse sediment which enters the side channel even more. It is unclear whether the model used is able to reproduce the effect of such a sill correctly as modelling a sill and reproducing the correct hydrodynamic and morphodynamic behaviour is not straightforward in a 2D model. Acknowledgements: This research is funded by STW, part of the Dutch Organization for Scientific Research under grant number P12-P14 (RiverCare Perspective Programme) project number 13516.

BAD and KATP channels regulate neuron excitability and epileptiform activity

PubMed Central

Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L

2018-01-01

Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad (BCL-2 agonist of cell death) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (KATP) channels. Here we investigated the effect of BAD manipulation on KATP channel activity and excitability in acute brain slices. We found that BAD’s influence on neuronal KATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal KATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of KATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a ‘dentate gate’ function that is reinforced by increased KATP channel activity. PMID:29368690

Investigation of InP/InGaAs metamorphic co-integrated complementary doping-channel field-effect transistors for logic application

NASA Astrophysics Data System (ADS)

Tsai, Jung-Hui

2014-01-01

DC performance of InP/InGaAs metamorphic co-integrated complementary doping-channel field-effect transistors (DCFETs) grown on a low-cost GaAs substrate is first demonstrated. In the complementary DCFETs, the n-channel device was fabricated on the InxGa1-xP metamorphic linearly graded buffer layer and the p-channel field-effect transistor was stacked on the top of the n-channel device. Particularly, the saturation voltage of the n-channel device is substantially reduced to decrease the VOL and VIH values attributed that two-dimensional electron gas is formed and could be modulated in the n-InGaAs channel. Experimentally, a maximum extrinsic transconductance of 215 (17) mS/mm and a maximum saturation current density of 43 (-27) mA/mm are obtained in the n-channel (p-channel) device. Furthermore, the noise margins NMH and NML are up to 0.842 and 0.330 V at a supply voltage of 1.5 V in the complementary logic inverter application.

Modulation of the olfactory CNG channel by Ptdlns(3,4,5)P3.

PubMed

Zhainazarov, A B; Spehr, M; Wetzel, C H; Hatt, H; Ache, B W

2004-09-01

Recent data suggest that the 3-phosphoinositides can modulate cyclic nucleotide signaling in rat olfactory receptor neurons (ORNs). Given the ability of diverse lipids to modulate ion channels, we asked whether phosphatidylinositol 3,4,5-trisphosphate (PIP3) can regulate the olfactory cyclic nucleotide-gated (CNG) channel as a possible mechanism for this modulation. We show that applying PIP3 to the intracellular side of inside-out patches from rat ORNs inhibits activation of the olfactory CNG channel by cAMP. The effect of PIP3 is immediate and partially reversible, and reflects an increase in the EC50 of cAMP, not a reduction in the single-channel current amplitude. The effect of PIP3 is significantly stronger than that of PIP2; other phospholipids tested have no appreciable effect on channel activity. PIP3 similarly inhibits the recombinant heteromeric (A2/A4) and homomeric (A2) olfactory CNG channel expressed in HEK293 cells, suggesting that PIP3 acts directly on the channel. These findings indicate that 3-phosphoinositides can be functionally important regulators of CNG channels.

Effect of stochastic gating on channel-facilitated transport of non-interacting and strongly repelling solutes.

PubMed

Berezhkovskii, Alexander M; Bezrukov, Sergey M

2017-08-28

Ligand- or voltage-driven stochastic gating-the structural rearrangements by which the channel switches between its open and closed states-is a fundamental property of biological membrane channels. Gating underlies the channel's ability to respond to different stimuli and, therefore, to be functionally regulated by the changing environment. The accepted understanding of the gating effect on the solute flux through the channel is that the mean flux is the product of the flux through the open channel and the probability of finding the channel in the open state. Here, using a diffusion model of channel-facilitated transport, we show that this is true only when the gating is much slower than the dynamics of solute translocation through the channel. If this condition breaks, the mean flux could differ from this simple estimate by orders of magnitude.

Effect of stochastic gating on channel-facilitated transport of non-interacting and strongly repelling solutes

NASA Astrophysics Data System (ADS)

Berezhkovskii, Alexander M.; Bezrukov, Sergey M.

2017-08-01

Ligand- or voltage-driven stochastic gating—the structural rearrangements by which the channel switches between its open and closed states—is a fundamental property of biological membrane channels. Gating underlies the channel's ability to respond to different stimuli and, therefore, to be functionally regulated by the changing environment. The accepted understanding of the gating effect on the solute flux through the channel is that the mean flux is the product of the flux through the open channel and the probability of finding the channel in the open state. Here, using a diffusion model of channel-facilitated transport, we show that this is true only when the gating is much slower than the dynamics of solute translocation through the channel. If this condition breaks, the mean flux could differ from this simple estimate by orders of magnitude.

Channel morphology effect on water transport through graphene bilayers.

PubMed

Liu, Bo; Wu, Renbing; Law, Adrian Wing-Keung; Feng, Xi-Qiao; Bai, Lichun; Zhou, Kun

2016-12-08

The application of few-layered graphene-derived functional thin films for molecular filtration and separation has recently attracted intensive interests. In practice, the morphology of the nanochannel formed by the graphene (GE) layers is not ideally flat and can be affected by various factors. This work investigates the effect of channel morphology on the water transport behaviors through the GE bilayers via molecular dynamics simulations. The simulation results show that the water flow velocity and transport resistance highly depend on the curvature of the graphene layers, particularly when they are curved in non-synergic patterns. To understand the channel morphology effect, the distributions of water density, dipole moment orientation and hydrogen bonds inside the channel are investigated, and the potential energy surface with different distances to the basal GE layer is analyzed. It shows that the channel morphology significantly changes the distribution of the water molecules and their orientation and interaction inside the channel. The energy barrier for water molecules transport through the channel also significantly depends on the channel morphology.

Channel morphology effect on water transport through graphene bilayers

PubMed Central

Liu, Bo; Wu, Renbing; Law, Adrian Wing-Keung; Feng, Xi-Qiao; Bai, Lichun; Zhou, Kun

2016-01-01

The application of few-layered graphene-derived functional thin films for molecular filtration and separation has recently attracted intensive interests. In practice, the morphology of the nanochannel formed by the graphene (GE) layers is not ideally flat and can be affected by various factors. This work investigates the effect of channel morphology on the water transport behaviors through the GE bilayers via molecular dynamics simulations. The simulation results show that the water flow velocity and transport resistance highly depend on the curvature of the graphene layers, particularly when they are curved in non-synergic patterns. To understand the channel morphology effect, the distributions of water density, dipole moment orientation and hydrogen bonds inside the channel are investigated, and the potential energy surface with different distances to the basal GE layer is analyzed. It shows that the channel morphology significantly changes the distribution of the water molecules and their orientation and interaction inside the channel. The energy barrier for water molecules transport through the channel also significantly depends on the channel morphology. PMID:27929106

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor.

PubMed

Bannister, Mark L; Alvarez-Laviada, Anita; Thomas, N Lowri; Mason, Sammy A; Coleman, Sharon; du Plessis, Christo L; Moran, Abbygail T; Neill-Hall, David; Osman, Hasnah; Bagley, Mark C; MacLeod, Kenneth T; George, Christopher H; Williams, Alan J

2016-08-01

Flecainide is a use-dependent blocker of cardiac Na(+) channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na(+) channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca(2) (+) -release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na(+) and/or RyR2 channels. We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca(2) (+) sparks in intact adult rat cardiac myocytes. Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca(2) (+) spark frequency. Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca(2) (+) sparks is likely, by analogy with flecainide, to result from Na(+) channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na(+) and RyR2 channels. © 2016 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Comparative effects of sodium channel blockers in short term rat whole embryo culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se; Sköld, Anna-Carin; Ericson, Ann-Christin

2013-10-15

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effectmore » on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.« less

Load-adaptive practical multi-channel communications in wireless sensor networks.

PubMed

Islam, Md Shariful; Alam, Muhammad Mahbub; Hong, Choong Seon; Lee, Sungwon

2010-01-01

In recent years, a significant number of sensor node prototypes have been designed that provide communications in multiple channels. This multi-channel feature can be effectively exploited to increase the overall capacity and performance of wireless sensor networks (WSNs). In this paper, we present a multi-channel communications system for WSNs that is referred to as load-adaptive practical multi-channel communications (LPMC). LPMC estimates the active load of a channel at the sink since it has a more comprehensive view of the network behavior, and dynamically adds or removes channels based on the estimated load. LPMC updates the routing path to balance the loads of the channels. The nodes in a path use the same channel; therefore, they do not need to switch channels to receive or forward packets. LPMC has been evaluated through extensive simulations, and the results demonstrate that it can effectively increase the delivery ratio, network throughput, and channel utilization, and that it can decrease the end-to-end delay and energy consumption.

Fading channel simulator

DOEpatents

Argo, Paul E.; Fitzgerald, T. Joseph

1993-01-01

Fading channel effects on a transmitted communication signal are simulated with both frequency and time variations using a channel scattering function to affect the transmitted signal. A conventional channel scattering function is converted to a series of channel realizations by multiplying the square root of the channel scattering function by a complex number of which the real and imaginary parts are each independent variables. The two-dimensional inverse-FFT of this complex-valued channel realization yields a matrix of channel coefficients that provide a complete frequency-time description of the channel. The transmitted radio signal is segmented to provide a series of transmitted signal and each segment is subject to FFT to generate a series of signal coefficient matrices. The channel coefficient matrices and signal coefficient matrices are then multiplied and subjected to inverse-FFT to output a signal representing the received affected radio signal. A variety of channel scattering functions can be used to characterize the response of a transmitter-receiver system to such atmospheric effects.

Numerical Study on the Effects of Gravity and Surface Tension on Condensation Process in Square Minichannel

NASA Astrophysics Data System (ADS)

Li, Panpan; Chen, Zhenqian; Shi, Juan

2018-02-01

A volume of fluid (VOF) method is adopted to simulate the condensation of R134a in a horizontal single square minichannel with 1 mm side length. The effect of gravity, surface tension and gas-liquid interfacial shear stress are taken into account. The result denotes that condensation is first appeared at the corner of channel, and then the condensation is stretched at the effect of surface tension until the whole channel boundary covered. The effect of gravity on the distribution of the liquid film depends on the channel length. In short channel, the gravity shows no significant effect, the distribution shape of steam in the cross section of the channel is approximately circular. In long channel, due to the influence of gravity, the liquid converges at the bottom under the effect of gravity, and the thickness of the liquid film at the bottom is obviously higher than that of the upper part of the channel. The effect of surface tension on condensation is also analysed. The surface tension can enhance the condensation heat transfer significantly when the inlet mass flux is low. Whilst, at high mass flux, the enhancement of surface tension on heat transfer is unobvious and can be neglected.

Ca2+ channel blockers interact with alpha 2-adrenergic receptors in rabbit ileum.

PubMed

Homaidan, F R; Donowitz, M; Wicks, J; Cusolito, S; el Sabban, M E; Weiland, G A; Sharp, W G

1988-04-01

An interaction between Ca2+ channel blockers and alpha 2-adrenergic receptors has been demonstrated in rabbit ileum by studying the effect of clonidine on active electrolyte transport, under short-circuited conditions, in the presence and absence of several Ca2+ channel blocking agents. Clonidine, verapamil, diltiazem, cadmium, and nitrendipine all decrease short-circuit current and stimulate NaCl absorption to different extents with clonidine having the largest effect. Exposure to verapamil, diltiazem, and cadmium inhibited the effects of clonidine on transport, whereas nitrendipine had no such effect. Verapamil, diltiazem, and cadmium, but not nitrendipine, also decreased the specific binding of [3H]alpha 2-adrenergic agents to a preparation of ileal basolateral membranes explaining the observed decrease in the transport effects of clonidine. The effective concentrations of the Ca2+ channel blockers that inhibited the effects of clonidine on transport were fairly similar to the concentrations needed to inhibit its specific binding. The displacement of clonidine by calcium channel blockers is ascribed to a nonspecific effect of these agents, although the possibility that their effects are exerted via their binding to the calcium channels is not excluded.

Inhibitory effects of magnolol on voltage-gated Na+ and K+ channels of NG108-15 cells.

PubMed

Gong, Chi-Li; Wong, Kar-Lok; Cheng, Ka-Shun; Kuo, Chang-Shin; Chao, Chia-Chia; Tsai, Min-Fan; Leung, Yuk-Man

2012-05-05

Magnolol, a polyphenolic compound isolated from Houpu, a Chinese herb from the bark of Magnolia officinalis, has been reported to have in vitro and in vivo neuroprotective effects. In spite of these reported beneficial effects, studies on the direct impact of magnolol on neuronal ion channels have been scarce. Whether magnolol affects voltage-gated Na(+) channels (VGSC) and voltage-gated K(+) (Kv) channels is unknown. Using the whole-cell voltage-clamp method, we studied the effects of magnolol on voltage-gated ion channels in neuronal NG108-15 cells. Magnolol inhibited VGSC channels with mild state-dependence (IC(50) of 15 and 30 μM, at holding potentials of -70 and -100 mV, respectively). No frequency-dependence was observed in magnolol block. Magnolol caused a left-shift of 18 mV in the steady-state inactivation curve but did not affect the voltage-dependence of activation. Magnolol inhibited Kv channels with an IC(50) of 21 μM, and it caused a 20-mV left-shift in the steady-state inactivation curve without affecting the voltage-dependence of activation. In conclusion, magnolol is an inhibitor of both VGSC and Kv channels and these inhibitory effects may in part contribute to some of the reported neuroprotective effects of magnolol. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons.

PubMed

Bravo-Martínez, Jorge; Arenas, Isabel; Vivas, Oscar; Rebolledo-Antúnez, Santiago; Vázquez-García, Mario; Larrazolo, Arturo; García, David E

2012-10-01

No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

Linear stability analysis and nonlinear simulation of the channeling effect on viscous fingering instability in miscible displacement

NASA Astrophysics Data System (ADS)

Shahnazari, M. R.; Maleka Ashtiani, I.; Saberi, A.

2018-03-01

In this paper, the effect of channeling on viscous fingering instability of miscible displacement in porous media is studied. In fact, channeling is introduced as a solution to stabilize the viscous fingering instability. In this solution, narrow channels were placed next to the walls, and by considering an exponential function to model the channeling effect, a heterogeneous media is assumed. In linear stability analysis, the governing equations are transferred to Fourier space, and by introducing a novel numerical method, the transferred equations are analyzed. The growth rate based on the wave number diagram has been drawn up in three sections of the medium. It is found that the flow becomes more stable at the center and unstable along the walls when the permeability ratio is increased. Also when the permeability ratio is approximately equal to one, the channeling has no significant effect. In nonlinear simulations, by using stream function and vortices, new equations have been rewritten and it is shown that channeling has a profound effect on the growth of the fingers and mechanisms. In addition to the superposition of velocity vectors and concentration contours, the development of instability is investigated using the mixing length and sweep efficiency diagram. The results show that although channeling reduces instability, it increases the displacement process time.

Using 15-minute acoustic data to analyze suspended-sediment dynamics in the Rio Grande in the Big Bend Region

USGS Publications Warehouse

Dean, David; Topping, David; Griffiths, Ronald; Sabol, Thomas; Schmidt, John C.; Bennett, Jeffery B.

2015-01-01

The Rio Grande in the Big Bend region is subject to rapid geomorphic change consisting of channel narrowing during years of low flow, and channel widening during rare, large, long duration floods. Since the 1940s, there have been large declines in mean and peak stream flow, and the channel has progressively narrowed. Large, channel widening floods are infrequent and have failed to widen the channel to widths measured prior to the onset of channel narrowing in the 1940s. Before the most recent channel-widening flood in September 2008, the Rio Grande in the Big Bend was more than 50 percent narrower than measured in the 1940s. Channel narrowing results in increased flood frequency and flood magnitude due to the loss of channel capacity and flood conveyance (Dean and Schmidt, 2011). Channel narrowing also results in the loss of important aquatic habitats such as backwaters and side-channels, because these habitats accumulate sediment and are converted to floodplains. Environmental managers are attempting to construct an environmental flow program for the purposes of minimizing channel narrowing during low flow years such that channel capacity, flood conveyance, and important aquatic habitats are maintained. Effective mitigation of channel narrowing processes requires an in-depth understanding of the predominant sediment source areas, the quantity of sediment input from those source areas, the parts of the flow regime responsible for the greatest sediment deposition, and the effect of managed flows in ameliorating the sediment loading that occurs within the channel. Here, we analyze data collected with acoustic instrumentation at high temporal resolution to quantify suspended-sediment transport during a variety of flood types. We also investigate the effect of long duration managed flows in promoting sediment export and minimizing channel narrowing.

Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse.

PubMed Central

Chen, W; Lee, R C

1994-01-01

The effects of large magnitude transmembrane potential pulses on voltage-gated Na and K channel behavior in frog skeletal muscle membrane were studied using a modified double vaseline-gap voltage clamp. The effects of electroconformational damage to ionic channels were separated from damage to lipid bilayer (electroporation). A 4 ms transmembrane potential pulse of -600 mV resulted in a reduction of both Na and K channel conductivities. The supraphysiologic pulses also reduced ionic selectivity of the K channels against Na+ ions, resulting in a depolarization of the membrane resting potential. However, TTX and TEA binding effects were unaltered. The kinetics of spontaneous reversal of the electroconformational damage of channel proteins was found to be dependent on the magnitude of imposed membrane potential pulse. These results suggest that muscle and nerve dysfunction after electrical shock may be in part caused by electroconformational damage to voltage-gated ion channels. PMID:7948676

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Effect of Channel Thickness, Annealing Temperature and Channel Length on Nanoscale Ga2O3-In2O3-ZnO Thin Film Transistor Performance.

PubMed

Kumaresan, Yogeenth; Pak, Yusin; Lim, Namsoo; Lee, Ryeri; Song, Hui; Kim, Tae Heon; Choi, Boran; Jung, Gun Young

2016-06-01

We demonstrated the effect of active layer (channel) thickness and annealing temperature on the electrical performances of Ga2O3-In2O3-ZnO (GIZO) thin film transistor (TFT) having nanoscale channel width (W/L: 500 nm/100 μm). We found that the electron carrier concentration of the channel was decreased significantly with increasing the annealing temperature (100 degrees C to 300 degrees C). Accordingly, the threshold voltage (V(T)) was shifted towards positive voltage (-12.2 V to 10.8 V). In case of channel thickness, the V(T) was shifted towards negative voltage with increasing the channel thickness. The device with channel thickness of 90 nm annealed at 200 degrees C revealed the best device performances in terms of mobility (10.86 cm2/Vs) and V(T) (0.8 V). The effect of channel length was also studied, in which the channel width, thickness and annealing temperature were kept constant such as 500 nm, 90 nm and 200 degrees C, respectively. The channel length influenced the on-current level significantly with small variation of V(T), resulting in lower value of on/off current ratio with increasing the channel length. The device with channel length of 0.5 μm showed enhanced on/off current ratio of 10(6) with minimum V(T) of 0.26 V.

Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine.

PubMed

Zhang, Fan; Cheng, Yanxin; Li, Hong; Jia, Qingzhong; Zhang, Hailin; Zhao, Senming

2015-01-01

Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures. A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons. Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential. Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents. © 2015 S. Karger AG, Basel.

State-dependent block of CNG channels by dequalinium.

PubMed

Rosenbaum, Tamara; Gordon-Shaag, Ariela; Islas, León D; Cooper, Jeremy; Munari, Mika; Gordon, Sharona E

2004-03-01

Cyclic nucleotide-gated (CNG) ion channels are nonselective cation channels with a high permeability for Ca(2+). Not surprisingly, they are blocked by a number of Ca(2+) channel blockers including tetracaine, pimozide, and diltiazem. We studied the effects of dequalinium, an extracellular blocker of the small conductance Ca(2+)-activated K(+) channel. We previously noted that dequalinium is a high-affinity blocker of CNGA1 channels from the intracellular side, with little or no state dependence at 0 mV. Here we examined block by dequalinium at a broad range of voltages in both CNGA1 and CNGA2 channels. We found that dequalinium block was mildly state dependent for both channels, with the affinity for closed channels 3-5 times higher than that for open channels. Mutations in the S4-S5 linker did not alter the affinity of open channels for dequalinium, but increased the affinity of closed channels by 10-20-fold. The state-specific effect of these mutations raises the question of whether/how the S4-S5 linker alters the binding of a blocker within the ion permeation pathway.

Online written consultation, telephone consultation and offline appointment: An examination of the channel effect in online health communities.

PubMed

Wu, Hong; Lu, Naiji

2017-11-01

The emergence of online health communities broadens and diversifies channels for patient-doctor interaction. Given limited medical resources, online health communities aim to provide better treatment by decreasing medical costs, making full use of available resources and providing more diverse channels for patients. This research examines how online channel usage affects offline channels, i.e., "Online Booking, Service in Hospitals" (OBSH), and how the channel effects change with doctors' online and offline reputation. The study uses data of 4254 doctors from a Chinese online health community. Our findings demonstrate a strong relationship between online health communities and offline hospital communication with an important moderating role for reputation. There are significant channel effects, wherein written consultation complements OBSH (β=3.320, p<0.10), but telephone consultation can be a readily substitute for OBSH (β=-9.854, p<0.001). We also find that doctors with higher online and offline reputations can attract more patients to use the OBSH (β online =0.433, p<0.001; β offline =2.318&2.123, p<0.001). Third, channel effects fluctuate, relative to doctors' online and offline reputations: doctors with higher online reputations mitigate substitution effects between telephone consultation and OBSH (β=0.064, p<0.01), and doctors with higher offline reputations mitigate complementary effects between written consultation and OBSH (β=-1.586&-1.417, p<0.001). This study contributes to both knowledge and practice. This study shows that there is channel effect in healthcare, websites' managers can encourage physicians to provide online services, especially for these physicians who do not have enough patients. Copyright © 2017 Elsevier B.V. All rights reserved.

THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

PubMed Central

Doheny, Helen C; O'Reilly, Michael J; Sexton, Donal J; Morrison, John J

2007-01-01

Background PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. Methods Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. Results Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. Conclusion These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31. PMID:17367527

A Combined Finite-Element/Discrete-Particle Analysis of a Side-Vent-Channel-Based Concept for Improved Blast-Survivability of Light Tactical Vehicles

DTIC Science & Technology

2013-01-01

design of side- vent-channels. The results obtained confirmed the beneficial effects of the side-vent-channels in reducing the blast momentum , although...confirmed the beneficial effects of the side-vent-channels in reducing the blast momentum , although the extent of these effects is relatively small (3...products against the surrounding medium is associated with exchange of linear momentum and various energy components (e.g. potential, thermal

Effect of matching between the magnetic field and channel length on the performance of low sputtering Hall thrusters

NASA Astrophysics Data System (ADS)

Ding, Yongjie; Boyang, Jia; Sun, Hezhi; Wei, Liqiu; Peng, Wuji; Li, Peng; Yu, Daren

2018-02-01

Discharge characteristics of a non-wall-loss Hall thruster were studied under different channel lengths using a design based on pushing a magnetic field through a double permanent magnet ring. The effect of different magnetic field intensities and channel lengths on ionization, efficiency, and plume divergence angle were studied. The experimental results show that propellant utilization is improved for optimal matching between the magnetic field and channel length. While matching the magnetic field and channel length, the ionization position of the neutral gas changes. The ion flow is effectively controlled, allowing the thrust force, specific impulse, and efficiency to be improved. Our study shows that the channel length is an important design parameter to consider for improving the performance of non-wall-loss Hall thrusters.

Three-player quantum Kolkata restaurant problem under decoherence

NASA Astrophysics Data System (ADS)

Ramzan, M.

2013-01-01

Effect of quantum decoherence in a three-player quantum Kolkata restaurant problem is investigated using tripartite entangled qutrit states. Different qutrit channels such as, amplitude damping, depolarizing, phase damping, trit-phase flip and phase flip channels are considered to analyze the behaviour of players payoffs. It is seen that Alice's payoff is heavily influenced by the amplitude damping channel as compared to the depolarizing and flipping channels. However, for higher level of decoherence, Alice's payoff is strongly affected by depolarizing noise. Whereas the behaviour of phase damping channel is symmetrical around 50% decoherence. It is also seen that for maximum decoherence ( p = 1), the influence of amplitude damping channel dominates over depolarizing and flipping channels. Whereas, phase damping channel has no effect on the Alice's payoff. Therefore, the problem becomes noiseless at maximum decoherence in case of phase damping channel. Furthermore, the Nash equilibrium of the problem does not change under decoherence.

Capacity of Pulse-Position Modulation (PPM) on Gaussian and Webb Channels

NASA Technical Reports Server (NTRS)

Dolinar, S.; Divsalar, D.; Hamkins, J.; Pollara, F.

2000-01-01

This article computes the capacity of various idealized soft-decision channels modeling an optical channel using an avalanche photodiode detector (APD) and pulse-position modulation (PPM). The capacity of this optical channel depends in a complicated way on the physical parameters of the APD and the constraints imposed by the PPM orthogonal signaling set. This article attempts to identify and separate the effects of several fundamental parameters on the capacity of the APD-detected optical PPM channel. First, an overall signal-to-noise ratio (SNR) parameter is de ned such that the capacity as a function of a bit-normalized version of this SNR drops precipitously toward zero at quasi-brick-wall limits on bit SNR that are numerically the same as the well-understood brick-wall limits for the standard additive white Gaussian noise (AWGN) channel. A second parameter is used to quantify the effects on capacity of one unique facet of the optical PPM channel (as compared with the standard AWGN channel) that causes the noise variance to be higher in signal slots than in nonsignal slots. This nonuniform noise variance yields interesting capacity effects even when the channel model is AWGN. A third parameter is used to measure the effects on capacity of the difference between an AWGN model and a non-Gaussian model proposed by Webb (see reference in [2]) for approximating the statistics of the APD-detected optical channel. Finally, a fourth parameter is used to quantify the blending of a Webb model with a pure AWGN model to account for thermal noise. Numerical results show that the capacity of M-ary orthogonal signaling on the Webb channel exhibits the same brick-wall Shannon limit, (M ln 2)=(M 1), as on the AWGN channel ( 1:59 dB for large M). Results also compare the capacity obtained by hard- and soft-output channels and indicate that soft-output channels o er a 3-dB advantage.

Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

PubMed

Hallaq, Haifa; Wang, Dao W; Kunic, Jennifer D; George, Alfred L; Wells, K Sam; Murray, Katherine T

2012-02-01

Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells. In human embryonic kidney cells that stably expressed SCN5A with green fluorescent protein (GFP) fused to the channel COOH-terminus (SCN5A-GFP), Na(+) currents were suppressed by an exposure to PKC activation. Using confocal microscopy, colocalization of SCN5A-GFP channels with the plasma membrane under control and stimulated conditions was quantified. A separate population of SCN5A channels containing an extracellular epitope was immunolabeled to permit temporally stable labeling of the plasma membrane. Our results demonstrated that Na(+) channels were preferentially trafficked away from the plasma membrane by PKC activation, with a major contribution by Ca(2+)-sensitive or conventional PKC isoforms, whereas stimulation of protein kinase A (PKA) had the opposite effect. Removal of the conserved PKC site Ser(1503) or exposure to the NADPH oxidase inhibitor apocynin eliminated the PKC-mediated effect to alter channel trafficking, indicating that both channel phosphorylation and ROS were required. Experiments using fluorescence recovery after photobleaching demonstrated that both PKC and PKA also modified channel mobility in a manner consistent with the dynamics of channel distribution. These results demonstrate that the activation of protein kinases can acutely regulate the intracellular distribution and molecular mobility of cardiac Na(+) channels in living cells.

Functional and pharmacological consequences of the distribution of voltage-gated calcium channels in the renal blood vessels.

PubMed

Hansen, P B L

2013-04-01

Calcium channel blockers are widely used to treat hypertension because they inhibit voltage-gated calcium channels that mediate transmembrane calcium influx in, for example, vascular smooth muscle and cardiomyocytes. The calcium channel family consists of several subfamilies, of which the L-type is usually associated with vascular contractility. However, the L-, T- and P-/Q-types of calcium channels are present in the renal vasculature and are differentially involved in controlling vascular contractility, thereby contributing to regulation of kidney function and blood pressure. In the preglomerular vascular bed, all the three channel families are present. However, the T-type channel is the only channel in cortical efferent arterioles which is in contrast to the juxtamedullary efferent arteriole, and that leads to diverse functional effects of L- and T-type channel inhibition. Furthermore, by different mechanisms, T-type channels may contribute to both constriction and dilation of the arterioles. Finally, P-/Q-type channels are involved in the regulation of human intrarenal arterial contractility. The calcium blockers used in the clinic affect not only L-type but also P-/Q- and T-type channels. Therefore, the distinct effect obtained by inhibiting a given subtype or set of channels under experimental settings should be considered when choosing a calcium blocker for treatment. T-type channels seem to be crucial for regulating the GFR and the filtration fraction. Use of blockers is expected to lead to preferential efferent vasodilation, reduction of glomerular pressure and proteinuria. Therefore, renovascular T-type channels might provide novel therapeutic targets, and may have superior renoprotective effects compared to conventional calcium blockers. Acta Physiologica © 2013 Scandinavian Physiological Society.

Sediment and Vegetation Controls on Delta Channel Networks

NASA Astrophysics Data System (ADS)

Lauzon, R.; Murray, A. B.; Piliouras, A.; Kim, W.

2016-12-01

Numerous factors control the patterns of distributary channels formed on a delta, including water and sediment discharge, grain size, sea level rise rates, and vegetation type. In turn, these channel networks influence the shape and evolution of a delta, including what types of plant and animal life - such as humans - it can support. Previous fluvial modeling and flume experiments, outside of the delta context, have addressed how interactions between sediment and vegetation, through their influence on lateral transport of sediment, determine what type of channel networks develops. Similar interactions likely also shape delta flow patterns. Vegetation introduces cohesion, tending to reduce channel migration rates and strengthen existing channel banks, reinforcing existing channels and resulting in localized, relatively stable flow patterns. On the other hand, sediment transport processes can result in lateral migration and frequent switching of active channels, resulting in flow resembling that of a braided stream. While previous studies of deltas have indirectly explored the effects of vegetation through the introduction of cohesive sediment, we directly incorporate key effects of vegetation on flow and sediment transport into the delta-building model DeltaRCM to explore how these effects influence delta channel network formation. Model development is informed by laboratory flume experiments at UT Austin. Here we present initial results of experiments exploring the effects of sea level rise rate, sediment grain size, vegetation type, and vegetation growth rate on delta channel network morphology. These results support the hypothesis that the ability for lateral transport of sediment to occur plays a key role in determining the evolution of delta channel networks and delta morphology.

BAD and KATP channels regulate neuron excitability and epileptiform activity.

PubMed

Martínez-François, Juan Ramón; Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L; Danial, Nika N; Yellen, Gary

2018-01-25

Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad ( B CL-2 a gonist of cell d eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (K ATP ) channels. Here we investigated the effect of BAD manipulation on K ATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K ATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K ATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of K ATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased K ATP channel activity. © 2018, Martínez-François et al.

DRIFT CONTROL IN AN ANALYTICAL GAMMA RAY SPECTROMETER

DOEpatents

Fite, L.E.

1963-08-20

A device for automatically and continuously controlling the over-all drift of a multi-channel analyzer so as to permit the accurate processing of spectrometric analytical data by a digital computer is described. Two sources of reference pulses, one of which is stored in the lower channels and the other being stored in the higher channels of a 256 channel analyzer, are provided. The reference pulses are processed in the same manner as the data pulses. The channels that should contain the reference pulses and the adjacent channels above and below those channels are monitored by comparison circuits such that any drift, upward or downward, of the reference pulses is detected to effect a change in high voltage supply in response to a drift in the upper channel, and to effect a change in the lower discriminator level of the analog to digital converter of the analyzer in response to a drift in the lower channel, thereby maintaining the pulses in the proper channels. (AEC)

Developmentally-regulated sodium channel subunits are differentially sensitive to {alpha}-cyano containing pyrethroids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meacham, Connie A.; Brodfuehrer, Peter D.; Watkins, Jennifer A.

2008-09-15

Juvenile rats have been reported to be more sensitive to the acute neurotoxic effects of the pyrethroid deltamethrin than adults. While toxicokinetic differences between juveniles and adults are documented, toxicodynamic differences have not been examined. Voltage-gated sodium channels, the primary targets of pyrethroids, are comprised of {alpha} and {beta} subunits, each of which have multiple isoforms that are expressed in a developmentally-regulated manner. To begin to test whether toxicodynamic differences could contribute to age-dependent deltamethrin toxicity, deltamethrin effects were examined on sodium currents in Xenopus laevis oocytes injected with different combinations of rat {alpha} (Na{sub v}1.2 or Na{sub v}1.3) andmore » {beta} ({beta}{sub 1} or {beta}{sub 3}) subunits. Deltamethrin induced tail currents in all isoform combinations and increased the percent of modified channels in a concentration-dependent manner. Effects of deltamethrin were dependent on subunit combination; Na{sub v}1.3-containing channels were modified to a greater extent than were Na{sub v}1.2-containing channels. In the presence of a {beta} subunit, deltamethrin effects were significantly greater, an effect most pronounced for Na{sub v}1.3 channels; Na{sub v}1.3/{beta}{sub 3} channels were more sensitive to deltamethrin than Na{sub v}1.2/{beta}{sub 1} channels. Na{sub v}1.3/{beta}{sub 3} channels are expressed embryonically, while the Na{sub v}1.2 and {beta}{sub 1} subunits predominate in adults, supporting the hypothesis for age-dependent toxicodynamic differences. Structure-activity relationships for sensitivity of these subunit combinations were examined for other pyrethroids. Permethrin and tetramethrin did not modify currents mediated by either subunit combination. Cypermethrin, {beta}-cyfluthrin, esfenvalerate and fenpropathrin all modified sodium channel function; effects were significantly greater on Na{sub v}1.3/{beta}{sub 3} than on Na{sub v}1.2/{beta}{sub 1} channels. These data demonstrate a greater sensitivity of Na{sub v}1.3 vs Na{sub v}1.2 channels to deltamethrin and other cyano-containing pyrethroids, particularly in the presence of a {beta} subunit.« less

Note: A dual-channel sensor for dew point measurement based on quartz crystal microbalance.

PubMed

Li, Ning; Meng, Xiaofeng; Nie, Jing

2017-05-01

A new sensor with dual-channel was designed for eliminating the temperature effect on the frequency measurement of the quartz crystal microbalance (QCM) in dew point detection. The sensor uses active temperature control, produces condensation on the surface of QCM, and then detects the dew point. Both the single-channel and the dual-channel methods were conducted based on the device. The measurement error of the single-channel method was less than 0.5 °C at the dew point range of -2 °C-10 °C while the dual-channel was 0.3 °C. The results showed that the dual-channel method was able to eliminate the temperature effect and yield better measurement accuracy.

Note: A dual-channel sensor for dew point measurement based on quartz crystal microbalance

NASA Astrophysics Data System (ADS)

Li, Ning; Meng, Xiaofeng; Nie, Jing

2017-05-01

A new sensor with dual-channel was designed for eliminating the temperature effect on the frequency measurement of the quartz crystal microbalance (QCM) in dew point detection. The sensor uses active temperature control, produces condensation on the surface of QCM, and then detects the dew point. Both the single-channel and the dual-channel methods were conducted based on the device. The measurement error of the single-channel method was less than 0.5 °C at the dew point range of -2 °C-10 °C while the dual-channel was 0.3 °C. The results showed that the dual-channel method was able to eliminate the temperature effect and yield better measurement accuracy.

Surface Effect on Oil Transportation in Nanochannel: a Molecular Dynamics Study.

PubMed

Zheng, Haixia; Du, Yonggang; Xue, Qingzhong; Zhu, Lei; Li, Xiaofang; Lu, Shuangfang; Jin, Yakang

2017-12-01

In this work, we investigate the dynamics mechanism of oil transportation in nanochannel using molecular dynamics simulations. It is demonstrated that the interaction between oil molecules and nanochannel has a great effect on the transportation properties of oil in nanochannel. Because of different interactions between oil molecules and channel, the center of mass (COM) displacement of oil in a 6-nm channel is over 30 times larger than that in a 2-nm channel, and the diffusion coefficient of oil molecules at the center of a 6-nm channel is almost two times more than that near the channel surface. Besides, it is found that polarity of oil molecules has the effect on impeding oil transportation, because the electrostatic interaction between polar oil molecules and channel is far larger than that between nonpolar oil molecules and channel. In addition, channel component is found to play an important role in oil transportation in nanochannel, for example, the COM displacement of oil in gold channel is very few due to great interaction between oil and gold substrate. It is also found that nano-sized roughness of channel surface greatly influences the speed and flow pattern of oil. Our findings would contribute to revealing the mechanism of oil transportation in nanochannels and therefore are very important for design of oil extraction in nanochannels.

Differential efficacy of GoSlo-SR compounds on BKα and BKαγ1–4 channels

PubMed Central

Kshatri, Aravind S.; Li, Qin; Yan, Jiusheng; Large, Roddy J.; Sergeant, Gerard P.; McHale, Noel G.; Thornbury, Keith D.; Hollywood, Mark A.

2017-01-01

ABSTRACT Large conductance, voltage and Ca2+ activated K+ channels (BK channels) are abundantly expressed throughout the body and are important regulators of smooth muscle tone and neuronal excitability. Their dysfunction is implicated in various diseases including overactive bladder, hypertension and erectile dysfunction. Therefore, BK channel openers bear significant therapeutic potential to treat the above diseases. GoSlo-SR compounds were designed to be potent and efficacious BK channel openers. Although their structural activity relationships, activation in both BKα and BKαβ channels and the hypothetical mode of action of these compounds has been studied in detail in recent years, their effectiveness to open the BKαγ channels still remains unexplored. In this study, we have examined the efficacy of 3 closely related GoSlo-SR openers, GoSlo-SR-5-6 (SR-5-6), GoSlo-SR-5-44 (SR-5-44) and GoSlo-SR-5-130 (SR-5-130) using inside out patches on BKα channels coexpressed with 4 different LRRC (γ1–4) subunits in HEK293 cells. Our data suggests that the activation effects due to SR-5-6 were not significantly affected in the presence of γ1–4 subunits. Interestingly, the effects of more efficacious BK channel opener SR-5-44 were altered by different γ subunits. In cells expressing BKα channels, the shift in V1/2 (ΔV1/2) induced by SR-5-44 (3 μM) was −76 ± 3 mV, whereas it was significantly reduced by ∼70 % in BKαγ1 channels (ΔV1/2= −23 ± 3, p < 0.001, ANOVA). In BKαγ2 channels the ΔV1/2 was −36 ± 1 mV, which was less than that observed in BKαγ3 and BKαγ4 channels where the ΔV1/2 was −47 ± 5 mV, and −82 ± 5 mV, respectively. Additionally, the excitatory effects of a ‘β specific’ BK channel opener, SR-5-130 were only partially restored in the patches containing BKαγ1–4 channels. Together this data highlights that subtle modifications in GoSlo-SR structures alter their effectiveness on BK channels with accessory γ subunits and this study might provide a scaffold for the development of more tissue specific BK channel openers. PMID:27440457

Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium.

PubMed

Noble, Karen; Floyd, Rachel; Shmygol, Andre; Shmygol, Anatoly; Mobasheri, A; Wray, Susan

2010-01-01

Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels. 2009 Elsevier Ltd. All rights reserved.

A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs.

PubMed

Mo, Yuanfu; Yu, Dexin; Song, Jun; Zheng, Kun; Guo, Yajuan

2015-01-01

In a vehicular ad hoc network (VANET), the periodic exchange of single-hop status information broadcasts (beacon frames) produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network.

A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs

PubMed Central

Mo, Yuanfu; Yu, Dexin; Song, Jun; Zheng, Kun; Guo, Yajuan

2015-01-01

In a vehicular ad hoc network (VANET), the periodic exchange of single-hop status information broadcasts (beacon frames) produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network. PMID:26571042

A universal steady state I-V relationship for membrane current

NASA Technical Reports Server (NTRS)

Chernyak, Y. B.; Cohen, R. J. (Principal Investigator)

1995-01-01

A purely electrical mechanism for the gating of membrane ionic channel gives rise to a simple I-V relationship for membrane current. Our approach is based on the known presence of gating charge, which is an established property of the membrane channel gating. The gating charge is systematically treated as a polarization of the channel protein which varies with the external electric field and modifies the effective potential through which the ions migrate in the channel. Two polarization effects have been considered: 1) the up or down shift of the whole potential function, and 2) the change in the effective electric field inside the channel which is due to familiar effect of the effective reduction of the electric field inside a dielectric body because of the presence of surface charges on its surface. Both effects are linear in the channel polarization. The ionic current is described by a steady state solution of the Nernst-Planck equation with the potential directly controlled by the gating charge system. The solution describes reasonably well the steady state and peak-current I-V relationships for different channels, and when applied adiabatically, explains the time lag between the gating charge current and the rise of the ionic current. The approach developed can be useful as an effective way to model the ionic currents in axons, cardiac cells and other excitable tissues.

Simulation study of short-channel effects of tunnel field-effect transistors

NASA Astrophysics Data System (ADS)

Fukuda, Koichi; Asai, Hidehiro; Hattori, Junichi; Mori, Takahiro; Morita, Yukinori; Mizubayashi, Wataru; Masahara, Meishoku; Migita, Shinji; Ota, Hiroyuki; Endo, Kazuhiro; Matsukawa, Takashi

2018-04-01

Short-channel effects of tunnel field-effect transistors (FETs) are investigated in detail using simulations of a nonlocal band-to-band tunneling model. Discussion is limited to silicon. Several simulation scenarios were considered to address different effects, such as source overlap and drain offset effects. Adopting the drain offset to suppress the drain leakage current suppressed the short channel effects. The physical mechanism underlying the short-channel behavior of the tunnel FETs (TFETs) was very different from that of metal-oxide-semiconductor FETs (MOSFETs). The minimal gate lengths that do not lose on-state current by one order are shown to be 3 nm for single-gate structures and 2 nm for double gate structures, as determined from the drain offset structure.

Critical heat flux for water boiling in channels. Modern state, typical regularities, unsolved problems, and ways for solving them (a review)

NASA Astrophysics Data System (ADS)

Bobkov, V. P.

2015-02-01

Some general matters concerned with description of burnout in channels are outlined. Data obtained from experimental investigations on critical heat fluxes (CHF) in different channels, CHF data banks, the main determining parameters, CHF basic dependences, and a system of correction functions are discussed. Two methods for estimating the CHF description errors are analyzed. The influence of operating parameters, transverse sizes of channels, and conditions at their inlet are analyzed. The effects of heat-transfer surface shape and heat supply arrangement are considered for concentric annular channels. The notions of a thermal boundary layer and an elementary thermal cell during burnout in channels with an intricate cross section are defined. New notions for describing CHF in rod assemblies are introduced: bundle effect, thermal misalignment, assembly-section-averaged and local parameters (for an elementary cell), cell-wise CHF analysis in bundles, and standard and nonstandard cells. Possible influence of wall thermophysical properties on CHF in dense assemblies and other effects are considered. Thermal interaction of nonequivalent cells and the effect of heat supply arrangement over the cell perimeter are analyzed. Special attention is paid to description of the effect the heat release nonuniformity along the channels has on CHF. Objectives to be pursued by studies of CHF in channels of different cross-section shapes are formulated.

Cilnidipine, an L/N-type calcium channel blocker prevents acquisition and expression of ethanol-induced locomotor sensitization in mice.

PubMed

Bhutada, Pravinkumar; Mundhada, Yogita; Patil, Jayshree; Rahigude, Anand; Zambare, Krushna; Deshmukh, Prashant; Tanwar, Dhanshree; Jain, Kishor

2012-04-11

Several evidences indicated the involvement of L- and N-type calcium channels in behavioral effects of drugs of abuse, including ethanol. Calcium channels are implicated in ethanol-induced behaviors and neurochemical responses. Calcium channel antagonists block the psychostimulants induced behavioral sensitization. Recently, it is demonstrated that L-, N- and T-type calcium channel blockers attenuate the acute locomotor stimulant effects of ethanol. However, no evidence indicated the role of calcium channels in ethanol-induced psychomotor sensitization. Therefore, present study evaluated the influence of cilnidipine, an L/N-type calcium channel blocker on acquisition and expression of ethanol-induced locomotor sensitization. The results revealed that cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) attenuates the expression of sensitization to locomotor stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) during development of sensitization blocks acquisition and attenuates expression of sensitization to locomotor stimulant effect of ethanol. Cilnidipine per se did not influence locomotor activity in tested doses. Further, cilnidipine had no influence on effect of ethanol on rotarod performance. These results support the hypothesis that neuroadaptive changes in calcium channels participate in the acquisition and the expression of ethanol-induced locomotor sensitization. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test.

PubMed

Budni, Josiane; Gadotti, Vinícius M; Kaster, Manuella P; Santos, Adair R S; Rodrigues, Ana Lúcia S

2007-12-01

The administration of agmatine elicits an antidepressant-like effect in the mouse forced swimming test by a mechanism dependent on the inhibition of the NMDA receptors and the L-arginine-nitric oxide (NO) pathway. Since it has been reported that the NO can activate different types of potassium (K(+)) channels in several tissues, the present study investigates the possibility of synergistic interactions between different types of K(+) channel inhibitors and agmatine in the forced swimming test. Treatment of mice by i.c.v. route with subeffective doses of tetraethylammonium (a non specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channels inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site), augmented the effect of agmatine (0.001 mg/kg, i.p.) in the forced swimming test. Furthermore, the administration of agmatine and the K(+) channel inhibitors, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time elicited by an active dose of agmatine (10 mg/kg, i.p.) in the forced swimming test was prevented by the pre-treatment of mice with the K(+) channel openers cromakalim (10 microg/site, i.c.v.) and minoxidil (10 microg/site, i.c.v.), without affecting locomotion. Together these data raise the possibility that the antidepressant-like effect of agmatine in the forced swimming test is related to its modulatory effects on neuronal excitability, via inhibition of K(+) channels.

Mechanism of resveratrol-induced relaxation in the human gallbladder.

PubMed

Tsai, Ching-Chung; Lee, Ming-Che; Tey, Shu-Leei; Liu, Ching-Wen; Huang, Shih-Che

2017-05-08

Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips. We studied the relaxant effects of resveratrol in human gallbladder. In addition, we also investigated mechanism of resveratrol-induced relaxation in human gallbladder by tetraethylammonium (a non-selective potassium channels blocker), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channel), glibenclamide (an ATP-sensitive potassium channel blocker), charybdotoxin (an inhibitor of large conductance calcium-activated potassium channels and slowly inactivating voltage-gated potassium channels), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-Nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), and ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker). The present study showed that resveratrol has relaxant effects in human gallbladder muscle strips. In addition, we found that resveratrol-induced relaxation in human gallbladder is associated with nitric oxide, ATP-sensitive potassium channel, and large conductance calcium-activated potassium channel pathways. This study provides the first evidence concerning the relaxant effects of resveratrol in human gallbladder muscle strips. Furthermore, these results demonstrate that resveratrol is a potential new drug or health supplement in the treatment of biliary colic.

Sidedness of Carbamazepine Accessibility to Voltage-Gated Sodium Channels

PubMed Central

Jo, Sooyeon

2014-01-01

Voltage-gated sodium channels are inhibited by many local anesthetics, antiarrhythmics, and antiepileptic drugs. The local anesthetic lidocaine appears to be able to access its binding site in the sodium channel only from the membrane phase or from the internal face of the channel. In contrast, the antiepileptic drug carbamazepine was found to inhibit voltage-gated sodium channels only with external, but not internal, application, implying a major difference. We investigated this point using both whole-cell and inside-out patch recordings from human Nav1.7 channels in a stable cell line. In the whole-cell configuration, carbamazepine inhibited sodium current within seconds when applied externally, but had little or no effect when applied internally for up to 15 minutes, confirming previous results. However, carbamazepine inhibited sodium channels effectively and rapidly when applied to the internal face of the membrane using inside-out patch recording. We found that lidocaine also has little or no effect when applied intracellularly in whole-cell recording, but blocks effectively and rapidly when applied to the internal surface using inside-out patches. In contrast, the cationic lidocaine derivative QX-314 (N-ethyl-lidocaine) blocks effectively when applied internally with whole-cell dialysis, as well as when applied to inside-out patches. We conclude that carbamazepine and lidocaine access the sodium channel in similar ways and hypothesize that their lack of effect with internal dialysis in whole-cell recording reflects rapid exit through membrane near the pipette recording site. This effect likely limits the ability of any compound with significant membrane permeability to be applied intracellularly by whole-cell dialysis. PMID:24319110

Differential state-dependent modification of rat Na{sub v}1.6 sodium channels expressed in human embryonic kidney (HEK293) cells by the pyrethroid insecticides tefluthrin and deltamethrin

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Bingjun; Soderlund, David M., E-mail: dms6@cornell.edu

2011-12-15

We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}1 and {beta}2 auxiliary subunits in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on expressed sodium currents using the whole-cell patch clamp technique. Both pyrethroids produced concentration-dependent, resting modification of Na{sub v}1.6 channels, prolonging the kinetics of channel inactivation and deactivation to produce persistent 'late' currents during depolarization and tail currents following repolarization. Both pyrethroids also produced concentration dependent hyperpolarizing shifts in the voltage dependence of channel activation and steady-state inactivation. Maximal shifts in activation, determined from the voltagemore » dependence of the pyrethroid-induced late and tail currents, were {approx} 25 mV for tefluthrin and {approx} 20 mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of {approx} 5-10 mV in the voltage dependence of steady-state inactivation. In addition to their effects on the voltage dependence of inactivation, both compounds caused concentration-dependent increases in the fraction of sodium current that was resistant to inactivation following strong depolarizing prepulses. We assessed the use-dependent effects of tefluthrin and deltamethrin on Na{sub v}1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7 Hz on the extent of channel modification. Repetitive depolarization at either frequency increased modification by deltamethrin by {approx} 2.3-fold but had no effect on modification by tefluthrin. Tefluthrin and deltamethrin were equally potent as modifiers of Na{sub v}1.6 channels in HEK293 cells using the conditions producing maximal modification as the basis for comparison. These findings show that the actions of tefluthrin and deltamethrin of Na{sub v}1.6 channels in HEK293 cells differ from the effects of these compounds on Na{sub v}1.6 channels in Xenopus oocytes and more closely reflect the actions of pyrethroids on channels in their native neuronal environment. -- Highlights: Black-Right-Pointing-Pointer We expressed rat Na{sub v}1.6 voltage-gated sodium channels in HEK293 cells. Black-Right-Pointing-Pointer Tefluthrin and deltamethrin caused resting modification of Na{sub v}1.6 channels. Black-Right-Pointing-Pointer Only deltamethrin exhibited use-dependent enhancement of modification. Black-Right-Pointing-Pointer State-dependent effects of pyrethroids are influenced by the cellular context. Black-Right-Pointing-Pointer Channels in HEK293 cells exhibit properties similar to native neuronal channels.« less

CW Interference Effects on High Data Rate Transmission Through the ACTS Wideband Channel

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Ngo, Duc H.; Tran, Quang K.; Tran, Diepchi T.; Yu, John; Kachmar, Brian A.; Svoboda, James S.

1996-01-01

Satellite communications channels are susceptible to various sources of interference. Wideband channels have a proportionally greater probability of receiving interference than narrowband channels. NASA's Advanced Communications Technology Satellite (ACTS) includes a 900 MHz bandwidth hardlimiting transponder which has provided an opportunity for the study of interference effects of wideband channels. A series of interference tests using two independent ACTS ground terminals measured the effects of continuous-wave (CW) uplink interference on the bit-error rate of a 220 Mbps digitally modulated carrier. These results indicate the susceptibility of high data rate transmissions to CW interference and are compared to results obtained with a laboratory hardware-based system simulation and a computer simulation.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

A two-dimensional analytical modeling for channel potential and threshold voltage of short channel triple material symmetrical gate Stack (TMGS) DG-MOSFET

NASA Astrophysics Data System (ADS)

Tripathi, Shweta

2016-10-01

In the present work, a two-dimensional (2D) analytical framework of triple material symmetrical gate stack (TMGS) DG-MOSFET is presented in order to subdue the short channel effects. A lightly doped channel along with triple material gate having different work functions and symmetrical gate stack structure, showcases substantial betterment in quashing short channel effects to a good extent. The device functioning amends in terms of improved exemption to threshold voltage roll-off, thereby suppressing the short channel effects. The encroachments of respective device arguments on the threshold voltage of the proposed structure are examined in detail. The significant outcomes are compared with the numerical simulation data obtained by using 2D ATLAS™ device simulator to affirm and formalize the proposed device structure.

The Geomorphically Effective Hydrograph: An Emerging Concept For Interpreting Channel Morphology And Evolution

NASA Astrophysics Data System (ADS)

Grant, G.; Hempel, L. A.; Marwan, H.; Eaton, B. C.; Lewis, S.

2017-12-01

Predicting how alluvial channels adjust to changes in their flow and sediment regimes is one of the Holy Grails of geomorphology. Consider Lane's balance - one of the most widely recognized conceptual models in geomorphology - which graphically shows how a change in any one of the driving variables of slope, grain size, sediment transport rate, or discharge can be accommodated by changes in the other variables. Much of the history of process geomorphology addresses how channels respond to these controlling factors. Yet the emphasis has been disproportionately focused on the effects and consequences of changing sediment transport rates or grain size. Much less attention has been paid to how changing discharge itself, particularly over short, event-based timescales influences the channel. Discharge has typically been treated as a single value - often the bankfull discharge - with little attention paid to how the unsteady nature of flow during floods may influence the morphology of the channel. More attention has been paid recently to the effect of hydrograph shape on channel characteristics, notably the texture of the channel bed. There is little theory and scant data, however, that highlights how the hydrograph affects the channel. We have begun to address this problem through models and targeted experiments. Our goal is to explore the idea of the geomorphically effective hydrograph: the concept that hydrographs with different forms, durations, and sequences play a major, controlling role in shaping the form and organization of alluvial channels. We report on results from both field studies and flume experiments that lend support to this hypothesis. We compare channel forms in channels with radically different flow regimes. The distinctive rectangular shape, constant slope, and absence of alluvial bars in spring-fed channels are in sharp contrast to the more asymmetric channels with regular pool/riffle patterns observed in systems where discharge varies over orders of magnitude. Flume studies reveal how channel organization, defined as the tendency to form regularly-spaced pools, riffles, and bars, is related to the flashiness of the hydrograph. Drawing on these and other studies, we develop a conceptual model that accounts for hydrograph shape as an overarching control on channel development and evolution.

Micro-channel filling flow considering surface tension effect

NASA Astrophysics Data System (ADS)

Kim, Dong Sung; Lee, Kwang-Cheol; Kwon, Tai Hun; Lee, Seung S.

2002-05-01

Understanding filling flow into micro-channels is important in designing micro-injection molding, micro-fluidic devices and an MIMIC (micromolding in capillaries) process. In this paper, we investigated, both experimentally and numerically, 'transient filling' flow into micro-channels, which differs from steady-state completely 'filled' flow in micro-channels. An experimental flow visualization system was devised to facilitate observation of flow characteristics in filling into micro-channels. Three sets of micro-channels of various widths of different thicknesses (20, 30, and 40 μm) were fabricated using SU-8 on the silicon substrate to find a geometric effect with regard to pressure gradient, viscous force and, in particular, surface tension. A numerical analysis system has also been developed taking into account the surface tension effect with a contact angle concept. Experimental observations indicate that surface tension significantly affects the filling flow to such an extent that even a flow blockage phenomenon was observed at channels of small width and thickness. A numerical analysis system also confirms that the flow blockage phenomenon could take place due to the flow hindrance effect of surface tension, which is consistent with experimental observation. For proper numerical simulations, two correction factors have also been proposed to correct the conventional hydraulic radius for the filling flow in rectangular cross-sectioned channels.

Effects of channel thickness on oxide thin film transistor with double-stacked channel layer

NASA Astrophysics Data System (ADS)

Lee, Kimoon; Kim, Yong-Hoon; Yoon, Sung-Min; Kim, Jiwan; Oh, Min Suk

2017-11-01

To improve the field effect mobility and control the threshold voltage ( V th ) of oxide thin film transistors (TFTs), we fabricated the oxide TFTs with double-stacked channel layers which consist of thick Zn-Sn-O (ZTO) and very thin In-Zn-O (IZO) layers. We investigated the effects of the thickness of thin conductive layer and the conductivity of thick layer on oxide TFTs with doublestacked channel layer. When we changed the thickness of thin conductive IZO channel layer, the resistivity values were changed. This resistivity of thin channel layer affected on the saturation field effect mobility and the off current of TFTs. In case of the thick ZTO channel layer which was deposited by sputtering in Ar: O2 = 10: 1, the device showed better performances than that which was deposited in Ar: O2 = 1: 1. Our TFTs showed high mobility ( μ FE ) of 40.7 cm2/Vs and V th of 4.3 V. We assumed that high mobility and the controlled V th were caused by thin conductive IZO layer and thick stable ZTO layer. Therefore, this double-stacked channel structure can be very promising way to improve the electrical characteristics of various oxide thin film transistors.

Scaling Trends and Tradeoffs between Short Channel Effect and Channel Boosting Characteristics in Sub-20 nm Bulk/Silicon-on-Insulator NAND Flash Memory

NASA Astrophysics Data System (ADS)

Miyaji, Kousuke; Hung, Chinglin; Takeuchi, Ken

2012-04-01

The scaling trends and limitation in sub-20 nm a bulk and silicon-on-insulator (SOI) NAND flash memory is studied by the three-dimensional (3D) device simulation focusing on short channel effects (SCE), channel boost leakage and channel voltage boosting characteristics during the program-inhibit operation. Although increasing punch-through stopper doping concentration is effective for suppressing SCE in bulk NAND cells, the generation of junction leakage becomes serious. On the other hand, SCE can be suppressed by thinning the buried oxide (BOX) in SOI NAND cells. However, the boosted channel voltage decreases by the higher BOX capacitance. It is concluded that the scaling limitation is dominated by the junction leakage and channel boosting capability for bulk and SOI NAND flash cells, respectively, and the scaling limit is decreased to 9 nm using SOI NAND flash memory cells from 13 nm in bulk NAND flash memory cells.

Effect of activators and inhibitors of K+ channels on insulin secretion in the amphibian pancreas.

PubMed

Francini, F; Pirotte, B; Gagliardino, J J

1997-02-01

The aim of this study was to obtain pharmacological evidence for the presence and participation of K+ channels in amphibian pancreatic islets. Pancreases from the toad Bufo arenarum were thus incubated with activators or blockers of K+ channels and the immunoreactive insulin released into the medium was measured by radioimmunoassay. Two K(+)-ATP channel openers (diazoxide and BPDZ44) inhibited; while a K(+)-ATP channel blocker (tolbutamide) and metabolizable sugars (glucose, glyceraldehyde) significantly stimulated the output of insulin. Although a nonmetabolizable sugar (galactose) failed to increase insulin release, dinitrophenol decreased the secretagogue effect of glucose. By contrast, although somatostatin and clonidine blocked the release of insulin, tetraethylammonium significantly stimulated secretion. For each compound tested, the effects on both insulin secretion and B-cell K+ channel activity were similar to those observed in the mammalian pancreas. These findings point to the existence of mammalian-like K+ channels in the B-cells of some amphibians.

Free-space optical channel simulator for weak-turbulence conditions.

PubMed

Bykhovsky, Dima

2015-11-01

Free-space optical (FSO) communication may be severely influenced by the inevitable turbulence effect that results in channel gain fluctuations and fading. The objective of this paper is to provide a simple and effective simulator of the weak-turbulence FSO channel that emulates the influence of the temporal covariance effect. Specifically, the proposed model is based on lognormal distributed samples with a corresponding correlation time. The simulator is based on the solution of the first-order stochastic differential equation (SDE). The results of the provided SDE analysis reveal its efficacy for turbulent channel modeling.

A Numerical Model Study of the Effect of Channel Deepening on Shoaling and Salinity Intrusion in the Savannah Estuary

DTIC Science & Technology

1989-12-01

H tY) T , iv OFTECHNICAL REPORT HL-89-26 A NUMERICAL MODEL STUDY OF THE EFFECT SOF CHANNEL DEEPENING ON SHOALING AND SALINITY INTRUSION IN THE... Study of the Effect of Channel Deepening on Shoaling and Salinity Intrusion in the Savannah Estuary 12. PERSONAL AUTHOR(S) Johnson, B. H.; Trawle, M. J...a multiple-connected system of channels. Results from a study in the Savannah Estuary show good agreement with 1985 field data on tides, velocities

Orbital two-channel Kondo effect in epitaxial ferromagnetic L1 0-MnAl films

DOE PAGES

Zhu, L. J.; Nie, S. H.; Xiong, P.; ...

2016-02-24

The orbital two-channel Kondo effect displaying exotic non-Fermi liquid behaviour arises in the intricate scenario of two conduction electrons compensating a pseudo-spin-1/2 impurity of two-level system. Despite extensive efforts for several decades, no material system has been clearly identified to exhibit all three transport regimes characteristic of the two-channel Kondo effect in the same sample, leaving the interpretation of the experimental results a subject of debate. Here we present a transport study suggestive of a robust orbital two-channel Kondo effect in epitaxial ferromagnetic L1 0-MnAl films, as evidenced by a magnetic field-independent resistivity upturn with a clear transition from logarithmic-more » to square-root temperature dependence and deviation from it in three distinct temperature regimes. Lastly, our results also provide an experimental indication of the presence of two-channel Kondo physics in a ferromagnet, pointing to considerable robustness of the orbital two-channel Kondo effect even in the presence of spin polarization of the conduction electrons.« less

Orbital two-channel Kondo effect in epitaxial ferromagnetic L1 0-MnAl films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, L. J.; Nie, S. H.; Xiong, P.

The orbital two-channel Kondo effect displaying exotic non-Fermi liquid behaviour arises in the intricate scenario of two conduction electrons compensating a pseudo-spin-1/2 impurity of two-level system. Despite extensive efforts for several decades, no material system has been clearly identified to exhibit all three transport regimes characteristic of the two-channel Kondo effect in the same sample, leaving the interpretation of the experimental results a subject of debate. Here we present a transport study suggestive of a robust orbital two-channel Kondo effect in epitaxial ferromagnetic L1 0-MnAl films, as evidenced by a magnetic field-independent resistivity upturn with a clear transition from logarithmic-more » to square-root temperature dependence and deviation from it in three distinct temperature regimes. Lastly, our results also provide an experimental indication of the presence of two-channel Kondo physics in a ferromagnet, pointing to considerable robustness of the orbital two-channel Kondo effect even in the presence of spin polarization of the conduction electrons.« less

The action of blocking agents applied to the inner face of Ca(2+)-activated K+ channels from human erythrocytes.

PubMed

Dunn, P M

1998-09-15

The actions of clotrimazole and cetiedil, two drugs known to inhibit the Gardos channel, have been studied on single intermediate conductance calcium-activated potassium (IKCa) channels in inside out patches from human red blood cells, and compared with those of TEA and Ba2+ applied to the cytoplasmic face of the membrane. TEA produced a fast block which was observed as a reduction in the amplitude of the single channel current. This effect was weakly voltage dependent with the fraction of the membrane potential sensed by TEA at its binding site (delta) of 0.18 and a Kd at 0 mV of 20.5 mM. Ba2+ was a very potent blocker of the channel, breaking the single channel activity up into bursts, inter-spersed with silent periods lasting several seconds. The effect of Ba2+ was very voltage sensitive, delta = 0.44, and a Kd at 0 mV of 0.15 microM. Clotrimazole applied to the inner face of the membrane at a concentration < or = 1 microM produced a slow block resulting in bursts of channel activity separated by quiescent periods lasting many seconds. The effect of clotrimazole was mimicked by a quaternary derivative UCL 1559, in keeping with an action at the cytoplasmic face of the channel. A high concentration of cetiedil (100 microM) produced only a weak block of the channel. The kinetics of this action were very slow, with burst and inter-burst intervals lasting several minutes. While inhibition of the Gardos channel by cetiedil is unlikely to involve an intracellular site of action, if clotrimazole is able to penetrate the membrane, part of its effect may result from binding to an intracellular site on the channel.

Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

PubMed Central

Jordan, J. B.; Easton, P. L.; Hinton, J. F.

2005-01-01

The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp→Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two β6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics. PMID:15501932

Effects of phenylalanine substitutions in gramicidin A on the kinetics of channel formation in vesicles and channel structure in SDS micelles.

PubMed

Jordan, J B; Easton, P L; Hinton, J F

2005-01-01

The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp-->Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two beta6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics.

Potassium channels in brain mitochondria.

PubMed

Bednarczyk, Piotr

2009-01-01

Potassium channels are the most widely distributed class of ion channels. These channels are transmembrane proteins known to play important roles in both normal and pathophysiological functions in all cell types. Various potassium channels are recognised as potential therapeutic targets in the treatment of Parkinson's disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition to their importance as therapeutic targets, certain potassium channels are known for their beneficial roles in anaesthesia, cardioprotection and neuroprotection. Some types of potassium channels present in the plasma membrane of various cells have been found in the inner mitochondrial membrane as well. Potassium channels have been proposed to regulate mitochondrial membrane potential, respiration, matrix volume and Ca(+) ion homeostasis. It has been proposed that mitochondrial potassium channels mediate ischaemic preconditioning in various tissues. However, the specificity of a pharmacological agents and the mechanisms underlying their effects on ischaemic preconditioning remain controversial. The following potassium channels from various tissues have been identified in the inner mitochondrial membrane: ATP-regulated (mitoK(ATP)) channel, large conductance Ca(2+)-regulated (mitoBK(Ca)) channel, intermediate conductance Ca(2+)-regulated (mitoIK(Ca)) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore domain (mitoTASK-3) channel. It has been shown that increased potassium flux into brain mitochondria induced by either the mitoK(ATP) channel or mitoBK(Ca) channel affects the beneficial effects on neuronal cell survival under pathological conditions. Recently, differential distribution of mitoBK(Ca) channels has been observed in neuronal mitochondria. These findings may suggest a neuroprotective role for the mitoBK(Ca) channel in specific brain structures. This minireview summarises current data on brain mitochondrial potassium channels and the efforts to identify their molecular correlates.

Investigation of piezoresistive effect in p-channel metal–oxide–semiconductor field-effect transistors fabricated on circular silicon-on-insulator diaphragms using cost-effective minimal-fab process

NASA Astrophysics Data System (ADS)

Liu, Yongxun; Tanaka, Hiroyuki; Umeyama, Norio; Koga, Kazuhiro; Khumpuang, Sommawan; Nagao, Masayoshi; Matsukawa, Takashi; Hara, Shiro

2018-06-01

P-channel metal–oxide–semiconductor field-effect transistors (PMOSFETs) with the 〈110〉 or 〈100〉 channel direction have been successfully fabricated on circular silicon-on-insulator (SOI) diaphragms using a cost-effective minimal-fab process, and their electrical characteristics have been systematically investigated before and after the SOI diaphragm formation. It was found that almost the same subthreshold slope (S-slope) and threshold voltage (V t) are observed in the fabricated PMOSFETs before and after the SOI diaphragm formation, and they are independent of the channel direction. On the other hand, significant variations in drain current were observed in the fabricated PMOSFETs with the 〈110〉 channel direction after the SOI diaphragm formation owing to the residual mechanical stress-induced piezoresistive effect. It was also confirmed that electrical characteristics of the fabricated PMOSFETs with the 〈100〉 channel direction are almost the same before and after the SOI diaphragm formation, i.e., not sensitive to the mechanical stress. Moreover, the drain current variations at different directions of mechanical stress and current flow were systematically investigated and discussed.

Space shuttle orbit maneuvering engine reusable thrust chamber. Task 13: Subscale helium ingestion and two dimensional heating test report

NASA Technical Reports Server (NTRS)

Tobin, R. D.

1974-01-01

Descriptions are given of the test hardware, facility, procedures, and results of electrically heated tube, channel and panel tests conducted to determine effects of helium ingestion, two dimensional conduction, and plugged coolant channels on operating limits of convectively cooled chambers typical of space shuttle orbit maneuvering engine designs. Helium ingestion in froth form, was studied in tubular and rectangular single channel test sections. Plugged channel simulation was investigated in a three channel panel. Burn-out limits (transition of film boiling) were studied in both single channel and panel test sections to determine 2-D conduction effects as compared to tubular test results.

Carbamazepine as a novel small molecule corrector of trafficking-impaired ATP-sensitive potassium channels identified in congenital hyperinsulinism.

PubMed

Chen, Pei-Chun; Olson, Erik M; Zhou, Qing; Kryukova, Yelena; Sampson, Heidi M; Thomas, David Y; Shyng, Show-Ling

2013-07-19

ATP-sensitive potassium (KATP) channels consisting of sulfonylurea receptor 1 (SUR1) and the potassium channel Kir6.2 play a key role in insulin secretion by coupling metabolic signals to β-cell membrane potential. Mutations in SUR1 and Kir6.2 that impair channel trafficking to the cell surface lead to loss of channel function and congenital hyperinsulinism. We report that carbamazepine, an anticonvulsant, corrects the trafficking defects of mutant KATP channels previously identified in congenital hyperinsulinism. Strikingly, of the 19 SUR1 mutations examined, only those located in the first transmembrane domain of SUR1 responded to the drug. We show that unlike that reported for several other protein misfolding diseases, carbamazepine did not correct KATP channel trafficking defects by activating autophagy; rather, it directly improved the biogenesis efficiency of mutant channels along the secretory pathway. In addition to its effect on channel trafficking, carbamazepine also inhibited KATP channel activity. Upon subsequent removal of carbamazepine, however, the function of rescued channels was recovered. Importantly, combination of the KATP channel opener diazoxide and carbamazepine led to enhanced mutant channel function without carbamazepine washout. The corrector effect of carbamazepine on mutant KATP channels was also demonstrated in rat and human β-cells with an accompanying increase in channel activity. Our findings identify carbamazepine as a novel small molecule corrector that may be used to restore KATP channel expression and function in a subset of congenital hyperinsulinism patients.

Linear conduction in N-type organic field effect transistors with nanometric channel lengths and graphene as electrodes

NASA Astrophysics Data System (ADS)

Chianese, F.; Candini, A.; Affronte, M.; Mishra, N.; Coletti, C.; Cassinese, A.

2018-05-01

In this work, we test graphene electrodes in nanometric channel n-type Organic Field Effect Transistors (OFETs) based on thermally evaporated thin films of the perylene-3,4,9,10-tetracarboxylic acid diimide derivative. By a thorough comparison with short channel transistors made with reference gold electrodes, we found that the output characteristics of the graphene-based devices respond linearly to the applied bias, in contrast with the supralinear trend of gold-based transistors. Moreover, short channel effects are considerably suppressed in graphene electrode devices. More specifically, current on/off ratios independent of the channel length (L) and enhanced response for high longitudinal biases are demonstrated for L down to ˜140 nm. These results are rationalized taking into account the morphological and electronic characteristics of graphene, showing that the use of graphene electrodes may help to overcome the problem of Space Charge Limited Current in short channel OFETs.

End region and current consolidation effects upon the performance of an MHD channel for the ETF conceptual design. [Engineering Test Facility

NASA Technical Reports Server (NTRS)

Wang, S. Y.; Smith, J. M.

1982-01-01

It is noted that operating conditions which yielded a peak thermodynamic efficiency (41%) for an EFT-size MHD/steam power plant were previously (Wang et al., 1981; Staiger, 1981) identified by considering only the active region (the primary portion for power production) of an MHD channel. These previous efforts are extended here to include an investigation of the effects of the channel end regions on overall power generation. Considering these effects, the peak plant thermodynamic efficiency is found to be slightly lowered (40.7%); the channel operating point for peak efficiency is shifted to the supersonic mode (Mach number of approximately 1.1) rather than the previous subsonic operation (Mach number of approximately 0.9). Also discussed is the sensitivity of the channel performance to the B-field, diffuser recovery coefficient, channel load parameter, Mach number, and combustor pressure.

Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart.

PubMed

Murata, Mitsushige; Cingolani, Eugenio; McDonald, Amy D; Donahue, J Kevin; Marbán, Eduardo

2004-08-20

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.

Influence of an anomalous dimension effect on thermal instability in amorphous-InGaZnO thin-film transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Kuan-Hsien; Chou, Wu-Ching, E-mail: tcchang3708@gmail.com, E-mail: wuchingchou@mail.nctu.edu.tw; Chang, Ting-Chang, E-mail: tcchang3708@gmail.com, E-mail: wuchingchou@mail.nctu.edu.tw

2014-10-21

This paper investigates abnormal dimension-dependent thermal instability in amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistors. Device dimension should theoretically have no effects on threshold voltage, except for in short channel devices. Unlike short channel drain-induced source barrier lowering effect, threshold voltage increases with increasing drain voltage. Furthermore, for devices with either a relatively large channel width or a short channel length, the output drain current decreases instead of saturating with an increase in drain voltage. Moreover, the wider the channel and the shorter the channel length, the larger the threshold voltage and output on-state current degradation that is observed. Because of themore » surrounding oxide and other thermal insulating material and the low thermal conductivity of the IGZO layer, the self-heating effect will be pronounced in wider/shorter channel length devices and those with a larger operating drain bias. To further clarify the physical mechanism, fast I{sub D}-V{sub G} and modulated peak/base pulse time I{sub D}-V{sub D} measurements are utilized to demonstrate the self-heating induced anomalous dimension-dependent threshold voltage variation and on-state current degradation.« less

[Effects of phoxim and fenvalerate on TTX-S and TTX-R sodium channels in the DRG neurons of adult rat].

PubMed

Wang, X; Xiao, H; Dai, X; Liu, X; Yu, X; Wu, J

2000-05-01

To study the joint neurotoxic effects of phoxim (Pho) and fenvalerate (Fen) on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) currents in dorsal root ganglion (DRG) neurons of adult rat. Whole cell patch clamp technique was used to test the effects of Pho and Fen on TTX-S and TTX-R sodium currents in DRG neurons. The inactivation of TTX-R sodium channel was obviously slowed down by Fen. The tau(Na) of peak currents at doses of 10, 50 and 100 micromol/L Fen and control groups were (8.10 +/- 2.41) ms, (11.78 +/- 2.76) ms, P < 0.01, (8.76 +/-1.94) ms, P < 0.05 and (6.41 +/- 1.32) ms respectively. The inactivation of TTX-R sodium channel tail currents was also significantly delayed by Fen. The tau(Na) of the tail currents at doses of 10, 50, 100 micromol/L Fen and control groups were 6.11 +/- 0.52 (P < 0.05), 7.82 +/- 0.82 (P < 0.05), 7.23 +/- 1.09 (P < 0.05) and (4.91 +/- 0.97) ms separately. As compared with TTX-R sodium channel, the TTX-S sodium channel was less responsive to Fen exposure, which only led to slowly decay TTX-S sodium tail currents. There was no any effect of Pho on the TTX-S and TTX-R sodium channels. The mixed treatment of a Pho and Fen did not show joint effect on the sodium currents. Both the peak and tail currents are changed by Fen, however, Fen has more remarkable effects on TTX-R than on TTX-S sodium channel. The combined exposure to Pho and Fen shows no joint effect on the sodium channel.

Whittle's "Channel One": Effects on Impulsive Preadolescents' Desire for Advertised Products.

ERIC Educational Resources Information Center

Tozzo-Lyles, Teresa A.; Walsh-Childers, Kim

A field experiment tested effects of "Channel One" commercials on impulsive preadolescent students' purchasing preferences, such as product liking and likelihood of buying regularly advertised products. A total of 67 sixth-grade middle school students participated in the field experiment. Students who viewed "Channel One' daily were…

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation—A Computational Study

NASA Astrophysics Data System (ADS)

Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

2017-01-01

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment.

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation-A Computational Study.

PubMed

Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

2017-01-13

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment.

Effects of unsaturated fatty acids on the kinetics of voltage‐gated proton channels heterologously expressed in cultured cells

PubMed Central

Kawanabe, Akira

2016-01-01

Key points Arachidonic acid (AA) greatly enhances the activity of the voltage‐gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear.In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells.The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage‐dependence of activation.Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms.Application of phospholipase A2, which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Abstract Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage‐gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside‐out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current–voltage relationship. In monomeric channels lacking the coiled‐coil region of the channel protein, the shift in the current–voltage relationship was diminished but activation and deactivation remained accelerated. Studies with several AA derivatives showed that double bonds and hydrophilic head groups are essential for the effect of AA, although charge was not important. The application of phospholipase A2 (PLA2), which generates AA from cell membrane phospholipids, stimulated mHv1 activity to a similar extent as direct application of ∼20 μm AA, suggesting that endogenous AA may regulate Hv channel activity. PMID:26563684

Hall-effect Thruster Channel Surface Properties Investigation (PREPRINT)

DTIC Science & Technology

2011-03-03

Article 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Hall-effect Thruster Channel Surface Properties Investigation 5b...13. SUPPLEMENTARY NOTES For publication in the AIAA Journal of Propulsion and Power. 14. ABSTRACT Surface properties of Hall-effect thruster...incorporated into thruster simulations, and these models must account for evolution of channel surface properties due to thruster operation. Results from

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

PubMed Central

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

2015-01-01

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

What did we learn from PEGASEAS forum "Science and Governance of the Channel Marine Ecosystem"?

PubMed

Evariste, Emmanuelle; Claquin, Pascal; Robin, Jean-Paul; Auber, Arnaud; McQuatters-Gollop, Abigail; Fletcher, Stephen; Glegg, Gillian; Dauvin, Jean-Claude

2015-04-15

As one of the busiest marine ecosystems in the world, the English Channel is subjected to strong pressures due to the human activities occurring within it. Effective governance is required to improve the combined management of different activities and so secure the benefits provided by the Channel ecosystem. In July 2014, a Cross-Channel Forum, entitled "Science and Governance of the Channel Marine Ecosystem", was held in Caen (France) as part of the INTERREG project "Promoting Effective Governance of the Channel Ecosystem" (PEGASEAS). Here we use outputs from the Forum as a framework for providing Channel-specific advice and recommendations on marine governance themes, including the identification of knowledge gaps, which may form the foundation of future projects for the next INTERREG project call (2015-2020). Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of scaling voltage and size on the performance of Side-contacted Field Effect Diode

NASA Astrophysics Data System (ADS)

Touchaei, Behnam Jafari; Manavizadeh, Negin

2018-05-01

Side-contacted Fild Effect Diode (S-FED), with low leakage current and high Ion/Ioff ratio, has been recently introduced to suppress short channel effects in nanoscale regime. The voltage and size scalability of S-FEDs and effects on the power consumption, propagation delay time, and power delay product have been studied in this article. The most attractive properties are related to channel length to channel thickness ratio in the S-FED which reduces in comparison with MOSFET significantly, while gates control over the channel improve and the off-state current reduces dramatically. This promising advantage is not only capable to improve important S-FED's characteristics such as subthreshold slope but also eliminate Latch-up and floating body effect.

Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

PubMed

Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

2013-01-01

Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

Benzonatate inhibition of voltage-gated sodium currents.

PubMed

Evans, M Steven; Maglinger, G Benton; Fletcher, Anita M; Johnson, Stephen R

2016-02-01

Benzonatate was FDA-approved in 1958 as an antitussive. Its mechanism of action is thought to be anesthesia of vagal sensory nerve fibers that mediate cough. Vagal sensory neurons highly express the Nav1.7 subtype of voltage-gated sodium channels, and inhibition of this channel inhibits the cough reflex. Local anesthetics inhibit voltage-gated sodium channels, but there are no reports of whether benzonatate affects these channels. Our hypothesis is that benzonatate inhibits Nav1.7 voltage-gated sodium channels. We used whole cell voltage clamp recording to test the effects of benzonatate on voltage-gated sodium (Na(+)) currents in two murine cell lines, catecholamine A differentiated (CAD) cells, which express primarily Nav1.7, and N1E-115, which express primarily Nav1.3. We found that, like local anesthetics, benzonatate strongly and reversibly inhibits voltage-gated Na(+) channels. Benzonatate causes both tonic and phasic inhibition. It has greater effects on channel inactivation than on activation, and its potency is much greater at depolarized potentials, indicating inactivated-state-specific effects. Na(+) currents in CAD cells and N1E-115 cells are similarly affected, indicating that benzonatate is not Na(+) channel subtype-specific. Benzonatate is a mixture of polyethoxy esters of 4-(butylamino) benzoic acid having varying degrees of hydrophobicity. We found that Na(+) currents are inhibited most potently by a benzonatate fraction containing the 9-ethoxy component. Detectable effects of benzonatate occur at concentrations as low as 0.3 μM, which has been reported in humans. We conclude that benzonatate has local anesthetic-like effects on voltage-gated sodium channels, including Nav1.7, which is a possible mechanism for cough suppression by the drug. Copyright © 2015 Elsevier Ltd. All rights reserved.

Incorporating Born solvation energy into the three-dimensional Poisson-Nernst-Planck model to study ion selectivity in KcsA K+ channels

NASA Astrophysics Data System (ADS)

Liu, Xuejiao; Lu, Benzhuo

2017-12-01

Potassium channels are much more permeable to potassium than sodium ions, although potassium ions are larger and both carry the same positive charge. This puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP) theory of electrodiffusion because the PNP model treats all ions as point charges, does not incorporate ion size information, and therefore cannot discriminate potassium from sodium ions. The PNP model can qualitatively capture some macroscopic properties of certain channel systems such as current-voltage characteristics, conductance rectification, and inverse membrane potential. However, the traditional PNP model is a continuum mean-field model and has no or underestimates the discrete ion effects, in particular the ion solvation or self-energy (which can be described by Born model). It is known that the dehydration effect (closely related to ion size) is crucial to selective permeation in potassium channels. Therefore, we incorporated Born solvation energy into the PNP model to account for ion hydration and dehydration effects when passing through inhomogeneous dielectric channel environments. A variational approach was adopted to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite element simulations were performed. The BPNP model can distinguish different ion species by ion radius and predict selectivity for K+ over Na+ in KcsA channels. Furthermore, ion current rectification in the KcsA channel was observed by both the PNP and BPNP models. The I -V curve of the BPNP model for the KcsA channel indicated an inward rectifier effect for K+ (rectification ratio of ˜3 /2 ) but indicated an outward rectifier effect for Na+ (rectification ratio of ˜1 /6 ) .

Comparative production of channel catfish and channel x blue hybrid catfish subjected to two minimum dissolved oxygen concentrations

USDA-ARS?s Scientific Manuscript database

The effect of daily minimum dissolved oxygen concentration on growth and yield (kg/ha) of the channel catfish (Ictalurus punctatus) and the channel x blue hybrid catfish (I. punctatus female x I. furcatus male), which shared the Jubilee strain of channel catfish as the maternal parent, was evaluated...

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

PubMed Central

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

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth muscle cells, assayed by measuring intracellular collagen content. We observed increased intracellular levels of ascorbate under supplementation with elevated doses of ascorbic acid, as well as its lipid soluble derivative ascorbyl palmitate. Nifedipine reduced ascorbic acid intracellular influx in cultured aortic smooth muscle cells with nifedipine (50 µM) compared to control. Adverse effects of nifedipine were neutralized either by an increased level of cell supplementation with ascorbic acid or by substituting it with ascorbyl palmitate. These studies suggest that adverse effects of channel blockers could be caused by their weakening the arterial wall integrity by interfering with proper extracellular matrix formation. In conclusion, these studies confirm the adverse effects of channel blockers on collagen type l and lV deposition, the key ECM components essential for maintaining optimal structural integrity of the arterial walls. Ascorbate supplementation reversed channel blocker inhibition of these collagen types synthesis and deposition. The results of this study imply the benefits of ascorbate and ascorbate palmitate supplementation in medical management of cardiovascular disease in order to compensate for adverse effects of channel blockers. PMID:27335688

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

PubMed

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

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth muscle cells, assayed by measuring intracellular collagen content. We observed increased intracellular levels of ascorbate under supplementation with elevated doses of ascorbic acid, as well as its lipid soluble derivative ascorbyl palmitate. Nifedipine reduced ascorbic acid intracellular influx in cultured aortic smooth muscle cells with nifedipine (50 µM) compared to control. Adverse effects of nifedipine were neutralized either by an increased level of cell supplementation with ascorbic acid or by substituting it with ascorbyl palmitate. These studies suggest that adverse effects of channel blockers could be caused by their weakening the arterial wall integrity by interfering with proper extracellular matrix formation. In conclusion, these studies confirm the adverse effects of channel blockers on collagen type l and lV deposition, the key ECM components essential for maintaining optimal structural integrity of the arterial walls. Ascorbate supplementation reversed channel blocker inhibition of these collagen types synthesis and deposition. The results of this study imply the benefits of ascorbate and ascorbate palmitate supplementation in medical management of cardiovascular disease in order to compensate for adverse effects of channel blockers.

Bovine chromaffin cells possess FTX-sensitive calcium channels.

PubMed

Gandía, L; Albillos, A; García, A G

1993-07-30

The effects of the synthetic analogue of the toxin from the venom of the funnel-web spider Agenelopsis aperta (sFTX) on whole-cell Ba2+ currents through Ca2+ channels were studied in cultured bovine chromaffin cells. sFTX selectively and reversibly blocked a significant component (55 +/- 3%) of the whole-cell IBa. Effects of sFTX were additive to those of omega-conotoxin GVIA, a selective blocker of N-type Ca2+ channels, and those of furnidipine, a novel dihydropyridine L-type Ca2+ channel blocker. We conclude that the cultured bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-type component in their whole-cell currents through their Ca2+ channels.

Noise effect on fidelity of two-qubit teleportation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu Xueyuan; Gu Ying; Gong Qihuang

2010-05-15

We investigate the effect of noise on a class of four-qubit entangled channels for two-qubit teleportation from Alice to Bob. These entangled channels include both parallel Bell pairs and inseparable channels with genuine multipartite entanglement. For the situation where only Bob's share of the entangled channel is subject to decoherence, we show by deriving a general expression for the teleported state that teleportation using noisy inseparable channels is equivalent to teleportation using noisy Bell pairs. When Alice's qubits are also subject to noise, we find that the inseparable channels never give a higher teleportation fidelity than Bell pairs, even inmore » the presence of collective noise. Our results can shed some light on practical two-qubit teleportation.« less

A 700 V narrow channel nJFET with low pinch-off voltage and suppressed drain-induced barrier lowering effect

NASA Astrophysics Data System (ADS)

Mao, Kun; Qiao, Ming; Zhang, WenTong; Zhang, Bo; Li, Zhaoji

2014-11-01

This paper proposes a 700 V narrow channel region triple-RESURF (reduced surface field) n-type junction field-effect transistor (NCT-nJFET). Compared to traditional structures, low pinch-off voltage (VP) with unobvious drain-induced barrier lowering (DIBL) effect and large saturated current (IDsat) are achieved. This is because p-type buried layer (Pbury) and PWELL are introduced to shape narrow n-type channel in JFET channel region. DIBL sensitivity (SDIBL) is firstly introduced in this paper to analyze the DIBL effect of high-voltage long-channel JFET. Ultra-high breakdown voltage is obtained by triple RESURF technology. Experimental results show that proposed NCT-nJFET achieves 24-V VP, 3.5% SDIBL, 2.3-mA IDsat, 800-V OFF-state breakdown voltage (OFF-BV) and 650-V ON-state breakdown voltage when VGS equals 0 V (ON-BV).

Performance analysis of SOI MOSFET with rectangular recessed channel

NASA Astrophysics Data System (ADS)

Singh, M.; Mishra, S.; Mohanty, S. S.; Mishra, G. P.

2016-03-01

In this paper a two dimensional (2D) rectangular recessed channel-silicon on insulator metal oxide semiconductor field effect transistor (RRC-SOI MOSFET), using the concept of groove between source and drain regions, which is one of the channel engineering technique to suppress the short channel effect (SCE). This suppression is mainly due to corner potential barrier of the groove and the simulation is carried out by using ATLAS 2D device simulator. To have further improvement of SCE in RRC-SOI MOSFET, three more devices are designed by using dual material gate (DMG) and gate dielectric technique, which results in formation of devices i.e. DMRRC-SOI,MLSMRRC-SOI, MLDMRRC-SOI MOSFET. The effect of different structures of RRC-SOI on AC and RF parameters are investigated and the importance of these devices over RRC MOSFET regarding short channel effect is analyzed.

Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons

PubMed Central

Evans, M. Steven; Cheng, Xiangying; Jeffry, Joseph A.; Disney, Kimberly E.; Premkumar, Louis S.

2011-01-01

Objective To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors. Background TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia (DRG), TRPV1-containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system. Methods We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI. Results Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, trigeminal ganglion, and in the trigeminal nucleus caudalis. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents (sEPSCs) in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 μM), a selective anti-migraine drug inhibited TRPV1-mediated inward currents in TG. and capsaicin-elicited sEPSCs in TNC slices. The same effects of capsaicin and sumatriptan were found in acutely dissociated DiI-labeled TG neurons innervating cerebral dura. Conclusion Our results build on previous work indicating that TRPV1 channels in trigeminal nociceptors play a role in craniofacial pain. Our findings that TRPV1 is inhibited by the specific antimigraine drug sumatriptan, and that TRPV1 channels are functional in neurons projecting to cerebral dura suggests a specific role for these channels in migraine or cluster headache. PMID:22289052

Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells.

PubMed

Sato, Toshiaki; Takizawa, Taichi; Saito, Tomoaki; Kobayashi, Satoru; Hara, Yukio; Nakaya, Haruaki

2003-12-01

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.

N- and P-type Ca2+ channels are involved in acetylcholine release at a neuroneuronal synapse: only the N-type channel is the target of neuromodulators.

PubMed Central

Fossier, P; Baux, G; Tauc, L

1994-01-01

Cholinergic transmission in an identified neuro-neuronal synapse of the Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthetic analog (sFTx). This specific blocker of voltage-dependent P-type Ca2+ channels did not interfere with the effect of the N-type Ca2+ channel blocker omega-conotoxin, which could further decrease synaptic transmission after a previous application of FTx. Similar results were obtained when the reversal order of application of these two Ca2+ channel blockers was used. Both P- and N-type Ca2+ currents trigger acetylcholine release in the presynaptic neuron. The neuromodulatory effects of FMRF-amide, histamine, and buccalin on transmitter release disappeared after the blockade of the N-type Ca2+ channels but remained still effective in the presence of FTx. These results indicate that only N-type Ca2+ channels appear to be sensitive to the neuromodulators we have identified. PMID:7910963

N- and P-type Ca2+ channels are involved in acetylcholine release at a neuroneuronal synapse: only the N-type channel is the target of neuromodulators.

PubMed

Fossier, P; Baux, G; Tauc, L

1994-05-24

Cholinergic transmission in an identified neuro-neuronal synapse of the Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthetic analog (sFTx). This specific blocker of voltage-dependent P-type Ca2+ channels did not interfere with the effect of the N-type Ca2+ channel blocker omega-conotoxin, which could further decrease synaptic transmission after a previous application of FTx. Similar results were obtained when the reversal order of application of these two Ca2+ channel blockers was used. Both P- and N-type Ca2+ currents trigger acetylcholine release in the presynaptic neuron. The neuromodulatory effects of FMRF-amide, histamine, and buccalin on transmitter release disappeared after the blockade of the N-type Ca2+ channels but remained still effective in the presence of FTx. These results indicate that only N-type Ca2+ channels appear to be sensitive to the neuromodulators we have identified.

A biomedical solicitation examination of nanoparticles as drug agents to minimize the hemodynamics of a stenotic channel

NASA Astrophysics Data System (ADS)

Ijaz, S.; Nadeem, S.

2017-11-01

A theoretical examination is presented in this analysis to study the flow of a bio-nanofluid through a curved stenotic channel. The curved channel is considered with an overlapping stenotic region. The effect of convective conditions is incorporated to discuss the heat transfer characteristic. The mathematical problem of a curved stenotic channel is formulated and then solved by using the exact technique. To discuss the hemodynamics of a curved stenotic channel the expression of resistance to blood is evaluated by dividing the channel into pre-stenotic, stenotic and post stenotic region. In this investigation gold, silver and copper nanoparticles are used as drug carriers. The outcomes of the graphical illustration reveal that with an increase in nanoparticle concentration hemodynamics effects of stenosed curved channel are reduced and they also conclude that the drug Au nanoparticles are more effective to minimize hemodynamics when compared to the drug Ag and Cu nanoparticles. This analysis finds valuable theoretical information for nanoparticles used as drug agents in the field of bio-inspired applications.

Calculation of the electron wave function in a graded-channel double-heterojunction modulation-doped field-effect transistor

NASA Technical Reports Server (NTRS)

Mui, D. S. L.; Patil, M. B.; Morkoc, H.

1989-01-01

Three double-heterojunction modulation-doped field-effect transistor structures with different channel composition are investigated theoretically. All of these transistors have an In(x)Ga(1-x)As channel sandwiched between two doped Al(0.3)Ga(0.7)As barriers with undoped spacer layers. In one of the structures, x varies from 0 from either heterojunction to 0.15 at the center of the channel quadratically; in the other two, constant values of x of 0 and 0.15 are used. The Poisson and Schroedinger equations are solved self-consistently for the electron wave function in all three cases. The results showed that the two-dimensional electron gas (2DEG) concentration in the channel of the quadratically graded structure is higher than the x = 0 one and slightly lower than the x = 0.15 one, and the mean distance of the 2DEG is closer to the center of the channel for this transistor than the other two. These two effects have important implications on the electron mobility in the channel.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels.

PubMed

Lombardo, Joseph; Harrington, Melissa A

2016-11-01

KCNQ/K v 7 channels form a slow noninactivating K + current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K v 7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K + current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K v 7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/K v 7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K v 7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K v 7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K v 7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K v 7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K v 7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. Copyright © 2016 the American Physiological Society.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels

PubMed Central

Lombardo, Joseph

2016-01-01

KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. PMID:27512022

Effects of metomindate hydrochloride and tricaine methanesulfonate on the short term cortisol response in channel catfish

USDA-ARS?s Scientific Manuscript database

The effects of metomidate hydrochloride and tricaine methanesulfonate (MS-222) on cortisol stress response of channel catfish, Ictalurus punctatus, were examined during 10 minutes of sedation. Channel catfish were assigned to three treatments: 1. Metomidate hydrochloride (12.5 mg/L), 2. MS-222 (100...

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

PubMed

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

2014-11-01

Sulfonylureas, which stimulate insulin secretion from pancreatic β-cells, are widely used to treat both type 2 diabetes and neonatal diabetes. These drugs mediate their effects by binding to the sulfonylurea receptor subunit (SUR) of the ATP-sensitive K(+) (KATP) channel and inducing channel closure. The mechanism of channel inhibition is unusually complex. First, sulfonylureas act as partial antagonists of channel activity, and second, their effect is modulated by MgADP. We analyzed the molecular basis of the interactions between the sulfonylurea gliclazide and Mg-nucleotides on β-cell and cardiac types of KATP channel (Kir6.2/SUR1 and Kir6.2/SUR2A, respectively) heterologously expressed in Xenopus laevis oocytes. The SUR2A-Y1206S mutation was used to confer gliclazide sensitivity on SUR2A. We found that both MgATP and MgADP increased gliclazide inhibition of Kir6.2/SUR1 channels and reduced inhibition of Kir6.2/SUR2A-Y1206S. The latter effect can be attributed to stabilization of the cardiac channel open state by Mg-nucleotides. Using a Kir6.2 mutation that renders the KATP channel insensitive to nucleotide inhibition (Kir6.2-G334D), we showed that gliclazide abolishes the stimulatory effects of MgADP and MgATP on β-cell KATP channels. Detailed analysis suggests that the drug both reduces nucleotide binding to SUR1 and impairs the efficacy with which nucleotide binding is translated into pore opening. Mutation of one (or both) of the Walker A lysines in the catalytic site of the nucleotide-binding domains of SUR1 may have a similar effect to gliclazide on MgADP binding and transduction, but it does not appear to impair MgATP binding. Our results have implications for the therapeutic use of sulfonylureas. © 2014 Proks et al.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koenig, Xaver; Kovar, Michael; Rubi, Lena

The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologouslymore » expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential source of cardiac arrhythmias. • 18-Methoxycoronaridine has a lower affinity for cardiac ion channels than ibogaine.« less

L-type calcium channel blockade attenuates morphine withdrawal: in vivo interaction between L-type calcium channels and corticosterone.

PubMed

Esmaeili-Mahani, Saeed; Fathi, Yadollah; Motamedi, Fereshteh; Hosseinpanah, Farhad; Ahmadiani, Abolhassan

2008-02-01

Both opioids and calcium channel blockers could affect hypothalamic-pituitary-adrenal (HPA) axis function. Nifedipine, as a calcium channel blocker, can attenuate the development of morphine dependence; however, the role of the HPA axis in this effect has not been elucidated. We examined the effect of nifedipine on the induction of morphine dependency in intact and adrenalectomized (ADX) male rats, as assessed by the naloxone precipitation test. We also evaluated the effect of this drug on HPA activity induced by naloxone. Our results showed that despite the demonstration of dependence in both groups of rats, nifedipine is more effective in preventing of withdrawal signs in ADX rats than in sham-operated rats. In groups that received morphine and nifedipine concomitantly, naloxone-induced corticosterone secretion was attenuated. Thus, we have shown the involvement of the HPA axis in the effect of nifedipine on the development of morphine dependency and additionally demonstrated an in vivo interaction between the L-type Ca2+ channels and corticosterone.

The effect of nozzle-exit-channel shape on resultant fiber diameter in melt-electrospinning

NASA Astrophysics Data System (ADS)

Esmaeilirad, Ahmad; Ko, Junghyuk; Rukosuyev, Maxym V.; Lee, Jason K.; Lee, Patrick C.; Jun, Martin B. G.

2017-01-01

In recent decades, electrospinning using a molten poly (ε-caprolactone) resin has gained attention for creating fibrous tissue scaffolds. The topography and diameter control of such electrospun microfibers is an important issue for their different applications in tissue engineering. Charge density, initial nozzle-exit-channel cross-sectional area, nozzle to collector distance, viscosity, and processing temperature are the most important input parameters that affect the final electrospun fiber diameters. In this paper we will show that the effect of nozzle-exit-channel shape is as important as the other effective parameters in a resultant fiber diameter. However, to the best of our knowledge, the effect of nozzle-exit-channel shapes on a resultant fiber diameter have not been studied before. Comparing rectangular and circular nozzles with almost the same exit-channel cross-sectional areas in a similar processing condition showed that using a rectangular nozzle resulted in decreasing final fiber diameter up to 50%. Furthermore, the effect of processing temperature on the final fiber topography was investigated.

Bladder contractility is modulated by Kv7 channels in pig detrusor.

PubMed

Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja; Sheykhzade, Majid; Nordling, Jørgen; Bouchelouche, Pierre

2013-09-05

Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view to determining the effects of the following potassium channel activators: ML213 (Kv7.2/Kv7.4 channels) and retigabine (Kv7.2-7.5 channels). Retigabine produced a concentration-dependent relaxation of carbachol- and electric field-induced contractions. The potency was similar in magnitude to that of ML213-induced relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P<0.05), which in turn confirmed Kv7 channel selectivity. Subtype-selective effects were further investigated by incubating the detrusor with 10µM chromanol 293B (Kv7.1 channel blocker). Regardless of the experimental protocol, this did not cause a further increase in the evoked contraction. In contrast, the addition of XE991 potentiated the KCl-induced contractions, but not those induced by carbachol or electric field, indicating the presence of a phosphatidyl-inositol-4,5-biphosphate-dependent mechanism amongst the Kv7 channels in detrusor. qRT-PCR studies of the mRNA transcript level of Kv7.3-7.5 channels displayed a higher level of Kv7.4 transcript in detrusor compared to that present in brain cortex and heart tissues. Thus, we have shown that Kv7.4 channels are expressed and functionally active in pig detrusor, and that the use of selective Kv7.4 channel modulators in the treatment of detrusor overactivity seems promising. © 2013 Elsevier B.V. All rights reserved.

The anti-diabetic drug repaglinide induces vasorelaxation via activation of PKA and PKG in aortic smooth muscle.

PubMed

Kim, Hye Won; Li, Hongliang; Kim, Han Sol; Shin, Sung Eun; Jung, Won-Kyo; Ha, Kwon-Soo; Han, Eun-Taek; Hong, Seok-Ho; Choi, Il-Whan; Firth, Amy L; Bang, Hyoweon; Park, Won Sun

2016-09-01

We investigated the vasorelaxant effect of repaglinide and its related signaling pathways using phenylephrine (Phe)-induced pre-contracted aortic rings. Repaglinide induced vasorelaxation in a concentration-dependent manner. The repaglinide-induced vasorelaxation was not affected by removal of the endothelium. In addition, application of a nitric oxide synthase inhibitor (L-NAME) and a small-conductance Ca(2+)-activated K(+) (SKCa) channel inhibitor (apamin) did not alter the vasorelaxant effect of repaglinide on endothelium-intact arteries. Pretreatment with an adenylyl cyclase inhibitor (SQ 22536) or a PKA inhibitor (KT 5720) effectively reduced repaglinide-induced vasorelaxation. Also, pretreatment with a guanylyl cyclase inhibitor (ODQ) or a PKG inhibitor (KT 5823) inhibited repaglinide-induced vasorelaxation. However, pretreatment with a voltage-dependent K(+) (Kv) channel inhibitor (4-AP), ATP-sensitive K(+) (KATP) channel inhibitor (glibenclamide), large-conductance Ca(2+)-activated K(+) (BKCa) channel inhibitor (paxilline), or the inwardly rectifying K(+) (Kir) channel inhibitor (Ba(2+)) did not affect the vasorelaxant effect of repaglinide. Furthermore, pretreatment with a Ca(2+) inhibitor (nifedipine) and a sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor (thapsigargin) did not affect the vasorelaxant effect of repaglinide. The vasorelaxant effect of repaglinide was not affected by elevated glucose (50mM). Based on these results, we conclude that repaglinide induces vasorelaxation via activation of adenylyl cyclase/PKA and guanylyl cyclase/PKG signaling pathways independently of the endothelium, K(+) channels, Ca(2+) channels, and intracellular Ca(2+) ([Ca(2+)]i). Copyright © 2016 Elsevier Inc. All rights reserved.

Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.

PubMed

Moussaieff, Arieh; Rimmerman, Neta; Bregman, Tatiana; Straiker, Alex; Felder, Christian C; Shoham, Shai; Kashman, Yoel; Huang, Susan M; Lee, Hyosang; Shohami, Esther; Mackie, Ken; Caterina, Michael J; Walker, J Michael; Fride, Ester; Mechoulam, Raphael

2008-08-01

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3(-/-) mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3(+/+) mice. It had no effect on keratinocytes from TRPV3(-/-) mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.

Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current.

PubMed

Wang, H; Shi, H; Zhang, L; Pourrier, M; Yang, B; Nattel, S; Wang, Z

2000-09-05

Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. This study aimed at establishing ionic mechanisms underlying potential electrophysiological effects of nicotine. Effects of nicotine on Kv4.3 and Kv4.2 channels expressed in Xenopus oocytes were studied at the whole-cell and single-channel levels. The effects of nicotine on the transient outward K(+) current (I:(to)) were studied by use of whole-cell patch-clamp techniques in canine ventricular myocytes. Nicotine potently inhibited Kv4 current. The concentration for half-maximal inhibition (IC(50)) was 40+/-4 nmol/L, and the current was abolished by 100 micromol/L nicotine. The IC(50) for block of native I:(to) was 270+/-43 nmol/L. The steady-state activation properties of Kv4.3 and I:(to) were unaltered by nicotine, whereas positive shifts of the inactivation curves were observed. Of the total inhibition of Kv4.3 and I:(to) by nicotine, 40% was due to tonic block and 60% was attributable to use-dependent block. Activation, inactivation, and reactivation kinetics were not significantly changed by nicotine. Nicotine reduced single-channel conductance, open probability, and open time but increased the closed time of Kv4.3. The effects of nicotine were not altered by antagonists to various neurotransmitter receptors, indicating direct effects on I:(to) channels. Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. This action may contribute to the ability of nicotine to affect cardiac electrophysiology and induce arrhythmias.

Desensitization of chemical activation by auxiliary subunits: convergence of molecular determinants critical for augmenting KCNQ1 potassium channels.

PubMed

Gao, Zhaobing; Xiong, Qiaojie; Sun, Haiyan; Li, Min

2008-08-15

Chemical openers for KCNQ potassium channels are useful probes both for understanding channel gating and for developing therapeutics. The five KCNQ isoforms (KCNQ1 to KCNQ5, or Kv7.1 to Kv7.5) are differentially localized. Therefore, the molecular specificity of chemical openers is an important subject of investigation. Native KCNQ1 normally exists in complex with auxiliary subunits known as KCNE. In cardiac myocytes, the KCNQ1-KCNE1 (IsK or minK) channel is thought to underlie the I(Ks) current, a component critical for membrane repolarization during cardiac action potential. Hence, the molecular and pharmacological differences between KCNQ1 and KCNQ1-KCNE1 channels have been important topics. Zinc pyrithione (ZnPy) is a newly identified KCNQ channel opener, which potently activates KCNQ2, KCNQ4, and KCNQ5. However, the ZnPy effects on cardiac KCNQ1 potassium channels remain largely unknown. Here we show that ZnPy effectively augments the KCNQ1 current, exhibiting an increase in current amplitude, reduction of inactivation, and slowing of both activation and deactivation. Some of these are reminiscent of effects by KCNE1. In addition, neither the heteromultimeric KCNQ1-KCNE1 channels nor native I(Ks) current displayed any sensitivity to ZnPy, indicating that the static occupancy by a KCNE subunit desensitizes the reversible effects by a chemical opener. Site-directed mutagenesis of KCNQ1 reveals that residues critical for the potentiation effects by either ZnPy or KCNE are clustered together in the S6 region overlapping with the critical gating determinants. Thus, the convergence of potentiation effects and molecular determinants critical for both an auxiliary subunit and a chemical opener argue for a mechanistic overlap in causing potentiation.

Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P.

PubMed

Huang, Dongyang; Huang, Sha; Gao, Haixia; Liu, Yani; Qi, Jinlong; Chen, Pingping; Wang, Caixue; Scragg, Jason L; Vakurov, Alexander; Peers, Chris; Du, Xiaona; Zhang, Hailin; Gamper, Nikita

2016-08-10

Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca(2+) channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K(+) channels described earlier. Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca(2+) current and concurrent enhancement of anti-algesic M-type K(+) current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233-251.

Channel interaction limits melodic pitch perception in simulated cochlear implants

PubMed Central

Crew, Joseph D.; Galvin, John J.; Fu, Qian-Jie

2012-01-01

In cochlear implants (CIs), melodic pitch perception is limited by the spectral resolution, which in turn is limited by the number of spectral channels as well as interactions between adjacent channels. This study investigated the effect of channel interaction on melodic contour identification (MCI) in normal-hearing subjects listening to novel 16-channel sinewave vocoders that simulated channel interaction in CI signal processing. MCI performance worsened as the degree of channel interaction increased. Although greater numbers of spectral channels may be beneficial to melodic pitch perception, the present data suggest that it is also important to improve independence among spectral channels. PMID:23145706

Inhibitory effects of cortisone and hydrocortisone on human Kv1.5 channel currents.

PubMed

Yu, Jing; Park, Mi-Hyeong; Jo, Su-Hyun

2015-01-05

Glucocorticoids are the primary hormones that respond to stress and protect organisms from dangerous situations. The glucocorticoids hydrocortisone and its dormant form, cortisone, affect the cardiovascular system with changes such as increased blood pressure and cardioprotection. Kv1.5 channels play a critical role in the maintenance of cellular membrane potential and are widely expressed in pancreatic β-cells, neurons, myocytes, and smooth muscle cells of the pulmonary vasculature. We examined the electrophysiological effects of both cortisone and hydrocortisone on human Kv1.5 channels expressed in Xenopus oocytes using a two-microelectrode voltage clamp technique. Both cortisone and hydrocortisone rapidly and irreversibly suppressed the amplitude of Kv1.5 channel current with IC50 values of 50.2±4.2μM and 33.4±3.2μM, respectively, while sustained the current trace shape of Kv1.5 current. The inhibitory effect of cortisone on Kv1.5 decreased progressively from -10mV to +30mV, while hydrocortisone׳s inhibition of the channel did not change across the same voltage range. Both cortisone and hydrocortisone blocked Kv1.5 channel currents in a non-use-dependent manner and neither altered the channel׳s steady-state activation or inactivation curves. These results show that cortisone and hydrocortisone inhibited Kv1.5 channel currents differently, and that Kv1.5 channels were more sensitive to hydrocortisone than to cortisone. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of chlorogenic acid on voltage-gated potassium channels of trigeminal ganglion neurons in an inflammatory environment.

PubMed

Liu, Fei; Lu, Xiao-Wen; Zhang, Yu-Jiao; Kou, Liang; Song, Ning; Wu, Min-Ke; Wang, Min; Wang, Hang; Shen, Jie-Fei

2016-10-01

Chlorogenic acid (CGA) composed of coffee acid and quinic acid is an effective ingredient of many foods and medicines and widely exhibits biological effects. Recently, it is reported to have analgesic effect. However, little is known about the analgesic mechanism of CGA. In this study, whole-cell patch-clamp recordings were performed on two main subtypes (I K,A and I K,V channels) of voltage-gated potassium (K V ) channels in small-diameter(<30μm) trigemianl ganglion neurons to analyze the effects of CGA in an inflammatory environment created by Prostaglandin E 2 (PGE 2 ). On one hand, the activation and inactivation V 1/2 values of I K,A and I K,V channels showed an elevation towards a depolarizing shift caused by PGE 2 . On the other hand, the activation and inactivation V 1/2 values of the two channels had a reduction towards a hyperpolarizing shift caused by CGA under PGE 2 pretreatment. Our results demonstrated that CGA may exhibited an analgesic effect by promoting K V channels activation and inactivation under inflammatory condition, which provided a novel molecular and ionic mechanism underlying anti-inflammatory pain of CGA. Copyright © 2016 Elsevier Inc. All rights reserved.

Chopper-stabilized phase detector

NASA Technical Reports Server (NTRS)

Hopkins, P. M.

1978-01-01

Phase-detector circuit for binary-tracking loops and other binary-data acquisition systems minimizes effects of drift, gain imbalance, and voltage offset in detector circuitry. Input signal passes simultaneously through two channels where it is mixed with early and late codes that are alternately switched between channels. Code switching is synchronized with polarity switching of detector output of each channel so that each channel uses each detector for half time. Net result is that dc offset errors are canceled, and effect of gain imbalance is simply change in sensitivity.

Characteristics and molecular basis of celecoxib modulation on Kv7 potassium channels

PubMed Central

Du, XN; Zhang, X; Qi, JL; An, HL; Li, JW; Wan, YM; Fu, Y; Gao, HX; Gao, ZB; Zhan, Y; Zhang, HL

2011-01-01

BACKGROUND AND PURPOSE Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used for the treatment of pain and inflammation. Emerging and accumulating evidence suggests that celecoxib can affect cellular targets other than COX, such as ion channels. In this study, we characterized the effects of celecoxib on Kv7 K+ channels and compared its effects with the well-established Kv7 channel opener retigabine. EXPERIMENTAL APPROACH A perforated whole-cell patch technique was used to record Kv7currents expressed in HEK 293 cells and M-type currents from rat superior cervical ganglion neurons. KEY RESULTS Celecoxib enhanced Kv7.2–7.4, Kv7.2/7.3 and Kv7.3/7.5 currents but inhibited Kv7.1 and Kv7.1/KCNE1 currents and these effects were concentration dependent. The IC50 value for inhibition of Kv7.1 channels was approximately 4 µM and the EC50 values for activation of Kv7.2–7.4, Kv7.2/Kv7.3 and Kv7.3/Kv7.5 channels were approximately 2–5 µM. The effects of celecoxib were manifested by increasing current amplitudes, shifting the voltage-dependent activation curve in a more negative direction and slowing the deactivation of Kv7 currents. 2,5-Dimethyl-celecoxib, a celecoxib analogue devoid of COX inhibition activity, has similar but greater effects on Kv7currents. Kv7.2(A235T) and Kv7.2(W236L) mutant channels, which have greatly attenuated responses to retigabine, showed a reversed response to celecoxib, from activation to inhibition. CONCLUSIONS AND IMPLICATIONS These results suggest that Kv7 channels are targets of celecoxib action and provide new mechanistic evidence for understanding the effects of celecoxib. They also provide a new approach to developing Kv7 modulators and for studying the structure–function relationship of Kv7 channels. PMID:21564087

The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

PubMed

Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

2016-03-01

Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Screening effects in flow through rough channels.

PubMed

Andrade, J S; Araújo, A D; Filoche, M; Sapoval, B

2007-05-11

A surprising similarity is found between the distribution of hydrodynamic stress on the wall of an irregular channel and the distribution of flux from a purely Laplacian field on the same geometry. This finding is a direct outcome of numerical simulations of the Navier-Stokes equations for flow at low Reynolds numbers in two-dimensional channels with rough walls presenting either deterministic or random self-similar geometries. For high Reynolds numbers, the distribution of wall stresses on deterministic and random fractal rough channels becomes substantially dependent on the microscopic details of the walls geometry. Finally, the effects on the flow behavior of the channel symmetry and aspect ratio are also investigated.

Flow boiling with enhancement devices for cold plate coolant channel design

NASA Technical Reports Server (NTRS)

Boyd, Ronald D., Sr.

1989-01-01

A research program to study the effect of enhancement devices on flow boiling heat transfer in coolant channels, which are heated either from the top side or uniformly, is discussed. Freon 11 is the working fluid involved. The specific objectives are: (1) examine the variations in both the mean and local (axial and circumferential) heat transfer coefficients for a circular coolant channel with either smooth walls or with both a twisted tape and spiral finned walls, (2) examine the effect channel diameter (and the length-to-diameter aspect ratio) variations for the smooth wall channel, and (3) develop an improved data reduction analysis.

Capacities of quantum amplifier channels

NASA Astrophysics Data System (ADS)

Qi, Haoyu; Wilde, Mark M.

2017-01-01

Quantum amplifier channels are at the core of several physical processes. Not only do they model the optical process of spontaneous parametric down-conversion, but the transformation corresponding to an amplifier channel also describes the physics of the dynamical Casimir effect in superconducting circuits, the Unruh effect, and Hawking radiation. Here we study the communication capabilities of quantum amplifier channels. Invoking a recently established minimum output-entropy theorem for single-mode phase-insensitive Gaussian channels, we determine capacities of quantum-limited amplifier channels in three different scenarios. First, we establish the capacities of quantum-limited amplifier channels for one of the most general communication tasks, characterized by the trade-off between classical communication, quantum communication, and entanglement generation or consumption. Second, we establish capacities of quantum-limited amplifier channels for the trade-off between public classical communication, private classical communication, and secret key generation. Third, we determine the capacity region for a broadcast channel induced by the quantum-limited amplifier channel, and we also show that a fully quantum strategy outperforms those achieved by classical coherent-detection strategies. In all three scenarios, we find that the capacities significantly outperform communication rates achieved with a naive time-sharing strategy.

Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments.

PubMed

Mattusch, Corinna; Kratzer, Stephan; Buerge, Martina; Kreuzer, Matthias; Engel, Tatiana; Kopp, Claudia; Biel, Martin; Hammelmann, Verena; Ying, Shui-Wang; Goldstein, Peter A; Kochs, Eberhard; Haseneder, Rainer; Rammes, Gerhard

2015-05-01

The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined. The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels. Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated Ih current amplitude by 33.4 ± 12.2% (at -133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V1/2) from -98.8 ± 1.6 to -108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2 mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo. Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon.

Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity

PubMed Central

Ader, Christian; Schneider, Robert; Hornig, Sönke; Velisetty, Phanindra; Vardanyan, Vitya; Giller, Karin; Ohmert, Iris; Becker, Stefan; Pongs, Olaf; Baldus, Marc

2009-01-01

Potassium (K+)-channel gating is choreographed by a complex interplay between external stimuli, K+ concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA–Kv1.3 channel to delineate K+, pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K+ and channel blockers distinctly affect the open probability of both the inactivation gate comprising the selectivity filter of the channel and the activation gate. The results indicate that the two gates are coupled and that effects of the permeant K+ ion on the inactivation gate modulate activation-gate opening. Our data suggest a mechanism for controlling coordinated and sequential opening and closing of activation and inactivation gates in the K+-channel pore. PMID:19661921

Channel Noise-Enhanced Synchronization Transitions Induced by Time Delay in Adaptive Neuronal Networks with Spike-Timing-Dependent Plasticity

NASA Astrophysics Data System (ADS)

Xie, Huijuan; Gong, Yubing; Wang, Baoying

In this paper, we numerically study the effect of channel noise on synchronization transitions induced by time delay in adaptive scale-free Hodgkin-Huxley neuronal networks with spike-timing-dependent plasticity (STDP). It is found that synchronization transitions by time delay vary as channel noise intensity is changed and become most pronounced when channel noise intensity is optimal. This phenomenon depends on STDP and network average degree, and it can be either enhanced or suppressed as network average degree increases depending on channel noise intensity. These results show that there are optimal channel noise and network average degree that can enhance the synchronization transitions by time delay in the adaptive neuronal networks. These findings could be helpful for better understanding of the regulation effect of channel noise on synchronization of neuronal networks. They could find potential implications for information transmission in neural systems.

n-Alcohols Inhibit Voltage-Gated Na+ Channels Expressed in Xenopus Oocytes

PubMed Central

Horishita, Takafumi; Harris, R. Adron

2008-01-01

Voltage-gated sodium channels are essential for the initiation and propagation of action potentials in excitable cells and are known as a target of local anesthetics. In addition, inhibition of sodium channels by volatile anesthetics has been proposed as a mechanism of general anesthesia. The n-alcohols produce anesthesia, and their potency increases with carbon number until a “cut-off” is reached. In this study, we examined effects of a range of n-alcohols on Nav1.2 subunits to determine the alcohol cut-off for this channel. We also studied the effect of a short-chain alcohol (ethanol) and a long-chain alcohol (octanol) on Nav1.2, Nav1.4, Nav1.6, and Nav1.8 subunits, and we investigated the effects of alcohol on channel kinetics. Ethanol and octanol inhibited sodium currents of all subunits, and the inhibition of the Nav1.2 channel by n-alcohols indicated a cut-off at nonanol. Ethanol and octanol produced open-channel block, which was more pronounced for Nav1.8 than for the other sodium channels. Inhibition of Nav1.2 was due to decreased activation and increased inactivation. These results suggest that sodium channels may have a hydrophobic binding site for n-alcohols and demonstrate the differences in the kinetic mechanisms of inhibition for n-alcohols and inhaled anesthetics. PMID:18434586

Biogeomorphic feedbacks in the Southwestern USA: exploring the mechanisms of geomorphic change and the effectiveness of mitigation measures

NASA Astrophysics Data System (ADS)

Dean, D. J.; Diehl, R. M.; Topping, D. J.

2017-12-01

Water development and the proliferation of riparian plants have resulted in extensive geomorphic change to rivers worldwide. In many dryland rivers of the Southwestern U.S., these phenomena have contributed to conditions of sediment accumulation leading to channel narrowing, floodplain aggradation, and loss of fluvial habitat. Using a series of field and laboratory measurements, we demonstrate how biogeomorphic feedbacks have promoted channel contraction. Experimental evidence shows that vegetation can have a substantial effect on local hydraulics and sediment-transport fields, depending on plant morphology, but that the impact of plants on physical processes is mediated by flow and sediment supply. In the Little Colorado River in Arizona, water management practices, variations in climate/hydrology, and the resultant expansion of riparian vegetation have resulted in channel narrowing, increases in sinuosity and drag, and decreases in channel slope. These changes have created a biogeomorphic feedback by disrupting downstream flood conveyance; flood travel time has increased resulting in flow attenuation, declines in peak discharge, and continued sediment accumulation at large scales. In the Rio Grande in Big Bend National Park, channel narrowing and floodplain aggradation has led to the loss of channel capacity and an increase in overbank flooding even though discharges have declined. Vegetation expansion into channel environments has exacerbated this condition by reducing channel-margin flow velocities, increasing sediment deposition, and reducing bank erosion thereby creating a biogeomorphic feedback leading to additional narrowing. An understanding of the mechanisms that have driven geomorphic changes in river channels may help to formulate effective mitigation measures. Vegetation removal can have local and reach-scale effects on channel morphology; however, the effectiveness of these actions is dependent upon many variables including the flow regime and upstream sediment supply. At larger scales, the construction of continuous mass-balance sediment budgets, such as on the Rio Grande and the Yampa and Green rivers in Dinosaur National Monument, can help managers tailor upstream water releases required to maintain sufficient channel complexity or to maximize sediment export.

Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker

PubMed Central

Ta, Chau M; Adomaviciene, Aiste; Rorsman, Nils J G; Garnett, Hannah

2016-01-01

Background and Purpose Calcium‐activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene‐9‐carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined. Experimental Approach Patch‐clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels. Key Results In the presence of high intracellular Ca2+, A9C inhibited TMEM16A currents in a voltage‐dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca2+ concentrations, was also voltage‐dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open‐channel block mechanism. Activation was due to a dramatic leftward shift in the steady‐state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl−, suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects. Conclusions and Implications A9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels. PMID:26562072

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate

PubMed Central

Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris

2017-01-01

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP2). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP2. Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes. PMID:28716904

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.

PubMed

Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris; Gamper, Nikita

2017-08-01

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP 2 ). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP 2 Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes.

An allosteric model of the molecular interactions of excitation- contraction coupling in skeletal muscle

PubMed Central

1993-01-01

A contact interaction is proposed to exist between the voltage sensor of the transverse tubular membrane of skeletal muscle and the calcium release channel of the sarcoplasmic reticulum. This interaction is given a quantitative formulation inspired in the Monod, Wyman, and Changeux model of allosteric transitions in hemoglobin (Monod, J., J. Wyman, and J.-P. Changeux. 1965. Journal of Molecular Biology. 12:88- 118), and analogous to one proposed by Marks and Jones for voltage- dependent Ca channels (Marks, T. N., and S. W. Jones. 1992. Journal of General Physiology. 99:367-390). The allosteric protein is the calcium release channel, a homotetramer, with two accessible states, closed and open. The kinetics and equilibrium of this transition are modulated by voltage sensors (dihydropyridine receptors) pictured as four units per release channel, each undergoing independent voltage-driven transitions between two states (resting and activating). For each voltage sensor that moves to the activating state, the tendency of the channel to open increases by an equal (large) factor. The equilibrium and kinetic equations of the model are solved and shown to reproduce well a number of experimentally measured relationships including: charge movement (Q) vs. voltage, open probability of the release channel (Po) vs. voltage, the transfer function relationship Po vs. Q, and the kinetics of charge movement, release activation, and deactivation. The main consequence of the assumption of allosteric coupling is that primary effects on the release channel are transmitted backward to the voltage sensor and give secondary effects. Thus, the model reproduces well the effects of perchlorate, described in the two previous articles, under the assumption that the primary effect is to increase the intrinsic tendency of the release channel to open, with no direct effects on the voltage sensor. This modification of the open-closed equilibrium of the release channel causes a shift in the equilibrium dependency of charge movement with voltage. The paradoxical slowing of charge movement by perchlorate also results from reciprocal effects of the channel on the allosterically coupled voltage sensors. The observations of the previous articles plus the simulations in this article constitute functional evidence of allosteric transmission. PMID:8245819

Propofol inhibits carbachol-induced chloride secretion by directly targeting the basolateral K+ channel in rat ileum epithelium.

PubMed

Tang, S-H; Wang, H-Y; Sun, H; An, N; Xiao, L; Sun, Q; Zhao, D-B

2017-02-01

Propofol is a widely used intravenous general anesthetic. Acetylcholine (ACh) is critical in controlling epithelial ion transport. This study was to investigate the effects of propofol on ACh-evoked secretion in rat ileum epithelium. The Ussing chamber technique was used to investigate the effects of propofol on carbachol (CCh)-evoked short-circuit currents (Isc). Propofol (10 -2 -10 -6  mol/L) attenuated CCh-evoked Isc of rat ileum mucosa in a dose-dependent manner. The inhibitory effect of propofol was only evident after application to the serosal side. Pretreatment with tetrodotoxin (TTX, 0.3 μmol/L, n=5) had no effect on propofol-induced inhibitory effect, whereas serosal application of K + channel inhibitor, glibenclamide, but not, an ATP-sensitive K + channel inhibitor, largely reduced the inhibitory effect of propofol. In addition, pretreatment with either hexamethonium bromide (HB, nicotinic nACh receptor antagonist) or Cl - channel blockers niflumic acid and cystic fibrosis transmembrane conductance regulator (inh)-172 did not produce any effect on the propofol-induced inhibitory effect. Propofol inhibits CCh-induced intestinal secretion by directly targeting basolateral K + channels. © 2016 John Wiley & Sons Ltd.

Electrothermal flow effects in insulating (electrodeless) dielectrophoresis systems.

PubMed

Hawkins, Benjamin G; Kirby, Brian J

2010-11-01

We simulate electrothermally induced flow in polymeric, insulator-based dielectrophoresis (iDEP) systems with DC-offset, AC electric fields at finite thermal Péclet number, and we identify key regimes where electrothermal (ET) effects enhance particle deflection and trapping. We study a single, two-dimensional constriction in channel depth with parametric variations in electric field, channel geometry, fluid conductivity, particle electrophoretic (EP) mobility, and channel electroosmotic (EO) mobility. We report the effects of increasing particle EP mobility, channel EO mobility, and AC and DC field magnitudes on the mean constriction temperature and particle behavior. Specifically, we quantify particle deflection and trapping, referring to the deviation of particles from their pathlines due to dielectrophoresis as they pass a constriction and the stagnation of particles due to negative dielectrophoresis near a constriction, respectively. This work includes the coupling between fluid, heat, and electromagnetic phenomena via temperature-dependent physical parameters. Results indicate that the temperature distribution depends strongly on the fluid conductivity and electric field magnitude, and particle deflection and trapping depend strongly on the channel geometry. Electrothermal (ET) effects perturb the EO flow field, creating vorticity near the channel constriction and enhancing the deflection and trapping effects. ET effects alter particle deflection and trapping responses in insulator-based dielectrophoresis devices, especially at intermediate device aspect ratios (2 ≤ r ≤ 7) in solutions of higher conductivity (σ m ≥ 1 × 10(-3)S/m). The impact of ET effects on particle deflection and trapping are diminished when particle EP mobility or channel EO mobility is high. In almost all cases, ET effects enhance negative dielectrophoretic particle deflection and trapping phenomena. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding Charge Collection Mechanisms in InGaAs FinFETs Using High-Speed Pulsed-Laser Transient Testing With Tunable Wavelength

NASA Astrophysics Data System (ADS)

Ni, Kai; Sternberg, Andrew L.; Zhang, En Xia; Kozub, John A.; Jiang, Rong; Schrimpf, Ronald D.; Reed, Robert A.; Fleetwood, Daniel M.; Alles, Michael L.; McMorrow, Dale; Lin, Jianqiang; Vardi, Alon; del Alamo, Jesús

2017-08-01

A tunable wavelength laser system and high-resolution transient capture system are introduced to characterize transients in high-mobility MOSFETs. The experimental configuration enables resolution of fast transient signals and new understanding of charge collection mechanisms. The channel layer is critical in the charge collection process for the InGaAs FinFETs examined here. The transient current mainly comes from the channel current, due to shunt effects and parasitic bipolar effects, instead of the junction collection. The charge amplification factor is found to be as high as 14, which makes this technology relatively sensitive to transient radiation. The peak current is inversely proportional to the device gate length. Simulations show that the parasitic bipolar effect is due to source-to-channel barrier lowering caused by hole accumulation in the source and channel. Charge deposited in the channel causes prompt current, while charge deposited below the channel causes delayed and slow current.

Channel correlation of free space optical communication systems with receiver diversity in non-Kolmogorov atmospheric turbulence

NASA Astrophysics Data System (ADS)

Ma, Jing; Fu, Yulong; Tan, Liying; Yu, Siyuan; Xie, Xiaolong

2018-05-01

Spatial diversity as an effective technique to mitigate the turbulence fading has been widely utilized in free space optical (FSO) communication systems. The received signals, however, will suffer from channel correlation due to insufficient spacing between component antennas. In this paper, the new expressions of the channel correlation coefficient and specifically its components (the large- and small-scale channel correlation coefficients) for a plane wave with aperture effects are derived for horizontal link in moderate-to-strong turbulence, using a non-Kolmogorov spectrum that has a generalized power law in the range of 3-4 instead of the fixed classical Kolmogorov power law of 11/3. And then the influence of power law variations on the channel correlation coefficient and its components are analysed. The numerical results indicated that various value of the power law lead to varying effects on the channel correlation coefficient and its components. This work will help with the further investigation on the fading correlation in spatial diversity systems.

Effect of pore architecture on oxygen diffusion in 3D scaffolds for tissue engineering.

PubMed

Ahn, Geunseon; Park, Jeong Hun; Kang, Taeyun; Lee, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

2010-10-01

The aim of this study was to maximize oxygen diffusion within a three-dimensional scaffold in order to improve cell viability and proliferation. To evaluate the effect of pore architecture on oxygen diffusion, we designed a regular channel shape with uniform diameter, referred to as cylinder shaped, and a new channel shape with a channel diameter gradient, referred to as cone shaped. A numerical analysis predicted higher oxygen concentration in the cone-shaped channels than in the cylinder-shaped channels, throughout the scaffold. To confirm these numerical results, we examined cell proliferation and viability in 2D constructs and 3D scaffolds. Cell culture experiments revealed that cell proliferation and viability were superior in the constructs and scaffolds with cone-shaped channels.

Evaluation of in-channel amperometric detection using a dual-channel microchip electrophoresis device and a two-electrode potentiostat for reverse polarity separations

PubMed Central

Meneses, Diogenes; Gunasekara, Dulan B.; Pichetsurnthorn, Pann; da Silva, José A. F.; de Abreu, Fabiane C.; Lunte, Susan M.

2015-01-01

In-channel amperometric detection combined with dual-channel microchip electrophoresis is evaluated using a two-electrode isolated potentiostat for reverse polarity separations. The device consists of two separate channels with the working and reference electrodes placed at identical positions relative to the end of the channel, enabling noise subtraction. In previous reports of this configuration, normal polarity and a three-electrode detection system were used. In the two-electrode detection system described here, the electrode in the reference channel acts as both the counter and reference. The effect of electrode placement in the channels on noise and detector response was investigated using nitrite, tyrosine, and hydrogen peroxide as model compounds. The effects of electrode material and size and type of reference electrode on noise and the potential shift of hydrodynamic voltammograms for the model compounds were determined. In addition, the performance of two- and three-electrode configurations using Pt and Ag/AgCl reference electrodes was compared. Although the signal was attenuated with the Pt reference, the noise was also significantly reduced. It was found that lower LOD were obtained for all three compounds with the dual-channel configuration compared to single-channel, in-channel detection. The dual-channel method was then used for the detection of nitrite in a dermal microdialysis sample obtained from a sheep following nitroglycerin administration. PMID:25256669

Effects of egg quality and method of incubation on the hatching success of channel X blue hybrid catfish eggs

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the effects of egg quality of stripped eggs from channel catfish (Ictalurus punctatus) and method of incubation of fertilized hybrid catfish eggs on hatching success. Stripped eggs from 17 channel catfish females were evaluated in a 2 x 2 factorial...

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation—A Computational Study

PubMed Central

Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

2017-01-01

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment. PMID:28084429

Piezoelectric coupling in a field-effect transistor with a nanohybrid channel of ZnO nanorods grown vertically on graphene.

PubMed

Quang Dang, Vinh; Kim, Do-Il; Thai Duy, Le; Kim, Bo-Yeong; Hwang, Byeong-Ung; Jang, Mi; Shin, Kyung-Sik; Kim, Sang-Woo; Lee, Nae-Eung

2014-12-21

Piezoelectric coupling phenomena in a graphene field-effect transistor (GFET) with a nano-hybrid channel of chemical-vapor-deposited Gr (CVD Gr) and vertically aligned ZnO nanorods (NRs) under mechanical pressurization were investigated. Transfer characteristics of the hybrid channel GFET clearly indicated that the piezoelectric effect of ZnO NRs under static or dynamic pressure modulated the channel conductivity (σ) and caused a positive shift of 0.25% per kPa in the Dirac point. However, the GFET without ZnO NRs showed no change in either σ or the Dirac point. Analysis of the Dirac point shifts indicated transfer of electrons from the CVD Gr to ZnO NRs due to modulation of their interfacial barrier height under pressure. High responsiveness of the hybrid channel device with fast response and recovery times was evident in the time-dependent behavior at a small gate bias. In addition, the hybrid channel FET could be gated by mechanical pressurization only. Therefore, a piezoelectric-coupled hybrid channel GFET can be used as a pressure-sensing device with low power consumption and a fast response time. Hybridization of piezoelectric 1D nanomaterials with a 2D semiconducting channel in FETs enables a new design for future nanodevices.

Cellular defibrillation: interaction of micro-scale electric fields with voltage-gated ion channels.

PubMed

Kargol, Armin; Malkinski, Leszek; Eskandari, Rahmatollah; Carter, Maya; Livingston, Daniel

2015-09-01

We study the effect of micro-scale electric fields on voltage-gated ion channels in mammalian cell membranes. Such micro- and nano-scale electric fields mimic the effects of multiferroic nanoparticles that were recently proposed [1] as a novel way of controlling the function of voltage-sensing biomolecules such as ion channels. This article describes experimental procedures and initial results that reveal the effect of the electric field, in close proximity of cells, on the ion transport through voltage-gated ion channels. We present two configurations of the whole-cell patch-clamping apparatus that were used to detect the effect of external stimulation on ionic currents and discuss preliminary results that indicate modulation of the ionic currents consistent with the applied stimulus.

In silico determination of the effect of multi-target drugs on calcium dynamics signaling network underlying sea urchin spermatozoa motility.

PubMed

Espinal-Enríquez, Jesús; Darszon, Alberto; Guerrero, Adán; Martínez-Mekler, Gustavo

2014-01-01

The motility of spermatozoa of both Lytechinus pictus and Strongylocentrotus purpuratus sea urchin species is modulated by the egg-derived decapeptide speract via an oscillatory [Ca2+]-dependent signaling pathway. Comprehension of this pathway is hence directly related to the understanding of regulated sperm swimming. Niflumic acid (NFA), a nonsteroidal anti-inflammatory drug alters several ion channels. Though unspecific, NFA profoundly affects how sea urchin sperm respond to speract, increasing the [Ca2+]i oscillation period, amplitude, peak and average level values of the responses in immobilized and swimming cells. A previous logical network model we developed for the [Ca2+] dynamics of speract signaling cascade in sea urchin sperm allows integrated dissection of individual and multiple actions of NFA. Among the channels affected by NFA are: hyperpolarization-activated and cyclic nucleotide gated Na+ channels (HCN), [Ca2+]-dependent Cl- channels (CaCC) and [Ca2+]-dependent K+ channels (CaKC), all present in the sea urchin genome. Here, using our model we investigated the effect of blocking in silico HCN and CaCC channels suggested by experiments. Regarding CaKC channels, arguments can be provided for either their blockage or activation by NFA. Our study yielded two scenarios compliant with experimental observations: i) under CaKC inhibition, this [Ca2+]-dependent K+ channel should be different from the Slo1 channel and ii) under activation of the CaKC channel, another [Ca2+] channel not considered previously in the network is required, such as the pH-dependent CatSper channel. Additionally, our findings predict cause-effect relations resulting from a selective inhibition of those channels. Knowledge of these relations may be of consequence for a variety of electrophysiological studies and have an impact on drug related investigations. Our study contributes to a better grasp of the network dynamics and suggests further experimental work.

In Silico Determination of the Effect of Multi-Target Drugs on Calcium Dynamics Signaling Network Underlying Sea Urchin Spermatozoa Motility

PubMed Central

Espinal-Enríquez, Jesús; Darszon, Alberto; Guerrero, Adán; Martínez-Mekler, Gustavo

2014-01-01

The motility of spermatozoa of both Lytechinus pictus and Strongylocentrotus purpuratus sea urchin species is modulated by the egg-derived decapeptide speract via an oscillatory [Ca2+]-dependent signaling pathway. Comprehension of this pathway is hence directly related to the understanding of regulated sperm swimming. Niflumic acid (NFA), a nonsteroidal anti-inflammatory drug alters several ion channels. Though unspecific, NFA profoundly affects how sea urchin sperm respond to speract, increasing the [Ca2+]i oscillation period, amplitude, peak and average level values of the responses in immobilized and swimming cells. A previous logical network model we developed for the [Ca2+] dynamics of speract signaling cascade in sea urchin sperm allows integrated dissection of individual and multiple actions of NFA. Among the channels affected by NFA are: hyperpolarization-activated and cyclic nucleotide gated Na+ channels (HCN), [Ca2+]-dependent Cl− channels (CaCC) and [Ca2+]-dependent K+ channels (CaKC), all present in the sea urchin genome. Here, using our model we investigated the effect of blocking in silico HCN and CaCC channels suggested by experiments. Regarding CaKC channels, arguments can be provided for either their blockage or activation by NFA. Our study yielded two scenarios compliant with experimental observations: i) under CaKC inhibition, this [Ca2+]-dependent K+ channel should be different from the Slo1 channel and ii) under activation of the CaKC channel, another [Ca2+] channel not considered previously in the network is required, such as the pH-dependent CatSper channel. Additionally, our findings predict cause-effect relations resulting from a selective inhibition of those channels. Knowledge of these relations may be of consequence for a variety of electrophysiological studies and have an impact on drug related investigations. Our study contributes to a better grasp of the network dynamics and suggests further experimental work. PMID:25162222

Modulation of inward rectifier potassium channel by toosendanin, a presynaptic blocker.

PubMed

Wang, Z F; Shi, Y L

2001-07-01

The effect of toosendanin, a presynaptic blocker, on the inward rectifier potassium channel (K(Kir)) of hippocampal CA1 pyramidal neurons of rats was studied by the single-channel patch-clamp technique. The results showed that toosendanin had an inhibitory effect on K(Kir) in an excised inside-out patch of the neuron under a symmetrical 150 mM K(+) condition. By decreasing the slower open time constant and increasing the slower close time constant, toosendanin (1x10(-6)-1x10(-4) g/ml) significantly reduced the open probability of the channel in a concentration-dependent manner. Meanwhile, a dose-dependent reduction in unitary conductance of the channel was also detected after toosendanin application. These data offer an explanation for toosendanin-induced facilitation of neurotransmitter release and antibotulismic effect of the drug.

Improving Audience Learning from Television News through Between-Channel Redundancy.

ERIC Educational Resources Information Center

Reese, Stephen D.

A study tested the effects of between-channel redundancy on television news learning. Redundancy, defined as shared information, was proposed as an explanatory variable that considers the relationship between information in three channels: the audio, the nonverbal pictorial, and visual-verbal print channel. It was hypothesized that pictures would…

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test.

PubMed

Nazari, Seyedeh Khadijeh; Nikoui, Vahid; Ostadhadi, Sattar; Chegini, Zahra Hadi; Oryan, Shahrbanoo; Bakhtiarian, Azam

2016-12-01

Previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of baclofen in the forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of K ATP channels, after determination of sub-effective doses of glibenclamide as a K ATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. Baclofen at dose 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant-like effect of baclofen (1mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. Our study for the first time revealed that antidepressant-like effect of baclofen on mice is K ATP -dependent, and baclofen seems that exert this effect by blocking the K ATP channels. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Differential Effects of TRPA and TRPV Channels on Behaviors of Caenorhabditis elegans

PubMed Central

Thies, Jennifer; Neutzler, Vanessa; O’Leary, Fidelma; Liu, He

2016-01-01

TRPA and TRPV ion channels are members of the transient receptor potential (TRP) cation channel superfamily, which mediates various sensory transductions. In Caenorhabditis elegans, the TRPV channels are known to affect chemosensation, while the TRPA-1 channel is associated with thermosensation and mechanosensation. We examined thermosensation, chemosensation, and osmosensation in strains lacking TRPA-1 or TRPV channels. We found that TRPV channel knockout worms exhibited similar behavioral deficits associated with thermotaxis as the TRPA-1 channel knockout, suggesting a dual role for TRPV channels. In contrast, chemosensation responses, assessed by both avoidance reversal behavior and NaCl osmosensation, were dependent on TRPV channels but seemed independent of TRPA-1 channel. Our findings suggest that, in addition to TRPA-1 channel, TRPV channels are necessary for thermotaxis and may activate, or modulate, the function of TRPA-1 channels. In contrast, TRPA-1 channels do not have a dual responsibility, as they have no functional role in odorant avoidance or osmosensation. PMID:27168724

BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Storm, Johan F

2007-01-01

Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

Down-regulation of ether-a-go-go-related gene potassium channel protein through sustained stimulation of AT1 receptor by angiotensin II.

PubMed

Cai, Yue; Wang, Yuhong; Xu, Jia; Zuo, Xu; Xu, Yanfang

2014-09-26

We investigated the effects of AT1 receptor stimulation by angiotensin II (Ang II) on human ether-a-go-go-related gene (hERG) potassium channel protein in a heterogeneous expression system with the human embryonic kidney (HEK) 293 cells which stably expressed hERG channel protein and were transiently transfected with the human AT1 receptors (HEK293/hERG). Western-blot analysis showed that Ang II significantly decreased the expression of mature hERG channel protein (155-kDa band) in a time- and dose-dependent manner without affecting the level of immature hERG channel protein (135-kDa band). The relative intensity of 155-kDa band was 64.7±6.8% of control (P<0.01) after treatment of Ang II at 100nM for 24h. To investigate the effect of Ang II on the degradation of mature hERG channel protein, we blocked forward trafficking from ER to Golgi with a Golgi transit inhibitor brefeldin A (10μM). Ang II significantly enhanced the time-dependent reduction of mature hERG channel protein. In addition, the proteasomal inhibitor lactacystin (5μM) inhibited Ang II-mediated the reduction of mature hERG channel protein, but the lysosomal inhibitor bafilomycin A1 (1μM) had no effect on the protein. The protein kinase C (PKC) inhibitor bisindolylmaleimide 1 (1μM) antagonized the reduction of mature hERG channel protein induced by Ang II. The results indicate that sustained stimulation of AT1 receptors by Ang II reduces the mature hERG channel protein via accelerating channel proteasomal degradation involving the PKC pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of the putative potassium channel activator WAY-120,491 on 86Rb efflux from the rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lodge, N.J.; Cohen, R.B.; Havens, C.N.

1991-02-01

WAY-120,491 ((-)-(3S-trans)-2-(3,4-dihydro-3-hydroxy-2,2-dimethyl-6-(trifluoromet hox y)- 2H-1-benzopyran-4-yl)-2,3-dihydro-1H-isoindol-1-one) is a novel antihypertensive agent. We have investigated the effects of this compound on contractile force and 86Rb efflux, using the rabbit aorta, in order to assess its K channel activator properties. K channel blockers and ionic conditions thought to modulate specific K channel types have been used to provide insight into the K channel(s) affected by this compound. WAY-120,491 evoked relaxation of precontracted rabbit aortic rings and increased the rate of 86Rb efflux from strips of rabbit aorta; both effects occurring in a concentration-dependent manner. The WAY-120,491 (1 microM)-induced 86Rb efflux was inhibited bymore » tetraethylammonium (IC50 = 0.38 mM), indicating that the increased efflux was mediated by K channels. Glyburide completely blocked the WAY-120,491 (1 microM)-evoked 86Rb efflux with 50% block occurring at a concentration of 0.48 microM. Glyburide also antagonized the WAY-120,491-induced relaxation of aortic rings. Omission of Ca from the solution bathing the aorta did not inhibit the WAY-120,491 induced 86Rb efflux but rather caused an augmentation of the response. It is concluded that WAY-120,491 may be classified as a K channel opener. Furthermore, the K channel upon which WAY-120,491 acts exhibits some characteristics normally associated with the ATP regulated K channel although the involvement of other K channel types has not been ruled out.« less

Methamphetamine acutely inhibits voltage-gated calcium channels but chronically up-regulates L-type channels.

PubMed

Andres, Marilou A; Cooke, Ian M; Bellinger, Frederick P; Berry, Marla J; Zaporteza, Maribel M; Rueli, Rachel H; Barayuga, Stephanie M; Chang, Linda

2015-07-01

In neurons, calcium (Ca(2+) ) channels regulate a wide variety of functions ranging from synaptic transmission to gene expression. They also induce neuroplastic changes that alter gene expression following psychostimulant administration. Ca(2+) channel blockers have been considered as potential therapeutic agents for the treatment of methamphetamine (METH) dependence because of their ability to reduce drug craving among METH users. Here, we studied the effects of METH exposure on voltage-gated Ca(2+) channels using SH-SY5Y cells as a model of dopaminergic neurons. We found that METH has different short- and long-term effects. A short-term effect involves immediate (< 5 min) direct inhibition of Ca(2+) ion movements through Ca(2+) channels. Longer exposure to METH (20 min or 48 h) selectively up-regulates the expression of only the CACNA1C gene, thus increasing the number of L-type Ca(2+) channels. This up-regulation of CACNA1C is associated with the expression of the cAMP-responsive element-binding protein (CREB), a known regulator of CACNA1C gene expression, and the MYC gene, which encodes a transcription factor that putatively binds to a site proximal to the CACNA1C gene transcription initiation site. The short-term inhibition of Ca(2+) ion movement and later, the up-regulation of Ca(2+) channel gene expression together suggest the operation of cAMP-responsive element-binding protein- and C-MYC-mediated mechanisms to compensate for Ca(2+) channel inhibition by METH. Increased Ca(2+) current density and subsequent increased intracellular Ca(2+) may contribute to the neurodegeneration accompanying chronic METH abuse. Methamphetamine (METH) exposure has both short- and long-term effects. Acutely, methamphetamine directly inhibits voltage-gated calcium channels. Chronically, neurons compensate by up-regulating the L-type Ca(2+) channel gene, CACNA1C. This compensatory mechanism is mediated by transcription factors C-MYC and CREB, in which CREB is linked to the dopamine D1 receptor signaling pathway. These findings suggest Ca(2+) -mediated neurotoxicity owing to over-expression of calcium channels. © 2015 International Society for Neurochemistry.

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin.

PubMed

Barker, Bryan S; Ottolini, Matteo; Wagnon, Jacy L; Hollander, Rachel M; Meisler, Miriam H; Patel, Manoj K

2016-09-01

SCN8A encephalopathy (early infantile epileptic encephalopathy; EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav 1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0 and 18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard antiepileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μm) on mutant and wild-type (WT) channels were compared. Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, whereas inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μm) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use-dependent block of I1327V mutant channels relative to WT. SCN8A - I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain-of-function mutations of SCN8A. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin

PubMed Central

Barker, Bryan S.; Ottolini, Matteo; Wagnon, Jacy L.; Hollander, Rachel; Meisler, Miriam H.; Patel, Manoj K.

2016-01-01

Objective SCN8A encephalopathy (EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0–18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard anti-epileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. Methods The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μM) on mutant and wild type (WT) channels were compared. Results Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, while inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μM) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use dependent block of I1327V mutant channels relative to WT. Significance SCN8A – I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain-of-function mutations of SCN8A. PMID:27375106

Calcium channel antagonists in the treatment of hypertension.

PubMed

Weber, Michael A

2002-01-01

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.

LRO Diviner Nonlinear Response and Opposition Effect Corrections

NASA Astrophysics Data System (ADS)

Gyalay, S.; Aye, K. M.; Paige, D. A.

2016-12-01

Aboard the Lunar Reconnaissance Orbiter, the Diviner Lunar Radiometer Experiment measures thermal radiation to determine the brightness temperature of the lunar surface. As with the Mars Climate Sounder (upon which Diviner is based), we use pre-flight calibration data to correct for the nonlinear response in Diviner's detectors, which in-turn accounts for much of the detector non-uniformity within channels. Furthermore, channels 8 and 9 exhibit unexpectedly high brightness temperatures close to the equator around midday, with even higher brightness temperatures when observing lunar highlands as opposed to maria. Unexpectedly high brightness temperatures around midday at the equator is reminiscent of the opposition effect known to exist on the Moon at low phase angles in Visual to Near Infra-Red (VNIR) wavelengths. Diviner channel 2 data (which detects solar radiation reflected by the Moon) shows this opposition effect, which is more pronounced in the highlands than the maria. We interpret a correlation we observe between channel 2 detected radiance and channel 8 and 9 brightness temperature as due to incomplete blocking of reflected solar radiation. This leads us to an opposition effect correction for Diviner channels 8 and 9 dependent on Diviner's solar channel data. Whether this is a direct leak of VNIR light upon the detectors, or solar heating of blocking filters, which then radiate infrared radiation upon the detectors, is yet to be determined. We can use the nonlinearity and opposition effect corrections to recharacterize the spectral emissivity of the lunar regolith, which we can then compare to laboratory spectra.

Dominant-negative suppression of big brain ion channel activity by mutation of a conserved glutamate in the first transmembrane domain.

PubMed

Yool, Andrea J

2007-01-01

The neurogenic protein Drosophila big brain (BIB), which is involved in the process of neuroblast determination, and the water channel aquaporin-1 (AQP1) are among a subset of the major intrinsic protein (MIP) channels that have been found to show gated monovalent cation channel activity. A glutamate residue in the first transmembrane (M1) domain is conserved throughout the MIP family. Mutation of this residue to asparagine in BIB (E71N) knocks out ion channel activity, and when coexpressed with BIB wild-type as shown here generates a dominant-negative effect on ion channel function, measured in the Xenopus oocyte expression system using two-electrode voltage clamp. cRNAs for wild-type and mutant BIB or AQP1 channels were injected individually or as mixtures. The magnitude of the BIB ionic conductance response was greatly reduced by coexpression of the mutant E71N subunit, suggesting a dominant-negative mechanism of action. The analogous mutation in AQP1 (E17N) did not impair ion channel activation by cGMP, but did knock out water channel function, although not via a dominant-negative effect. This contrast in sensitivity between BIB and AQP1 to mutation of the M1 glutamate suggests the possibility of interesting structural differences in the molecular basis of the ion permeation between these two classes of channels. The dominant-negative construct of BIB could be a tool for testing a role for BIB ion channels during nervous system development in Drosophila. The neurogenic protein Drosophila big brain (BIB), which is involved in the process of neuroblast determination, and the water channel aquaporin-1 (AQP1) are among a subset of the major intrinsic protein (MIP) channels that have been found to show gated monovalent cation channel activity. A glutamate residue in the first transmembrane (M1) domain is conserved throughout the MIP family. Mutation of this residue to asparagine in BIB (E71N) knocks out ion channel activity, and when coexpressed with BIB wild-type as shown here generates a dominant-negative effect on ion channel function, measured in the Xenopus oocyte expression system using two-electrode voltage clamp. cRNAs for wild-type and mutant BIB or AQP1 channels were injected individually or as mixtures. The magnitude of the BIB ionic conductance response was greatly reduced by coexpression of the mutant E71N subunit, suggesting a dominant-negative mechanism of action. The analogous mutation in AQP1 (E17N) did not impair ion channel activation by cGMP, but did knock out water channel function, although not via a dominant-negative effect. This contrast in sensitivity between BIB and AQP1 to mutation of the M1 glutamate suggests the possibility of interesting structural differences in the molecular basis of the ion permeation between these two classes of channels. The dominant-negative construct of BIB could be a tool for testing a role for BIB ion channels during nervous system development in Drosophila.

The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels.

PubMed

Gomes Castro, Allisson Jhonatan; Cazarolli, Luisa Helena; Bretanha, Lizandra C; Sulis, Paola Miranda; Rey Padilla, Diana Patricia; Aragón Novoa, Diana Marcela; Dambrós, Betina Fernanda; Pizzolatti, Moacir G; Mena Barreto Silva, Fátima Regina

2018-06-15

Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium. Additionally, the downstream activation of PKC, which is necessary for the effect of BA on calcium influx, is involved in the full stimulatory response of the triterpene. BA stimulated the static secretion of insulin in pancreatic islets, indicating that the abrupt calcium influx may be a key step in its secretagogue effect. As such, BA stimulates insulin secretion through the activation of electrophysiological mechanisms, such as the closure of potassium channels and opening of calcium and chloride channels, inducing cellular depolarization associated with metabolic-biochemical effects, in turn activating PKC and ensuring the secretion of insulin. Copyright © 2018 Elsevier Inc. All rights reserved.

Synthesis, QSAR and calcium channel modulator activity of new hexahydroquinoline derivatives containing nitroimidazole.

PubMed

Miri, Ramin; Javidnia, Katayoun; Mirkhani, Hossein; Hemmateenejad, Bahram; Sepeher, Zahra; Zalpour, Masomeh; Behzad, Taherh; Khoshneviszadeh, Mehdi; Edraki, Najmeh; Mehdipour, Ahmad R

2007-10-01

The discovery that 1,4-dihydropyridine class of calcium channel antagonists inhibit Ca2+ influx represented a major therapeutic advance in the treatment of cardiovascular disease. In contrast to the effects of known calcium channel blockers of the Nifedipine-type, the so-called calcium channel agonists, such as Bay K8644 and CGP 28392, increase calcium influx by binding at the same receptor regions. Our goal was to discover a dual cardioselective Ca2+-channel agonist/vascular selective smooth muscle Ca2+ channel antagonist third-generation 1,4-dihydropyridine drug which would have a suitable therapeutic profile for treating congestive heart failure (CHF) patients. A series of unsymmetrical alkyl, cycloalkyl and aryl ester analogues of 2-methyl-4-(1-methyl)-5-nitro-2-imidazolyl-5-oxo-1,4,5,6,7, 8-hexahydroquinolin-3-arboxylate were synthesized using modified Hantzsch reaction. All compounds show calcium antagonist activity on guinea-pig ileum longitudinal smooth muscle and some of them show agonist effect activity on guinea-pig auricle. Effect of structural parameters on the Ca2+ channel agonist/antagonist was evaluated by quantitative structure-activity relationship analysis. These compounds could be considered as a synthon for developing a suitable drug for treating CHF patients.

Sterol Regulation of Voltage-Gated K+ Channels.

PubMed

Balajthy, Andras; Hajdu, Peter; Panyi, Gyorgy; Varga, Zoltan

2017-01-01

Cholesterol is an essential lipid building block of the cellular plasma membrane. In addition to its structural role, it regulates the fluidity and raft structure of the membrane and influences the course of numerous membrane-linked signaling pathways and the function of transmembrane proteins, including ion channels. This is supported by a vast body of scientific data, which demonstrates the modulation of ion channels with a great variety of ion selectivity, gating, and tissue distribution by changes in membrane cholesterol. Here, we review what is currently known about the modulation of voltage-gated K + (Kv) channels by changes in membrane cholesterol content, considering raft association of the channels, the roles of cholesterol recognition sites, and those of adaptor proteins in cholesterol-Kv channel interactions. We specifically focus on Kv1.3, the dominant K + channel of human T cells. Effects of cholesterol depletion and enrichment and 7-dehydrocholesterol enrichment on Kv1.3 gating are discussed in the context of the immunological synapse and the comparison of the in vitro effects of sterol modifications on Kv1.3 function with ex vivo effects on cells from hypercholesterolemic and Smith-Lemli-Opitz patients. © 2017 Elsevier Inc. All rights reserved.

Single-channel mixed signal blind source separation algorithm based on multiple ICA processing

NASA Astrophysics Data System (ADS)

Cheng, Xiefeng; Li, Ji

2017-01-01

Take separating the fetal heart sound signal from the mixed signal that get from the electronic stethoscope as the research background, the paper puts forward a single-channel mixed signal blind source separation algorithm based on multiple ICA processing. Firstly, according to the empirical mode decomposition (EMD), the single-channel mixed signal get multiple orthogonal signal components which are processed by ICA. The multiple independent signal components are called independent sub component of the mixed signal. Then by combining with the multiple independent sub component into single-channel mixed signal, the single-channel signal is expanded to multipath signals, which turns the under-determined blind source separation problem into a well-posed blind source separation problem. Further, the estimate signal of source signal is get by doing the ICA processing. Finally, if the separation effect is not very ideal, combined with the last time's separation effect to the single-channel mixed signal, and keep doing the ICA processing for more times until the desired estimated signal of source signal is get. The simulation results show that the algorithm has good separation effect for the single-channel mixed physiological signals.

Nucleus accumbens hyperpolarization-activated cyclic nucleotide-gated channels modulate methamphetamine self-administration in rats.

PubMed

Cao, Dan-Ni; Song, Rui; Zhang, Shu-Zhuo; Wu, Ning; Li, Jin

2016-08-01

Methamphetamine addiction is believed to primarily result from increased dopamine release and the inhibition of dopamine uptake. Some evidence suggests that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in the functional modulation of dopaminergic neurons and the pathophysiology of related diseases. However, little is known about the effects of HCN channels on methamphetamine addiction. The present study investigated the role of brain HCN channels in methamphetamine addiction. Acute intracerebroventricular (i.c.v.) injection or bilateral intra-accumbens microinjections of non-selective HCN channel blocker ZD7288 (0.3125 and 0.625 μg) significantly reduced both methamphetamine (0.0125 or 0.05 mg/kg/infusion)-induced self-administration under fixed ratio 2 reinforcement and the breakpoint of methamphetamine (0.05 mg/kg/infusion) under progressive ratio reinforcement in rats. Moreover, compared with i.c.v. injection, bilateral intra-accumbens microinjections of ZD7288 exerted stronger inhibitory effects, suggesting that blockade of HCN channels in the nucleus accumbens reduced the reinforcing effects of and motivation for methamphetamine. We also found that ZD7288 (0.625 and 1.25 μg, i.c.v.) significantly decreased methamphetamine (1 mg/kg, intraperitoneal (i.p.))-induced hyperactivity with no effect on the spontaneous activity in rats. Finally, in vivo microdialysis experiments showed that the HCN channel blockade using ZD7288 (0.625 and 1.25 μg, i.c.v.) decreased methamphetamine (1 mg/kg, i.p.)-induced elevation of extracellular dopamine levels in the nucleus accumbens. These results indicate that HCN channels in the nucleus accumbens are involved in the reinforcing properties of methamphetamine and highlight the importance of HCN channels in the regulation of dopamine neurotransmission underlying methamphetamine addiction.

Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea-pig.

PubMed Central

Kaibara, M; Kameyama, M

1988-01-01

1. The inhibitory effects of intracellular protons (Hi+) on the L-type Ca2+ channel activity were investigated in single ventricular myocytes of guinea-pigs by using the patch-clamp method in the open-cell-attached patch configuration, where 'run down' of the channel was partially prevented. 2. Hi+ reduced the unitary Ba2+ current of the Ca2+ channel by 10-20% without changing the maximum slope conductance. 3. Hi+ did not alter the number of channels in patches containing one or two channels. 4. Hi+ markedly reduced the mean current normalized by the unitary current, which gave the open-state probability multiplied by the number of channels in the patch. The dose-response curve between Hi+ and the open-state probability indicated half-maximum inhibition at pHi 6.6 and an apparent Hill coefficient of 1. 5. Hi+ shifted both the steady-state activation and inactivation curves in a negative direction by 10-15 mV, and the effects were reversible. 6. Hi+ did not affect the fast open-closed kinetics represented by the C-C-O scheme, apart from increasing the slow time constant of the closed time. 7. Hi+ increased the percentage of blank sweeps and reduced that of non-blank sweeps resulting in a decreased probability of channel opening. 8. Photo-oxidation with Rose Bengal abolished the reducing effect of Hi+ on the open-state probability (Po) in two out of ten experiments, suggesting the possible involvement of histidine residues in the Hi+ effect. 9. The above results indicate that Hi+ inhibits the Ba2+ current mainly by affecting the slow gating mechanism of the channel. PMID:2855346

Impact of optical phonon scattering on inversion channel mobility in 4H-SiC trenched MOSFETs

NASA Astrophysics Data System (ADS)

Kutsuki, Katsuhiro; Kawaji, Sachiko; Watanabe, Yukihiko; Onishi, Toru; Fujiwara, Hirokazu; Yamamoto, Kensaku; Yamamoto, Toshimasa

2017-04-01

Temperature characteristics of the channel mobility were investigated for 4H-SiC trenched MOSFETs in the range from 30 to 200 °C. The conventional model of channel mobility limited by carrier scattering is based on Si-MOSFETs and shows a greatly different channel mobility from the experimental value, especially at high temperatures. On the other hand, our improved mobility model taking into account optical phonon scattering yielded results in excellent agreement with experimental results. Moreover, the major factors limiting the channel mobility were found to be Coulomb scattering in a low effective field (<0.7 MV/cm) and optical phonon scattering in a high effective field.

Effects of caffeine on cytoplasmic free Ca2+ concentration in pancreatic beta-cells are mediated by interaction with ATP-sensitive K+ channels and L-type voltage-gated Ca2+ channels but not the ryanodine receptor.

PubMed Central

Islam, M S; Larsson, O; Nilsson, T; Berggren, P O

1995-01-01

In the pancreatic beta-cell, an increase in the cytoplasmic free Ca2+ concentration ([Ca2+]i) by caffeine is believed to indicate mobilization of Ca2+ from intracellular stores, through activation of a ryanodine receptor-like channel. It is not known whether other mechanisms, as well, underlie caffeine-induced changes in [Ca2+]i. We studied the effects of caffeine on [Ca2+]i by using dual-wavelength excitation microfluorimetry in fura-2-loaded beta-cells. In the presence of a non-stimulatory concentration of glucose, caffeine (10-50 mM) consistently increased [Ca2+]i. The effect was completely blocked by omission of extracellular Ca2+ and by blockers of the L-type voltage-gated Ca2+ channel, such as D-600 or nifedipine. Depletion of agonist-sensitive intracellular Ca2+ pools by thapsigargin did not inhibit the stimulatory effect of caffeine on [Ca2+]i. Moreover, this effect of caffeine was not due to an increase in cyclic AMP, since forskolin and 3-isobutyl-1-methylxanthine (IBMX) failed to raise [Ca2+]i in unstimulated beta-cells. In beta-cells, glucose and sulphonylureas increase [Ca2+]i by causing closure of ATP-sensitive K+ channels (KATP channels). Caffeine also caused inhibition of KATP channel activity, as measured in excised inside-out patches. Accordingly, caffeine (> 10 mM) induced insulin release from beta-cells in the presence of a non-stimulatory concentration of glucose (3 mM). Hence, membrane depolarization and opening of voltage-gated L-type Ca2+ channels were the underlying mechanisms whereby the xanthine drug increased [Ca2+]i and induced insulin release. Paradoxically, in glucose-stimulated beta-cells, caffeine (> 10 mM) lowered [Ca2+]i. This effect was due to the fact that caffeine reduced depolarization-induced whole-cell Ca2+ current through the L-type voltage-gated Ca2+ channel in a dose-dependent manner. Lower concentrations of caffeine (2.5-5.0 mM), when added after glucose-stimulated increase in [Ca2+]i, induced fast oscillations in [Ca2+]i. The latter effect was likely to be attributable to the cyclic AMP-elevating action of caffeine, leading to phosphorylation of voltage-gated Ca2+ channels. Hence, in beta-cells, caffeine-induced changes in [Ca2+]i are not due to any interaction with intracellular Ca2+ pools. In these cells, a direct interference with KATP channel- and L-type voltage-gated Ca(2+)-channel activity is the underlying mechanism by which caffeine increases or decreases [Ca2+]i. Images Figure 9 PMID:7702559

BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells.

PubMed

Hirono, Moritoshi; Ogawa, Yasuhiro; Misono, Kaori; Zollinger, Daniel R; Trimmer, James S; Rasband, Matthew N; Misonou, Hiroaki

2015-05-06

In myelinated axons, K(+) channels are clustered in distinct membrane domains to regulate action potentials (APs). At nodes of Ranvier, Kv7 channels are expressed with Na(+) channels, whereas Kv1 channels flank nodes at juxtaparanodes. Regulation of axonal APs by K(+) channels would be particularly important in fast-spiking projection neurons such as cerebellar Purkinje cells. Here, we show that BK/Slo1 channels are clustered at the paranodal junctions of myelinated Purkinje cell axons of rat and mouse. The paranodal junction is formed by a set of cell-adhesion molecules, including Caspr, between the node and juxtaparanodes in which it separates nodal from internodal membrane domains. Remarkably, only Purkinje cell axons have detectable paranodal BK channels, whose clustering requires the formation of the paranodal junction via Caspr. Thus, BK channels occupy this unique domain in Purkinje cell axons along with the other K(+) channel complexes at nodes and juxtaparanodes. To investigate the physiological role of novel paranodal BK channels, we examined the effect of BK channel blockers on antidromic AP conduction. We found that local application of blockers to the axon resulted in a significant increase in antidromic AP failure at frequencies above 100 Hz. We also found that Ni(2+) elicited a similar effect on APs, indicating the involvement of Ni(2+)-sensitive Ca(2+) channels. Furthermore, axonal application of BK channel blockers decreased the inhibitory synaptic response in the deep cerebellar nuclei. Thus, paranodal BK channels uniquely support high-fidelity firing of APs in myelinated Purkinje cell axons, thereby underpinning the output of the cerebellar cortex. Copyright © 2015 the authors 0270-6474/15/357082-13$15.00/0.

TRPV1 channels in cardiovascular system: A double edged sword?

PubMed

Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2017-02-01

Apart from modulating nociception, there is vital role of TRPV 1 channels in modulating atherosclerosis, congestive heart failure, systemic hypertension, pulmonary hypertension, hemorrhagic shock and vascular remodeling. TRPV 1 channel activation has shielding effect against the development of atherosclerosis and systemic hypertension. TRPV 1 channel activation alleviates the formation of atherosclerotic lesions via increasing the expression of cholesterol efflux regulatory protein, UCP 2 and enhancing autophagy. Furthermore, activation of these channels enhances Na + excretion and NO release to reduce the blood pressure. TRPV 1 channel activation in the cardiac sensory neurons and subsequent CGRP release reduces ischemia-reperfusion injury. Activation of these channels during conditioning enhances CGRP and SP release from the sensory nerve fibers innervating the heart to induce cardioprotection. However, activation of these channels may elicit detrimental effects in pulmonary hypertension, hemorrhage and vascular remodeling. Activation of TRPV 1 channels enhances smooth muscle cell proliferation to promote pulmonary hypertension. Moreover, TRPV 1 channel inhibition reduces massive catecholamine release, improves survival during hemorrhage. Activation of these channels enhances vascular remodeling via enhancing NO release. Furthermore, dual role of TRPV 1 channels has been reported in the perpetuation of congestive heart failure. On one hand, TRPV 1 channel activation increases the expression of UCP2, PPAR- δ and mitochondrial sirtuin 3 to decrease oxidative stress and reduce heart injury. On the other hand, activation of these channels may enhance the expression of hypertrophic fibrotic proteins viz. GATA4, MMP to promote cardiac fibrosis. The present review discusses the dual role of activation of TRPV 1 channels in diseases associated with cardiovascular system. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain

PubMed Central

Moussaieff, Arieh; Rimmerman, Neta; Bregman, Tatiana; Straiker, Alex; Felder, Christian C.; Shoham, Shai; Kashman, Yoel; Huang, Susan M.; Lee, Hyosang; Shohami, Esther; Mackie, Ken; Caterina, Michael J.; Walker, J. Michael; Fride, Ester; Mechoulam, Raphael

2008-01-01

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3−/− mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3+/+ mice. It had no effect on keratinocytes from TRPV3−/− mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.—Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., Mechoulam, R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. PMID:18492727

The facilitating effect of systemic administration of Kv7/M channel blocker XE991 on LTP induction in the hippocampal CA1 area independent of muscarinic activation.

PubMed

Song, Ming-Ke; Cui, Yong-Yao; Zhang, Wei-Wei; Zhu, Liang; Lu, Yang; Chen, Hong-Zhuan

2009-09-11

A large amount of in vitro studies demonstrate suppression of M-current in hippocampal neurons by Kv7/M channel blocker results in depolarization of membrane potential and release of neurotransmitters, such as acetylcholine and glutamate, suggesting that Kv7/M channel may play important roles in regulating synaptic plasticity. In the present study, we examined the in vivo effect of Kv7/M channel inhibition on the long-term potentiation (LTP) induction at basal dendrites in hippocampal CA1 area of urethane-anaesthetized rats. The Kv7/M channel was inhibited by intraperitoneal injection of XE991 (10mg/kg) and the LTP of field excitatory postsynaptic potential (fEPSP) was induced by supra-threshold high frequency stimulation (S1 HFS). A weak protocol which was just below the threshold for evoking LTP was used as sub-threshold high frequency stimulation (S2 HFS). XE991 did not significantly alter the slope of fEPSP and the magnitude of LTP induced by S1 HFS, suggesting that Kv7/M channel inhibition had little or no effect on glutamatergic transmission under basal conditions. However, XE991 could make S2 HFS evoke LTP even after the application of the muscarinic cholinergic (mACh) receptor antagonist scopolamine, suggesting that Kv7/M channel inhibition lowered the threshold for LTP induction and the effect was independent of muscarinic activation. Based on the above findings, we concluded that the facilitating effect of XE991 on LTP induction is not mediated by its ability to enhance the release of acetylcholine; therefore, Kv7/M channel blockers may provide a therapeutic benefit to cholinergic deficiency-related cognitive impairment, e.g., Alzheimer's disease.

Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons

PubMed Central

Kimm, Tilia; Khaliq, Zayd M.

2015-01-01

Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency–current (f–I) relationship, whereas BK channel inhibition had little effect on the f–I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f–I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. SIGNIFICANCE STATEMENT This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both channel types participate in action potential repolarization about equally, they have contrasting and partially opposite effects in regulating neuronal firing at frequencies typical of bursting. Our analysis shows that this results from their different kinetic properties, with fast-activating BK channels serving to short-circuit activation of Kv2 channels, which tend to slow firing by producing a deep afterhyperpolarization. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. PMID:26674866

Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

PubMed

Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

2015-12-16

Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both channel types participate in action potential repolarization about equally, they have contrasting and partially opposite effects in regulating neuronal firing at frequencies typical of bursting. Our analysis shows that this results from their different kinetic properties, with fast-activating BK channels serving to short-circuit activation of Kv2 channels, which tend to slow firing by producing a deep afterhyperpolarization. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. Copyright © 2015 the authors 0270-6474/15/3516404-14$15.00/0.

Fractional channel multichannel analyzer

DOEpatents

Brackenbush, L.W.; Anderson, G.A.

1994-08-23

A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynchronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board. 9 figs.

Fractional channel multichannel analyzer

DOEpatents

Brackenbush, Larry W.; Anderson, Gordon A.

1994-01-01

A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynscronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board.

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

PubMed

Sanacora, G; Smith, M A; Pathak, S; Su, H-L; Boeijinga, P H; McCarthy, D J; Quirk, M C

2014-09-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

The effect of luteinizing hormone releasing hormone analog regime and stage of oocyte maturity for induced ovulation of channel catfish Ictalurus punctatus

USDA-ARS?s Scientific Manuscript database

The effective LHRHa (luteinizing hormone releasing hormone analog) dose based on the gonadal maturity of channel catfish, Ictalurus punctatus to optimize channel x blue hybrid catfish production was evaluated in 4 trials (twice in early part of the season and twice in the peak spawning season) in a ...

Diadenosine tetraphosphate-gating of recombinant pancreatic ATP-sensitive K(+) channels.

PubMed

Jovanovic, S; Jovanovic, A

2001-02-01

Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic beta cells where targets ATP-sensitive K(+) (K(ATP)) channels, depolarizes the cell membrane and induces insulin secretion. However, whether Ap4A inhibit pancreatic K(ATP) channels by targeting protein channel complex itself was unknown. Therefore, we coexpressed pancreatic K(ATP) channel subunits, Kir6.2 and SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel behavior using the inside-out configuration of the patch-clamp technique. Ap4A inhibited channel opening in a concentration-dependent manner. Analysis of single channels demonstrated that Ap4A did not change intraburst kinetic behavior of K(ATP) channels, but rather decreased burst duration and increased between-burst duration. It is concluded that Ap4A antagonizes K(ATP) channel opening by targeting channel subunits themselves and by keeping channels longer in closed interburst states.

Acidosis Differentially Modulates Inactivation in NaV1.2, NaV1.4, and NaV1.5 Channels

PubMed Central

Vilin, Yury Y.; Peters, Colin H.; Ruben, Peter C.

2012-01-01

NaV channels play a crucial role in neuronal and muscle excitability. Using whole-cell recordings we studied effects of low extracellular pH on the biophysical properties of NaV1.2, NaV1.4, and NaV1.5, expressed in cultured mammalian cells. Low pH produced different effects on different channel subtypes. Whereas NaV1.4 exhibited very low sensitivity to acidosis, primarily limited to partial block of macroscopic currents, the effects of low pH on gating in NaV1.2 and NaV1.5 were profound. In NaV1.2 low pH reduced apparent valence of steady-state fast inactivation, shifted the τ(V) to depolarizing potentials and decreased channels availability during onset to slow and use-dependent inactivation (UDI). In contrast, low pH delayed open-state inactivation in NaV1.5, right-shifted the voltage-dependence of window current, and increased channel availability during onset to slow and UDI. These results suggest that protons affect channel availability in an isoform-specific manner. A computer model incorporating these results demonstrates their effects on membrane excitability. PMID:22701426

Effects of preparation relief and flow channels on seating full coverage castings during cementation.

PubMed

Webb, E L; Murray, H V; Holland, G A; Taylor, D F

1983-06-01

Machined steel dies were used to study the effects of three die modifications on seating full coverage castings during cementation. The die modifications consisted of occlusal channels, occlusal surface relief, and axial channels. Fourteen specimens having one or more forms of die modification were compared with two control specimens having no die modifications. Statistical analysis of the data revealed that the addition of four axial channels to the simulated preparation on the steel die produced a significant reduction in the mean marginal discrepancy during cementation. Occlusal modifications alone failed to produce significant reductions in marginal discrepancies when compared with the control specimens. Occlusal modifications in conjunction with axial channels failed to produce further significant reductions in marginal discrepancies when compared with those reductions observed in specimens having only axial channels.

Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl− channels

PubMed Central

Fan, Hai-Tian; Morishima, Shigeru; Kida, Hajime; Okada, Yasunobu

2001-01-01

Some phenol derivatives are known to block volume-sensitive Cl− channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport and anion antiport, have not been examined. In the present study, we investigated the effects of phloretin on volume-sensitive Cl− channels in comparison with cyclic AMP-activated CFTR Cl− channels and Ca2+-activated Cl− channels using the whole-cell patch-clamp technique.Extracellular application of phloretin (over 10 μM) voltage-independently, and in a concentration-dependent manner (IC50 ∼30 μM), inhibited the Cl− current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.In contrast, at 30 μM phloretin failed to inhibit cyclic AMP-activated Cl− currents in T84 and C127/CFTR cells. Higher concentrations (over 100 μM) of phloretin, however, partially inhibited the CFTR Cl− currents in a voltage-dependent manner.At 30 and 300 μM, phloretin showed no inhibitory effect on Ca2+-dependent Cl− currents induced by ionomycin in T84 cells.It is concluded that phloretin preferentially blocks volume-sensitive Cl− channels at low concentrations (below 100 μM) and also inhibits cyclic AMP-activated Cl− channels at higher concentrations, whereas phloretin does not inhibit Ca2+-activated Cl− channels in epithelial cells. PMID:11487521

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Cheol Hyoun; Hee Kim, So; Gu Yun, Myeong

In this study, we proposed the artificially designed channel structure in oxide thin-film transistors (TFTs) called a “step-composition gradient channel.” We demonstrated Al step-composition gradient Al-Zn-O (AZO) channel structures consisting of three AZO layers with different Al contents. The effects of stacking sequence in the step-composition gradient channel on performance and electrical stability of bottom-gate TFT devices were investigated with two channels of inverse stacking order (ascending/descending step-composition). The TFT with ascending step-composition channel structure (5 → 10 → 14 at. % Al composition) showed relatively negative threshold voltage (−3.7 V) and good instability characteristics with a reduced threshold voltage shift (Δmore » 1.4 V), which was related to the alignment of the conduction band off-set within the channel layer depending on the Al contents. Finally, the reduced Al composition in the initial layer of ascending step-composition channel resulted in the best field effect mobility of 4.5 cm{sup 2}/V s. We presented a unique active layer of the “step-composition gradient channel” in the oxide TFTs and explained the mechanism of adequate channel design.« less

Calcium channel subtypes differ at two types of cholinergic synapse in lumbar sympathetic neurones of guinea-pigs.

PubMed

Ireland, D R; Davies, P J; McLachlan, E M

1999-01-01

1. The involvement of different presynaptic Ca2+ channels in transmission at 'weak' (subthreshold) and 'strong' (suprathreshold) synapses was investigated in guinea-pig paravertebral ganglia isolated in vitro. Selective Ca2+ channel antagonists were used to block excitatory synaptic currents evoked by stimulating single preganglionic axons. 2. The N-type Ca2+ channel blocker, omega-conotoxin GVIA (100 nM), reduced peak synaptic conductance by similar amounts at weak synapses (by 39 +/- 6 %) and strong synapses (34 +/- 6 %). 3. The P-type Ca2+ channel blocker, omega-agatoxin IVA (40 nM), significantly reduced transmitter release at weak synapses (by 42 +/- 6 %) but had only a small effect at strong synapses (reduced by 6 +/- 2 %). 4. Blockers of Q-, L- or T-type Ca2+ channels had no significant effects on peak synaptic conductance at either type of synapse. 5. We conclude that the two functionally distinct types of preganglionic terminal in sympathetic ganglia which synapse on the same neurone differ in their expression of particular types of voltage-dependent Ca2+ channels. Both types utilize N-type channels and channels resistant to blockade by specific antagonists, but Ca2+ entry through P-type channels makes a substantial contribution to acetylcholine release only at weak synapses.

Calcium channel subtypes differ at two types of cholinergic synapse in lumbar sympathetic neurones of guinea-pigs

PubMed Central

Ireland, David R; Davies, Philip J; McLachlan, Elspeth M

1999-01-01

The involvement of different presynaptic Ca2+ channels in transmission at ‘weak’ (subthreshold) and ‘strong’ (suprathreshold) synapses was investigated in guinea-pig paravertebral ganglia isolated in vitro. Selective Ca2+ channel antagonists were used to block excitatory synaptic currents evoked by stimulating single preganglionic axons.The N-type Ca2+ channel blocker, ω-conotoxin GVIA (100 nm), reduced peak synaptic conductance by similar amounts at weak synapses (by 39 ± 6%) and strong synapses (34 ± 6%).The P-type Ca2+ channel blocker, ω-agatoxin IVA (40 nm), significantly reduced transmitter release at weak synapses (by 42 ± 6%) but had only a small effect at strong synapses (reduced by 6 ± 2%).Blockers of Q-, L- or T-type Ca2+ channels had no significant effects on peak synaptic conductance at either type of synapse.We conclude that the two functionally distinct types of preganglionic terminal in sympathetic ganglia which synapse on the same neurone differ in their expression of particular types of voltage-dependent Ca2+ channels. Both types utilize N-type channels and channels resistant to blockade by specific antagonists, but Ca2+ entry through P-type channels makes a substantial contribution to acetylcholine release only at weak synapses. PMID:9831716

Effects of channel blocking on information transmission and energy efficiency in squid giant axons.

PubMed

Liu, Yujiang; Yue, Yuan; Yu, Yuguo; Liu, Liwei; Yu, Lianchun

2018-04-01

Action potentials are the information carriers of neural systems. The generation of action potentials involves the cooperative opening and closing of sodium and potassium channels. This process is metabolically expensive because the ions flowing through open channels need to be restored to maintain concentration gradients of these ions. Toxins like tetraethylammonium can block working ion channels, thus affecting the function and energy cost of neurons. In this paper, by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects of channel blocking with toxins on the information transmission and energy efficiency in squid giant axons. We found that gradually blocking sodium channels will sequentially maximize the information transmission and energy efficiency of the axons, whereas moderate blocking of potassium channels will have little impact on the information transmission and will decrease the energy efficiency. Heavy blocking of potassium channels will cause self-sustained oscillation of membrane potentials. Simultaneously blocking sodium and potassium channels with the same ratio increases both information transmission and energy efficiency. Our results are in line with previous studies suggesting that information processing capacity and energy efficiency can be maximized by regulating the number of active ion channels, and this indicates a viable avenue for future experimentation.

Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.

PubMed Central

Wickenden, A. D.; Grimwood, S.; Grant, T. L.; Todd, M. H.

1991-01-01

1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed. PMID:1878752

Digital nonlinearity compensation in high-capacity optical communication systems considering signal spectral broadening effect.

PubMed

Xu, Tianhua; Karanov, Boris; Shevchenko, Nikita A; Lavery, Domaniç; Liga, Gabriele; Killey, Robert I; Bayvel, Polina

2017-10-11

Nyquist-spaced transmission and digital signal processing have proved effective in maximising the spectral efficiency and reach of optical communication systems. In these systems, Kerr nonlinearity determines the performance limits, and leads to spectral broadening of the signals propagating in the fibre. Although digital nonlinearity compensation was validated to be promising for mitigating Kerr nonlinearities, the impact of spectral broadening on nonlinearity compensation has never been quantified. In this paper, the performance of multi-channel digital back-propagation (MC-DBP) for compensating fibre nonlinearities in Nyquist-spaced optical communication systems is investigated, when the effect of signal spectral broadening is considered. It is found that accounting for the spectral broadening effect is crucial for achieving the best performance of DBP in both single-channel and multi-channel communication systems, independent of modulation formats used. For multi-channel systems, the degradation of DBP performance due to neglecting the spectral broadening effect in the compensation is more significant for outer channels. Our work also quantified the minimum bandwidths of optical receivers and signal processing devices to ensure the optimal compensation of deterministic nonlinear distortions.

Two-ply channels for faster wicking in paper-based microfluidic devices.

PubMed

Camplisson, Conor K; Schilling, Kevin M; Pedrotti, William L; Stone, Howard A; Martinez, Andres W

2015-12-07

This article describes the development of porous two-ply channels for paper-based microfluidic devices that wick fluids significantly faster than conventional, porous, single-ply channels. The two-ply channels were made by stacking two single-ply channels on top of each other and were fabricated entirely out of paper, wax and toner using two commercially available printers, a convection oven and a thermal laminator. The wicking in paper-based channels was studied and modeled using a modified Lucas-Washburn equation to account for the effect of evaporation, and a paper-based titration device incorporating two-ply channels was demonstrated.

The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations.

PubMed

Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J

2017-10-01

Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

On channel interactions in nested Hall thrusters

NASA Astrophysics Data System (ADS)

Cusson, S. E.; Georgin, M. P.; Dragnea, H. C.; Dale, E. T.; Dhaliwal, V.; Boyd, I. D.; Gallimore, A. D.

2018-04-01

Nested Hall thrusters use multiple, concentric discharge channels to increase thrust density. They have shown enhanced performance in multi-channel operation relative to the superposition of individual channels. The X2, a two-channel nested Hall thruster, was used to investigate the mechanism behind this improved performance. It is shown that the local pressure near the thruster exit plane is an order of magnitude higher in two-channel operation. This is due to the increased neutral flow inherent to the multi-channel operation. Due to the proximity of the discharge channels in nested Hall thrusters, these local pressure effects are shown to be responsible for the enhanced production of thrust during multi-channel operation via two mechanisms. The first mechanism is the reduction of the divergence angle due to an upstream shift of the acceleration region. The displacement of the acceleration region was detected using laser induced fluorescence measurements of the ion velocity profile. Analysis of the change in beam divergence indicates that, at an operating condition of 150 V and 30 A, this effect increases the thrust by 8.7 ± 1.2 mN. The second mechanism is neutral ingestion from the adjacent channel resulting in a 2.0 + 0/-0.2 mN increase in thrust. Combined, these mechanisms are shown to explain, within uncertainty, the 17 ± 6.2 mN improvement in thrust during dual channel operation of the X2.

Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane.

PubMed

Schmidt, Daniel; MacKinnon, Roderick

2008-12-09

Voltage-dependent K(+) (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K(+) channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.

Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane

PubMed Central

Schmidt, Daniel; MacKinnon, Roderick

2008-01-01

Voltage-dependent K+ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K+ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane. PMID:19050073

Numerical study of the effects of lamp configuration and reactor wall roughness in an open channel water disinfection UV reactor.

PubMed

Sultan, Tipu

2016-07-01

This article describes the assessment of a numerical procedure used to determine the UV lamp configuration and surface roughness effects on an open channel water disinfection UV reactor. The performance of the open channel water disinfection UV reactor was numerically analyzed on the basis of the performance indictor reduction equivalent dose (RED). The RED values were calculated as a function of the Reynolds number to monitor the performance. The flow through the open channel UV reactor was modelled using a k-ε model with scalable wall function, a discrete ordinate (DO) model for fluence rate calculation, a volume of fluid (VOF) model to locate the unknown free surface, a discrete phase model (DPM) to track the pathogen transport, and a modified law of the wall to incorporate the reactor wall roughness effects. The performance analysis was carried out using commercial CFD software (ANSYS Fluent 15.0). Four case studies were analyzed based on open channel UV reactor type (horizontal and vertical) and lamp configuration (parallel and staggered). The results show that lamp configuration can play an important role in the performance of an open channel water disinfection UV reactor. The effects of the reactor wall roughness were Reynolds number dependent. The proposed methodology is useful for performance optimization of an open channel water disinfection UV reactor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contribution of Sialic Acid to the Voltage Dependence of Sodium Channel Gating

PubMed Central

Bennett, Eric; Urcan, Mary S.; Tinkle, Sally S.; Koszowski, Adam G.; Levinson, Simon R.

1997-01-01

A potential role for sialic acid in the voltage-dependent gating of rat skeletal muscle sodium channels (rSkM1) was investigated using Chinese hamster ovary (CHO) cells stably transfected with rSkM1. Changes in the voltage dependence of channel gating were observed after enzymatic (neuraminidase) removal of sialic acid from cells expressing rSkM1 and through the expression of rSkM1 in a sialylation-deficient cell line (lec2). The steady-state half-activation voltages (Va) of channels under each condition of reduced sialylation were ∼10 mV more depolarized than control channels. The voltage dependence of the time constants of channel activation and inactivation were also shifted in the same direction and by a similar magnitude. In addition, recombinant deletion of likely glycosylation sites from the rSkM1 sequence resulted in mutant channels that gated at voltages up to 10 mV more positive than wild-type channels. Thus three independent means of reducing channel sialylation show very similar effects on the voltage dependence of channel gating. Finally, steady-state activation voltages for channels subjected to reduced sialylation conditions were much less sensitive to the effects of external calcium than those measured under control conditions, indicating that sialic acid directly contributes to the negative surface potential. These results are consistent with an electrostatic mechanism by which external, negatively charged sialic acid residues on rSkM1 alter the electric field sensed by channel gating elements. PMID:9089440

Surface acoustic waves voltage controlled directional coupler

NASA Astrophysics Data System (ADS)

Golan, G.; Griffel, G.; Yanilov, E.; Ruschin, S.; Seidman, A.; Croitoru, N.

1988-10-01

An important condition for the development of surface wave integrated-acoustic devices is the ability to guide and control the propagation of the acoustic energy. This can be implemented by deposition of metallic "loading" channels on an anisotropic piezoelectric substrate. Deposition of such two parallel channels causes an effective coupling of acoustic energy from one channel to the other. A basic requirement for this coupling effect is the existence of the two basic modes: a symmetrical and a nonsymmetrical one. A mode map that shows the number of sustained modes as a function of the device parameters (i.e., channel width; distance between channels; material velocity; and acoustical exciting frequency) is presented. This kind of map can help significantly in the design process of such a device. In this paper we devise an advanced acoustical "Y" coupler with the ability to control its effective coupling by an externally applied voltage, thereby causing modulation of the output intensities of the signals.

Study on the reduction and hysteresis effect of soil nitrogen pollution by Alfalfa in channel buffer bank

NASA Astrophysics Data System (ADS)

Chi, Yixia; Xue, Lianqing; Zhang, Zhanyu; Li, Dongying

2018-01-01

Based on the simulation experiments of solute transport in channel buffer bank and pot experiments, this study analyzed the transport of nitrogen pollution from farmland drains along the South-North Water Transfer east route project; and compared the nitrogen transport rule and purification effect of alfalfa in channel buffer bank soil under situations of bare land and alfalfa mulching. The results showed that: (1) soil nitrogen content decreased gradually with the width increase of channel buffer bank by the soil adsorption and decomposition; (2) the migration rates of nitrogen were 0.06 g·kg-1 by the alfalfa mulching; (3) the removed rates of nitrogen from the soil were 0.088 g·kg-1 by cutting alfalfa; (4) the residual nitrogen of soil with alfalfa was 10% of the bare land. Alfalfa in channel buffer bank had obvious reduction and hysteresis effect to soil nitrogen pollution.

Promoting new practices to increase access to and retention in addiction treatment: an analysis of five communication channels.

PubMed

Johnson, Kimberly A; Ford, James H; McCluskey, Matthew

2012-11-01

Addiction treatment programs adopt evidence-based practices slowly, in part because adopting a new practice is a process, not an event. Using different communication channels may have a different effect at different points in the process. This paper reports the effectiveness of five communication channels in getting substance abuse treatment programs to adopt new business practices. In this study, national trade media coverage produced the greatest interest among programs and the greatest number of decisions to adopt. Conference presentations produced fewer decisions to adopt than national media, but were the most effective channel when compared to the number of programs they reached. Peers were the greatest influence in moving clinic staff from the decision to adopt to implementation. These findings give preliminary evidence for using different communication channels at different times during an effort to promote the adoption of best practices. Copyright © 2012 Elsevier Ltd. All rights reserved.

Simulation of radiation from lightning return strokes - The effects of tortuosity

NASA Technical Reports Server (NTRS)

Levine, D. M.; Meneghini, R.

1978-01-01

A Monte Carlo simulation has been developed for the electromagnetic fields radiated from a tortuous lightning channel. This was done using a piecewise linear model for the channel and employing for each element the field radiated by a traveling wave on an arbitrarily oriented filament over a conducting plane. The simulation reproduces experimental data reasonably well and has been used to study the effects of tortuosity on the fields radiated by return strokes. Tortuosity can significantly modify the radiated waveform, tending to render it less representative of the current pulse and more nearly unipolar than one would expect based on the theory for a long straight channel. In the frequency domain the effect of tortuosity is an increase in high frequency energy as compared with an equivalent straight channel. The extent of this increase depends on the mean length of the elements comprising the channel and can be significant.

Further characterization of the effect of ethanol on voltage-gated Ca(2+) channel function in developing CA3 hippocampal pyramidal neurons.

PubMed

Morton, Russell A; Valenzuela, C Fernando

2016-02-15

Developmental ethanol exposure damages the hippocampus, a brain region involved in learning and memory. Alterations in synaptic transmission and plasticity may play a role in this effect of ethanol. We previously reported that acute and repeated exposure to ethanol during the third trimester-equivalent inhibits long-term potentiation of GABAA receptor-dependent synaptic currents in CA3 pyramidal neurons through a mechanism that depends on retrograde release of brain-derived neurotrophic factor driven by activation of voltage-gated Ca(2+) channels (Zucca and Valenzuela, 2010). We found evidence indicating that voltage-gated Ca(2+) channels are inhibited in the presence of ethanol, an effect that may play a role in its mechanism of action. Here, we further investigated the acute effect of ethanol on the function of voltage-gated Ca(2+) channels in CA3 pyramidal neurons using Ca(2+) imaging techniques. These experiments revealed that acute ethanol exposure inhibits voltage-gated Ca(2+) channels both in somatic and proximal dendritic compartments. To investigate the long-term consequences of ethanol on voltage-gated Ca(2+) channels, we used patch-clamp electrophysiological techniques to assess the function of L-type voltage-gated Ca(2+) channels during and following ten days of vapor ethanol exposure. During ethanol withdrawal periods, the function of these channels was not significantly affected by vapor chamber exposure. Taken together with our previous findings, our results suggest that 3(rd) trimester-equivalent ethanol exposure transiently inhibits L-type voltage-gated Ca(2+) channel function in CA3 pyramidal neurons and that compensatory mechanisms restore their function during ethanol withdrawal. Transient inhibition of these channels by ethanol may be, in part, responsible for the hippocampal abnormalities associated with developmental exposure to this agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BK(Ca) channel activity in cultured endothelial cells of human coronary artery.

PubMed

Liu, Yen-Chin; Lo, Yi-Ching; Huang, Chin-Wei; Wu, Sheng-Nan

2003-11-15

ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K(+) outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17beta-estradiol. Under current-clamp condition, ICI-182,780 (3microM) depolarized the membrane potentials of the cells, and magnolol (10 microM) or nordihydroguaiaretic acid (10 microM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca(2+)-activated K(+) channels (BK(Ca) channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC(50) value of 3 microM. After BK(Ca) channel activity was suppressed by 2-methoxyestradiol (3 microM), subsequent application of ICI-182,780 (3 microM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BK(Ca) channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC(50) value of 2 microM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BK(Ca) channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BK(Ca) channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

Compound-Specific Effects of Mutations at Val787 in DII-S6 of Nav1.4 Sodium Channels on the Action of Sodium Channel Inhibitor Insecticides

PubMed Central

von Stein, Richard T.; Soderlund, David M.

2012-01-01

Sodium channel inhibitor (SCI) insecticides are hypothesized to inhibit voltage-gated sodium channels by binding selectively to the slow-inactivated state. Replacement of valine at position 787 in the S6 segment of homology domain II of the rat Nav1.4 sodium channel by lysine (V787K) enchances slow inactivation of this channel whereas replacement by alanine or cysteine (V787A, V787C) inhibits slow inactivation. To test the hypothesis that SCI insecticides bind selectively to the slow-inactivated state, we constructed mutated Nav1.4/V787A, Nav1.4/V787C, and Nav1.4/V787K cDNAs, expressed wildtype and mutated channels with the auxiliary β1 subunit in Xenopus oocytes, and used the two-electrode voltage clamp technique to examine the effects of these mutations on channel inhibition by four SCI insecticides (indoxacarb, its bioactivated metabolite DCJW, metaflumizone, and RH3421). Mutations at Val787 affected SCI insecticide sensitivity in a manner that was independent of mutation-induced changes in slow inactivation gating. Sensitivity to inhibition by 10 μM indoxacarb was significantly increased in all three mutated channels, whereas sensitivity to inhibition by 10 μM metaflumizone was significantly reduced in Nav1.4/V787A channels and completely abolished in Nav1.4/V787K channels. The effects of Val787 mutations on metaflumizone were correlated with the hydrophobicity of the substituted amino acid rather than the extent of slow inactivation. None of the mutations at Val787 significantly affected the sensitivity to inhibition by DCJW or RH3421. These results demonstrate that the impact of mutations at Val787 on sodium channel inhibition by SCI insecticides depends on the specific insecticide examined and is independent of mutation-induced changes in slow inactivation gating. We propose that Val787 may be a unique determinant of metaflumizone binding. PMID:22983119

Modeling Paragenesis: Erosion Opposite to Gravity in Cave Channels

NASA Astrophysics Data System (ADS)

Cooper, M. P.; Covington, M. D.

2017-12-01

Sediment plays an important role in bedrock channels, providing both tools and cover that influence patterns of bed erosion. It has also been shown that sediment load influences bedrock channel width, with increased sediment leading to wider channels. A variety of models have been developed to explore these effects. In caves, it is hypothesized that sediments covering the floors of fully flooded channels that are forming beneath the water table (phreatic zone) can force dissolution upwards towards the water table, leading to upward erosion balanced by gradual deposition of sediment within the channel bottom. This strange process is termed paragenesis, and while there are conceptual and experimental models of the process, no prior mathematical models of cave passage evolution has captured these effects. Consequently, there is little quantitative understanding of the processes that drive paragenesis and how they link to the morphology of the cave channels that develop. We adapt a previously developed algorithm for estimating boundary shear stress within channels with free-surface flows to enable calculation of boundary shear stress in pipe-full conditions. This model successfully duplicates scaling relationships in surface channels, and geometries of caves formed in the phreatic zone such as phreatic tubes. Once sediment flux is incorporated the model successfully duplicates the hypothesized processes of paragenetic gallery formation: the cover effect prevents dissolution in the direction of gravity; passages are enlarged upwards reducing the sediment transport capacity; sediment is deposited and the process drives a continuing feedback loop. Simulations reveal that equilibrium paragenetic channel widths scale with both sediment flux and discharge. Unlike in open channel settings, increased sediment load actually narrows paragenetic channels. The cross section evolution model also reveals that the existence of equilibrium widths in such galleries requires erosion to scale with shear stress, suggesting a role of either mechanical erosion or transport limited dissolution. These types of erosion contrast with current numerical models of speleogenesis, where chemically limited dissolution, a process independent of shear stress, is predicted to occur in most turbulent flow settings.

Red-green opponent channel mediation of control of human ocular accommodation.

PubMed Central

Kotulak, J C; Morse, S E; Billock, V A

1995-01-01

1. It has been hypothesized, but not verified empirically, that the control of human ocular accommodation is mediated by either the red-green or yellow-blue colour channels. Our goal was to determine experimentally whether the red-green channel by itself could influence the accommodative response. 2. To find out, we isolated the red-green channel through chromatic bandpass filtering and measured accommodation under dynamic and static conditions. The effect of this filtering was to modulate the red-green channel without disturbing either the yellow-blue or luminance channels. 3. Accommodative gain (ratio of response to stimulus amplitude) declined monotonically with decreasing bandwidth under dynamic conditions. Because the outputs of both the luminance and yellow-blue colour channels did not vary with bandwidth, the only explanation is that the red-green opponent process was responsible for the effect. 4. Under static conditions, however, accommodation was independent of bandwidth. This may be attributable to the decreased sensitivity to chromatic contrast that occurs at low temporal frequencies. PMID:7738858

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

PubMed

Li, Guangke; Sang, Nan

2009-01-01

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

Models of second-order effects in metal-oxide-semiconductor field-effect transistors for computer applications

NASA Technical Reports Server (NTRS)

Benumof, Reuben; Zoutendyk, John; Coss, James

1988-01-01

Second-order effects in metal-oxide-semiconductor field-effect transistors (MOSFETs) are important for devices with dimensions of 2 microns or less. The short and narrow channel effects and drain-induced barrier lowering primarily affect threshold voltage, but formulas for drain current must also take these effects into account. In addition, the drain current is sensitive to channel length modulation due to pinch-off or velocity saturation and is diminished by electron mobility degradation due to normal and lateral electric fields in the channel. A model of a MOSFET including these considerations and emphasizing charge conservation is discussed.

Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

PubMed Central

González, G; Zaldívar, D; Carrillo, ED; Hernández, A; García, MC; Sánchez, JA

2010-01-01

BACKGROUND AND PURPOSE Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K+ (mitoKATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca2+ homeostasis during PPC, particularly changes in Ca2+ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca2+ channels. EXPERIMENTAL APPROACH PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca2+ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the α1c subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTS PPC was accompanied by a 50% reduction in α1c subunit levels, and by a reversible fall in L-type current amplitude and Ca2+ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the α1c subunit and Ca2+ channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONS PPC downregulated the α1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca2+ channel, which in turn reduced Ca2+ influx, which may attenuate Ca2+ overload during reperfusion. PMID:20636393

Modulation of channel activity and gadolinium block of MscL by static magnetic fields.

PubMed

Petrov, Evgeny; Martinac, Boris

2007-02-01

The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of living organisms. Experimental studies of the magnetic sense have, however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by these organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. In this study we have investigated the effect of static magnetic fields (SMFs) of moderate intensity on the activity and gadolinium block of MscL, the bacterial MS channel of large conductance, which has served as a model channel to study the basic physical principles of mechanosensory transduction in living cells. In addition to showing that direct application of the magnetic field decreased the activity of the MscL channel, our study demonstrates for the first time that SMFs can reverse the effect of gadolinium, a well-known blocker of MS channels. The results of our study are consistent with a notion that (1) the effects of SMFs on the MscL channels may result from changes in physical properties of the lipid bilayer due to diamagnetic anisotropy of phospholipid molecules and consequently (2) cooperative superdiamagnetism of phospholipid molecules under influence of SMFs could cause displacement of Gd(3+) ions from the membrane bilayer and thus remove the MscL channel block.

Charge movement in gating-locked HCN channels reveals weak coupling of voltage sensors and gate.

PubMed

Ryu, Sujung; Yellen, Gary

2012-11-01

HCN (hyperpolarization-activated cyclic nucleotide gated) pacemaker channels have an architecture similar to that of voltage-gated K(+) channels, but they open with the opposite voltage dependence. HCN channels use essentially the same positively charged voltage sensors and intracellular activation gates as K(+) channels, but apparently these two components are coupled differently. In this study, we examine the energetics of coupling between the voltage sensor and the pore by using cysteine mutant channels for which low concentrations of Cd(2+) ions freeze the open-closed gating machinery but still allow the sensors to move. We were able to lock mutant channels either into open or into closed states by the application of Cd(2+) and measure the effect on voltage sensor movement. Cd(2+) did not immobilize the gating charge, as expected for strict coupling, but rather it produced shifts in the voltage dependence of voltage sensor charge movement, consistent with its effect of confining transitions to either closed or open states. From the magnitude of the Cd(2+)-induced shifts, we estimate that each voltage sensor produces a roughly three- to sevenfold effect on the open-closed equilibrium, corresponding to a coupling energy of ∼1.3-2 kT per sensor. Such coupling is not only opposite in sign to the coupling in K(+) channels, but also much weaker.

Phosphoinositide regulation of TRPV1 revisited

PubMed Central

Rohacs, Tibor

2015-01-01

The heat- and capsaicin-sensitive Transient Receptor Potential Vanilloid 1 ion channel (TRPV1) is regulated by plasma membrane phosphoinositides. The effects of these lipids on this channel have been controversial. Recent articles re-ignited the debate and also offered resolution to place some of the data in a coherent picture. This review summarizes the literature on this topic and provides a detailed and critical discussion on the experimental evidence for the various effects of phosphatidylinositol 4,5-bisphosphayte [PI(4,5)P2 or PIP2] on TRPV1. We conclude that PI(4,5)P2 and potentially its precursor PI(4)P are positive cofactors for TRPV1, acting via direct interaction with the channel, and their depletion by Ca2+-induced activation of phospholipase Cδ isoforms (PLCδ) limits channel activity during capsaicin-induced desensitization. Other negatively charged lipids at higher concentrations can also support channel activity, which may explain some controversies in the literature. PI(4,5)P2 also partially inhibits channel activity in some experimental settings, and relief from this inhibition upon PLCβ activation may contribute to sensitization. The negative effect of PI(4,5)P2 is more controversial and its mechanism is less well understood. Other TRP channels from the TRPV and TRPC families may also undergo similar dual regulation by phosphoinositides, thus the complexity of TRPV1 regulation is not unique to this channel. PMID:25754030

Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dargent, B.; Couraud, F.

1990-08-01

To address the issue of whether regulatory feedback exists between the electrical activity of a neuron and ion-channel density, the authors investigated the effect of Na{sup +}-channel activators (scorpion {alpha} toxin, batrachotoxin, and veratridine) on the density of Na{sup +} channels in fetal rat brain neurons in vitro. A partial but rapid (t{sub 1/2}, 15 min) disappearance of surface Na{sup +} channels was observed as measured by a decrease in the specific binding of ({sup 3}H)saxitoxin and {sup 125}I-labeled scorpion {beta} toxin and a decrease in specific {sup 22}Na{sup +} uptake. Moreover, the increase in the number of Na{sup +}more » channels that normally occurs during neuronal maturation in vitro was inhibited by chronic channel activator treatment. The induced disappearance of Na{sup +} channels was abolished by tetrodotoxin, was found to be dependent on the external Na{sup +} concentration, and was prevented when either choline (a nonpermeant ion) or Li{sup +} (a permeant ion) was substituted for Na{sup +}. Amphotericin B, a Na{sup +} ionophore, and monensin were able to mimick the effect of Na{sup +}-channel activators, while a KCl depolarization failed to do this. This feedback regulation seems to be a neuronal property since Na{sup +}-channel density in cultured astrocytes was not affected by channel activator treatment or by amphotericin B. The present evidence suggests that an increase in intracellular Na{sup +} concentration, whether elicited by Na{sup +}-channel activators or mediated by a Na{sup +} ionophore, can induce a decrease in surface Na{sup +} channels and therefore is involved in down-regulation of Na{sup +}-channel density in fetal rat brain neurons in vitro.« less

Effect of channel width variation on sediment transport in mixed alluvial-bedrock rivers - from case study to concept

NASA Astrophysics Data System (ADS)

Cook, Kristen; Turowski, Jens; Hovius, Niels

2017-04-01

In mixed bedrock-alluvial rivers, the response of the system to a flood event can be affected by a number of factors, including coarse sediment availability in the channel, sediment supply from the hillslopes, bedrock-controlled changes in channel width, and the shape of the hydrograph. Local hydraulics and therefore bedload transport capacity depend on discharge and channel geometry, typically quantified by channel width and bed slope. However, the influence of channel width on total bedload transport capacity depends on discharge. For a given slope, narrow channels are more efficient than wide ones at low discharges, while wider channels are more efficient at higher discharges. Therefore, abrupt changes in downstream channel width may affect bedload flux through a channel and have important influences on channel behavior. We use the model sedFlow (Heimann et al., 2014) to explore this effect. We ran the model in a 4.5 km long channel, the center of which contains a 1 km gorge section with a width of 15 m, bounded upstream and downstream by sections with widths of 50 m. We imposed a discharge time series with a random sequence of floods of different size. The channel responds to the imposed floods in complex ways. At high discharges, the gorge reach transports less total sediment than the wide reaches, leading to aggradation in the upper part of the gorge and upstream and erosion in the lower part of the gorge and downstream. At lower discharges, the gorge becomes more efficient at transporting sediment and the trends reverse. The channel may experience both of these regimes during the peak and recession periods of a single flood, leading to a highly dynamic channel bed. This is consistent with observations from the Daan River gorge in western Taiwan, where we observe substantial intra-flood variations in channel bed elevation. Our modeling suggests that width differences alone can drive substantial variations in sediment flux and bed response, without the need for variations in sediment supply or mobility. Because the relationship between channel width and sediment transport capacity depends on the discharge, the long-term response of a channel with variable width depends on the entire hydrograph, not just on the flood peak. In addition, the net effect of a flood depends strongly on the preceding sequence of floods, as the long profile and channel slopes are continually adjusting to different forcing. Therefore modeling studies that use uniform discharge or a step function discharge will miss these dynamics. The fluctuations in sediment transport rates that result from width variations can lead to intermittent bed exposure, driving incision in different segments of the channel during different segments of the hydrograph.

The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum

PubMed Central

Dobrev, Dobromir; Milde, Alexander S; Andreas, Klaus; Ravens, Ursula

1999-01-01

The putative inhibitory effects of verapamil and diltiazem on neuronal non-L-type Ca2+ channels were studied by investigating their effects on either K+- or veratridine-evoked [3H]-dopamine ([3H]-DA) release in rat striatal slices. Involvement of N-, P- and Q-type channels was identified by sensitivity of [3H]-DA release to ω-conotoxin GVIA (ω-CTx-GVIA), ω-agatoxin IVA (ω-Aga-IVA) and ω-conotoxin MVIIC (ω-CTx-MVIIC), respectively.KCl (50 mM)-evoked [3H]-DA release was abolished in the absence of Ca2+, and was insensitive to dihydropyridines (up to 30 μM). It was significantly blocked by ω-CTx-GVIA (1 μM), ω-Aga-IVA (30 nM) and was confirmed to be abolished by ω-CTx-MVIIC (3 μM), indicating involvement of N-, P- and Q-type channel subtypes.Verapamil and diltiazem inhibited K+-evoked [3H]-DA release in a concentration-dependent manner. The inhibitory effects of verapamil or diltiazem (each 30 μM) were fully additive to the effect of ω-CTx-GVIA (1 μM), whereas co-application with ω-Aga-IVA (30 nM) produced similar effects to those of ω-Aga-IVA alone.As shown previously, veratridine-evoked [3H]-DA release in Ca2+ containing medium exclusively involves Q-type Ca2+ channels. Here, diltiazem (30 μM) did not inhibit veratridine-evoked [3H]-DA release, whereas verapamil (30 μM) partially inhibited it, indicating possible involvement of Q-type channels in verapamil-induced inhibition. However, verapamil (30 μM) inhibited this release even in the absence of extracellular Ca2+, suggesting that Na+ rather than Q-type Ca2+ channels are involved.Taken together, our results suggest that verapamil can block P- and at higher concentrations possibly N- and Q-type Ca2+ channels linked to [3H]-DA release, whereas diltiazem appears to block P-type Ca2+ channels only. PMID:10385261

[The role of opiate receptors and ATP-dependent potassium channels of mitochondria in the formation of myocardial adaptive resistance to the arrhythmogenic effect of ischemia and reperfusion].

PubMed

Lishmanov, Iu B; Naryzhnaia, N V; Krylatov, A V; Maslov, L N; Bogomaz, S A; Ugdyzhekova, D S; Gross, G J; Stefano, J B

2003-01-01

Preliminary stimulation of opiate receptors (ORs) by intravenous administration of mu agonist DALDA (0.5 mg/kg), delta 1 agonist DPDPE (0.5 mg/kg), and kappa agonist (-)-U-50.488 (1 mg/kg) increases rat myocardial resistance to arrhythmogenic effect of coronary occlusion (10 min) and reperfusion (10 min). Activation of delta 2 ORs (DSLET, 0.5 mg/kg) has no effect on the incidence rate of ischemic and reperfusion arrhythmias. Preliminary administration of glibenclamide (0.3 mg/kg), an inhibitor of KATP channels, blocks the antiarrhythmic effect of DALDA and DPDPE. Repeated short-term exposures of rats to immobilization within two weeks increases the heart tolerance to the arrhythmogenic effect of coronary occlusion and reperfusion. This effect disappears after administration of CTAP (0.5 mg/kg), a mu antagonist, or injection of 5-hydroxydecanoate (5 mg/kg), an inhibitor of mitochondrial KATP channels. The selective antagonists of delta and kappa ORs have no effect on cardiac adaptation-induced resistance to the arrhythmogenic effect of ischemia and reperfusion. We believe that stimulation of mu, delta, and kappa ORs increases myocardial tolerance to the arrhythmogenic effect of ischemia and reperfusion through activation of KATP channels. The antiarrhythmic effect of the adaptation is mediated by stimulation of mu ORs and mitochondrial KATP channels.

All-optical UWB generation and modulation using SOA-XPM effect and DWDM-based multi-channel frequency discrimination.

PubMed

Wang, Fei; Dong, Jianji; Xu, Enming; Zhang, Xinliang

2010-11-22

An all-optical UWB pulses generation and modulation scheme using cross phase modulation (XPM) effect of semiconductor optical amplifier (SOA) and DWDM-based multi-channel frequency discrimination is proposed and demonstrated, which has potential application in multiuser UWB-Over-Fiber communication systems. When a Gaussian pulse light and a wavelength-tunable CW probe light are together injected into the SOA, the probe light out from the SOA will have a temporal chirp due to SOA-XPM effect. When the chirped probe light is tuned to the slopes of single DWDM channel transmittance curve, the optical phase modulation to intensity modulation conversion is achieved at DWDM that serves as a multi-channel frequency discriminator, the inverted polarity Gaussian monocycle and doublet pulse is detected by a photodetector, respectively. If the probe lights are simultaneously aimed to different slopes of several DWDM channels, multi-channel or binary-phase-coded UWB signal generation can be acquired. Using proposed scheme, pulse amplitude modulation (PAM), pulse polarity modulation (PPM) and pulse shape modulation (PSM) to UWB pulses also can be conveniently realized.

Ultrashort Channel Length Black Phosphorus Field-Effect Transistors.

PubMed

Miao, Jinshui; Zhang, Suoming; Cai, Le; Scherr, Martin; Wang, Chuan

2015-09-22

This paper reports high-performance top-gated black phosphorus (BP) field-effect transistors with channel lengths down to 20 nm fabricated using a facile angle evaporation process. By controlling the evaporation angle, the channel length of the transistors can be reproducibly controlled to be anywhere between 20 and 70 nm. The as-fabricated 20 nm top-gated BP transistors exhibit respectable on-state current (174 μA/μm) and transconductance (70 μS/μm) at a VDS of 0.1 V. Due to the use of two-dimensional BP as the channel material, the transistors exhibit relatively small short channel effects, preserving a decent on-off current ratio of 10(2) even at an extremely small channel length of 20 nm. Additionally, unlike the unencapsulated BP devices, which are known to be chemically unstable in ambient conditions, the top-gated BP transistors passivated by the Al2O3 gate dielectric layer remain stable without noticeable degradation in device performance after being stored in ambient conditions for more than 1 week. This work demonstrates the great promise of atomically thin BP for applications in ultimately scaled transistors.

Mitragynine and its potential blocking effects on specific cardiac potassium channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tay, Yea Lu; Teah, Yi Fan; Chong, Yoong Min

2016-08-15

Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac I{sub Kr} current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, I{sub K1}, a Kir current mediated by Kir2.1 channel and I{sub KACh}, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on themore » current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC{sub 50} value of 1.62 μM and 1.15 μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit I{sub KACh} current with an IC{sub 50} value of 3.32 μM but has no significant effects on I{sub K1}. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks. - Highlights: • The potential cardiac potassium channel blocking properties of mitragynine were investigated. • Mitragynine blocks hERG channel and I{sub Kr} in hERG-transfected HEK293 cells and hERG cRNA-injected Xenopus oocytes. • Mitragynine inhibits the hERG protein but not the mRNA expression. • Mitragynine inhibits GIRK channel. • Simultaneous hERG and GIRK channel blockade may cause additive cardiotoxicity risks.« less

Dalitz plot distributions in presence of triangle singularities

DOE PAGES

Szczepaniak, Adam P.

2016-03-25

We discuss properties of three-particle Dalitz distributions in coupled channel systems in presence of triangle singularities. The single channel case was discussed long ago where it was found that as a consequence of unitarity, effects of a triangle singularity seen in the Dalitz plot are not seen in Dalitz plot projections. In the coupled channel case we find the same is true for the sum of intensities of all interacting channels. As a result, unlike the single channel case, however, triangle singularities do remain visible in Dalitz plot projections of individual channels.

Modeling channel interference in an orbital angular momentum-multiplexed laser link

NASA Astrophysics Data System (ADS)

Anguita, Jaime A.; Neifeld, Mark A.; Vasic, Bane V.

2009-08-01

We study the effects of optical turbulence on the energy crosstalk among constituent orbital angular momentum (OAM) states in a vortex-based multi-channel laser communication link and determine channel interference in terms of turbulence strength and OAM state separation. We characterize the channel interference as a function of C2n and transmit OAM state, and propose probability models to predict the random fluctuations in the received signals for such architecture. Simulations indicate that turbulence-induced channel interference is mutually correlated across receive channels.

Dalitz plot distributions in presence of triangle singularities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szczepaniak, Adam P.

We discuss properties of three-particle Dalitz distributions in coupled channel systems in presence of triangle singularities. The single channel case was discussed long ago where it was found that as a consequence of unitarity, effects of a triangle singularity seen in the Dalitz plot are not seen in Dalitz plot projections. In the coupled channel case we find the same is true for the sum of intensities of all interacting channels. As a result, unlike the single channel case, however, triangle singularities do remain visible in Dalitz plot projections of individual channels.

Designing Effective Persuasive Systems Utilizing the Power of Entanglement: Communication Channel, Strategy and Affect

NASA Astrophysics Data System (ADS)

Li, Haiqing; Chatterjee, Samir

With rapid advances in information and communication technology, computer-mediated communication (CMC) technologies are utilizing multiple IT platforms such as email, websites, cell-phones/PDAs, social networking sites, and gaming environments. However, no studies have compared the effectiveness of a persuasive system using such alternative channels and various persuasive techniques. Moreover, how affective computing impacts the effectiveness of persuasive systems is not clear. This study proposes (1) persuasive technology channels in combination with persuasive strategies will have different persuasive effectiveness; (2) Adding positive emotion to a message that leads to a better overall user experience could increase persuasive effectiveness. The affective computing or emotion information was added to the experiment using emoticons. The initial results of a pilot study show that computer-mediated communication channels along with various persuasive strategies can affect the persuasive effectiveness to varying degrees. These results also shows that adding a positive emoticon to a message leads to a better user experience which increases the overall persuasive effectiveness of a system.

Modulation of Gardos channel activity by oxidants and oxygen tension: effects of 1-chloro-2,4-dinitrobenzene and phenazine methosulphate.

PubMed

Gibson, John S; Muzyamba, Morris C

2004-05-01

We compare the effects of 1-chloro-2,4-dinitrobenzene (CDNB) and phenazine methosulphate (PMS) on Gardos channel activity in normal human red cells. Both stimulate channel activity, both are dependent on the presence of extracellular Ca2+, and neither is affected by inhibitors of protein (de)phosphorylation. Of the two, PMS has a considerably greater effect. In addition, a major difference is that whilst CDNB has a greater stimulatory effect in oxygenated cells, by contrast, PMS is more effective in deoxygenated cells. These actions are correlated with ca. 30% inhibition of the plasma membrane Ca2+ pump (PMCA) and an increased sensitivity of the Gardos channel to Ca2+ (EC50 falling to about 150 nM). These findings are important in understanding how oxidants alter red cell cation permeability and may be relevant to the abnormal permeability phenotype shown by deoxygenated sickle cells.

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

PubMed Central

Pinelli, Laurent; Nissant, Antoine; Edwards, Aurélie; Paulais, Marc

2016-01-01

ClC-K2, a member of the ClC family of Cl− channels and transporters, forms the major basolateral Cl− conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl− absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl−, and Ca2+ on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca2+ strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl− has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl−/HCO3− exchange in type B intercalated cells. PMID:27574292

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

PubMed

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

2016-09-01

ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. © 2016 Pinelli et al.

Stream channel responses to streamflow diversion on small streams of the Snake River drainage, Idaho

Treesearch

Carolyn C. Bohn; John G. King

2000-01-01

The effects on channels of small, low-head seasonal water diversions in the Snake River drainage were investigated. Channels below small diversions were compared to the channels immediately above the same diversions to determine if differences in flow conveyance, substrate sediment size distribution, or streamside vegetation density were present. Estimates of flow...

Effects of urbanization on streamflow, sediment loads, and channel morphology in Pheasant Branch Basin near Middleton, Wisconsin

USGS Publications Warehouse

Krug, W.R.; Goddard, G.L.

1986-01-01

Increases in flood flow would tend to enlarge the channel. An increase in the mean annual flood by a factor of 2. 0 to 2.4 will cause a 40 to 50 percent increase in channel width and a 30 to 40 percent increase in channel depth.

Cross-Layer Design for Space-Time coded MIMO Systems over Rice Fading Channel

NASA Astrophysics Data System (ADS)

Yu, Xiangbin; Zhou, Tingting; Liu, Xiaoshuai; Yin, Xin

A cross-layer design (CLD) scheme for space-time coded MIMO systems over Rice fading channel is presented by combining adaptive modulation and automatic repeat request, and the corresponding system performance is investigated well. The fading gain switching thresholds subject to a target packet error rate (PER) and fixed power constraint are derived. According to these results, and using the generalized Marcum Q-function, the calculation formulae of the average spectrum efficiency (SE) and PER of the system with CLD are derived. As a result, closed-form expressions for average SE and PER are obtained. These expressions include some existing expressions in Rayleigh channel as special cases. With these expressions, the system performance in Rice fading channel is evaluated effectively. Numerical results verify the validity of the theoretical analysis. The results show that the system performance in Rice channel is effectively improved as Rice factor increases, and outperforms that in Rayleigh channel.

Regulation of TRP channels by steroids: Implications in physiology and diseases.

PubMed

Kumar, Ashutosh; Kumari, Shikha; Majhi, Rakesh Kumar; Swain, Nirlipta; Yadav, Manoj; Goswami, Chandan

2015-09-01

While effects of different steroids on the gene expression and regulation are well established, it is proven that steroids can also exert rapid non-genomic actions in several tissues and cells. In most cases, these non-genomic rapid effects of steroids are actually due to intracellular mobilization of Ca(2+)- and other ions suggesting that Ca(2+) channels are involved in such effects. Transient Receptor Potential (TRP) ion channels or TRPs are the largest group of non-selective and polymodal ion channels which cause Ca(2+)-influx in response to different physical and chemical stimuli. While non-genomic actions of different steroids on different ion channels have been established to some extent, involvement of TRPs in such functions is largely unexplored. In this review, we critically analyze the literature and summarize how different steroids as well as their metabolic precursors and derivatives can exert non-genomic effects by acting on different TRPs qualitatively and/or quantitatively. Such effects have physiological repercussion on systems such as in sperm cells, immune cells, bone cells, neuronal cells and many others. Different TRPs are also endogenously expressed in diverse steroid-producing tissues and thus may have importance in steroid synthesis as well, a process which is tightly controlled by the intracellular Ca(2+) concentrations. Tissue and cell-specific expression of TRP channels are also regulated by different steroids. Understanding of the crosstalk between TRP channels and different steroids may have strong significance in physiological, endocrinological and pharmacological context and in future these compounds can also be used as potential biomedicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Generalized method calculating the effective diffusion coefficient in periodic channels.

PubMed

Kalinay, Pavol

2015-01-07

The method calculating the effective diffusion coefficient in an arbitrary periodic two-dimensional channel, presented in our previous paper [P. Kalinay, J. Chem. Phys. 141, 144101 (2014)], is generalized to 3D channels of cylindrical symmetry, as well as to 2D or 3D channels with particles driven by a constant longitudinal external driving force. The next possible extensions are also indicated. The former calculation was based on calculus in the complex plane, suitable for the stationary diffusion in 2D domains. The method is reformulated here using standard tools of functional analysis, enabling the generalization.

[Single channel analysis of aconitine blockade of calcium channels in rat myocardiocytes].

PubMed

Chen, L; Ma, C; Cai, B C; Lu, Y M; Wu, H

1995-01-01

Ventricular myocardiocytes from neonatal Wistar rats were isolated and cultured. Aconitine, Ca2+ channel blocker verapamil or Ca2+ channel activator BAY K8644 were added to the bath solution separately. Using the cell-attached configuration of the patch clamp technique, the single channel activities of L type Ca2+ channel were recorded before and after addition of all three drugs. The results showed the blocking effect of aconitine (50 micrograms.ml-1) on L type Ca2+ channels. Its mechanism may be relevant to the decrease in both open state probability and the mean open time of Ca2+ channel. The difference was statistically significant compared with control group (P < 0.01). The amplitude of Ba2+ currents, which flow through open L type Ca2+ channel was unchanged.

Stimulation effect of wide type CFTR chloride channel by the naturally occurring flavonoid tangeretin.

PubMed

Jiang, Yu; Yu, Bo; Wang, Xue; Sui, Yujie; Zhang, Yaofang; Yang, Shuang; Yang, Hong; Ma, Tonghui

2014-12-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed in the apical membrane of serous epithelial cells. Both deficiency and overactivation of CFTR may cause fluid and salt secretion related diseases. In the present study, we identified tangeretin from Pericarpium Citri Reticulatae Viride as a CFTR activator using high-throughput screening based on FRT cell-based fluorescence assay. The activation effect of tangeretin on CFTR chloride channel and the possible underlying mechanisms were investigated. Fluorescence quenching tests showed that tangeretin dose- and time-dependently activated CFTR chloride channel, the activity had rapid and reversible characteristics and the activation effect could be completely reversed by the CFTR specific blocker CFTRinh-172. Primary mechanism studies indicated that the activation effect of tangeretin on CFTR chloride channel was FSK dependent as well as had additional effect with FSK and IBMX suggesting that tangeretin activates CFTR by direct interacting with the protein. Ex-vivo tests revealed that tangeretin could accelerate the speed of the submucosal gland fluid secretion. Short-circuit current measurement demonstrated that tangeretin activated rat colonic mucosa chloride current. Thus, CFTR Cl(-) channel is a molecular target of natural compound tangeretin. Tangeretin may have potential use for the treatment of CFTR-related diseases like cystic fibrosis, bronchiectasis and habitual constipation. Copyright © 2014 Elsevier B.V. All rights reserved.

Simulation of cooling efficiency via miniaturised channels in multilayer LTCC for power electronics

NASA Astrophysics Data System (ADS)

Pietrikova, Alena; Girasek, Tomas; Lukacs, Peter; Welker, Tilo; Müller, Jens

2017-03-01

The aim of this paper is detailed investigation of thermal resistance, flow analysis and distribution of coolant as well as thermal distribution inside multilayer LTCC substrates with embedded channels for power electronic devices by simulation software. For this reason four various structures of internal channels in the multilayer LTCC substrates were designed and simulated. The impact of the volume flow, structures of channels, and power loss of chip was simulated, calculated and analyzed by using the simulation software Mentor Graphics FloEFDTM. The structure, size and location of channels have the significant impact on thermal resistance, pressure of coolant as well as the effectivity of cooling power components (chips) that can be placed on the top of LTCC substrate. The main contribution of this paper is thermal analyze, optimization and impact of 4 various cooling channels embedded in LTCC multilayer structure. Paper investigate, the effect of volume flow in cooling channels for achieving the least thermal resistance of LTCC substrate that is loaded by power thermal chips. Paper shows on the impact of the first chips thermal load on the second chip as well as. This possible new technology could ensure in the case of practical realization effective cooling and increasing reliability of high power modules.

Laser pulse propagation in inhomogeneous magnetoplasma channels and wakefield acceleration

NASA Astrophysics Data System (ADS)

Sharma, B. S.; Jain, Archana; Jaiman, N. K.; Gupta, D. N.; Jang, D. G.; Suk, H.; Kulagin, V. V.

2014-02-01

Wakefield excitation in a preformed inhomogeneous parabolic plasma channel by an intense relativistic (≃1019 W/cm2) circularly polarized Gaussian laser pulse is investigated analytically and numerically in the presence of an external longitudinal magnetic field. A three dimensional envelope equation for the evolution of the laser pulse is derived, which includes the effect of the nonparaxial and applied external magnetic field. A relation for the channel radius with the laser spot size is derived and examines numerically to see the external magnetic field effect. It is observed that the channel radius depends on the applied external magnetic field. An analytical expression for the wakefield is derived and validated with the help of a two dimensional particle in cell (2D PIC) simulation code. It is shown that the electromagnetic nature of the wakes in an inhomogeneous plasma channel makes their excitation nonlocal, which results in change of fields with time and external magnetic field due to phase mixing of the plasma oscillations with spatially varying frequencies. The magnetic field effect on perturbation of the plasma density and decreasing length is also analyzed numerically. In addition, it has been shown that the electron energy gain in the inhomogeneous parabolic magnetoplasma channel can be increased significantly compared with the homogeneous plasma channel.

Coupled-channels analyses for 9,11Li + 208Pb fusion reactions with multi-neutron transfer couplings

NASA Astrophysics Data System (ADS)

Choi, Ki-Seok; Cheoun, Myung-Ki; So, W. Y.; Hagino, K.; Kim, K. S.

2018-05-01

We discuss the role of two-neutron transfer processes in the fusion reaction of the 9,11Li + 208Pb systems. We first analyze the 9Li + 208Pb reaction by taking into account the coupling to the 7Li + 210Pb channel. To this end, we assume that two neutrons are directly transferred to a single effective channel in 210Pb and solve the coupled-channels equations with the two channels. By adjusting the coupling strength and the effective Q-value, we successfully reproduce the experimental fusion cross sections for this system. We then analyze the 11Li + 208Pb reaction in a similar manner, that is, by taking into account three effective channels with 11Li + 208Pb, 9Li + 210Pb, and 7Li + 212Pb partitions. In order to take into account the halo structure of the 11Li nucleus, we construct the potential between 11Li and 208Pb with a double folding procedure, while we employ a Woods-Saxon type potential with the global Akyüz-Winther parameters for the other channels. Our calculation indicates that the multiple two-neutron transfer process plays a crucial role in the 11Li + 208Pb fusion reaction at energies around the Coulomb barrier.

Connexin channels and phospholipids: association and modulation

PubMed Central

Locke, Darren; Harris, Andrew L

2009-01-01

Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion This study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents. PMID:19686581

On a quantum particle in laser channels

NASA Astrophysics Data System (ADS)

Dik, A. V.; Frolov, E. N.; Dabagov, S. B.

2018-02-01

In this paper the effective potential describing interaction of a scalar quantum particle with arbitrary nonuniform laser field is derived for a wide spectrum of the particle energies. The presented method allows to take into account all the features of the effective potential for a scalar particle. The derived expression for effective potential for quantum particle has the same form as the one presented earlier for a classical particle. A special case for channeling of a quantum particle as well as accompanying channeling radiation in a field formed by two crossed plane laser waves is considered. It is shown that relativistic particles moving near the laser channel bottom should be examined as quantum ones at both arbitrarily large longitudinal energies and laser fields of accessible intensities.

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.

PubMed

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.

Channel geometric scales effect on performance and optimization for serpentine proton exchange membrane fuel cell (PEMFC)

NASA Astrophysics Data System (ADS)

Youcef, Kerkoub; Ahmed, Benzaoui; Ziari, Yasmina; Fadila, Haddad

2017-02-01

A three dimensional computational fluid dynamics model is proposed in this paper to investigate the effect of flow field design and dimensions of bipolar plates on performance of serpentine proton exchange membrane fuel cell (PEMFC). A complete fuel cell of 25 cm2 with 25 channels have been used. The aim of the work is to investigate the effect of flow channels and ribs scales on overall performance of PEM fuel cell. Therefore, geometric aspect ratio parameter defined as (width of flow channel/width of rib) is used. Influences of the ribs and openings current collector scales have been studied and analyzed in order to find the optimum ratio between them to enhance the production of courant density of PEM fuel cell. Six kind of serpentine designs have been used in this paper included different aspect ratio varying from 0.25 to 2.33 while the active surface area and number of channels are keeping constant. Aspect ratio 0.25 corresponding of (0.4 mm channel width/ 1.6mm ribs width), and Aspect ratio2.33 corresponding of (0.6 mm channel width/ 1.4mm ribs width. The results show that the best flow field designs (giving the maximum density of current) are which there dimensions of channels width is minimal and ribs width is maximal (Γ≈0.25). Also decreasing width of channels enhance the pressure drop inside the PEM fuel cell, this causes an increase of gazes velocity and enhance convection process, therefore more power generation.

NUTRIENT CHANNELS AND STIRRING ENHANCED THE COMPOSITION AND STIFFNESS OF LARGE CARTILAGE CONSTRUCTS

PubMed Central

Cigan, Alexander D.; Nims, Robert J.; Albro, Michael B.; Vunjak-Novakovic, Gordana; Hung, Clark T.; Ateshian, Gerard A.

2014-01-01

A significant challenge in cartilage tissue engineering is to successfully culture functional tissues that are sufficiently large to treat osteoarthritic joints. Transport limitations due to nutrient consumption by peripheral cells produce heterogeneous constructs with matrix-deficient centers. Incorporation of nutrient channels into large constructs is a promising technique for alleviating transport limitations, in conjunction with simple yet effective methods for enhancing media flow through channels. Cultivation of cylindrical channeled constructs flat in culture dishes, with or without orbital shaking, produced asymmetric constructs with poor tissue properties. We therefore explored a method for exposing the entire construct surface to the culture media, while promoting flow through the channels. To this end, chondrocyte-seeded agarose constructs (Ø10 mm, 2.34 mm thick), with zero or three nutrient channels (Ø1 mm), were suspended on their sides in custom culture racks and subjected to three media stirring modes for 56 days: uniaxial rocking, orbital shaking, or static control. Orbital shaking led to the highest construct EY, glycosaminoglycan (GAG), and collagen contents, whereas rocking had detrimental effects on GAG and collagen versus static control. Nutrient channels increased EY as well as GAG homogeneity, and the beneficial effects of channels were most marked in orbitally shaken samples. Under these conditions, the constructs developed symmetrically and reached or exceeded native levels of EY (~400 kPa) and glycosaminoglycans (GAG; ~9%/ww). These results suggest that the cultivation of channeled constructs in culture racks with orbital shaking is a promising method for engineering mechanically competent large cartilage constructs. PMID:25458579

Nutrient channels and stirring enhanced the composition and stiffness of large cartilage constructs.

PubMed

Cigan, Alexander D; Nims, Robert J; Albro, Michael B; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

2014-12-18

A significant challenge in cartilage tissue engineering is to successfully culture functional tissues that are sufficiently large to treat osteoarthritic joints. Transport limitations due to nutrient consumption by peripheral cells produce heterogeneous constructs with matrix-deficient centers. Incorporation of nutrient channels into large constructs is a promising technique for alleviating transport limitations, in conjunction with simple yet effective methods for enhancing media flow through channels. Cultivation of cylindrical channeled constructs flat in culture dishes, with or without orbital shaking, produced asymmetric constructs with poor tissue properties. We therefore explored a method for exposing the entire construct surface to the culture media, while promoting flow through the channels. To this end, chondrocyte-seeded agarose constructs (∅10mm, 2.34mm thick), with zero or three nutrient channels (∅1mm), were suspended on their sides in custom culture racks and subjected to three media stirring modes for 56 days: uniaxial rocking, orbital shaking, or static control. Orbital shaking led to the highest construct EY, sulfated glycosaminoglycan (sGAG), and collagen contents, whereas rocking had detrimental effects on sGAG and collagen versus static control. Nutrient channels increased EY as well as sGAG homogeneity, and the beneficial effects of channels were most marked in orbitally shaken samples. Under these conditions, the constructs developed symmetrically and reached or exceeded native levels of EY (~400kPa) and sGAG (~9%/ww). These results suggest that the cultivation of channeled constructs in culture racks with orbital shaking is a promising method for engineering mechanically competent large cartilage constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alterations by glyburide of effects of BRL 34915 and P 1060 on contraction, 86Rb efflux and the maxi-K+ channel in rat portal vein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, S.L.; Kim, H.S.; Okolie, P.

1990-05-01

Effects of the K+ channel blocking agent, glyburide, on the actions of two K+ channel openers, BRL 34915 (cromakalim) and P 1060 (Leo), a potent pinacidil derivative (N-(t-butyl)-N{double prime}-cyano-N{prime}-3-pyridyl-guanidine), were ascertained. Tension responses and {sup 86}Rb fluxes in rat portal vein strips and single channel electrophysiological recordings in enzymatically dissociated rat portal vein cells were obtained. Glyburide (0.3 microM) increased spontaneous contractile activity and caused concentration-dependent shifts in the relaxation responses to BRL 34915 and P 1060. Increases in {sup 86}Rb efflux were obtained only at much higher concentrations of BRL 34915 or P 1060, and these increases were blockedmore » only at higher concentrations of glyburide (5.0 microM). BRL 34915 and P 1060 specifically increase the open-state probability of the Ca+(+)-activated K+ (maxi-K+) channel, and these actions are blocked by glyburide and also by charybdotoxin. Changes in single channel activity and contractile responsiveness occur at similar concentrations of agonists and antagonists. Thus, the membrane channel in rat portal vein affected by glyburide, BRL 34915 and P 1060 appears to be the Ca+(+)-activated maxi-K+ channel (that does not show ATP dependence under the conditions of these experiments). Concentrations of agonists and antagonists effective on maxi-K+ channel activity correspond to those affecting contractile responsiveness and are lower than those eliciting changes in {sup 86}Rb flux.« less

The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK

PubMed Central

Beltrán, Leopoldo R.; Dawid, Corinna; Beltrán, Madeline; Gisselmann, Guenter; Degenhardt, Katharina; Mathie, Klaus; Hofmann, Thomas; Hatt, Hanns

2013-01-01

For a long time, the focus of trigeminal chemoperception has rested almost exclusively on TRP channels. However, two-pore domain (K2P) potassium channels have recently been identified as targets for substances associated with typical trigeminal sensations, such as numbing and tingling. In addition, they have been shown to be modulated by several TRP agonists. We investigated whether the pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect on human K2P channels. For this purpose, we evaluated the effects of these pungent substances on both wild-type and mutant K2P channels by means of two-electrode voltage-clamp experiments using Xenopus laevis oocytes. All four pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1), TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose-dependent and, with the exception of polygodial on TASK-1, fully reversible. However, only piperine exhibited an IC50 similar to its reported EC50 on TRP channels. Finally, we observed for TASK-3 that mutating H98 to E markedly decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not by polygodial. Our data contribute to the relatively sparse knowledge concerning the pharmacology of K2P channels and also raise the question of whether K2P channels could be involved in the pungency perception of piperine. PMID:24302912

Kondo effect in the seven-orbital Anderson model hybridized with Γ8 conduction electrons

NASA Astrophysics Data System (ADS)

Hotta, Takashi

2018-05-01

We clarify the two-channel Kondo effect in the seven-orbital Anderson model hybridized with Γ8 conduction electrons by employing a numerical renormalization group method. From the numerical analysis for the case with two local f electrons, corresponding to Pr3+ or U4+ ion, we confirm that a residual entropy of 0.5 log 2 , a characteristic of two-channel Kondo phenomena, appears for the local Γ3 non-Kramers doublet state. For further understanding on the Γ3 state, the effective model is constructed on the basis of a j-j coupling scheme. Then, we rediscover the two-channel s-d model concerning quadrupole degrees of freedom. Finally, we briefly introduce our recent result on the two-channel Kondo effect for the case with three local f electrons.

Cardioprotective effect of diadenosine tetraphosphate (AP4A) preservation in hypothermic storage and its relation with mitochondrial ATP-sensitive potassium channels.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Kitakaze, M; Matsuda, H

2000-01-15

The preconditioning effect of diadenosine tetraphosphate (AP4A) was reported in ischemia/reperfused hearts, but its effect in heart preservation was unknown. According to the possible role of mitochondrial ATP-sensitive potassium channel (mK(ATP) channel) in the effect of ischemic preconditioning, the contribution of mK(ATP) channel to the effect of AP4A was tested. Isolated rat hearts were arrested and preserved by Eurocollin's (EC) solution at 4 degrees C for 8 hr. AP4A (80 microM) or AP4A with the 5-hydroxydecanoic acid (100 microM), a selective inhibitor of the mK(ATP) channel, was added into the EC solution. The preischemic and postischemic cardiac functions were evaluated on a buffer-perfused Langendorff apparatus before storage and after 20 min of reperfusion. AP4A administration improved the recovery of poststorage cardiac functions (the rate-pressure production, left ventricular systolic pressure, heart rate, coronary flow rate, and derivative of left ventricular systolic pressure; P<0.05) and reduced the leakage of lactate dehydrate and creatine kinase during reperfusion, compared with EC alone. Those effects of AP4A were completely reversed by 5-hydroxydecanoic acid administration in combination subjects. AP4A administration protects the heart through opening of the mK(ATP) channel during hypothermic preservation. Thus, addition of AP4A into cardioplegia may be a novel method of ischemic preconditioning in the transplantation context.

Dean vortices with wall flux in a curved channel membrane system. 2: The velocity field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, K.Y.; Brewster, M.E.; Belfort, G.

1996-02-01

The velocity and pressure fields and the effect of wall flux on these fields in a spiral channel are presented. As fluid flows inward through a spiral channel with constant gap and permeable walls, the streamwise flux decreases while the curvature increases. Thus, by balancing the stabilizing effect of wall suction with the destabilizing effect of increasing curvature, established vortices can be maintained along the spiral channel. This approach is used to prescribe spiral geometries with different wall fluxes. Using a weakly nonlinear stability analysis, the influence of wall flux on the characteristics of Dean vortices is obtained. The criticalmore » Dean number is reduced when suction is through the inner wall only, is slightly reduced when suction is equal through both walls, and is increased when suction is through the outer wall only. The magnitude of change is proportional to a ratio of small numbers that measures the importance of the effect of curvature. In membrane filtration applications the wall flux is typically 2 to 5 orders of magnitude less than the streamwise flow. If the radius of curvature of the channel is of the order of 100 times the channel gap, the effect on the critical Dean number is within 2% of the no-wall flux case. If the radius of curvature is sufficiently large, however, it is possible to observe effects on the critical Dean number that approach O(1) in magnitude for certain parameter ranges.« less

Fast flow of Jakobshavn Isbræ and its subglacial drainage system

NASA Astrophysics Data System (ADS)

Werder, M. A.; Joughin, I. R.

2013-12-01

Jakobshavn Isbræ and many other outlet glaciers of present and past ice sheets lie in deep troughs which often have several overdeepened sections. The subglacial drainage system of such glaciers is heavily influenced by two effects caused by the pressure dependence of the melting point of water. The melting point decreases with increasing water pressure, this enhances wall-melt in downward sloping channels and diminishes wall-melt in upward sloping channels. Thus the first effect is the well known shutdown of channels on steep adverse bed slopes of overdeepenings and the associated high water pressure/low effective pressure. The second effect is a 2D effect and has not received much/any attention so far: the orientation of a channel will be deflected from the direction of the (negative) hydraulic potential gradient (which drives the water flow) towards the steepest slope of the bed. This leads to the enhanced formation of side channels dipping into the trough at about a 45° angle. This efficient connection between the margin and the trough equalizes the hydraulic potential, again leading to higher water pressure in the trough. We investigate these two effects with the 2D subglacial drainage system model GlaDS using Jakobshavn Isbræ as an example. We compare model runs with the pressure melt term disabled and enabled. With the term disabled the main channel situated in the trough is continuous and produces a large depression in the hydraulic potential and consequently high effective pressure in the trough (1-2MPa). Conversely, with the term enabled the main channel becomes discontinuous on steep adverse bed slopes and many side channels form on the margins of the trough. This leads to a hydraulic potential in the trough which is higher than in the surrounding area and consequently the effective pressure is low (0-1MPa). Low effective pressure leads to reduced basal drag and thus to more basal sliding. The modeled large decrease of effective pressure in the trough due to the pressure dependence of the melting point of water suggests that basal drag will be small and that sliding speeds are large. Thus, this may be one of the leading causes for the fast flow of Jakobshavn Isbræ and other glaciers in deep troughs.

The effect of basal channels on oceanic ice-shelf melting

NASA Astrophysics Data System (ADS)

Millgate, Thomas; Holland, Paul R.; Jenkins, Adrian; Johnson, Helen L.

2013-12-01

The presence of ice-shelf basal channels has been noted in a number of Antarctic and Greenland ice shelves, but their impact on basal melting is not fully understood. Here we use the Massachusetts Institute of Technology general circulation model to investigate the effect of ice-shelf basal channels on oceanic melt rate for an idealized ice shelf resembling the floating tongue of Petermann Glacier in Greenland. The introduction of basal channels prevents the formation of a single geostrophically balanced boundary current; instead the flow is diverted up the right-hand (Coriolis-favored) side of each channel, with a return flow in the opposite direction on the left-hand side. As the prescribed number of basal channels is increased the mean basal melt rate decreases, in agreement with previous studies. For a small number of relatively wide channels the subice flow is found to be a largely geostrophic horizontal circulation. The reduction in melt rate is then caused by an increase in the relative contribution of weakly melting channel crests and keels. For a larger number of relatively narrow channels, the subice flow changes to a vertical overturning circulation. This change in circulation results in a weaker sensitivity of melt rates to channel size. The transition between the two regimes is governed by the Rossby radius of deformation. Our results explain why basal channels play an important role in regulating basal melting, increasing the stability of ice shelves.

Flying-patch patch-clamp study of G22E-MscL mutant under high hydrostatic pressure.

PubMed

Petrov, Evgeny; Rohde, Paul R; Martinac, Boris

2011-04-06

High hydrostatic pressure (HHP) present in natural environments impacts on cell membrane biophysical properties and protein quaternary structure. We have investigated the effect of high hydrostatic pressure on G22E-MscL, a spontaneously opening mutant of Escherichia coli MscL, the bacterial mechanosensitive channel of large conductance. Patch-clamp technique combined with a flying-patch device and hydraulic setup allowed the study of the effects of HHP up to 90 MPa (as near the bottom of the Marianas Trench) on the MscL mutant channel reconstituted into liposome membranes, in addition to recording in situ from the mutant channels expressed in E. coli giant spheroplasts. In general, against thermodynamic predictions, hydrostatic pressure in the range of 0.1-90 MPa increased channel open probability by favoring the open state of the channel. Furthermore, hydrostatic pressure affected the channel kinetics, as manifested by the propensity of the channel to gate at subconducting levels with an increase in pressure. We propose that the presence of water molecules around the hydrophobic gate of the G22E MscL channel induce hydration of the hydrophobic lock under HHP causing frequent channel openings and preventing the channel closure in the absence of membrane tension. Furthermore, our study indicates that HHP can be used as a valuable experimental approach toward better understanding of the gating mechanism in complex channels such as MscL. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

NPPB structure-specifically activates TRPA1 channels.

PubMed

Liu, Kun; Samuel, Manoj; Ho, Melisa; Harrison, Richard K; Paslay, Jeff W

2010-07-01

TRPA1 channels have been found to play an important role in mammalian pain sensation, especially when the pain is caused by chemicals on site of inflammation. A large number of structurally diverse chemicals are found to activate TRPA1 channels, implicating a potential chemosensor in neuronal nociception. Identification of the channel activation by cysteine modification through covalent chemical reaction provides arguments for the diversity of the agonist structures. However, it is largely unknown how nonreactive compounds activate TRPA1 channels. Here, we report that NPPB, a classic Cl(-) channel blocker, potently activated human TRPA1 channels overexpressed in mammalian HEK-293 cells. This effect was confirmed in Ca(2+) imaging assay, patch clamp whole cell and single channel recordings. The NPPB response was quick, fully reversible and replicable, contrary to the effect of covalent modification by AITC. The mutagenesis studies revealed a refreshed look at several mutations known to be critical for the actions of AITC and menthol. The blocking profile of NPPB on these mutants showed that the NPPB activation was similar to that of FTS and different from AITC and menthol. The results indicated a possible close interaction between S5 and N-terminal domains of the channel. We also tested a group of NPPB analogs on TRPA1 channel activities. The results demonstrated that NPPB activation was tightly associated with chemical structure. None of the single chemical group was sufficient to activate the channel, indicating that NPPB activated TRPA1 through a structure-specific mechanism. (c) 2010 Elsevier Inc. All rights reserved.

Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

PubMed

Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

2018-06-01

Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na + /K + -ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K + channels, voltage-activated calcium channel, and Na + /K + -ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K + channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K + channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca 2+ -activated K + channels-SK Ca ), iberiotoxin (a selective blocker of large-conductance Ca 2+ -activated K + channels-BK Ca ), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na + /K + -ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SK Ca and BK Ca ) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na + /K + -ATPase activity.

Channeling, channel density and mass recovery in aquifer transport, with application to the MADE experiment

NASA Astrophysics Data System (ADS)

Fiori, A.

2014-12-01

Channeling effects in heterogeneous formations are studied through a new quantity denoted as channel density a(x,t). Focusing on advection only, a(x,t) is defined as the relative number of streamtubes (or channels) containing solute between x and x + dx at a given time t, regardless of the mass that they carry. The channel density generally differs from the widely employed longitudinal mass distribution m(x,t), and their difference increases with time and the degree of heterogeneity. The difference between a and m reflects the nonuniformity of mass distribution relative to the plume geometry. In particular, the "fast" channels typically carry a larger fraction of mass than their share in their relative volume, which in turn can be rather small. Detecting such channels by a network of monitoring wells may be a challenging task, which might explain the poor solute recovery of some field experiments at increasing times. After application of the proposed concepts to the simple case of stratified formations, we model the channel density and mass distribution pertaining to the MADE experiment, which exhibited poor mass recovery at large times. The results presented in this study emphasize the possible channeling effects at MADE and the general difficulty in sampling the leading edge of the plume, which in turn may contain a significant fraction of the plume mass.

The role of entropic potential in voltage activation and K+ transport through Kv 1.2 channels

NASA Astrophysics Data System (ADS)

Wawrzkiewicz-Jałowiecka, Agata; Grzywna, Zbigniew J.

2018-03-01

We analyze the entropic effects of inner pore geometry changes of Kv 1.2 channel during membrane depolarization and their implications for the rate of transmembrane transport of potassium ions. We base this on the idea that spatial confinements within the channel pore give rise to entropic barriers which can both effectively affect the stability of open macroconformation and influence channel's ability to conduct the potassium ions through the membrane. First, we calculate the differences in entropy between voltage-activated and resting states of the channel. As a template, we take a set of structures of channel pore in an open state at different membrane potentials generated in our previous research. The obtained results indicate that tendency to occupy open states at membrane depolarization is entropy facilitated. Second, we describe the differences in rates of K+ transport through the channel pore at different voltages based on the results of appropriate random walk simulations in entropic and electric potentials. The simulated single channel currents (I) suggest that the geometry changes during membrane depolarization are an important factor contributing to the observed flow of potassium ions through the channel. Nevertheless, the charge distribution within the channel pore (especially at the extracellular entrance) seems most prominent for the observed I/Imax relation at a qualitative level at analyzed voltages.

Neotectonic effects on sinuosity and channel migration, Belle Fourche River, Western South Dakota

USGS Publications Warehouse

Gomez, Basil; Marron, Donna C.

1991-01-01

Short-term instability in the behaviour of a small, meandering alluvial channel is identified from the relation between sinuosity and either floodplain slope or channel slope within 17 reaches along an 81-kilometre section of the Belle Fourche River in western South Dakota. In reaches 1 to 4 and 11 to 17 the channel is relatively stable and sinuosity varies inversely with channel slope. In reaches 5 to 10, sinuosity is positively related to floodplain slope. Sinuosity increases markedly in reaches 5, 6, and 7 (which are immediately downstream from a discontinuity in the long profile of the floodplain) in association with an increase in floodplain slope. Immediately upstream from the discontinuity, bankfull channel depth and sinuosity decrease and the area of the floodplain reworked by meander migration between 1939 and 1981 increases, in association with a decrease in floodplain slope. Channel behaviour in reaches 5 to 10 is best explained as a consequence of neotectonic activity, as indicated by changes in elevation recorded along geodetic survey lines that cross lineaments that may delimit the eastern boundary of the Black Hills uplift. Sinuosity acts as a barometer of the effects of neotectonic activity on alluvial channels. Initial indications of channel and floodplain instability due to neotectonic activity may be derived from evidence of anomalously active channel migration, as documented from photographic or topographic sources.

Do TRPC channels support working memory? Comparing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators.

PubMed

Reboreda, Antonio; Theissen, Frederik M; Valero-Aracama, Maria J; Arboit, Alberto; Corbu, Mihaela A; Yoshida, Motoharu

2018-03-01

Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks. If TRPC channels are indeed a central mechanism for working memory, manipulations which impair or facilitate working memory should have a similar effect on TRPC channel modulation. However, modulations of working memory and TRPC channels were never systematically compared, and it remains unanswered whether TRPC channels indeed contribute to working memory in vivo or not. In this article, we review the effects of G-protein coupled receptors (GPCR) and neuromodulators, including acetylcholine, noradrenalin, serotonin and dopamine, on working memory and TRPC channels. Based on comparisons, we argue that GPCR and downstream signaling pathways that activate TRPC, generally support working memory, while those that suppress TRPC channels impair it. However, depending on the channel types, areas, and systems tested, this is not the case in all studies. Further work to clarify involvement of specific TRPC channels in working memory tasks and how they are affected by neuromodulators is still necessary in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Downstream reduction of rural channel size with contrasting urban effects in small coastal streams of southeastern Australia

NASA Astrophysics Data System (ADS)

Nanson, G. C.; Young, R. W.

1981-07-01

Although most streams show a downstream increase in channel size corresponding to a downstream increase in flood discharges, those flowing off the Illawarra escarpment of New South Wales show a marked reduction of channel size, accompanied by a down-stream increase in flood frequency in their lower reaches. Within the confined and steeply sloping valleys of the escarpment foothills, bed and bank sediments are relatively coarse and uncohesive, and channels increase in size, corresponding to increasing discharge downstream. However, once these streams emerge into more open rural valleys at lower slopes and are accompanied by extensive floodplains formed of fine cohesive sediment, there is a dramatic reduction in channel size. This decrease in channel size apparently results from a sudden decline in channel slope and associated stream power, the cohesive nature of downstream alluvium, its retention on the channel banks by a dense cover of pasture grasses, and the availability of an extensive floodplain to carry displaced floodwater. Under these conditions floodwaters very frequently spill out over the floodplain and the downstream channel-flow becomes a relatively unimportant component of the total peak discharge. This emphasizes the importance of these floodplains as a part of the total channel system. In situations where urban development has increased peak runoff and reduced the available area of effective floodplain, stream channels formed in this fine alluvium rapidly entrench and increase in cross-sectional area by 2-3 times. Minor man-induced channel alteration and maintenance appears to trigger this enlargement.

The Onset of Channelling in a Fluidized Mud Layer

NASA Astrophysics Data System (ADS)

Papanicolaou, T.; Tsakiris, A. G.; Billing, B. M.

2012-12-01

Fluidization of a soil occurs when the drag force exerted on the soil grains by upwelling water equals the submerged weight of the soil grains, hence reducing the effective (or contact) stress between the soil grains to zero. In nature, fluidization is commonly encountered in localized portions of highly saturated mud layers found in tidal flats, estuaries and lakes, where upward flow is initiated by significant pore water pressure gradients triggered by wave or tidal action. The water propagates through the fluidized mud layer by forming channels (or vents), carrying the fluidized mud to the surface and forming mud volcano structures. The presence of these fluidization channels alters the mud layer structure with implications on its hydraulic and geotechnical properties, such as the hydraulic conductivity. Despite the importance of these channels, the conditions that lead to their formation and their effects on the mud layer structure still remain poorly documented. The present study couples experimental and theoretical methods aimed at quantifying the conditions, under which fluidization of a saturated mud layer is accompanied by the formation of channels, and assessing the effects of channeling on the mud layer structure. Fluidization and channel formation in a mud layer were reproduced in the laboratory using a carefully designed fluidization column attached to a pressurized vessel (plenum). To eliminate any effects of the material, the mud was produced from pure kaolin clay and deionized water. Local porosity measurements along the mud layer prior, during and after fluidization were conducted using an Americium-241 gamma source placed on a fully automated carriage. Different water inflow rates, q, were applied to the base of the mud layer and the plenum pressure was monitored throughout the experiment. These experiments revealed that for high q values, a single vertical channel formed and erupted at the center of the fluidization column. Instead for low q values, the experiments suggested that a channel network formed within the mud layer leading to the eruption of multiple channels on the mud layer surface. The gamma source measurements captured quantitatively the porosity increase as the channel formed. The experiments were complemented with a theoretical analysis using the two-phase, flow mass and momentum governing equations. This analysis aims to establish a relation between the applied pressure, the fluid velocity and the local porosity of mud during the formation of the channels.

Diverse Roles for Auxiliary Subunits in Phosphorylation-Dependent Regulation of Mammalian Brain Voltage-Gated Potassium Channels

PubMed Central

Vacher, Helene; Trimmer, James S.

2012-01-01

Voltage-gated ion channels are a diverse family of signaling proteins that mediate rapid electrical signaling events. Among these, voltage-gated potassium or Kv channels are the most diverse, in part due to the large number of principal (or α) subunits and auxiliary subunits that can assemble in different combinations to generate Kv channel complexes with distinct structures and functions. The diversity of Kv channels underlies much of the variability in the active properties between different mammalian central neurons, and the dynamic changes that lead to experience-dependent plasticity in intrinsic excitability. Recent studies have revealed that Kv channel α subunits and auxiliary subunits are extensively phosphorylated, contributing to additional structural and functional diversity. Here we highlight recent studies that show that auxiliary subunits exert some of their profound effects on dendritic Kv4 and axonal Kv1 channels through phosphorylation-dependent mechanisms, either due to phosphorylation on the auxiliary subunit itself, or by influencing the extent and/or impact of α subunit phosphorylation. The complex effects of auxiliary subunits and phosphorylation provide a potent mechanism to generate additional diversity in the structure and function of Kv4 and Kv1 channels, as well as allowing for dynamic reversible regulation of these important ion channels. PMID:21822597

The effects of diets containing standard soybean oil, soybean oil enhanced with conjugated linoleic acids, menhaden fish oil, or an algal docosahexaenoic acid supplement on juvenile channel catfish performance, hematology

USDA-ARS?s Scientific Manuscript database

Current commercial diets for Channel Catfish contain little or no marine fish oil to reduce diet cost and address environmental concerns. However, there is conflicting data on the effects of fish oil and other lipid sources in juvenile Channel Catfish, and some novel lipids have not been tested agai...

Downstream effects of the Pelton-Round Butte hydroelectric project on bedload, transport, channel morphology, and channel-bed texture, lower Deschutes River, Oregon.

Treesearch

Heidi Fassnacht; Ellen M. McClure; Gordon E. Grant; Peter C. Klingeman

2003-01-01

Field, laboratory, and historical data provide the basis for interpreting the effects of the Pelton-Round Butte dam complex on the surface water hydrology and geomorphology of the lower Deschutes River, Oregon, USA. The river's response to upstream impoundment and flow regulation is evaluated in terms of changes in predicted bedload transport rates, channel...

Characterization of cocaine-induced block of cardiac sodium channels.

PubMed

Crumb, W J; Clarkson, C W

1990-03-01

Recent evidence suggests that cocaine can produce marked cardiac arrhythmias and sudden death. A possible mechanism for this effect is slowing of impulse conduction due to block of cardiac Na channels. We therefore investigated its effects on Na channels in isolated guinea pig ventricular myocytes using the whole-cell variant of the patch clamp technique. Cocaine (10-50 microM) was found to reduce Na current in a use-dependent manner. The time course for block development and recovery were characterized. At 30 microM cocaine, two phases of block development were defined: a rapid phase (tau = 5.7 +/- 4.9 ms) and a slower phase (tau = 2.3 +/- 0.7 s). Recovery from block at -140 mV was also defined by two phases: (tau f = 136 +/- 61 ms, tau s = 8.5 +/- 1.7 s) (n = 6). To further clarify the molecular mechanisms of cocaine action on cardiac Na channels, we characterized its effects using the guarded receptor model, obtaining estimated Kd values of 328, 19, and 8 microM for channels predominantly in the rested, activated, and inactivated states. These data indicate that cocaine can block cardiac Na channels in a use-dependent manner and provides a possible cellular explanation for its cardiotoxic effects.

Antisense oligodeoxynucleotide inhibition of a swelling-activated cation channel in osteoblast-like osteosarcoma cells

NASA Technical Reports Server (NTRS)

Duncan, R. L.; Kizer, N.; Barry, E. L.; Friedman, P. A.; Hruska, K. A.

1996-01-01

By patch-clamp analysis, we have shown that chronic, intermittent mechanical strain (CMS) increases the activity of stretch-activated cation channels of osteoblast-like UMR-106.01 cells. CMS also produces a swelling-activated whole-cell conductance (Gm) regulated by varying strain levels. We questioned whether the swelling-activated conductance was produced by stretch-activated cation channel activity. We have identified a gene involved in the increase in conductance by using antisense oligodeoxynucleotides (ODN) derived from the alpha 1-subunit genes of calcium channels found in UMR-106.01 cells (alpha1S, alpha1C, and alpha1D). We demonstrate that alpha 1C antisense ODNs abolish the increase in Gm in response to hypotonic swelling following CMS. Antisense ODNs to alpha1S and alpha1D, sense ODNs to alpha1C, and sham permeabilization had no effect on the conductance increase. In addition, during cell-attached patch-clamp studies, antisense ODNs to alpha1c completely blocked the swelling-activated and stretch-activated nonselective cation channel response to strain. Antisense ODNs to alpha1S treatment produced no effect on either swelling-activated or stretch-activated cation channel activity. There were differences in the stretch-activated and swelling-activated cation channel activity, but whether they represent different channels could not be determined from our data. Our data indicate that the alpha1C gene product is involved in the Gm and the activation of the swelling-activated cation channels induced by CMS. The possibility that swelling-activated cation channel genes are members of the calcium channel superfamily exists, but if alpha1c is not the swelling-activated cation channel itself, then its expression is required for induction of swelling-activated cation channel activity by CMS.

Effect of chloride channel inhibitors on cytosolic Ca2+ levels and Ca2+-activated K+ (Gardos) channel activity in human red blood cells.

PubMed

Kucherenko, Yuliya V; Wagner-Britz, Lisa; Bernhardt, Ingolf; Lang, Florian

2013-04-01

DIDS, NPPB, tannic acid (TA) and AO1 are widely used inhibitors of Cl(-) channels. Some Cl(-) channel inhibitors (NPPB, DIDS, niflumic acid) were shown to affect phosphatidylserine (PS) scrambling and, thus, the life span of human red blood cells (hRBCs). Since a number of publications suggest Ca(2+) dependence of PS scrambling, we explored whether inhibitors of Cl(-) channels (DIDS, NPPB) or of Ca(2+)-activated Cl(-) channels (DIDS, NPPB, TA, AO1) modified intracellular free Ca(2+) concentration ([Ca(2+)]i) and activity of Ca(2+)-activated K(+) (Gardos) channel in hRBCs. According to Fluo-3 fluorescence in flow cytometry, a short treatment (15 min, +37 °C) with Cl(-) channels inhibitors decreased [Ca(2+)]i in the following order: TA > AO1 > DIDS > NPPB. According to forward scatter, the decrease of [Ca(2+)]i was accompanied by a slight but significant increase in cell volume following DIDS, NPPB and AO1 treatments. TA treatment resulted in cell shrinkage. According to whole-cell patch-clamp experiments, TA activated and NPPB and AO1 inhibited Gardos channels. The Cl(-) channel blockers further modified the alterations of [Ca(2+)]i following ATP depletion (glucose deprivation, iodoacetic acid, 6-inosine), oxidative stress (1 mM t-BHP) and treatment with Ca(2+) ionophore ionomycin (1 μM). The ability of the Cl(-) channel inhibitors to modulate PS scrambling did not correlate with their influence on [Ca(2+)]i as TA and AO1 had a particularly strong decreasing effect on [Ca(2+)]i but at the same time enhanced PS exposure. In conclusion, Cl(-) channel inhibitors affect Gardos channels, influence Ca(2+) homeostasis and induce PS exposure of hRBCs by Ca(2+)-independent mechanisms.

Disease-associated mutations in CNGB3 promote cytotoxicity in photoreceptor-derived cells

PubMed Central

Liu, Chunming; Sherpa, Tshering

2013-01-01

Purpose To determine if achromatopsia associated F525N and T383fsX mutations in the CNGB3 subunit of cone photoreceptor cyclic nucleotide-gated (CNG) channels increases susceptibility to cell death in photoreceptor-derived cells. Methods Photoreceptor-derived 661W cells were transfected with cDNA encoding wild-type (WT) CNGA3 subunits plus WT or mutant CNGB3 subunits, and incubated with the membrane-permeable CNG channel activators 8-(4-chlorophenylthio) guanosine 3′,5′-cyclic monophosphate (CPT-cGMP) or CPT-adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Cell viability under these conditions was determined by measuring lactate dehydrogenase release. Channel ligand sensitivity was calibrated by patch-clamp recording after expression of WT or mutant channels in Xenopus oocytes. Results Coexpression of CNGA3 with CNGB3 subunits containing F525N or T383fsX mutations produced channels exhibiting increased apparent affinity for CPT-cGMP compared to WT channels. Consistent with these effects, cytotoxicity in the presence of 0.1 μM CPT-cGMP was enhanced relative to WT channels, and the increase in cell death was more pronounced for the mutation with the largest gain-of-function effect on channel gating, F525N. Increased susceptibility to cell death was prevented by application of the CNG channel blocker L-cis-diltiazem. Increased cytotoxicity was also found to be dependent on the presence of extracellular calcium. Conclusions These results indicate a connection between disease-associated mutations in cone CNG channel subunits, altered CNG channel-activation properties, and photoreceptor cytotoxicity. The rescue of cell viability via CNG channel block or removal of extracellular calcium suggests that cytotoxicity in this model depends on calcium entry through hyperactive CNG channels. PMID:23805033

Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels

PubMed Central

Xia, Menghang; Shahane, Sampada; Huang, Ruili; Titus, Steven A.; Shum, Enoch; Zhao, Yong; Southall, Noel; Zheng, Wei; Witt, Kristine L.; Tice, Raymond R.; Austin, Christopher P.

2011-01-01

The human ether-a-go-go-related gene (hERG) channel, a member of a family of voltage-gated potassium (K+) channels, plays a critical role in the repolarization of the cardiac action potential. The reduction of hERG channel activity as a result of adverse drug effects or genetic mutations may cause QT interval prolongation and potentially lead to acquired long QT syndrome. Thus, screening for hERG channel activity is important in drug development. Cardiotoxicity associated with the inhibition of hERG channels by environmental chemicals is also a public health concern. To assess the inhibitory effects of environmental chemicals on hERG channel function, we screened the National Toxicology Program (NTP) collection of 1408 compounds by measuring thallium influx into cells through hERG channels. Seventeen compounds with hERG channel inhibition were identified with IC50 potencies ranging from 0.26 to 22 μM. Twelve of these compounds were confirmed as hERG channel blockers in an automated whole cell patch clamp experiment. In addition, we investigated the structure-activity relationship of seven compounds belonging to the quaternary ammonium compound (QAC) series on hERG channel inhibition. Among four active QAC compounds, tetra-n-octylammonium bromide was the most potent with an IC50 value of 260 nM in the thallium influx assay and 80 nM in the patch clamp assay. The potency of this class of hERG channel inhibitors appears to depend on the number and length of their aliphatic side-chains surrounding the charged nitrogen. Profiling environmental compound libraries for hERG channel inhibition provides information useful in prioritizing these compounds for cardiotoxicity assessment in vivo. PMID:21362439

Channel coding in the space station data system network

NASA Technical Reports Server (NTRS)

Healy, T.

1982-01-01

A detailed discussion of the use of channel coding for error correction, privacy/secrecy, channel separation, and synchronization is presented. Channel coding, in one form or another, is an established and common element in data systems. No analysis and design of a major new system would fail to consider ways in which channel coding could make the system more effective. The presence of channel coding on TDRS, Shuttle, the Advanced Communication Technology Satellite Program system, the JSC-proposed Space Operations Center, and the proposed 30/20 GHz Satellite Communication System strongly support the requirement for the utilization of coding for the communications channel. The designers of the space station data system have to consider the use of channel coding.

Effect of ceramic membrane channel geometry and uniform transmembrane pressure on limiting flux and serum protein removal during skim milk microfiltration.

PubMed

Adams, Michael C; Hurt, Emily E; Barbano, David M

2015-11-01

Our objectives were to determine the effects of a ceramic microfiltration (MF) membrane's retentate flow channel geometry (round or diamond-shaped) and uniform transmembrane pressure (UTP) on limiting flux (LF) and serum protein (SP) removal during skim milk MF at a temperature of 50°C, a retentate protein concentration of 8.5%, and an average cross-flow velocity of 7 m·s(-1). Performance of membranes with round and diamond flow channels was compared in UTP mode. Performance of the membrane with round flow channels was compared with and without UTP. Using UTP with round flow channel MF membranes increased the LF by 5% when compared with not using UTP, but SP removal was not affected by the use of UTP. Using membranes with round channels instead of diamond-shaped channels in UTP mode increased the LF by 24%. This increase was associated with a 25% increase in Reynolds number and can be explained by lower shear at the vertices of the diamond-shaped channel's surface. The SP removal factor of the diamond channel system was higher than the SP removal factor of the round channel system below the LF. However, the diamond channel system passed more casein into the MF permeate than the round channel system. Because only one batch of each membrane was tested in our study, it was not possible to determine if the differences in protein rejection between channel geometries were due to the membrane design or random manufacturing variation. Despite the lower LF of the diamond channel system, the 47% increase in membrane module surface area of the diamond channel system produced a modular permeate removal rate that was at least 19% higher than the round channel system. Consequently, using diamond channel membranes instead of round channel membranes could reduce some of the costs associated with ceramic MF of skim milk if fewer membrane modules could be used to attain the required membrane area. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Kv7 (KCNQ) channel openers induce hypothermia in the mouse.

PubMed

Kristensen, Line V; Sandager-Nielsen, Karin; Hansen, Henrik H

2011-01-20

Kv7 channels, encoded by corresponding kcnq genes, are expressed both centrally and peripherally where they serve to dampen neuronal activity. While Kv7 channel openers have shown efficacy in neurological and neuropsychiatric disease models, the impact of Kv7 channel activation on physiological endpoint markers have not been addressed in detail. In this study we assessed the effect of a range of Kv7 channel openers with different affinity for neuronal Kv7.2-5 channel subunits on body temperature regulation in mice. Female NMRI mice were acutely exposed to vehicle (10% Tween-80, i.p.), retigabine (3-30 mg/kg, i.p., pan-Kv7 channel opener), (S)BMS-204352 (60-240 mg/kg, i.p., Kv7.4/5 channel-preferring opener), ICA-27243 (1-10mg/kg, i.p., Kv7.2/3 channel-preferring opener), or S-(1) (10-60 mg/kg, i.p., Kv7.2/3 channel-preferring opener), and rectal body temperature was measured 15-120 min post-injection. Retigabine (>10mg/kg), ICA-27243 (≥ 10 mg/kg), and S-(1) (≥ 30 mg/kg) dose-dependently lowered rectal body temperature with maximal doses of each Kv7 channel opener inducing a marked drop (>4°C) in rectal temperature. The Kv7 channel openers showed differential temporal pharmacodynamics, which likely reflects their different pharmacokinetic profiles. Pretreatment with the pan-Kv7 channel blocker XE-991 (1.0mg/kg, i.p.) completely reversed the hypothermic effect of the pan-Kv7 opener, retigabine (15 mg/kg), whereas ICA-27243-induced hypothermia (10mg/kg) could only be partially prevented by XE-991. Because ICA-27743 and S-(1) are Kv7.2/3 channel subunit-preferring compounds, this suggests that the Kv7.2/3 channel isoform is the predominant substrate for Kv7 channel opener-evoked hypothermia. These data indicate the physiological relevance of Kv7 channel function on body temperature regulation which may potentially reside from central inhibitory Kv7 channel activity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Analysis of synchronous digital-modulation schemes for satellite communication

NASA Technical Reports Server (NTRS)

Takhar, G. S.; Gupta, S. C.

1975-01-01

The multipath communication channel for space communications is modeled as a multiplicative channel. This paper discusses the effects of multiplicative channel processes on the symbol error rate for quadrature modulation (QM) digital modulation schemes. An expression for the upper bound on the probability of error is derived and numerically evaluated. The results are compared with those obtained for additive channels.

Coupling of laser energy into plasma channels

NASA Astrophysics Data System (ADS)

Dimitrov, D. A.; Giacone, R. E.; Bruhwiler, D. L.; Busby, R.; Cary, J. R.; Geddes, C. G. R.; Esarey, E.; Leemans, W. P.

2007-04-01

Diffractive spreading of a laser pulse imposes severe limitations on the acceleration length and maximum electron energy in the laser wake field accelerator (LWFA). Optical guiding of a laser pulse via plasma channels can extend the laser-plasma interaction distance over many Rayleigh lengths. Energy efficient coupling of laser pulses into and through plasma channels is very important for optimal LWFA performance. Results from simulation parameter studies on channel guiding using the particle-in-cell (PIC) code VORPAL [C. Nieter and J. R. Cary, J. Comput. Phys. 196, 448 (2004)] are presented and discussed. The effects that density ramp length and the position of the laser pulse focus have on coupling into channels are considered. Moreover, the effect of laser energy leakage out of the channel domain and the effects of tunneling ionization of a neutral gas on the guided laser pulse are also investigated. Power spectral diagnostics were developed and used to separate pump depletion from energy leakage. The results of these simulations show that increasing the density ramp length decreases the efficiency of coupling a laser pulse to a channel and increases the energy loss when the pulse is vacuum focused at the channel entrance. Then, large spot size oscillations result in increased energy leakage. To further analyze the coupling, a differential equation is derived for the laser spot size evolution in the plasma density ramp and channel profiles are simulated. From the numerical solution of this equation, the optimal spot size and location for coupling into a plasma channel with a density ramp are determined. This result is confirmed by the PIC simulations. They show that specifying a vacuum focus location of the pulse in front of the top of the density ramp leads to an actual focus at the top of the ramp due to plasma focusing, resulting in reduced spot size oscillations. In this case, the leakage is significantly reduced and is negligibly affected by ramp length, allowing for efficient use of channels with long ramps.

Riparian vegetation controls on channels formed in non-cohesive sediment

NASA Astrophysics Data System (ADS)

Gran, K.; Tal, M.; Paola, C.

2002-05-01

Riparian vegetation can significantly influence the morphology of a river, affecting channel geometry and flow dynamics. In channels formed in non-cohesive material, vegetation is the main source of bank cohesion and could affect the overall behavior of the river, potentially constraining the flow from a multi-thread channel to a single-thread channel. To examine the effects of riparian vegetation on streams formed in non-cohesive material, we conducted a series of physical experiments at the St. Anthony Falls Laboratory. The first set of experiments examines the effects of varying densities of vegetation on braided stream dynamics. Water discharge, sediment discharge, and grain size were held constant. For each run, we allowed a braided system to develop, then halved the discharge, and seeded the flume with alfalfa (Medicago sativa). After ten to fourteen days of growth, we returned the discharge to its original value and continued the run for 30-36 hours. Our results show that the influence of vegetation on the overall river pattern varied systematically with the spatial density of plant stems. The vegetation reduced the number of active channels and increased bank stability, leading to lower lateral migration rates, narrower and deeper channels, and an increase in channel relief. All these effects increased with vegetation density. Vegetation also influenced flow dynamics, increasing the variance of flow direction in the vegetated runs, and increasing scour depths through strong downwelling where the flow collided with relatively resistant banks. This oblique bank collision provides a new mechanism for producing secondary flows. We found these bank collision driven secondary flows to be more important than the classical curvature-driven mechanism in the vegetated runs. The next set of experiments examines more closely how the channel pattern evolves through time, allowing for both channel migration and successive vegetation growth. In these on-going experiments, vegetation is reseeded following repeat high flow events, simulating the natural process of vegetation encroachment on the floodplain and channel.

Effect of channel size on sweet potato storage root enlargement in the Tuskegee University hydroponic nutrient film system

NASA Technical Reports Server (NTRS)

Morris, Carlton E.; Martinez, Edwin; Bonsi, C. K.; Mortley, Desmond G.; Hill, Walter A.; Ogbuehi, Cyriacus R.; Loretan, Phil A.

1989-01-01

The potential of the sweet potato as a food source for future long term manned space missions is being evaluated for NASA's Controlled Ecological Life Support Systems (CELSS) program. Sweet potatoes have been successfully grown in a specially designed Tuskegee University nutrient film technique (TU NFT) system. This hydroponic system yielded storage roots as high as 1790 g/plant fresh weight. In order to determine the effect of channel size on the yield of sweet potatoes, the width and depth of the growing channels were varied in two separate experiments. Widths were studied using the rectangular TU NFT channels with widths of 15 cm (6 in), 30 cm (12 in) and 45 cm (18 in). Channel depths of 5 cm (2 in), 10 cm (4 in), and 15 cm (6 in) were studied using a standard NASA fan shaped Biomass Production Chamber (BPC) channel. A comparison of preliminary results indicated that, except for storage root number, the growth and yield of sweet potatoes were not affected by channel width. Storage root yield was affected by channel depth although storage root number and foliage growth were not. Both experiments are being repeated.

Model microswimmers in channels with varying cross section

NASA Astrophysics Data System (ADS)

Malgaretti, Paolo; Stark, Holger

2017-05-01

We study different types of microswimmers moving in channels with varying cross section and thereby interacting hydrodynamically with the channel walls. Starting from the Smoluchowski equation for a dilute suspension, for which interactions among swimmers can be neglected, we derive analytic expressions for the lateral probability distribution between plane channel walls. For weakly corrugated channels, we extend the Fick-Jacobs approach to microswimmers and thereby derive an effective equation for the probability distribution along the channel axis. Two regimes arise dominated either by entropic forces due to the geometrical confinement or by the active motion. In particular, our results show that the accumulation of microswimmers at channel walls is sensitive to both the underlying swimming mechanism and the geometry of the channels. Finally, for asymmetric channel corrugation, our model predicts a rectification of microswimmers along the channel, the strength and direction of which strongly depends on the swimmer type.

Unbounded number of channel uses may be required to detect quantum capacity.

PubMed

Cubitt, Toby; Elkouss, David; Matthews, William; Ozols, Maris; Pérez-García, David; Strelchuk, Sergii

2015-03-31

Transmitting data reliably over noisy communication channels is one of the most important applications of information theory, and is well understood for channels modelled by classical physics. However, when quantum effects are involved, we do not know how to compute channel capacities. This is because the formula for the quantum capacity involves maximizing the coherent information over an unbounded number of channel uses. In fact, entanglement across channel uses can even increase the coherent information from zero to non-zero. Here we study the number of channel uses necessary to detect positive coherent information. In all previous known examples, two channel uses already sufficed. It might be that only a finite number of channel uses is always sufficient. We show that this is not the case: for any number of uses, there are channels for which the coherent information is zero, but which nonetheless have capacity.

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users.

PubMed

Galvin, John J; Oba, Sandra I; Başkent, Deniz; Chatterjee, Monita; Fu, Qian-Jie

2015-01-01

Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure ("which interval is different?"). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2-4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Besides the increased loudness, the present results also suggest that multiple envelope representations may contribute to the multi-channel advantage observed in previous AMFD studies. The different patterns of results for the wide and narrow spacing suggest a peripheral contribution to multi-channel temporal processing. Because the effect of target AM frequency was non-monotonic in this study, adaptive procedures may not be suitable to measure AMFD thresholds with interfering envelopes. Envelope interactions among multiple channels may be quite complex, depending on the envelope information presented to each channel and the relative independence of the stimulated channels.

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users

PubMed Central

2015-01-01

Rationale Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. Methods In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure (“which interval is different?”). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2–4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Conclusions Besides the increased loudness, the present results also suggest that multiple envelope representations may contribute to the multi-channel advantage observed in previous AMFD studies. The different patterns of results for the wide and narrow spacing suggest a peripheral contribution to multi-channel temporal processing. Because the effect of target AM frequency was non-monotonic in this study, adaptive procedures may not be suitable to measure AMFD thresholds with interfering envelopes. Envelope interactions among multiple channels may be quite complex, depending on the envelope information presented to each channel and the relative independence of the stimulated channels. PMID:26431043

Pharmacological characterization of the voltage-dependent Ca2+ channels present in synaptosomes from rat and chicken central nervous system.

PubMed

Alvarez Maubecin, V; Sanchez, V N; Rosato Siri, M D; Cherksey, B D; Sugimori, M; Llinás, R; Uchitel, O D

1995-06-01

The voltage-dependent calcium channels present in mammalian and chicken brain synaptosomes were characterized pharmacologically using specific blockers of L-type channels (1,4-dihydropyridines), N-type channels (omega-conotoxin GVIA), and P-type channels [funnel web toxin (FTX) and omega-agatoxin IVA]. K(+)-induced Ca2+ uptake by chicken synaptosomes was blocked by omega-conotoxin GVIA (IC50 = 250 nM). This toxin at 5 microM did not block Ca2+ entry into rat frontal cortex synaptosomes. FTX and omega-agatoxin IVA blocked Ca2+ uptake by rat synaptosomes (IC50 = 0.17 microliter/ml and 40 nM, respectively). Likewise, in chicken synaptosomes, FTX and omega-agatoxin IVA affected Ca2+ uptake, FTX (3 microliters/ml) exerted a maximal inhibition of 40% with an IC50 similar to the one obtained in rat preparations, whereas with omega-agatoxin IVA saturation was not reached even at 5 microM. In chicken preparations, the combined effect of saturating concentrations of FTX (1 microliter/ml) and different concentrations of omega-conotoxin GVIA showed no additive effects. However, the effect of saturating concentrations of FTX and omega-conotoxin GVIA was never greater than the one observed with omega-conotoxin GVIA. We also found that 60% of the Ca2+ uptake by rat and chicken synaptosomes was inhibited by omega-conotoxin MVIID (1 microM), a toxin that has a high index of discrimination against N-type channels. Conversely, nitrendipine (10 microM) had no significant effect on Ca2+ uptake in either the rat or the chicken. In conclusion, Ca2+ uptake by rat synaptosomes is potently inhibited by different P-type Ca2+ channel blockers, thus indicating that P-type channels are predominant in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of rapid urbanization on streamflow, erosion, and sedimentation in a desert stream in the American Southwest

USGS Publications Warehouse

Whitney, John W.; Glancy, Patrick A.; Buckingham , Susan E.; Ehrenberg, Arthur C.

2015-01-01

Rapid urbanization has resulted in a series of sequential effects on a desert stream in the American Southwest. Lower Las Vegas Wash was a dry wash characterized by infrequent flood deposition when Las Vegas, Nevada was established in 1905. Wastewater effluent was discharged into the wash in low volumes for over 3 decades. Wastewater volumes increased commensurably with accelerated population growth during the late 20th century and created a sequence of feedback effects on the floodplain. Initially slow saturation of the valley fill created a desert oasis of dense floodplain vegetation and wetlands. Annual streamflow began in 1958 and erosion began a decade later with shallow incision in discontinuous channel segments. Increasing baseflow gradually enlarged channels; headcutting was active during the 1970s to 1984. The incised channels concentrated storm runoff, which accelerated local channel erosion, and in 1984 the headcuts were integrated during a series of monsoon floods. Wetlands were drained and most floodplain vegetation destroyed. Channel erosion continued unabated until engineering interventions began in the 21st century. No natural channel recovery occurred after initial urbanization effects because streamflow never stabilized in the late 20th century. A 6.6 M m3 sediment slug, eroded from the wash in ∼25 years, was deposited in Las Vegas Bay in Lake Mead. Falling reservoir levels during the 21st century are responsible for sediment redistribution and infilling of the bay. Close monitoring of impacts is recommended when urban wastewater and storm runoff are discharged on a desert wash. Channel interventions, when necessary, are advised in order to prevent costly engineering schemes of channel stabilization, flood control, and floodplain restoration.

Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

PubMed Central

Patel, Ameera X.; Burdakov, Denis

2015-01-01

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems. PMID:25816008

Electric potentiation of gravikinesis in Paramecium is possibly mediated by filaments.

PubMed

Machemer, H

1998-01-01

Sensitivity of Paramecium to mechanical stress including gravitational force is organized along two opposing gradients of membrane channel distribution: depolarizing Ca channels and hyperpolarizing K channels. Mechanoreceptor channels reside in the membrane of the cell soma and are activated, when the weight of the cytoplasm deforms the "lower" plasma membrane. Channel distribution is such as to generate ciliary activation which can counteract sedimentation of the cells: a reduction in downward swimming rate and an augmentation in upward swimming rate. Application of weak DC fields does not only induce the well-known cathodal orientation and swimming of Paramecium toward the cathode (galvano-taxis). We document that swimming velocity is augmented up to 175% as a function of the voltage gradient between 0.3 V/cm and 0.8 V/cm (galvanokinesis). A gradient of 0.3 V/cm was highly effective in raising the common negative gravikinesis of downward swimmers threefold. The gravikinesis of upward swimmers reversed polarity under field stimulation inducing cells to augment sedimentation effects (positive gravikinesis). Both effects of electric-field stimulation on ciliary activation are of the depolarizing type: reduction in the frequency of normally beating cilia. Analysis of the data shows that a voltage-sensitivity of gravireceptor channels would not account for the observed potentiation of negative gravikinesis. It is suggested that a previously described voltage-dependent Ca channel of the soma membrane interferes with a Ca(2+)-sensitive, peripheral filament system, which directly connects to gravireceptor channels.

18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

PubMed Central

Du, Yi-mei; Xia, Cheng-kun; Zhao, Ning; Dong, Qian; Lei, Ming; Xia, Jia-hong

2012-01-01

Aim: To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na+ current, HERG and Kv1.5 channel currents. Methods: Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant ΔKPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents. Results: Superfusion of 18β-glycyrrhetinic acid (18β-GA, 1–100 μmol/L) blocked both the peak current (INa,P) and late current (INa,L) generated by WT and ΔKPQ Nav1.5 channels in a concentration-dependent manner, while 18α-glycyrrhetinic acid (18α-GA) at the same concentrations had no effects. 18β-GA preferentially blocked INa,L (IC50=37.2±14.4 μmol/L) to INa,P (IC50=100.4±11.2 μmol/L) generated by ΔKPQ Nav1.5 channels. In human atrial myocytes, 18β-GA (30 μmol/L) inhibited 47% of INa,P and 87% of INa,L induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of 18β-GA (100 μmol/L) had no effects on HERG and Kv1.5 channel currents. Conclusion: 18β-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels. PMID:22609834

Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du Yuzhe; Nomura, Yoshiko; Luo Ningguang

2009-01-15

Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an {alpha}-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report themore » identification of a residue G{sup 1111} and two positively charged lysines immediately downstream of G{sup 1111} in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G{sup 1111}, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G{sup 1111} had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spathis, C., E-mail: cspathis@ece.upatras.gr; Birbas, A.; Georgakopoulou, K.

Device white noise levels in short channel Metal-Oxide-Semiconductor Field-Effect Transistors (MOSFETs) dictate the performance and reliability of high-frequency circuits ranging from high-speed microprocessors to Low-Noise Amplifiers (LNAs) and microwave circuits. Recent experimental noise measurements with very short devices demonstrate the existence of suppressed shot noise, contrary to the predictions of classical channel thermal noise models. In this work we show that, as the dimensions continue to shrink, shot noise has to be considered when the channel resistance becomes comparable to the barrier resistance at the source-channel junction. By adopting a semi-classical approach and taking retrospectively into account transport, short-channel andmore » quantum effects, we investigate the partitioning between shot and thermal noise, and formulate a predictive model that describes the noise characteristics of modern devices.« less

Effects of fade distribution on a mobile satellite downlink and uplink performance in a frequency reuse cellular configuration

NASA Technical Reports Server (NTRS)

Boutin, Karl; Lecours, Michel; Pelletier, Marcel; Delisle, Gilles Y.

1990-01-01

In a mobile satellite system with a frequency reuse cellular configuration, significant co-channel interference can be experienced due to the antenna sidelobe level. The signal will be subjected not only to its own fading, but also to the effect of the varying degree of fading on co-channel interferer, and this interference will behave differently in the up and in the down link. This paper presents a quantitative evaluation of the combined effects of fades and co-channel interference on a mobile satellite link.

[Effect of calcium channel blockers on developing nervous syndrome of high pressure and nitrogen narcosis in mice].

PubMed

Sledkov, A I

1997-01-01

In the experiments conducted on mice which prior to compression in a heliox environment have been injected the blockers of various types of calcium channels (flunarezine, verapramil and nifedipine) as well as bemethyl (actoprotector) and oxymethacye (antioxidant) there escaped detection of noticeable effect of these drugs on developing the high pressure nervous syndrome (HPNS). On exposure to the hyperbaric nitrogen-oxygen environment verapromil (phenylalkulamine blocker of L-type calcium channels) had a protection effect with respect to a convulsive component of the nitrogen narcosis.

Direct simulation Monte Carlo method for gas flows in micro-channels with bends with added curvature

NASA Astrophysics Data System (ADS)

Tisovský, Tomáš; Vít, Tomáš

Gas flows in micro-channels are simulated using an open source Direct Simulation Monte Carlo (DSMC) code dsmcFOAM for general application to rarefied gas flow written within the framework of the open source C++ toolbox called OpenFOAM. Aim of this paper is to investigate the flow in micro-channel with bend with added curvature. Results are compared with flows in channel without added curvature and equivalent straight channel. Effects of micro-channel bend was already thoroughly investigated by White et al. Geometry proposed by White is also used here for refference.

The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine.

PubMed

Al-Karagholi, Mohammad Al-Mahdi; Hansen, Jakob Møller; Severinsen, Johanne; Jansen-Olesen, Inger; Ashina, Messoud

2017-08-23

To review the distribution and function of K ATP channels, describe the use of K ATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. K ATP channels are widely present in the trigeminovascular system and play an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic K ATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that K ATP channel opening may cause headache, possibly due to vascular mechanisms. Whether K ATP channel openers can provoke migraine in migraine sufferers is not known. We suggest that K ATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target.

LE135, a retinoid acid receptor antagonist, produces pain through direct activation of TRP channels

PubMed Central

Yin, Shijin; Luo, Jialie; Qian, Aihua; Yu, Weihua; Hu, Hongzhen

2014-01-01

Background and PurposeRetinoids, through their activation of retinoic acid receptors (RARs) and retinoid X receptors, regulate diverse cellular processes, and pharmacological intervention in their actions has been successful in the treatment of skin disorders and cancers. Despite the many beneficial effects, administration of retinoids causes irritating side effects with unknown mechanisms. Here, we demonstrate that LE135 [4-(7,8,9,10-tetrahydro-5,7,7,10,10-pentamethyl-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid], a selective antagonist of RARβ, is a potent activator of the capsaicin (TRPV1) and wasabi (TRPA1) receptors, two critical pain-initiating cation channels. Experimental ApproachWe performed to investigate the excitatory effects of LE135 on TRPV1 and TRPA1 channels expressed in HEK293T cells and in dorsal root ganglia neurons with calcium imaging and patch-clamp recordings. We also used site-directed mutagenesis of the channels to determine the structural basis of LE135-induced activation of TRPV1 and TRPA1 channels and behavioural testing to examine if pharmacological inhibition and genetic deletion of the channels affected LE135-evoked pain-related behaviours. Key ResultsLE135 activated both the capsaicin receptor (TRPV1) and the allyl isothiocyanate receptor (TRPA1) heterologously expressed in HEK293T cells and endogenously expressed by sensory nociceptors. Mutations disrupting the capsaicin-binding site attenuated LE135 activation of TRPV1 channels and a single mutation (K170R) eliminated TRPA1 activity evoked by LE135. Intraplantar injection of LE135 evoked pain-related behaviours. Both TRPV1 and TRPA1 channels were involved in LE135-elicited pain-related responses, as shown by pharmacological and genetic ablation studies. Conclusions and ImplicationsThis blocker of retinoid acid signalling also exerted non-genomic effects through activating the pain-initiating TRPV1 and TRPA1 channels. PMID:24308840

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

PubMed Central

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

LE135, a retinoid acid receptor antagonist, produces pain through direct activation of TRP channels.

PubMed

Yin, Shijin; Luo, Jialie; Qian, Aihua; Yu, Weihua; Hu, Hongzhen

2014-03-01

Retinoids, through their activation of retinoic acid receptors (RARs) and retinoid X receptors, regulate diverse cellular processes, and pharmacological intervention in their actions has been successful in the treatment of skin disorders and cancers. Despite the many beneficial effects, administration of retinoids causes irritating side effects with unknown mechanisms. Here, we demonstrate that LE135 [4-(7,8,9,10-tetrahydro-5,7,7,10,10-pentamethyl-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid], a selective antagonist of RARβ , is a potent activator of the capsaicin (TRPV1) and wasabi (TRPA1) receptors, two critical pain-initiating cation channels. We performed to investigate the excitatory effects of LE135 on TRPV1 and TRPA1 channels expressed in HEK293T cells and in dorsal root ganglia neurons with calcium imaging and patch-clamp recordings. We also used site-directed mutagenesis of the channels to determine the structural basis of LE135-induced activation of TRPV1 and TRPA1 channels and behavioural testing to examine if pharmacological inhibition and genetic deletion of the channels affected LE135-evoked pain-related behaviours. LE135 activated both the capsaicin receptor (TRPV1) and the allyl isothiocyanate receptor (TRPA1) heterologously expressed in HEK293T cells and endogenously expressed by sensory nociceptors. Mutations disrupting the capsaicin-binding site attenuated LE135 activation of TRPV1 channels and a single mutation (K170R) eliminated TRPA1 activity evoked by LE135. Intraplantar injection of LE135 evoked pain-related behaviours. Both TRPV1 and TRPA1 channels were involved in LE135-elicited pain-related responses, as shown by pharmacological and genetic ablation studies. This blocker of retinoid acid signalling also exerted non-genomic effects through activating the pain-initiating TRPV1 and TRPA1 channels. © 2013 The British Pharmacological Society.

Flow resistance dynamics in step‐pool stream channels: 1. Large woody debris and controls on total resistance

USGS Publications Warehouse

Wilcox, Andrew C.; Wohl, Ellen E.

2006-01-01

Flow resistance dynamics in step‐pool channels were investigated through physical modeling using a laboratory flume. Variables contributing to flow resistance in step‐pool channels were manipulated in order to measure the effects of various large woody debris (LWD) configurations, steps, grains, discharge, and slope on total flow resistance. This entailed nearly 400 flume runs, organized into a series of factorial experiments. Factorial analyses of variance indicated significant two‐way and three‐way interaction effects between steps, grains, and LWD, illustrating the complexity of flow resistance in these channels. Interactions between steps and LWD resulted in substantially greater flow resistance for steps with LWD than for steps lacking LWD. LWD position contributed to these interactions, whereby LWD pieces located near the lip of steps, analogous to step‐forming debris in natural channels, increased the effective height of steps and created substantially higher flow resistance than pieces located farther upstream on step treads. Step geometry and LWD density and orientation also had highly significant effects on flow resistance. Flow resistance dynamics and the resistance effect of bed roughness configurations were strongly discharge‐dependent; discharge had both highly significant main effects on resistance and highly significant interactions with all other variables.

Laboratory Modelling of the Effect of Bend Orientation on the Morphological Development of Alluvial Channels

NASA Astrophysics Data System (ADS)

Good, R. G. R.; Sullivan, C.; Binns, A. D.

2017-12-01

Bend orientation, or skewness, in natural streams is often caused by riparian vegetation or underlying geology that lead to a meandering stream following a non-sinuous path. The bend orientation affects how the fluid momentum interacts with the bed and banks, which can alter the location and shape of bedforms as well as the channel planform geometry. An experimental study in a laboratory sand flume with movable bed and banks (5.6 m long, 1.9 m wide; D50 = 0.7 mm; B = 0.2m; 3 wavelengths) was carried out to quantify the effect of bend orientation on bedform development and planform changes. While previous research in the literature has found that channels with an upstream bend orientation had a less developed secondary flow than a downstream orientation, few studies on the morphological development of streams having varying bend orientation have been conducted. In total, three runs were carried out using channels with upstream, downstream, and no skewness. The runs progressed in a series of time-steps to monitor the morphological evolution of the streams with time. Sediment transport rates were quantified at the outlet, flow was measured using an ultrasonic flow meter at the inlet, flow depths were measured at the apex of the bends, and channel morphology was measured at each time step using Structure-from-Motion photogrammetry with Agisoft Photoscan. Bend orientation was found to influence the position of the point bar development as well as the locations of maximum and minimum channel migration. Relative to the bend apex, point bars tended to be positioned in the same direction as the channel skewness. Channel width showed the greatest variation with the upstream orientation, with the channel narrowing before the apex where the channel flows in the up-valley direction, and widening downstream of the apex. These results show that the channel orientation influences the morphological development of the channel bed and banks. The effect of velocity structure and turbulence regime on the morphological development in the three bend orientations was analysed by comparing morphological and flow data at each time step. Results from this research will benefit the design of future engineered channels, as certain channel orientations may be preferable for managing erosion and sediment transport within a watershed.

Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors

PubMed Central

Xu, Xiaojun; Sepich, Caraline; Lukas, Ronald J; Zhu, Guonian; Chang, Yongchang

2016-01-01

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor. PMID:27049309

The joint measurement entanglement can significantly offset the effect of a noisy channel in teleportation

NASA Astrophysics Data System (ADS)

Roa, Luis; Ladrón de Guevara, María L.; Soto-Moscoso, Matias; Catalán, Pamela

2018-05-01

In our work we consider the following problem in the context of teleportation: an unknown pure state has to be teleported and there are two laboratories which can perform the task. One laboratory uses a pure non-maximally entangled channel but has a capability of performing the joint measurement on bases with a constrained degree of entanglement; the other lab makes use of a mixed X-state channel but can perform a joint measurement on bases with higher entanglement degrees. We compare the average teleportation fidelity achieved in both cases, finding that the fidelity achieved with the X-state can surpass the obtained with a pure channel, even though the X-state is less entangled than the latter. We find the conditions under which this effect occurs. Our results evidence that the entanglement of the joint measurement plays a role as important as the entanglement of the channel in order to optimize the teleportation process. We include an example showing that the average fidelity of teleportation obtained with a Werner state channel can be greater than that obtained with a Bell state channel.

Performance of convolutional codes on fading channels typical of planetary entry missions

NASA Technical Reports Server (NTRS)

Modestino, J. W.; Mui, S. Y.; Reale, T. J.

1974-01-01

The performance of convolutional codes in fading channels typical of the planetary entry channel is examined in detail. The signal fading is due primarily to turbulent atmospheric scattering of the RF signal transmitted from an entry probe through a planetary atmosphere. Short constraint length convolutional codes are considered in conjunction with binary phase-shift keyed modulation and Viterbi maximum likelihood decoding, and for longer constraint length codes sequential decoding utilizing both the Fano and Zigangirov-Jelinek (ZJ) algorithms are considered. Careful consideration is given to the modeling of the channel in terms of a few meaningful parameters which can be correlated closely with theoretical propagation studies. For short constraint length codes the bit error probability performance was investigated as a function of E sub b/N sub o parameterized by the fading channel parameters. For longer constraint length codes the effect was examined of the fading channel parameters on the computational requirements of both the Fano and ZJ algorithms. The effects of simple block interleaving in combatting the memory of the channel is explored, using the analytic approach or digital computer simulation.

Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors.

PubMed

Xu, Xiaojun; Sepich, Caraline; Lukas, Ronald J; Zhu, Guonian; Chang, Yongchang

2016-05-13

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of the magnetic field gradient on the wall power deposition of Hall thrusters

NASA Astrophysics Data System (ADS)

Ding, Yongjie; Li, Peng; Zhang, Xu; Wei, Liqiu; Sun, Hezhi; Peng, Wuji; Yu, Daren

2017-04-01

The effect of the magnetic field gradient in the discharge channel of a Hall thruster on the ionization of the neutral gas and power deposition on the wall is studied through adopting the 2D-3V particle-in-cell (PIC) and Monte Carlo collisions (MCC) model. The research shows that by gradually increasing the magnetic field gradient while keeping the maximum magnetic intensity at the channel exit and the anode position unchanged, the ionization region moves towards the channel exit and then a second ionization region appears near the anode region. Meanwhile, power deposition on the walls decreases initially and then increases. To avoid power deposition on the walls produced by electrons and ions which are ionized in the second ionization region, the anode position is moved towards the channel exit as the magnetic field gradient is increased; when the anode position remains at the zero magnetic field position, power deposition on the walls decreases, which can effectively reduce the temperature and thermal load of the discharge channel.

Channel scaling and field-effect mobility extraction in amorphous InZnO thin film transistors

NASA Astrophysics Data System (ADS)

Lee, Sunghwan; Song, Yang; Park, Hongsik; Zaslavsky, A.; Paine, D. C.

2017-09-01

Amorphous oxide semiconductors (AOSs) based on indium oxides are of great interest for next generation ultra-high definition displays that require much smaller pixel driving elements. We describe the scaling behavior in amorphous InZnO thin film transistors (TFTs) with a significant decrease in the extracted field-effect mobility μFE with channel length L (from 39.3 to 9.9 cm2/V·s as L is reduced from 50 to 5 μm). Transmission line model measurements reveal that channel scaling leads to a significant μFE underestimation due to contact resistance (RC) at the metallization/channel interface. Therefore, we suggest a method of extracting correct μFE when the TFT performance is significantly affected by RC. The corrected μFE values are higher (45.4 cm2/V·s) and nearly independent of L. The results show the critical effect of contact resistance on μFE measurements and suggest strategies to determine accurate μFE when a TFT channel is scaled.

Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels.

PubMed

Thörn Pérez, Carolina; Hill, Russell H; Grillner, Sten

2015-01-01

Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion.

Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels

PubMed Central

Thörn Pérez, Carolina; Hill, Russell H.; Grillner, Sten

2015-01-01

Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion. PMID:26197458

2D modeling based comprehensive analysis of short channel effects in DMG strained VSTB FET

NASA Astrophysics Data System (ADS)

Saha, Priyanka; Banerjee, Pritha; Sarkar, Subir Kumar

2018-06-01

The paper aims to develop two dimensional analytical model of the proposed dual material (DM) Vertical Super Thin Body (VSTB) strained Field Effect Transistor (FET) with focus on its short channel behaviour in nanometer regime. Electrostatic potential across gate/channel and dielectric wall/channel interface is derived by solving 2D Poisson's equation with parabolic approximation method by applying appropriate boundary conditions. Threshold voltage is then calculated by using the criteria of minimum surface potential considering both gate and dielectric wall side potential. Performance analysis of the present structure is demonstrated in terms of potential, electric field, threshold voltage characteristics and subthreshold behaviour by varying various device parameters and applied biases. Effect of application of strain in channel is further explored to establish the superiority of the proposed device in comparison to conventional VSTB FET counterpart. All analytical results are compared with Silvaco ATLAS device simulated data to substantiate the accuracy of our derived model.

Effects of Volatile Aromatic Anesthetics on Voltage-Gated Na+ Channels Expressed in Xenopus Oocytes

PubMed Central

Horishita, Takafumi; Eger, Edmond I; Harris, R. Adron

2008-01-01

Background Many inhaled anesthetics inhibit voltage-gated sodium channels at clinically relevant concentrations, and suppression of neurotransmitter release by these agents results, at least partly, from decreased presynaptic sodium channel activity. Volatile aromatic anesthetics can inhibit N-methyl-D-aspartate (NMDA) receptor function and enhance γ-amino butyric acid A (GABAA) receptor function, but these effects depend strongly on the chemical properties of the aromatic ompounds. The present study tested whether diverse aromatic anesthetics consistently inhibit sodium channel function. Methods We studied the effect of eight aromatic anesthetics on Nav1.2 sodium channels with β1 subunits, using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Results All aromatic anesthetics inhibited INa (sodium currents) at a holding potential which produce half-maximal current (V1/2) (partial depolarization); inhibition was modest with 1,3,5-trifluorobenzene (8 ± 2%), pentafluorobenzene (13 ± 2%), and hexafluorobenzene (13 ± 2%), but greater with benzene (37 ± 2%), fluorobenzene (39 ± 2%), 1,2-difluorobenzene (48 ± 2%), 1,4-difluorobenzene (31 ± 3%), and 1,2,4-trifluorobenzene (33 ± 1%). Such dichotomous effects were noted by others for NMDA and GABAA receptors. Parallel, but much smaller inhibition, was found for INa at a holding potential which produced near maximal current (−90 mV) (VH-90), and hexafluorobenzene caused small (6 ± 1%) potentiation of this current. These changes in sodium channel function were correlated with effectiveness for inhibiting NMDA receptors, with lipid solubility of the compounds, with molecular volume, and with cation-π interactions. Conclusion Aromatic compounds vary in their actions on the kinetics of sodium channel gating and this may underlie their variable inhibition. The range of inhibition produced by MAC concentrations of inhaled anesthetics indicates that sodium channel inhibition may underlie the action of some of these anesthetics but not others. PMID:18931215

Far-Field Plume Measurements of a Nested-Channel Hall-Effect Thruster (PREPRINT)

DTIC Science & Technology

2010-12-13

nude Faraday probe, retarding potential analyzer, and ExB probe. Data from these probes were used to calculate utilization efficiencies from existing...USA Far-field plume measurements were performed on the X2 nested-channel Hall-effect thruster using an ar- ray of diagnostics, including a nude Faraday...mode to nested-channel mode by utilizing a traditional array of far-field diagnostics, which include a nude Faraday probe, retarding potential analyzer

Specifics of heat and mass transfer in spherical dimples under the effect of external factors

NASA Astrophysics Data System (ADS)

Shchukin, A. V.; Il'inkov, A. V.; Takmovtsev, V. V.; Khabibullin, I. I.

2017-06-01

The specifics are examined of heat transfer enhancement with spherical dimples under the effect of factors important for practice and characteristic of cooling systems of gas-turbine engines and power units. This experimental investigation deals with the effect of the following factors on the flow in a channel with hemispherical dimples: continuous air swirl in an annulus with dimples on its concave wall, dimples on the convex or concave wall of a curved rectangular channel, imposition of regular velocity fluctuations on the external flow in a straight rectangular channel, and adverse or favorable pressure gradient along the flow direction. The flow is turbulent. Reynolds numbers based on the channel hydraulic diameter are on the order of 104. Results of the investigation of a model of a two-cavity diffuser dimple proposed by the authors are presented. It has been found that results for channels with spherical dimples and for smooth channels differ not only quantitatively but also qualitatively. Thus, if the effect of centrifugal mass forces on convex and concave surfaces with hemispherical dimples and in a smooth channel is almost the same (quantitative and qualitative indicators are identical), the pressure gradient in the flow direction brings about the drastically opposite results. At the same time, the quantitative contribution to a change in heat transfer in hemispherical dimples is different and depends on the impact type. The results are discussed with the use of physical models created on the basis of the results of flow visualization studies and data on the turbulence intensity, pressure coefficient, etc. Results of the investigations suggest that application of spherical dimples under nonstandard conditions requires the calculated heat transfer to be corrected to account for one or another effect.

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

PubMed Central

Kobayashi, Toru; Washiyama, Kazuo; Ikeda, Kazutaka

2010-01-01

Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attention-deficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K+ (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentration-dependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A1 adenosine receptors or by intracellularly applied GTPγS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain- and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function. PMID:20393461

New Flexible Channels for Room Temperature Tunneling Field Effect Transistors.

PubMed

Hao, Boyi; Asthana, Anjana; Hazaveh, Paniz Khanmohammadi; Bergstrom, Paul L; Banyai, Douglas; Savaikar, Madhusudan A; Jaszczak, John A; Yap, Yoke Khin

2016-02-05

Tunneling field effect transistors (TFETs) have been proposed to overcome the fundamental issues of Si based transistors, such as short channel effect, finite leakage current, and high contact resistance. Unfortunately, most if not all TFETs are operational only at cryogenic temperatures. Here we report that iron (Fe) quantum dots functionalized boron nitride nanotubes (QDs-BNNTs) can be used as the flexible tunneling channels of TFETs at room temperatures. The electrical insulating BNNTs are used as the one-dimensional (1D) substrates to confine the uniform formation of Fe QDs on their surface as the flexible tunneling channel. Consistent semiconductor-like transport behaviors under various bending conditions are detected by scanning tunneling spectroscopy in a transmission electron microscopy system (in-situ STM-TEM). As suggested by computer simulation, the uniform distribution of Fe QDs enable an averaging effect on the possible electron tunneling pathways, which is responsible for the consistent transport properties that are not sensitive to bending.

The Promise of Microelectrode Array Approaches for Toxicity Testing: Examples with Neuroactive Chemicals

EPA Science Inventory

While high-throughput patch clamping formats provide rapid characterization of chemical effects on ion channel function and kinetics, the limitations of such systems often include the need for channel by channel characterization, requirements for transfected, rather than primary ...

Generation of efficient 33 GHz optical combs using cascaded stimulated Brillouin scattering effects in optical fiber

NASA Astrophysics Data System (ADS)

Al-Mansoori, M. H.; Al-Sheriyani, A.; Al-Nassri, S.; Hasoon, F. N.

2017-06-01

In this paper, we demonstrate a multi-wavelength Brillouin-erbium fiber laser (BEFL) with ~33 GHz frequency spacing using cascaded stimulated Brillouin scattering effects in optical fiber. The proposed laser structure exhibits a stable output channel with a tuning range of 19 nm, from 1549 nm to 1568 nm. The number of stable output channels produced is six channels with a triple-Brillouin frequency spacing. The output channels exhibit high output power and high optical signal-to-noise ratios (OSNRs). The laser structure has the potential to be used as a multi-wavelength source for optical communication systems.

Numerical investigation of interfacial transport resistance due to water droplets in proton exchange membrane fuel cell air channels

NASA Astrophysics Data System (ADS)

Koz, Mustafa; Kandlikar, Satish G.

2013-12-01

Oxygen transport resistance at the air flow channel and gas diffusion layer (GDL) interface is needed in modelling the performance of a proton exchange membrane fuel cell (PEMFC). This resistance is expressed through the non-dimensional Sherwood number (Sh). The effect of the presence of a droplet on Sh is studied numerically in an isolated air flow channel using a commercially available package, COMSOL Multiphysics®. A droplet is represented as a solid obstruction placed on the GDL-channel interface and centred along the channel width. The effect of a single droplet is first studied for a range of superficial mean air velocities and droplet sizes. Secondly, the effect of droplet spacing on Sh is studied through simulations of two consecutive droplets. Lastly, multiple droplets in a row are studied as a more representative case of a PEMFC air flow channel. The results show that the droplets significantly increase Sh above the fully developed value in the wake region. This enhancement increases with the number of droplets, droplet size, and superficial mean air velocity. Moreover, the analogy between mass and heat transfer is investigated by comparing Sh to the equivalent Nusselt number.

Ultrashort channel silicon nanowire transistors with nickel silicide source/drain contacts.

PubMed

Tang, Wei; Dayeh, Shadi A; Picraux, S Tom; Huang, Jian Yu; Tu, King-Ning

2012-08-08

We demonstrate the shortest transistor channel length (17 nm) fabricated on a vapor-liquid-solid (VLS) grown silicon nanowire (NW) by a controlled reaction with Ni leads on an in situ transmission electron microscope (TEM) heating stage at a moderate temperature of 400 °C. NiSi(2) is the leading phase, and the silicide-silicon interface is an atomically sharp type-A interface. At such channel lengths, high maximum on-currents of 890 (μA/μm) and a maximum transconductance of 430 (μS/μm) were obtained, which pushes forward the performance of bottom-up Si NW Schottky barrier field-effect transistors (SB-FETs). Through accurate control over the silicidation reaction, we provide a systematic study of channel length dependent carrier transport in a large number of SB-FETs with channel lengths in the range of 17 nm to 3.6 μm. Our device results corroborate with our transport simulations and reveal a characteristic type of short channel effects in SB-FETs, both in on- and off-state, which is different from that in conventional MOSFETs, and that limits transport parameter extraction from SB-FETs using conventional field-effect transconductance measurements.

Current-voltage characteristics influenced by the nanochannel diameter and surface charge density in a fluidic field-effect-transistor.

PubMed

Singh, Kunwar Pal; Guo, Chunlei

2017-06-21

The nanochannel diameter and surface charge density have a significant impact on current-voltage characteristics in a nanofluidic transistor. We have simulated the effect of the channel diameter and surface charge density on current-voltage characteristics of a fluidic nanochannel with positive surface charge on its walls and a gate electrode on its surface. Anion depletion/enrichment leads to a decrease/increase in ion current with gate potential. The ion current tends to increase linearly with gate potential for narrow channels at high surface charge densities and narrow channels are more effective to control the ion current at high surface charge densities. The current-voltage characteristics are highly nonlinear for wide channels at low surface charge densities and they show different regions of current change with gate potential. The ion current decreases with gate potential after attaining a peak value for wide channels at low values of surface charge densities. At low surface charge densities, the ion current can be controlled by a narrow range of gate potentials for wide channels. The current change with source drain voltage shows ohmic, limiting and overlimiting regions.

Variability and reliability analysis in self-assembled multichannel carbon nanotube field-effect transistors

NASA Astrophysics Data System (ADS)

Hu, Zhaoying; Tulevski, George S.; Hannon, James B.; Afzali, Ali; Liehr, Michael; Park, Hongsik

2015-06-01

Carbon nanotubes (CNTs) have been widely studied as a channel material of scaled transistors for high-speed and low-power logic applications. In order to have sufficient drive current, it is widely assumed that CNT-based logic devices will have multiple CNTs in each channel. Understanding the effects of the number of CNTs on device performance can aid in the design of CNT field-effect transistors (CNTFETs). We have fabricated multi-CNT-channel CNTFETs with an 80-nm channel length using precise self-assembly methods. We describe compact statistical models and Monte Carlo simulations to analyze failure probability and the variability of the on-state current and threshold voltage. The results show that multichannel CNTFETs are more resilient to process variation and random environmental fluctuations than single-CNT devices.

GIDL analysis of the process variation effect in gate-all-around nanowire FET

NASA Astrophysics Data System (ADS)

Kim, Shinkeun; Seo, Youngsoo; Lee, Jangkyu; Kang, Myounggon; Shin, Hyungcheol

2018-02-01

In this paper, the gate-induced drain leakage (GIDL) is analyzed on gate-all-around (GAA) Nanowire FET (NW FET) with ellipse-shaped channel induced by process variation effect (PVE). The fabrication process of nanowire can lead to change the shape of channel cross section from circle to ellipse. The effect of distorted channel shape is investigated and verified by technology computer-aided design (TCAD) simulation in terms of the GIDL current. The simulation results demonstrate that the components of GIDL current are two mechanisms of longitudinal band-to-band tunneling (L-BTBT) at body/drain junction and transverse band-to-band tunneling (T-BTBT) at gate/drain junction. These two mechanisms are investigated on channel radius (rnw) and aspect ratio of ellipse-shape respectively and together.

Polarization induced doped transistor

DOEpatents

Xing, Huili; Jena, Debdeep; Nomoto, Kazuki; Song, Bo; Zhu, Mingda; Hu, Zongyang

2016-06-07

A nitride-based field effect transistor (FET) comprises a compositionally graded and polarization induced doped p-layer underlying at least one gate contact and a compositionally graded and doped n-channel underlying a source contact. The n-channel is converted from the p-layer to the n-channel by ion implantation, a buffer underlies the doped p-layer and the n-channel, and a drain underlies the buffer.

Impact of the F508del mutation on ovine CFTR, a Cl− channel with enhanced conductance and ATP-dependent gating

PubMed Central

Cai, Zhiwei; Palmai-Pallag, Timea; Khuituan, Pissared; Mutolo, Michael J; Boinot, Clément; Liu, Beihui; Scott-Ward, Toby S; Callebaut, Isabelle; Harris, Ann; Sheppard, David N

2015-01-01

Cross-species comparative studies are a powerful approach to understanding the epithelial Cl− channel cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in the genetic disease cystic fibrosis (CF). Here, we investigate the single-channel behaviour of ovine CFTR and the impact of the most common CF mutation, F508del-CFTR, using excised inside-out membrane patches from transiently transfected CHO cells. Like human CFTR, ovine CFTR formed a weakly inwardly rectifying Cl− channel regulated by PKA-dependent phosphorylation, inhibited by the open-channel blocker glibenclamide. However, for three reasons, ovine CFTR was noticeably more active than human CFTR. First, single-channel conductance was increased. Second, open probability was augmented because the frequency and duration of channel openings were increased. Third, with enhanced affinity and efficacy, ATP more strongly stimulated ovine CFTR channel gating. Consistent with these data, the CFTR modulator phloxine B failed to potentiate ovine CFTR Cl− currents. Similar to its impact on human CFTR, the F508del mutation caused a temperature-sensitive folding defect, which disrupted ovine CFTR protein processing and reduced membrane stability. However, the F508del mutation had reduced impact on ovine CFTR channel gating in contrast to its marked effects on human CFTR. We conclude that ovine CFTR forms a regulated Cl− channel with enhanced conductance and ATP-dependent channel gating. This phylogenetic analysis of CFTR structure and function demonstrates that subtle changes in structure have pronounced effects on channel function and the consequences of the CF mutation F508del. Key points Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), a gated pathway for chloride movement, causes the common life-shortening genetic disease cystic fibrosis (CF). Towards the development of a sheep model of CF, we have investigated the function of sheep CFTR. We found that sheep CFTR was noticeably more active than human CFTR, while the most common CF mutation, F508del, had reduced impact on sheep CFTR function. Our results demonstrate that subtle changes in protein structure have marked effects on CFTR function and the consequences of the CF mutation F508del. PMID:25763566

Ryanodine receptors regulate arterial diameter and wall [Ca2+] in cerebral arteries of rat via Ca2+-dependent K+ channels

PubMed Central

Knot, Harm J; Standen, Nicholas B; Nelson, Mark T

1998-01-01

The effects of inhibitors of ryanodine-sensitive calcium release (RyR) channels in the sarcoplasmic reticulum (SR) and Ca2+-dependent potassium (KCa) channels on the membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg) cerebral arteries (100–200 μm) were studied using digital fluorescence video imaging of arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial membrane potential. Ryanodine (10 μm), an inhibitor of RyR channels, depolarized by 9 mV, increased intracellular [Ca2+] by 46 nm and constricted pressurized (to 60 mmHg) arteries with myogenic tone by 44 μm (∼22 %). Iberiotoxin (100 nm), a blocker of KCa channels, under the same conditions, depolarized the arteries by 10 mV, increased arterial wall calcium by 51 nm, and constricted by 37 μm (∼19 %). The effects of ryanodine and iberiotoxin were not additive and were blocked by inhibitors of voltage-dependent Ca2+ channels. Caffeine (10 mm), an activator of RyR channels, transiently increased arterial wall [Ca2+] by 136 ± 9 nm in control arteries and by 158 ± 12 nm in the presence of iberiotoxin. Caffeine was relatively ineffective in the presence of ryanodine, increasing [calcium] by 18 ± 5 nm. In the presence of blockers of voltage-dependent Ca2+ channels (nimodipine, diltiazem), ryanodine and inhibitors of the SR calcium ATPase (thapsigargin, cyclopiazonic acid) were without effect on arterial wall [Ca2+] and diameter. These results suggest that local Ca2+ release originating from RyR channels (Ca2+ sparks) in the SR of arterial smooth muscle regulates myogenic tone in cerebral arteries solely through activation of KCa channels, which regulate membrane potential through tonic hyperpolarization, thus limiting Ca2+ entry through L-type voltage-dependent Ca2+ channels. KCa channels therefore act as a negative feedback control element regulating arterial diameter through a reduction in global intracellular free [Ca2+]. PMID:9490841

Applications of Classical and Quantum Mechanical Channeling in Condensed Matter Physics

NASA Astrophysics Data System (ADS)

Haakenaasen, Randi

1995-01-01

The first part of this work involves ion channeling measurements on the high temperature superconductor rm YBa_{2}Cu_{3}O _{7-delta}(YBCO). The experiments were motivated by several previous reports of anomalous behavior in the displacements of the Cu and O atoms in the vicinity of the critical temperature rm(T _{c}) in several high temperature superconductors. Our measurements were complimentary to previous experiments in that we used thin film YBCO (as opposed to bulk single crystals) and focused on a small region around rm T_{c}. We mapped out the channeling parameters chi _{min} and Psi_ {1/2} in a 30 K region around rm T_{c} in 1-2 K steps in thin film YBCO(001) on MgO. Neither of our measurements showed any discontinuities in chi _{min} or Psi_ {1/2} near the superconducting phase transition, and we therefore have no reason to expect anything but a smooth increase in atomic vibrations in this region. We conclude that any anomalous behavior in atomic displacements deduced from previous channeling experiments is not essential to superconductivity. In the second part of the work positrons were used to study quantum mechanical channeling effects. We clearly observed and quantitatively accounted for quantum interference effects, including Bragg diffraction, in the forward transmission of channeled MeV positrons through a single crystal. Experimental scans across the (100), (110), and (111) planes in Si showed excellent agreement with theoretical dynamical diffraction calculations, giving us confidence that we can accurately predict the spatial and momentum distributions of channeled positrons. New experiments are envisioned in which the channeling effect is combined with 2 quantum annihilation in flight measurements to determine valence electron and magnetic spin distributions in a crystal. Since the channeling effect focuses the positrons to the interstices of the crystal, the annihilation rate will reflect the valence electron density. Furthermore, the annihilation rate is sensitive to electron spin polarization, opening up the possibility of making measurements on magnetic materials. Detailed estimates for the count rates of such experiments are presented, indicating the feasibility of developing positron channeling into a new tool in solid state physics.

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility

PubMed Central

Provence, Aaron; Malysz, John

2015-01-01

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1–KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca2+ imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K+ (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca2+ concentration in DSM cells, an effect blocked by the L-type Ca2+ channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. PMID:26087697

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility.

PubMed

Provence, Aaron; Malysz, John; Petkov, Georgi V

2015-09-01

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1-KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca(2+) imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K(+) (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca(2+) concentration in DSM cells, an effect blocked by the L-type Ca(2+) channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans.

PubMed

MacDonald, Patrick E; De Marinis, Yang Zhang; Ramracheya, Reshma; Salehi, Albert; Ma, Xiaosong; Johnson, Paul R V; Cox, Roger; Eliasson, Lena; Rorsman, Patrik

2007-06-01

Glucagon, secreted from pancreatic islet alpha cells, stimulates gluconeogenesis and liver glycogen breakdown. The mechanism regulating glucagon release is debated, and variously attributed to neuronal control, paracrine control by neighbouring beta cells, or to an intrinsic glucose sensing by the alpha cells themselves. We examined hormone secretion and Ca(2+) responses of alpha and beta cells within intact rodent and human islets. Glucose-dependent suppression of glucagon release persisted when paracrine GABA or Zn(2+) signalling was blocked, but was reversed by low concentrations (1-20 muM) of the ATP-sensitive K(+) (KATP) channel opener diazoxide, which had no effect on insulin release or beta cell responses. This effect was prevented by the KATP channel blocker tolbutamide (100 muM). Higher diazoxide concentrations (>/=30 muM) decreased glucagon and insulin secretion, and alpha- and beta-cell Ca(2+) responses, in parallel. In the absence of glucose, tolbutamide at low concentrations (<1 muM) stimulated glucagon secretion, whereas high concentrations (>10 muM) were inhibitory. In the presence of a maximally inhibitory concentration of tolbutamide (0.5 mM), glucose had no additional suppressive effect. Downstream of the KATP channel, inhibition of voltage-gated Na(+) (TTX) and N-type Ca(2+) channels (omega-conotoxin), but not L-type Ca(2+) channels (nifedipine), prevented glucagon secretion. Both the N-type Ca(2+) channels and alpha-cell exocytosis were inactivated at depolarised membrane potentials. Rodent and human glucagon secretion is regulated by an alpha-cell KATP channel-dependent mechanism. We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion.

Geomorphic effects of rural-to-urban land use conversion on three streams in the Central Redbed Plains of Oklahoma

NASA Astrophysics Data System (ADS)

Kang, Ranbir S.; Marston, Richard A.

2006-09-01

This research evaluates the impact of rural-to-urban land use conversion on channel morphology and riparian vegetation for three streams in the Central Redbed Plains geomorphic province (central Great Plains ecoregion) of Oklahoma. The Deep Fork Creek watershed is largely urbanized; the Skeleton Creek watershed is largely rural; and the Stillwater Creek watershed is experiencing a rapid transition from rural to urban land cover. Each channel was divided into reaches based on tributary junctions, sinuosity, and slope. Field surveys were conducted at transects in a total of 90 reaches, including measurements of channel units, channel cross-section at bankfull stage, and riparian vegetation. Historical aerial photographs were available for only Stillwater Creek watershed, which were used to document land cover in this watershed, especially changes in the extent of urban areas (impervious cover). The three streams have very low gradients (< 0.001), width-to-depth ratios < 10, and cohesive channel banks, but have incised into red Permian shales and sandstone. The riparian vegetation is dominated by cottonwoods, ash, and elm trees that provide a dense root mat on stream banks where the riparian vegetation is intact. Channels increased in width and depth in the downstream direction as is normally expected, but the substrate materials and channel units remained unchanged. Statistical analyses demonstrated that urbanization did not explain spatial patterns of changes in any variables. These three channels in the central Redbed Plains are responding as flumes during peak flows, funneling runoff and the wash-load sediment downstream in major runoff events without any effect on channel dimensions. Therefore, local geological conditions (similar bedrock, cohesive substrates and similar riparian vegetation) are mitigating the effects of urbanization.

Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons.

PubMed

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

2017-03-01

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

Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes.

PubMed

Liin, S I; Karlsson, U; Bentzen, B H; Schmitt, N; Elinder, F

2016-09-01

Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurones. Effects of fatty acids and fatty acid analogues on mouse dorsal root ganglion neurones and on the human KV 7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology. Extracellular application of physiologically relevant concentrations of the polyunsaturated fatty acid docosahexaenoic acid hyperpolarized the resting membrane potential (-2.4 mV by 30 μm) and increased the threshold current to evoke action potentials in dorsal root ganglion neurones. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes, by shifting the conductance-vs.-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μm). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel. These findings suggest that circulating polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty acids reduce neuronal excitability. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Restoration and recovery of hurricane-damaged mangroves using the knickpoint retreat effect and tides as dredging tools.

PubMed

Bashan, Yoav; Moreno, Manuel; Salazar, Bernardo G; Alvarez, Leonardo

2013-02-15

In 2001, a hurricane moved a large sand dune, blocking the sole outlet channel of a mangrove. In the absence of daily tidal flow, the two ponds containing the mangrove vegetation evaporated, the secondary drainage channels were lost, and a salt crust formed on the bed of the ponds. The mangrove lost most of its trees and the remaining suffered from osmotic shock that led to defoliation. Restoration involved creating a knickpoint retreat (waterfall retreat effect) and tidal flow as a dredging mechanism to restore the outlet and form secondary channels in the ponds. During a very low tide, we deepened the mouth of the outlet channel by 1 m below high tide level to form a small waterfall when high tides receded. During successive tides, this one-step knickpoint deteriorated and formed a series of low rapids. With a steep gradient, the rapids retreated upstream into the ponds, first reopening the outlet channel and then carving new secondary channels in the pond mud flat. The excavation process of the outlet channel was repeated three times and was sufficient to effectively improve the hydrology of the entire pond system; allowing adequate flooding and draining of the mangrove ponds. Hydrology analysis tested by the Engelund-Hansen sediment transport formula established that the output of sediment from the ecosystem is greater than the input of sand into the mangroves. This is keeping the main channel continuously open. After eight years, tidal flow continues to keep the channels open; the salt crust has disappeared; the trees have recovered, and a large area of new vegetation has emerged. Copyright © 2012 Elsevier Ltd. All rights reserved.

Levcromakalim- and isoprenaline-induced relaxation of human isolated airways--role of the epithelium and of K+ channel activation.

PubMed

Black, J L; Johnson, P R; McKay, K O; Carey, D; Armour, C L

1994-06-01

In this study we have investigated the mechanism of action of levcromakalim and isoprenaline in human isolated airways with respect to the K+ channels they activate and the possibility that these smooth muscle relaxants activate K+ channels on the airway epithelium. Mechanical removal of the epithelial layer (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect the relaxation responses to levcromakalim or isoprenaline, either in terms of maximal relaxation or sensitivity. Whilst having no effect on isoprenaline-induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline) to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively. Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa channels in outside-out patches of hippocampal granule cells. Moreover, tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim-induced relaxation. This study has demonstrated that the relaxation responses elicited in human bronchus to isoprenaline and levcromakalim are likely to be the result of direct effects on the smooth muscle with no contribution from epithelial receptors or K+ channels. The actions of levcromakalim appear to be mediated only via activation of KATP channels. Further, we have made the important observation that, under the experimental conditions of our study, isoprenaline does not activate the KCa channel to produce relaxation in human bronchus.

DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the β1-subunit

PubMed Central

Scornik, Fabiana S.; Bucciero, Ronald S.; Wu, Yuesheng; Selga, Elisabet; Bosch Calero, Cristina; Brugada, Ramon

2013-01-01

The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca2+-activated K+ (BK) channel activator with selectivity for its β1- or β4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming α-subunit and a smooth muscle-abundant regulatory β1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the β1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies mostly on its α-subunit. We studied BK channels from wild-type and transgenic β1-knockout mice in excised patches. BK channels from brain arteries, with or without the β1-subunit, were similarly activated by DiBAC4(3). In addition, we found that saturating concentrations of DiBAC4(3) (∼30 μM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as −300 mV. This “sweet spot” for persistent activation is independent of Ca2+ and/or the β1–4-subunits and is fully achieved when DiBAC4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. PMID:23542916

Local anesthetic inhibition of a bacterial sodium channel

PubMed Central

Lee, Sora; Goodchild, Samuel J.

2012-01-01

Recent structural breakthroughs with the voltage-gated sodium channel from Arcobacter butzleri suggest that such bacterial channels may provide a structural platform to advance the understanding of eukaryotic sodium channel gating and pharmacology. We therefore set out to determine whether compounds known to interact with eukaryotic NaVs could also inhibit the bacterial channel from Bacillus halodurans and NaChBac and whether they did so through similar mechanisms as in their eukaryotic homologues. The data show that the archetypal local anesthetic (LA) lidocaine inhibits resting NaChBac channels with a dissociation constant (Kd) of 260 µM, and channels displayed a left-shifted steady-state inactivation gating relationship in the presence of the drug. Extracellular application of QX-314 to expressed NaChBac channels had no effect on sodium current, whereas internal exposure via injection of a bolus of the quaternary derivative rapidly reduced sodium conductance, consistent with a hydrophilic cytoplasmic access pathway to an internal binding site. However, the neutral derivative benzocaine applied externally inhibited NaChBac channels, suggesting that hydrophobic pathways can also provide drug access to inhibit channels. Alternatively, ranolazine, a putative preopen state blocker of eukaryotic NaVs, displayed a Kd of 60 µM and left-shifted the NaChBac activation-voltage relationship. In each case, block enhanced entry into the inactivated state of the channel, an effect that is well described by a simple kinetic scheme. The data suggest that although significant differences exist, LA block of eukaryotic NaVs also occurs in bacterial sodium channels and that NaChBac shares pharmacological homology to the resting state of vertebrate NaV homologues. PMID:22641643

Effects of KCNQ channel modulators on the M-type potassium current in primate retinal pigment epithelium.

PubMed

Pattnaik, Bikash R; Hughes, Bret A

2012-03-01

Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in monkey retinal pigment epithelium (RPE) and showed that the M-type current in RPE cells is blocked by the specific KCNQ channel blocker XE991. Using patch-clamp electrophysiology, we investigated the pharmacological sensitivity of the M-type current in isolated monkey RPE cells to elucidate the subunit composition of the channel. Most RPE cells exhibited an M-type current with a voltage for half-maximal activation of approximately -35 mV. The M-type current activation followed a double-exponential time course and was essentially complete within 1 s. The M-type current was inhibited by micromolar concentrations of the nonselective KCNQ channel blockers linopirdine and XE991 but was relatively insensitive to block by 10 μM chromanol 293B or 135 mM tetraethylammonium (TEA), two KCNQ1 channel blockers. The M-type current was activated by 1) 10 μM retigabine, an opener of all KCNQ channels except KCNQ1, 2) 10 μM zinc pyrithione, which augments all KCNQ channels except KCNQ3, and 3) 50 μM N-ethylmaleimide, which activates KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3, channels. Application of cAMP, which activates KCNQ1 and KCNQ4 channels, had no significant effect on the M-type current. Finally, diclofenac, which activates KCNQ2/3 and KCNQ4 channels but inhibits KCNQ5 channels, inhibited the M-type current in the majority of RPE cells but activated it in others. The results indicate that the M-type current in monkey RPE is likely mediated by channels encoded by KCNQ4 and KCNQ5 subunits.

First results from different investigations on MHD flow in multichannel U-Bends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reimann, J.; Barleon, L.; Molokov, S.

1995-04-01

In electrically coupled multichannel ducts with a U-bend geometry, MHD effects can result in strongly non-uniform distributions of flow rates Q{sub i} and pressure drops {Delta}p{sub i} in the individual channels. A multichannel U-bend geometry is part of the KfK self-cooled Pb-17Li blanket design for a fusion reactor (radial-toroidal-radial channels). However, inserts are proposed which decouple electrically the radial channels. The multi-channel effects (MCDs) were investigated by (i) Screening test with InGaSn at LAS, Riga, and (ii) more detailed experiments with NaK at KfK, Karlsruhe. Different flow channel geometries and channel numbers between 1 and 5 were used. Hartmann numbersmore » and interaction parameters were varied between O {le} M {le} 2300 and O {le} N {le} 40000. In parallel, a theoretical analysis was performed, based on the method of core flow approximation (CFA) which is valid for M {r_arrow} {infinity} and N {r_arrow} {infinity}. Significant MCEs occur in all ducts with totally electrically coupled channels. For the mode {Delta}p{sub i} = const, the flow rates in the outer channels can become significantly larger than those in the inner channels. For Q{sub i} = const, the highest pressure drop occurs in the middle channel and the lowest in the outer channels. The CFA predicts correctly the ratios of the pressure drops of the single channels but gives lower values than observed experimentally. No marked MCE was found for flow geometry which is similar to the KfK design, i.e., a fairly uniform flow rate and pressure drop distribution was observed for all values of M and N.« less

Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase.

PubMed

Shyng, S L; Barbieri, A; Gumusboga, A; Cukras, C; Pike, L; Davis, J N; Stahl, P D; Nichols, C G

2000-01-18

ATP-sensitive potassium channels (K(ATP) channels) regulate cell excitability in response to metabolic changes. K(ATP) channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K(+) channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), activate K(ATP) channels and antagonize ATP inhibition of K(ATP) channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP(2) levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed K(ATP) channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K(1/2), the half maximal inhibitory concentration, approximately 60 microM) than the sensitivities from control cells (K(1/2) approximately 10 microM). An inactive form of the PIP5K had little effect on the K(1/2) of wild-type channels but increased the ATP-sensitivity of a mutant K(ATP) channel that has an intrinsically lower ATP sensitivity (from K(1/2) approximately 450 microM to K(1/2) approximately 100 microM), suggesting a decrease in membrane PIP(2) levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP(2) and PI-3,4,5-P(3) levels, is a significant determinant of the physiological nucleotide sensitivity of K(ATP) channels.

Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase

PubMed Central

Shyng, S.-L.; Barbieri, A.; Gumusboga, A.; Cukras, C.; Pike, L.; Davis, J. N.; Stahl, P. D.; Nichols, C. G.

2000-01-01

ATP-sensitive potassium channels (KATP channels) regulate cell excitability in response to metabolic changes. KATP channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K+ channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), activate KATP channels and antagonize ATP inhibition of KATP channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP2 levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed KATP channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K1/2, the half maximal inhibitory concentration, ≈ 60 μM) than the sensitivities from control cells (K1/2 ≈ 10 μM). An inactive form of the PIP5K had little effect on the K1/2 of wild-type channels but increased the ATP-sensitivity of a mutant KATP channel that has an intrinsically lower ATP sensitivity (from K1/2 ≈ 450 μM to K1/2 ≈ 100 μM), suggesting a decrease in membrane PIP2 levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP2 and PI-3,4,5-P3 levels, is a significant determinant of the physiological nucleotide sensitivity of KATP channels. PMID:10639183

The Influence of Landslides on Channel Flood Response: A Case Study from the Colorado Front Range

NASA Astrophysics Data System (ADS)

Bennett, G. L.; Ryan, S. E.; Sholtes, J.; Rathburn, S. L.

2016-12-01

Studies have identified the role of thresholds and gradients in stream power in inducing geomorphic change during floods. At much longer time scales, empirical and modeling studies suggest the role of landslides in modifying channel response to external forcing (e.g. tectonic uplift); landslide-delivered sediment may behave as a tool, enhancing channel incision, or as cover, reducing channel incision. However, the influence of landslides on channel response to an individual flood event remains to be elucidated. Here we explore the influence of landslides on channel response to a 200-yr flood in Colorado, USA. From 9 - 15th September 2013 up to 450 mm of rain fell across a 100 km-wide swath of the Colorado Front Range, triggering >1000 landslides and inducing major flooding in several catchments. The flood caused extensive channel erosion, deposition and planform change, resulting in significant damage to property and infrastructure and even loss of life. We use a combination of pre and post flood LiDAR and field mapping to quantify geomorphic change in several catchments spanning the flooded region. We make a reach-by-reach analysis of channel geomorphic change metrics (e.g. volume of erosion) in relation to landslide sediment input and total stream power as calculated from radar-based rainfall measurements. Preliminary results suggest that landslide-sediment input may complicate the predictive relationship between channel erosion and stream power. Low volumes of landslide sediment input appear to enhance channel erosion (a tools effect), whilst very large volumes appear to reduce channel erosion (a cover effect). These results have implications for predicting channel response to floods and for flood planning and mitigation.

Side-entry laser-beam zigzag irradiation of multiple channels in a microchip for simultaneous and highly sensitive detection of fluorescent analytes.

PubMed

Anazawa, Takashi; Yokoi, Takahide; Uchiho, Yuichi

2015-09-01

A simple and highly sensitive technique for laser-induced fluorescence detection on multiple channels in a plastic microchip was developed, and its effectiveness was demonstrated by laser-beam ray-trace simulations and experiments. In the microchip, with refractive index nC, A channels and B channels are arrayed alternately and respectively filled with materials with refractive indexes nA for electrophoresis analysis and nB for laser-beam control. It was shown that a laser beam entering from the side of the channel array traveled straight and irradiated all A channels simultaneously and effectively because the refractive actions by the A and B channels were counterbalanced according to the condition nA < nC < nB. This technique is thus called "side-entry laser-beam zigzag irradiation". As a demonstration of the technique, when nC = 1.53, nA = 1.41, nB = 1.66, and the cross sections of both eight A channels and seven B channels were the same isosceles trapezoids with 97° base angle, laser-beam irradiation efficiency on the eight A channels by the simulations was 89% on average and coefficient of variation was 4.4%. These results are far superior to those achieved by other conventional methods such as laser-beam expansion and scanning. Furthermore, fluorescence intensity on the eight A channels determined by the experiments agreed well with that determined by the simulations. Therefore, highly sensitive and uniform fluorescence detection on eight A channels was achieved. It is also possible to fabricate the microchips at low cost by plastic-injection molding and to make a simple and compact detection system, thereby promoting actual use of the proposed side-entry laser-beam zigzag irradiation in various fields.

Direct and remote modulation of L-channels in chromaffin cells: distinct actions on alpha1C and alpha1D subunits?

PubMed

Baldelli, Pietro; Hernández-Guijo, Jesus Miguel; Carabelli, Valentina; Novara, Monica; Cesetti, Tiziana; Andrés-Mateos, Eva; Montiel, Carmen; Carbone, Emilio

2004-02-01

Understanding precisely the functioning of voltage-gated Ca2+ channels and their modulation by signaling molecules will help clarifying the Ca(2+)-dependent mechanisms controlling exocytosis in chromaffin cells. In recent years, we have learned more about the various pathways through which Ca2+ channels can be up- or down-modulated by hormones and neurotransmitters and how these changes may condition chromaffin cell activity and catecolamine release. Recently, the attention has been focused on the modulation of L-channels (CaV 1), which represent the major Ca2+ current component in rat and human chromaffin cells. L-channels are effectively inhibited by the released content of secretory granules or by applying mixtures of exogenous ATP, opioids, and adrenaline through the activation of receptor-coupled G proteins. This unusual inhibition persists in a wide range of potentials and results from a direct (membrane-delimited) interaction of G protein subunits with the L-channels co-localized in membrane microareas. Inhibition of L-channels can be reversed when the cAMP/PKA pathway is activated by membrane permeable cAMP analog or when cells are exposed to isoprenaline (remote action), suggesting the existence of parallel and opposite effects on L-channel gating by distinctly activated membrane autoreceptors. Here, the authors review the molecular components underlying these two opposing signaling pathways and present new evidence supporting the presence of two L-channel types in rat chromaffin cells (alpha1C and alpha1D), which open new interesting issues concerning Ca(2+)-channel modulation. In light of recent findings on the regulation of exocytosis by Ca(2+)-channel modulation, the authors explore the possible role of L-channels in the autocontrol of catecholamine release.

Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field.

PubMed

Moran, Magdalene M; Szallasi, Arpad

2018-06-01

Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of transient receptor potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 cation channels as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically. TRPV1 channel antagonists have suffered from side effects related to the channel's role in temperature sensation; however, high dose formulations of capsaicin have reached the market and shown therapeutic utility. A number of potent, small molecule antagonists of TRPA1 channels have recently advanced into clinical trials for the treatment of inflammatory and neuropathic pain, and TRPM8 antagonists are following closely behind for cold allodynia. TRPV3, TRPV4, TRPM2 and TRPM3 channels have also been of significant interest. This review discusses the preclinical promise and status of novel analgesic agents that target TRP channels and the challenges that these compounds may face in development and clinical practice. This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc. © 2017 The British Pharmacological Society.

Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl− channels by non-sulphonylurea hypoglycaemic agents

PubMed Central

Cai, Z; Lansdell, K A; Sheppard, D N

1999-01-01

Hypoglycaemia-inducing sulphonylureas, such as glibenclamide, inhibit cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels. In search of modulators of CFTR, we investigated the effects of the non-sulphonylurea hypoglycaemic agents meglitinide, repaglinide, and mitiglinide (KAD-1229) on CFTR Cl− channels in excised inside-out membrane patches from C127 cells expressing wild-type human CFTR. When added to the intracellular solution, meglitinide and mitiglinide inhibited CFTR Cl− currents with half-maximal concentrations of 164±19 μM and 148±36 μM, respectively. However, repaglinide only weakly inhibited CFTR Cl− currents. To understand better how non-sulphonylurea hypoglycaemic agents inhibit CFTR, we studied single channels. Channel blockade by both meglitinide and mitiglinide was characterized by flickery closures and a significant decrease in open probability (Po). In contrast, repaglinide was without effect on either channel gating or Po, but caused a small decrease in single-channel current amplitude. Analysis of the dwell time distributions of single channels indicated that both meglitinide and mitiglinide greatly decreased the open time of CFTR. Mitiglinide-induced channel closures were about 3-fold longer than those of meglitinide. Inhibition of CFTR by meglitinide and mitiglinide was voltage-dependent: at positive voltages channel blockade was relieved. The data demonstrate that non-sulphonylurea hypoglycaemic agents inhibit CFTR. This indicates that these agents have a wider specificity of action than previously recognized. Like glibenclamide, non-sulphonylurea hypoglycaemic agents may inhibit CFTR by occluding the channel pore and preventing Cl− permeation. PMID:10498841

Ca2+ and Mn2+ Influx Through Receptor-Mediated Activation of Nonspecific Cation Channels in Mast Cells

NASA Astrophysics Data System (ADS)

Fasolato, Cristina; Hoth, Markus; Matthews, Gary; Penner, Reinhold

1993-04-01

Whole-cell patch-clamp recordings of membrane currents and Fura-2 measurements of free intracellular calcium concentration ([Ca2+]_i) were used to study calcium influx through receptor-activated cation channels in rat peritoneal mast cells. Cation channels were activated by the secretagogue compound 48/80, whereas a possible concomitant Ca2+ entry through pathways activated by depletion of calcium stores was blocked by dialyzing cells with heparin. Heparin effectively suppressed the transient Ca2+ release induced by 48/80 and abrogated inositol 1,4,5-trisphosphate-induced calcium influx without affecting activation of 50-pS cation channels. There was a clear correlation between changes in [Ca2+]_i and the activity of 50-pS channels. The changes in [Ca2+]_i increased with elevation of extracellular Ca2+. At the same time, inward currents through 50-pS channels were diminished as more Ca2+ permeated. This effect was due to a decrease in slope conductance and a reduction in the open probability of the cation channels. In physiological solutions, 3.6% of the total current was carried by Ca2+. The cation channels were not only permeable to Ca2+ but also to Mn2+, as evidenced by the quench of Fura-2 fluorescence. Mn2+ current through 50-pS channels could not be resolved at the single-channel level. Our results suggest that 50-pS cation channels partially contribute to sustained increases of [Ca2+]_i in mast cells following receptor activation.

Sodium channel slow inactivation as a therapeutic target for myotonia congenita

PubMed Central

Novak, Kevin R; Norman, Jennifer; Mitchell, Jacob R; Pinter, Martin J; Rich, Mark M

2014-01-01

Objective Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm up and to use this information to guide development of novel therapy. Methods To determine the mechanism underlying warm-up, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warm-up in a mouse model of myotonia congenita. Results Changes in action potentials suggested slow inactivation of sodium channels as an important contributor to warm-up. These data suggested enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are FDA-approved for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine’s hypoexcitability side effects. Interpretation We conclude ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita. PMID:25515836

Analgesic ineffectiveness of lacosamide after spinal nerve ligation and its sodium channel activity in injured neurons.

PubMed

Hagenacker, T; Schäfer, N; Büsselberg, D; Schäfers, M

2013-07-01

Lacosamide is a novel anti-epileptic drug that enhances the slow- and not fast-inactivating state of voltage-gated sodium channels. Lacosamide has demonstrated analgesic efficacy in several animal studies but preclinical studies on neuropathic pain models are rare, and recent clinical trials showed no superior analgesic effects. Here, we examine whether an acute or chronic administration of lacosamide (3-60 mg/kg, i.p.) attenuates pain behaviour induced by spinal nerve ligation (SNL). To validate the inhibitory efficacy of lacosamide on voltage-gated sodium channels, sodium currents in naïve and SNL-injured dorsal root ganglion (DRG) neurons were recorded using whole-cell patch clamping. Lacosamide only marginally attenuated thermal hyperalgesia, but not tactile allodynia when applied once 7 or 14 days after SNL and showed no analgesic effect when applied daily for 19 days. In naïve neurons, 100 μmol/L lacosamide inhibited sodium channel currents by 58% and enhanced the slow inactivation (87% for lacosamide vs. 47% for control). In contrast, lacosamide inhibited sodium currents in injured DRG neurons by only 15%, while the effects on slow inactivation were diminished. Isolated currents from the NaV 1.8 channel subtype were only marginally changed by lacosamide. The reduced effectiveness of lacosamide on voltage-gated sodium channel currents in injured DRG neurons may contribute to the reduced analgesic effect observed for the SNL model. © 2012 European Federation of International Association for the Study of Pain Chapters.

Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats

PubMed Central

Todorovic, Slobodan M; Rastogi, A J; Jevtovic-Todorovic, Vesna

2003-01-01

Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage- and ligand-gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood. Therefore, we studied the potential analgesic effects of commonly used anticonvulsant agents in peripheral nociception. We injected anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used anticonvulsants such as voltage-gated Na+ channel blockers, phenytoin and carbamazepine, and voltage-gated Ca2+ channel blockers, gabapentin and ethosuximide, induced dose-dependent analgesia in the injected paw, with ED50 values of 0.30, 0.32 and 8, 410 μg per 100 μl, respectively. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of anticonvulsants that elicited local analgesia. Hill slope coefficients for the tested anticonvulsants indicate that the dose–response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide. Our data strongly suggest that cellular targets like voltage-gated Na+ and Ca2+ channels, similar to those that mediate the effects of anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied anticonvulsants that block voltage-gated Na+ and Ca2+ channels may be useful analgesics. PMID:12970103

Effects of channel tap spacing on delay-lock tracking

NASA Astrophysics Data System (ADS)

Dana, Roger A.; Milner, Brian R.; Bogusch, Robert L.

1995-12-01

High fidelity simulations of communication links operating through frequency selective fading channels require both accurate channel models and faithful reproduction of the received signal. In modern radio receivers, processing beyond the analog-to-digital converter (A/D) is done digitally, so a high fidelity simulation is actually an emulation of this digital signal processing. The 'simulation' occurs in constructing the output of the A/D. One approach to constructing the A/D output is to convolve the channel impulse response function with the combined impulse response of the transmitted modulation and the A/D. For both link simulations and hardware channel simulators, the channel impulse response function is then generated with a finite number of samples per chip, and the convolution is implemented in a tapped delay line. In this paper we discuss the effects of the channel model tap spacing on the performance of delay locked loops (DLLs) in both direct sequence and frequency hopped spread spectrum systems. A frequency selective fading channel is considered, and the channel impulse response function is constructed with an integer number of taps per modulation symbol or chip. The tracking loop time delay is computed theoretically for this tapped delay line channel model and is compared to the results of high fidelity simulations of actual DLLs. A surprising result is obtained. The performance of the DLL depends strongly on the number of taps per chip. As this number increases the DLL delay approaches the theoretical limit.

Activity-dependent downregulation of M-Type (Kv7) K⁺ channels surface expression requires the activation of iGluRs/Ca²⁺/PKC signaling pathway in hippocampal neuron.

PubMed

Li, Cai; Lu, Qing; Huang, Pengcheng; Fu, Tianli; Li, Changjun; Guo, Lianjun; Xu, Xulin

2015-08-01

M-type (Kv7) K(+) channels, encoded by KCNQ2-KCNQ5 genes, play a pivotal role in controlling neuronal excitability. However, precisely how neuronal activity regulates Kv7 channel translocation has not yet been fully defined. Here we reported activity-dependent changes in Kv7 channel subunits Kv7.2 and Kv7.3 surface expression by glutamate (glu). In the present study, we found that treatment with glutamate rapidly caused a specific decrease in M-current as well as Kv7 channel surface expression in primary cultured hippocampal neurons. The glutamate effects were mimicked by NMDA and AMPA. The glutamate effects on Kv7 channels were partially attenuated by pre-treatment of NMDA receptors antagonist d,l-APV or AMPA-KA receptors antagonist CNQX. The signal required Ca(2+) influx through L-type Ca(2+) channel and intracellular Ca(2+) elevations. PKC activation was involved in the glutamate-induced reduction of Kv7 channel surface expression. Moreover, a significant reduction of Kv7 channel surface expression occurred following glycine-induced "chem"-LTP in vitro and hippocampus-dependent behavioral learning training in vivo. These results demonstrated that activity-dependent reduction of Kv7 channel surface expression through activation of ionotropic glutamate receptors (iGluRs)/Ca(2+)/PKC signaling pathway might be an important molecular mechanism for regulation of neuronal excitability and synaptic plasticity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice.

PubMed

Sheikhi, Mehdi; Shirzadian, Armin; Dehdashtian, Amir; Amiri, Shayan; Ostadhadi, Sattar; Ghasemi, Mehdi; Dehpour, Ahmad Reza

2016-09-01

Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem. Copyright © 2016 Elsevier Inc. All rights reserved.

Correction of thin cirrus effects in AVIRIS images using the sensitive 1.375-micron cirrus detecting channel

NASA Technical Reports Server (NTRS)

Gao, Bo-Cai; Kaufman, Yorman J.

1995-01-01

Using spectral imaging data acquired with the Airborne Visible Infrared Imaging Spectrometer (AVIRIS) from an ER-2 aircraft at 20 km altitude during various field programs, it was found that narrow channels near the center of the strong 1.38-micrometer water vapor band are very effective in detecting think cirrus clouds. Based on this observation from AVIRIS data, Gao and Kaufman proposed to put a channel centered at 1.375 micrometers with a width of 30 nm on the Moderate Resolution Imaging Spectrometer (MODIS) for remote sensing of cirrus clouds from space. The sensitivity of the 1.375-micrometer MODIS channel to detect thin cirrus clouds during the day time is expected to be one to two orders of magnitude better than the current infrared emission techniques. As a result, much larger fraction of the satellite data is expected to be identified as being covered by cirrus clouds, some of them so thin that their obscuration of the surface is very small. In order to make better studies of surface reflectance properties, thin cirrus effects must be removed from satellite images. Therefore, there is a need to study radiative properties of thin cirrus clouds, so that a strategy for correction or removal of the thin cirrus effects, similar to the correction of atmospheric aerosol effect, can be formed. In this extended abstract, we describe an empirical approach for removing/correcting thin cirrus effects in AVIRIS images using channels near 1.375 microns - one step beyond the detection of cirrus clouds using these channels.

Effective mobility enhancement of amorphous In-Ga-Zn-O thin-film transistors by holographically generated periodic conductor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Jaewook; Kim, Joonwoo; Jeong, Soon Moon

In this study, we demonstrate a mobility enhancement structure for fully transparent amorphous indium-gallium-zinc-oxide thin-film transistors (a-IGZO TFTs) by embedding a holographically generated periodic nano-conductor in the back-channel regions. The intrinsic field-effect mobility was enhanced up to 2 times compared to that of a reference sample. The enhancement originated from a decrease in the effective channel length due to the highly conductive nano-conductor region. By combining conventional and holographic lithography, the performance of the a-IGZO TFT can be effectively improved without varying the composition of the channel layer.

Effective mobility enhancement of amorphous In-Ga-Zn-O thin-film transistors by holographically generated periodic conductor

NASA Astrophysics Data System (ADS)

Jeong, Jaewook; Kim, Joonwoo; Kim, Donghyun; Jeon, Heonsu; Jeong, Soon Moon; Hong, Yongtaek

2016-08-01

In this study, we demonstrate a mobility enhancement structure for fully transparent amorphous indium-gallium-zinc-oxide thin-film transistors (a-IGZO TFTs) by embedding a holographically generated periodic nano-conductor in the back-channel regions. The intrinsic field-effect mobility was enhanced up to 2 times compared to that of a reference sample. The enhancement originated from a decrease in the effective channel length due to the highly conductive nano-conductor region. By combining conventional and holographic lithography, the performance of the a-IGZO TFT can be effectively improved without varying the composition of the channel layer.

Modeling of dislocation channel width evolution in irradiated metals

DOE PAGES

Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

2017-11-08

Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. And based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopymore » (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Furthermore, examinations of the effect of the so-called “source-broadening” mechanism of channel formation showed that its effect is simply to add a minimum thickness to the channel without affecting channel dependence on the given parameters.« less

Modeling of dislocation channel width evolution in irradiated metals

NASA Astrophysics Data System (ADS)

Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

2018-02-01

Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. Based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopy (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Further, examinations of the effect of the so-called "source-broadening" mechanism of channel formation showed that its effect is simply to add a minimum thickness to the channel without affecting channel dependence on the given parameters.

Modeling of dislocation channel width evolution in irradiated metals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. And based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopymore » (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Furthermore, examinations of the effect of the so-called “source-broadening” mechanism of channel formation showed that its effect is simply to add a minimum thickness to the channel without affecting channel dependence on the given parameters.« less

Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(+)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices.

PubMed

Valentijn, K; Tranchand Bunel, D; Vaudry, H

1992-07-01

The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps4 and Ps5, are released by K(+)-induced depolarization through activation of voltage-sensitive calcium channels. The calcium channels appear to have a pharmacological profile different from that of L- and N-type channels. Although, their insensitivity to low Cd2+ concentrations and sensitivity to Ni2+ ions would support the involvement of T-type calcium channels, the lack of effect of amiloride suggests that they belong to a yet undefined class of calcium channels.

Effects of an extreme flood on river morphology (case study: Karoon River, Iran)

NASA Astrophysics Data System (ADS)

Yousefi, Saleh; Mirzaee, Somayeh; Keesstra, Saskia; Surian, Nicola; Pourghasemi, Hamid Reza; Zakizadeh, Hamid Reza; Tabibian, Sahar

2018-03-01

An extreme flood occurred on 14 April 2016 in the Karoon River, Iran. The occurred flood discharge was the highest discharge recorded over the last 60 years in the Karoon River. Using the OLI Landsat images taken on 8 April 2016 (before the flood) and 24 April 2016 (after the flood) the geomorphic effects were detected in different land cover types within the 155-km-long study reach. The results show that the flood significantly affected the channel width and the main effect was high mobilization of channel sediments and severe bank erosion in the meandering reaches. According to field surveys, the flood occupied the channel corridor and even the floodplain parts. However, the channel pattern was not significantly altered, although the results show that the average channel width increased from 192 to 256 m. Statistical results indicate a significant change for active channel width and sinuosity index at 99% confidence level for both indexes. The flood-induced morphological changes varied significantly for different land cover types along the Karoon River. Specifically, the channel has widened less in residential areas than in other land cover types because of the occurrence of bank protection structures. However, the value of bank retreat in residential and protected sides of the Karoon River is more than what we expected during the study of extreme flood.

TNF-{alpha} promotes cell survival through stimulation of K{sup +} channel and NF{kappa}B activity in corneal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Ling; Reinach, Peter; Lu, Luo

2005-11-15

Tumor necrosis factor (TNF-{alpha}) in various cell types induces either cell death or mitogenesis through different signaling pathways. In the present study, we determined in human corneal epithelial cells how TNF-{alpha} also promotes cell survival. Human corneal epithelial (HCE) cells were cultured in DMEM/F-12 medium containing 10% FBS. TNF-{alpha} stimulation induced activation of a voltage-gated K{sup +} channel detected by measuring single channel activity using patch clamp techniques. The effect of TNF-{alpha} on downstream events included NF{kappa}B nuclear translocation and increases in DNA binding activities, but did not elicit ERK, JNK, or p38 limb signaling activation. TNF-{alpha} induced increases inmore » p21 expression resulting in partial cell cycle attenuation in the G{sub 1} phase. Cell cycle progression was also mapped by flow cytometer analysis. Blockade of TNF-{alpha}-induced K{sup +} channel activity effectively prevented NF{kappa}B nuclear translocation and binding to DNA, diminishing the cell-survival protective effect of TNF-{alpha}. In conclusion, TNF-{alpha} promotes survival of HCE cells through sequential stimulation of K{sup +} channel and NF{kappa}B activities. This response to TNF-{alpha} is dependent on stimulating K{sup +} channel activity because following suppression of K{sup +} channel activity TNF-{alpha} failed to activate NF{kappa}B nuclear translocation and binding to nuclear DNA.« less

Economic effects of immigrants on native and foreign-born workers: complementarity, substitutability, and other channels of influence.

PubMed

Greenwood, M J; Hunt, G L

1995-04-01

The authors use Standard Metropolitan Statistical Area (SMSA) data constructed from 1980 census microdata files and other sources to estimate a structural model of native/foreign-born labor demand and labor supply which distinguishes the effects upon real wages of each type of labor and on the employment of natives. The authors specify, econometrically estimate, and simulate the structural model which incorporates not only a production structure channel through which immigrants influence area real wages and employment, but also demand and native labor supply channels. It is noted that while these are not the only channels through which immigrants may affect native workers, the model nonetheless constitutes a step in the direction of a general equilibrium approach. In the production structure channel, immigrants and natives are found to be substitutes in production. Immigration lowers foreign-born wage rates and leads to lower wages for natives. The negative effects of the production channel usually are ameliorated through the demand channel. Further, immigrants add to local demand through their earnings and potentially through non-labor income, while also lowering unit costs and local prices which enhances real incomes and potentially net exports, and thus the demands for local output and area labor. The author discusses findings of interest from the simulation results based upon an analysis of all areas.

LPS from Escherichia coli protects against indomethacin-induced gastropathy in rats--role of ATP-sensitive potassium channels.

PubMed

Gomes, Antoniella S; Lima, Lívia M F; Santos, Camila L; Cunha, Fernando Q; Ribeiro, Ronaldo A; Souza, Marcellus H L P

2006-10-10

The effect of lipopolysaccharide (LPS) in gastric protection has not been elucidated, but ATP-sensitive potassium (K(ATP)) channels are known to be involved in gastric defense. We evaluated the effect of LPS administration on indomethacin-induced gastropathy, and the role of K(ATP) channels in this event. Rats received intravenous (i.v.) LPS administration. After 1/2, 6, 24 or 48 h, indomethacin was injected. 3H later, gastric damage and myeloperoxidase activity were determined. Another group received LPS and 5 h later, glibenclamide, diazoxide or glibenclamide plus diazoxide. After 1 h, the rats received indomethacin and 3 h later, gastric damage and myeloperoxidase activity were evaluated. LPS reduced dose dependently gastric damage and myeloperoxidase activity induced by indomethacin. Glibenclamide reversed this LPS effect on indomethacin-induced gastropathy. Glibenclamide plus diazoxide administration did not change this LPS effect. Thus LPS has a protective effect against indomethacin-induced gastropathy, probably through activation of K(ATP) channels.

Tri-Coding of Information.

ERIC Educational Resources Information Center

Simpson, Timothy J.

Paivio's Dual Coding Theory has received widespread recognition for its connection between visual and aural channels of internal information processing. The use of only two channels, however, cannot satisfactorily explain the effects witnessed every day. This paper presents a study suggesting the presence a third, kinesthetic channel, currently…

Photonic channels for quantum communication

PubMed

van Enk SJ; Cirac; Zoller

1998-01-09

A general photonic channel for quantum communication is defined. By means of local quantum computing with a few auxiliary atoms, this channel can be reduced to one with effectively less noise. A scheme based on quantum interference is proposed that iteratively improves the fidelity of distant entangled particles.

Pricing Models for Dual-channel Reverse Supply Chain Considering Regional Differences under “Internet Recycling” Mode in China

NASA Astrophysics Data System (ADS)

Wu, Di; Li, Peng; Chen, Juhong

2018-01-01

In recent years, the Internet technology has been deeply influencing recycling industry to make it more intelligent and interconnected. However, most existing papers on “Internet Recycling” neglected the problem of pricing strategy under online and offline channels for different levels of recyclers. Moreover, the effect of regional differences has been emphasized a lot in dual-channel forward supply chain, but recycling field has seldom been concerned about it. In this paper, a recycling system consisting of one recycling center and several third-party recyclers (TPR) was investigated based on traditional mode and dual-channel mode. The dual-channel reverse supply chain model is transformed from traditional mode by the introduction of online channel. It involves two recycling modes, as recycling centre for online recovery and “Recycling center+TPR” for offline recovery. By establishing pricing strategies based on Stackelberg game model, the impacts of regional differences were analysed. Finally, numerical analysis was given to illustrate the effectiveness of the pricing mechanisms and strategies.

Electron mobility of two-dimensional electron gas in InGaN heterostructures: Effects of alloy disorder and random dipole scatterings

NASA Astrophysics Data System (ADS)

Hoshino, Tomoki; Mori, Nobuya

2018-04-01

InGaN has a smaller electron effective mass and is expected to be used as a channel material for high-electron-mobility transistors. However, it is an alloy semiconductor with a random distribution of atoms, which introduces additional scattering mechanisms: alloy disorder and random dipole scatterings. In this work, we calculate the electron mobility in InGaN- and GaN-channel high-electron-mobility transistors (HEMTs) while taking into account acoustic deformation potential, polar optical phonon, alloy disorder, and random dipole scatterings. For InGaN-channel HEMTs, we find that not only alloy disorder but also random dipole scattering has a strong impact on the electron mobility and it significantly decreases as the In mole fraction of the channel increases. Our calculation also shows that the channel thickness w dependence of the mobility is rather weak when w > 1 nm for In0.1Ga0.9N-channel HEMTs.

Efficient algorithms for solution of interference cancellation and channel estimation for mobile OFDM system

NASA Astrophysics Data System (ADS)

Fan, Tong-liang; Wen, Yu-cang; Kadri, Chaibou

Orthogonal frequency-division multiplexing (OFDM) is robust against frequency selective fading because of the increase of the symbol duration. However, the time-varying nature of the channel causes inter-carrier interference (ICI) which destroys the orthogonal of sub-carriers and degrades the system performance severely. To alleviate the detrimental effect of ICI, there is a need for ICI mitigation within one OFDM symbol. We propose an iterative Inter-Carrier Interference (ICI) estimation and cancellation technique for OFDM systems based on regularized constrained total least squares. In the proposed scheme, ICI aren't treated as additional additive white Gaussian noise (AWGN). The effect of Inter-Carrier Interference (ICI) and inter-symbol interference (ISI) on channel estimation is regarded as perturbation of channel. We propose a novel algorithm for channel estimation o based on regularized constrained total least squares. Computer simulations show that significant improvement can be obtained by the proposed scheme in fast fading channels.

Sniffer Channel Selection for Monitoring Wireless LANs

NASA Astrophysics Data System (ADS)

Song, Yuan; Chen, Xian; Kim, Yoo-Ah; Wang, Bing; Chen, Guanling

Wireless sniffers are often used to monitor APs in wireless LANs (WLANs) for network management, fault detection, traffic characterization, and optimizing deployment. It is cost effective to deploy single-radio sniffers that can monitor multiple nearby APs. However, since nearby APs often operate on orthogonal channels, a sniffer needs to switch among multiple channels to monitor its nearby APs. In this paper, we formulate and solve two optimization problems on sniffer channel selection. Both problems require that each AP be monitored by at least one sniffer. In addition, one optimization problem requires minimizing the maximum number of channels that a sniffer listens to, and the other requires minimizing the total number of channels that the sniffers listen to. We propose a novel LP-relaxation based algorithm, and two simple greedy heuristics for the above two optimization problems. Through simulation, we demonstrate that all the algorithms are effective in achieving their optimization goals, and the LP-based algorithm outperforms the greedy heuristics.

Real-time software-based end-to-end wireless visual communications simulation platform

NASA Astrophysics Data System (ADS)

Chen, Ting-Chung; Chang, Li-Fung; Wong, Andria H.; Sun, Ming-Ting; Hsing, T. Russell

1995-04-01

Wireless channel impairments pose many challenges to real-time visual communications. In this paper, we describe a real-time software based wireless visual communications simulation platform which can be used for performance evaluation in real-time. This simulation platform consists of two personal computers serving as hosts. Major components of each PC host include a real-time programmable video code, a wireless channel simulator, and a network interface for data transport between the two hosts. The three major components are interfaced in real-time to show the interaction of various wireless channels and video coding algorithms. The programmable features in the above components allow users to do performance evaluation of user-controlled wireless channel effects without physically carrying out these experiments which are limited in scope, time-consuming, and costly. Using this simulation platform as a testbed, we have experimented with several wireless channel effects including Rayleigh fading, antenna diversity, channel filtering, symbol timing, modulation, and packet loss.

Role of aquaporin and sodium channel in pleural water movement.

PubMed

Jiang, Jinjun; Hu, Jie; Bai, Chunxue

2003-12-16

The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or isosmolar fluid was infused into the pleural space in anesthetized wildtype and AQP1 null mice. Pleural fluid was sampled at specified times to quantify the osmolality and volume. The sodium channel activator terbutaline increased isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride decreased it by 15%, but had no effect on osmotically driven water transport. AQP1 deletion significantly decreased osmotic water transport in pleural space by twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous injection of HgCl2 decreased osmotic pleural water movement by 43%. These results provided evidence for a role of a sodium channel in pleural fluid absorption; AQP1 plays a major role in osmotic liquid transport but it does not affect isosmolar fluid clearance.

End region and current consolidation effects upon the performance of an MHD channel for the ETF conceptual design

NASA Technical Reports Server (NTRS)

Wang, S. Y.; Smith, J. M.

1981-01-01

The effects of MHD channel end regions on the overall power generation were considered. The peak plant thermodynamic efficiency was found to be slightly lower than for the active region (41%). The channel operating point for the peak efficiency was shifted to the supersonic mode (Mach No., M sub c approx. 1.1) rather than the previous subsonic operation (M sub c approx. 0.9). The sensitivity of the channel performance to the B-field, diffuser recovery coefficient, channel load parameter, Mach number, and combustor pressure is also discussed. In addition, methods for operating the channel in a constant-current mode are investigated. This mode is highly desirable from the standpoint of simplifying the current and voltage consolidation for the inverter system. This simplification could result in significant savings in the cost of the equipment. The initial results indicate that this simplification is possible, even under a strict Hall field constraint, with resonable plant thermodynamic efficiency (40.5%).

Reconstitution of a Kv channel into lipid membranes for structural and functional studies.

PubMed

Lee, Sungsoo; Zheng, Hui; Shi, Liang; Jiang, Qiu-Xing

2013-07-13

To study the lipid-protein interaction in a reductionistic fashion, it is necessary to incorporate the membrane proteins into membranes of well-defined lipid composition. We are studying the lipid-dependent gating effects in a prototype voltage-gated potassium (Kv) channel, and have worked out detailed procedures to reconstitute the channels into different membrane systems. Our reconstitution procedures take consideration of both detergent-induced fusion of vesicles and the fusion of protein/detergent micelles with the lipid/detergent mixed micelles as well as the importance of reaching an equilibrium distribution of lipids among the protein/detergent/lipid and the detergent/lipid mixed micelles. Our data suggested that the insertion of the channels in the lipid vesicles is relatively random in orientations, and the reconstitution efficiency is so high that no detectable protein aggregates were seen in fractionation experiments. We have utilized the reconstituted channels to determine the conformational states of the channels in different lipids, record electrical activities of a small number of channels incorporated in planar lipid bilayers, screen for conformation-specific ligands from a phage-displayed peptide library, and support the growth of 2D crystals of the channels in membranes. The reconstitution procedures described here may be adapted for studying other membrane proteins in lipid bilayers, especially for the investigation of the lipid effects on the eukaryotic voltage-gated ion channels.

The effect of ratio between rigid plant height and water depth on the manning’s coefficient in open channel

NASA Astrophysics Data System (ADS)

Rizalihadi, M.; Ziana; Shaskia, Nina; Asharly, H.

2018-05-01

One of the important factors in channel dimension is the Manning’s coefficient ( n ). This coefficient is influenced not only by the channel roughness but also by the presence of plants in the channel. The aim of the study is to see the effect of the ratio between the height of the rigid plant and water depth on the Manning’s coefficient (n) in open channel. The study was conducted in open channel with 15.5 m long, 0.5 m wide and 1.0 m high, in which at the center of the channel is planted with the rigid plants with a density of 42 plants/m2. The flow was run with a discharge of 0.013 m3/s at 6 ratios of Hplants/Hwater, namely: 0; 0.2; 0.6; 0.8; 1,0 and 1,2, to obtain the velocity and water profiles. Then the value of n is analyzed using Manning’s equation. The results showed that the mean velocity becomes decrease 17.81-34.01% as increase the ratio of Hplants/Hwater. This results in increasing n value to become 1.22-1.52 times compared to the unplanted channel ( no =0.038). So, it can be concluded that the ratio between the rigid plant’s height and water depth in the open channel can affect the value of Manning coefficient.

High-performance PbS quantum dot vertical field-effect phototransistor using graphene as a transparent electrode

NASA Astrophysics Data System (ADS)

Che, Yongli; Zhang, Yating; Cao, Xiaolong; Song, Xiaoxian; Zhang, Haiting; Cao, Mingxuan; Dai, Haitao; Yang, Junbo; Zhang, Guizhong; Yao, Jianquan

2016-12-01

Solution processed photoactive PbS quantum dots (QDs) were used as channel in high-performance near-infrared vertical field-effect phototransistor (VFEpT) where monolayer graphene embedded as transparent electrode. In this vertical architecture, the PbS QD channel was sandwiched and naturally protected between the drain and source electrodes, which made the device ultrashort channel length (110 nm) simply the thickness of the channel layer. The VFEpT exhibited ambipolar operation with high mobilities of μe = 3.5 cm2/V s in n-channel operation and μh = 3.3 cm2/V s in p-channel operation at low operation voltages. By using the photoactive PbS QDs as channel material, the VFEpT exhibited good photoresponse properties with a responsivity of 4.2 × 102 A/W, an external quantum efficiency of 6.4 × 104% and a photodetectivity of 2.1 × 109 Jones at the light irradiance of 36 mW/cm2. Additionally, the VFEpT showed excellent on/off switching with good stability and reproducibility and fast response speed with a short rise time of 12 ms in n-channel operation and 10.6 ms in p-channel operation. These high mobilities, good photoresponse properties and simplistic fabrication of our VFEpTs provided a facile route to the high-performance inorganic photodetectors.

Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels.

PubMed

Sihn, Choong-Ryoul; Kim, Hyo Jeong; Woltz, Ryan L; Yarov-Yarovoy, Vladimir; Yang, Pei-Chi; Xu, Jun; Clancy, Colleen E; Zhang, Xiao-Dong; Chiamvimonvat, Nipavan; Yamoah, Ebenezer N

2016-01-29

Calmodulin (CaM), a Ca(2+)-sensing protein, is constitutively bound to IQ domains of the C termini of human Kv7 (hKv7, KCNQ) channels to mediate Ca(2+)-dependent reduction of Kv7 currents. However, the mechanism remains unclear. We report that CaM binds to two isoforms of the hKv7.4 channel in a Ca(2+)-independent manner but that only the long isoform (hKv7.4a) is regulated by Ca(2+)/CaM. Ca(2+)/CaM mediate reduction of the hKv7.4a channel by decreasing the channel open probability and altering activation kinetics. We took advantage of a known missense mutation (G321S) that has been linked to progressive hearing loss to further examine the inhibitory effects of Ca(2+)/CaM on the Kv7.4 channel. Using multidisciplinary techniques, we demonstrate that the G321S mutation may destabilize CaM binding, leading to a decrease in the inhibitory effects of Ca(2+) on the channels. Our study utilizes an expression system to dissect the biophysical properties of the WT and mutant Kv7.4 channels. This report provides mechanistic insights into the critical roles of Ca(2+)/CaM regulation of the Kv7.4 channel under physiological and pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characteristics of suspended and streambed sediment within constructed chutes and the main channel at Upper Hamburg and Glovers Point Bends, Missouri River, Nebraska, 2008

USGS Publications Warehouse

Woodward, Brenda K.; Rus, David L.

2011-01-01

The U.S. Army Corps of Engineers, Omaha District, as part of the Missouri River Bank Stabilization and Navigation Mitigation Project, has constructed 17 off-channel chutes along the channelized Missouri River, downstream from Sioux City, Iowa, to increase habitat diversity. To better understand characteristics of suspended and streambed sediment within these constructed chutes, the U.S. Geological Survey investigated specific aspects of chute design and function in relation to sediment characteristics including: (1) effects of inlet structures; (2) changes occurring between the inlet and the outlet of a chute; (3) effects of chutes on sediment characteristics in the main channel; and (4) differences in chute dynamics between sampled chutes. Two chutes differing in design, location, and dynamics were studied, Upper Hamburg Bend near Nebraska City, Nebr., and Glovers Point Bend near Winnebago, Nebr. Each site was characterized using five or more sampling transects (two in the chute and three to four in the main channel) designed to bracket sediment exchanges between chutes and the main channel. A sixth transect was included at the Upper Hamburg Bend study site to account for the effects of a nontarget chute having its inlet midway between the inlet and outlet of the primary chute. Representative samples of suspended and streambed sediment were collected at each transect, along with measurements of turbidity and streamflow, between June and November 2008. Four sets of samples were collected at the Glovers Point Bend study site and five sample sets were collected from the Upper Hamburg Bend study site. Results from paired t-tests and standard t-tests indicated that the inlet structure design, passing inflow only from the top of the main-channel water column, reduced the supply of coarse-grained suspended sediment entering the chutes. Statistical comparisons did not indicate differences between the inlet and outlet of either chute; however, anecdotal evidence of recent bank erosion and in-channel deposition was observed in both chutes during the study period. Chutes had little effect on Missouri River main-channel sediment characteristics, which could be explained by the much greater streamflow of the main channel. Between-chute comparisons showed no significant differences in the suspended-sediment characteristics; however, the Upper Hamburg Bend chute had a coarser streambed, wider channel, and much greater streamflow than did the Glovers Point Bend chute.

Temporal and spatial scales of geomorphic adjustments to reduced competency following flow regulation in bedload-dominated systems

NASA Astrophysics Data System (ADS)

Curtis, Katherine E.; Renshaw, Carl E.; Magilligan, Francis J.; Dade, William B.

2010-05-01

Because of the combined effects of reduced sediment transport capacity and competency following flow regulation, morphological changes are expected to occur in channels downstream from dams and, specifically, at tributary junctions where local inputs of water and sediment occur. Using a combination of historical aerial photographs, mainstem- and tributary-channel pebble counts, and HEC-RAS flow modeling for two watersheds in south-central VT, one unregulated and the other regulated since 1961, we document the time series of post-regulation channel narrowing and associated bar growth due to the influx of tributary sediment. Channel adjustments at regulated tributary junctions have been significant in ca. 50 years following impoundment, with channels downstream of the confluences narrowing over 15% after an initial ca. 20-year lag before the onset of accelerated narrowing. Moreover, flow modeling suggests that downstream of regulated confluences, the modern median grain size ( d50) along the channel bed is immobile. No significant channel narrowing has occurred either above or below unregulated tributary junctions or on the mainstem upstream of regulated confluences. However, greater channel sediment fining is observed upstream of regulated confluences than above unregulated confluences. Thus, the primary mode of mainstem channel adjustment differs up- and downstream of regulated tributaries. These confluence effects have occurred where the tributary drainage area is only 0.2 times that of the mainstem, well below the threshold ratio of 0.6 required for significant geomorphic effects at unregulated confluences, highlighting the geomorphic scale shift of dams. Lastly, we evaluate the downstream length required for a river to recover from the impacts of impoundment and demonstrate that even distal locations are impacted by flow regulation. Unlike the impacts of flow regulation in the western US where channel incision and bar erosion predominate following impoundment, we find that in situations where bed incision is minimal and where sediment loads are low but bed caliber high, bar growth and channel narrowing are significant adjustments at tributary junctions following impoundment. Therefore, at our sites the effects of dams on reduced competency may be more profound than on reduced sediment transport capacity, highlighting the importance of geologic and geomorphic settings in understanding fluvial responses to impoundment.

Regulation of human cardiac potassium channels by full-length KCNE3 and KCNE4.

PubMed

Abbott, Geoffrey W

2016-12-06

Voltage-gated potassium (Kv) channels comprise pore-forming α subunits and a multiplicity of regulatory proteins, including the cardiac-expressed and cardiac arrhythmia-linked transmembrane KCNE subunits. After recently uncovering novel, N-terminally extended (L) KCNE3 and KCNE4 isoforms and detecting their transcripts in human atrium, reported here are their functional effects on human cardiac Kv channel α subunits expressed in Xenopus laevis oocytes. As previously reported for short isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1.1; neither form regulated the HCN1 pacemaker channel. Unlike KCNE4S, KCNE4L was a potent inhibitor of Kv4.2 and Kv4.3; co-expression of cytosolic β subunit KChIP2, which regulates Kv4 channels in cardiac myocytes, partially relieved Kv4.3 but not Kv4.2 inhibition. Inhibition of Kv4.2 and Kv4.3 by KCNE3L was weaker, and its inhibition of Kv4.2 abolished by KChIP2. KCNE3L and KCNE4L also exhibited subunit-specific effects on Kv4 channel complex inactivation kinetics, voltage dependence and recovery. Further supporting the potential physiological significance of the robust functional effects of KCNE4L on Kv4 channels, KCNE4L protein was detected in human atrium, where it co-localized with Kv4.3. The findings establish functional effects of novel human cardiac-expressed KCNE isoforms and further contribute to our understanding of the potential mechanisms influencing cardiomyocyte repolarization.

Do preclinical seizure models preselect certain adverse effects of antiepileptic drugs.

PubMed

Meldrum, Brian

2002-06-01

Classical screening tests (maximal electroshock, MES, and threshold pentylenetetrazol, PTZ) employ non-epileptic rodents and identify antiepileptic drugs (AEDs) with mechanisms of action associated with significant CNS side effects. Thus MES identifies drugs acting on Na+ channels that produce cerebellar toxicity. It may be possible to produce novel AEDs more selectively targeted at voltage-sensitive (VS) ion channels. There is little specific evidence for the likely success of this strategy with subunit selective agents targeted at the different VS Na+ channels. Drugs targeted at specific VS Ca++ channels (T, N, P/Q types) may be useful in generalised seizures. There are many as yet unexplored possibilities relating to K+ channels. GABA related drugs acting on PTZ clonic seizures tend to induce sedation and muscle hypotonia. Studies in mice, particularly with knock-in mutations, but also with subunit selective agents acting via the GABA(A) benzodiazepine site, suggest that it is possible to produce agents which do or do not induce particular side effects (sedative, hypnotic, anxiolytic, muscle relaxant, amnesia, anaesthesia). Whether these findings transfer to man has yet to be established. Acquired epilepsy in rodents (e.g. kindling or spontaneous seizures following chemically- or electrically-induced status epilepticus) or acquired epilepsy in man (following prolonged febrile seizures or traumatic brain injury) is associated with multiple changes in the function and subunit composition of ion channels and receptor molecules. Optimal screening of novel AEDs, both for efficacy and side effects, requires models with receptor and ion channel changes similar to those in the target human syndrome.

Kv7 channels in the nucleus accumbens are altered by chronic drinking and are targets for reducing alcohol consumption.

PubMed

McGuier, Natalie S; Griffin, William C; Gass, Justin T; Padula, Audrey E; Chesler, Elissa J; Mulholland, Patrick J

2016-11-01

Alcohol use disorders (AUDs) are a major public health issue and produce enormous societal and economic burdens. Current Food and Drug Administration (FDA)-approved pharmacotherapies for treating AUDs suffer from deleterious side effects and are only effective in a subset of individuals. It is therefore essential to find improved medications for the management of AUDs. Emerging evidence suggests that anticonvulsants are a promising class of drugs for treating individuals with AUDs. In these studies, we used integrative functional genomics to demonstrate that genes that encode Kv7 channels (i.e. Kcnq2/3) are related to alcohol (ethanol) consumption, preference and acceptance in rodents. We then tested the ability of the FDA-approved anticonvulsant retigabine, a Kv7 channel opener, to reduce voluntary ethanol consumption of Wistar rats in a two-bottle choice intermittent alcohol access paradigm. Systemic administration and microinjections of retigabine into the nucleus accumbens significantly reduced alcohol drinking, and retigabine was more effective at reducing intake in high- versus low-drinking populations of Wistar rats. Prolonged voluntary drinking increased the sensitivity to the proconvulsant effects of pharmacological blockade of Kv7 channels and altered surface trafficking and SUMOylation patterns of Kv7.2 channels in the nucleus accumbens. These data implicate Kcnq2/3 in the regulation of ethanol drinking and demonstrate that long-term drinking produces neuroadaptations in Kv7 channels. In addition, these results have identified retigabine as a potential pharmacotherapy for treating AUDs and Kv7 channels as a novel therapeutic target for reducing heavy drinking. © 2015 Society for the Study of Addiction.

Turbulence-induced channel crosstalk in an orbital angular momentum-multiplexed free-space optical link

NASA Astrophysics Data System (ADS)

Anguita, Jaime A.; Neifeld, Mark A.; Vasic, Bane V.

2008-05-01

A multichannel free-space optical (FSO) communication system based on orbital angular momentum (OAM)-carrying beams is studied. We numerically analyze the effects of atmospheric turbulence on the system and find that turbulence induces attenuation and crosstalk among channels. Based on a model in which the constituent channels are binary symmetric and crosstalk is a Gaussian noise source, we find optimal sets of OAM states at each turbulence condition studied and determine the aggregate capacity of the multichannel system at those conditions. OAM-multiplexed FSO systems that operate in the weak turbulence regime are found to offer good performance. We verify that the aggregate capacity decreases as the turbulence increases. A per-channel bit-error rate evaluation is presented to show the uneven effects of crosstalk on the constituent channels.

Dependence of interface charge trapping on channel engineering in pentacene field effect transistors.

PubMed

Lee, Sunwoo; Park, Junghyuck; Park, In-Sung; Ahn, Jinho

2014-07-01

We investigate the dependence of charge carrier mobility by trap states at various interface regions through channel engineering. Prior to evaluation of interface trap density, the electrical performance in pentaene field effect transistors (FET) with high-k gate oxide are also investigated depending on four channel engineering. As a channel engineering, gas treatment, coatings of thin polymer layer, and chemical surface modification using small molecules were carried out. After channel engineering, the performance of device as well as interface trap density calculated by conductance method are remarkably improved. It is found that the reduced interface trap density is closely related to decreasing the sub-threshold swing and improving the mobility. Particularly, we also found that performance of device such as mobility, subthreshold swing, and interface trap density after gas same is comparable to those of OTS.

K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid beta-protein precursor genes and neuronal death in rat hippocampus.

PubMed Central

Heurteaux, C; Bertaina, V; Widmann, C; Lazdunski, M

1993-01-01

Transient global forebrain ischemia induces in rat brain a large increase of expression of the immediate early genes c-fos and c-jun and of the mRNAs for the 70-kDa heat-shock protein and for the form of the amyloid beta-protein precursor including the Kunitz-type protease-inhibitor domain. At 24 hr after ischemia, this increased expression is particularly observed in regions that are vulnerable to the deleterious effects of ischemia, such as pyramidal cells of the CA1 field in the hippocampus. In an attempt to find conditions which prevent the deleterious effects of ischemia, representatives of three different classes of K+ channel openers, (-)-cromakalim, nicorandil, and pinacidil, were administered both before ischemia and during the reperfusion period. This treatment totally blocked the ischemia-induced expression of the different genes. In addition it markedly protected neuronal cells against degeneration. The mechanism of the neuroprotective effects involves the opening of ATP-sensitive K+ channels since glipizide, a specific blocker of that type of channel, abolished the beneficial effects of K+ channel openers. The various classes of K+ channel openers seem to deserve attention as potential drugs for cerebral ischemia. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8415718

Two-channel Kondo effect and renormalization flow with macroscopic quantum charge states.

PubMed

Iftikhar, Z; Jezouin, S; Anthore, A; Gennser, U; Parmentier, F D; Cavanna, A; Pierre, F

2015-10-08

Many-body correlations and macroscopic quantum behaviours are fascinating condensed matter problems. A powerful test-bed for the many-body concepts and methods is the Kondo effect, which entails the coupling of a quantum impurity to a continuum of states. It is central in highly correlated systems and can be explored with tunable nanostructures. Although Kondo physics is usually associated with the hybridization of itinerant electrons with microscopic magnetic moments, theory predicts that it can arise whenever degenerate quantum states are coupled to a continuum. Here we demonstrate the previously elusive 'charge' Kondo effect in a hybrid metal-semiconductor implementation of a single-electron transistor, with a quantum pseudospin of 1/2 constituted by two degenerate macroscopic charge states of a metallic island. In contrast to other Kondo nanostructures, each conduction channel connecting the island to an electrode constitutes a distinct and fully tunable Kondo channel, thereby providing unprecedented access to the two-channel Kondo effect and a clear path to multi-channel Kondo physics. Using a weakly coupled probe, we find the renormalization flow, as temperature is reduced, of two Kondo channels competing to screen the charge pseudospin. This provides a direct view of how the predicted quantum phase transition develops across the symmetric quantum critical point. Detuning the pseudospin away from degeneracy, we demonstrate, on a fully characterized device, quantitative agreement with the predictions for the finite-temperature crossover from quantum criticality.

Novel pharmacological targets for the rhythm control management of atrial fibrillation.

PubMed

Burashnikov, Alexander; Antzelevitch, Charles

2011-12-01

Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Development of safe and effective pharmacological treatments for AF is one of the greatest unmet medical needs facing our society. In spite of significant progress in non-pharmacological AF treatments (largely due to the use of catheter ablation techniques), anti-arrhythmic agents (AADs) remain first line therapy for rhythm control management of AF for most AF patients. When considering efficacy, safety and tolerability, currently available AADs for rhythm control of AF are less than optimal. Ion channel inhibition remains the principal strategy for termination of AF and prevention of its recurrence. Practical clinical experience indicates that multi-ion channel blockers are generally more optimal for rhythm control of AF compared to ion channel-selective blockers. Recent studies suggest that atrial-selective sodium channel block can lead to safe and effective suppression of AF and that concurrent inhibition of potassium ion channels may potentiate this effect. An important limitation of the ion channel block approach for AF treatment is that non-electrical factors (largely structural remodeling) may importantly determine the generation of AF, so that "upstream therapy", aimed at preventing or reversing structural remodeling, may be required for effective rhythm control management. This review focuses on novel pharmacological targets for the rhythm control management of AF. Copyright © 2011 Elsevier Inc. All rights reserved.

In-service communication channel sensing based on reflectometry for TWDM-PON systems

NASA Astrophysics Data System (ADS)

Iida, Daisuke; Kuwano, Shigeru; Terada, Jun

2014-05-01

Many base stations are accommodated in TWDM-PON based mobile backhaul and fronthaul networks for future radio access, and failed connections in an optical network unit (ONU) wavelength channel severely degrade system performance. A cost effective in-service ONU wavelength channel monitor is essential to ensure proper system operation without failed connections. To address this issue we propose a reflectometry-based remote sensing method that provides wavelength channel information with the optical line terminal (OLT)-ONU distance. The method realizes real-time monitoring of ONU wavelength channels without signal quality degradation. Experimental results show it achieves wavelength channel distinction with high distance resolution.

Monte Carlo simulation of a noisy quantum channel with memory.

PubMed

Akhalwaya, Ismail; Moodley, Mervlyn; Petruccione, Francesco

2015-10-01

The classical capacity of quantum channels is well understood for channels with uncorrelated noise. For the case of correlated noise, however, there are still open questions. We calculate the classical capacity of a forgetful channel constructed by Markov switching between two depolarizing channels. Techniques have previously been applied to approximate the output entropy of this channel and thus its capacity. In this paper, we use a Metropolis-Hastings Monte Carlo approach to numerically calculate the entropy. The algorithm is implemented in parallel and its performance is studied and optimized. The effects of memory on the capacity are explored and previous results are confirmed to higher precision.

Saturation of conductance in single ion channels: the blocking effect of the near reaction field.

PubMed

Nadler, Boaz; Schuss, Zeev; Hollerbach, Uwe; Eisenberg, R S

2004-11-01

The ionic current flowing through a protein channel in the membrane of a biological cell depends on the concentration of the permeant ion, as well as on many other variables. As the concentration increases, the rate of arrival of bath ions to the channel's entrance increases, and typically so does the net current. This concentration dependence is part of traditional diffusion and rate models that predict Michaelis-Menten current-concentration relations for a single ion channel. Such models, however, neglect other effects of bath concentrations on the net current. The net current depends not only on the entrance rate of ions into the channel, but also on forces acting on ions inside the channel. These forces, in turn, depend not only on the applied potential and charge distribution of the channel, but also on the long-range Coulombic interactions with the surrounding bath ions. In this paper, we study the effects of bath concentrations on the average force on an ion in a single ion channel. We show that the force of the reaction field on a discrete ion inside a channel embedded in an uncharged lipid membrane contains a blocking (shielding) term that is proportional to the square root of the ionic bath concentration. We then show that different blocking strengths yield different behavior of the current-concentration and conductance-concentration curves. Our theory shows that at low concentrations, when the blocking force is weak, conductance grows linearly with concentration, as in traditional models, e.g., Michaelis-Menten formulations. As the concentration increases to a range of moderate shielding, conductance grows as the square root of concentration, whereas at high concentrations, with high shielding, conductance may actually decrease with increasing concentrations: the conductance-concentration curve can invert. Therefore, electrostatic interactions between bath ions and the single ion inside the channel can explain the different regimes of conductance-concentration relations observed in experiments.

Ferritin ion channel disorder inhibits Fe(II)/O2 reactivity at distant sites.

PubMed

Tosha, Takehiko; Behera, Rabindra K; Theil, Elizabeth C

2012-11-05

Ferritins, a complex, mineralized, protein nanocage family essential for life, provide iron concentrates and oxidant protection. Protein-based ion channels and Fe(II)/O(2) catalysis initiate conversion of thousands of Fe atoms to caged, ferritin Fe(2)O(3)·H(2)O minerals. The ion channels consist of six helical segments, contributed by 3 of 12 or 24 polypeptide subunits, around the 3-fold cage axes. The channel structure guides entering Fe(II) ions toward multiple, catalytic, diiron sites buried inside ferritin protein helices, ~20 Å away from channel internal exits. The catalytic product, Fe(III)-O(H)-Fe(III), is a mineral precursor; mineral nucleation begins inside the protein cage with mineral growth in the central protein cavity (5-8 nm diameter). Amino acid substitutions that changed ionic or hydrophobic channel interactions R72D, D122R, and L134P increased ion channel structural disorder (protein crystallographic analyses) and increased Fe(II) exit [chelated Fe(II) after ferric mineral reduction/dissolution]. Since substitutions of some channel carboxylate residues diminished ferritin catalysis with no effect on Fe(II) exit, such as E130A and D127A, we investigated catalysis in ferritins with altered Fe(II) exit, R72D, D122R and L134P. The results indicate that simply changing the ionic properties of the channels, as in the R72D variant, need not change the forward catalytic rate. However, both D122R and L134P, which had dramatic effects on ferritin catalysis, also caused larger effects on channel structure and order, contrasting with R72D. All three amino acid substitutions, however, decreased the stability of the catalytic intermediate, diferric peroxo, even though overall ferritin cage structure is very stable, resisting 80 °C and 6 M urea. The localized structural changes in ferritin subdomains that affect ferritin function over long distances illustrate new properties of the protein cage in natural ferritin function and for applied ferritin uses.

Crowd counting via region based multi-channel convolution neural network

NASA Astrophysics Data System (ADS)

Cao, Xiaoguang; Gao, Siqi; Bai, Xiangzhi

2017-11-01

This paper proposed a novel region based multi-channel convolution neural network architecture for crowd counting. In order to effectively solve the perspective distortion in crowd datasets with a great diversity of scales, this work combines the main channel and three branch channels. These channels extract both the global and region features. And the results are used to estimate density map. Moreover, kernels with ladder-shaped sizes are designed across all the branch channels, which generate adaptive region features. Also, branch channels use relatively deep and shallow network to achieve more accurate detector. By using these strategies, the proposed architecture achieves state-of-the-art performance on ShanghaiTech datasets and competitive performance on UCF_CC_50 datasets.

Effects of WDRC release time and number of channels on output SNR and speech recognition

PubMed Central

Alexander, Joshua M.; Masterson, Katie

2014-01-01

Objectives The purpose of this study was to investigate the joint effects that wide dynamic range compression (WDRC) release time (RT) and number of channels have on recognition of sentences in the presence of steady and modulated maskers at different signal-to-noise ratios (SNRs). How the different combinations of WDRC parameters affect output SNR and the role this plays in the observed findings was also investigated. Design Twenty-four listeners with mild to moderate sensorineural hearing loss identified sentences mixed with steady or modulated maskers at 3 SNRs (−5, 0, +5 dB) that had been processed using a hearing aid simulator with 6 combinations of RT (40 and 640 ms) and number of channels (4, 8, and 16). Compression parameters were set using the Desired Sensation Level v5.0a prescriptive fitting method. For each condition, amplified speech and masker levels and the resultant long-term output SNR were measured. Results Speech recognition with WDRC depended on the combination of RT and number of channels, with the greatest effects observed at 0 dB input SNR, in which mean speech recognition scores varied by 10–12% across WDRC manipulations. Overall, effect sizes were generally small. Across both masker types and the three SNRs tested, the best speech recognition was obtained with 8 channels, regardless of RT. Increased speech levels, which favor audibility, were associated with the short RT and with an increase in the number of channels. These same conditions also increased masker levels by an even greater amount, for a net decrease in the long-term output SNR. Changes in long-term SNR across WDRC conditions were found to be strongly associated with changes in the temporal envelope shape as quantified by the Envelope Difference Index, however, neither of these factors fully explained the observed differences in speech recognition. Conclusions A primary finding of this study was that the number of channels had a modest effect when analyzed at each level of RT, with results suggesting that selecting 8 channels for a given RT might be the safest choice. Effects were smaller for RT, with results suggesting that short RT was slightly better when only 4 channels were used and that long RT was better when 16 channels were used. Individual differences in how listeners were influenced by audibility, output SNR, temporal distortion, and spectral distortion may have contributed to the size of the effects found in this study. Because only general suppositions could made for how each of these factors may have influenced the overall results of this study, future research would benefit from exploring the predictive value of these and other factors in selecting the processing parameters that maximize speech recognition for individuals. PMID:25470368

Novel ion channel targets in atrial fibrillation.

PubMed

Hancox, Jules C; James, Andrew F; Marrion, Neil V; Zhang, Henggui; Thomas, Dierk

2016-08-01

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodeling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Data from animal models support atrial-ventricular differences in INa kinetics and also suggest atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and ventricular action and resting potentials. SK and K2P channels (particularly K2P 3.1) offer potentially attractive atrial-selective targets. Work is needed to identify the underlying basis of SK current that contributes to (patho)physiological atrial repolarization and settings in which SK inhibition is anti- versus pro-arrhythmic. Although K2P3.1 appears to be a promising target with comparatively selective drugs for experimental use, a lack of selective pharmacology hinders evaluation of other K2P channels as potential atrial-selective targets.

GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner

PubMed Central

Kotecki, Lydia; Hearing, Matthew; McCall, Nora M.; Marron Fernandez de Velasco, Ezequiel; Pravetoni, Marco; Arora, Devinder; Victoria, Nicole C.; Munoz, Michaelanne B.; Xia, Zhilian; Slesinger, Paul A.; Weaver, C. David

2015-01-01

G-protein-gated inwardly rectifying K+ (GIRK/Kir3) channel activation underlies key physiological effects of opioids, including analgesia and dependence. GIRK channel activation has also been implicated in the opioid-induced inhibition of midbrain GABA neurons and consequent disinhibition of dopamine (DA) neurons in the ventral tegmental area (VTA). Drug-induced disinhibition of VTA DA neurons has been linked to reward-related behaviors and underlies opioid-induced motor activation. Here, we demonstrate that mouse VTA GABA neurons express a GIRK channel formed by GIRK1 and GIRK2 subunits. Nevertheless, neither constitutive genetic ablation of Girk1 or Girk2, nor the selective ablation of GIRK channels in GABA neurons, diminished morphine-induced motor activity in mice. Moreover, direct activation of GIRK channels in midbrain GABA neurons did not enhance motor activity. In contrast, genetic manipulations that selectively enhanced or suppressed GIRK channel function in midbrain DA neurons correlated with decreased and increased sensitivity, respectively, to the motor-stimulatory effect of systemic morphine. Collectively, these data support the contention that the unique GIRK channel subtype in VTA DA neurons, the GIRK2/GIRK3 heteromer, regulates the sensitivity of the mouse mesolimbic DA system to drugs with addictive potential. PMID:25948263

Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells.

PubMed

Jiang, Bo; Cao, Kun; Wang, Rui

2004-12-15

Protopine is an isoquinoline alkaloid purified from Corydalis tubers and other families of medicinal plants. The purpose of the present study was to investigate the effects of protopine on K(ATP) channels and big conductance (BKCa) channels. Protopine concentration-dependently inhibited K(ATP) channel currents in human embryonic kidney cells (HEK-293) which were cotransfected with Kir6.1 and sulfonylurea receptor 1 (SUR1) subunits, but not that with Kir6.1 cDNA transfection alone. At 25 muM, protopine reversibly decreased Kir6.1/SUR1 currents densities from -17.4+/-3 to -13.2+/-2.4 pA/pF at -60 mV (n=5, P<0.05). The heterologously expressed mSlo-encoded BK(Ca) channel currents in HEK-293 cells were not affected by protopine (25 muM), although iberiotoxin (100 nM) significantly inhibited the expressed BK(Ca) currents (n=5, P<0.05). In summary, protopine selectively inhibited K(ATP) channels by targeting on SUR1 subunit. This discovery may help design specific agents to selectively modulate the function of Kir6.1/SUR1 channel complex and facilitate the understanding of the structure-function relationship of specific subtype of K(ATP) channels.

Pharmacological enhancement of calcium-activated potassium channel function reduces the effects of repeated stress on fear memory

PubMed Central

Atchley, Derek; Hankosky, Emily R.; Gasparotto, Kaylyn; Rosenkranz, J. Amiel

2012-01-01

Repeated stress impacts emotion, and can induce mood and anxiety disorders. These disorders are characterized by imbalance of emotional responses. The amygdala is fundamental in expression of emotion, and is hyperactive in many patients with mood or anxiety disorders. Stress also leads to hyperactivity of the amygdala in humans. In rodent studies, repeated stress causes hyperactivity of the amygdala, and increases fear conditioning behavior that is mediated by the basolateral amygdala (BLA). Calcium-activated potassium (KCa) channels regulate BLA neuronal activity, and evidence suggests reduced small conductance KCa (SK) channel function in male rats exposed to repeated stress. Pharmacological enhancement of SK channels reverses the BLA neuronal hyperexcitability caused by repeated stress. However, it is not known if pharmacological targeting of SK channels can repair the effects of repeated stress on amygdala-dependent behaviors. The purpose of this study was to test whether enhancement of SK channel function reverses the effects of repeated restraint on BLA-dependent auditory fear conditioning. We found that repeated restraint stress increased the expression of cued conditioned fear in male rats. However, 1-EBIO (1 or 10 mg/kg) or CyPPA (5 mg/kg) administered 30 minutes prior to testing of fear expression brought conditioned freezing to control levels, with little impact on fear expression in control handled rats. These results demonstrate that enhancement of SK channel function can reduce the abnormalities of BLA-dependent fear memory caused by repeated stress. Furthermore, this indicates that pharmacological targeting of SK channels may provide a novel target for alleviation of psychiatric symptoms associated with amygdala hyperactivity. PMID:22487247

Channel-planform evolution in four rivers of Olympic National Park, Washington, U.S.A.: The roles of physical drivers and trophic cascades

USGS Publications Warehouse

East, Amy E.; Jenkins, Kurt J.; Happe, Patricia J.; Bountry, Jennifer A.; Beechie, Timothy J.; Mastin, Mark C.; Sankey, Joel B.; Randle, Timothy J.

2017-01-01

Identifying the relative contributions of physical and ecological processes to channel evolution remains a substantial challenge in fluvial geomorphology. We use a 74-year aerial photographic record of the Hoh, Queets, Quinault, and Elwha Rivers, Olympic National Park, Washington, U.S.A., to investigate whether physical or trophic-cascade-driven ecological factors—excessive elk impacts after wolves were extirpated a century ago—are the dominant controls on channel planform of these gravel-bed rivers. We find that channel width and braiding show strong relationships with recent flood history. All four rivers have widened significantly in recent decades, consistent with increased flood activity since the 1970s. Channel planform also reflects sediment-supply changes, evident from landslide response on the Elwha River. We surmise that the Hoh River, which shows a multi-decadal trend toward greater braiding, is adjusting to increased sediment supply associated with rapid glacial retreat. In this sediment-routing system with high connectivity, such climate-driven signals appear to propagate downstream without being buffered substantially by sediment storage. Legacy effects of anthropogenic modification likely also affect the Quinault River planform. We infer no correspondence between channel geomorphic evolution and elk abundance, suggesting that trophic-cascade effects in this setting are subsidiary to physical controls on channel morphology. Our findings differ from previous interpretations of Olympic National Park fluvial dynamics and contrast with the classic example of Yellowstone National Park, where legacy effects of elk overuse are apparent in channel morphology; we attribute these differences to hydrologic regime and large-wood availability.

Sodium channel blockers as therapeutic target for treating epilepsy: recent updates.

PubMed

Zuliani, Valentina; Fantini, Marco; Rivara, Mirko

2012-01-01

The voltage-gated sodium channels (VGSCs) are a family of membrane proteins forming a pore, through which they selectively conduct sodium ions inward and outward cell's plasma membranes in response to variations of membrane potentials, playing a fundamental role in controlling cellular excitability. Growing evidences suggest that abnormal VGSCs are involved in the pathophysiology of both acquired and inherited epilepsy. Approximately two dozen drugs are currently marketed for the treatment of epilepsy and most of them act as sodium channel blockers, preventing the return of the channels to the active state by stabilizing the inactive form. Despite the many drugs on the market, 30% of patients continue to experience seizures even in the presence of optimal doses of AEDs, while others continue to suffer from medication induced side effects. Thus, there is a great need to continue the search for new AEDs that are not only more effective, but also have a better side effects profile. For this reason, many efforts have been made in the recent years to identify new sodium channel blockers for the treatment of epilepsy. These studies have led to different classes of compounds, characterized by a great structural diversity. The aim of this review is to provide an introduction on the structure and function of the sodium channels, followed by a brief historical perspective on the sodium channel blockers in use as anticonvulsant drugs. Moreover, it will focus on the medicinal chemistry of the sodium channel blockers recently published (2008-2011) and the drug design/molecular modeling studies related to the receptor.

Toxic effects of environmental rare earth elements on delayed outward potassium channels and their mechanisms from a microscopic perspective.

PubMed

Wang, Lihong; He, Jingfang; Xia, Ao; Cheng, Mengzhu; Yang, Qing; Du, Chunlei; Wei, Haiyan; Huang, Xiaohua; Zhou, Qing

2017-08-01

The wide applications cause a large amount of rare earth elements (REEs) to be released into the environment, and ultimately into the human body through food chain. Toxic effects of REEs on humans have been extensively studied, but their toxic effects and binding targets in cells are not understood. Delayed outward potassium channels (K + channels) are good targets for exogenous substances or clinical drugs. To evaluate cellular toxicities of REEs and clarify toxic mechanisms, the toxicities of REEs on the K + channel and their structural basis were investigated. The results showed that delayed outward potassium channels on the plasma membrane are the targets of REEs acting on living organisms, and the changes in the thermodynamic and kinetic characteristics of the K + channel are the reasons of diseases induced by REEs. Two types of REEs, a light REE La 3+ and a heavy REE Tb 3+ , displayed different intensity of toxicities on the K + channel, in which the toxicity of Tb 3+ was stronger than that of La 3+ . More interestingly, in comparison with that of heavy metal Cd 2+ , the cytotoxicities of the light and heavy REEs showed discriminative differences, and the cytotoxicity of Tb 3+ was higher than that of Cd 2+ , while the cytotoxicity of La 3+ was lower than that of Cd 2+ . These different cytotoxicities of La 3+ , Tb 3+ and Cd 2+ on human resulted from the varying binding abilities of the metals to this channel protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

PubMed Central

Flores, Pedro L.; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

2017-01-01

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels. PMID:28672825

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes.

PubMed

Flores, Pedro L; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

2017-06-25

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

A III-V nanowire channel on silicon for high-performance vertical transistors.

PubMed

Tomioka, Katsuhiro; Yoshimura, Masatoshi; Fukui, Takashi

2012-08-09

Silicon transistors are expected to have new gate architectures, channel materials and switching mechanisms in ten years' time. The trend in transistor scaling has already led to a change in gate structure from two dimensions to three, used in fin field-effect transistors, to avoid problems inherent in miniaturization such as high off-state leakage current and the short-channel effect. At present, planar and fin architectures using III-V materials, specifically InGaAs, are being explored as alternative fast channels on silicon because of their high electron mobility and high-quality interface with gate dielectrics. The idea of surrounding-gate transistors, in which the gate is wrapped around a nanowire channel to provide the best possible electrostatic gate control, using InGaAs channels on silicon, however, has been less well investigated because of difficulties in integrating free-standing InGaAs nanostructures on silicon. Here we report the position-controlled growth of vertical InGaAs nanowires on silicon without any buffering technique and demonstrate surrounding-gate transistors using InGaAs nanowires and InGaAs/InP/InAlAs/InGaAs core-multishell nanowires as channels. Surrounding-gate transistors using core-multishell nanowire channels with a six-sided, high-electron-mobility transistor structure greatly enhance the on-state current and transconductance while keeping good gate controllability. These devices provide a route to making vertically oriented transistors for the next generation of field-effect transistors and may be useful as building blocks for wireless networks on silicon platforms.

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age

PubMed Central

Oiki, Shigetoshi

2015-01-01

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the ‘frozen’ crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. PMID:25833254

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age.

PubMed

Oiki, Shigetoshi

2015-06-15

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

75 FR 13236 - Television Broadcasting Services; Oklahoma City, OK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

...] Television Broadcasting Services; Oklahoma City, OK AGENCY: Federal Communications Commission. ACTION: Final... licensee of KWTV-DT, channel 9, Oklahoma City, requesting the substitution of channel 39 for channel 9 at Oklahoma City. DATES: This rule is effective March 19, 2010. FOR FURTHER INFORMATION CONTACT: Adrienne Y...

Assessment of the effects of regional channel stability and sediment transport on roadway hydraulic structures : final report.

DOT National Transportation Integrated Search

2014-06-01

Rivers and streams evolve all the time. As a result, no stream channel is absolutely stable. Channels evolve at various speeds both vertically (degradation/aggradation) and horizontally (meander : migration). They also respond to man-made changes ran...

Simulation of the effect of a magnetically insulated anode on a low-power cylindrical Hall thruster

NASA Astrophysics Data System (ADS)

Yongjie, DING; Hong, LI; Boyang, JIA; Peng, LI; Liqiu, WEI; Yu, XU; Wuji, PENG; Hezhi, SUN; Yong, CAO; Daren, YU

2018-03-01

The intersection point of the characteristic magnetic field line (CMFL) crossing the anode boundary with the discharge channel wall, and its influence on thruster performance and the energy and flux of ions bombarding the channel wall, have been studied numerically. The simulation results demonstrate that with the increase in distance from the crossover point of the CMFL with the channel wall to the bottom of the thruster channel, the ionization rate in the discharge channel gradually increases; meanwhile, the ion energy and ion current density bombarding the channel wall decreases. When the point of the CMFL with the channel wall is at the channel outlet, the thrust, specific impulse, and efficiency are at a maximum, while the ion energy and ion current density bombarding the channel wall are at a minimum. Therefore, to improve the performance and lifetime of the thruster, it is important to control the point of intersection of the CMFL with the channel wall.

Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma.

PubMed

Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

2016-01-01

Background : Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods : Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results : Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion : The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone.

Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma

PubMed Central

Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

2016-01-01

Background: Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods: Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results: Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion: The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone. PMID:27471568

Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr.

1991-06-01

We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) inducedmore » uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.« less

Analysis of Hanle-effect signals observed in Si-channel spin accumulation devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takamura, Yota, E-mail: takamura@spin.pe.titech.ac.jp; Department of Physical Electronics, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8552; Akushichi, Taiju

2014-05-07

We reexamined curve-fitting analysis for spin-accumulation signals observed in Si-channel spin-accumulation devices, employing widely-used Lorentz functions and a new formula developed from the spin diffusion equation. A Si-channel spin-accumulation device with a high quality ferromagnetic spin injector was fabricated, and its observed spin-accumulation signals were verified. Experimentally obtained Hanle-effect signals for spin accumulation were not able to be fitted by a single Lorentz function and were reproduced by the newly developed formula. Our developed formula can represent spin-accumulation signals and thus analyze Hanle-effect signals.

Compact and cost-effective multi-channel optical spectrometer for fine FBG sensing in IoT technology

NASA Astrophysics Data System (ADS)

Konishi, Tsuyoshi; Yamasaki, Yu

2018-02-01

Optical fiber sensor networks have attracted much attention in IoT technology and a fiber Bragg grating is one of key sensor devices there because of their advantages in a high affinity for optical fiber networks, compactness, immunity to electromagnetic interference and so on. Nevertheless, its sensitivity is not always satisfactory so as to be usable together with widespread cost-effective multi-channel spectrometers. In this paper, we introduce a new cost-effective approach for a portable multi-channel spectrometer with high spectral resolution and demonstrates some preliminary experimental results for fine FBG sensing.

Propylparaben reduces the excitability of hippocampal neurons by blocking sodium channels.

PubMed

Lara-Valderrábano, Leonardo; Rocha, Luisa; Galván, Emilio J

2016-12-01

Propylparaben (PPB) is an antimicrobial preservative widely used in food, cosmetics, and pharmaceutics. Virtual screening methodologies predicted anticonvulsant activity of PPB that was confirmed in vivo. Thus, we explored the effects of PPB on the excitability of hippocampal neurons by using standard patch clamp techniques. Bath perfusion of PPB reduced the fast-inactivating sodium current (I Na ) amplitude, causing a hyperpolarizing shift in the inactivation curve of the I Na, and markedly delayed the sodium channel recovery from the inactivation state. Also, PPB effectively suppressed the riluzole-sensitive, persistent sodium current (I NaP ). PPB perfusion also modified the action potential kinetics, and higher concentrations of PPB suppressed the spike activity. Nevertheless, the modulatory effects of PPB did not occur when PPB was internally applied by whole-cell dialysis. These results indicate that PPB reduces the excitability of CA1 pyramidal neurons by modulating voltage-dependent sodium channels. The mechanistic basis of this effect is a marked delay in the recovery from inactivation state of the voltage-sensitive sodium channels. Our results indicate that similar to local anesthetics and anticonvulsant drugs that act on sodium channels, PPB acts in a use-dependent manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Two-channel Kondo physics from arsenic bond oscillations in zirconium arsenide selenide

NASA Astrophysics Data System (ADS)

Kirchner, Stefan; Cichorek, Tomasz; Bochenek, L.; Schmidt, Marcus; Niewa, Rainer; Czulucki, A.; Auffermann, G.; Steglich, Frank; Kniep, Ruediger

2015-03-01

The two-channel Kondo effect is a fascinating but extremely fragile many-body state that has been theoretically discussed extensively. we address metallic compounds of a specific (PbFCl) structure for which a - AT 1 / 2 term to ρ (T) is frequently observed, in line with the two-channel Kondo effect. The origin of this anomalous behavior has remained enigmatic since here, solely the interaction between electrons may account for this behavior, and the two-channel Kondo state is not expected to occur. By combining chemical and structural investigations with various physical property measurements we show that the magnetic field-independent - AT 1 / 2 term to the low-T resistivity observed over two decades in ZrAsxSey with 1.90 <= x + y <= 1.99 originates from vacancies in the layer exclusively built up by As. Furthermore, we can trace back the two-channel Kondo effect in this material to a dynamic Jahn-Teller effect operating at these vacancies. All physical properties of the investigated compounds support this conclusion. Our findings will be relevant also for other metallic systems with pnictogen-pnictogen bondings, e.g., cage-forming compounds like the skutterudites.

Theoretical and experimental studies of turbo product code with time diversity in free space optical communication.

PubMed

Han, Yaoqiang; Dang, Anhong; Ren, Yongxiong; Tang, Junxiong; Guo, Hong

2010-12-20

In free space optical communication (FSOC) systems, channel fading caused by atmospheric turbulence degrades the system performance seriously. However, channel coding combined with diversity techniques can be exploited to mitigate channel fading. In this paper, based on the experimental study of the channel fading effects, we propose to use turbo product code (TPC) as the channel coding scheme, which features good resistance to burst errors and no error floor. However, only channel coding cannot cope with burst errors caused by channel fading, interleaving is also used. We investigate the efficiency of interleaving for different interleaving depths, and then the optimum interleaving depth for TPC is also determined. Finally, an experimental study of TPC with interleaving is demonstrated, and we show that TPC with interleaving can significantly mitigate channel fading in FSOC systems.

Origin of the performances degradation of two-dimensional-based metal-oxide-semiconductor field effect transistors in the sub-10 nm regime: A first-principles study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Anh Khoa Augustin; IMEC, 75 Kapeldreef, B-3001 Leuven; Pourtois, Geoffrey

2016-01-25

The impact of the scaling of the channel length on the performances of metal-oxide-semiconductor field effect transistors, based on two-dimensional (2D) channel materials, is theoretically investigated, using density functional theory combined with the non-equilibrium Green's function method. It is found that the scaling of the channel length below 10 nm leads to strong device performance degradations. Our simulations reveal that this degradation is essentially due to the tunneling current flowing between the source and the drain in these aggressively scaled devices. It is shown that this electron tunneling process is modulated by the effective mass of the 2D channel material, andmore » sets the limit of the scaling in future transistor designs.« less

Effects of Land-Cover Change, Floods, and Stream Position on Geomorphic Processes - Implications for Restoration Activities

USGS Publications Warehouse

Fitzpatrick, F.A.; ,

2001-01-01

A geomorphic study for North Fish Creek, a northern Wisconsin tributary to Lake Superior was analyzed to determine the hydrologic and geomorphic changes caused by clear-cut logging and agricultural activity. Discharge magnitude estimated with HEC-2 for full-channel capacities indicate that modern full-channel discharges are about twice as large as pre-1946 full-channel discharges. Flood-plain deposition rates were high along the transitional main stem after European settlement. Restoration and protection activities would be most effective if focused on watershed practices to reduce runoff and on channel restoration that reduce buff and bank erosion in the upper and transitional main stems.

Effectiveness of public health messaging and communication channels during smoke events: A rapid systematic review.

PubMed

Fish, Jennifer A; Peters, Micah D J; Ramsey, Imogen; Sharplin, Greg; Corsini, Nadia; Eckert, Marion

2017-05-15

Exposure to smoke emitted from wildfire and planned burns (i.e., smoke events) has been associated with numerous negative health outcomes, including respiratory symptoms and conditions. This rapid review investigates recent evidence (post-2009) regarding the effectiveness of public health messaging during smoke events. The objectives were to determine the effectiveness of various communication channels used and public health messages disseminated during smoke events, for general and at-risk populations. A search of 12 databases and grey literature yielded 1775 unique articles, of which 10 were included in this review. Principal results were: 1) Smoke-related public health messages are communicated via a variety of channels, but limited evidence is available regarding their effectiveness for the general public or at-risk groups. 2) Messages that use simple language are more commonly recalled, understood, and complied with. Compliance differs according to socio-demographic characteristics. 3) At-risk groups may be advised to stay indoors before the general population, in order to protect the most vulnerable people in a community. The research included in this review was observational and predominantly descriptive, and is therefore unable to sufficiently answer questions regarding effectiveness. Experimental research, as well as evaluations, are required to examine the effectiveness of modern communication channels, channels to reach at-risk groups, and the 'stay indoors' message. Copyright © 2017 Elsevier Ltd. All rights reserved.

Marine Toxins Targeting Ion Channels

PubMed Central

Arias, Hugo R.

2006-01-01

This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs), as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs), are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV), Ca2+ (CaV), and K+ (KV) channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR), and the ATP-activated (P2XnR) receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+), whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−). In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers) of ion channel functions to treat or to alleviate a specific ion channel-linked disease (e.g., channelopaties).

Single-channel kinetics of BK (Slo1) channels

PubMed Central

Geng, Yanyan; Magleby, Karl L.

2014-01-01

Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1) channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM) models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD) attached to four surrounding transmembrane voltage sensing domains (VSD) and a large intracellular cytosolic domain (CTD), also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with five closed states on the upper tier and five open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states) to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states. PMID:25653620

Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling.

PubMed

Ogihara, Takuo; Kano, Takashi; Kakinuma, Chihaya

2009-01-01

Currently, a new type of calcium channel blockers, which can inhibit not only L-type calcium channels abundantly expressed in vascular smooth muscles, but also N-type calcium channels that abound in the sympathetic nerve endings, have been developed. In this study, analysis on a like-for-like basis of the L- and N-type calcium channel-inhibitory activity of typical dihydropyridine-type calcium-channel blockers (DHPs) was performed. Moreover, to understand the differences of N-type calcium channel inhibition among DHPs, the binding of DHPs to the channel was investigated by means of hypothetical three-dimensional pharmacophore modeling using multiple calculated low-energy conformers of the DHPs. All of the tested compounds, i.e. cilnidipine (CAS 132203-70-4), efonidipine (CAS 111011-76-8), amlodipine (CAS 111470-99-6), benidipine (CAS 85387-35-5), azelnidipine (CAS 123524-52-7) and nifedipine (CAS 21829-25-4), potently inhibited the L-type calcium channel, whereas only cilnidipine inhibited the N-type calcium channel (IC50 value: 51.2 nM). A virtual three-dimensional structure of the N-type calcium channel was generated by using the structure of the peptide omega-conotoxin GVIA, a standard inhibitor of the channel, and cilnidipine was found to fit well into this pharmacophore model. Lipophilic potential maps of omega-conotoxin GVIA and cilnidipine supported this finding. Conformational overlay of cilnidipine and the other DHPs indicated that amlodipine and nifedipine were not compatible with the pharmacophore model because they did not contain an aromatic ring that was functionally equivalent to Tyr13 of omega-conotoxin GVIA. Azelnidipine, benidipine, and efonidipine, which have this type of aromatic ring, were not positively identified due to intrusions into the excluded volume. Estimation of virtual three-dimensional structures of proteins, such as ion channels, by using standard substrates and/or inhibitors may be a useful method to explore the mechanisms of pharmacological and toxicological effects of substrates and/or inhibitors, and to discover new drugs.

Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels.

PubMed Central

Brown, R L; Snow, S D; Haley, T L

1998-01-01

In the visual and olfactory systems, cyclic nucleotide-gated (CNG) ion channels convert stimulus-induced changes in the internal concentrations of cGMP and cAMP into changes in membrane potential. Although it is known that significant activation of these channels requires the binding of three or more molecules of ligand, the detailed molecular mechanism remains obscure. We have probed the structural changes that occur during channel activation by using sulfhydryl-reactive methanethiosulfonate (MTS) reagents and N-ethylmaleimide (NEM). When expressed in Xenopus oocytes, the alpha-subunit of the bovine retinal channel forms homomultimeric channels that are activated by cGMP with a K1/2 of approximately 100 microM. Cyclic AMP, on the other hand, is a very poor activator; a saturating concentration elicits only 1% of the maximum current produced by cGMP. Treatment of excised patches with MTS-ethyltrimethylamine (MTSET) or NEM dramatically potentiated the channel's response to both cyclic nucleotides. After MTSET treatment, the dose-response relation for cGMP was shifted by over two orders of magnitude to lower concentrations. The effect on channel activation by cAMP was even more striking. After modification, the channels were fully activated by cAMP with a K1/2 of approximately 60 microM. This potentiation was abolished by conversion of Cys481 to a nonreactive alanine residue. Potentiation occurred more rapidly in the presence of saturating cGMP, indicating that this region of the channel is more accessible when the channel is open. Cys481 is located in a linker region between the transmembrane and cGMP-binding domains of the channel. These results suggest that this region of the channel undergoes significant movement during the activation process and is critical for coupling ligand binding to pore opening. Potentiation, however, is not mediated by the recently reported interaction between the amino- and carboxy-terminal regions of the alpha-subunit. Deletion of the entire amino-terminal domain had little effect on potentiation by MTSET. PMID:9675183

Destiny-yield relationship for channel catfish reared in a biofloc technology production system

USDA-ARS?s Scientific Manuscript database

The effect of stocking density on yield of stocker channel catfish and water quality in a biofloc technology production system was studied in this completely randomized design experiment. Fingerling channel catfish (Ictalurus punctatus; 48.0 g/fish, 17.8 cm/fish) were stocked into nine continuously ...

Effects of DO cencentration on growth of juvenile channel catfish

USDA-ARS?s Scientific Manuscript database

Dissolved oxygen (DO) concentration has a major impact on feed consumption of channel catfish when raised in ponds; as DO concentration falls below 3.0 mg/L at night, feed consumption is negatively impacted. Channel catfish fry may experience a wide range of oxygen conditions in the hatchery depend...

Technique minimizes the effects of dropouts on telemetry records

NASA Technical Reports Server (NTRS)

Anderson, T. O.; Hurd, W. J.

1972-01-01

Recorder deficiencies are minimized by using two-channel system to prepare two tapes, each having noise, wow and flutter, and dropout characteristics of channel on which it was made. Processing tapes by computer and combining signals from two channels produce single tape free of dropouts caused by recording process.

Based on the CSI regional segmentation indoor localization algorithm

NASA Astrophysics Data System (ADS)

Zeng, Xi; Lin, Wei; Lan, Jingwei

2017-08-01

To solve the problem of high cost and low accuracy, the method of Channel State Information (CSI) regional segmentation are proposed in the indoor positioning. Because Channel State Information (CSI) stability, and effective against multipath effect, we used the Channel State Information (CSI) to segment location area. The method Acquisition CSI the influence of different link to pinpoint the location of the area. Then the method can improve the accuracy of positioning, and reduce the cost of the fingerprint localization algorithm.

Scanning gate study of organic thin-film field-effect transistor

NASA Astrophysics Data System (ADS)

Aoki, N.; Sudou, K.; Matsusaki, K.; Okamoto, K.; Ochiai, Y.

2008-03-01

Scanning gate microscopy (SGM) has been applied for a study of organic thin-film field effect transistor (OFET). In contrast to one-dimensional nano-material such a carbon nanonube or nano-structure such a quantum point contact, visualization a transport characteristic of OFET channel is basically rather difficult since the channel width is much larger than the size of the SGM tip. Nevertheless, Schottky barriers are successfully visualized at the boundary between the metal electrodes and the OFET channel at ambient atmosphere.

Combined effects of VX-770 and VX-809 on several functional abnormalities of F508del-CFTR channels.

PubMed

Kopeikin, Z; Yuksek, Z; Yang, H-Y; Bompadre, S G

2014-09-01

The most common cystic fibrosis-associated mutation, the deletion of phenylalanine 508 (F508del), results in channels with poor membrane expression and impaired function. VX-770, a clinically approved drug for treatment of CF patients carrying the G551D mutation, and VX-809, a corrector shown in vitro to increase membrane expression of mutant channels, are currently undergoing clinical trials, but functional data at the molecular level is still lacking. The effect of VX-770 and VX-809 on the multiple functional defects of F508del-CFTR was assessed via excised inside-out patch-clamp experiments. VX-770 completely restores the low opening-rate of F508del-CFTR, with smaller open-time increase, in temperature-corrected and VX-809-treated channels. The shorter locked-open time of hydrolysis-deficient F508del-CFTR is also prolonged by VX-770. VX-809 does not improve channel function by itself as previously reported. The results from these studies can be interpreted as an equilibrium shift toward the open-channel conformation of F508del-CFTR channels. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A Novel DFT-Based DOA Estimation by a Virtual Array Extension Using Simple Multiplications for FMCW Radar

PubMed Central

Kim, Bongseok; Kim, Sangdong; Lee, Jonghun

2018-01-01

We propose a novel discrete Fourier transform (DFT)-based direction of arrival (DOA) estimation by a virtual array extension using simple multiplications for frequency modulated continuous wave (FMCW) radar. DFT-based DOA estimation is usually employed in radar systems because it provides the advantage of low complexity for real-time signal processing. In order to enhance the resolution of DOA estimation or to decrease the missing detection probability, it is essential to have a considerable number of channel signals. However, due to constraints of space and cost, it is not easy to increase the number of channel signals. In order to address this issue, we increase the number of effective channel signals by generating virtual channel signals using simple multiplications of the given channel signals. The increase in channel signals allows the proposed scheme to detect DOA more accurately than the conventional scheme while using the same number of channel signals. Simulation results show that the proposed scheme achieves improved DOA estimation compared to the conventional DFT-based method. Furthermore, the effectiveness of the proposed scheme in a practical environment is verified through the experiment. PMID:29758016

Recent Developments Regarding Voltage-Gated Sodium Channel Blockers for the Treatment of Inherited and Acquired Neuropathic Pain Syndromes

PubMed Central

Theile, Jonathan W.; Cummins, Theodore R.

2011-01-01

Chronic and neuropathic pain constitute significant health problems affecting millions of individuals each year. Pain sensations typically originate in sensory neurons of the peripheral nervous system which relay information to the central nervous system (CNS). Pathological pain sensations can arise as result of changes in excitability of these peripheral sensory neurons. Voltage-gated sodium channels are key determinants regulating action potential generation and propagation; thus, changes in sodium channel function can have profound effects on neuronal excitability and pain signaling. At present, most of the clinically available sodium channel blockers used to treat pain are non-selective across sodium channel isoforms and can contribute to cardio-toxicity, motor impairments, and CNS side effects. Numerous strides have been made over the last decade in an effort to develop more selective and efficacious sodium channel blockers to treat pain. The purpose of this review is to highlight some of the more recent developments put forth by research universities and pharmaceutical companies alike in the pursuit of developing more targeted sodium channel therapies for the treatment of a variety of neuropathic pain conditions. PMID:22007172

Quantum ballistic transport by interacting two-electron states in quasi-one-dimensional channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Danhong; Center for High Technology Materials, University of New Mexico, 1313 Goddard St SE, Albuquerque, New Mexico 87106; Gumbs, Godfrey

2015-11-15

For quantum ballistic transport of electrons through a short conduction channel, the role of Coulomb interaction may significantly modify the energy levels of two-electron states at low temperatures as the channel becomes wide. In this regime, the Coulomb effect on the two-electron states is calculated and found to lead to four split energy levels, including two anticrossing-level and two crossing-level states. Moreover, due to the interplay of anticrossing and crossing effects, our calculations reveal that the ground two-electron state will switch from one anticrossing state (strong confinement) to a crossing state (intermediate confinement) as the channel width gradually increases andmore » then back to the original anticrossing state (weak confinement) as the channel width becomes larger than a threshold value. This switching behavior leaves a footprint in the ballistic conductance as well as in the diffusion thermoelectric power of electrons. Such a switching is related to the triple spin degeneracy as well as to the Coulomb repulsion in the central region of the channel, which separates two electrons away and pushes them to different channel edges. The conductance reoccurrence region expands from the weak to the intermediate confinement regime with increasing electron density.« less

Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

PubMed Central

Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

2015-01-01

Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer. PMID:26373820

Transient receptor potential ion channels in primary sensory neurons as targets for novel analgesics

PubMed Central

Sousa-Valente, J; Andreou, A P; Urban, L; Nagy, I

2014-01-01

The last decade has witnessed an explosion in novel findings relating to the molecules involved in mediating the sensation of pain in humans. Transient receptor potential (TRP) ion channels emerged as the greatest group of molecules involved in the transduction of various physical stimuli into neuronal signals in primary sensory neurons, as well as, in the development of pain. Here, we review the role of TRP ion channels in primary sensory neurons in the development of pain associated with peripheral pathologies and possible strategies to translate preclinical data into the development of effective new analgesics. Based on available evidence, we argue that nociception-related TRP channels on primary sensory neurons provide highly valuable targets for the development of novel analgesics and that, in order to reduce possible undesirable side effects, novel analgesics should prevent the translocation from the cytoplasm to the cell membrane and the sensitization of the channels rather than blocking the channel pore or binding sites for exogenous or endogenous activators. LINKED ARTICLES This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-10 PMID:24283624

Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current

PubMed Central

Bant, Jason S.; Aman, Teresa K.; Raman, Indira M.

2013-01-01

Na channels that generate resurgent current express an intracellular endogenous open-channel blocking protein, whose rapid binding upon depolarization and unbinding upon repolarization minimizes fast and slow inactivation. Na channels also bind exogenous compounds, such as lidocaine, which functionally stabilize inactivation. Like the endogenous blocking protein, these use-dependent inhibitors bind most effectively at depolarized potentials, raising the question of how lidocaine-like compounds affect neurons with resurgent Na current. We therefore recorded lidocaine inhibition of voltage-clamped, tetrodotoxin-sensitive Na currents in mouse Purkinje neurons, which express a native blocking protein, and in mouse hippocampal CA3 pyramidal neurons with and without a peptide from the cytoplasmic tail of NaVβ4 (the β4 peptide), which mimics endogenous open-channel block. To control channel states during drug exposure, lidocaine was applied with rapid-solution exchange techniques during steps to specific voltages. Inhibition of Na currents by lidocaine was diminished by either the β4 peptide or the native blocking protein. In peptide-free CA3 cells, prolonging channel opening with a site-3 toxin, anemone toxin II, reduced lidocaine inhibition; this effect was largely occluded by open-channel blockers, suggesting that lidocaine binding is favored by inactivation but prevented by open-channel block. In constant 100 μM lidocaine, current-clamped Purkinje cells continued to fire spontaneously. Similarly, the β4 peptide reduced lidocaine-dependent suppression of spiking in CA3 neurons in slices. Thus, the open-channel blocking protein responsible for resurgent current acts as a natural antagonist of lidocaine. Neurons with resurgent current may therefore be less susceptible to use-dependent Na channel inhibitors used as local anesthetic, antiarrhythmic, and anticonvulsant drugs. PMID:23486968

Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve.

PubMed

Bräu, M E; Vogel, W; Hempelmann, G

1998-10-01

Local anesthetics suppress excitability by interfering with ion channel function. Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to the ion channels and may influence the evaluation of local anesthetic potencies. Investigating ion channels in excised membrane patches avoids these diffusion barriers. We investigated the effect of local anesthetics with voltage-dependent Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus laevis using the patch clamp method. The outside-out configuration was chosen to apply drugs to the external face of the membrane. Local anesthetics reversibly blocked the transient Na+ inward current, as well as the steady-state K+ outward current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from concentration-effect curves for Na+ current block were: tetracaine 0.7 microM, etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149 microM, and lidocaine 204 microM. The values for voltage-dependent K+ current block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM, lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM. Correlation of potencies with octanol:buffer partition coefficients (logP0) revealed that ester-bound local anesthetics were more potent in blocking Na+ channels than amide drugs. Within these groups, lipophilicity governed local anesthetic potency. We conclude that local anesthetic action on peripheral nerve ion channels is mediated via lipophilic drug-channel interactions. Half-maximal blocking concentrations of commonly used local anesthetics for Na+ and K+ channel block were determined on small membrane patches of peripheral nerve fibers. Because drugs can directly diffuse to the ion channel in this model, these data result from direct interactions of the drugs with ion channels.

Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium.

PubMed

Wrighton, David C; Muench, Stephen P; Lippiat, Jonathan D

2015-09-01

The Slo3 (KCa 5.1) channel is a major component of mammalian KSper (sperm potassium conductance) channels and inhibition of these channels by quinine and barium alters sperm motility. The aim of this investigation was to determine the mechanism by which these drugs inhibit Slo3 channels. Mouse (m) Slo3 (KCa 5.1) channels or mutant forms were expressed in Xenopus oocytes and currents recorded with 2-electrode voltage-clamp. Gain-of-function mSlo3 mutations were used to explore the state-dependence of the inhibition. The interaction between quinidine and mSlo3 channels was modelled by in silico docking. Several drugs known to block KSper also affected mSlo3 channels with similar levels of inhibition. The inhibition induced by extracellular barium was prevented by increasing the extracellular potassium concentration. R196Q and F304Y mutations in the mSlo3 voltage sensor and pore, respectively, both increased channel activity. The F304Y mutation did not alter the effects of barium, but increased the potency of inhibition by both quinine and quinidine approximately 10-fold; this effect was not observed with the R196Q mutation. Block of mSlo3 channels by quinine, quinidine and barium is not state-dependent. Barium inhibits mSlo3 outside the cell by interacting with the selectivity filter, whereas quinine and quinidine act from the inside, by binding in a hydrophobic pocket formed by the S6 segment of each subunit. Furthermore, we propose that the Slo3 channel activation gate lies deep within the pore between F304 in the S6 segment and the selectivity filter. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycaemia.

PubMed

Morales-Cano, Daniel; Moreno, Laura; Barreira, Bianca; Pandolfi, Rachele; Chamorro, Virginia; Jimenez, Rosario; Villamor, Eduardo; Duarte, Juan; Perez-Vizcaino, Francisco; Cogolludo, Angel

2015-04-01

Voltage-gated potassium channels encoded by KCNQ genes (Kv7 channels) are emerging as important regulators of vascular tone. In this study, we analysed the contribution of Kv7 channels to the vasodilation induced by hypoxia and the cyclic AMP pathway in the coronary circulation. We also assessed their regional distribution and possible impairment by diabetes. We examined the effects of Kv7 channel modulators on K+ currents and vascular reactivity in rat left and right coronary arteries (LCAs and RCAs, respectively). Currents from LCA were more sensitive to Kv7 channel inhibitors (XE991, linopirdine) and activators (flupirtine, retigabine) than those from RCA. Accordingly, LCAs were more sensitive than RCAs to the relaxation induced by Kv7 channel enhancers. Likewise, relaxation induced by the adenylyl cyclase activator forskolin and hypoxia, which were mediated through Kv7 channel activation, were greater in LCA than in RCA. KCNQ1 and KCNQ5 expression was markedly higher in LCA than in RCA. After incubation with high glucose (HG, 30 mmol/L), myocytes from LCA, but not from RCA, were more depolarized and showed reduced Kv7 currents. In HG-incubated LCA, the effects of Kv7 channel modulators and forskolin were diminished, and the expression of KCNQ1 and KCNQ5 was reduced. Finally, vascular responses induced by Kv7 channel modulators were impaired in LCA, but not in RCA, from type 1 diabetic rats. Our results reveal that the high expression and function of Kv7 channels in the LCA and their down-regulation by diabetes critically determine the sensitivity to key regulators of coronary tone. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

A Channelization-Based DOA Estimation Method for Wideband Signals

PubMed Central

Guo, Rui; Zhang, Yue; Lin, Qianqiang; Chen, Zengping

2016-01-01

In this paper, we propose a novel direction of arrival (DOA) estimation method for wideband signals with sensor arrays. The proposed method splits the wideband array output into multiple frequency sub-channels and estimates the signal parameters using a digital channelization receiver. Based on the output sub-channels, a channelization-based incoherent signal subspace method (Channelization-ISM) and a channelization-based test of orthogonality of projected subspaces method (Channelization-TOPS) are proposed. Channelization-ISM applies narrowband signal subspace methods on each sub-channel independently. Then the arithmetic mean or geometric mean of the estimated DOAs from each sub-channel gives the final result. Channelization-TOPS measures the orthogonality between the signal and the noise subspaces of the output sub-channels to estimate DOAs. The proposed channelization-based method isolates signals in different bandwidths reasonably and improves the output SNR. It outperforms the conventional ISM and TOPS methods on estimation accuracy and dynamic range, especially in real environments. Besides, the parallel processing architecture makes it easy to implement on hardware. A wideband digital array radar (DAR) using direct wideband radio frequency (RF) digitization is presented. Experiments carried out in a microwave anechoic chamber with the wideband DAR are presented to demonstrate the performance. The results verify the effectiveness of the proposed method. PMID:27384566

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradler, Kamil; Hayden, Patrick; Touchette, Dave

Coding theorems in quantum Shannon theory express the ultimate rates at which a sender can transmit information over a noisy quantum channel. More often than not, the known formulas expressing these transmission rates are intractable, requiring an optimization over an infinite number of uses of the channel. Researchers have rarely found quantum channels with a tractable classical or quantum capacity, but when such a finding occurs, it demonstrates a complete understanding of that channel's capabilities for transmitting classical or quantum information. Here we show that the three-dimensional capacity region for entanglement-assisted transmission of classical and quantum information is tractable formore » the Hadamard class of channels. Examples of Hadamard channels include generalized dephasing channels, cloning channels, and the Unruh channel. The generalized dephasing channels and the cloning channels are natural processes that occur in quantum systems through the loss of quantum coherence or stimulated emission, respectively. The Unruh channel is a noisy process that occurs in relativistic quantum information theory as a result of the Unruh effect and bears a strong relationship to the cloning channels. We give exact formulas for the entanglement-assisted classical and quantum communication capacity regions of these channels. The coding strategy for each of these examples is superior to a naieve time-sharing strategy, and we introduce a measure to determine this improvement.« less

Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels.

PubMed

Chachin, Motohiko; Yamada, Mitsuhiko; Fujita, Akikazu; Matsuoka, Tetsuro; Matsushita, Kenji; Kurachi, Yoshihisa

2003-03-01

A novel antidiabetic agent, nateglinide, is a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety. We examined with the patch-clamp method the effect of nateglinide on recombinant ATP-sensitive K(+) (K(ATP)) channels expressed in human embryonic kidney 293T cells transfected with a Kir6.2 subunit and either of a sulfonylurea receptor (SUR) 1, SUR2A, and SUR2B. In inside-out patches, nateglinide reversibly inhibited the spontaneous openings of all three types of SUR/Kir6.2 channels. Nateglinide inhibited SUR1/Kir6.2 channels with high and low affinities (K(i) = 75 nM and 114 microM) but SUR2A/Kir6.2 and SUR2B/Kir6.2 channels only with low affinity (K(i) = 105 and 111 microM, respectively). Nateglinide inhibited the K(ATP) current mediated by Kir6.2 lacking C-terminal 26 amino acids only with low affinity (K(i) = 290 microM) in the absence of SUR. Replacement of serine at position 1237 of SUR1 to tyrosine [SUR1(S1237Y)] specifically abolished the high-affinity inhibition of SUR1/Kir6.2 channels by nateglinide. MgADP or MgUDP (100 microM) augmented the inhibitory effect of nateglinide on SUR1/Kir6.2 but not SUR1(S1237Y)/Kir6.2 or SUR2A/Kir6.2 channels. This augmenting effect of MgADP was also observed with the SUR1/Kir6.2(K185Q) channel, which was not inhibited by MgADP, but not with the SUR1(K1384A)/Kir6.2 channel, which was not activated by MgADP. These results indicate that therapeutic concentrations of nateglinide (approximately 10 microM) may selectively inhibit pancreatic type SUR1/Kir6.2 channels through SUR1, especially when the channel is activated by intracellular MgADP, even though the agent does not contain either a sulfonylurea or benzamido moiety.

Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Na{sub v}1.8 sodium channels expressed in Xenopus oocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, J.-S.; Soderlund, David M.

2006-03-15

Pyrethroid insecticides bind to voltage-sensitive sodium channels and modify their gating kinetics, thereby disrupting nerve function. This paper describes the action of 11 structurally diverse commercial pyrethroid insecticides on the rat Na{sub v}1.8 sodium channel isoform, the principal carrier of the tetrodotoxin-resistant, pyrethroid-sensitive sodium current of sensory neurons, expressed in Xenopus laevis oocytes. All 11 compounds produced characteristic sodium tail currents following a depolarizing pulse that ranged from rapidly-decaying monoexponential currents (allethrin, cismethrin and permethrin) to persistent biexponential currents (cyfluthrin, cyhalothrin, cypermethrin and deltamethrin). Tail currents for the remaining compounds (bifenthrin, fenpropathrin, fenvalerate and tefluthrin) were monoexponential and decayed withmore » kinetics intermediate between these extremes. Reconstruction of currents carried solely by the pyrethroid-modified subpopulation of channels revealed two types of pyrethroid-modified currents. The first type, found with cismethrin, allethrin, permethrin and tefluthrin, activated relatively rapidly and inactivated partially during a 40-ms depolarization. The second type, found with cypermethrin, cyfluthrin, cyhalothrin, deltamethrin, fenpropathrin and fenvalerate, activated more slowly and did not detectably inactivate during a 40-ms depolarization. Only bifenthrin did not produce modified currents that fit clearly into either of these categories. In all cases, the rate of activation of modified channels was strongly correlated with the rate of tail current decay following repolarization. Modification of Na{sub v}1.8 sodium channels by cyfluthrin, cyhalothrin, cypermethrin and deltamethrin was enhanced 2.3- to 3.4-fold by repetitive stimulation; this effect appeared to result from the accumulation of persistently open channels rather than preferential binding to open channel states. Fenpropathrin was the most effective compound against Na{sub v}1.8 sodium channels from the perspective of either resting or use-dependent modification. When use dependence is taken into account, cypermethrin, deltamethrin and tefluthrin approached the effectiveness of fenpropathrin. The selective expression of Na{sub v}1.8 sodium channels in nociceptive neurons suggests that these channels may be important targets for pyrethroids in the production of paresthesia following dermal expo0010su.« less

PERTURBATION OF VOLTAGE-SENSITIVE Ca2+ CHANNEL FUNCTION BY VOLATILE ORGANIC SOLVENTS.

EPA Science Inventory

The mechanisms underlying the acute neurophysiological and behavioral effects of volatile organic compounds (VOCs) remain to be elucidated. However, the function of neuronal ion channels is perturbed by VOCs. The present study examined effects of toluene (TOL), trichloroethylene ...

Impact of satellite aeronautical channel on modem specifications

DOT National Transportation Integrated Search

1974-03-01

The report analyzes the effects of surface-scattered multipath on the performance of ranging and data modems such as might be used on the aircraft-satellite channel of an air-traffic control system. An exact analysis is carried out on the effects of ...

Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activityin Nociceptors

DTIC Science & Technology

2015-10-01

Funding support (other than DoD) Mission Connect-TIRR Foundation, "Neuroprotective Effect of Targeting KCNQ/ Kv7 Channels in Spinal Cord Injury...the function of a sodium ion channel , Nav1.8, that is selectively expressed in primary afferent neurons (especially nociceptors) ameliorate reflex...our finding that antisense knockdown of TRPV1 channels or pharmacological blockade of TRPV1 channels -- which are expressed most abundantly in

Paid and Unpaid Online Recruitment for Health Interventions in Young Adults.

PubMed

Musiat, Peter; Winsall, Megan; Orlowski, Simone; Antezana, Gaston; Schrader, Geoffrey; Battersby, Malcolm; Bidargaddi, Niranjan

2016-12-01

There is a growing need to identify new and innovative approaches to recruit representative samples of young adults in health intervention research. The current study used a data set of screening information from an online well-being intervention trial of young adults, to investigate cost-effectiveness of different recruitment strategies and whether the clinical and demographic characteristics of participants differed depending on paid or unpaid online recruitment sources. Data were collected from 334 18- to 25-year-old Australians. The study was advertised through a variety of paid and unpaid online recruitment channels (e.g., Google, Facebook, Twitter, YouTube, recruitment agency), with response rates to different recruitment channels tracked using unique Web links. Well-being of participants was measured using the Mental Health Continuum Short Form. Analyses consisted of independent t tests and χ 2 tests. Overall, unpaid recruitment channels had a considerably higher yield than paid recruitment channels. Of paid recruitment channels, a recruitment agency and paid Facebook advertisements attracted the largest number of individuals. This study also found differences between paid and unpaid online recruitment channels with regard to the well-being and mood of participants. Although the success of online recruitment channels is likely subject to a complex interplay between the number of exposures, the targeted sample, the wording, and placement of the advertisement, as well as study characteristics, our study demonstrated that unpaid recruitment channels are more effective than paid channels and that paid and unpaid channels may result in samples with different characteristics. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.

Susceptibility of ATP-sensitive K+ channels to cell stress through mediation of phosphoinositides as examined by photoirradiation

PubMed Central

Fan, Zheng; Neff, Robert A

2000-01-01

Cell stress is implicated in a number of pathological states of metabolism, such as ischaemia, reperfusion and apoptosis in heart, neurons and other tissues. While it is known that the ATP-sensitive K+ (KATP) channel plays a role during metabolic abnormality, little information is available about the direct response of this channel to cell stress. Using photoirradiation stimulation, we studied the effects of cell stress on both native and cloned KATP channels. Single KATP channel currents were recorded from cell-attached and inside-out patches of rat ventricular myocytes and COS-1 cells coexpressing SUR2 and Kir6.2. KATP channel activity increased within < 1 min upon irradiation. The activity resulted from increased maximal open probability and decreased ATP inhibition. The effects remained after the irradiation was stopped. Irradiation also affected the channels formed only by Kir6.2ΔC35. The irradiation-induced activation was comparable to that induced by phosphoinositides. Analysis of phosphatidylinositol composition revealed an elevated phosphatidylinositol bisphosphate level with irradiation. Wortmannin, an inhibitor of phosphatidylinositol kinases, decreased both the irradiation-induced channel activity and the production of phosphatidylinositol bisphosphates. Radical scavengers also reduced the irradiation-induced activation, suggesting a role for free radicals, an immediate product of photoirradiation. We conclude that photoirradiation can modify the single-channel properties of KATP, which appears to be mediated by phosphoinositides. Our study suggests that cellular stress may be linked with KATP channels, and we offer a putative mechanism for such a linkage. PMID:11118500

Angiotensin II Inhibits the ROMK-like Small Conductance K Channel in Renal Cortical Collecting Duct during Dietary Potassium Restriction*

PubMed Central

Wei, Yuan; Zavilowitz, Beth; Satlin, Lisa M.; Wang, Wen-Hui

2010-01-01

Base-line urinary potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal potassium (NK) or low potassium (LK) diet to test the hypothesis that AngII directly inhibits ROMK channel activity. We found that AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent manner. The AngII-induced reduction in channel activity was mediated by AT1 receptor (AT1R) binding, because pretreatment of CCDs with losartan but not PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response. Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C (PLC) and protein kinase C (PKC), respectively, abolished the AngII-induced decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in this response. Studies by others suggest that AngII stimulates an Src family protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium abolished the inhibitory effect of AngII or the PKC activator phorbol 12-myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A significantly attenuated the inhibitory effect of AngII on ROMK channel activity. We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary potassium restriction. PMID:17194699

Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction.

PubMed

Wei, Yuan; Zavilowitz, Beth; Satlin, Lisa M; Wang, Wen-Hui

2007-03-02

Base-line urinary potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal potassium (NK) or low potassium (LK) diet to test the hypothesis that AngII directly inhibits ROMK channel activity. We found that AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent manner. The AngII-induced reduction in channel activity was mediated by AT1 receptor (AT1R) binding, because pretreatment of CCDs with losartan but not PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response. Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C (PLC) and protein kinase C (PKC), respectively, abolished the AngII-induced decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in this response. Studies by others suggest that AngII stimulates an Src family protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium abolished the inhibitory effect of AngII or the PKC activator phorbol 12-myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A significantly attenuated the inhibitory effect of AngII on ROMK channel activity. We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary potassium restriction.

Cardiac metabolic effects of KNa1.2 channel deletion and evidence for its mitochondrial localization.

PubMed

Smith, Charles O; Wang, Yves T; Nadtochiy, Sergiy M; Miller, James H; Jonas, Elizabeth A; Dirksen, Robert T; Nehrke, Keith; Brookes, Paul S

2018-06-04

Controversy surrounds the molecular identity of mitochondrial K + channels that are important for protection against cardiac ischemia-reperfusion injury. Although K Na 1.2 (sodium-activated potassium channel encoded by Kcn2) is necessary for cardioprotection by volatile anesthetics, electrophysiological evidence for a channel of this type in mitochondria is lacking. The endogenous physiological role of a potential mito-K Na 1.2 channel is also unclear. In this study, single channel patch-clamp of 27 independent cardiac mitochondrial inner membrane (mitoplast) preparations from wild-type (WT) mice yielded 6 channels matching the known ion sensitivity, ion selectivity, pharmacology, and conductance properties of K Na 1.2 (slope conductance, 138 ± 1 pS). However, similar experiments on 40 preparations from Kcnt2 -/- mice yielded no such channels. The K Na opener bithionol uncoupled respiration in WT but not Kcnt2 -/- cardiomyocytes. Furthermore, when oxidizing only fat as substrate, Kcnt2 -/- cardiomyocytes and hearts were less responsive to increases in energetic demand. Kcnt2 -/- mice also had elevated body fat, but no baseline differences in the cardiac metabolome. These data support the existence of a cardiac mitochondrial K Na 1.2 channel, and a role for cardiac K Na 1.2 in regulating metabolism under conditions of high energetic demand.-Smith, C. O., Wang, Y. T., Nadtochiy, S. M., Miller, J. H., Jonas, E. A., Dirksen, R. T., Nehrke, K., Brookes, P. S. Cardiac metabolic effects of K Na 1.2 channel deletion and evidence for its mitochondrial localization.

Contribution of the AIRS Shortwave Sounding Channels to Retrieval Accuracy

NASA Technical Reports Server (NTRS)

Susskind, Joel; Kouvaris, Louis

2006-01-01

AIRS contains 2376 high spectral resolution channels between 650/cm and 2665/cm, including channels in both the 15 micron (near 667/cm) and 4.2 micron (near 2400/cm) COP sounding bands. Use of temperature sounding channels in the 15 micron CO2 band has considerable heritage in infra-red remote sensing. Channels in the 4.2 micron CO2 band have potential advantages for temperature sounding purposes because they are essentially insensitive to absorption by water vapor and ozone, and also have considerably sharper lower tropospheric temperature sounding weighting functions than do the 15 micron temperature sounding channels. Potential drawbacks with regard to use of 4.2 micron channels arise from effects on the observed radiances of solar radiation reflected by the surface and clouds, as well as effects of non-local thermodynamic equilibrium on shortwave observations during the day. These are of no practical consequences, however, when properly accounted for. We show results of experiments performed utilizing different spectral regions of AIRS, conducted with the AIRS Science Team candidate Version 5 algorithm. Experiments were performed using temperature sounding channels within the entire AIRS spectral coverage, within only the spectral region 650/cm to 1614 /cm; and within only the spectral region 1000/cm-2665/cm. These show the relative importance of utilizing only 15 micron temperature sounding channels, only the 4.2 micron temperature sounding channels, and both, with regards to sounding accuracy. The spectral region 2380/cm to 2400/cm is shown to contribute significantly to improve sounding accuracy in the lower troposphere, both day and night.

Human hair follicles contain two forms of ATP-sensitive potassium channels, only one of which is sensitive to minoxidil.

PubMed

Shorter, Katie; Farjo, Nilofer P; Picksley, Steven M; Randall, Valerie A

2008-06-01

Hair disorders cause psychological distress but are generally poorly controlled; more effective treatments are required. Despite the long-standing use of minoxidil for balding, its mechanism is unclear; suggestions include action on vasculature or follicle cells. Similar drugs also stimulate hair, implicating ATP-sensitive potassium (K(ATP)) channels. To investigate whether K(ATP) channels are present in human follicles, we used organ culture, molecular biological, and immunohistological approaches. Minoxidil and tolbutamide, a K(ATP) channel blocker, opposed each other's effects on the growing phase (anagen) of scalp follicles cultured in media with and without insulin. Reverse transcriptase-polymerase chain reaction identified K(ATP) channel component gene expression including regulatory sulfonylurea receptors (SUR) SUR1 and SUR2B but not SUR2A and pore-forming subunits (Kir) Kir6.1 and Kir6.2. When hair bulb tissues were examined separately, epithelial matrix expressed SUR1 and Kir6.2, whereas both dermal papilla and sheath exhibited SUR2B and Kir6.1. Immunohistochemistry demonstrated similar protein distributions. Thus, human follicles respond biologically to K(ATP) channel regulators in culture and express genes and proteins for two K(ATP) channels, Kir6.2/SUR1 and Kir6.1/SUR2B; minoxidil only stimulates SUR2 channels. These findings indicate that human follicular dermal papillae contain K(ATP) channels that can respond to minoxidil and that tolbutamide may suppress hair growth clinically; novel drugs designed specifically for these channels could treat hair disorders.

Separate channels for the analysis of the shape and the movement of moving visual stimulus.

PubMed

Tolhurst, D J

1973-06-01

1. The effects of temporal modulation on the properties of spatial frequency channels have been investigated using adaptation.2. Adapting to drifting sinusoidal gratings caused threshold elevation that was both spatial frequency and direction specific. Little systematic difference was found between the band widths of the elevation curves for drifting and stationary gratings.3. It was confirmed that adaptation fails to reveal channels at low spatial frequencies when stationary gratings are used. However, channels were revealed at frequencies at least as low as 0.66 c/deg when the test gratings were made to move. These channels are adapted only a little by stationary gratings, confirming their dependence on movement.4. The existence of movement-sensitive channels at low spatial frequencies explains the well known observation that temporal modulation greatly increases the sensitivity of the visual system to low spatial frequencies.5. Temporal modulation was effective at revealing these channels only when the flicker or movement of the test patterns was apparent to the observer; only at low spatial frequencies did patterns, modulated at low rates, actually appear to be temporarily modulated at threshold. At higher spatial frequencies, they were indistinguishable from stationary patterns until the contrast was some way above the detection threshold.6. It is suggested, therefore, that the movement-sensitive channels are responsible for signalling the occurrence of movement; the channels at higher spatial frequencies give no information about temporal changes. These two systems of channels are compared to the Y- and X-cells respectively of the cat.

Mechanism of Tacrine Block at Adult Human Muscle Nicotinic Acetylcholine Receptors

PubMed Central

Prince, Richard J.; Pennington, Richard A.; Sine, Steven M.

2002-01-01

We used single-channel kinetic analysis to study the inhibitory effects of tacrine on human adult nicotinic receptors (nAChRs) transiently expressed in HEK 293 cells. Single channel recording from cell-attached patches revealed concentration- and voltage-dependent decreases in mean channel open probability produced by tacrine (IC50 4.6 μM at −70 mV, 1.6 μM at −150 mV). Two main effects of tacrine were apparent in the open- and closed-time distributions. First, the mean channel open time decreased with increasing tacrine concentration in a voltage-dependent manner, strongly suggesting that tacrine acts as an open-channel blocker. Second, tacrine produced a new class of closings whose duration increased with increasing tacrine concentration. Concentration dependence of closed-times is not predicted by sequential models of channel block, suggesting that tacrine blocks the nAChR by an unusual mechanism. To probe tacrine's mechanism of action we fitted a series of kinetic models to our data using maximum likelihood techniques. Models incorporating two tacrine binding sites in the open receptor channel gave dramatically improved fits to our data compared with the classic sequential model, which contains one site. Improved fits relative to the sequential model were also obtained with schemes incorporating a binding site in the closed channel, but only if it is assumed that the channel cannot gate with tacrine bound. Overall, the best description of our data was obtained with a model that combined two binding sites in the open channel with a single site in the closed state of the receptor. PMID:12198092

Mobility of Protozoa through Narrow Channels

PubMed Central

Wang, Wei; Shor, Leslie M.; LeBoeuf, Eugene J.; Wikswo, John P.; Kosson, David S.

2005-01-01

Microbes in the environment are profoundly affected by chemical and physical heterogeneities occurring on a spatial scale of millimeters to micrometers. Physical refuges are critical for maintaining stable bacterial populations in the presence of high predation pressure by protozoa. The effects of microscale heterogeneity, however, are difficult to replicate and observe using conventional experimental techniques. The objective of this research was to investigate the effect of spatial constraints on the mobility of six species of marine protozoa. Microfluidic devices were created with small channels similar in size to pore spaces in soil or sediment systems. Individuals from each species of protozoa tested were able to rapidly discover and move within these channels. The time required for locating the channel entrance from the source well increased with protozoan size and decreased with channel height. Protozoa of every species were able to pass constrictions with dimensions equal to or smaller than the individual's unconstrained cross-sectional area. Channel geometry was also an important factor affecting protozoan mobility. Linear rates of motion for various species of protozoa varied by channel size. In relatively wide channels, typical rates of motion were 300 to 500 μm s−1 (or about 1 m per hour). As the channel dimensions decreased, however, motilities slowed more than an order of magnitude to 20 μm s−1. Protozoa were consistently observed to exhibit several strategies for successfully traversing channel reductions. The empirical results and qualitative observations resulting from this research help define the physical limitations on protozoan grazing, a critical process affecting microbes in the environment. PMID:16085857

Electric Dipolar Kondo Effect Emerging from a Vibrating Magnetic Ion

NASA Astrophysics Data System (ADS)

Hotta, Takashi; Ueda, Kazuo

2012-06-01

When a magnetic ion vibrates in a metal, it inevitably introduces a new channel of hybridization with conduction electrons, and in general, the vibrating ion induces an electric dipole moment. In such a situation, we find that magnetic and nonmagnetic Kondo effects alternatively occur due to the screening of the spin moment and electric dipole moment of the vibrating ion. In particular, the electric dipolar two-channel Kondo effect is found to occur for a weak Coulomb interaction. We also show that a magnetically robust heavy-electron state appears near the fixed point of the electric dipolar two-channel Kondo effect. We believe that the vibrating magnetic ion opens a new door in Kondo physics.

An anion channel in Arabidopsis hypocotyls activated by blue light

NASA Technical Reports Server (NTRS)

Cho, M. H.; Spalding, E. P.; Evans, M. L. (Principal Investigator)

1996-01-01

A rapid, transient depolarization of the plasma membrane in seedling stems is one of the earliest effects of blue light detected in plants. It appears to play a role in transducing blue light into inhibition of hypocotyl (stem) elongation, and perhaps other responses. The possibility that activation of a Cl- conductance is part of the depolarization mechanism was raised previously and addressed here. By patch clamping hypocotyl cells isolated from dark-grown (etiolated) Arabidopsis seedlings, blue light was found to activate an anion channel residing at the plasma membrane. An anion-channel blocker commonly known as NPPB 15-nitro-2-(3-phenylpropylamino)-benzoic acid] potently and reversibly blocked this anion channel. NPPB also blocked the blue-light-induced depolarization in vivo and decreased the inhibitory effect of blue light on hypocotyl elongation. These results indicate that activation of this anion channel plays a role in transducing blue light into growth inhibition.

Probing the effect of electron channelling on atomic resolution energy dispersive X-ray quantification.

PubMed

MacArthur, Katherine E; Brown, Hamish G; Findlay, Scott D; Allen, Leslie J

2017-11-01

Advances in microscope stability, aberration correction and detector design now make it readily possible to achieve atomic resolution energy dispersive X-ray mapping for dose resilient samples. These maps show impressive atomic-scale qualitative detail as to where the elements reside within a given sample. Unfortunately, while electron channelling is exploited to provide atomic resolution data, this very process makes the images rather more complex to interpret quantitatively than if no electron channelling occurred. Here we propose small sample tilt as a means for suppressing channelling and improving quantification of composition, whilst maintaining atomic-scale resolution. Only by knowing composition and thickness of the sample is it possible to determine the atomic configuration within each column. The effects of neighbouring atomic columns with differing composition and of residual channelling on our ability to extract exact column-by-column composition are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Expected number of quantum channels in quantum networks.

PubMed

Chen, Xi; Wang, He-Ming; Ji, Dan-Tong; Mu, Liang-Zhu; Fan, Heng

2015-07-15

Quantum communication between nodes in quantum networks plays an important role in quantum information processing. Here, we proposed the use of the expected number of quantum channels as a measure of the efficiency of quantum communication for quantum networks. This measure quantified the amount of quantum information that can be teleported between nodes in a quantum network, which differs from classical case in that the quantum channels will be consumed if teleportation is performed. We further demonstrated that the expected number of quantum channels represents local correlations depicted by effective circles. Significantly, capacity of quantum communication of quantum networks quantified by ENQC is independent of distance for the communicating nodes, if the effective circles of communication nodes are not overlapped. The expected number of quantum channels can be enhanced through transformations of the lattice configurations of quantum networks via entanglement swapping. Our results can shed lights on the study of quantum communication in quantum networks.

Expected number of quantum channels in quantum networks

PubMed Central

Chen, Xi; Wang, He-Ming; Ji, Dan-Tong; Mu, Liang-Zhu; Fan, Heng

2015-01-01

Quantum communication between nodes in quantum networks plays an important role in quantum information processing. Here, we proposed the use of the expected number of quantum channels as a measure of the efficiency of quantum communication for quantum networks. This measure quantified the amount of quantum information that can be teleported between nodes in a quantum network, which differs from classical case in that the quantum channels will be consumed if teleportation is performed. We further demonstrated that the expected number of quantum channels represents local correlations depicted by effective circles. Significantly, capacity of quantum communication of quantum networks quantified by ENQC is independent of distance for the communicating nodes, if the effective circles of communication nodes are not overlapped. The expected number of quantum channels can be enhanced through transformations of the lattice configurations of quantum networks via entanglement swapping. Our results can shed lights on the study of quantum communication in quantum networks. PMID:26173556

Control of single-photon routing in a T-shaped waveguide by another atom

NASA Astrophysics Data System (ADS)

Huang, Jin-Song; Wang, Jing-Wen; Wang, Yan; Li, Yan-Ling; Huang, You-Wen

2018-04-01

Quantum routers with a high routing rate of much more than 0.5 are of great importance for quantum networks. We provide a scheme to perform bidirectional high routing-rate transfer in a T-shaped coupled-resonator waveguide (CRW), which extends a recent unidirectional scheme proposed by Lu et al. (Opt Express 23:22955, 2015). By locating an extra two-level atom in the infinite CRW channel of the T-shaped CRW with a three-level system, an effective potential is generated. Our numerical results show that high routing capability from the infinite CRW channel to the semi-infinite channel can be achieved, and routing capability from the semi-infinite CRW channel to the infinite channel can also be significantly enhanced, with the help of the effective potential. Therefore, the proposed double-atom configuration could be utilized as a bidirectional quantum routing controller to implement high transfer rate routing of single photons.

Multiple-channel detection of cellular activities by ion-sensitive transistors

NASA Astrophysics Data System (ADS)

Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

2018-04-01

An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

Slip Effects on Mixed Convective Peristaltic Transport of Copper-Water Nanofluid in an Inclined Channel

PubMed Central

Abbasi, Fahad Munir; Hayat, Tasawar; Ahmad, Bashir; Chen, Guo-Qian

2014-01-01

Peristaltic transport of copper-water nanofluid in an inclined channel is reported in the presence of mixed convection. Both velocity and thermal slip conditions are considered. Mathematical modelling has been carried out using the long wavelength and low Reynolds number approximations. Resulting coupled system of equations is solved numerically. Quantities of interest are analyzed through graphs. Numerical values of heat transfer rate at the wall for different parameters are obtained and examined. Results showed that addition of copper nanoparticles reduces the pressure gradient, axial velocity at the center of channel, trapping and temperature. Velocity slip parameter has a decreasing effect on the velocity near the center of channel. Temperature of nanofluid increases with increase in the Grashoff number and channel inclination angle. It is further concluded that the heat transfer rate at the wall increases considerably in the presence of copper nanoparticles. PMID:25170908

Evaluation of wavelength groups for discrimination of agricultural cover types. [remote sensing of environment in INDIANA

NASA Technical Reports Server (NTRS)

Kumar, R.

1978-01-01

Multispectral scanner data in twelve spectral channels, in the wavelength range 0.46 to 11.7 mm, acquired in July 1971 for three flightlines, were analyzed by applying automatic pattern recognition techniques. These twelve spectral channels were divided into four wavelength groups (W1, W2, W3 and W4), each consisting of three wavelength channels -- with respect to their estimated probability of correct classification (P sub c) in discriminating agricultural cover types. The same analysis was also done for the data acquired in August, to investigate the effect of time on these results. The effect of deletion of each of the wavelength groups on P sub C in the subsets of one to nine channels, is given. Values of P sub C for all possible combinations of wavelength groups, in the subsets of one to eleven channels are also given.

Germanium Based Field-Effect Transistors: Challenges and Opportunities

PubMed Central

Goley, Patrick S.; Hudait, Mantu K.

2014-01-01

The performance of strained silicon (Si) as the channel material for today’s metal-oxide-semiconductor field-effect transistors may be reaching a plateau. New channel materials with high carrier mobility are being investigated as alternatives and have the potential to unlock an era of ultra-low-power and high-speed microelectronic devices. Chief among these new materials is germanium (Ge). This work reviews the two major remaining challenges that Ge based devices must overcome if they are to replace Si as the channel material, namely, heterogeneous integration of Ge on Si substrates, and developing a suitable gate stack. Next, Ge is compared to compound III-V materials in terms of p-channel device performance to review how it became the first choice for PMOS devices. Different Ge device architectures, including surface channel and quantum well configurations, are reviewed. Finally, state-of-the-art Ge device results and future prospects are also discussed. PMID:28788569

Temperature sensitivity of ligand-gated ion channels: ryanodine receptor case

NASA Astrophysics Data System (ADS)

Iaparov, B. I.; Moskvin, A. S.; Solovyova, O. E.

2017-11-01

Temperature influences all biochemical processes, in particular, excitation-contraction coupling(ECC) in cardiac cells. In this work we propose a theoretical explanation of temperature effects on an isolated ryanodine receptor calcium release channel (RyR channel) within the electron-conformational (EC) model. We show that the EC model with an Arrhenius-like temperature dependence of the “internal” and “external” frictions and a specific thermosensitivity of the tunnelling “open ↔ closed” transitions can provide both qualitative and quantitative description of the temperature effects for isolated RyR channels. Interestingly that a small change of the activation energy for the “internal” friction can make an ion channel either heat-inhibited or heat-activated while the “external” friction doesn’t play a key role in temperature sensitivity: neglect of “external” friction doesn’t change the channel’s temperature sensitivity qualitatively.

Influence of the narrow {111} planes on axial and planar ion channeling.

PubMed

Motapothula, M; Dang, Z Y; Venkatesan, T; Breese, M B H; Rana, M A; Osman, A

2012-05-11

We report channeling patterns where clearly resolved effects of the narrow {111} planes are observed in axial and planar alignments for 2 MeV protons passing through a 55 nm [001] silicon membrane. At certain axes, such as <213> and <314>, the offset in atomic rows forming the narrow {111} planes results in shielding from the large potential at the wide {111} planes, producing a region of shallow, asymmetric potential from which axial channeling patterns have no plane of symmetry. At small tilts from such axes, different behavior is observed from the wide and narrow {111} planes. At planar alignment, distinctive channeling effects due to the narrow planes are observed. As a consequence of the shallow potential well at the narrow planes, incident protons suffer dechanneled trajectories which are excluded from channeling within the wide planes, resulting in an anomalously large scattered beam at {111} alignment.

Atomic basis for therapeutic activation of neuronal potassium channels

NASA Astrophysics Data System (ADS)

Kim, Robin Y.; Yau, Michael C.; Galpin, Jason D.; Seebohm, Guiscard; Ahern, Christopher A.; Pless, Stephan A.; Kurata, Harley T.

2015-09-01

Retigabine is a recently approved anticonvulsant that acts by potentiating neuronal M-current generated by KCNQ2-5 channels, interacting with a conserved Trp residue in the channel pore domain. Using unnatural amino-acid mutagenesis, we subtly altered the properties of this Trp to reveal specific chemical interactions required for retigabine action. Introduction of a non-natural isosteric H-bond-deficient Trp analogue abolishes channel potentiation, indicating that retigabine effects rely strongly on formation of a H-bond with the conserved pore Trp. Supporting this model, substitution with fluorinated Trp analogues, with increased H-bonding propensity, strengthens retigabine potency. In addition, potency of numerous retigabine analogues correlates with the negative electrostatic surface potential of a carbonyl/carbamate oxygen atom present in most KCNQ activators. These findings functionally pinpoint an atomic-scale interaction essential for effects of retigabine and provide stringent constraints that may guide rational improvement of the emerging drug class of KCNQ channel activators.

Photoconductivity, pH Sensitivity, Noise, and Channel Length Effects in Si Nanowire FET Sensors

NASA Astrophysics Data System (ADS)

Gasparyan, Ferdinand; Zadorozhnyi, Ihor; Khondkaryan, Hrant; Arakelyan, Armen; Vitusevich, Svetlana

2018-03-01

Silicon nanowire (NW) field-effect transistor (FET) sensors of various lengths were fabricated. Transport properties of Si NW FET sensors were investigated involving noise spectroscopy and current-voltage (I-V) characterization. The static I-V dependencies demonstrate the high quality of fabricated silicon FETs without leakage current. Transport and noise properties of NW FET structures were investigated under different light illumination conditions, as well as in sensor configuration in an aqueous solution with different pH values. Furthermore, we studied channel length effects on the photoconductivity, noise, and pH sensitivity. The magnitude of the channel current is approximately inversely proportional to the length of the current channel, and the pH sensitivity increases with the increase of channel length approaching the Nernst limit value of 59.5 mV/pH. We demonstrate that dominant 1/f-noise can be screened by the generation-recombination plateau at certain pH of the solution or external optical excitation. The characteristic frequency of the generation-recombination noise component decreases with increasing of illumination power. Moreover, it is shown that the measured value of the slope of 1/f-noise spectral density dependence on the current channel length is 2.7 which is close to the theoretically predicted value of 3.