A 128-channel picoammeter system and its application on charged particle beam current distribution measurements.

PubMed

Yu, Deyang; Liu, Junliang; Xue, Yingli; Zhang, Mingwu; Cai, Xiaohong; Hu, Jianjun; Dong, Jinmei; Li, Xin

2015-11-01

A 128-channel picoammeter system is constructed based on instrumentation amplifiers. Taking advantage of a high electric potential and narrow bandwidth in DC energetic charged beam measurements, a current resolution better than 5 fA can be achieved. Two sets of 128-channel strip electrodes are implemented on printed circuit boards and are employed for ion and electron beam current distribution measurements. Tests with 60 keV O(3+) ions and 2 keV electrons show that it can provide exact boundaries when a positive charged particle beam current distribution is measured.

Evolution simulation of lightning discharge based on a magnetohydrodynamics method

NASA Astrophysics Data System (ADS)

Fusheng, WANG; Xiangteng, MA; Han, CHEN; Yao, ZHANG

2018-07-01

In order to solve the load problem for aircraft lightning strikes, lightning channel evolution is simulated under the key physical parameters for aircraft lightning current component C. A numerical model of the discharge channel is established, based on magnetohydrodynamics (MHD) and performed by FLUENT software. With the aid of user-defined functions and a user-defined scalar, the Lorentz force, Joule heating and material parameters of an air thermal plasma are added. A three-dimensional lightning arc channel is simulated and the arc evolution in space is obtained. The results show that the temperature distribution of the lightning channel is symmetrical and that the hottest region occurs at the center of the lightning channel. The distributions of potential and current density are obtained, showing that the difference in electric potential or energy between two points tends to make the arc channel develop downwards. The arc channel comes into expansion on the anode surface due to stagnation of the thermal plasma and there exists impingement on the copper plate when the arc channel comes into contact with the anode plate.

Measuring Method for Lightning Channel Temperature.

PubMed

Li, X; Zhang, J; Chen, L; Xue, Q; Zhu, R

2016-09-26

In this paper, we demonstrate the temperature of lightning channel utilizing the theory of lightning spectra and the model of local thermodynamic equilibrium (LTE). The impulse current generator platform (ICGS) was used to simulate the lightning discharge channel, and the spectral energy of infrared spectroscopy (930 nm) and the visible spectroscopy (648.2 nm) of the simulated lightning has been calculated. Results indicate that the peaks of luminous intensity of both infrared and visible spectra increase with the lightning current intensity in range of 5-50 kA. Based on the results, the temperature of the lightning channel is derived to be 6140.8-10424 K. Moreover, the temperature of the channel is approximately exponential to the lightning current intensity, which shows good agreement with that of the natural lightning cases.

Measuring Method for Lightning Channel Temperature

NASA Astrophysics Data System (ADS)

Li, X.; Zhang, J.; Chen, L.; Xue, Q.; Zhu, R.

2016-09-01

In this paper, we demonstrate the temperature of lightning channel utilizing the theory of lightning spectra and the model of local thermodynamic equilibrium (LTE). The impulse current generator platform (ICGS) was used to simulate the lightning discharge channel, and the spectral energy of infrared spectroscopy (930 nm) and the visible spectroscopy (648.2 nm) of the simulated lightning has been calculated. Results indicate that the peaks of luminous intensity of both infrared and visible spectra increase with the lightning current intensity in range of 5-50 kA. Based on the results, the temperature of the lightning channel is derived to be 6140.8-10424 K. Moreover, the temperature of the channel is approximately exponential to the lightning current intensity, which shows good agreement with that of the natural lightning cases.

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.

The evolution of discharge current and channel radius in cloud-to-ground lightning return stroke process

NASA Astrophysics Data System (ADS)

Fan, Tingting; Yuan, Ping; Wang, Xuejuan; Cen, Jianyong; Chang, Xuan; Zhao, Yanyan

2017-09-01

The spectra of two negative cloud-to-ground lightning discharge processes with multi-return strokes are obtained by a slit-less high-speed spectrograph, which the temporal resolution is 110 μs. Combined with the synchronous electrical observation data and theoretical calculation, the physical characteristics during return strokes process are analysed. A positive correlation between discharge current and intensity of ionic lines in the spectra is verified, and based on this feature, the current evolution characteristics during four return strokes are investigated. The results show that the time from peak current to the half-peak value estimated by multi point-fitting is about 101 μs-139 μs. The Joule heat in per unit length of four return strokes channel is in the order of 105J/m-106 J/m. The radius of arc discharge channel is positively related to the discharge current, and the more intense the current is, the greater the radius of channel is. Furthermore, the evolution for radius of arc core channel in the process of return stroke is consistent with the change trend of discharge current after the peak value. Compared with the decay of the current, the temperature decreases more slowly.

Detection of single ion channel activity with carbon nanotubes

NASA Astrophysics Data System (ADS)

Zhou, Weiwei; Wang, Yung Yu; Lim, Tae-Sun; Pham, Ted; Jain, Dheeraj; Burke, Peter J.

2015-03-01

Many processes in life are based on ion currents and membrane voltages controlled by a sophisticated and diverse family of membrane proteins (ion channels), which are comparable in size to the most advanced nanoelectronic components currently under development. Here we demonstrate an electrical assay of individual ion channel activity by measuring the dynamic opening and closing of the ion channel nanopores using single-walled carbon nanotubes (SWNTs). Two canonical dynamic ion channels (gramicidin A (gA) and alamethicin) and one static biological nanopore (α-hemolysin (α-HL)) were successfully incorporated into supported lipid bilayers (SLBs, an artificial cell membrane), which in turn were interfaced to the carbon nanotubes through a variety of polymer-cushion surface functionalization schemes. The ion channel current directly charges the quantum capacitance of a single nanotube in a network of purified semiconducting nanotubes. This work forms the foundation for a scalable, massively parallel architecture of 1d nanoelectronic devices interrogating electrophysiology at the single ion channel level.

MO-DE-207A-05: Dictionary Learning Based Reconstruction with Low-Rank Constraint for Low-Dose Spectral CT

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

Xu, Q; Stanford University School of Medicine, Stanford, CA; Liu, H

Purpose: Spectral CT enabled by an energy-resolved photon-counting detector outperforms conventional CT in terms of material discrimination, contrast resolution, etc. One reconstruction method for spectral CT is to generate a color image from a reconstructed component in each energy channel. However, given the radiation dose, the number of photons in each channel is limited, which will result in strong noise in each channel and affect the final color reconstruction. Here we propose a novel dictionary learning method for spectral CT that combines dictionary-based sparse representation method and the patch based low-rank constraint to simultaneously improve the reconstruction in each channelmore » and to address the inter-channel correlations to further improve the reconstruction. Methods: The proposed method has two important features: (1) guarantee of the patch based sparsity in each energy channel, which is the result of the dictionary based sparse representation constraint; (2) the explicit consideration of the correlations among different energy channels, which is realized by patch-by-patch nuclear norm-based low-rank constraint. For each channel, the dictionary consists of two sub-dictionaries. One is learned from the average of the images in all energy channels, and the other is learned from the average of the images in all energy channels except the current channel. With average operation to reduce noise, these two dictionaries can effectively preserve the structural details and get rid of artifacts caused by noise. Combining them together can express all structural information in current channel. Results: Dictionary learning based methods can obtain better results than FBP and the TV-based method. With low-rank constraint, the image quality can be further improved in the channel with more noise. The final color result by the proposed method has the best visual quality. Conclusion: The proposed method can effectively improve the image quality of low-dose spectral CT. This work is partially supported by the National Natural Science Foundation of China (No. 61302136), and the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2014JQ8317).« less

High throughput screening technologies for ion channels

PubMed Central

Yu, Hai-bo; Li, Min; Wang, Wei-ping; Wang, Xiao-liang

2016-01-01

Ion channels are involved in a variety of fundamental physiological processes, and their malfunction causes numerous human diseases. Therefore, ion channels represent a class of attractive drug targets and a class of important off-targets for in vitro pharmacological profiling. In the past decades, the rapid progress in developing functional assays and instrumentation has enabled high throughput screening (HTS) campaigns on an expanding list of channel types. Chronologically, HTS methods for ion channels include the ligand binding assay, flux-based assay, fluorescence-based assay, and automated electrophysiological assay. In this review we summarize the current HTS technologies for different ion channel classes and their applications. PMID:26657056

Measuring Method for Lightning Channel Temperature

PubMed Central

Li, X.; Zhang, J.; Chen, L.; Xue, Q.; Zhu, R.

2016-01-01

In this paper, we demonstrate the temperature of lightning channel utilizing the theory of lightning spectra and the model of local thermodynamic equilibrium (LTE). The impulse current generator platform (ICGS) was used to simulate the lightning discharge channel, and the spectral energy of infrared spectroscopy (930 nm) and the visible spectroscopy (648.2 nm) of the simulated lightning has been calculated. Results indicate that the peaks of luminous intensity of both infrared and visible spectra increase with the lightning current intensity in range of 5–50 kA. Based on the results, the temperature of the lightning channel is derived to be 6140.8–10424 K. Moreover, the temperature of the channel is approximately exponential to the lightning current intensity, which shows good agreement with that of the natural lightning cases. PMID:27665937

Field effect transistors based on phosphorene nanoribbon with selective edge-adsorption: A first-principles study

NASA Astrophysics Data System (ADS)

Hu, Mengli; Yang, Zhixiong; Zhou, Wenzhe; Li, Aolin; Pan, Jiangling; Ouyang, Fangping

2018-04-01

By using density functional theory (DFT) and nonequilibrium Green's function (NEGF), field effect transistor (FET) based on zigzag shaped phosphorene nanoribbons (ZPNR) are investigated. The FETs are constructed with bare-edged ZPNRs as electrodes and H, Cl or OH adsorbed ZPNRs as channel. It is found FETs with the three kinds of channel show similar transport properties. The FET is p-type with a maximum current on/off ratio of 104 and a minimum off-current of 1 nA. The working mode of FETs is dependent on the parity of channel length. It can be either enhancement mode or depletion mode and the off-state current shows an even-odd oscillation. The current oscillations are interpreted with density of states (DOS) analysis and methods of evolution operator and tight-binding Hamiltonian. Operating mechanism of the designed FETs is also presented with projected local density of states and band diagrams.

M Current-Based Therapies for Nerve Agent Seizures

DTIC Science & Technology

2013-07-01

Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Seizures, status epilepticus Cholinergic, M Current...Channel openers in cholinergic overstimulation-induced status epilepticus . Body: We proposed to study the effects of organophosphates and muscarinic...test whether drugs that open M channels would terminate status epilepticus induced by an organophosphate and cholinergic agonist (Li/Pilocarpine). Two

Transport properties and device-design of Z-shaped MoS2 nanoribbon planar junctions

NASA Astrophysics Data System (ADS)

Zhang, Hua; Zhou, Wenzhe; Liu, Qi; Yang, Zhixiong; Pan, Jiangling; Ouyang, Fangping; Xu, Hui

2017-09-01

Based on MoS2 nanoribbons, metal-semiconductor-metal planar junction devices were constructed. The electronic and transport properties of the devices were studied by using density function theory (DFT) and nonequilibrium Green's functions (NEGF). It is found that a band gap about 0.4 eV occurs in the planar junction. The electron and hole transmissions of the devices are mainly contributed by the Mo atomic orbitals. The electron transport channel is located at the edge of armchair MoS2 nanoribbon, while the hole transport channel is delocalized in the channel region. The I-V curve of the two-probe device shows typical transport behavior of Schottky barrier, and the threshold voltage is of about 0.2 V. The field effect transistors (FET) based on the planar junction turn out to be good bipolar transistors, the maximum current on/off ratio can reach up to 1 × 104, and the subthreshold swing is 243 mV/dec. It is found that the off-state current is dependent on the length and width of the channel, while the on-state current is almost unaffected. The switching performance of the FET is improved with increasing the length of the channel, and shows oscillation behavior with the change of the channel width.

Shipborne LF-VLF oceanic lightning observations and modeling

NASA Astrophysics Data System (ADS)

Zoghzoghy, F. G.; Cohen, M. B.; Said, R. K.; Lehtinen, N. G.; Inan, U. S.

2015-10-01

Approximately 90% of natural lightning occurs over land, but recent observations, using Global Lightning Detection (GLD360) geolocation peak current estimates and satellite optical data, suggested that cloud-to-ground flashes are on average stronger over the ocean. We present initial statistics from a novel experiment using a Low Frequency (LF) magnetic field receiver system installed aboard the National Oceanic Atmospheric Agency (NOAA) Ronald W. Brown research vessel that allowed the detection of impulsive radio emissions from deep-oceanic discharges at short distances. Thousands of LF waveforms were recorded, facilitating the comparison of oceanic waveforms to their land counterparts. A computationally efficient electromagnetic radiation model that accounts for propagation over lossy and curved ground is constructed and compared with previously published models. We include the effects of Earth curvature on LF ground wave propagation and quantify the effects of channel-base current risetime, channel-base current falltime, and return stroke speed on the radiated LF waveforms observed at a given distance. We compare simulation results to data and conclude that previously reported larger GLD360 peak current estimates over the ocean are unlikely to fully result from differences in channel-base current risetime, falltime, or return stroke speed between ocean and land flashes.

Characteristics of M-component in rocket-triggered lightning and a discussion on its mechanism

NASA Astrophysics Data System (ADS)

Jiang, Rubin; Qie, Xiushu; Yang, Jing; Wang, Caixia; Zhao, Yang

2013-09-01

The current and electric field pulses associated with M-component following dart leader-return stroke sequences in negative rocket-triggered lightning flashes were analyzed in detail by using the data from Shandong Artificially Triggering Lightning Experiment, conducted from 2005 to 2010. For 63 M-components with current waveforms superimposed on the relatively steady continuing current, the geometric mean values of the peak current, duration, and charge transfer were 276 A, 1.21 ms, and 101 mC, respectively. The behaviors of the channel base current versus close electric field changes and the observation facts by different authors were carefully examined for investigation on mechanism of the M-component. A modified model based on Rakov's "two-wave" theory is proposed and confirms that the evolution of M-component through the lightning channel involves a downward wave transferring negative charge from the upper to the lower channel and an upward wave draining the charge transported by the downward wave. The upward wave serves to deplete the negative charge by the downward wave at its interface and makes the charge density of the channel beneath the interface layer to be roughly zero. Such modified concept is recognized to be reasonable by the simulated results showing a good agreement between the calculated and the measured E-field waveforms.

Lightning Return-Stroke Current Waveforms Aloft, from Measured Field Change, Current, and Channel Geometry

NASA Technical Reports Server (NTRS)

Willett, J. C.; LeVine, D. M.; Idone, V. P.

2006-01-01

Three-dimensional reconstructions of six rocket-triggered lightning channels are derived from stereo photographs. These reconstructed channels are used to infer the behavior of the current in return strokes above the ground from current waveforms measured at the channel base and electric-field-change waveforms measured at a range of 5.2 kilometers for 24 return strokes in these channels. Streak photographs of 14 of the same strokes are analyzed to determine the rise times, propagation speeds, and amplitudes of relative light intensity for comparison with the electrical inferences. Results include the following: 1) The fine structure of the field-change waveforms that were radiated by these subsequent return strokes can be explained, in large part, by channel geometry. 2) The average 10 - 90% rise time of the stroke current increased by about a factor of seven in our sample, from an observed 0.31 plus or minus 0.17 microseconds at the surface to an inferred 2.2 plus or minus 0.5 microcseconds at 1 kilometer path length above the surface. 3) The three-dimensional propagation speed of the current front averaged 1.80 plus or minus 0.24 X 10(exp 8) meters per second over channel lengths typically greater than 1 kilometer. 4) Assuming that the measured current was entirely due to the return stroke forced an unreasonably large and abrupt reduction in inferred current amplitude over the first few tens of meters above the surface, especially in cases when the leader was bright relative to its stroke. Therefore, a significant fraction of the current at the surface was probably due to the leader, at least in such cases. 5) Peak return-stroke currents decreased by approximately 37 plus or minus 12% from 100 meters to 1 kilometer of path length above the surface. Because of uncertainty about how to partition the measured current between leader and return stroke, we are unable to infer the variation of current amplitude near the ground.

Voltage-dependent inward currents in smooth muscle cells of skeletal muscle arterioles

PubMed Central

Shirokov, Roman E.

2018-01-01

Voltage-dependent inward currents responsible for the depolarizing phase of action potentials were characterized in smooth muscle cells of 4th order arterioles in mouse skeletal muscle. Currents through L-type Ca2+ channels were expected to be dominant; however, action potentials were not eliminated in nominally Ca2+-free bathing solution or by addition of L-type Ca2+ channel blocker nifedipine (10 μM). Instead, Na+ channel blocker tetrodotoxin (TTX, 1 μM) reduced the maximal velocity of the upstroke at low, but not at normal (2 mM), Ca2+ in the bath. The magnitude of TTX-sensitive currents recorded with 140 mM Na+ was about 20 pA/pF. TTX-sensitive currents decreased five-fold when Ca2+ increased from 2 to 10 mM. The currents reduced three-fold in the presence of 10 mM caffeine, but remained unaltered by 1 mM of isobutylmethylxanthine (IBMX). In addition to L-type Ca2+ currents (15 pA/pF in 20 mM Ca2+), we also found Ca2+ currents that are resistant to 10 μM nifedipine (5 pA/pF in 20 mM Ca2+). Based on their biophysical properties, these Ca2+ currents are likely to be through voltage-gated T-type Ca2+ channels. Our results suggest that Na+ and at least two types (T- and L-) of Ca2+ voltage-gated channels contribute to depolarization of smooth muscle cells in skeletal muscle arterioles. Voltage-gated Na+ channels appear to be under a tight control by Ca2+ signaling. PMID:29694371

Machine-Learning Based Channel Quality and Stability Estimation for Stream-Based Multichannel Wireless Sensor Networks.

PubMed

Rehan, Waqas; Fischer, Stefan; Rehan, Maaz

2016-09-12

Wireless sensor networks (WSNs) have become more and more diversified and are today able to also support high data rate applications, such as multimedia. In this case, per-packet channel handshaking/switching may result in inducing additional overheads, such as energy consumption, delays and, therefore, data loss. One of the solutions is to perform stream-based channel allocation where channel handshaking is performed once before transmitting the whole data stream. Deciding stream-based channel allocation is more critical in case of multichannel WSNs where channels of different quality/stability are available and the wish for high performance requires sensor nodes to switch to the best among the available channels. In this work, we will focus on devising mechanisms that perform channel quality/stability estimation in order to improve the accommodation of stream-based communication in multichannel wireless sensor networks. For performing channel quality assessment, we have formulated a composite metric, which we call channel rank measurement (CRM), that can demarcate channels into good, intermediate and bad quality on the basis of the standard deviation of the received signal strength indicator (RSSI) and the average of the link quality indicator (LQI) of the received packets. CRM is then used to generate a data set for training a supervised machine learning-based algorithm (which we call Normal Equation based Channel quality prediction (NEC) algorithm) in such a way that it may perform instantaneous channel rank estimation of any channel. Subsequently, two robust extensions of the NEC algorithm are proposed (which we call Normal Equation based Weighted Moving Average Channel quality prediction (NEWMAC) algorithm and Normal Equation based Aggregate Maturity Criteria with Beta Tracking based Channel weight prediction (NEAMCBTC) algorithm), that can perform channel quality estimation on the basis of both current and past values of channel rank estimation. In the end, simulations are made using MATLAB, and the results show that the Extended version of NEAMCBTC algorithm (Ext-NEAMCBTC) outperforms the compared techniques in terms of channel quality and stability assessment. It also minimizes channel switching overheads (in terms of switching delays and energy consumption) for accommodating stream-based communication in multichannel WSNs.

Machine-Learning Based Channel Quality and Stability Estimation for Stream-Based Multichannel Wireless Sensor Networks

PubMed Central

Rehan, Waqas; Fischer, Stefan; Rehan, Maaz

2016-01-01

Wireless sensor networks (WSNs) have become more and more diversified and are today able to also support high data rate applications, such as multimedia. In this case, per-packet channel handshaking/switching may result in inducing additional overheads, such as energy consumption, delays and, therefore, data loss. One of the solutions is to perform stream-based channel allocation where channel handshaking is performed once before transmitting the whole data stream. Deciding stream-based channel allocation is more critical in case of multichannel WSNs where channels of different quality/stability are available and the wish for high performance requires sensor nodes to switch to the best among the available channels. In this work, we will focus on devising mechanisms that perform channel quality/stability estimation in order to improve the accommodation of stream-based communication in multichannel wireless sensor networks. For performing channel quality assessment, we have formulated a composite metric, which we call channel rank measurement (CRM), that can demarcate channels into good, intermediate and bad quality on the basis of the standard deviation of the received signal strength indicator (RSSI) and the average of the link quality indicator (LQI) of the received packets. CRM is then used to generate a data set for training a supervised machine learning-based algorithm (which we call Normal Equation based Channel quality prediction (NEC) algorithm) in such a way that it may perform instantaneous channel rank estimation of any channel. Subsequently, two robust extensions of the NEC algorithm are proposed (which we call Normal Equation based Weighted Moving Average Channel quality prediction (NEWMAC) algorithm and Normal Equation based Aggregate Maturity Criteria with Beta Tracking based Channel weight prediction (NEAMCBTC) algorithm), that can perform channel quality estimation on the basis of both current and past values of channel rank estimation. In the end, simulations are made using MATLAB, and the results show that the Extended version of NEAMCBTC algorithm (Ext-NEAMCBTC) outperforms the compared techniques in terms of channel quality and stability assessment. It also minimizes channel switching overheads (in terms of switching delays and energy consumption) for accommodating stream-based communication in multichannel WSNs. PMID:27626429

In situ and online monitoring of hydrodynamic flow profiles in microfluidic channels based upon microelectrochemistry: concept, theory, and validation.

PubMed

Amatore, Christian; Oleinick, Alexander; Klymenko, Oleksiy V; Svir, Irina

2005-08-12

Herein, we propose a method for reconstructing any plausible macroscopic hydrodynamic flow profile occurring locally within a rectangular microfluidic channel. The method is based on experimental currents measured at single or double microband electrodes embedded in one channel wall. A perfectly adequate quasiconformal mapping of spatial coordinates introduced in our previous work [Electrochem. Commun. 2004, 6, 1123] and an exponentially expanding time grid, initially proposed [J. Electroanal. Chem. 2003, 557, 75] in conjunction with the solution of the corresponding variational problem approached by the Ritz method are used for the numerical reconstruction of flow profiles. Herein, the concept of the method is presented and developed theoretically and its validity is tested on the basis of the use of pseudoexperimental currents emulated by simulation of the diffusion-convection problem in a channel flow cell, to which a random Gaussian current noise is added. The flow profiles reconstructed by our method compare successfully with those introduced a priori into the simulations, even when these include significant distortions compared with either classical Poiseuille or electro-osmotic flows.

Two-dimensional velocity, optical risetime, and peak current estimates for natural positive lightning return strokes

NASA Technical Reports Server (NTRS)

Mach, Douglas M.; Rust, W. D.

1993-01-01

Velocities, optical risetimes, and transmission line model peak currents for seven natural positive return strokes are reported. The average 2D positive return stroke velocity for channel segments of less than 500 m in length starting near the base of the channel is 0.8 +/- 0.3 x 10 exp 8 m/s, which is slower than the present corresponding average velocity for natural negative first return strokes of 1.7 +/- 0.7 x 10 exp 8/s. It is inferred that positive stroke peak currents in the literature, which assume the same velocity as negative strokes, are low by a factor of 2. The average 2D positive return stroke velocity for channel segments of greater than 500 m starting near the base of the channel is 0.9 +/- 0.4 x 10 exp 8 m/s. The corresponding average velocity for the present natural negative first strokes is 1.2 +/- 0.6 x 10 exp 8 m/s. No significant velocity change with height is found for positive return strokes.

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

Thermal power and heat energy of cloud-to-ground lightning process

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

Wang, Xuejuan; Yuan, Ping; Xue, Simin

2016-07-15

A cloud-to-ground lightning flash with nine return strokes has been recorded using a high speed slitless spectrograph and a system composed of a fast antenna and a slow antenna. Based on the spectral data and the synchronous electric field changes that were caused by the lightning, the electrical conductivity, the channel radii, the resistance per unit length, the peak current, the thermal power at the instant of peak current, and the heat energy per unit length during the first 5 μs in the discharge channel have all been calculated. The results indicate that the channel radii have linear relationships with themore » peak current. The thermal power at the peak current time increases with increasing resistance, but exponential decays with the square of the peak current.« less

Utilizing Schottky barriers to suppress short-channel effects in organic transistors

NASA Astrophysics Data System (ADS)

Fernández, Anton F.; Zojer, Karin

2017-10-01

Transistors with short channel lengths exhibit profound deviations from the ideally expected behavior. One of the undesired short-channel effects is an enlarged OFF current that is associated with a premature turn on of the transistor. We present an efficient approach to suppress the OFF current, defined as the current at zero gate source bias, in short-channel organic transistors. We employ two-dimensional device simulations based on the drift-diffusion model to demonstrate that intentionally incorporating a Schottky barrier for injection enhances the ON-OFF ratio in both staggered and coplanar transistor architectures. The Schottky barrier is identified to directly counteract the origin of enlarged OFF currents: Short channels promote a drain-induced barrier lowering. The latter permits unhindered injection of charges even at reverse gate-source bias. An additional Schottky barrier hampers injection for such points of operations. We explain how it is possible to find the Schottky barrier of the smallest height necessary to exactly compensate for the premature turn on. This approach offers a substantial enhancement of the ON-OFF ratio. We show that this roots in the fact that such optimal barrier heights offer an excellent compromise between an OFF current diminished by orders of magnitude and an only slightly reduced ON current.

A hydrophilic polymer based microfluidic system with planar patch clamp electrode array for electrophysiological measurement from cells.

PubMed

Xu, Baojian; Ye, WeiWei; Zhang, Yu; Shi, JingYu; Chan, ChunYu; Yao, XiaoQiang; Yang, Mo

2014-03-15

This paper presents a microfluidic planar patch clamp system based on a hydrophilic polymer poly(ethylene glycol) diacrylate (PEGDA) for whole cell current recording. The whole chip is fabricated by UV-assisted molding method for both microfluidic channel structure and planar electrode partition. This hydrophilic patch clamp chip has demonstrated a relatively high gigaseal success rate of 44% without surface modification compared with PDMS based patch clamp devices. This chip also shows a capability of rapid intracellular and extracellular solution exchange with high stability of gigaseals. The capillary flow kinetic experiments demonstrate that the flow rates of PEGDA microfluidic channels are around two orders of magnitude greater than those for PDMS-glass channels with the same channel dimensions. This hydrophilic polymer based patch clamp chips have significant advantages over current PDMS elastomer based systems such as no need for surface modification, much higher success rate of cell gigaseals and rapid solution exchange with stable cell gigaseals. Our results indicate the potential of these devices to serve as useful tools for pharmaceutical screening and biosensing tasks. © 2013 Elsevier B.V. All rights reserved.

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

Development of a Microprocessor-Based Asynchronous Data Communications Line Tester.

DTIC Science & Technology

1981-12-01

either RS232 or 20 mA current loop 13. Current loop optically isolated 14. Current loop selectable for either active or pasive mode 15. Address...Executin Invoking the execution of the software is therefore a matter of power-up and reset. The software will wait for a response from the console (any key...SIO has two channels as previously mentioned. Addressing the SIO then is a matter of addressing these two channels. The port addrecses are user defined

Functional ion channels in human pulmonary artery smooth muscle cells: Voltage-dependent cation channels

PubMed Central

Firth, Amy L.; Remillard, Carmelle V.; Platoshyn, Oleksandr; Fantozzi, Ivana; Ko, Eun A.; Yuan, Jason X.-J.

2011-01-01

The activity of voltage-gated ion channels is critical for the maintenance of cellular membrane potential and generation of action potentials. In turn, membrane potential regulates cellular ion homeostasis, triggering the opening and closing of ion channels in the plasma membrane and, thus, enabling ion transport across the membrane. Such transmembrane ion fluxes are important for excitation–contraction coupling in pulmonary artery smooth muscle cells (PASMC). Families of voltage-dependent cation channels known to be present in PASMC include voltage-gated K+ (Kv) channels, voltage-dependent Ca2+-activated K+ (Kca) channels, L- and T- type voltage-dependent Ca2+ channels, voltage-gated Na+ channels and voltage-gated proton channels. When cells are dialyzed with Ca2+-free K+- solutions, depolarization elicits four components of 4-aminopyridine (4-AP)-sensitive Kvcurrents based on the kinetics of current activation and inactivation. In cell-attached membrane patches, depolarization elicits a wide range of single-channel K+ currents, with conductances ranging between 6 and 290 pS. Macroscopic 4-AP-sensitive Kv currents and iberiotoxin-sensitive Kca currents are also observed. Transcripts of (a) two Na+ channel α-subunit genes (SCN5A and SCN6A), (b) six Ca2+ channel α–subunit genes (α1A, α1B, α1X, α1D, α1Eand α1G) and many regulatory subunits (α2δ1, β1-4, and γ6), (c) 22 Kv channel α–subunit genes (Kv1.1 - Kv1.7, Kv1.10, Kv2.1, Kv3.1, Kv3.3, Kv3.4, Kv4.1, Kv4.2, Kv5.1, Kv 6.1-Kv6.3, Kv9.1, Kv9.3, Kv10.1 and Kv11.1) and three Kv channel β-subunit genes (Kvβ1-3) and (d) four Kca channel α–subunit genes (Sloα1 and SK2-SK4) and four Kca channel β-subunit genes (Kcaβ1-4) have been detected in PASMC. Tetrodotoxin-sensitive and rapidly inactivating Na+ currents have been recorded with properties similar to those in cardiac myocytes. In the presence of 20 mM external Ca2+, membrane depolarization from a holding potential of -100 mV elicits a rapidly inactivating T-type Ca2+ current, while depolarization from a holding potential of -70 mV elicits a slowly inactivating dihydropyridine-sensitive L-type Ca2+ current. This review will focus on describing the electrophysiological properties and molecular identities of these voltage-dependent cation channels in PASMC and their contribution to the regulation of pulmonary vascular function and its potential role in the pathogenesis of pulmonary vascular disease. PMID:21927714

Depositional architecture and evolution of the Late Miocene slope channel-fan-system in the northeastern shelf-margin of South China Sea

NASA Astrophysics Data System (ADS)

Jiang, Jing; Lin, Changsong; Zhang, Zhongtao; Tian, Hongxun; Tao, Ze; Liu, Hanyao

2016-04-01

The Upper Miocene in the Pearl River Mouth Basin of northwestern shelf-margin of South China Sea Basin contains a series of slope channel - fan systems. Their depositional architecture and evolution are documented in this investigation based on an integrated analysis of cores, logs, and seismic data. Four depositional-palaeogeomorphological elements have been identified in the slope channel-fan systems as follows: broad, shallow and unconfined or partly confined outer-shelf to shelf-break channels; deeply incised and confined unidirectionally migrating slope channels; broad or U-shaped, unconfined erosional-depositional channels; frontal splays-lobes and nonchannelized sheets. The slope channels are mostly oriented NW-SE, which migrated unidirectionally northeastwards and intensively eroded almost the whole shelf-slope zone. The channel infillings are mainly mudstones, interbedded with siltstones. They might be formed by gravity flow erosion as bypassing channels. They were filled with limited gravity flow sediments at the base and mostly filled with lateral accretionary packages of bottom current deposits. At the end of the channels, a series of small-scale slope fans developed and coalesced into fan aprons along the base of the slope. The unconfined erosional-depositional channels at the upper parts of the fan-apron-systems display compound infill patterns, and commonly have concave erosional bases and convex tops. The frontal splays-lobes representing middle to distal deposits of fan-apron-systems have flat-mounded or gull-wing geometries, and the internal architectures include bidirectional downlap, progradation, and chaotic infillings. The distal nonchannelized turbidite sheets are characterized by thin-bedded, parallel to sub-parallel sheet-like geometries. Three major unconformities or obvious erosional surfaces in the channel-fan systems of the Upper Miocene are recognized, and indicate the falling of sea-level. The depositional architecture of sequences varies from the upper slope to the slope base transitional to basin plain. The basal erosion and the unidirectionally migrating characters of the slope channels were supposed to be the result of the interaction of bottom currents and gravity flows. The intensive development of the channel-fan systems over the shelf slope might be related to the Dongsha Tectonic uplift which may resulted in stepped slope and concomitantly intensified gravity flow in the study area in Late Miocene.

Method and system for a gas tube switch-based voltage source high voltage direct current transmission system

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

She, Xu; Chokhawala, Rahul Shantilal; Zhou, Rui

A voltage source converter based high-voltage direct-current (HVDC) transmission system includes a voltage source converter (VSC)-based power converter channel. The VSC-based power converter channel includes an AC-DC converter and a DC-AC inverter electrically coupled to the AC-DC converter. The AC-DC converter and a DC-AC inverter include at least one gas tube switching device coupled in electrical anti-parallel with a respective gas tube diode. The VSC-based power converter channel includes a commutating circuit communicatively coupled to one or more of the at least one gas tube switching devices. The commutating circuit is configured to "switch on" a respective one of themore » one or more gas tube switching devices during a first portion of an operational cycle and "switch off" the respective one of the one or more gas tube switching devices during a second portion of the operational cycle.« less

Comparison of effect of 5 MeV proton and Co-60 gamma irradiation on silicon NPN rf power transistors and N-channel depletion MOSFETs

NASA Astrophysics Data System (ADS)

Gnana Prakash, A. P.; Pradeep, T. M.; Hegde, Vinayakprasanna N.; Pushpa, N.; Bajpai, P. K.; Patel, S. P.; Trivedi, Tarkeshwar; Bhushan, K. G.

2017-12-01

NPN transistors and N-channel depletion metal oxide semiconductor field effect transistors (MOSFETs) were irradiated with 5 MeV protons and 60Co gamma radiation in the dose ranging from 1 Mrad(Si) to 100 Mrad(Si). The different electrical characteristics of the NPN transistor such as Gummel characteristics, excess base current (ΔIB), dc current gain (hFE), transconductance (gm), displacement damage factor (K) and output characteristics were studied as a function of total dose. The different electrical characteristics of N-channel MOSFETs such as threshold voltage (Vth), density of interface trapped charges (ΔNit), density of oxide trapped charges (ΔNot), transconductance (gm), mobility (µ) and drain saturation current (IDSat) were studied systematically before and after irradiation in the same dose ranges. A considerable increase in the base current (IB) and decrease in the hFE, gm and collector saturation current (ICSat) were observed after irradiation in the case of the NPN transistor. In the N-channel MOSFETs, the ΔNit and ΔNot were found to increase and Vth, gm, µ and IDSat were found to decrease with increase in the radiation dose. The 5 MeV proton irradiation results of both the NPN transistor and N-channel MOSFETs were compared with 60Co gamma-irradiated devices in the same dose ranges. It was observed that the degradation in 5 MeV proton-irradiated devices is more when compared with the 60Co gamma-irradiated devices at higher total doses.

Design and simulation of novel flow field plate geometry for proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Ruan, Hanxia; Wu, Chaoqun; Liu, Shuliang; Chen, Tao

2016-10-01

Bipolar plate is one of the many important components of proton exchange membrane fuel cell (PEMFC) stacks as it supplies fuel and oxidant to the membrane-electrode assembly (MEA), removes water, collects produced current and provides mechanical support for the single cells in the stack. The flow field design of a bipolar plate greatly affects the performance of a PEMFC. It must uniformly distribute the reactant gases over the MEA and prevent product water flooding. This paper aims at improving the fuel cell performance by optimizing flow field designs and flow channel configurations. To achieve this, a novel biomimetic flow channel for flow field designs is proposed based on Murray's Law. Computational fluid dynamics based simulations were performed to compare three different designs (parallel, serpentine and biomimetic channel, respectively) in terms of current density distribution, power density distribution, pressure distribution, temperature distribution, and hydrogen mass fraction distribution. It was found that flow field designs with biomimetic flow channel perform better than that with convectional flow channel under the same operating conditions.

Population Density and Moment-based Approaches to Modeling Domain Calcium-mediated Inactivation of L-type Calcium Channels.

PubMed

Wang, Xiao; Hardcastle, Kiah; Weinberg, Seth H; Smith, Gregory D

2016-03-01

We present a population density and moment-based description of the stochastic dynamics of domain [Formula: see text]-mediated inactivation of L-type [Formula: see text] channels. Our approach accounts for the effect of heterogeneity of local [Formula: see text] signals on whole cell [Formula: see text] currents; however, in contrast with prior work, e.g., Sherman et al. (Biophys J 58(4):985-995, 1990), we do not assume that [Formula: see text] domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain model of an L-type [Formula: see text] channel introduced by Greenstein and Winslow (Biophys J 83(6):2918-2945, 2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell [Formula: see text] current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of [Formula: see text] inactivation that may occur via slow heterogeneous domain [[Formula: see text

Voltage-dependent ion channels in the mouse RPE: comparison with Norrie disease mice.

PubMed

Wollmann, Guido; Lenzner, Steffen; Berger, Wolfgang; Rosenthal, Rita; Karl, Mike O; Strauss, Olaf

2006-03-01

We studied electrophysiological properties of cultured retinal pigment epithelial (RPE) cells from mouse and a mouse model for Norrie disease. Wild-type RPE cells revealed the expression of ion channels known from other species: delayed-rectifier K(+) channels composed of Kv1.3 subunits, inward rectifier K(+) channels, Ca(V)1.3 L-type Ca(2+) channels and outwardly rectifying Cl(-) channels. Expression pattern and the ion channel characteristics current density, blocker sensitivity, kinetics and voltage-dependence were compared in cells from wild-type and Norrie mice. Although no significant differences were observed, our study provides a base for future studies on ion channel function and dysfunction in transgenic mouse models.

Teleportation with Multiple Accelerated Partners

NASA Astrophysics Data System (ADS)

Sagheer, A.; Hamdoun, H.; Metwally, N.

2015-09-01

As the current revolution in communication is underway, quantum teleportation can increase the level of security in quantum communication applications. In this paper, we present a quantum teleportation procedure that capable to teleport either accelerated or non-accelerated information through different quantum channels. These quantum channels are based on accelerated multi-qubit states, where each qubit of each of these channels represents a partner. Namely, these states are the W state, Greenberger-Horne-Zeilinger (GHZ) state, and the GHZ-like state. Here, we show that the fidelity of teleporting accelerated information is higher than the fidelity of teleporting non-accelerated information, both through a quantum channel that is based on accelerated state. Also, the comparison among the performance of these three channels shows that the degree of fidelity depends on type of the used channel, type of the measurement, and value of the acceleration. The result of comparison concludes that teleporting information through channel that is based on the GHZ state is more robust than teleporting information through channels that are based on the other two states. For future work, the proposed procedure can be generalized later to achieve communication through a wider quantum network.

Molecular Targets for Antiepileptic Drug Development

PubMed Central

Meldrum, Brian S.; Rogawski, Michael A.

2007-01-01

Summary This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the α subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, α2–δ voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABAA receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABAB and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current Ih; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABAA receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies. PMID:17199015

Comparative use of side and main channels by small-bodied fish in a large, unimpounded river

USGS Publications Warehouse

Reinhold, Ann Marie; Bramblett, Robert G.; Zale, Alexander V.; Roberts, David W.; Poole, Geoffrey C.

2016-01-01

Ecological theory and field studies suggest that lateral floodplain connectivity and habitat heterogeneity provided by side channels impart favourable habitat conditions for lotic fishes, especially fluvial fishes dependent on large patches of shallow, slow velocity habitats for some portion of their life cycle. However, anthropogenic modification of large, temperate floodplain rivers has led to extensive channel simplification and side-channel loss. Highly modified rivers consist of simplified channels in contracted, less dynamic floodplains.Most research examining the seasonal importance of side channels for fish assemblages in large rivers has been carried out in heavily modified rivers, where side-channel extents are substantially reduced from pre-settlement times, and has often overlooked small-bodied fishes. Inferences about the ecological importance of side channels for small-bodied fishes in large rivers can be ascertained only from investigations of large rivers with largely intact floodplains. The Yellowstone River, our study area, is a rare example of one such river.We targeted small-bodied fishes and compared their habitat use in side and main channels in two geomorphically distinct types of river bends during early and late snowmelt runoff, and autumn base flow. Species compositions of side and main channels differed throughout hydroperiods concurrent with the seasonal redistribution of the availability of shallow, slow current-velocity habitats. More species of fish used side channels than main channels during runoff. Additionally, catch rates of small fishes were generally greater in side channels than in main channels and quantitative assemblage compositions differed between channel types during runoff, but not during base flow. Presence of and access to diverse habitats facilitated the development and persistence of diverse fish assemblages in our study area.Physical dissimilarities between side and main channels may have differentially structured the side- and main-channel fish assemblages during runoff. Patches of shallow, slow current-velocity (SSCV) habitats in side channels were larger and had slightly slower water velocities than SSCV habitat patches in main channels during runoff, but not during base flow.Our findings establish a baseline importance of side channels to riverine fishes in a large, temperate river without heavy anthropogenic modification. Establishing this baseline contributes to basic fluvial ecology and provides empirical justification for restoration efforts that reconnect large rivers with their floodplains.

Impact of Channel, Stress-Relaxed Buffer, and S/D Si1- x Ge x Stressor on the Performance of 7-nm FinFET CMOS Design with the Implementation of Stress Engineering

NASA Astrophysics Data System (ADS)

Othman, Nurul Aida Farhana; Hatta, Sharifah Fatmadiana Wan Muhamad; Soin, Norhayati

2018-04-01

Stress-engineered fin-shaped field effect transistors (FinFET) using germanium (Ge) is a promising performance booster to replace silicon (Si) due to its high holes mobility. This paper presents a three-dimensional simulation by the Sentaurus technology computer-aided design to study the effects of stressors—channel stress, stress-relaxed buffer (SRB), and source/drain (S/D) epitaxial stress—on different bases of FinFET, specifically silicon germanium (SiGe) and Ge-based, whereby the latter is achieved by manipulating the Ge mole fraction inside the three layers; their effects on the devices' figures-of-merits were recorded. The simulation generates an advanced calibration process, by which the drift diffusion simulation was adopted for ballistic transport effects. The results show that current enhancement in p-type FinFET (p-FinFET) with 110% is almost twice that in n-type FinFET (n-FinFET) with 57%, with increasing strain inside the channel suggesting that the use of strain is more effective for holes. In SiGe-based n-FinFET, the use of a high-strained SRB layer can improve the drive current up to 112%, while the high-strain S/D epitaxial for Ge-based p-FinFET can enhance the on-state current to 262%. Further investigations show that the channel and S/D doping are affecting the performances of SiGe-based FinFET with similar importance. It is observed that doping concentrations play an important role in threshold voltage adjustment as well as in drive current and subthreshold leakage improvements.

The activation of calcium and calcium-activated potassium channels in mammalian colonic smooth muscle by substance P.

PubMed Central

Mayer, E A; Loo, D D; Snape, W J; Sachs, G

1990-01-01

1. The regulation of Ca2(+)-activated K+ channels by the agonist substance P in freshly dissociated smooth muscle cells from the rabbit longitudinal colonic muscle was characterized using the patch clamp technique. 2. In the cell-attached recording mode, when pipette and bath solutions contained equal [K+] (126 mM), the Ca2(+)-activated K+ channels showed a linear current-voltage relationship (between -50 mV and 50 mV) with a slope conductance of 210 +/- 35 pS (n = 12). Reversal potential measurements indicated that the channel was highly selective for K+ over Na+ (PK/PNa = 110). 3. Channels were activated by depolarizing membrane voltages and cytosolic Ca2+, and in inside-out patches channel activation depended sigmoidally on voltage and [Ca2+]. The potential for half-activation at a cytosolic [Ca2+] of 5 x 10(-6) M was 0 mV. A tenfold increase in cytosolic Ca2+ resulted in a 60 mV shift of the sigmoidal voltage activation curve to more negative potentials. 4. Threshold concentrations of substance P (10(-12) M), which did not result in cell contraction, caused a prolonged activation of K+ channels. The K+ channels were observed to open in clusters: simultaneous opening of multiple channels was interrupted by complete, prolonged channel closure. 5. Lowering bath [Ca2+] to submicromolar concentrations abolished the effect of substance P. The activation of K+ channels by substance P (10(-12) M) was also inhibited by the dihydropyridine nifedipine (10(-6) M), a blocker of L-type Ca2+ channels. 6. In the whole-cell recording mode, with the pipette solution containing 126 mM-KCl, 0.77 mM-EGTA and 1 mM-ATP, depolarization from a holding potential of -70 mV elicited outward currents which increased to steady-state values. These were K+ currents as they were blocked by TEA (tetraethylammonium, 30 mM) and Ba2+ (1 mM) and were abolished when pipette K+ was replaced by Cs+. 7. The depolarization-activated outward current was not affected by lowering extracellular [Ca2+] or by the Ca2+ channel antagonists Cd2+ (200 microM), nifedipine (10(-6)-10(-5) M) or verapamil (10(-6) M). The current was greatly reduced when the EGTA concentration in the pipette solution was increased from 0.77 to 10 mM. 8. When the pipette solution contained CsCl, membrane depolarization activated inward currents. The peak inward current was identified as current through L-type Ca2+ channels based on its voltage- and time-dependent kinetics, and its modulation by dihydropyridines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1691293

An improved large signal model of InP HEMTs

NASA Astrophysics Data System (ADS)

Li, Tianhao; Li, Wenjun; Liu, Jun

2018-05-01

An improved large signal model for InP HEMTs is proposed in this paper. The channel current and charge model equations are constructed based on the Angelov model equations. Both the equations for channel current and gate charge models were all continuous and high order drivable, and the proposed gate charge model satisfied the charge conservation. For the strong leakage induced barrier reduction effect of InP HEMTs, the Angelov current model equations are improved. The channel current model could fit DC performance of devices. A 2 × 25 μm × 70 nm InP HEMT device is used to demonstrate the extraction and validation of the model, in which the model has predicted the DC I–V, C–V and bias related S parameters accurately. Project supported by the National Natural Science Foundation of China (No. 61331006).

Tide-surge Interaction Intensified by the Taiwan Strait

NASA Astrophysics Data System (ADS)

Zhang, Wen-Zhou; Shi, Fengyan; Hong, Hua-Sheng; Shang, Shao-Ping; Kirby, James T.

2010-06-01

The Taiwan Strait is a long and wide shelf-channel where the hydrodynamics is extremely complex, being characterized by strong tides, and where storm surges frequently occur during the typhoon season. Obvious oscillations due to tide-surge interaction were observed by tide gauges along the northern Fujian coast, the west bank of the Taiwan Strait, during Typhoon Dan (1999). Numerical experiments indicate that nonlinear bottom friction (described by the quadratic formula) is a major factor to predict these oscillations while the nonlinear advective terms and the shallow water effect have little contribution. It is found that the tide-surge interaction in the northern portion of the Taiwan Strait is intensified by the strait. Simulations based on simplified topographies with and without the island of Taiwan show that, in the presence of the island, the channel effect strengthens tidal currents and tends to align the major axes of tidal ellipses along the channel direction. Storm-induced currents are also strengthened by the channel. The pattern of strong tidal currents and storm-induced currents along the channel direction enhances tide-surge interaction via the nonlinear bottom friction, resulting in the obvious oscillations along the northern Fujian coast.

Computational study of graphene-based vertical field effect transistor

NASA Astrophysics Data System (ADS)

Chen, Wenchao; Rinzler, Andrew; Guo, Jing

2013-03-01

Poisson and drift-diffusion equations are solved in a three-dimensional device structure to simulate graphene-based vertical field effect transistors (GVFETs). Operation mechanisms of the GVFET with and without punched holes in the graphene source contact are presented and compared. The graphene-channel Schottky barrier can be modulated by gate electric field due to graphene's low density of states. For the graphene contact with punched holes, the contact barrier thinning and lowering around punched hole edge allow orders of magnitude higher tunneling current compared to the region away from the punched hole edge, which is responsible for significant performance improvement as already verified by experiments. Small hole size is preferred due to less electrostatic screening from channel inversion layer, which gives large electric field around the punched hole edge, thus, leading to a thinner and lower barrier. Bilayer and trilayer graphenes as the source contact degrade the performance improvement because stronger electrostatic screening leads to smaller contact barrier lowering and thinning. High punched hole area percentage improves current performance by allowing more gate electric field to modulate the graphene-channel barrier. Low effective mass channel material gives better on-off current ratio.

Bipolar cloud-to-ground lightning flash observations

NASA Astrophysics Data System (ADS)

Saba, Marcelo M. F.; Schumann, Carina; Warner, Tom A.; Helsdon, John H.; Schulz, Wolfgang; Orville, Richard E.

2013-10-01

lightning is usually defined as a lightning flash where the current waveform exhibits a polarity reversal. There are very few reported cases of cloud-to-ground (CG) bipolar flashes using only one channel in the literature. Reports on this type of bipolar flashes are not common due to the fact that in order to confirm that currents of both polarities follow the same channel to the ground, one necessarily needs video records. This study presents five clear observations of single-channel bipolar CG flashes. High-speed video and electric field measurement observations are used and analyzed. Based on the video images obtained and based on previous observations of positive CG flashes with high-speed cameras, we suggest that positive leader branches which do not participate in the initial return stroke of a positive cloud-to-ground flash later generate recoil leaders whose negative ends, upon reaching the branch point, traverse the return stroke channel path to the ground resulting in a subsequent return stroke of opposite polarity.

Structural studies of enzyme-based microfluidic biofuel cells

NASA Astrophysics Data System (ADS)

Togo, Makoto; Takamura, Akimasa; Asai, Tatsuya; Kaji, Hirokazu; Nishizawa, Matsuhiko

An enzyme-based glucose/O 2 biofuel cell was constructed within a microfluidic channel to study the influence of electrode configuration and fluidic channel height on cell performance. The cell was composed of a bilirubin oxidase (BOD)-adsorbed O 2 cathode and a glucose anode prepared by co-immobilization of glucose dehydrogenase (GDH), diaphorase (Dp) and VK 3-pendant poly- L-lysine. The consumption of O 2 at the upstream cathode protected the downstream anode from interfering O 2 molecules, and consequently improved the cell performance (maximum cell current) ca. 10% for the present cell. The cell performance was also affected by the channel height. The output current and power of a 0.1 mm-height cell was significantly less than those of a 1 mm-height cell because of the depletion of O 2, as determined by the shape of the E- I curve at the cathode. On the other hand, the volume density of current and power was several times higher for the narrower cell.

A spin current rectifier

NASA Astrophysics Data System (ADS)

Eyni, Zahra; Mohammadpour, Hakimeh

2017-12-01

Current modulation and rectification is an important subject of electronics as well as spintronics. In this paper, an efficient rectifying mesoscopic device is introduced. The device is a two terminal device on the 2D plane of electron gas. The lateral contacts are half-metal ferromagnetic with antiparallel magnetizations and the central channel region is taken as ferromagnetic or normal in the presence of an applied magnetic field. The device functionality is based on the modification of spin-current by tuning the strength of the magnetic field or equivalently by the exchange coupling of the channel to the substrate. The result is that the (spin-) current depends on the polarity of the bias voltage. Converting an alternating bias voltage to direct current is the main achievement of this model device with an additional profit of rectified spin-current. We analyze the results in terms of the spin-dependent barrier in the channel. Detecting the strength of the magnetic field by spin polarization is also suggested.

Calcium-calmodulin-dependent kinase II modulates Kv4.2 channel expression and upregulates neuronal A-type potassium currents.

PubMed

Varga, Andrew W; Yuan, Li-Lian; Anderson, Anne E; Schrader, Laura A; Wu, Gang-Yi; Gatchel, Jennifer R; Johnston, Daniel; Sweatt, J David

2004-04-07

Calcium-calmodulin-dependent kinase II (CaMKII) has a long history of involvement in synaptic plasticity, yet little focus has been given to potassium channels as CaMKII targets despite their importance in repolarizing EPSPs and action potentials and regulating neuronal membrane excitability. We now show that Kv4.2 acts as a substrate for CaMKII in vitro and have identified CaMKII phosphorylation sites as Ser438 and Ser459. To test whether CaMKII phosphorylation of Kv4.2 affects channel biophysics, we expressed wild-type or mutant Kv4.2 and the K(+) channel interacting protein, KChIP3, with or without a constitutively active form of CaMKII in Xenopus oocytes and measured the voltage dependence of activation and inactivation in each of these conditions. CaMKII phosphorylation had no effect on channel biophysical properties. However, we found that levels of Kv4.2 protein are increased with CaMKII phosphorylation in transfected COS cells, an effect attributable to direct channel phosphorylation based on site-directed mutagenesis studies. We also obtained corroborating physiological data showing increased surface A-type channel expression as revealed by increases in peak K(+) current amplitudes with CaMKII phosphorylation. Furthermore, endogenous A-currents in hippocampal pyramidal neurons were increased in amplitude after introduction of constitutively active CaMKII, which results in a decrease in neuronal excitability in response to current injections. Thus CaMKII can directly modulate neuronal excitability by increasing cell-surface expression of A-type K(+) channels.

Functional Na+ Channels in Cell Adhesion probed by Transistor Recording

PubMed Central

Schmidtner, Markus; Fromherz, Peter

2006-01-01

Cell membranes in a tissue are in close contact to each other, embedded in the extracellular matrix. Standard electrophysiological methods are not able to characterize ion channels under these conditions. Here we consider the area of cell adhesion on a solid substrate as a model system. We used HEK 293 cells cultured on fibronectin and studied the activation of NaV1.4 sodium channels in the adherent membrane with field-effect transistors in a silicon substrate. Under voltage clamp, we compared the transistor response with the whole-cell current. We observed that the extracellular voltage in the cell-chip contact was proportional to the total membrane current. The relation was calibrated by alternating-current stimulation. We found that Na+ channels are present in the area of cell adhesion on fibronectin with a functionality and a density that is indistinguishable from the free membrane. The experiment provides a basis for studying selective accumulation and depletion of ion channels in cell adhesion and also for a development of cell-based biosensoric devices and neuroelectronic systems. PMID:16227504

Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation.

PubMed

Schmidt, Constanze; Wiedmann, Felix; Voigt, Niels; Zhou, Xiao-Bo; Heijman, Jordi; Lang, Siegfried; Albert, Virginia; Kallenberger, Stefan; Ruhparwar, Arjang; Szabó, Gábor; Kallenbach, Klaus; Karck, Matthias; Borggrefe, Martin; Biliczki, Peter; Ehrlich, Joachim R; Baczkó, István; Lugenbiel, Patrick; Schweizer, Patrick A; Donner, Birgit C; Katus, Hugo A; Dobrev, Dobromir; Thomas, Dierk

2015-07-14

Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K(2P)3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K(2P)) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K(2P)3.1 subunits exhibited predominantly atrial expression, and atrial K(2P)3.1 transcript levels were highest among functional K(2P) channels. K(2P)3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K(2P)3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K(2P)3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Enhancement of atrium-selective K(2P)3.1 currents contributes to APD shortening in patients with chronic AF, and K(2P)3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K(2P)3.1 as a novel drug target for mechanism-based AF therapy. © 2015 American Heart Association, Inc.

First direct observations linking confined supercritical turbidity currents to their depositional architecture and facies characteristics

NASA Astrophysics Data System (ADS)

Hage, S.; Cartigny, M.; Hughes Clarke, J. E.; Clare, M. A.; Sumner, E.; Hubbard, S. M.; Talling, P.; Lintern, G.; Stacey, C.; Vardy, M. E.; Hunt, J.; Vendettuoli, D.; Yokokawa, M.; Hizzett, J. L.; Vellinga, A. J.; Azpiroz, M.

2017-12-01

Turbidity currents transfer globally significant amounts of sediment via submarine channels from the continental margin to deep submarine fans. Submarine channel inception is thought to result from erosive, supercritical turbidity currents that are common in proximal settings of the marine realm. Recent monitoring of submarine processes have provided the first measurements of supercritical turbidity currents (Hughes Clarke, 2016), demonstrating that they drive the upstream migration of crescentic bedforms in confined submarine channels. Although upstream-migrating bedforms are common in confined channels across the world's oceans, there is considerable debate over the type of deposits that they produce. It is important to understand what types of deposit record these supercritical bedforms to potentially identify them from geological archives. For the first time, we combine direct measurements from supercritical field-scale turbidity currents with the facies and depositional architecture resulting from such flows. We show how the subsurface architecture evolves in a highly active channel at Squamish submarine delta, British Columbia, Canada. Repeated upstream migration of bedforms is found to create two main deposit geometries. First, regular back-stepping beds result from flow deceleration on the slightly-inclined sides of the bedforms. Second, lens-shaped scour fills composed of massive deposits result from erosion of the back-stepping beds by subsequent turbidity currents. We relate our findings to a range of ancient outcrop studies to demonstrate that supercritical flows are common in proximal settings through the geological record. This study provides the first direct observation-based model to identify confined supercritical turbidity currents and their associated upslope-migrating bedforms in the sedimentary record. This is important for correctly identifying the proximal sites of ancient submarine channels that served as past conduits for globally significant quantities of sediment to reach the deep sea.

An underlap field-effect transistor for electrical detection of influenza

NASA Astrophysics Data System (ADS)

Lee, Kwang-Won; Choi, Sung-Jin; Ahn, Jae-Hyuk; Moon, Dong-Il; Park, Tae Jung; Lee, Sang Yup; Choi, Yang-Kyu

2010-01-01

An underlap channel-embedded field-effect transistor (FET) is proposed for label-free biomolecule detection. Specifically, silica binding protein fused with avian influenza (AI) surface antigen and avian influenza antibody (anti-AI) were designed as a receptor molecule and a target material, respectively. The drain current was significantly decreased after the binding of negatively charged anti-AI on the underlap channel. A set of control experiments supports that only the biomolecules on the underlap channel effectively modulate the drain current. With the merits of a simple fabrication process, complementary metal-oxide-semiconductor compatibility, and enhanced sensitivity, the underlap FET could be a promising candidate for a chip-based biosensor.

Overcharging below the nanoscale: Multivalent cations reverse the ion selectivity of a biological channel

NASA Astrophysics Data System (ADS)

García-Giménez, Elena; Alcaraz, Antonio; Aguilella, Vicente M.

2010-02-01

We report charge inversion within a nanoscopic biological protein ion channel in salts of multivalent ions. The presence of positive divalent and trivalent counterions reverses the cationic selectivity of the OmpF channel, a general diffusion porin located in the outer membrane of E. coli. We discuss the conditions under which charge inversion can be inferred from the change in sign of the measured quantity, the channel zero current potential. By comparing experimental results in protein channels whose charge has been modified after site-directed mutagenesis, the predictions of current theories of charge inversion are critically examined. It is emphasized that charge inversion does not necessarily increase with the bare surface charge density of the interface and that even this concept of surface charge density may become meaningless in some biological ion channels. Thus, any theory based on electrostatic correlations or chemical binding should explicitly take into account the particular structure of the charged interface.

Interest in Health Behavior Intervention Delivery Modalities Among Cancer Survivors: A Cross-Sectional Study

PubMed Central

Basen-Engquist, Karen; Cox, Matthew G; Lyons, Elizabeth J; Carmack, Cindy L; Blalock, Janice A; Demark-Wahnefried, Wendy

2016-01-01

Background Effective, broad-reaching channels are important for the delivery of health behavior interventions in order to meet the needs of the growing population of cancer survivors in the United States. New technology presents opportunities to increase the reach of health behavior change interventions and therefore their overall impact. However, evidence suggests that older adults may be slower in their adoption of these technologies than the general population. Survivors’ interest for more traditional channels of delivery (eg, clinic) versus new technology-based channels (eg, smartphones) may depend on a variety of factors, including demographics, current health status, and the behavior requiring intervention. Objective The aim of this study was to determine the factors that predict cancer survivors’ interest in new technology-based health behavior intervention modalities versus traditional modalities. Methods Surveys were mailed to 1871 survivors of breast, prostate, and colorectal cancer. Participants’ demographics, diet and physical activity behaviors, interest in health behavior interventions, and interest in intervention delivery modalities were collected. Using path analysis, we explored the relationship between four intervention modality variables (ie, clinic, telephone, computer, and smartphone) and potential predictors of modality interest. Results In total, 1053 respondents to the survey (56.3% response rate); 847 provided complete data for this analysis. Delivery channel interest was highest for computer-based interventions (236/847, 27.9% very/extremely interested) and lowest for smartphone–based interventions (73/847, 8.6%), with interest in clinic-based (147/847, 17.3%) and telephone-delivered (143/847, 16.9%) falling in between. Use of other technology platforms, such as Web cameras and social networking sites, was positively predictive of interest in technology-based delivery channels. Older survivors were less likely to report interest in smartphone–based diet interventions. Physical activity, fruit and vegetable consumption, weight status, and age moderated relationships between interest in targeted intervention behavior and modality. Conclusions This study identified several predictors of survivor interest in various health behavior intervention delivery modalities. Overall, computer-based interventions were found to be most acceptable, while smartphones were the least. Factors related to survivors’ current technology use and health status play a role in their interest for technology-based intervention versus more traditional delivery channels. Future health behavior change research in this population should consider participants’ demographic, clinical, and lifestyle characteristics when selecting a delivery channel. Furthermore, current health behavior interventions for older cancer survivors may be best delivered over the Internet. Smartphone interventions may be feasible in the future following further adoption and familiarization by this particular population. PMID:28410164

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.

A high-performance channel engineered charge-plasma-based MOSFET with high-κ spacer

NASA Astrophysics Data System (ADS)

Shan, Chan; Wang, Ying; Luo, Xin; Bao, Meng-tian; Yu, Cheng-hao; Cao, Fei

2017-12-01

In this paper, the performance of graded channel double-gate MOSFET (GC-DGFET) that utilizes the charge-plasma concept and a high-κ spacer is investigated through 2-D device simulations. The results demonstrate that GC-DGFET with high-κ spacer can effectively improve the ON-state driving current (ION) and reduce the OFF-leakage current (IOFF). We find that reduction of the initial energy barrier between the source and channel is the origin of this ION enhancement. The reason for the IOFF reduction is identified to be the extension of the effective channel length owing to the fringing field via high-κ spacers. Consequently, these devices offer enhanced performance by reducing the total gate-to-gate capacitance (Cgg) and decreasing the intrinsic delay (τ).

Sample pre-concentration with high enrichment factors at a fixed location in paper-based microfluidic devices.

PubMed

Yeh, Shih-Hao; Chou, Kuang-Hua; Yang, Ruey-Jen

2016-03-07

The lack of sensitivity is a major problem among microfluidic paper-based analytical devices (μPADs) for early disease detection and diagnosis. Accordingly, the present study presents a method for improving the enrichment factor of low-concentration biomarkers by using shallow paper-based channels realized through a double-sided wax-printing process. In addition, the enrichment factor is further enhanced by exploiting the ion concentration polarization (ICP) effect on the cathodic side of the nanoporous membrane, in which a stationary sample plug is obtained. The occurrence of ICP on the shallow-channel μPAD is confirmed by measuring the current-voltage response as the external voltage is increased from 0 to 210 V (or the field strength from 0 to 1.05 × 10(4) V m(-1)) over 600 s. In addition, to the best of our knowledge, the electroosmotic flow (EOF) speed on the μPAD fabricated with a wax-channel is measured for the first time using a current monitoring method. The experimental results show that for a fluorescein sample, the concentration factor is increased from 130-fold in a conventional full-thickness paper channel to 944-fold in the proposed shallow channel. Furthermore, for a fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) sample, the proposed shallow-channel μPAD achieves an 835-fold improvement in the concentration factor. The concentration technique presented here provides a novel strategy for enhancing the detection sensitivity of μPAD applications.

Fabrication of assembled ZnO/TiO2 heterojunction thin film transistors using solution processing technique

NASA Astrophysics Data System (ADS)

Liau, Leo Chau-Kuang; Lin, Yun-Guo

2015-01-01

Ceramic-based metal-oxide-semiconductor (MOS) field-effect thin film transistors (TFTs), which were assembled by ZnO and TiO2 heterojunction films coated using solution processing technique, were fabricated and characterized. The fabrication of the device began with the preparation of ZnO and TiO2 films by spin coating. The ZnO and TiO2 films that were stacked together and annealed at 450 °C were characterized as a p-n junction diode. Two types of the devices, p-channel and n-channel TFTs, were produced using different assemblies of ZnO and TiO2 films. Results show that the p-channel TFTs (p-TFTs) and n-channel TFTs (n-TFTs) using the assemblies of ZnO and TiO2 films were demonstrated by source-drain current vs. drain voltage (IDS-VDS) measurements. Several electronic properties of the p- and n- TFTs, such as threshold voltage (Vth), on-off ratio, channel mobility, and subthreshold swing (SS), were determined by current-voltage (I-V) data analysis. The ZnO/TiO2-based TFTs can be produced using solution processing technique and an assembly approach.

Interannual Variations of Surface Currents and Transports in the Sicily Channel Derived From Coastal Altimetry

NASA Astrophysics Data System (ADS)

Jebri, Fatma; Zakardjian, Bruno; Birol, Florence; Bouffard, Jérôme; Jullion, Loïc.; Sammari, Cherif

2017-11-01

A 20 year coastal altimetry data set (X-TRACK) is used, for the first time, to gain insight into the long-term interannual variations of the surface circulation in the Sicily Channel. First, a spectral along with a time/space diagram analysis are applied to the monthly means. They reveal a regionally coherent current patterns from track to track with a marked interannual variability that is unequally shared between the Atlantic Tunisian Current and Atlantic Ionian Stream inflows in the Sicily Channel and the Bifurcation Tyrrhenian Current outflow northeast of Sicily. Second, an empirical altimetry-based transport-like technique is proposed to quantify volume budgets inside the closed boxes formed by the crossing of the altimetry tracks and coastlines over the study area. A set of hydrographic measurements is used to validate the method. The inferred altimetry transports give a well-balanced mean eastward Atlantic Waters baroclinic flow of 0.4 Sv and standard deviations of 0.2 Sv on a yearly basis throughout the Sicily Channel and toward the Ionian Sea, which is fairly coherent with those found in the literature. Furthermore, the analysis allows to quantify the intrusions of Atlantic Waters over the Tunisian Shelf (0.12 ± 0.1 Sv) and highlights two main modes of variability of the main surface waters path over the Sicily Channel through the Bifurcation Atlantic Tunisian Current and Atlantic Ionian Stream systems. Some physical mechanisms are finally discussed with regards to changes in the observed currents and transports.

Infrared traffic image enhancement algorithm based on dark channel prior and gamma correction

NASA Astrophysics Data System (ADS)

Zheng, Lintao; Shi, Hengliang; Gu, Ming

2017-07-01

The infrared traffic image acquired by the intelligent traffic surveillance equipment has low contrast, little hierarchical differences in perceptions of image and the blurred vision effect. Therefore, infrared traffic image enhancement, being an indispensable key step, is applied to nearly all infrared imaging based traffic engineering applications. In this paper, we propose an infrared traffic image enhancement algorithm that is based on dark channel prior and gamma correction. In existing research dark channel prior, known as a famous image dehazing method, here is used to do infrared image enhancement for the first time. Initially, in the proposed algorithm, the original degraded infrared traffic image is transformed with dark channel prior as the initial enhanced result. A further adjustment based on the gamma curve is needed because initial enhanced result has lower brightness. Comprehensive validation experiments reveal that the proposed algorithm outperforms the current state-of-the-art algorithms.

VO2 film temperature dynamics at low-frequency current self-oscillations

NASA Astrophysics Data System (ADS)

Bortnikov, S. G.; Aliev, V. Sh.; Badmaeva, I. A.; Mzhelskiy, I. V.

2018-02-01

Low-frequency (˜2 Hz) current self-oscillations were first obtained in a millimeter-sized two-terminal planar device with a vanadium dioxide (VO2) film. The film temperature distribution dynamics was investigated within one oscillation period. It was established that the formation and disappearance of a conductive channel occur in a film in less than 60 ms with oscillation period 560 ms. The experimentally observed temperature in the channel region reached 413 K, being understated due to a low infrared microscope performance (integration time 10 ms). The VO2 film temperature distribution dynamics was simulated by solving a 2D problem of the electric current flow and heat transfer in the film. The calculation showed that the thermally initiated resistance switching in the film occurs in less than 4 ms at a channel temperature reaching ˜1000 K. The experimental results and simulation are consistent with the current self-oscillation mechanism based on the current pinching and dielectric relaxation in the VO2 film at the metal-insulator phase transition.

Performance improvement induced by asymmetric Y2O3-coated device structure to carbon-nanotube-film based photodetectors

NASA Astrophysics Data System (ADS)

Wang, Fanglin; Xu, Haitao; Huang, Huixin; Ma, Ze; Wang, Sheng; Peng, Lian-Mao

2017-11-01

Film-based semiconducting carbon nanotube (CNT) photodetectors are promising candidates for industrial applications. However, unintentional doping from the environment such as water/oxygen (H2O/O2) redox, polymers, etc. changes the doping level of the CNT film. Here, we evaluate the performance of film-based barrier-free bipolar diodes (BFBDs), which are basically semiconducting CNT films asymmetrically contacted by perfect n-type ohmic contact (scandium, Sc) and p-type ohmic contact (palladium, Pd) at the two ends of the diode. We show that normal BFBD devices have large variances of forward current, reverse current, and photocurrent for different doping levels of the channel. We propose an asymmetric Y2O3-coated BFBD device in which the channel is covered by a layer of an Y2O3 film and an overlap between the Sc electrode and the Y2O3 film is designed. The Y2O3 film provides p-type doping to the channel. The overlap section increases the length of the base of the pn junction, and the diffusion current of holes is suppressed. In this way, the rectifier factors (current ratio when voltages are at +0.5 V and -0.5 V) of the asymmetric Y2O3-coated BFBD devices are around two orders of magnitude larger and the photocurrent generation is more stable compared to that of normal devices. Our results provide a way to conquer the influence of unintentional doping from the environment and suppress reverse current in pn diodes. This is beneficial to applications of CNT-based photodetectors and of importance for inspiring methods to improve the performances of devices based on other low dimensional materials.

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

PubMed

Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

2015-01-01

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

Rip currents and alongshore flows in single channels dredged in the surf zone

NASA Astrophysics Data System (ADS)

Moulton, Melissa; Elgar, Steve; Raubenheimer, Britt; Warner, John C.; Kumar, Nirnimesh

2017-05-01

To investigate the dynamics of flows near nonuniform bathymetry, single channels (on average 30 m wide and 1.5 m deep) were dredged across the surf zone at five different times, and the subsequent evolution of currents and morphology was observed for a range of wave and tidal conditions. In addition, circulation was simulated with the numerical modeling system COAWST, initialized with the observed incident waves and channel bathymetry, and with an extended set of wave conditions and channel geometries. The simulated flows are consistent with alongshore flows and rip-current circulation patterns observed in the surf zone. Near the offshore-directed flows that develop in the channel, the dominant terms in modeled momentum balances are wave-breaking accelerations, pressure gradients, advection, and the vortex force. The balances vary spatially, and are sensitive to wave conditions and the channel geometry. The observed and modeled maximum offshore-directed flow speeds are correlated with a parameter based on the alongshore gradient in breaking-wave-driven-setup across the nonuniform bathymetry (a function of wave height and angle, water depths in the channel and on the sandbar, and a breaking threshold) and the breaking-wave-driven alongshore flow speed. The offshore-directed flow speed increases with dissipation on the bar and reaches a maximum (when the surf zone is saturated) set by the vertical scale of the bathymetric variability.

Recent Advances in the Pathogenesis and Drug Action in Periodic Paralyses and Related Channelopathies

PubMed Central

Tricarico, Domenico; Camerino, Diana Conte

2011-01-01

The periodic paralysis (PP) are rare autosomal-dominant disorders associated to mutations in the skeletal muscle sodium, calcium, and potassium channel genes characterized by muscle fiber depolarization with un-excitability, episodes of weakness with variations in serum potassium concentrations. Recent advances in thyrotoxic PP and hypokalemic PP (hypoPP) confirm the involvement of the muscle potassium channels in the pathogenesis of the diseases and their role as target of action for drugs of therapeutic interest. The novelty in the gating pore currents theory help to explain the disease symptoms, and open the possibility to more specifically target the disease. It is now known that the fiber depolarization in the hypoPP is due to an unbalance between the novel identified depolarizing gating pore currents (Igp) carried by protons or Na+ ions flowing through aberrant alternative pathways of the mutant subunits and repolarizing inwardly rectifying potassium channel (Kir) currents which also includes the ATP-sensitive subtype. Abnormal activation of the Igp or deficiency in the Kir channels predispose to fiber depolarization. One pharmacological strategy is based on blocking the Igp without affecting normal channel gating. It remains safe and effective the proposal of targeting the KATP, Kir channels, or BK channels by drugs capable to specifically open at nanomolar concentrations the skeletal muscle subtypes with less side effects. PMID:21687503

Rip currents and alongshore flows in single channels dredged in the surf zone

USGS Publications Warehouse

Moulton, Melissa; Elgar, Steve; Raubenheimer, Britt; Warner, John C.; Kumar, Nirnimesh

2017-01-01

To investigate the dynamics of flows near nonuniform bathymetry, single channels (on average 30 m wide and 1.5 m deep) were dredged across the surf zone at five different times, and the subsequent evolution of currents and morphology was observed for a range of wave and tidal conditions. In addition, circulation was simulated with the numerical modeling system COAWST, initialized with the observed incident waves and channel bathymetry, and with an extended set of wave conditions and channel geometries. The simulated flows are consistent with alongshore flows and rip-current circulation patterns observed in the surf zone. Near the offshore-directed flows that develop in the channel, the dominant terms in modeled momentum balances are wave-breaking accelerations, pressure gradients, advection, and the vortex force. The balances vary spatially, and are sensitive to wave conditions and the channel geometry. The observed and modeled maximum offshore-directed flow speeds are correlated with a parameter based on the alongshore gradient in breaking-wave-driven-setup across the nonuniform bathymetry (a function of wave height and angle, water depths in the channel and on the sandbar, and a breaking threshold) and the breaking-wave-driven alongshore flow speed. The offshore-directed flow speed increases with dissipation on the bar and reaches a maximum (when the surf zone is saturated) set by the vertical scale of the bathymetric variability.

Charge-based MOSFET model based on the Hermite interpolation polynomial

NASA Astrophysics Data System (ADS)

Colalongo, Luigi; Richelli, Anna; Kovacs, Zsolt

2017-04-01

An accurate charge-based compact MOSFET model is developed using the third order Hermite interpolation polynomial to approximate the relation between surface potential and inversion charge in the channel. This new formulation of the drain current retains the same simplicity of the most advanced charge-based compact MOSFET models such as BSIM, ACM and EKV, but it is developed without requiring the crude linearization of the inversion charge. Hence, the asymmetry and the non-linearity in the channel are accurately accounted for. Nevertheless, the expression of the drain current can be worked out to be analytically equivalent to BSIM, ACM and EKV. Furthermore, thanks to this new mathematical approach the slope factor is rigorously defined in all regions of operation and no empirical assumption is required.

Discrimination of Single Base Pair Differences Among Individual DNA Molecules Using a Nanopore

NASA Technical Reports Server (NTRS)

Vercoutere, Wenonah; DeGuzman, Veronica

2003-01-01

The protein toxin alpha-hemolysin form nanometer scale channels across lipid membranes. Our lab uses a single channel in an artificial lipid bilayer in a patch clamp device to capture and examine individual DNA molecules. This nanopore detector used with a support vector machine (SVM) can analyze DNA hairpin molecules on the millisecond time scale. We distinguish duplex stem length, base pair mismatches, loop length, and single base pair differences. The residual current fluxes also reveal structural molecular dynamics elements. DNA end-fraying (terminal base pair dissociation) can be observed as near full blockades, or spikes, in current. This technique can be used to investigate other biological processes dependent on DNA end-fraying, such as the processing of HIV DNA by HIV integrase.

Nine-channel wavelength tunable single mode laser array based on slots.

PubMed

Guo, Wei-Hua; Lu, Qiaoyin; Nawrocka, Marta; Abdullaev, Azat; O'Callaghan, James; Donegan, John F

2013-04-22

A 9-channel wavelength tunable single-mode laser array based on slots is presented. The fabricated laser array demonstrated a threshold current in a range of 19~21 mA with the SOA unbiased at 20°C under continuous wave condition. Stable single mode performances have been observed with side-mode suppression-ratio (SMSR) > 50 dB. The output power higher than 37 mW was obtained at the SOA injected current of 70 mA for all the 9 channels within the laser array. A wavelength quasi-continuous tuning range of about 27 nm has been achieved for the laser array with the temperature variations from 10°C to 45°C. This array platform is of a single growth and monolithically integrable. It can be easily fabricated by standard photolithography. In addition, it potentially removes the yield problem due to the uncertainty of the facet cleaving.

An alternative low-loss stack topology for vanadium redox flow battery: Comparative assessment

NASA Astrophysics Data System (ADS)

Moro, Federico; Trovò, Andrea; Bortolin, Stefano; Del, Davide, , Col; Guarnieri, Massimo

2017-02-01

Two vanadium redox flow battery topologies have been compared. In the conventional series stack, bipolar plates connect cells electrically in series and hydraulically in parallel. The alternative topology consists of cells connected in parallel inside stacks by means of monopolar plates in order to reduce shunt currents along channels and manifolds. Channelled and flat current collectors interposed between cells were considered in both topologies. In order to compute the stack losses, an equivalent circuit model of a VRFB cell was built from a 2D FEM multiphysics numerical model based on Comsol®, accounting for coupled electrical, electrochemical, and charge and mass transport phenomena. Shunt currents were computed inside the cells with 3D FEM models and in the piping and manifolds by means of equivalent circuits solved with Matlab®. Hydraulic losses were computed with analytical models in piping and manifolds and with 3D numerical analyses based on ANSYS Fluent® in the cell porous electrodes. Total losses in the alternative topology resulted one order of magnitude lower than in an equivalent conventional battery. The alternative topology with channelled current collectors exhibits the lowest shunt currents and hydraulic losses, with round-trip efficiency higher by about 10%, as compared to the conventional topology.

F-actin-based Ca signaling-a critical comparison with the current concept of Ca signaling.

PubMed

Lange, Klaus; Gartzke, Joachim

2006-11-01

A short comparative survey on the current idea of Ca signaling and the alternative concept of F-actin-based Ca signaling is given. The two hypotheses differ in one central aspect, the mechanism of Ca storage. The current theory rests on the assumption of Ca-accumulating endoplasmic/sarcoplasmic reticulum-derived vesicles equipped with an ATP-dependent Ca pump and IP3- or ryanodine-sensitive channel-receptors for Ca-release. The alternative hypothesis proceeds from the idea of Ca storage at the high-affinity binding sites of actin filaments. Cellular sites of F-actin-based Ca storage are microvilli and the submembrane cytoskeleton. Several specific features of Ca signaling such as store-channel coupling, quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake kinetics, and Ca-induced Ca release (CICR), which are not adequately described by the current concept, are inherent properties of the F-actin system and its dynamic state of treadmilling. Copyright 2006 Wiley-Liss, Inc.

A self-limiting regulation of vasoconstrictor-activated TRPC3/C6/C7 channels coupled to PI(4,5)P2-diacylglycerol signalling

PubMed Central

Imai, Yuko; Itsuki, Kyohei; Okamura, Yasushi; Inoue, Ryuji; Mori, Masayuki X

2012-01-01

Activation of transient receptor potential (TRP) canonical TRPC3/C6/C7 channels by diacylglycerol (DAG) upon stimulation of phospholipase C (PLC)-coupled receptors results in the breakdown of phosphoinositides (PIPs). The critical importance of PIPs to various ion-transporting molecules is well documented, but their function in relation to TRPC3/C6/C7 channels remains controversial. By using an ectopic voltage-sensing PIP phosphatase (DrVSP), we found that dephosphorylation of PIPs robustly inhibits currents induced by carbachol (CCh), 1-oleolyl-2-acetyl-sn-glycerol (OAG) or RHC80267 in TRPC3, TRPC6 and TRPC7 channels, though the strength of the DrVSP-mediated inhibition (VMI) varied among the channels with a rank order of C7 > C6 > C3. Pharmacological and molecular interventions suggest that depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is most likely the critical event for VMI in all three channels. When the PLC catalytic signal was vigorously activated through overexpression of the muscarinic type-I receptor (M1R), the inactivation of macroscopic TRPC currents was greatly accelerated in the same rank order as the VMI, and VMI of these currents was attenuated or lost. VMI was also rarely detected in vasopressin-induced TRPC6-like currents in A7r5 vascular smooth muscle cells, indicating that the inactivation by PI(4,5)P2 depletion underlies the physiological condition. Simultaneous fluorescence resonance energy transfer (FRET)-based measurement of PI(4,5)P2 levels and TRPC6 currents confirmed that VMI magnitude reflects the degree of PI(4,5)P2 depletion. These results demonstrate that TRPC3/C6/C7 channels are differentially regulated by depletion of PI(4,5)P2, and that the bimodal signal produced by PLC activation controls these channels in a self-limiting manner. PMID:22183723

Non-synaptic ion channels in insects--basic properties of currents and their modulation in neurons and skeletal muscles.

PubMed

Wicher, D; Walther, C; Wicher, C

2001-08-01

Insects are favoured objects for studying information processing in restricted neuronal networks, e.g. motor pattern generation or sensory perception. The analysis of the underlying processes requires knowledge of the electrical properties of the cells involved. These properties are determined by the expression pattern of ionic channels and by the regulation of their function, e.g. by neuromodulators. We here review the presently available knowledge on insect non-synaptic ion channels and ionic currents in neurons and skeletal muscles. The first part of this article covers genetic and structural informations, the localization of channels, their electrophysiological and pharmacological properties, and known effects of second messengers and modulators such as neuropeptides or biogenic amines. In a second part we describe in detail modulation of ionic currents in three particularly well investigated preparations, i.e. Drosophila photoreceptor, cockroach DUM (dorsal unpaired median) neuron and locust jumping muscle. Ion channel structures are almost exclusively known for the fruitfly Drosophila, and most of the information on their function has also been obtained in this animal, mainly based on mutational analysis and investigation of heterologously expressed channels. Now the entire genome of Drosophila has been sequenced, it seems almost completely known which types of channel genes--and how many of them--exist in this animal. There is much knowledge of the various types of channels formed by 6-transmembrane--spanning segments (6TM channels) including those where four 6TM domains are joined within one large protein (e.g. classical Na+ channel). In comparison, two TM channels and 4TM (or tandem) channels so far have hardly been explored. There are, however, various well characterized ionic conductances, e.g. for Ca2+, Cl- or K+, in other insect preparations for which the channels are not yet known. In some of the larger insects, i.e. bee, cockroach, locust and moth, rather detailed information has been established on the role of ionic currents in certain physiological or behavioural contexts. On the whole, however, knowledge of non-synaptic ion channels in such insects is still fragmentary. Modulation of ion currents usually involves activation of more or less elaborate signal transduction cascades. The three detailed examples for modulation presented in the second part indicate, amongst other things, that one type of modulator usually leads to concerted changes of several ion currents and that the effects of different modulators in one type of cell may overlap. Modulators participate in the adaptive changes of the various cells responsible for different physiological or behavioural states. Further study of their effects on the single cell level should help to understand how small sets of cells cooperate in order to produce the appropriate output.

ZnO-based multiple channel and multiple gate FinMOSFETs

NASA Astrophysics Data System (ADS)

Lee, Ching-Ting; Huang, Hung-Lin; Tseng, Chun-Yen; Lee, Hsin-Ying

2016-02-01

In recent years, zinc oxide (ZnO)-based metal-oxide-semiconductor field-effect transistors (MOSFETs) have attracted much attention, because ZnO-based semiconductors possess several advantages, including large exciton binding energy, nontoxicity, biocompatibility, low material cost, and wide direct bandgap. Moreover, the ZnO-based MOSFET is one of most potential devices, due to the applications in microwave power amplifiers, logic circuits, large scale integrated circuits, and logic swing. In this study, to enhance the performances of the ZnO-based MOSFETs, the ZnObased multiple channel and multiple gate structured FinMOSFETs were fabricated using the simple laser interference photolithography method and the self-aligned photolithography method. The multiple channel structure possessed the additional sidewall depletion width control ability to improve the channel controllability, because the multiple channel sidewall portions were surrounded by the gate electrode. Furthermore, the multiple gate structure had a shorter distance between source and gate and a shorter gate length between two gates to enhance the gate operating performances. Besides, the shorter distance between source and gate could enhance the electron velocity in the channel fin structure of the multiple gate structure. In this work, ninety one channels and four gates were used in the FinMOSFETs. Consequently, the drain-source saturation current (IDSS) and maximum transconductance (gm) of the ZnO-based multiple channel and multiple gate structured FinFETs operated at a drain-source voltage (VDS) of 10 V and a gate-source voltage (VGS) of 0 V were respectively improved from 11.5 mA/mm to 13.7 mA/mm and from 4.1 mS/mm to 6.9 mS/mm in comparison with that of the conventional ZnO-based single channel and single gate MOSFETs.

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.

A simple analytical model of coupled single flow channel over porous electrode in vanadium redox flow battery with serpentine flow channel

NASA Astrophysics Data System (ADS)

Ke, Xinyou; Alexander, J. Iwan D.; Prahl, Joseph M.; Savinell, Robert F.

2015-08-01

A simple analytical model of a layered system comprised of a single passage of a serpentine flow channel and a parallel underlying porous electrode (or porous layer) is proposed. This analytical model is derived from Navier-Stokes motion in the flow channel and Darcy-Brinkman model in the porous layer. The continuities of flow velocity and normal stress are applied at the interface between the flow channel and the porous layer. The effects of the inlet volumetric flow rate, thickness of the flow channel and thickness of a typical carbon fiber paper porous layer on the volumetric flow rate within this porous layer are studied. The maximum current density based on the electrolyte volumetric flow rate is predicted, and found to be consistent with reported numerical simulation. It is found that, for a mean inlet flow velocity of 33.3 cm s-1, the analytical maximum current density is estimated to be 377 mA cm-2, which compares favorably with experimental result reported by others of ∼400 mA cm-2.

High sensitivity of spontaneous spike frequency to sodium leak current in a Lymnaea pacemaker neuron.

PubMed

Lu, T Z; Kostelecki, W; Sun, C L F; Dong, N; Pérez Velázquez, J L; Feng, Z-P

2016-12-01

The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K + and a small Na + component. We previously reported that a Na + -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na + current in rhythmic spiking of RPeD1 neurons. Whole-cell patch-clamp recording and computational modeling approaches were carried out in isolated RPeD1 neurons. The whole-cell current of the major ion channel components in RPeD1 neurons were characterized, and a conductance-based computational model of the rhythmic pacemaker activity was simulated with the experimental measurements. We found that the spiking rate is more sensitive to changes in the Na + leak current as compared to the K + leak current, suggesting a robust function of Na + leak current in regulating spontaneous neuronal firing activity. Our study provides new insight into our current understanding of the role of Na + leak current in intrinsic properties of pacemaker neurons. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Thermodynamic limitations on the temperature sensitivity of cell-membrane ion channels: Trouble with enthalpy uncertainty

NASA Astrophysics Data System (ADS)

Zheltikov, A. M.

2018-06-01

Energy exchange between a thermodynamic ensemble of heat- and cold-activated cell-membrane ion channels and the surrounding heat reservoir is shown to impose fundamental limitations on the performance of such channels as temperature-controlled gates for thermal cell activation. Analysis of unavoidable thermodynamic internal-energy fluctuations caused by energy exchange between the ion channels and the heat bath suggests that the resulting enthalpy uncertainty is too high for a robust ion-current gating by a single ion channel, implying that large ensembles of ion channels are needed for thermal cell activation. We argue, based on this thermodynamic analysis, that, had thermosensitive cell-membrane ion channels operated individually, rather than as large ensembles, robust thermal cell activation would have been impossible because of thermodynamic fluctuations.

A quantum wave based compact modeling approach for the current in ultra-short DG MOSFETs suitable for rapid multi-scale simulations

NASA Astrophysics Data System (ADS)

Hosenfeld, Fabian; Horst, Fabian; Iñíguez, Benjamín; Lime, François; Kloes, Alexander

2017-11-01

Source-to-drain (SD) tunneling decreases the device performance in MOSFETs falling below the 10 nm channel length. Modeling quantum mechanical effects including SD tunneling has gained more importance specially for compact model developers. The non-equilibrium Green's function (NEGF) has become a state-of-the-art method for nano-scaled device simulation in the past years. In the sense of a multi-scale simulation approach it is necessary to bridge the gap between compact models with their fast and efficient calculation of the device current, and numerical device models which consider quantum effects of nano-scaled devices. In this work, an NEGF based analytical model for nano-scaled double-gate (DG) MOSFETs is introduced. The model consists of a closed-form potential solution of a classical compact model and a 1D NEGF formalism for calculating the device current, taking into account quantum mechanical effects. The potential calculation omits the iterative coupling and allows the straightforward current calculation. The model is based on a ballistic NEGF approach whereby backscattering effects are considered as second order effect in a closed-form. The accuracy and scalability of the non-iterative DG MOSFET model is inspected in comparison with numerical NanoMOS TCAD data for various channel lengths. With the help of this model investigations on short-channel and temperature effects are performed.

Heavy metal multilayers for switching of magnetic unit via electrical current without magnetic field, method and applications

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

Ma, Qinli; Li, Yufan; Chien, Chia-ling

Provided is an electric-current-controllable magnetic unit, including: a substrate, an electric-current channel disposed on the substrate, the electric-current channel including a composite heavy-metal multilayer comprising at least one heavy-metal; a capping layer disposed over the electric-current channel; and at least one ferromagnetic layer disposed between the electric-current channel and the capping layer.

Interest in Health Behavior Intervention Delivery Modalities Among Cancer Survivors: A Cross-Sectional Study.

PubMed

Martin, Emily C; Basen-Engquist, Karen; Cox, Matthew G; Lyons, Elizabeth J; Carmack, Cindy L; Blalock, Janice A; Demark-Wahnefried, Wendy

2016-02-11

Effective, broad-reaching channels are important for the delivery of health behavior interventions in order to meet the needs of the growing population of cancer survivors in the United States. New technology presents opportunities to increase the reach of health behavior change interventions and therefore their overall impact. However, evidence suggests that older adults may be slower in their adoption of these technologies than the general population. Survivors' interest for more traditional channels of delivery (eg, clinic) versus new technology-based channels (eg, smartphones) may depend on a variety of factors, including demographics, current health status, and the behavior requiring intervention. The aim of this study was to determine the factors that predict cancer survivors' interest in new technology-based health behavior intervention modalities versus traditional modalities. Surveys were mailed to 1871 survivors of breast, prostate, and colorectal cancer. Participants' demographics, diet and physical activity behaviors, interest in health behavior interventions, and interest in intervention delivery modalities were collected. Using path analysis, we explored the relationship between four intervention modality variables (ie, clinic, telephone, computer, and smartphone) and potential predictors of modality interest. In total, 1053 respondents to the survey (56.3% response rate); 847 provided complete data for this analysis. Delivery channel interest was highest for computer-based interventions (236/847, 27.9% very/extremely interested) and lowest for smartphone-based interventions (73/847, 8.6%), with interest in clinic-based (147/847, 17.3%) and telephone-delivered (143/847, 16.9%) falling in between. Use of other technology platforms, such as Web cameras and social networking sites, was positively predictive of interest in technology-based delivery channels. Older survivors were less likely to report interest in smartphone-based diet interventions. Physical activity, fruit and vegetable consumption, weight status, and age moderated relationships between interest in targeted intervention behavior and modality. This study identified several predictors of survivor interest in various health behavior intervention delivery modalities. Overall, computer-based interventions were found to be most acceptable, while smartphones were the least. Factors related to survivors' current technology use and health status play a role in their interest for technology-based intervention versus more traditional delivery channels. Future health behavior change research in this population should consider participants' demographic, clinical, and lifestyle characteristics when selecting a delivery channel. Furthermore, current health behavior interventions for older cancer survivors may be best delivered over the Internet. Smartphone interventions may be feasible in the future following further adoption and familiarization by this particular population. ©Emily C Martin, Karen Basen-Engquist, Matthew G Cox, Elizabeth J Lyons, Cindy L Carmack, Janice A Blalock, Wendy Demark-Wahnefried. Originally published in JMIR Cancer (http://cancer.jmir.org), 11.02.2016.

Voltage Gated Ion Channel Function: Gating, Conduction, and the Role of Water and Protons

PubMed Central

Kariev, Alisher M.; Green, Michael E.

2012-01-01

Ion channels, which are found in every biological cell, regulate the concentration of electrolytes, and are responsible for multiple biological functions, including in particular the propagation of nerve impulses. The channels with the latter function are gated (opened) by a voltage signal, which allows Na+ into the cell and K+ out. These channels have several positively charged amino acids on a transmembrane domain of their voltage sensor, and it is generally considered, based primarily on two lines of experimental evidence, that these charges move with respect to the membrane to open the channel. At least three forms of motion, with greatly differing extents and mechanisms of motion, have been proposed. There is a “gating current”, a capacitative current preceding the channel opening, that corresponds to several charges (for one class of channel typically 12–13) crossing the membrane field, which may not require protein physically crossing a large fraction of the membrane. The coupling to the opening of the channel would in these models depend on the motion. The conduction itself is usually assumed to require the “gate” of the channel to be pulled apart to allow ions to enter as a section of the protein partially crosses the membrane, and a selectivity filter at the opposite end of the channel determines the ion which is allowed to pass through. We will here primarily consider K+ channels, although Na+ channels are similar. We propose that the mechanism of gating differs from that which is generally accepted, in that the positively charged residues need not move (there may be some motion, but not as gating current). Instead, protons may constitute the gating current, causing the gate to open; opening consists of only increasing the diameter at the gate from approximately 6 Å to approximately 12 Å. We propose in addition that the gate oscillates rather than simply opens, and the ion experiences a barrier to its motion across the channel that is tuned by the water present within the channel. Our own quantum calculations as well as numerous experiments of others are interpreted in terms of this hypothesis. It is also shown that the evidence that supports the motion of the sensor as the gating current can also be consistent with the hypothesis we present. PMID:22408417

Hybrid Structure Multichannel All-Fiber Current Sensor.

PubMed

Jiang, Junzhen; Zhang, Hao; He, Youwu; Qiu, Yishen

2017-08-02

We have experimentally developed a hybrid-structure multi-channel all-fiber current sensor with ordinary silica fiber using fiber loop architecture. According to the rationale of time division multiplexing, the sensor combines parallel and serial structures. The purpose of the hybrid-structure multi-channel all-fiber current sensor is to get more information from the different measured points simultaneously. In addition, the hybrid-structure fiber current sensor exhibited a good linear response for each channel. A three-channel experiment was performed in the study and showed that the system could detect different current positions. Each channel could individually detect the current and needed a separate calibration system. Furthermore, the three channels will not affect each other.

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.

The Influence of channel length to the characteristics of CuPc based OFET thin films

NASA Astrophysics Data System (ADS)

Sujarwata; Handayani, L.; Mosik; Fianti

2018-03-01

The main focus of this research is to characterize organic field effect transistor (OFET) thin films based on CuPc with a bottom-contact structure and varied channel length. OFET was prepared by Si substrate cleaning in the ultrasonic cleaner first, then deposition of the source and drain electrodes on the substrate with vacuum evaporation at room temperature, and finally CuPc thin film deposition among the source, drain, and gate electrodes. The distance between source anddrain electrodes is the channel length of the CuPc thin film. In this research, the channel length was varied; 100 μm, 200 μm and 300 μm, with the same active areas of 2.9-3.42 V and different current, IDS. The result showed that the shorter channel length causes, the bigger IDS flowing on the OFET

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

PubMed Central

Finnerty, Justin John

2015-01-01

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

Quality control and quality assurance plan for bridge channel-stability assessments in Massachusetts

USGS Publications Warehouse

Parker, Gene W.; Pinson, Harlow

1993-01-01

A quality control and quality assurance plan has been implemented as part of the Massachusetts bridge scour and channel-stability assessment program. This program is being conducted by the U.S. Geological Survey, Massachusetts-Rhode Island District, in cooperation with the Massachusetts Highway Department. Project personnel training, data-integrity verification, and new data-management technologies are being utilized in the channel-stability assessment process to improve current data-collection and management techniques. An automated data-collection procedure has been implemented to standardize channel-stability assessments on a regular basis within the State. An object-oriented data structure and new image management tools are used to produce a data base enabling management of multiple data object classes. Data will be reviewed by assessors and data base managers before being merged into a master bridge-scour data base, which includes automated data-verification routines.

Robust QKD-based private database queries based on alternative sequences of single-qubit measurements

NASA Astrophysics Data System (ADS)

Yang, YuGuang; Liu, ZhiChao; Chen, XiuBo; Zhou, YiHua; Shi, WeiMin

2017-12-01

Quantum channel noise may cause the user to obtain a wrong answer and thus misunderstand the database holder for existing QKD-based quantum private query (QPQ) protocols. In addition, an outside attacker may conceal his attack by exploiting the channel noise. We propose a new, robust QPQ protocol based on four-qubit decoherence-free (DF) states. In contrast to existing QPQ protocols against channel noise, only an alternative fixed sequence of single-qubit measurements is needed by the user (Alice) to measure the received DF states. This property makes it easy to implement the proposed protocol by exploiting current technologies. Moreover, to retain the advantage of flexible database queries, we reconstruct Alice's measurement operators so that Alice needs only conditioned sequences of single-qubit measurements.

Amphotericin B channels in phospholipid membrane-coated nanoporous silicon surfaces: implications for photovoltaic driving of ions across membranes.

PubMed

Yilma, Solomon; Liu, Nangou; Samoylov, Alexander; Lo, Ting; Brinker, C Jeffrey; Vodyanoy, Vitaly

2007-03-15

The antimycotic agent amphotericin B (AmB) functions by forming complexes with sterols to form ion channels that cause membrane leakage. When AmB and cholesterol mixed at 2:1 ratio were incorporated into phospholipid bilayer membranes formed on the tip of patch pipettes, ion channel current fluctuations with characteristic open and closed states were observed. These channels were also functional in phospholipid membranes formed on nanoporous silicon surfaces. Electrophysiological studies of AmB-cholesterol mixtures that were incorporated into phospholipid membranes formed on the surface of nanoporous (6.5 nm pore diameter) silicon plates revealed large conductance ion channels ( approximately 300 pS) with distinct open and closed states. Currents through the AmB-cholesterol channels on nanoporous silicon surfaces can be driven by voltage applied via conventional electrical circuits or by photovoltaic electrical potential entirely generated when the nanoporous silicon surface is illuminated with a narrow laser beam. Electrical recordings made during laser illumination of AmB-cholesterol containing membrane-coated nanoporous silicon surfaces revealed very large conductance ion channels with distinct open and closed states. Our findings indicate that nanoporous silicon surfaces can serve as mediums for ion-channel-based biosensors. The photovoltaic properties of nanoporous silicon surfaces show great promise for making such biosensors addressable via optical technologies.

Enhancing the Linear Dynamic Range in Multi-Channel Single Photon Detector beyond 7OD

PubMed Central

Gudkov, Dmytro; Gudkov, George; Gorbovitski, Boris; Gorfinkel, Vera

2015-01-01

We present design, implementation, and characterization of a single photon detector based on 32-channel PMT sensor [model H7260-20, Hamamatsu]. The developed high speed electronics enables the photon counting with linear dynamic range (LDR) up to 108count/s per detector's channel. The experimental characterization and Monte-Carlo simulations showed that in the single photon counting mode the LDR of the PMT sensor is limited by (i) “photon” pulse width (current pulse) of 900ps and (ii) substantial decrease of amplitudes of current pulses for count rates exceeding 108 count/s. The multi-channel architecture of the detector and the developed firm/software allow further expansion of the dynamic range of the device by 32-fold by using appropriate beam shaping. The developed single photon counting detector was tested for the detection of fluorescence labeled microbeads in capillary flow. PMID:27087788

New coherent laser communication detection scheme based on channel-switching method.

PubMed

Liu, Fuchuan; Sun, Jianfeng; Ma, Xiaoping; Hou, Peipei; Cai, Guangyu; Sun, Zhiwei; Lu, Zhiyong; Liu, Liren

2015-04-01

A new coherent laser communication detection scheme based on the channel-switching method is proposed. The detection front end of this scheme comprises a 90° optical hybrid and two balanced photodetectors which outputs the in-phase (I) channel and quadrature-phase (Q) channel signal current, respectively. With this method, the ultrahigh speed analog/digital transform of the signal of the I or Q channel is not required. The phase error between the signal and local lasers is obtained by simple analog circuit. Using the phase error signal, the signals of the I/Q channel are switched alternately. The principle of this detection scheme is presented. Moreover, the comparison of the sensitivity of this scheme with that of homodyne detection with an optical phase-locked loop is discussed. An experimental setup was constructed to verify the proposed detection scheme. The offline processing procedure and results are presented. This scheme could be realized through simple structure and has potential applications in cost-effective high-speed laser communication.

Cholinergic control of membrane conductance and intracellular free Ca2+ in outer hair cells of the guinea pig cochlea.

PubMed

Evans, M G; Lagostena, L; Darbon, P; Mammano, F

2000-09-01

We have studied the action of cholinergic agonists on outer hair cells, both in situ and isolated from the cochlea of the guinea pig, combining new fast CCD technology for Ca2+ imaging and conventional patch-clamp methods. Carbachol (1 mM) activated a current with a reversal potential near -70 mV and a bell-shaped I-V curve, suggesting that it was a Ca2+ activated K+ current. In a few cells, this current was preceded by a transient inward current, probably owing to an influx of Ca2+ and other cations through the acetylcholine (ACh) receptors. The amplitude of the Ca2+ signal was maximal in a circumscribed region at the basal pole of the cell and decreased steeply towards the apical pole, compatible with Ca2+ influx and/or Ca2+ induced Ca2+ release at the cells base. The time course of the Ca2+ rise was fastest at the base, but it was still slightly slower, and more rounded, than that of the K+ current. In some recordings the K+ current was observed without any measurable change of intracellular Ca2+. The K+ current was potentiated (18%) by caffeine (5 mM), and decreased (19%) by ryanodine (0.1 mM) in the majority of cells tested. The results are discussed in terms of a labile intracellular Ca2+ store located at the base of the cell, close to the Ca2+ permeable ACh receptor channels and Ca2+ activated K+ channels, whose contribution to the Ca2+ rise occurring in the region of the channels is variable, and probably dependent on its ability to refill with Ca2+.

The Roles of Protein Kinases in Learning and Memory

ERIC Educational Resources Information Center

Giese, Karl Peter; Mizuno, Keiko

2013-01-01

In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate…

Modeling of Single Noninactivating Na+ Channels: Evidence for Two Open and Several Fast Inactivated States

PubMed Central

The, Yu-Kai; Fernandes, Jacqueline; Popa, M. Oana; Alekov, Alexi K.; Timmer, Jens; Lerche, Holger

2006-01-01

Voltage-gated Na+ channels play a fundamental role in the excitability of nerve and muscle cells. Defects in fast Na+ channel inactivation can cause hereditary muscle diseases with hyper- or hypoexcitability of the sarcolemma. To explore the kinetics and gating mechanisms of noninactivating muscle Na+ channels on a molecular level, we analyzed single channel currents from wild-type and five mutant Na+ channels. The mutations were localized in different protein regions which have been previously shown to be important for fast inactivation (D3-D4-linker, D3/S4-S5, D4/S4-S5, D4/S6) and exhibited distinct grades of defective fast inactivation with varying levels of persistent Na+ currents caused by late channel reopenings. Different gating schemes were fitted to the data using hidden Markov models with a correction for time interval omission and compared statistically. For all investigated channels including the wild-type, two open states were necessary to describe our data. Whereas one inactivated state was sufficient to fit the single channel behavior of wild-type channels, modeling the mutants with impaired fast inactivation revealed evidence for several inactivated states. We propose a single gating scheme with two open and three inactivated states to describe the behavior of all five examined mutants. This scheme provides a biological interpretation of the collected data, based on previous investigations in voltage-gated Na+ and K+ channels. PMID:16513781

Effect of mesa structure formation on the electrical properties of zinc oxide thin film transistors.

PubMed

Singh, Shaivalini; Chakrabarti, P

2014-05-01

ZnO based bottom-gate thin film transistor (TFT) with SiO2 as insulating layer has been fabricated with two different structures. The effect of formation of mesa structure on the electrical characteristics of the TFTs has been studied. The formation of mesa structure of ZnO channel region can definitely result in better control over channel region and enhance value of channel mobility of ZnO TFT. As a result, by fabricating a mesa structured TFT, a better value of mobility and on-state current are achieved at low voltages. A typical saturation current of 1.85 x 10(-7) A under a gate bias of 50 V is obtained for non mesa structure TFT while for mesa structured TFT saturation current of 5 x 10(-5) A can be obtained at comparatively very low gate bias of 6.4 V.

Quantitative characterization of arc discharge as vacuum interface

DOE PAGES

Huang, S.; Zhu, K.; Lu, Y. R.; ...

2014-12-19

An arc discharge with channel diameters of 3 mm and 6 mm and lengths between 30mm and 60mm was experimentally investigated for its potential to function as plasma window, i.e., interface vacuum regions of different pressures. In this study, electron temperature of the plasma channel measured spectroscopically varied in the range of 7000K to 15000K, increasing with discharge current while decreasing with gas flow rate. The plasma window had a slightly positive I-V characteristics over the whole range of investigated current 30A–70 A. Measurements of pressure separation capability, which were determined by input current, gas flow rate, discharge channel diameter,more » and length, were well explained by viscosity effect and “thermal-block” effect. The experimental results of global parameters including temperature, gas flow rate, and voltage had a good agreement with the simulation results calculated by an axis-symmetry Fluent-based magneto-hydrodynamic model.« less

Single-Walled Carbon Nanotube Dominated Micron-Wide Stripe Patterned-Based Ferroelectric Field-Effect Transistors with HfO2 Defect Control Layer

NASA Astrophysics Data System (ADS)

Tan, Qiuhong; Wang, Qianjin; Liu, Yingkai; Yan, Hailong; Cai, Wude; Yang, Zhikun

2018-04-01

Ferroelectric field-effect transistors (FeFETs) with single-walled carbon nanotube (SWCNT) dominated micron-wide stripe patterned as channel, (Bi,Nd)4Ti3O12 films as insulator, and HfO2 films as defect control layer were developed and fabricated. The prepared SWCNT-FeFETs possess excellent properties such as large channel conductance, high on/off current ratio, high channel carrier mobility, great fatigue endurance performance, and data retention. Despite its thin capacitance equivalent thickness, the gate insulator with HfO2 defect control layer shows a low leakage current density of 3.1 × 10-9 A/cm2 at a gate voltage of - 3 V.

Single-Walled Carbon Nanotube Dominated Micron-Wide Stripe Patterned-Based Ferroelectric Field-Effect Transistors with HfO2 Defect Control Layer.

PubMed

Tan, Qiuhong; Wang, Qianjin; Liu, Yingkai; Yan, Hailong; Cai, Wude; Yang, Zhikun

2018-04-27

Ferroelectric field-effect transistors (FeFETs) with single-walled carbon nanotube (SWCNT) dominated micron-wide stripe patterned as channel, (Bi,Nd) 4 Ti 3 O 12 films as insulator, and HfO 2 films as defect control layer were developed and fabricated. The prepared SWCNT-FeFETs possess excellent properties such as large channel conductance, high on/off current ratio, high channel carrier mobility, great fatigue endurance performance, and data retention. Despite its thin capacitance equivalent thickness, the gate insulator with HfO 2 defect control layer shows a low leakage current density of 3.1 × 10 -9  A/cm 2 at a gate voltage of - 3 V.

Frame synchronization methods based on channel symbol measurements

NASA Technical Reports Server (NTRS)

Dolinar, S.; Cheung, K.-M.

1989-01-01

The current DSN frame synchronization procedure is based on monitoring the decoded bit stream for the appearance of a sync marker sequence that is transmitted once every data frame. The possibility of obtaining frame synchronization by processing the raw received channel symbols rather than the decoded bits is explored. Performance results are derived for three channel symbol sync methods, and these are compared with results for decoded bit sync methods reported elsewhere. It is shown that each class of methods has advantages or disadvantages under different assumptions on the frame length, the global acquisition strategy, and the desired measure of acquisition timeliness. It is shown that the sync statistics based on decoded bits are superior to the statistics based on channel symbols, if the desired operating region utilizes a probability of miss many orders of magnitude higher than the probability of false alarm. This operating point is applicable for very large frame lengths and minimal frame-to-frame verification strategy. On the other hand, the statistics based on channel symbols are superior if the desired operating point has a miss probability only a few orders of magnitude greater than the false alarm probability. This happens for small frames or when frame-to-frame verifications are required.

Characterization of individual polynucleotide molecules using a membrane channel

NASA Technical Reports Server (NTRS)

Kasianowicz, J. J.; Brandin, E.; Branton, D.; Deamer, D. W.

1996-01-01

We show that an electric field can drive single-stranded RNA and DNA molecules through a 2.6-nm diameter ion channel in a lipid bilayer membrane. Because the channel diameter can accommodate only a single strand of RNA or DNA, each polymer traverses the membrane as an extended chain that partially blocks the channel. The passage of each molecule is detected as a transient decrease of ionic current whose duration is proportional to polymer length. Channel blockades can therefore be used to measure polynucleotide length. With further improvements, the method could in principle provide direct, high-speed detection of the sequence of bases in single molecules of DNA or RNA.

Action potential propagation: ion current or intramembrane electric field?

PubMed

Martí, Albert; Pérez, Juan J; Madrenas, Jordi

2018-01-01

The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

Window-Based Channel Impulse Response Prediction for Time-Varying Ultra-Wideband Channels.

PubMed

Al-Samman, A M; Azmi, M H; Rahman, T A; Khan, I; Hindia, M N; Fattouh, A

2016-01-01

This work proposes channel impulse response (CIR) prediction for time-varying ultra-wideband (UWB) channels by exploiting the fast movement of channel taps within delay bins. Considering the sparsity of UWB channels, we introduce a window-based CIR (WB-CIR) to approximate the high temporal resolutions of UWB channels. A recursive least square (RLS) algorithm is adopted to predict the time evolution of the WB-CIR. For predicting the future WB-CIR tap of window wk, three RLS filter coefficients are computed from the observed WB-CIRs of the left wk-1, the current wk and the right wk+1 windows. The filter coefficient with the lowest RLS error is used to predict the future WB-CIR tap. To evaluate our proposed prediction method, UWB CIRs are collected through measurement campaigns in outdoor environments considering line-of-sight (LOS) and non-line-of-sight (NLOS) scenarios. Under similar computational complexity, our proposed method provides an improvement in prediction errors of approximately 80% for LOS and 63% for NLOS scenarios compared with a conventional method.

Window-Based Channel Impulse Response Prediction for Time-Varying Ultra-Wideband Channels

PubMed Central

Al-Samman, A. M.; Azmi, M. H.; Rahman, T. A.; Khan, I.; Hindia, M. N.; Fattouh, A.

2016-01-01

This work proposes channel impulse response (CIR) prediction for time-varying ultra-wideband (UWB) channels by exploiting the fast movement of channel taps within delay bins. Considering the sparsity of UWB channels, we introduce a window-based CIR (WB-CIR) to approximate the high temporal resolutions of UWB channels. A recursive least square (RLS) algorithm is adopted to predict the time evolution of the WB-CIR. For predicting the future WB-CIR tap of window wk, three RLS filter coefficients are computed from the observed WB-CIRs of the left wk−1, the current wk and the right wk+1 windows. The filter coefficient with the lowest RLS error is used to predict the future WB-CIR tap. To evaluate our proposed prediction method, UWB CIRs are collected through measurement campaigns in outdoor environments considering line-of-sight (LOS) and non-line-of-sight (NLOS) scenarios. Under similar computational complexity, our proposed method provides an improvement in prediction errors of approximately 80% for LOS and 63% for NLOS scenarios compared with a conventional method. PMID:27992445

Slack sodium-activated potassium channel membrane expression requires p38 mitogen-activated protein kinase phosphorylation.

PubMed

Gururaj, Sushmitha; Fleites, John; Bhattacharjee, Arin

2016-04-01

p38 MAPK has long been understood as an inducible kinase under conditions of cellular stress, but there is now increasing evidence to support its role in the regulation of neuronal function. Several phosphorylation targets have been identified, an appreciable number of which are ion channels, implicating the possible involvement of p38 MAPK in neuronal excitability. The KNa channel Slack is an important protein to be studied as it is highly and ubiquitously expressed in DRG neurons and is important in the maintenance of their firing accommodation. We sought to examine if the Slack channel could be a substrate of p38 MAPK activity. First, we found that the Slack C-terminus contains two putative p38 MAPK phosphorylation sites that are highly conserved across species. Second, we show via electrophysiology experiments that KNa currents and further, Slack currents, are subject to tonic modulation by p38 MAPK. Third, biochemical approaches revealed that Slack channel regulation by p38 MAPK occurs through direct phosphorylation at the two putative sites of interaction, and mutating both sites prevented surface expression of Slack channels. Based on these results, we conclude that p38 MAPK is an obligate regulator of Slack channel function via the trafficking of channels into the membrane. The present study identifies Slack KNa channels as p38 MAPK substrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Slack Sodium-activated Potassium Channel Membrane Expression Requires p38 Mitogen-Activated Protein Kinase Phosphorylation

PubMed Central

Gururaj, Sushmitha; Fleites, John; Bhattacharjee, Arin

2016-01-01

p38 MAPK has long been understood as an inducible kinase under conditions of cellular stress, but there is now increasing evidence to support its role in the regulation of neuronal function. Several phosphorylation targets have been identified, an appreciable number of which are ion channels, implicating the possible involvement of p38 MAPK in neuronal excitability. The KNa channel Slack is an important protein to be studied as it is highly and ubiquitously expressed in DRG neurons and is important in the maintenance of their firing accommodation. We sought to examine if the Slack channel could be a substrate of p38 MAPK activity. First, we found that the Slack C-terminus contains two putative p38 MAPK phosphorylation sites that are highly conserved across species. Second, we show via electrophysiology experiments that KNa currents and further, Slack currents, are subject to tonic modulation by p38 MAPK. Third, biochemical approaches revealed that Slack channel regulation by p38 MAPK occurs through direct phosphorylation at the two putative sites of interaction, and mutating both sites prevented surface expression of Slack channels. Based on these results, we conclude that p38 MAPK is an obligate regulator of Slack channel function via the trafficking of channels into the membrane. The present study identifies Slack KNa channels as p38 MAPK substrates. PMID:26721627

Mycoplasma orale infection affects K+ and Cl- currents in the HSG salivary gland cell line.

PubMed

Izutsu, K T; Fatherazi, S; Belton, C M; Oda, D; Cartwright, F D; Kenny, G E

1996-06-01

The relations between K+ channel and Cl- channel currents and mycoplasma infection status were studied longitudinally in HSG cells, a human submandibular gland cell line. The K+ channel currents were disrupted by the occurrence of mycoplasma infection: muscarinic activation of K+ channels and K+ channel expression as estimated by ionomycin- or hypotonically induced K+ current responses were all decreased. Similar decreases in ionomycin- and hypotonically induced responses were observed for Cl- channels, but only the latter decrease was statistically significant. Also, Cl- currents could be elicited more frequently than K+ currents (63% of cases versus 0%) in infected cells when tested by exposure to hypotonic media, indicating that mycoplasma infection affects K+ channels relatively more than Cl- channels. These changes occurred in the originally infected cells, were ameliorated when the infection was cleared with sparfloxacin, and recurred when the cells were reinfected. Such changes would be expected to result in hyposecretion of salivary fluid if they occurred in vivo.

Pinch-off mechanism in double-lateral-gate junctionless transistors fabricated by scanning probe microscope based lithography

PubMed Central

Dehzangi, Arash; Abedini, Alam; Abdullah, Ahmad Makarimi; Saion, Elias; Hutagalung, Sabar D; Hamidon, Mohd N; Hassan, Jumiah

2012-01-01

Summary A double-lateral-gate p-type junctionless transistor is fabricated on a low-doped (1015) silicon-on-insulator wafer by a lithography technique based on scanning probe microscopy and two steps of wet chemical etching. The experimental transfer characteristics are obtained and compared with the numerical characteristics of the device. The simulation results are used to investigate the pinch-off mechanism, from the flat band to the off state. The study is based on the variation of the carrier density and the electric-field components. The device is a pinch-off transistor, which is normally in the on state and is driven into the off state by the application of a positive gate voltage. We demonstrate that the depletion starts from the bottom corner of the channel facing the gates and expands toward the center and top of the channel. Redistribution of the carriers due to the electric field emanating from the gates creates an electric field perpendicular to the current, toward the bottom of the channel, which provides the electrostatic squeezing of the current. PMID:23365794

Low-voltage organic electronics based on a gate-tunable injection barrier in vertical graphene-organic semiconductor heterostructures.

PubMed

Hlaing, Htay; Kim, Chang-Hyun; Carta, Fabio; Nam, Chang-Yong; Barton, Rob A; Petrone, Nicholas; Hone, James; Kymissis, Ioannis

2015-01-14

The vertical integration of graphene with inorganic semiconductors, oxide semiconductors, and newly emerging layered materials has recently been demonstrated as a promising route toward novel electronic and optoelectronic devices. Here, we report organic thin film transistors based on vertical heterojunctions of graphene and organic semiconductors. In these thin heterostructure devices, current modulation is accomplished by tuning of the injection barriers at the semiconductor/graphene interface with the application of a gate voltage. N-channel devices fabricated with a thin layer of C60 show a room temperature on/off ratio >10(4) and current density of up to 44 mAcm(-2). Because of the ultrashort channel intrinsic to the vertical structure, the device is fully operational at a driving voltage of 200 mV. A complementary p-channel device is also investigated, and a logic inverter based on two complementary transistors is demonstrated. The vertical integration of graphene with organic semiconductors via simple, scalable, and low-temperature fabrication processes opens up new opportunities to realize flexible, transparent organic electronic, and optoelectronic devices.

Systematic analysis of the contributions of stochastic voltage gated channels to neuronal noise

PubMed Central

O'Donnell, Cian; van Rossum, Mark C. W.

2014-01-01

Electrical signaling in neurons is mediated by the opening and closing of large numbers of individual ion channels. The ion channels' state transitions are stochastic and introduce fluctuations in the macroscopic current through ion channel populations. This creates an unavoidable source of intrinsic electrical noise for the neuron, leading to fluctuations in the membrane potential and spontaneous spikes. While this effect is well known, the impact of channel noise on single neuron dynamics remains poorly understood. Most results are based on numerical simulations. There is no agreement, even in theoretical studies, on which ion channel type is the dominant noise source, nor how inclusion of additional ion channel types affects voltage noise. Here we describe a framework to calculate voltage noise directly from an arbitrary set of ion channel models, and discuss how this can be use to estimate spontaneous spike rates. PMID:25360105

Photojunction field-effect transistor based on a colloidal quantum dot absorber channel layer.

PubMed

Adinolfi, Valerio; Kramer, Illan J; Labelle, André J; Sutherland, Brandon R; Hoogland, S; Sargent, Edward H

2015-01-27

The performance of photodetectors is judged via high responsivity, fast speed of response, and low background current. Many previously reported photodetectors based on size-tuned colloidal quantum dots (CQDs) have relied either on photodiodes, which, since they are primary photocarrier devices, lack gain; or photoconductors, which provide gain but at the expense of slow response (due to delayed charge carrier escape from sensitizing centers) and an inherent dark current vs responsivity trade-off. Here we report a photojunction field-effect transistor (photoJFET), which provides gain while breaking prior photoconductors' response/speed/dark current trade-off. This is achieved by ensuring that, in the dark, the channel is fully depleted due to a rectifying junction between a deep-work-function transparent conductive top contact (MoO3) and a moderately n-type CQD film (iodine treated PbS CQDs). We characterize the rectifying behavior of the junction and the linearity of the channel characteristics under illumination, and we observe a 10 μs rise time, a record for a gain-providing, low-dark-current CQD photodetector. We prove, using an analytical model validated using experimental measurements, that for a given response time the device provides a two-orders-of-magnitude improvement in photocurrent-to-dark-current ratio compared to photoconductors. The photoJFET, which relies on a junction gate-effect, enriches the growing family of CQD photosensitive transistors.

Correlation between ambient air and continuous bending stress for the electrical reliability of flexible pentacene-based thin-film transistors

NASA Astrophysics Data System (ADS)

Fan, Ching-Lin; Lin, Wei-Chun; Peng, Han-Hsing; Lin, Yu-Zuo; Huang, Bohr-Ran

2015-01-01

This study investigated how continuous bending stress affects the electrical characteristics of pentacene-based organic thin-film transistors (OTFTs) with poly(4-vinylphenol) (PVP) gate insulator in a vacuum and in ambient air. In tension mode, the strain direction of the fabricated devices was perpendicular to the device channel length. The OTFT devices that were bent in a vacuum exhibited a decreased on current because of cracking in the pentacene channel layer, which can obstruct the transport of charge carriers and deteriorate the on current of the OTFTs. The OTFT devices that were bent in ambient air exhibited a slightly decreased on current and considerably increased off current and subthreshold swing (SS). It was assumed that air moisture passed through the pentacene cracks into the interface between the PVP and pentacene layer, thereby yielding an increase in polar moisture traps, and leading to an increase in the conductivity of the pentacene, thus yielding a slightly decreased on current and considerably increased off current and SS.

A low-cost, scalable, current-sensing digital headstage for high channel count μECoG.

PubMed

Trumpis, Michael; Insanally, Michele; Zou, Jialin; Elsharif, Ashraf; Ghomashchi, Ali; Sertac Artan, N; Froemke, Robert C; Viventi, Jonathan

2017-04-01

High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (μECoG) array. We recorded both acute and chronic μECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 d. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of μECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels.

A low-cost, scalable, current-sensing digital headstage for high channel count μECoG

NASA Astrophysics Data System (ADS)

Trumpis, Michael; Insanally, Michele; Zou, Jialin; Elsharif, Ashraf; Ghomashchi, Ali; Sertac Artan, N.; Froemke, Robert C.; Viventi, Jonathan

2017-04-01

Objective. High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (μECoG) array. Approach. We recorded both acute and chronic μECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. Main results. The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 d. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. Significance. We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of μECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels.

A low-cost, scalable, current-sensing digital headstage for high channel count μECoG

PubMed Central

Trumpis, Michael; Insanally, Michele; Zou, Jialin; Elsharif, Ashraf; Ghomashchi, Ali; Artan, N. Sertac; Froemke, Robert C.; Viventi, Jonathan

2017-01-01

Objective High channel count electrode arrays allow for the monitoring of large-scale neural activity at high spatial resolution. Implantable arrays featuring many recording sites require compact, high bandwidth front-end electronics. In the present study, we investigated the use of a small, light weight, and low cost digital current-sensing integrated circuit for acquiring cortical surface signals from a 61-channel micro-electrocorticographic (μECoG) array. Approach We recorded both acute and chronic μECoG signal from rat auditory cortex using our novel digital current-sensing headstage. For direct comparison, separate recordings were made in the same anesthetized preparations using an analog voltage headstage. A model of electrode impedance explained the transformation between current- and voltage-sensed signals, and was used to reconstruct cortical potential. We evaluated the digital headstage using several metrics of the baseline and response signals. Main results The digital current headstage recorded neural signal with similar spatiotemporal statistics and auditory frequency tuning compared to the voltage signal. The signal-to-noise ratio of auditory evoked responses (AERs) was significantly stronger in the current signal. Stimulus decoding based on true and reconstructed voltage signals were not significantly different. Recordings from an implanted system showed AERs that were detectable and decodable for 52 days. The reconstruction filter mitigated the thermal current noise of the electrode impedance and enhanced overall SNR. Significance We developed and validated a novel approach to headstage acquisition that used current-input circuits to independently digitize 61 channels of μECoG measurements of the cortical field. These low-cost circuits, intended to measure photo-currents in digital imaging, not only provided a signal representing the local cortical field with virtually the same sensitivity and specificity as a traditional voltage headstage but also resulted in a small, light headstage that can easily be scaled to record from hundreds of channels. PMID:28102827

Experimental demonstration of OFDM/OQAM transmission with DFT-based channel estimation for visible laser light communications

NASA Astrophysics Data System (ADS)

He, Jing; Shi, Jin; Deng, Rui; Chen, Lin

2017-08-01

Recently, visible light communication (VLC) based on light-emitting diodes (LEDs) is considered as a candidate technology for fifth-generation (5G) communications, VLC is free of electromagnetic interference and it can simplify the integration of VLC into heterogeneous wireless networks. Due to the data rates of VLC system limited by the low pumping efficiency, small output power and narrow modulation bandwidth, visible laser light communication (VLLC) system with laser diode (LD) has paid more attention. In addition, orthogonal frequency division multiplexing/offset quadrature amplitude modulation (OFDM/OQAM) is currently attracting attention in optical communications. Due to the non-requirement of cyclic prefix (CP) and time-frequency domain well-localized pulse shapes, it can achieve high spectral efficiency. Moreover, OFDM/OQAM has lower out-of-band power leakage so that it increases the system robustness against inter-carrier interference (ICI) and frequency offset. In this paper, a Discrete Fourier Transform (DFT)-based channel estimation scheme combined with the interference approximation method (IAM) is proposed and experimentally demonstrated for VLLC OFDM/OQAM system. The performance of VLLC OFDM/OQAM system with and without DFT-based channel estimation is investigated. Moreover, the proposed DFT-based channel estimation scheme and the intra-symbol frequency-domain averaging (ISFA)-based method are also compared for the VLLC OFDM/OQAM system. The experimental results show that, the performance of EVM using the DFT-based channel estimation scheme is improved about 3dB compared with the conventional IAM method. In addition, the DFT-based channel estimation scheme can resist the channel noise effectively than that of the ISFA-based method.

Ion channels in artificial bolaamphiphile membranes deposited on sensor chips: optical detection in an ion-channel-based biosensor

NASA Astrophysics Data System (ADS)

Schalkhammer, Thomas G. M.; Weiss-Wichert, Christof; Smetazko, Michaela M.; Valina-Saba, Miriam

1997-06-01

Signal amplification using labels should be replaced by a technique monitoring the biochemical binding event directly. The use of a ligand coupled to an artificial gated membrane ion channel is a new promising strategy. Binding of protein- or DNA/RNA-analytes at ligand modified peptide channels results in an on/off-response of the channel current due to channel closure or distortion. The sensor consists of stable transmembrane channels with a ligand bound covalently at the peptide channel entrance, a sensor chip with a photostructurized hydrophobic polymer frame, a hydrophilic ion conducting membrane support, a lipid membrane incorporating the engineered ion channels, and a current amplifier or a sensitive fluorescence monitor. Detection of channel opening or closure can ether be obtained by directly monitoring membrane conductivity or a transient change of pH or ion concentration within the membrane compartment. This change can be induced by electrochemical or optical means and its decay is directly correlated to the permeability of the membrane. The ion concentration in the sub membrane compartment was monitored by incorporation of fluorescent indicator dyes. To obtain the stable sensor membrane the lipid layer had to be attached on a support and the floating of the second lipid membrane on top of the first one had to be prevented. Both problems do not occur using our new circular C44-C76 bolaamphiphilic lipids consisting of a long hydrophobic core region and two hydrophilic heads. Use of maleic ester-head groups enabled us to easily modify the lipids with amines, thioles, alcohols, phosphates, boronic acid as well as fluorescent dyes. The properties of these membranes were studied using LB and fluorescence techniques. Based on this detection principle miniaturized sensor chips with significantly enhanced sensitivity and large multi analyte arrays are under construction.

GLORIA imagery links sedimentation in Aleutian Trench to Yakutat margin via surveyor channel

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

Carlson, P.R.; Bruns, T.R.; Mann, D.M.

1990-06-01

GLORIA side-scan sonar imagery shows that the continental slope developing along the active margin of the Gulf of Alaska is devoid of large submarine canyons, in spite of the presence of large glacially formed sea valleys that cross the continental shelf. In the western and northern Gulf, discontinuous, actively growing deformation structures disrupt or divert the downslope transport of sediment into the Aleutian Trench. To the east of Middleton Island, the slope is intensively gullied and incised only by relatively small canyons. At the base of the gullied slope between Pamplona Spur and Alsek Valley, numerous small slope gullies coalescemore » into three turbidity current channels that merge to form the Surveyor deep-sea channel. About 350 km from the margin, the channel crosses the structural barrier formed by the Kodiak-Bowie Seamount chain and heads south for another 150 km where it bends northerly, perhaps influenced by the oceanic basement relief of the Patton Seamounts. The channel, now up to 5 km wide and deeply entrenched to 450 m, continues northerly for 200 km where it intercepts the Aleutian Trench, some 700 km from the Yakutat margin. South of Surveyor Channel, GLORIA imagery revealed evidence of another older channel. The older channel meanders through a gap in the seamount chain and eventually bends northwesterly. This now inactive, largely buried channel may have carried turbidity currents to the Aleutian Trench concurrent with the active Surveyor Channel.« less

Redox-mediated regulation of connexin proteins; focus on nitric oxide.

PubMed

García, Isaac E; Sánchez, Helmuth A; Martínez, Agustín D; Retamal, Mauricio A

2018-01-01

Connexins are membrane proteins that form hemichannels and gap junction channels at the plasma membrane. Through these channels connexins participate in autocrine and paracrine intercellular communication. Connexin-based channels are tightly regulated by membrane potential, phosphorylation, pH, redox potential, and divalent cations, among others, and the imbalance of this regulation have been linked to many acquired and genetic diseases. Concerning the redox potential regulation, the nitric oxide (NO) has been described as a modulator of the hemichannels and gap junction channels properties. However, how NO regulates these channels is not well understood. In this mini-review, we summarize the current knowledge about the effects of redox potential focused in NO on the trafficking, formation and functional properties of hemichannels and gap junction channels. Copyright © 2017 Elsevier B.V. All rights reserved.

Calcium channel currents in bovine adrenal chromaffin cells and their modulation by anaesthetic agents.

PubMed Central

Charlesworth, P; Pocock, G; Richards, C D

1994-01-01

1. The calcium channel currents of bovine adrenal chromaffin cells were characterized using a variety of voltage pulse protocols and selective channel blockers before examination of their modulation by anaesthetic agents. 2. All the anaesthetics studied (halothane, methoxyflurane, etomidate and methohexitone) inhibited the calcium channel currents in a concentration-dependent manner and increased the rate of current decay. 3. The anaesthetics did not shift the current-voltage relation nor did they change the voltage for half-maximal channel activation derived from analysis of the voltage dependence of the tail currents. None of the anaesthetics appeared to alter the time constant of tail current decay. 4. To complement earlier studies of the inhibitory actions of anaesthetics on K(+)-evoked catecholamine secretion and the associated Ca2+ uptake, the IC50 values for etomidate and methohexitone were determined using a biochemical assay. The IC50 values for anaesthetic inhibition of calcium channel currents corresponded closely with those for inhibition of K(+)-evoked calcium uptake and catecholamine secretion. 5. The inhibitory effect of the volatile anaesthetics and etomidate is best explained by dual action: a reduction in the probability of channel opening coupled with an increase in the rate of channel inactivation. Methohexitone appeared to inhibit the currents by a use-dependent slow block. PMID:7707224

Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K+ channels

PubMed Central

Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

2011-01-01

The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K+ currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss of function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude. PMID:21813698

Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels.

PubMed

Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

2011-08-03

The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude.

Lightning Return-Stroke Current Waveforms Aloft, From Measured Field Change, Current, and Channel Geometry

NASA Technical Reports Server (NTRS)

Willett, J. C.; LeVine, D. M.

2002-01-01

Direct current measurements are available near the attachment point from both natural cloud-to-ground lightning and rocket-triggered lightning, but little is known about the rise time and peak amplitude of return-stroke currents aloft. We present, as functions of height, current amplitudes, rise times, and effective propagation velocities that have been estimated with a novel remote-sensing technique from data on 24 subsequent return strokes in six different lightning flashes that were triggering at the NASA Kennedy Space Center, FL, during 1987. The unique feature of this data set is the stereo pairs of still photographs, from which three-dimensional channel geometries were determined previously. This has permitted us to calculate the fine structure of the electric-field-change (E) waveforms produced by these strokes, using the current waveforms measured at the channel base together with physically reasonable assumptions about the current distributions aloft. The computed waveforms have been compared with observed E waveforms from the same strokes, and our assumptions have been adjusted to maximize agreement. In spite of the non-uniqueness of solutions derived by this technique, several conclusions seem inescapable: 1) The effective propagation speed of the current up the channel is usually significantly (but not unreasonably) faster than the two-dimensional velocity measured by a streak camera for 14 of these strokes. 2) Given the deduced propagation speed, the peak amplitude of the current waveform often must decrease dramatically with height to prevent the electric field from being over-predicted. 3) The rise time of the current wave front must always increase rapidly with height in order to keep the fine structure of the calculated field consistent with the observations.

Dynamic ion-ion and water-ion interactions in ion channels.

PubMed Central

Wu, J V

1992-01-01

The dynamic interactions among ions and water molecules in ion channels are treated based on an assumption that ions at binding sites can be knocked off by both transient entering ions and local water molecules. The theory, when applied to a single-site model K+ channel, provides solutions for super- and subsaturations, flux-ratio exponent (n') greater than 1, osmotic streaming current, activity-dependent reversal potentials, and anomalous mole-fraction behavior. The analysis predicts that: (a) the saturation may but, in general, does not follow the Michaelis-Menten relation; (b) streaming current results from imbalanced water-ion knock-off interactions; (c) n' greater than 1 even for single-site channels, but it is unlikely to exceed 1.4 unless the pore is occupied by one or more ion(s); (d) in the calculation involving two permeant ion species with similar radii, the heavier ions show higher affinity; the ion-ion knock-off dissociation from the site is more effective when two interacting ions are identical. Therefore, the "multi-ion behaviors" found in most ion channels are the consequences of dynamic ion-ion and water-ion interactions. The presence of these interactions does not require two or more binding sites in channels. PMID:1376158

Rectification of Acetylcholine-Elicited Currents in PC12 Pheochromocytoma Cells

NASA Astrophysics Data System (ADS)

Ifune, C. K.; Steinbach, J. H.

1990-06-01

The current-voltage (I-V) relationship for acetylcholine-elicited currents in the rat pheochromocytoma cell line PC12 is nonlinear. Two voltage-dependent processes that could account for the whole-cell current rectification were examined, receptor channel gating and single receptor channel permeation. We found that both factors are involved in the rectification of the whole-cell currents. The voltage dependence of channel gating determines the shape of the I-V curve at negative potentials. The single-channel I-V relationship is inwardly rectifying and largely responsible for the characteristic shape of the whole-cell I-V curve at positive potentials. The rectification of the single-channel currents is produced by the voltage-dependent block of outward currents by intracellular Mg2+ ions.

Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

PubMed Central

Vidal, Jose; Ghovanloo, Maysam

2013-01-01

We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

Studies of the low-energy quasiparticle excitations in high-temperature superconducting cuprates with scanning tunneling spectroscopy and magnetization measurements

NASA Astrophysics Data System (ADS)

Boev, Ivan Krasimirov

In the present PhD work, three sophisticated models based on the "Engineering" modeling approach have been utilized to conveniently describe and thoroughly analyze details of Lightning events at the CN Tower. Both the CN Tower and the Lightning Channel are represented by a number of connected in series Transmission Line sections in order to account for the variations in the shape of the tower and for plasma processes that take place within the Lightning Channel. A sum of two Heidler functions is used to describe the "uncontaminated" Return Stroke current, which is injected at the attachment point between the CN Tower and the Lightning Channel. Reflections and refractions at all points of mismatched impedances are considered until their contribution becomes less than 1% of the originally injected current wave. In the proposed models, the problem with the current discontinuity at the Lightning Channel front, commonly taken care of by introducing a "turn-on" term when computing radiation fields, is uniquely treated by introducing reflected and transmitted components. For the first time, variable speed of propagation of the Return Stroke current front has been considered and its influence upon the predicted current distributions along the whole Lightning Channel path and upon the radiated distant fields analyzed. Furthermore, as another novelty, computation of the electromagnetic field is accomplished in Cartesian Coordinates. This fact permits to relax the requirement on the verticality of the Lightning Channel, normally imposed in Cylindrical Coordinates. Therefore, it becomes possible to study without difficulty the influence of a slanted Lightning Channel upon the surrounding electromagnetic field. Since the proposed sophisticated Five-Section Model has the capability to represent very closely the structure of the CN Tower and to emulate faithfully the shape of, as well as physical processes within the Lightning Channel, it is believed to have the potential of truthfully reproducing observed fields. The developed modeling approach can be easily adapted to study the anticipated radiated fields at tall structures even before construction.

Stopping electric field extension in a modified nanostructure based on SOI technology - A comprehensive numerical study

NASA Astrophysics Data System (ADS)

Anvarifard, Mohammad K.; Orouji, Ali A.

2017-11-01

This article has related a particular knowledge in order to reduce short channel effects (SCEs) in nano-devices based on silicon-on-insulator (SOI) MOSFETs. The device under study has been designed in 22 nm node technology with embedding Si3N4 extra oxide as a stopping layer of electric field and a useful heatsink for transferring generated heat. Two important subjects (DC characteristics and RF characteristics) have been investigated, simultaneously. Stopping electric field extension and enhancement of channel thermal conduction are introduced as an entrance gateway for this work so that improve the electrical characteristics, eventually. The inserted extra oxide made by the Si3N4 material has a vital impact on the modification of the electrical and thermal features in the proposed device. An immense comparison between the proposed SOI and conventional SOI showed that the proposed structure has higher electrical and thermal proficiency than the conventional structure in terms of main parameters such as short channel effects (SCEs), leakage current, floating body effect (FBE), self-heating effect (SHE), voltage gain, ratio of On-current to Off- current, transconductance, output conductance, minimum noise figure and power gain.

Molecular dynamics of alamethicin transmembrane channels from open-channel current noise analysis.

PubMed

Mak, D O; Webb, W W

1995-12-01

Conductance noise measurement of the open states of alamethicin transmembrane channels reveals excess noise attributable to cooperative low-frequency molecular dynamics that can generate fluctuations approximately 1 A rms in the effective channel pore radius. Single-channel currents through both persistent and nonpersistent channels with multiple conductance states formed by purified polypeptide alamethicin in artificial phospholipid bilayers isolated onto micropipettes with gigaohm seals were recorded using a voltage-clamp technique with low background noise (rms noise < 3 pA up to 20 kHz). Current noise power spectra between 100 Hz and 20 kHz of each open channel state showed little frequency dependence. Noise from undetected conductance state transitions was insignificant. Johnson and shot noises were evaluated. Current noise caused by electrolyte concentration fluctuation via diffusion was isolated by its dependence on buffer concentration. After removing these contributions, significant current noise remains in all persistent channel states and increases in higher conductance states. In nonpersistent channels, remaining noise occurs primarily in the lowest two states. These fluctuations of channel conductance are attributed to thermal oscillations of the channel molecular conformation and are modeled as a Langevin translational oscillation of alamethicin molecules moving radially from the channel pore, damped mostly by lipid bilayer viscosity.

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

Distribution of L-type calcium channels in rat thalamic neurones.

PubMed

Budde, T; Munsch, T; Pape, H C

1998-02-01

One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.

Simulation of polymer translocation through protein channels

PubMed Central

Muthukumar, M.; Kong, C. Y.

2006-01-01

A modeling algorithm is presented to compute simultaneously polymer conformations and ionic current, as single polymer molecules undergo translocation through protein channels. The method is based on a combination of Langevin dynamics for coarse-grained models of polymers and the Poisson–Nernst–Planck formalism for ionic current. For the illustrative example of ssDNA passing through the α-hemolysin pore, vivid details of conformational fluctuations of the polymer inside the vestibule and β-barrel compartments of the protein pore, and their consequent effects on the translocation time and extent of blocked ionic current are presented. In addition to yielding insights into several experimentally reported puzzles, our simulations offer experimental strategies to sequence polymers more efficiently. PMID:16567657

Spin Seebeck effect in a metal-single-molecule-magnet-metal junction

NASA Astrophysics Data System (ADS)

Niu, Pengbin; Liu, Lixiang; Su, Xiaoqiang; Dong, Lijuan; Luo, Hong-Gang

2018-01-01

We investigate the nonlinear regime of temperature-driven spin-related currents through a single molecular magnet (SMM), which is connected with two metal electrodes. Under a large spin approximation, the SMM is simplified to a natural two-channel model possessing spin-opposite configuration and Coulomb interaction. We find that in temperature-driven case the system can generate spin-polarized currents. More interestingly, at electron-hole symmetry point, the competition of the two channels induces a temperature-driven pure spin current. This device demonstrates that temperature-driven SMM junction shows some results different from the usual quantum dot model, which may be useful in the future design of thermal-based molecular spintronic devices.

Resurgent current of voltage-gated Na+ channels

PubMed Central

Lewis, Amanda H; Raman, Indira M

2014-01-01

Resurgent Na+ current results from a distinctive form of Na+ channel gating, originally identified in cerebellar Purkinje neurons. In these neurons, the tetrodotoxin-sensitive voltage-gated Na+ channels responsible for action potential firing have specialized mechanisms that reduce the likelihood that they accumulate in fast inactivated states, thereby shortening refractory periods and permitting rapid, repetitive, and/or burst firing. Under voltage clamp, step depolarizations evoke transient Na+ currents that rapidly activate and quickly decay, and step repolarizations elicit slower channel reopening, or a ‘resurgent’ current. The generation of resurgent current depends on a factor in the Na+ channel complex, probably a subunit such as NaVβ4 (Scn4b), which blocks open Na+ channels at positive voltages, competing with the fast inactivation gate, and unblocks at negative voltages, permitting recovery from an open channel block along with a flow of current. Following its initial discovery, resurgent Na+ current has been found in nearly 20 types of neurons. Emerging research suggests that resurgent current is preferentially increased in a variety of clinical conditions associated with altered cellular excitability. Here we review the biophysical, molecular and structural mechanisms of resurgent current and their relation to the normal functions of excitable cells as well as pathophysiology. PMID:25172941

Soft Wall Ion Channel in Continuum Representation with Application to Modeling Ion Currents in α-Hemolysin

PubMed Central

Simakov, Nikolay A.

2010-01-01

A soft repulsion (SR) model of short range interactions between mobile ions and protein atoms is introduced in the framework of continuum representation of the protein and solvent. The Poisson-Nernst-Plank (PNP) theory of ion transport through biological channels is modified to incorporate this soft wall protein model. Two sets of SR parameters are introduced: the first is parameterized for all essential amino acid residues using all atom molecular dynamic simulations; the second is a truncated Lennard – Jones potential. We have further designed an energy based algorithm for the determination of the ion accessible volume, which is appropriate for a particular system discretization. The effects of these models of short-range interaction were tested by computing current-voltage characteristics of the α-hemolysin channel. The introduced SR potentials significantly improve prediction of channel selectivity. In addition, we studied the effect of choice of some space-dependent diffusion coefficient distributions on the predicted current-voltage properties. We conclude that the diffusion coefficient distributions largely affect total currents and have little effect on rectifications, selectivity or reversal potential. The PNP-SR algorithm is implemented in a new efficient parallel Poisson, Poisson-Boltzman and PNP equation solver, also incorporated in a graphical molecular modeling package HARLEM. PMID:21028776

Evaluating interception of larval pallid sturgeon on the Lower Missouri River- data acquisition, interpolation, and visualization

NASA Astrophysics Data System (ADS)

Bulliner, E. A., IV; Erwin, S. O.; Anderson, B. J.; Wilson, H.; Jacobson, R. B.

2016-12-01

The transition from endogenous to exogenous feeding is an important life-stage transition for many riverine fish larvae. On the Missouri River, U.S., riverine alteration has decreased connectivity between the navigation channel and complex, food-producing and foraging areas on the channel margins, namely shallow side channels and sandbar complexes. A favored hypothesis, the interception hypothesis, for recruitment failure of pallid sturgeon is that drifting larvae are not able to exit the highly engineered navigation channel, and therefore starve. We present work exploring measures of hydraulic connectivity between the navigation channel and channel margins using multiple data-collection protocols with acoustic Doppler current profilers (ADCPs). As ADCP datasets alone often do not have high enough spatial resolution to characterize interception and connectivity sufficiently at the scale of drifting sturgeon larvae, they are often supplemented with physical and empirical models. Using boat-mounted ADCPs, we collected 3-dimensional current velocities with a variety of driving techniques (specifically, regularly spaced transects, reciprocal transects, and irregular patterns) around areas of potential larval interception. We then used toolkits based in Python to interpolate 3-dimensional velocity fields at spatial scales finer than the original measurements, and visualized resultant velocity vectors and flowlines in the software package Paraview. Using these visualizations, we investigated the necessary resolution of field measurements required to model connectivity with channel margin areas on large, highly engineered river ecosystems such as the Missouri River. We anticipate that results from this work will be used to help inform models of larval interception under current conditions. Furthermore, results from this work will be useful in developing monitoring strategies to evaluate the restoration of channel complexity to support ecological functions.

Effect of graded InGaN drain region and 'In' fraction in InGaN channel on performances of InGaN tunnel field-effect transistor

NASA Astrophysics Data System (ADS)

Duan, Xiaoling; Zhang, Jincheng; Wang, Shulong; Quan, Rudai; Hao, Yue

2017-12-01

An InGaN-based graded drain region tunnel field-effect transistor (GD-TFET) is proposed to suppress the ambipolar behavior. The simulation results with the trade-off between on-state current (Ion) and ambipolar current (Iambipolar) show decreased Iambipolar (1.9 × 10-14 A/μm) in comparison with that of conventional TFETs (2.0 × 10-8 A/μm). Furthermore, GD-TFET with high 'In' fraction InxGa1-xN source-side channel (SC- GD-TFET) is explored and exhibits 5.3 times Ion improvement and 60% average subthreshold swing (SSavg) reduction in comparison with GD-TFET by adjusting 'In' fraction in the InxGa1-xN source-side channel. The improvement is attributed to the confinement of BTBT in the source-side channel by the heterojunction. And then, the optimum value for source-side channel length (Lsc) is researched by DC performances results, which shows it falls into the range between Lsc = 10 nm and 20 nm.

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.

Cytosolic Nucleotides Block and Regulate the Arabidopsis Vacuolar Anion Channel AtALMT9*

PubMed Central

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-01-01

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al3+ to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. PMID:25028514

Cytosolic nucleotides block and regulate the Arabidopsis vacuolar anion channel AtALMT9.

PubMed

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-09-12

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al(3+) to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Sedimentological characteristics and depositional processes of sediment gravity flows in rift basins: The Palaeogene Dongying and Shahejie formations, Bohai Bay Basin, China

NASA Astrophysics Data System (ADS)

Liu, Lei; Chen, Hongde; Zhong, Yijiang; Wang, Jun; Xu, Changgui; Chen, Anqing; Du, Xiaofeng

2017-10-01

Sediment gravity flow deposits are common, particularly in sandy formations, but their origin has been a matter of debate and there is no consensus about the classification of such deposits. However, sediment gravity flow sandstones are economically important and have the potential to meet a growing demand in oil and gas exploration, so there is a drive to better understand them. This study focuses on sediment gravity flow deposits identified from well cores in Palaeogene deposits from the Liaodong Bay Depression in Bohai Bay Basin, China. We classify the sediment gravity flow deposits into eight lithofacies using lithological characteristics, grain size, and sedimentary structures, and interpret the associated depositional processes. Based on the scale, spatial distribution, and contact relationships of sediment gravity flow deposits, we defined six types of lithofacies associations (LAs) that reflect transformation processes and depositional morphology: LA1 (unconfined proximal breccia deposits), LA2 (confined channel deposits), LA3 (braided-channel lobe deposits), LA4 (unconfined lobe deposits), LA5 (distal sheet deposits), and LA6 (non-channelized sheet deposits). Finally, we established three depositional models that reflect the sedimentological characteristics and depositional processes of sediment gravity flow deposits: (1) slope-apron gravel-rich depositional model, which involves cohesive debris flows deposited as LA1 and dilute turbidity currents deposited as LA5; (2) non-channelized surge-like turbidity current depositional model, which mainly comprises sandy slumping, suspended load dominated turbidity currents, and dilute turbidity currents deposited as LA5 and LA6; and (3) channelized subaqueous-fan depositional model, which consists of non-cohesive bedload dominated turbidity currents, suspended load dominated turbidity currents, and dilute turbidity currents deposited as LA2-LA5, originating from sustained extrabasinal turbidity currents (hyperpycnal flow). The depositional models may be applicable to oil and gas exploration and production from sediment gravity flow systems in similar lacustrine depositional environments elsewhere.

Lightning NOx Statistics Derived by NASA Lightning Nitrogen Oxides Model (LNOM) Data Analyses

NASA Technical Reports Server (NTRS)

Koshak, William; Peterson, Harold

2013-01-01

What is the LNOM? The NASA Marshall Space Flight Center (MSFC) Lightning Nitrogen Oxides Model (LNOM) [Koshak et al., 2009, 2010, 2011; Koshak and Peterson 2011, 2013] analyzes VHF Lightning Mapping Array (LMA) and National Lightning Detection Network(TradeMark) (NLDN) data to estimate the lightning nitrogen oxides (LNOx) produced by individual flashes. Figure 1 provides an overview of LNOM functionality. Benefits of LNOM: (1) Does away with unrealistic "vertical stick" lightning channel models for estimating LNOx; (2) Uses ground-based VHF data that maps out the true channel in space and time to < 100 m accuracy; (3) Therefore, true channel segment height (ambient air density) is used to compute LNOx; (4) True channel length is used! (typically tens of kilometers since channel has many branches and "wiggles"); (5) Distinction between ground and cloud flashes are made; (6) For ground flashes, actual peak current from NLDN used to compute NOx from lightning return stroke; (7) NOx computed for several other lightning discharge processes (based on Cooray et al., 2009 theory): (a) Hot core of stepped leaders and dart leaders, (b) Corona sheath of stepped leader, (c) K-change, (d) Continuing Currents, and (e) M-components; and (8) LNOM statistics (see later) can be used to parameterize LNOx production for regional air quality models (like CMAQ), and for global chemical transport models (like GEOS-Chem).

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.

Fully transparent thin film transistors based on zinc oxide channel layer and molybdenum doped indium oxide electrodes

NASA Astrophysics Data System (ADS)

MÄ dzik, Mateusz; Elamurugu, Elangovan; Viegas, Jaime

2016-03-01

In this work we report the fabrication of thin film transistors (TFT) with zinc oxide channel and molybdenum doped indium oxide (IMO) electrodes, achieved by room temperature sputtering. A set of devices was fabricated, with varying channel width and length from 5μm to 300μm. Output and transfer characteristics were then extracted to study the performance of thin film transistors, namely threshold voltage and saturation current, enabling to determine optimal fabrication process parameters. Optical transmission in the UV-VIS-IR are also reported.

Zinc oxide integrated area efficient high output low power wavy channel thin film transistor

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

Hanna, A. N.; Ghoneim, M. T.; Bahabry, R. R.

2013-11-25

We report an atomic layer deposition based zinc oxide channel material integrated thin film transistor using wavy channel architecture allowing expansion of the transistor width in the vertical direction using the fin type features. The experimental devices show area efficiency, higher normalized output current, and relatively lower power consumption compared to the planar architecture. This performance gain is attributed to the increased device width and an enhanced applied electric field due to the architecture when compared to a back gated planar device with the same process conditions.

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

Design Optimization of Ge/GaAs-Based Heterojunction Gate-All-Around (GAA) Arch-Shaped Tunneling Field-Effect Transistor (A-TFET).

PubMed

Seo, Jae Hwa; Yoon, Young Jun; Kang, In Man

2018-09-01

The Ge/GaAs-based heterojunction gate-all-around (GAA) arch-shaped tunneling field-effect transistor (A-TFET) have been designed and optimized using technology computer-aided design (TCAD) simulations. In our previous work, the silicon-based A-TFET was designed and demonstrated. However, to progress the electrical characteristics of A-TFET, the III-V compound heterojunction structures which has enhanced electrical properties must be adopted. Thus, the germanium with gallium arsenide (Ge/GaAs) is considered as key materials of A-TFET. The proposed device has a Ge-based p-doped source, GaAs-based i-doped channel and GaAs-based n-doped drain. Due to the critical issues of device performances, the doping concentration of source and channel region (Dsource, Dchannel), height of source region (Hsource) and epitaxially grown thickness of channel (tepi) was selected as design optimization variables of Ge/GaAs-based GAA A-TFET. The DC characteristics such as on-state current (ion), off-state current (ioff), subthreshold-swing (S) were of extracted and analyzed. Finally, the proposed device has a gate length (LG) of 90 nm, Dsource 5 × 1019 cm-3, Dchannel of 1018 cm-3, tepi of 4 nm, Hsource of 90 nm, R of 10 nm and demonstrate an ion of 2 mA/μm, S of 12.9 mV/dec.

Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

PubMed

Wu, Wei; Sanguinetti, Michael C

2016-06-01

Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Inactivation of A currents and A channels on rat nodose neurons in culture

PubMed Central

1989-01-01

Cultured sensory neurons from nodose ganglia were investigated with whole-cell patch-clamp techniques and single-channel recordings to characterize the A current. Membrane depolarization from -40 mV holding potential activated the delayed rectifier current (IK) at potentials positive to -30 mV; this current had a sigmoidal time course and showed little or no inactivation. In most neurons, the A current was completely inactivated at the -40 mV holding potential and required hyperpolarization to remove the inactivation; the A current was isolated by subtracting the IK evoked by depolarizations from -40 mV from the total outward current evoked by depolarizations from -90 mV. The decay of the A current on several neurons had complex kinetics and was fit by the sum of three exponentials whose time constants were 10- 40 ms, 100-350 ms, and 1-3 s. At the single-channel level we found that one class of channel underlies the A current. The conductance of A channels varied with the square root of the external K concentration: it was 22 pS when exposed to 5.4 mM K externally, the increased to 40 pS when exposed to 140 mM K externally. A channels activated rapidly upon depolarization and the latency to first opening decreased with depolarization. The open time distributions followed a single exponential and the mean open time increased with depolarization. A channels inactivate in three different modes: some A channels inactivated with little reopening and gave rise to ensemble averages that decayed in 10-40 ms; other A channels opened and closed three to four times before inactivating and gave rise to ensemble averages that decayed in 100-350 ms; still other A channels opened and closed several hundred times and required seconds to inactivate. Channels gating in all three modes contributed to the macroscopic A current from the whole cell, but their relative contribution differed among neurons. In addition, A channels could go directly from the closed, or resting, state to the inactivated state without opening, and the probability for channels inactivating in this way was greater at less depolarized voltages. In addition, a few A channels appeared to go reversibly from a mode where inactivation occurred rapidly to a slow mode of inactivation. PMID:2592953

Disintegration of rocks based on magnetically isolated high voltage discharge

NASA Astrophysics Data System (ADS)

He, Mengbing; Jiang, Jinbo; Huang, Guoliang; Liu, Jun; Li, Chengzu

2013-02-01

Recently, a method utilizing pulsed power technology for disintegration of rocks arouses great interest of many researchers. In this paper, an improved method based on magnetic switch and the results shown that the uniform dielectrics like plastic can be broken down in water is presented, and the feasible mechanism explaining the breakdown of solid is proposed and proved experimentally. A high voltage pulse of 120 kV, rise time 0.2 μs was used to ignite the discharging channel in solids. When the plasma channel is formed in the solid, the resistance of the channel is quiet small; even if a relatively low voltage is applied on the channel on this occasion, it will produce high current to heat the plasma channel rapidly, and eventually disintegrate the solids. The feasibility of promising industrial application in the drilling and demolition of natural and artificial solid materials by the method we presented is verified by the experiment result in the paper.

Disintegration of rocks based on magnetically isolated high voltage discharge.

PubMed

He, Mengbing; Jiang, Jinbo; Huang, Guoliang; Liu, Jun; Li, Chengzu

2013-02-01

Recently, a method utilizing pulsed power technology for disintegration of rocks arouses great interest of many researchers. In this paper, an improved method based on magnetic switch and the results shown that the uniform dielectrics like plastic can be broken down in water is presented, and the feasible mechanism explaining the breakdown of solid is proposed and proved experimentally. A high voltage pulse of 120 kV, rise time 0.2 μs was used to ignite the discharging channel in solids. When the plasma channel is formed in the solid, the resistance of the channel is quiet small; even if a relatively low voltage is applied on the channel on this occasion, it will produce high current to heat the plasma channel rapidly, and eventually disintegrate the solids. The feasibility of promising industrial application in the drilling and demolition of natural and artificial solid materials by the method we presented is verified by the experiment result in the paper.

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.

A p-i-n junction diode based on locally doped carbon nanotube network

PubMed Central

Liu, Xiaodong; Chen, Changxin; Wei, Liangming; Hu, Nantao; Song, Chuanjuan; Liao, Chenghao; He, Rong; Dong, Xusheng; Wang, Ying; Liu, Qinran; Zhang, Yafei

2016-01-01

A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~104), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm. PMID:26996610

A p-i-n junction diode based on locally doped carbon nanotube network.

PubMed

Liu, Xiaodong; Chen, Changxin; Wei, Liangming; Hu, Nantao; Song, Chuanjuan; Liao, Chenghao; He, Rong; Dong, Xusheng; Wang, Ying; Liu, Qinran; Zhang, Yafei

2016-03-21

A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~10(4)), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm.

A p-i-n junction diode based on locally doped carbon nanotube network

NASA Astrophysics Data System (ADS)

Liu, Xiaodong; Chen, Changxin; Wei, Liangming; Hu, Nantao; Song, Chuanjuan; Liao, Chenghao; He, Rong; Dong, Xusheng; Wang, Ying; Liu, Qinran; Zhang, Yafei

2016-03-01

A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~104), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm.

Quantifying Process-Based Mitigation Strategies in Historical Context: Separating Multiple Cumulative Effects on River Meander Migration

PubMed Central

Fremier, Alexander K.; Girvetz, Evan H.; Greco, Steven E.; Larsen, Eric W.

2014-01-01

Environmental legislation in the US (i.e. NEPA) requires defining baseline conditions on current rather than historical ecosystem conditions. For ecosystems with long histories of multiple environmental impacts, this baseline method can subsequently lead to a significantly altered environment; this has been termed a ‘sliding baseline’. In river systems, cumulative effects caused by flow regulation, channel revetment and riparian vegetation removal significantly impact floodplain ecosystems by altering channel dynamics and precluding subsequent ecosystem processes, such as primary succession. To quantify these impacts on floodplain development processes, we used a model of river channel meander migration to illustrate the degree to which flow regulation and riprap impact migration rates, independently and synergistically, on the Sacramento River in California, USA. From pre-dam conditions, the cumulative effect of flow regulation alone on channel migration is a reduction by 38%, and 42–44% with four proposed water diversion project scenarios. In terms of depositional area, the proposed water project would reduce channel migration 51–71 ha in 130 years without current riprap in place, and 17–25 ha with riprap. Our results illustrate the utility of a modeling approach for quantifying cumulative impacts. Model-based quantification of environmental impacts allow scientists to separate cumulative and synergistic effects to analytically define mitigation measures. Additionally, by selecting an ecosystem process that is affected by multiple impacts, it is possible to consider process-based mitigation scenarios, such as the removal of riprap, to allow meander migration and create new floodplains and allow for riparian vegetation recruitment. PMID:24964145

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.

Optimal electrode selection for multi-channel electroencephalogram based detection of auditory steady-state responses.

PubMed

Van Dun, Bram; Wouters, Jan; Moonen, Marc

2009-07-01

Auditory steady-state responses (ASSRs) are used for hearing threshold estimation at audiometric frequencies. Hearing impaired newborns, in particular, benefit from this technique as it allows for a more precise diagnosis than traditional techniques, and a hearing aid can be better fitted at an early age. However, measurement duration of current single-channel techniques is still too long for clinical widespread use. This paper evaluates the practical performance of a multi-channel electroencephalogram (EEG) processing strategy based on a detection theory approach. A minimum electrode set is determined for ASSRs with frequencies between 80 and 110 Hz using eight-channel EEG measurements of ten normal-hearing adults. This set provides a near-optimal hearing threshold estimate for all subjects and improves response detection significantly for EEG data with numerous artifacts. Multi-channel processing does not significantly improve response detection for EEG data with few artifacts. In this case, best response detection is obtained when noise-weighted averaging is applied on single-channel data. The same test setup (eight channels, ten normal-hearing subjects) is also used to determine a minimum electrode setup for 10-Hz ASSRs. This configuration allows to record near-optimal signal-to-noise ratios for 80% of subjects.

Uncertainty Evaluations of the CRCS In-orbit Field Radiometric Calibration Methods for Thermal Infrared Channels of FENGYUN Meteorological Satellites

NASA Astrophysics Data System (ADS)

Zhang, Y.; Rong, Z.; Min, M.; Hao, X.; Yang, H.

2017-12-01

Meteorological satellites have become an irreplaceable weather and ocean-observing tool in China. These satellites are used to monitor natural disasters and improve the efficiency of many sectors of Chinese national economy. It is impossible to ignore the space-derived data in the fields of meteorology, hydrology, and agriculture, as well as disaster monitoring in China, a large agricultural country. For this reason, China is making a sustained effort to build and enhance its meteorological observing system and application system. The first Chinese polar-orbiting weather satellite was launched in 1988. Since then China has launched 14 meteorological satellites, 7 of which are sun synchronous and 7 of which are geostationary satellites; China will continue its two types of meteorological satellite programs. In order to achieve the in-orbit absolute radiometric calibration of the operational meteorological satellites' thermal infrared channels, China radiometric calibration sites (CRCS) established a set of in-orbit field absolute radiometric calibration methods (FCM) for thermal infrared channels (TIR) and the uncertainty of this method was evaluated and analyzed based on TERRA/AQUA MODIS observations. Comparisons between the MODIS at pupil brightness temperatures (BTs) and the simulated BTs at the top of atmosphere using radiative transfer model (RTM) based on field measurements showed that the accuracy of the current in-orbit field absolute radiometric calibration methods was better than 1.00K (@300K, K=1) in thermal infrared channels. Therefore, the current CRCS field calibration method for TIR channels applied to Chinese metrological satellites was with favorable calibration accuracy: for 10.5-11.5µm channel was better than 0.75K (@300K, K=1) and for 11.5-12.5µm channel was better than 0.85K (@300K, K=1).

Multi-channel electrical impedance tomography for regional tissue hydration monitoring.

PubMed

Chen, Xiaohui; Kao, Tzu-Jen; Ashe, Jeffrey M; Boverman, Gregory; Sabatini, James E; Davenport, David M

2014-06-01

Poor assessment of hydration status during hemodialysis can lead to under- or over-hydration in patients with consequences of increased morbidity and mortality. In current practice, fluid management is largely based on clinical assessments to estimate dry weight (normal hydration body weight). However, hemodialysis patients usually have co-morbidities that can make the signs of fluid status ambiguous. Therefore, achieving normal hydration status remains a major challenge for hemodialysis therapy. Electrical impedance technology has emerged as a promising method for hydration monitoring due to its non-invasive nature, low cost and ease-of-use. Conventional electrical impedance-based hydration monitoring systems employ single-channel current excitation (either 2-electrode or 4-electrode methods) to perturb and extract averaged impedance from bulk tissue and use generalized models from large populations to derive hydration estimates. In the present study, a prototype, single-frequency electrical impedance tomography (EIT) system with simultaneous multi-channel current excitation was used to enable regional hydration change detection. We demonstrated the capability to detect a difference in daily impedance change between left leg and right leg in healthy human subjects, who wore a compression sock only on one leg to reduce daily gravitational fluid accumulation. The impedance difference corresponded well with the difference of lower leg volume change between left leg and right leg measured by volumetry, which on average is ~35 ml, accounting for 0.7% of the lower leg volume. We have demonstrated the feasibility of using multi-channel EIT to extract hydration information in different tissue layers with minimal skin interference. Our simultaneous, multi-channel current excitation approach provides an effective method to separate electrode contact impedance and skin condition artifacts from hydration signals. The prototype system has the potential to be used in clinical settings for helping optimize patient fluid management during hemodialysis as well as for home monitoring of patients with congestive heart failure, chronic kidney disease, diabetes and other diseases with peripheral edema symptoms.

Dedicated multichannel readout ASIC coupled with single crystal diamond for dosimeter application

NASA Astrophysics Data System (ADS)

Fabbri, A.; Falco, M. D.; De Notaristefani, F.; Galasso, M.; Marinelli, M.; Orsolini Cencelli, V.; Tortora, L.; Verona, C.; Verona Rinati, G.

2013-02-01

This paper reports on the tests of a low-noise, multi-channel readout integrated circuit used as a readout electronic front-end for a diamond multi-pixel dosimeter. The system is developed for dose distribution measurement in radiotherapy applications. The first 10-channel prototype chip was designed and fabricated in a 0.18 um CMOS process. Every channel includes a charge integrator with a 10 pF capacitor and a double slope A/D converter. The diamond multi-pixel detector, based on CVD synthetic single crystal diamond Schottky diodes, is made by a 3 × 3 sensor matrix. The overall device has been tested under irradiation with 6 MeV radio therapeutic photon beams at the Policlinico ``Tor Vergata'' (PTV) hospital. Measurements show a 20 fA RMS leakage current from the front-end input stage and a negligible dark current from the diamond detector, a stable temporal response and a good linear behaviour as a function of both dose and dose rate. These characteristics were common to each tested channel.

Top-gated chemical vapor deposition grown graphene transistors with current saturation.

PubMed

Bai, Jingwei; Liao, Lei; Zhou, Hailong; Cheng, Rui; Liu, Lixin; Huang, Yu; Duan, Xiangfeng

2011-06-08

Graphene transistors are of considerable interest for radio frequency (rf) applications. In general, transistors with large transconductance and drain current saturation are desirable for rf performance, which is however nontrivial to achieve in graphene transistors. Here we report high-performance top-gated graphene transistors based on chemical vapor deposition (CVD) grown graphene with large transconductance and drain current saturation. The graphene transistors were fabricated with evaporated high dielectric constant material (HfO(2)) as the top-gate dielectrics. Length scaling studies of the transistors with channel length from 5.6 μm to 100 nm show that complete current saturation can be achieved in 5.6 μm devices and the saturation characteristics degrade as the channel length shrinks down to the 100-300 nm regime. The drain current saturation was primarily attributed to drain bias induced shift of the Dirac points. With the selective deposition of HfO(2) gate dielectrics, we have further demonstrated a simple scheme to realize a 300 nm channel length graphene transistors with self-aligned source-drain electrodes to achieve the highest transconductance of 250 μS/μm reported in CVD graphene to date.

Inferred flows of electric currents in solar active regions

NASA Technical Reports Server (NTRS)

Ding, Y. J.; Hong, Q. F.; Hagyard, M. J.; Deloach, A. C.

1985-01-01

Techniques to identify sources of major current systems in active regions and their channels of flow are explored. Measured photospheric vector magnetic fields together with high resolution white light and H-alpha photographs provide the data base to derive the current systems in the photosphere and chromosphere of a solar active region. Simple mathematical constructions of active region fields and currents are used to interpret these data under the assumptions that the fields in the lower atmosphere (below 200 km) may not be force free but those in the chromosphere and higher are. The results obtained for the complex active region AR 2372 are: (1) Spots exhibiting significant spiral structure in the penumbral filaments were the source of vertical currents at the photospheric surface; (2) Magnetic neutral lines where the transverse magnetic field was strongly sheared were channels along which a strong current system flowed; (3) The inferred current systems produced a neutral sheet and oppositely-flowing currents in the area of the magnetic delta configuration that was the site of flaring.

Gravity currents in rotating channels. Part 1. Steady-state theory

NASA Astrophysics Data System (ADS)

Hacker, J. N.; Linden, P. F.

2002-04-01

A theory is developed for the speed and structure of steady-state non-dissipative gravity currents in rotating channels. The theory is an extension of that of Benjamin (1968) for non-rotating gravity currents, and in a similar way makes use of the steady-state and perfect-fluid (incompressible, inviscid and immiscible) approximations, and supposes the existence of a hydrostatic ‘control point’ in the current some distance away from the nose. The model allows for fully non-hydrostatic and ageostrophic motion in a control volume V ahead of the control point, with the solution being determined by the requirements, consistent with the perfect-fluid approximation, of energy and momentum conservation in V, as expressed by Bernoulli's theorem and a generalized flow-force balance. The governing parameter in the problem, which expresses the strength of the background rotation, is the ratio W = B/R, where B is the channel width and R = (g[prime prime or minute]H)1/2/f is the internal Rossby radius of deformation based on the total depth of the ambient fluid H. Analytic solutions are determined for the particular case of zero front-relative flow within the gravity current. For each value of W there is a unique non-dissipative two-layer solution, and a non-dissipative one-layer solution which is specified by the value of the wall-depth h0. In the two-layer case, the non-dimensional propagation speed c = cf(g[prime prime or minute]H)[minus sign]1/2 increases smoothly from the non-rotating value of 0.5 as W increases, asymptoting to unity for W [rightward arrow] [infty infinity]. The gravity current separates from the left-hand wall of the channel at W = 0.67 and thereafter has decreasing width. The depth of the current at the right-hand wall, h0, increases, reaching the full depth at W = 1.90, after which point the interface outcrops on both the upper and lower boundaries, with the distance over which the interface slopes being 0.881R. In the one-layer case, the wall-depth based propagation speed Froude number c0 = cf(g[prime prime or minute]h0)[minus sign]1/2 = 21/2, as in the non-rotating one-layer case. The current separates from the left-hand wall of the channel at W0 [identical with] B/R0 = 2[minus sign]1/2, and thereafter has width 2[minus sign]1/2R0, where R0 = (g[prime prime or minute]h0)1/2/f is the wall-depth based deformation radius.

Eddy current proximity measurement of perpendicular tubes from within pressure tubes in CANDU nuclear reactors

NASA Astrophysics Data System (ADS)

Bennett, P. F. D.; Underhill, P. R.; Morelli, J.; Krause, T. W.

2018-04-01

Fuel channels in CANDU® (CANada Deuterium Uranium) nuclear reactors consist of two non-concentric tubes; an inner pressure tube (PT) and a larger diameter calandria tube (CT). Up to 400 horizontally mounted fuel channels are contained within a calandria vessel, which also holds the heavy water moderator. Certain fuel channels pass perpendicularly over horizontally oriented tubes (nozzles) that are part of the reactor's liquid injection shutdown system (LISS). Due to sag, these fuel channels are at risk of coming into contact with the LISS nozzles. In the event of contact between the LISS nozzle and CT, flow-induced vibrations from within the moderator could lead to fretting and deformation of the CT. LISS nozzle proximity to CTs is currently measured optically from within the calandria vessel, but from outside the fuel channels. Measurement by an independent means would provide confidence in optical results and supplement cases where optical observations are not possible. Separation of PT and CT, known as gap, is monitored from within the PT using a transmit-receive eddy current probe. Investigation of the eddy current based gap probe as a tool to also measure proximity of LISS nozzles was carried out experimentally in this work. Eddy current response as a function of LISS-PT proximity was recorded. When PT-CT gap, PT wall thickness, PT resistivity and probe lift-off variations were not present this dependence could be used to determine the LISS-PT proximity. This method has the potential to provide LISS-CT proximity using existing gap measurement data. Obtaining LISS nozzle proximity at multiple inspection intervals could be used to provide an estimate of the time to LISS-CT contact, and thereby provide a means of optimizing maintenance schedules.

Spin-Current-Controlled Modulation of the Magnon Spin Conductance in a Three-Terminal Magnon Transistor

NASA Astrophysics Data System (ADS)

Cornelissen, L. J.; Liu, J.; van Wees, B. J.; Duine, R. A.

2018-03-01

Efficient manipulation of magnon spin transport is crucial for developing magnon-based spintronic devices. In this Letter, we provide proof of principle of a method for modulating the diffusive transport of thermal magnons in an yttrium iron garnet channel between injector and detector contacts. The magnon spin conductance of the channel is altered by increasing or decreasing the magnon chemical potential via spin Hall injection of magnons by a third modulator electrode. We obtain a modulation efficiency of 1.6 %/mA at T =250 K . Finite element modeling shows that this could be increased to well above 10 %/mA by reducing the thickness of the channel, providing interesting prospects for the development of thermal-magnon-based logic circuits.

Characterisation of the LMS propagation channel at L- and S-bands: Narrowband experimental data and channel modelling

NASA Technical Reports Server (NTRS)

Sforza, Mario; Buonomo, Sergio

1993-01-01

During the period 1983-1992 the European Space Agency (ESA) carried out several experimental campaigns to investigate the propagation impairments of the Land Mobile Satellite (LMS) communication channel. A substantial amount of data covering quite a large range of elevation angles, environments, and frequencies was obtained. Results from the data analyses are currently used for system planning and design applications within the framework of the future ESA LMS projects. This comprehensive experimental data base is presently utilized also for channel modeling purposes and preliminary results are given. Cumulative Distribution Functions (PDF) and Duration of Fades (DoF) statistics at different elevation angles and environments were also included.

Phosphorus Doping Effect in a Zinc Oxide Channel Layer to Improve the Performance of Oxide Thin-Film Transistors

NASA Astrophysics Data System (ADS)

Han, Dong-Suk; Moon, Yeon-Keon; Lee, Sih; Kim, Kyung-Taek; Moon, Dae-Yong; Lee, Sang-Ho; Kim, Woong-Sun; Park, Jong-Wan

2012-09-01

In this study, we fabricated phosphorus-doped zinc oxide-based thin-film transistors (TFTs) using direct current (DC) magnetron sputtering at a relatively low temperature of 100°C. To improve the TFT device performance, including field-effect mobility and bias stress stability, phosphorus dopants were employed to suppress the generation of intrinsic defects in the ZnO-based semiconductor. The positive and negative bias stress stabilities were dramatically improved by introducing the phosphorus dopants, which could prevent turn-on voltage ( V ON) shift in the TFTs caused by charge trapping within the active channel layer. The study showed that phosphorus doping in ZnO was an effective method to control the electrical properties of the active channel layers and improve the bias stress stability of oxide-based TFTs.

The Advanced Gamma-ray Imaging System (AGIS): Camera Electronics Designs

NASA Astrophysics Data System (ADS)

Tajima, H.; Buckley, J.; Byrum, K.; Drake, G.; Falcone, A.; Funk, S.; Holder, J.; Horan, D.; Krawczynski, H.; Ong, R.; Swordy, S.; Wagner, R.; Williams, D.

2008-04-01

AGIS, a next generation of atmospheric Cherenkov telescope arrays, aims to achieve a sensitivity level of a milliCrab for gamma-ray observations in the energy band of 40 GeV to 100 TeV. Such improvement requires cost reduction of individual components with high reliability in order to equip the order of 100 telescopes necessary to achieve the sensitivity goal. We are exploring several design concepts to reduce the cost of camera electronics while improving their performance. These design concepts include systems based on multi-channel waveform sampling ASIC optimized for AGIS, a system based on IIT (image intensifier tube) for large channel (order of 1 million channels) readout as well as a multiplexed FADC system based on the current VERITAS readout design. Here we present trade-off in the studies of these design concepts.

The Advanced Gamma-ray Imaging System (AGIS): Camera Electronics Designs

NASA Astrophysics Data System (ADS)

Tajima, Hiroyasu; Buckley, J.; Byrum, K.; Drake, G.; Falcone, A.; Funk, S.; Holder, J.; Horan, D.; Krawczynski, H.; Ong, R.; Swordy, S.; Wagner, R.; Wakely, S.; Williams, D.; Camera Electronics Working Group; AGIS Collaboration

2008-03-01

AGIS, a next generation of atmospheric Cherenkov telescope arrays, aims to achieve a sensitivity level of a milliCrab for gamma-ray observations in in the energy band of 40 GeV to 100 TeV. Such improvement requires cost reduction of individual components with high reliability in order to equip the order of 100 telescopes necessary to achieve the sensitivity goal. We are exploring several design concepts to reduce the cost of camera electronics while improving their performance. These design concepts include systems based on multi-channel waveform sampling ASIC optimized for AGIS, a system based on IIT (image intensifier tube) for large channel (order of 1 million channels) readout as well as a multiplexed FADC system based on the current VERITAS readout design. Here we present trade-off studies of these design concepts.

Non-invasive paper-based microfluidic device for ultra-low detection of urea through enzyme catalysis

NASA Astrophysics Data System (ADS)

Suresh, Vignesh; Qunya, Ong; Kanta, Bera Lakshmi; Yuh, Lee Yeong; Chong, Karen S. L.

2018-03-01

This work describes the design, fabrication and characterization of a paper-based microfluidic device for ultra-low detection of urea through enzyme catalysis. The microfluidic system comprises an entry port, a fluidic channel, a reaction zone and two electrodes (contacts). Wax printing was used to create fluidic channels on the surface of a chromatography paper. Pre-conceptualized designs of the fluidic channel are wax-printed on the paper substrate while the electrodes are screen-printed. The paper printed with wax is heated to cause the wax reflow along the thickness of the paper that selectively creates hydrophilic and hydrophobic zones inside the paper. Urease immobilized in the reaction zone catalyses urea into releasing ions and, thereby, generating a current flow between the electrodes. A measure of current with respect to time at a fixed potential enables the detection of urea. The methodology enabled urea concentration down to 1 pM to be detected. The significance of this work lies in the use of simple and inexpensive paper-based substrates to achieve detection of ultra-low concentrations of analytes such as urea. The process is non-invasive and employs a less cumbersome two-electrode assembly.

Growth, Failure, and Erosion of Submarine Channel Levees on the Upper Mississippi Fan, Gulf of Mexico

NASA Astrophysics Data System (ADS)

Sawyer, D. E.; Flemings, P. B.; Nikolinakou, M. A.

2011-12-01

Late Pleistocene channel levees on the Mississippi Fan failed repeatedly along deep-seated listric faults. These growth faults begin at the top of the levee, as much as a kilometer away from the channel axis. They plunge 150-200 meters downward reaching their deepest point halfway towards the channel axis (0.5 km) along the base of a regional sand unit. They then rise toward the channel axis where they emerge. The erosion of toe-thrust material coupled with levee growth, promoted a dynamic equilibrium: turbidity currents flushed the channel axis and deposited new levee on the margins, which induced further displacement into the channel. With a geomechanical model we show that deep-seated failure occurred by undrained loading of an underlying low permeability mudstone. Excess pore pressure formed a low-strength layer that localized the detachment at the base of a regional sand. Our results show that deep-seated failure is expected when levee systems form above regional sand bodies that were deposited rapidly above low permeability mudstone. Furthermore, the presence of this failure style in channel-levee systems is a strong indicator that overpressures and low effective stresses were present during formation and thus record paleo-pressures. Understanding these systems is critical for the design of safe well penetrations, predicting hydraulic connectivity of deepwater channel sands, and the growth of submarine channel-levee systems. This study illuminates the linkages between sedimentation, erosion, and the mechanical stability of levees in submarine channel systems.

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

PubMed Central

McNally, Beth A.

2018-01-01

Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+i). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)—the brain’s circadian clock—BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+i are reduced. Here, to determine whether diurnal regulation of Ca2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca2+ channels (LTCCs) are the primary daytime Ca2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)–mediated Ca2+i release. The N- and P/Q-type Ca2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. PMID:29237755

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

PubMed

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

2018-02-05

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

Explorations of electric current system in solar active regions. I - Empirical inferences of the current flows

NASA Technical Reports Server (NTRS)

Ding, Y. J.; Hong, Q. F.; Hagyard, M. J.; Deloach, A. C.; Liu, X. P.

1987-01-01

Techniques to identify sources of electric current systems and their channels of flow in solar active regions are explored. Measured photospheric vector magnetic fields together with high-resolution white-light and H-alpha filtergrams provide the data base to derive the current systems in the photosphere and chromosphere. As an example, the techniques are then applied to infer current systems in AR 2372 in early April 1980.

The Blurred Line between Form and Process: A Comparison of Stream Channel Classification Frameworks

PubMed Central

Kasprak, Alan; Hough-Snee, Nate

2016-01-01

Stream classification provides a means to understand the diversity and distribution of channels and floodplains that occur across a landscape while identifying links between geomorphic form and process. Accordingly, stream classification is frequently employed as a watershed planning, management, and restoration tool. At the same time, there has been intense debate and criticism of particular frameworks, on the grounds that these frameworks classify stream reaches based largely on their physical form, rather than direct measurements of their component hydrogeomorphic processes. Despite this debate surrounding stream classifications, and their ongoing use in watershed management, direct comparisons of channel classification frameworks are rare. Here we implement four stream classification frameworks and explore the degree to which each make inferences about hydrogeomorphic process from channel form within the Middle Fork John Day Basin, a watershed of high conservation interest within the Columbia River Basin, U.S.A. We compare the results of the River Styles Framework, Natural Channel Classification, Rosgen Classification System, and a channel form-based statistical classification at 33 field-monitored sites. We found that the four frameworks consistently classified reach types into similar groups based on each reach or segment’s dominant hydrogeomorphic elements. Where classified channel types diverged, differences could be attributed to the (a) spatial scale of input data used, (b) the requisite metrics and their order in completing a framework’s decision tree and/or, (c) whether the framework attempts to classify current or historic channel form. Divergence in framework agreement was also observed at reaches where channel planform was decoupled from valley setting. Overall, the relative agreement between frameworks indicates that criticism of individual classifications for their use of form in grouping stream channels may be overstated. These form-based criticisms may also ignore the geomorphic tenet that channel form reflects formative hydrogeomorphic processes across a given landscape. PMID:26982076

Cell membrane organization is important for inner hair cell MET-channel gating

NASA Astrophysics Data System (ADS)

Effertz, Thomas; Scharr, Alexandra L.; Ricci, Anthony J.

2018-05-01

Specialized sensory cells, hair cells, translate mechanical stimuli into electro/chemical responses. This process, termed mechano-electrical transduction (MET), is localized to the hair cell's sensory organelle, the hair bundle. The mature hair bundle comprises three rows of actin filled stereocilia, arranged in a staircase pattern. Deflections towards the tallest row of stereocilia activate MET channels, residing at the top of stereocilia. While other MET channels can be activated or modulated by changes to their lipid environment, this remains unknown for the mammalian auditory MET channel. We show here that the effect of lipid and cholesterol depletion from the cell membrane affect the MET current as well. We used γ-cyclodextrin to extract lipids form the membrane, reversibly reducing the peak MET current, current adaptation, and decreasing the channels resting open probability. The recovery after γ-cyclodextrin treatment was slower than the initial peak current reduction, suggesting that a specific lipid organization is required for normal MET channel function, which requires time reestablish. Extraction of cholesterol, using Mβ-cyclodextrin, irreversibly reduces the peak MET current and reversibly increases the channel resting open probability, suggesting that cholesterol restricts MET channel opening. This restriction could be useful to increase the channel's signal to noise ratio. Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and could possibly restrict gating associated conformational changes of the MET channel.

Aperiodic linear networked control considering variable channel delays: application to robots coordination.

PubMed

Santos, Carlos; Espinosa, Felipe; Santiso, Enrique; Mazo, Manuel

2015-05-27

One of the main challenges in wireless cyber-physical systems is to reduce the load of the communication channel while preserving the control performance. In this way, communication resources are liberated for other applications sharing the channel bandwidth. The main contribution of this work is the design of a remote control solution based on an aperiodic and adaptive triggering mechanism considering the current network delay of multiple robotics units. Working with the actual network delay instead of the maximum one leads to abandoning this conservative assumption, since the triggering condition is fixed depending on the current state of the network. This way, the controller manages the usage of the wireless channel in order to reduce the channel delay and to improve the availability of the communication resources. The communication standard under study is the widespread IEEE 802.11g, whose channel delay is clearly uncertain. First, the adaptive self-triggered control is validated through the TrueTime simulation tool configured for the mentioned WiFi standard. Implementation results applying the aperiodic linear control laws on four P3-DX robots are also included. Both of them demonstrate the advantage of this solution in terms of network accessing and control performance with respect to periodic and non-adaptive self-triggered alternatives.

Modem design for a MOBILESAT terminal

NASA Technical Reports Server (NTRS)

Rice, M.; Miller, M. J.; Cowley, W. G.; Rowe, D.

1990-01-01

The implementation is described of a programmable digital signal processor based system, designed for use as a test bed in the development of a digital modem, codec, and channel simulator. Code was written to configure the system as a 5600 bps or 6600 bps QPSK modem. The test bed is currently being used in an experiment to evaluate the performance of digital speech over shadowed channels in the Australian mobile satellite (MOBILESAT) project.

Proteomic analysis highlights the molecular complexities of native Kv4 channel macromolecular complexes.

PubMed

Marionneau, Céline; Townsend, R Reid; Nerbonne, Jeanne M

2011-04-01

Voltage-gated K(+) (Kv) channels are key determinants of membrane excitability in the nervous and cardiovascular systems, functioning to control resting membrane potentials, shape action potential waveforms and influence the responses to neurotransmitters and neurohormones. Consistent with this functional diversity, multiple types of Kv currents, with distinct biophysical properties and cellular/subcellular distributions, have been identified. Rapidly activating and inactivating Kv currents, typically referred to as I(A) (A-type) in neurons, for example, regulate repetitive firing rates, action potential back-propagation (into dendrites) and modulate synaptic responses. Currents with similar properties, referred to as I(to,f) (fast transient outward), expressed in cardiomyocytes, control the early phase of myocardial action potential repolarization. A number of studies have demonstrated critical roles for pore-forming (α) subunits of the Kv4 subfamily in the generation of native neuronal I(A) and cardiac I(to,f) channels. Studies in heterologous cells have also suggested important roles for a number of Kv channel accessory and regulatory proteins in the generation of functional I(A) and I(to,f) channels. Quantitative mass spectrometry-based proteomic analysis is increasingly recognized as a rapid and, importantly, unbiased, approach to identify the components of native macromolecular protein complexes. The recent application of proteomic approaches to identify the components of native neuronal (and cardiac) Kv4 channel complexes has revealed even greater complexity than anticipated. The continued emphasis on development of improved biochemical and analytical proteomic methods seems certain to accelerate progress and to provide important new insights into the molecular determinants of native ion channel protein complexes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bias-selectable dual-band mid-/long-wavelength infrared photodetectors based on InAs/InAs{sub 1−x}Sb{sub x} type-II superlattices

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

Haddadi, A.; Chevallier, R.; Chen, G.

2015-01-05

A high performance bias-selectable mid-/long-wavelength infrared photodetector based on InAs/InAs{sub 1−x}Sb{sub x} type-II superlattices on GaSb substrate has been demonstrated. The mid- and long-wavelength channels' 50% cut-off wavelengths were ∼5.1 and ∼9.5 μm at 77 K. The mid-wavelength channel exhibited a quantum efficiency of 45% at 100 mV bias voltage under front-side illumination and without any anti-reflection coating. With a dark current density of 1 × 10{sup −7} A/cm{sup 2} under 100 mV applied bias, the mid-wavelength channel exhibited a specific detectivity of 8.2 × 10{sup 12 }cm·√(Hz)/W at 77 K. The long-wavelength channel exhibited a quantum efficiency of 40%, a dark current density of 5.7 × 10{sup −4} A/cm{sup 2} undermore » −150 mV applied bias at 77 K, providing a specific detectivity value of 1.64 × 10{sup 11 }cm·√(Hz)/W.« less

Performance optimization in electric field gradient focusing.

PubMed

Sun, Xuefei; Farnsworth, Paul B; Tolley, H Dennis; Warnick, Karl F; Woolley, Adam T; Lee, Milton L

2009-01-02

Electric field gradient focusing (EFGF) is a technique used to simultaneously separate and concentrate biomacromolecules, such as proteins, based on the opposing forces of an electric field gradient and a hydrodynamic flow. Recently, we reported EFGF devices fabricated completely from copolymers functionalized with poly(ethylene glycol), which display excellent resistance to protein adsorption. However, the previous devices did not provide the predicted linear electric field gradient and stable current. To improve performance, Tris-HCl buffer that was previously doped in the hydrogel was replaced with a phosphate buffer containing a salt (i.e., potassium chloride, KCl) with high mobility ions. The new devices exhibited stable current, good reproducibility, and a linear electric field distribution in agreement with the shaped gradient region design due to improved ion transport in the hydrogel. The field gradient was calculated based on theory to be approximately 5.76 V/cm(2) for R-phycoerythrin when the applied voltage was 500 V. The effect of EFGF separation channel dimensions was also investigated; a narrower focused band was achieved in a smaller diameter channel. The relationship between the bandwidth and channel diameter is consistent with theory. Three model proteins were resolved in an EFGF channel of this design. The improved device demonstrated 14,000-fold concentration of a protein sample (from 2 ng/mL to 27 microg/mL).

Measuring kinetics of complex single ion channel data using mean-variance histograms.

PubMed

Patlak, J B

1993-07-01

The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean-variance histogram technique provided a more credible analysis of the open, closed, and subconductance times for the patch. I also show that the method produces accurate results on simulated data in a wide variety of conditions, whereas the half-amplitude method, when applied to complex simulated data shows the same errors as were apparent in the real data. The utility and the limitations of this new method are discussed.

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.

Molecular Coupling between Voltage Sensor and Pore Opening in the Arabidopsis Inward Rectifier K+ Channel KAT1

PubMed Central

Latorre, Ramon; Olcese, Riccardo; Basso, Claudia; Gonzalez, Carlos; Muñoz, Fabian; Cosmelli, Diego; Alvarez, Osvaldo

2003-01-01

Animal and plant voltage-gated ion channels share a common architecture. They are made up of four subunits and the positive charges on helical S4 segments of the protein in animal K+ channels are the main voltage-sensing elements. The KAT1 channel cloned from Arabidopsis thaliana, despite its structural similarity to animal outward rectifier K+ channels is, however, an inward rectifier. Here we detected KAT1-gating currents due to the existence of an intrinsic voltage sensor in this channel. The measured gating currents evoked in response to hyperpolarizing voltage steps consist of a very fast (τ = 318 ± 34 μs at −180 mV) and a slower component (4.5 ± 0.5 ms at −180 mV) representing charge moved when most channels are closed. The observed gating currents precede in time the ionic currents and they are measurable at voltages (less than or equal to −60) at which the channel open probability is negligible (≈10−4). These two observations, together with the fact that there is a delay in the onset of the ionic currents, indicate that gating charge transits between several closed states before the KAT1 channel opens. To gain insight into the molecular mechanisms that give rise to the gating currents and lead to channel opening, we probed external accessibility of S4 domain residues to methanethiosulfonate-ethyltrimethylammonium (MTSET) in both closed and open cysteine-substituted KAT1 channels. The results demonstrate that the putative voltage–sensing charges of S4 move inward when the KAT1 channels open. PMID:14517271

Modeling of I-V characteristics in a 3-channel SFFT with nanobridges by gate current signals

NASA Astrophysics Data System (ADS)

Yu, Byunggyu; Kim, Young-Pil; Ko, Seok-Cheol

2018-04-01

A superconducting flux flow transistor (SFFT) with three channels and nanobridges was successfully fabricated by electron beam (e-beam) lithography and an Ar ion milling technique. The SFFT is composed of three weak links with a nearby gate current line. We explain the process to obtain the equation for the current-voltage characteristics and describe the method to induce external and internal magnetic fields by Biot-Savart's law. The equation can be used to predict the current-voltage curves for the 3-channel SFFT fabricated using e-beam lithography. I-V characteristics were simulated to analyze the SFFT with three channels and nanobridges by a Matlab program. From the I-V characteristics equation of the 3-channel SFFT, the drain currents and the output voltages as the gate current is applied are graphically compared with the measured value and the simulation value. The simulated I-V curves were in good agreement with the measured curves of the 3-channel SFFT with nanobridges.

Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.

PubMed

Nikolaev, Yury A; Dosen, Peter J; Laver, Derek R; van Helden, Dirk F; Hamill, Owen P

2015-05-22

The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)

Method and system for a gas tube-based current source high voltage direct current transmission system

DOEpatents

She, Xu; Chokhawala, Rahul Shantilal; Bray, James William; Sommerer, Timothy John; Zhou, Rui; Zhang, Di

2017-08-29

A high-voltage direct-current (HVDC) transmission system includes an alternating current (AC) electrical source and a power converter channel that includes an AC-DC converter electrically coupled to the electrical source and a DC-AC inverter electrically coupled to the AC-DC converter. The AC-DC converter and the DC-AC inverter each include a plurality of legs that includes at least one switching device. The power converter channel further includes a commutating circuit communicatively coupled to one or more switching devices. The commutating circuit is configured to "switch on" one of the switching devices during a first portion of a cycle of the H-bridge switching circuits and "switch off" the switching device during a second portion of the cycle of the first and second H-bridge switching circuits.

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

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.

Properties of Single K+ and Cl− Channels in Asclepias tuberosa Protoplasts 1

PubMed Central

Schauf, Charles L.; Wilson, Kathryn J.

1987-01-01

Potassium and chloride channels were characterized in Asclepias tuberosa suspension cell derived protoplasts by patch voltage-clamp. Whole-cell currents and single channels in excised patches had linear instantaneous current-voltage relations, reversing at the Nernst potentials for K+ and Cl−, respectively. Whole cell K+ currents activated exponentially during step depolarizations, while voltage-dependent Cl− channels were activated by hyperpolarizations. Single K+ channel conductance was 40 ± 5 pS with a mean open time of 4.5 milliseconds at 100 millivolts. Potassium channels were blocked by Cs+ and tetraethylammonium, but were insensitive to 4-aminopyridine. Chloride channels had a single-channel conductance of 100 ± 17 picosiemens, mean open time of 8.8 milliseconds, and were blocked by Zn2+ and ethacrynic acid. Whole-cell Cl− currents were inhibited by abscisic acid, and were unaffected by indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid. Since internal and external composition can be controlled, patch-clamped protoplasts are ideal systems for studying the role of ion channels in plant physiology and development. Images Fig. 5 PMID:16665712

TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear.

PubMed

Pan, Bifeng; Géléoc, Gwenaelle S; Asai, Yukako; Horwitz, Geoffrey C; Kurima, Kiyoto; Ishikawa, Kotaro; Kawashima, Yoshiyuki; Griffith, Andrew J; Holt, Jeffrey R

2013-08-07

Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea. Copyright © 2013 Elsevier Inc. All rights reserved.

Open channel noise. I. Noise in acetylcholine receptor currents suggests conformational fluctuations.

PubMed

Sigworth, F J

1985-05-01

The random passage of ions through an open channel is expected to result in shot noise fluctuations in the channel current. The patch-clamp technique now allows fluctuations of this size to be observed in single-channel currents. In the experiments reported here the acetylcholine-induced currents in cultured rat muscle cells were analyzed; fluctuations were found that were considerably larger than expected for shot noise. A low-frequency component, which was fitted with a Lorentzian, was examined in detail; it appears to arise from fluctuations in channel conductance of approximately 3% on a time scale of 1 ms. The characteristic relaxation time is voltage dependent and temperature dependent (Q10 approximately equal to 3) suggesting that the fluctuations arise from conformational fluctuations in the channel protein.

[How do antiepileptic drugs work?].

PubMed

Nakken, Karl O; Heuser, Kjell; Alfstad, Kristin; Taubøll, Erik

2014-01-14

There are currently around 25 antiepileptic drugs in use in Norway, of which 15 have entered the market in the last 20 years. All have somewhat different effect- and adverse effect profiles and mechanisms of action. Here we present a brief overview of current knowledge regarding the basic mechanisms of action of these drugs. The review is based on a discretionary selection of relevant articles found through a literature search in PubMed and our own clinical and research experience. There are, roughly speaking, four main mechanisms; 1) modulation of ion channels (sodium and calcium channel blockers, potassium channel openers), 2) potentiation of GABAergic inhibition, 3) reduction of glutamatergic excitation and 4) modulation of presynaptic neurotransmitter release. Some of the drugs have several mechanisms of action, and for some of them it is unclear which mechanism is clinically most important. To some extent, the drugs' mechanisms of action predict their effect against different types of epilepsy and seizures. For instance, sodium channel blockers work best against focal seizures, while calcium channel blockers work best against absences, a type of generalised seizure. Optimal treatment of patients with epilepsy requires not only thorough knowledge of seizure- and epilepsy classification, but also insight into the mechanisms of action of antiepileptic drugs.

Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes.

PubMed

Bekar, Lane K; Loewen, Matthew E; Cao, Kun; Sun, Xianfeng; Leis, Jerome; Wang, Rui; Forsyth, George W; Walz, Wolfgang

2005-03-01

Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity.

Magnetohydrodynamic electrode

DOEpatents

Marchant, David D.; Killpatrick, Don H.

1978-01-01

An electrode capable of withstanding high temperatures and suitable for use as a current collector in the channel of a magnetohydrodynamic (MHD) generator consists of a sintered powdered metal base portion, the upper surface of the base being coated with a first layer of nickel aluminide, an intermediate layer of a mixture of nickel aluminide - refractory ceramic on the first layer and a third or outer layer of a refractory ceramic material on the intermediate layer. The sintered powdered metal base resists spalling by the ceramic coatings and permits greater electrode compliance to thermal shock. The density of the powdered metal base can be varied to allow optimization of the thermal conductivity of the electrode and prevent excess heat loss from the channel.

How to resolve microsecond current fluctuations in single ion channels: The power of beta distributions

PubMed Central

Schroeder, Indra

2015-01-01

Abstract A main ingredient for the understanding of structure/function correlates of ion channels is the quantitative description of single-channel gating and conductance. However, a wealth of information provided from fast current fluctuations beyond the temporal resolution of the recording system is often ignored, even though it is close to the time window accessible to molecular dynamics simulations. This kind of current fluctuations provide a special technical challenge, because individual opening/closing or blocking/unblocking events cannot be resolved, and the resulting averaging over undetected events decreases the single-channel current. Here, I briefly summarize the history of fast-current fluctuation analysis and focus on the so-called “beta distributions.” This tool exploits characteristics of current fluctuation-induced excess noise on the current amplitude histograms to reconstruct the true single-channel current and kinetic parameters. A guideline for the analysis and recent applications demonstrate that a construction of theoretical beta distributions by Markov Model simulations offers maximum flexibility as compared to analytical solutions. PMID:26368656

VLSI Implementation of a 2.8 Gevent/s Packet-Based AER Interface with Routing and Event Sorting Functionality

PubMed Central

Scholze, Stefan; Schiefer, Stefan; Partzsch, Johannes; Hartmann, Stephan; Mayr, Christian Georg; Höppner, Sebastian; Eisenreich, Holger; Henker, Stephan; Vogginger, Bernhard; Schüffny, Rene

2011-01-01

State-of-the-art large-scale neuromorphic systems require sophisticated spike event communication between units of the neural network. We present a high-speed communication infrastructure for a waferscale neuromorphic system, based on application-specific neuromorphic communication ICs in an field programmable gate arrays (FPGA)-maintained environment. The ICs implement configurable axonal delays, as required for certain types of dynamic processing or for emulating spike-based learning among distant cortical areas. Measurements are presented which show the efficacy of these delays in influencing behavior of neuromorphic benchmarks. The specialized, dedicated address-event-representation communication in most current systems requires separate, low-bandwidth configuration channels. In contrast, the configuration of the waferscale neuromorphic system is also handled by the digital packet-based pulse channel, which transmits configuration data at the full bandwidth otherwise used for pulse transmission. The overall so-called pulse communication subgroup (ICs and FPGA) delivers a factor 25–50 more event transmission rate than other current neuromorphic communication infrastructures. PMID:22016720

Real Time Sensing and Discrimination of Single Chemicals Using Channel of Phi29 DNA Packaging Nanomotor

PubMed Central

Haque, Farzin; Lunn, Jennifer; Fang, Huaming; Smithrud, David; Guo, Peixuan

2012-01-01

A highly sensitive and reliable method to sense and identify a single chemical at extremely low concentrations and high contamination is important for environmental surveillance, homeland security, athlete drug monitoring, toxin/drug screening, and earlier disease diagnosis. This manuscript reports a method for precise detection of single chemicals. The hub of the bacteriophage phi29 DNA packaging motor is a connector consisting of twelve protein subunits encircled into a 3.6-nm channel as a path for dsDNA to enter during packaging and to exit during infection. The connector has previously been inserted into a lipid bilayer to serve as a membrane-embedded channel. Herein we report the modification of the phi29 channel to develop a class of sensors to detect single chemicals. The Lysine-234 of each protein subunit was mutated to cysteine, generating 12-SH ring lining the channel wall. Chemicals passing through this robust channel and interactions with the SH-group generated extremely reliable, precise, and sensitive current signatures as revealed by single channel conductance assays. Ethane (57 Daltons), thymine (167 Daltons), and benzene (105 Daltons) with reactive thioester moieties were clearly discriminated upon interaction with the available set of cysteine residues. The covalent attachment of each analyte induced discrete step-wise blockage in current signature with a corresponding decrease in conductance due to the physical blocking of the channel. Transient binding of the chemicals also produced characteristic fingerprints that were deduced from the unique blockage amplitude and pattern of the signals. This study shows that the phi29 connector can be used to sense chemicals with reactive thioesters or maleimide using single channel conduction assays based on their distinct fingerprints. The results demonstrated that this channel system could be further developed into very sensitive sensing devices. PMID:22458779

Probing structural features of Alzheimer's amyloid-β pores in bilayers using site-specific amino acid substitutions.

PubMed

Capone, Ricardo; Jang, Hyunbum; Kotler, Samuel A; Kagan, Bruce L; Nussinov, Ruth; Lal, Ratnesh

2012-01-24

A current hypothesis for the pathology of Alzheimer's disease (AD) proposes that amyloid-β (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The mechanism of ion flux is not fully understood because no experiment-based Aβ channel structures at atomic resolution are currently available (only a few polymorphic states have been predicted by computational models). Structural models and experimental evidence lend support to the view that the Aβ channel is an assembly of loosely associated mobile β-sheet subunits. Here, using planar lipid bilayers and molecular dynamics (MD) simulations, we show that amino acid substitutions can be used to infer which residues are essential for channel structure. We created two Aβ(1-42) peptides with point mutations: F19P and F20C. The substitution of Phe19 with Pro inhibited channel conductance. MD simulation suggests a collapsed pore of F19P channels at the lower bilayer leaflet. The kinks at the Pro residues in the pore-lining β-strands induce blockage of the solvated pore by the N-termini of the chains. The cysteine mutant is capable of forming channels, and the conductance behavior of F20C channels is similar to that of the wild type. Overall, the mutational analysis of the channel activity performed in this work tests the proposition that the channels consist of a β-sheet rich organization, with the charged/polar central strand containing the mutation sites lining the pore, and the C-terminal strands facing the hydrophobic lipid tails. A detailed understanding of channel formation and its structure should aid studies of drug design aiming to control unregulated Aβ-dependent ion fluxes.

Probing Structural Features of Alzheimer’s Amyloid-β Pores in Bilayers Using Site-Specific Amino Acid Substitutions

PubMed Central

2012-01-01

A current hypothesis for the pathology of Alzheimer’s disease (AD) proposes that amyloid-β (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The mechanism of ion flux is not fully understood because no experiment-based Aβ channel structures at atomic resolution are currently available (only a few polymorphic states have been predicted by computational models). Structural models and experimental evidence lend support to the view that the Aβ channel is an assembly of loosely associated mobile β-sheet subunits. Here, using planar lipid bilayers and molecular dynamics (MD) simulations, we show that amino acid substitutions can be used to infer which residues are essential for channel structure. We created two Aβ1–42 peptides with point mutations: F19P and F20C. The substitution of Phe19 with Pro inhibited channel conductance. MD simulation suggests a collapsed pore of F19P channels at the lower bilayer leaflet. The kinks at the Pro residues in the pore-lining β-strands induce blockage of the solvated pore by the N-termini of the chains. The cysteine mutant is capable of forming channels, and the conductance behavior of F20C channels is similar to that of the wild type. Overall, the mutational analysis of the channel activity performed in this work tests the proposition that the channels consist of a β-sheet rich organization, with the charged/polar central strand containing the mutation sites lining the pore, and the C-terminal strands facing the hydrophobic lipid tails. A detailed understanding of channel formation and its structure should aid studies of drug design aiming to control unregulated Aβ-dependent ion fluxes. PMID:22242635

Real-time sensing and discrimination of single chemicals using the channel of phi29 DNA packaging nanomotor.

PubMed

Haque, Farzin; Lunn, Jennifer; Fang, Huaming; Smithrud, David; Guo, Peixuan

2012-04-24

A highly sensitive and reliable method to sense and identify a single chemical at extremely low concentrations and high contamination is important for environmental surveillance, homeland security, athlete drug monitoring, toxin/drug screening, and earlier disease diagnosis. This article reports a method for precise detection of single chemicals. The hub of the bacteriophage phi29 DNA packaging motor is a connector consisting of 12 protein subunits encircled into a 3.6 nm channel as a path for dsDNA to enter during packaging and to exit during infection. The connector has previously been inserted into a lipid bilayer to serve as a membrane-embedded channel. Herein we report the modification of the phi29 channel to develop a class of sensors to detect single chemicals. The lysine-234 of each protein subunit was mutated to cysteine, generating 12-SH ring lining the channel wall. Chemicals passing through this robust channel and interactions with the SH group generated extremely reliable, precise, and sensitive current signatures as revealed by single channel conductance assays. Ethane (57 Da), thymine (167 Da), and benzene (105 Da) with reactive thioester moieties were clearly discriminated upon interaction with the available set of cysteine residues. The covalent attachment of each analyte induced discrete stepwise blockage in current signature with a corresponding decrease in conductance due to the physical blocking of the channel. Transient binding of the chemicals also produced characteristic fingerprints that were deduced from the unique blockage amplitude and pattern of the signals. This study shows that the phi29 connector can be used to sense chemicals with reactive thioesters or maleimide using single channel conduction assays based on their distinct fingerprints. The results demonstrated that this channel system could be further developed into very sensitive sensing devices.

Expression and permeation properties of the K(+) channel Kir7.1 in the retinal pigment epithelium.

PubMed

Shimura, M; Yuan, Y; Chang, J T; Zhang, S; Campochiaro, P A; Zack, D J; Hughes, B A

2001-03-01

Bovine Kir7.1 clones were obtained from a retinal pigment epithelium (RPE)-subtracted cDNA library. Human RPE cDNA library screening resulted in clones encoding full-length human Kir7.1. Northern blot analysis indicated that bovine Kir7.1 is highly expressed in the RPE. Human Kir7.1 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. The macroscopic Kir7.1 conductance exhibited mild inward rectification and an inverse dependence on extracellular K+ concentration ([K+]o). The selectivity sequence based on permeability ratios was K+ (1.0) approximately Rb+ (0.89) > Cs+ (0.013) > Na+ (0.003) approximately Li+ (0.001) and the sequence based on conductance ratios was Rb+ (9.5) > K+ (1.0) > Na+ (0.458) > Cs+ (0.331) > Li+ (0.139). Non-stationary noise analysis of Rb+ currents in cell-attached patches yielded a unitary conductance for Kir7.1 of approximately 2 pS. In whole-cell recordings from freshly isolated bovine RPE cells, the predominant current was a mild inwardly rectifying K+ current that exhibited an inverse dependence of conductance on [K+]o. The selectivity sequence based on permeability ratios was K+ (1.0) approximately Rb+ (0.89) > Cs+ (0.021) > Na+ (0.003) approximately Li+ (0.002) and the sequence based on conductance ratios was Rb+ (8.9) > K+ (1.0) > Na+ (0.59) > Cs+ (0.23) > Li+ (0.08). In cell-attached recordings with Rb+ in the pipette, inwardly rectifying currents were observed in nine of 12 patches of RPE apical membrane but in only one of 13 basolateral membrane patches. Non-stationary noise analysis of Rb+ currents in cell-attached apical membrane patches yielded a unitary conductance for RPE Kir of approximately 2 pS. On the basis of this molecular and electrophysiological evidence, we conclude that Kir7.1 channel subunits comprise the K+ conductance of the RPE apical membrane.

A Dihydropyridine-sensitive Voltage-dependent Calcium Channel in the Sarcolemmal Membrane of Crustacean Muscle

PubMed Central

Erxleben, Christian; Rathmayer, Werner

1997-01-01

Single-channel currents through calcium channels in muscle of a marine crustacean, the isopod Idotea baltica, were investigated in cell-attached patches. Inward barium currents were strongly voltage-dependent, and the channels were closed at the cell's resting membrane potential. The open probability (Po) increased e-fold for an 8.2 mV (±2.4, n = 13) depolarization. Channel openings were mainly brief (<0.3 ms) and evenly distributed throughout 100-ms pulses. Averaged, quasimacroscopic currents showed fast activation and deactivation and did not inactivate during 100-ms test pulses. Similarly, channel activity persisted at steadily depolarized holding potentials. With 200 mM Ba2+ as charge carrier, the average slope conductance from the unitary currents between +30 and +80 mV, was 20 pS (±2.6, n = 12). The proportion of long openings, which were very infrequent under control conditions, was greatly increased by preincubation of the muscle fibers with the calcium channel agonist, the dihydropyridine Bay K8644 (10–100 μM). Properties of these currents resemble those through the L-type calcium channels of mammalian nerve, smooth muscle, and cardiac muscle cells. PMID:9089439

Charge injection engineering of ambipolar field-effect transistors for high-performance organic complementary circuits.

PubMed

Baeg, Kang-Jun; Kim, Juhwan; Khim, Dongyoon; Caironi, Mario; Kim, Dong-Yu; You, In-Kyu; Quinn, Jordan R; Facchetti, Antonio; Noh, Yong-Young

2011-08-01

Ambipolar π-conjugated polymers may provide inexpensive large-area manufacturing of complementary integrated circuits (CICs) without requiring micro-patterning of the individual p- and n-channel semiconductors. However, current-generation ambipolar semiconductor-based CICs suffer from higher static power consumption, low operation frequencies, and degraded noise margins compared to complementary logics based on unipolar p- and n-channel organic field-effect transistors (OFETs). Here, we demonstrate a simple methodology to control charge injection and transport in ambipolar OFETs via engineering of the electrical contacts. Solution-processed caesium (Cs) salts, as electron-injection and hole-blocking layers at the interface between semiconductors and charge injection electrodes, significantly decrease the gold (Au) work function (∼4.1 eV) compared to that of a pristine Au electrode (∼4.7 eV). By controlling the electrode surface chemistry, excellent p-channel (hole mobility ∼0.1-0.6 cm(2)/(Vs)) and n-channel (electron mobility ∼0.1-0.3 cm(2)/(Vs)) OFET characteristics with the same semiconductor are demonstrated. Most importantly, in these OFETs the counterpart charge carrier currents are highly suppressed for depletion mode operation (I(off) < 70 nA when I(on) > 0.1-0.2 mA). Thus, high-performance, truly complementary inverters (high gain >50 and high noise margin >75% of ideal value) and ring oscillators (oscillation frequency ∼12 kHz) based on a solution-processed ambipolar polymer are demonstrated.

An Efficient VLSI Architecture for Multi-Channel Spike Sorting Using a Generalized Hebbian Algorithm

PubMed Central

Chen, Ying-Lun; Hwang, Wen-Jyi; Ke, Chi-En

2015-01-01

A novel VLSI architecture for multi-channel online spike sorting is presented in this paper. In the architecture, the spike detection is based on nonlinear energy operator (NEO), and the feature extraction is carried out by the generalized Hebbian algorithm (GHA). To lower the power consumption and area costs of the circuits, all of the channels share the same core for spike detection and feature extraction operations. Each channel has dedicated buffers for storing the detected spikes and the principal components of that channel. The proposed circuit also contains a clock gating system supplying the clock to only the buffers of channels currently using the computation core to further reduce the power consumption. The architecture has been implemented by an application-specific integrated circuit (ASIC) with 90-nm technology. Comparisons to the existing works show that the proposed architecture has lower power consumption and hardware area costs for real-time multi-channel spike detection and feature extraction. PMID:26287193

An Efficient VLSI Architecture for Multi-Channel Spike Sorting Using a Generalized Hebbian Algorithm.

PubMed

Chen, Ying-Lun; Hwang, Wen-Jyi; Ke, Chi-En

2015-08-13

A novel VLSI architecture for multi-channel online spike sorting is presented in this paper. In the architecture, the spike detection is based on nonlinear energy operator (NEO), and the feature extraction is carried out by the generalized Hebbian algorithm (GHA). To lower the power consumption and area costs of the circuits, all of the channels share the same core for spike detection and feature extraction operations. Each channel has dedicated buffers for storing the detected spikes and the principal components of that channel. The proposed circuit also contains a clock gating system supplying the clock to only the buffers of channels currently using the computation core to further reduce the power consumption. The architecture has been implemented by an application-specific integrated circuit (ASIC) with 90-nm technology. Comparisons to the existing works show that the proposed architecture has lower power consumption and hardware area costs for real-time multi-channel spike detection and feature extraction.

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

Inversion of Acoustic and Electromagnetic Recordings for Mapping Current Flow in Lightning Strikes

NASA Astrophysics Data System (ADS)

Anderson, J.; Johnson, J.; Arechiga, R. O.; Thomas, R. J.

2012-12-01

Acoustic recordings can be used to map current-carrying conduits in lightning strikes. Unlike stepped leaders, whose very high frequency (VHF) radio emissions have short (meter-scale) wavelengths and can be located by lightning-mapping arrays, current pulses emit longer (kilometer-scale) waves and cannot be mapped precisely by electromagnetic observations alone. While current pulses are constrained to conductive channels created by stepped leaders, these leaders often branch as they propagate, and most branches fail to carry current. Here, we present a method to use thunder recordings to map current pulses, and we apply it to acoustic and VHF data recorded in 2009 in the Magdalena mountains in central New Mexico, USA. Thunder is produced by rapid heating and expansion of the atmosphere along conductive channels in response to current flow, and therefore can be used to recover the geometry of the current-carrying channel. Toward this goal, we use VHF pulse maps to identify candidate conductive channels where we treat each channel as a superposition of finely-spaced acoustic point sources. We apply ray tracing in variable atmospheric structures to forward model the thunder that our microphone network would record for each candidate channel. Because multiple channels could potentially carry current, a non-linear inversion is performed to determine the acoustic source strength of each channel. For each combination of acoustic source strengths, synthetic thunder is modeled as a superposition of thunder signals produced by each channel, and a power envelope of this stack is then calculated. The inversion iteratively minimizes the misfit between power envelopes of recorded and modeled thunder. Because the atmospheric sound speed structure through which the waves propagate during these events is unknown, we repeat the procedure on many plausible atmospheres to find an optimal fit. We then determine the candidate channel, or channels, that minimizes residuals between synthetic and acoustic recordings. We demonstrate the usefulness of this method on both intracloud and cloud-to-ground strikes, and discuss factors affecting our ability to replicate recorded thunder.

Integrating Partial Polarization into a Metal-Ferroelectric-Semiconductor Field Effect Transistor Model

NASA Technical Reports Server (NTRS)

MacLeod, Todd C.; Ho, Fat Duen

1999-01-01

The ferroelectric channel in a Metal-Ferroelectric-Semiconductor Field Effect Transistor (MFSFET) can partially change its polarization when the gate voltage near the polarization threshold voltage. This causes the MFSFET Drain current to change with repeated pulses of the same gate voltage near the polarization threshold voltage. A previously developed model [11, based on the Fermi-Dirac function, assumed that for a given gate voltage and channel polarization, a sin-le Drain current value would be generated. A study has been done to characterize the effects of partial polarization on the Drain current of a MFSFET. These effects have been described mathematically and these equations have been incorporated into a more comprehensive mathematical model of the MFSFET. The model takes into account the hysteresis nature of the MFSFET and the time dependent decay as well as the effects of partial polarization. This model defines the Drain current based on calculating the degree of polarization from previous gate pulses, the present Gate voltage, and the amount of time since the last Gate volta-e pulse.

Self-Optimized Biological Channels in Facilitating the Transmembrane Movement of Charged Molecules

PubMed Central

Huyen, V. T. N.; Lap, Vu Cong; Nguyen, V. Lien

2016-01-01

We consider an anisotropically two-dimensional diffusion of a charged molecule (particle) through a large biological channel under an external voltage. The channel is modeled as a cylinder of three structure parameters: radius, length, and surface density of negative charges located at the channel interior-lining. These charges induce inside the channel a potential that plays a key role in controlling the particle current through the channel. It was shown that to facilitate the transmembrane particle movement the channel should be reasonably self-optimized so that its potential coincides with the resonant one, resulting in a large particle current across the channel. Observed facilitation appears to be an intrinsic property of biological channels, regardless of the external voltage or the particle concentration gradient. This facilitation is very selective in the sense that a channel of definite structure parameters can facilitate the transmembrane movement of only particles of proper valence at corresponding temperatures. Calculations also show that the modeled channel is nonohmic with the ion conductance which exhibits a resonance at the same channel potential as that identified in the current. PMID:27022394

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop*

PubMed Central

Monteil, Arnaud; Chausson, Patrick; Boutourlinsky, Katia; Mezghrani, Alexandre; Huc-Brandt, Sylvaine; Blesneac, Iulia; Bidaud, Isabelle; Lemmers, Céline; Leresche, Nathalie; Lambert, Régis C.; Lory, Philippe

2015-01-01

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser423–Pro542) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. PMID:25931121

Modeled and Observed Transitions Between Rip Currents and Alongshore Flows

NASA Astrophysics Data System (ADS)

Moulton, M.; Elgar, S.; Warner, J. C.; Raubenheimer, B.

2014-12-01

Predictions of rip currents, alongshore currents, and the temporal transitions between these circulation patterns are important for swimmer safety and for estimating the transport of sediments, biota, and pollutants in the nearshore. Here, field observations are combined with hydrodynamic modeling to determine the dominant processes that lead rip currents to turn on and off with changing waves, bathymetry, and tidal elevation. Waves, currents, mean sea levels, and bathymetry were measured near and within five shore-perpendicular channels (on average 2-m deep, 30-m wide) that were dredged with the propellers of a landing craft at different times on a long straight Atlantic Ocean beach near Duck, NC in summer 2012. The circulation was measured for a range of incident wave conditions and channel sizes, and included rapid transitions between strong (0.5 to 1 m/s) rip current jets flowing offshore through the channels and alongshore currents flowing across the channels with no rip currents. Meandering alongshore currents (alongshore currents combined with an offshore jet at the downstream edge of the channel) also were observed. Circulation patterns near and within idealized rip channels simulated with COAWST (a three-dimensional phase-averaged model that couples ROMS and SWAN) are compared with the observations. In addition, the model is used to investigate the hydrodynamic response to a range of wave conditions (angle, height, period) and bathymetries (channel width, depth, and length; tidal elevations; shape of sandbar or terrace). Rip current speeds are largest for the deepest perturbations, and decrease as incident wave angles become more oblique. For obliquely incident waves, the rip currents are shifted in the direction of the alongshore flow, with an increasing shift for increasing alongshore current speed or increasing bathymetric perturbation depth.

Superhydrophobic surfaces’ influence on streaming current based energy harvester

NASA Astrophysics Data System (ADS)

Fouché, Florent; Dargent, Thomas; Coffinier, Yannick; Treizebré, Anthony; Vlandas, Alexis; Senez, Vincent

2016-11-01

The purpose of this paper is to report the design, fabrication and characterization of silicon-based microfluidic channels with superhydrophobic walls for energy harvesting. We present the fabrication step of silicon based streaming current energy harvester and the nanostructuration of the microchannel walls. We characterize the superhydrophobic properties of the surface in a closed system. Our preliminary results on the electrical characterization of the device show a 43% increase of power harvested with our superhydrophobic surface compared to a planar hydrophobic surface.

Resolving the 3D spatial orientation of helix I in the closed state of the colicin E1 channel domain by FRET. Insights into the integration mechanism.

PubMed

Lugo, Miguel R; Ho, Derek; Merrill, A Rod

2016-10-15

Current evidence suggests that the closed-state membrane model for the channel-forming domain of colicin E1 involves eight amphipathic α-helices (helices I-VII and X) that adopt a two-dimensional arrangement on the membrane surface. Two central hydrophobic α-helices in colicin E1 (VIII and IX) adopt a transmembrane location-the umbrella model. Helices I and II have been shown to participate in the channel by forming a transmembrane segment (TM1) in the voltage-induced open channel state. Consequently, it is paramount to determine the relative location and orientation of helix I in the two-dimensional arrangement of the membrane. A new, low-resolution, three-dimensional model of the closed state of the colicin E1 channel was constructed based on FRET measurements between three naturally occurring Trp residues and three sites in helix I, in addition to previously reported FRET distances for the channel domain. Furthermore, a new mechanism for the channel integration process involving the transition of the soluble to membrane-bound form is presented based on a plethora of kinetic data for this process. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Predicting the planform configuration of the braided Toklat River, AK with a suite of rule-based models

USGS Publications Warehouse

Podolak, Charles J.

2013-01-01

An ensemble of rule-based models was constructed to assess possible future braided river planform configurations for the Toklat River in Denali National Park and Preserve, Alaska. This approach combined an analysis of large-scale influences on stability with several reduced-complexity models to produce the predictions at a practical level for managers concerned about the persistence of bank erosion while acknowledging the great uncertainty in any landscape prediction. First, a model of confluence angles reproduced observed angles of a major confluence, but showed limited susceptibility to a major rearrangement of the channel planform downstream. Second, a probabilistic map of channel locations was created with a two-parameter channel avulsion model. The predicted channel belt location was concentrated in the same area as the current channel belt. Finally, a suite of valley-scale channel and braid plain characteristics were extracted from a light detection and ranging (LiDAR)-derived surface. The characteristics demonstrated large-scale stabilizing topographic influences on channel planform. The combination of independent analyses increased confidence in the conclusion that the Toklat River braided planform is a dynamically stable system due to large and persistent valley-scale influences, and that a range of avulsive perturbations are likely to result in a relatively unchanged planform configuration in the short term.

47 CFR 90.355 - LMS operations below 512 MHz.

Code of Federal Regulations, 2010 CFR

2010-10-01

... established, provided that: (a) For transmission between vehicles and base stations, each frequency in a... LMS station and the nearest co-channel base station of another licensee operating a voice system is 75... MHz, 150-170 MHz, and 450-512 MHz bands may use either base-mobile frequencies currently assigned the...

Spin-Current-Controlled Modulation of the Magnon Spin Conductance in a Three-Terminal Magnon Transistor.

PubMed

Cornelissen, L J; Liu, J; van Wees, B J; Duine, R A

2018-03-02

Efficient manipulation of magnon spin transport is crucial for developing magnon-based spintronic devices. In this Letter, we provide proof of principle of a method for modulating the diffusive transport of thermal magnons in an yttrium iron garnet channel between injector and detector contacts. The magnon spin conductance of the channel is altered by increasing or decreasing the magnon chemical potential via spin Hall injection of magnons by a third modulator electrode. We obtain a modulation efficiency of 1.6%/mA at T=250  K. Finite element modeling shows that this could be increased to well above 10%/mA by reducing the thickness of the channel, providing interesting prospects for the development of thermal-magnon-based logic circuits.

Sedimentary architecture and depositional environment of Kudat Formation, Sabah, Malaysia

NASA Astrophysics Data System (ADS)

Ghaheri, Samira; Suhaili, Mohd; Sapari, Nasiman; Momeni, Mohammadsadegh

2017-12-01

Kudat Formation originated from deep marine environment. Three lithofacies association of deep marine turbidity channel was discovered in three Members of the Kudat Formation in Kudat Peninsula, Sabah, Malaysia. Turbidite and deep marine architecture elements was described based on detailed sedimentological studies. Four architecture elements were identified based on each facies association and their lithology properties and character: inner external levee that was formed by turbidity flows spill out from their confinement of channel belt; Lobes sheet that was formed during downslope debris flows associated with levee; Channel fill which sediments deposited from high to low density currents with different value of sediment concentration; and overbank terrace which was formed by rapid suspension sedimentation. The depositional environment of Kudat Formation is shelf to deep marine fan.

NECTAR: New electronics for the Cherenkov Telescope Array

NASA Astrophysics Data System (ADS)

Naumann, Christopher Lindsay; Bolmont, J.; Corona, P.; Delagnes, E.; Dzahini, D.; Feinstein, F.; Gascon, D.; Glicenstein, J.-F.; Nayman, P.; Rarbi, F.; Ribo, M.; Sanuy, A.; Siero, X.; Tavernet, J.-P.; Toussenel, F.; Vincent, P.; Vorobiov, S.

2012-12-01

The international CTA consortium is currently in the preparatory phase for the development of the next-generation Cherenkov Telescope Array (CTA [1]), based on the return of experience from the three major current-generation arrays H.E.S.S., MAGIC and VERITAS. To achieve an unprecedented sensitivity and energy range for TeV gamma rays, a new kind of flexible and powerful yet inexpensive front-end hardware will be required for the order of 105 channels of photodetectors in up to 100 telescopes. One possible solution is the NECTAr (New Electronics for the Cherenkov Telescope Array) system, based on the integration of as much as possible of the front-end electronics (amplifiers, fast analogue samplers, memory and ADCs) into a single ASIC for very fast readout performance and a significant reduction of the cost and the lower consumption per channel, while offering a high degree of flexibility both for the triggering and the readout of the telescope. The current status of its development is presented, along with newest results from measurements and simulation studies.

1.55 µm high speed low chirp electroabsorption modulated laser arrays based on SAG scheme.

PubMed

Cheng, Yuanbing; Wang, Qi Jie; Pan, Jiaoqing

2014-12-15

We demonstrate a cost-effective 1.55 µm low chirp 4 × 25 Gbit/s electroabsorption modulated laser (EML) array with 0.8 nm channel spacing by varying ridge width of the lasers and using selective area growth (SAG) integration scheme. The devices for all the 4 channels within the EML array show uniform threshold currents around 18 mA and high SMSRs over 45 dB. The output optical power of each channel is about 9 mW at an injection current of 100 mA. The typical chirp value of single EML measured by a fiber resonance method varied from 2.2 to -4 as the bias voltage was increased from 0 V to 2.5 V. These results show that the EML array is a suitable light source for 100 Gbit/s optical transmissions.

Ten-channel InP-based large-scale photonic integrated transmitter fabricated by SAG technology

NASA Astrophysics Data System (ADS)

Zhang, Can; Zhu, Hongliang; Liang, Song; Cui, Xiao; Wang, Huitao; Zhao, Lingjuan; Wang, Wei

2014-12-01

A 10-channel InP-based large-scale photonic integrated transmitter was fabricated by selective area growth (SAG) technology combined with butt-joint regrowth (BJR) technology. The SAG technology was utilized to fabricate the electroabsorption modulated distributed feedback (DFB) laser (EML) arrays at the same time. The design of coplanar electrodes for electroabsorption modulator (EAM) was used for the flip-chip bonding package. The lasing wavelength of DFB laser could be tuned by the integrated micro-heater to match the ITU grids, which only needs one electrode pad. The average output power of each channel is 250 μW with an injection current of 200 mA. The static extinction ratios of the EAMs for 10 channels tested are ranged from 15 to 27 dB with a reverse bias of 6 V. The frequencies of 3 dB bandwidth of the chip for each channel are around 14 GHz. The novel design and simple fabrication process show its enormous potential in reducing the cost of large-scale photonic integrated circuit (LS-PIC) transmitter with high chip yields.

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

PubMed

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

2015-01-01

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

Modulation frequency discrimination with single and multiple channels in cochlear implant users

PubMed Central

Galvin, John J.; Oba, Sandy; Başkent, Deniz; Fu, Qian-Jie

2015-01-01

Temporal envelope cues convey important speech information for cochlear implant (CI) users. Many studies have explored CI users’ single-channel temporal envelope processing. However, in clinical CI speech processors, temporal envelope information is processed by multiple channels. Previous studies have shown that amplitude modulation frequency discrimination (AMFD) thresholds are better when temporal envelopes are delivered to multiple rather than single channels. In clinical fitting, current levels on single channels must often be reduced to accommodate multi-channel loudness summation. As such, it is unclear whether the multi-channel advantage in AMFD observed in previous studies was due to coherent envelope information distributed across the cochlea or to greater loudness associated with multi-channel stimulation. In this study, single- and multi-channel AMFD thresholds were measured in CI users. Multi-channel component electrodes were either widely or narrowly spaced to vary the degree of overlap between neural populations. The reference amplitude modulation (AM) frequency was 100 Hz, and coherent modulation was applied to all channels. In Experiment 1, single- and multi-channel AMFD thresholds were measured at similar loudness. In this case, current levels on component channels were higher for single- than for multi-channel AM stimuli, and the modulation depth was approximately 100% of the perceptual dynamic range (i.e., between threshold and maximum acceptable loudness). Results showed no significant difference in AMFD thresholds between similarly loud single- and multi-channel modulated stimuli. In Experiment 2, single- and multi-channel AMFD thresholds were compared at substantially different loudness. In this case, current levels on component channels were the same for single-and multi-channel stimuli (“summation-adjusted” current levels) and the same range of modulation (in dB) was applied to the component channels for both single- and multi-channel testing. With the summation-adjusted current levels, loudness was lower with single than with multiple channels and the AM depth resulted in substantial stimulation below single-channel audibility, thereby reducing the perceptual range of AM. Results showed that AMFD thresholds were significantly better with multiple channels than with any of the single component channels. There was no significant effect of the distribution of electrodes on multi-channel AMFD thresholds. The results suggest that increased loudness due to multi-channel summation may contribute to the multi-channel advantage in AMFD, and that that overall loudness may matter more than the distribution of envelope information in the cochlea. PMID:25746914

A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection.

PubMed

Lo, Chi-Chun; Chien, Tsung-Yi; Chen, Yu-Chun; Tsai, Shang-Ho; Fang, Wai-Chi; Lin, Bor-Shyh

2016-02-06

Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype.

Changes in Ca(2+) channel expression upon differentiation of SN56 cholinergic cells.

PubMed

Kushmerick, C; Romano-Silva, M A; Gomez, M V; Prado, M A

2001-10-19

The SN56 cell line, a fusion of septal neurons and neuroblastoma cells, has been used as a model for central cholinergic neurons. These cells show increased expression of cholinergic neurochemical features upon differentiation, but little is known about how differentiation affects their electrophysiological properties. We examined the changes in Ca(2+) channel expression that occur as these cells undergo morphological differentiation in response to serum withdrawal and exposure to dibutyryl-cAMP. Undifferentiated cells expressed a T-type current with biophysical and pharmacological properties similar, although not identical, to those reported for the current generated by the alpha(1H) (CaV3.2) Ca(2+) channel subunit. Differentiated cells expressed, in addition to this T-type current, high voltage activated currents which were inhibited 38% by the L-type channel antagonist nifedipine (5 microM), 37% by the N-type channel antagonist omega-conotoxin-GVIA (1 microM), and 15% by the P/Q-type channel antagonist omega-agatoxin-IVA (200 nM). Current resistant to these inhibitors accounted for 15% of the high voltage activated current in differentiated SN56 cells. Our data demonstrate that differentiation increases the expression of neuronal type voltage gated Ca(2+) channels in this cell line, and that the channels expressed are comparable to those reported for native basal forebrain cholinergic neurons. This cell line should thus provide a useful model system to study the relationship between calcium currents and cholinergic function and dysfunction.

Analysis of DC and analog/RF performance on Cyl-GAA-TFET using distinct device geometry

NASA Astrophysics Data System (ADS)

Vishvakarma, S. K.; Beohar, Ankur; Vijayvargiya, Vikas; Trivedi, Priyal

2017-07-01

In this paper, analysis of DC and analog/RF performance on cylindrical gate-all-around tunnel field-effect transistor (TFET) has been made using distinct device geometry. Firstly, performance parameters of GAA-TFET are analyzed in terms of drain current, gate capacitances, transconductance, source-drain conductance at different radii and channel length. Furthermore, we also produce the geometrical analysis towards the optimized investigation of radio frequency parameters like cut-off frequency, maximum oscillation frequency and gain bandwidth product using a 3D technology computer-aided design ATLAS. Due to band-to-band tunneling based current mechanism unlike MOSFET, gate-bias dependence values as primary parameters of TFET differ. We also analyze that the maximum current occurs when radii of Si is around 8 nm due to high gate controllability over channel with reduced fringing effects and also there is no change in the current of TFET on varying its length from 100 to 40 nm. However current starts to increase when channel length is further reduced for 40 to 30 nm. Both of these trades-offs affect the RF performance of the device. Project supported by the Council of Scientific and Industrial Research (CSIR) Funded Research Project, Grant No. 22/0651/14/EMR-II, Government of India.

Potassium channels cloned from neuroblastoma cells display slowly inactivating outward currents in Xenopus oocytes.

PubMed

Ito, Y; Yokoyama, S; Higashida, H

1992-05-22

Messenger RNAs (mRNAs) specific for NGK1 and NGK2 potassium channels were synthesized from complementary DNAs (cDNAs) that had been cloned from mouse neuroblastoma x rat glioma hybrid NG108-15 cells. Outward pottasium currents were evoked by 5 s depolarizing voltage commands in Xenopus oocytes injected with NGK1- or NGK2-specific mRNAs. The NGK1 or NGK2 currents showed different activation and inactivation kinetics, and different pharmacological sensitivities. The threshold potential for activation of the NGK2 current (-14 mV) was more positive than that for the NGK1 (-36 mV). The NGK2 current showed faster inactivation during a 5 s depolarizing pulse than did the NGK1 current. Inactivation was best fit by time constants of 0.37, 1.5 and 19 s for the NGK2 current and 4.4 and 19 s for NGK1. Extracellularly applied tetraethylammonium chloride (TEA) was 1000 times more potent on the NGK2 current than the NGK1 current. Furthermore we examined outward current following co-injection of an equal amount of mRNAs for NGK1 and NGK2. The timecourse of inactivation differed from either alone or from a simple sum of the two individual currents. TEA sensitivity could not be explained by summation of the two homomultimeric channels. These findings suggest that both NGK1 and NGK2 proteins assemble to form heteromultimeric K+ channels in addition to homomultimeric K+ channels. NGK2 channels and the heteromultimeric channels may be responsible for the native transient outward current with slow inactivation in NG108-15 hybrid cells.

Modulation of neuronal sodium channels by the sea anemone peptide BDS-I

PubMed Central

Liu, Pin; Jo, Sooyeon

2012-01-01

Blood-depressing substance I (BDS-I), a 43 amino-acid peptide from sea anemone venom, is used as a specific inhibitor of Kv3-family potassium channels. We found that BDS-I acts with even higher potency to modulate specific types of voltage-dependent sodium channels. In rat dorsal root ganglion (DRG) neurons, 3 μM BDS-I strongly enhanced tetrodotoxin (TTX)-sensitive sodium current but weakly inhibited TTX-resistant sodium current. In rat superior cervical ganglion (SCG) neurons, which express only TTX-sensitive sodium current, BDS-I enhanced current elicited by small depolarizations and slowed decay of currents at all voltages (EC50 ∼ 300 nM). BDS-I acted with exceptionally high potency and efficacy on cloned human Nav1.7 channels, slowing inactivation by 6-fold, with an EC50 of approximately 3 nM. BDS-I also slowed inactivation of sodium currents in N1E-115 neuroblastoma cells (mainly from Nav1.3 channels), with an EC50 ∼ 600 nM. In hippocampal CA3 pyramidal neurons (mouse) and cerebellar Purkinje neurons (mouse and rat), BDS-I had only small effects on current decay (slowing inactivation by 20–50%), suggesting relatively weak sensitivity of Nav1.1 and Nav1.6 channels. The biggest effect of BDS-I in central neurons was to enhance resurgent current in Purkinje neurons, an effect reflected in enhancement of sodium current during the repolarization phase of Purkinje neuron action potentials. Overall, these results show that BDS-I acts to modulate sodium channel gating in a manner similar to previously known neurotoxin receptor site 3 anemone toxins but with different isoform sensitivity. Most notably, BDS-I acts with very high potency on human Nav1.7 channels. PMID:22442564

A novel frequency analysis method for assessing K(ir)2.1 and Na (v)1.5 currents.

PubMed

Rigby, J R; Poelzing, S

2012-04-01

Voltage clamping is an important tool for measuring individual currents from an electrically active cell. However, it is difficult to isolate individual currents without pharmacological or voltage inhibition. Herein, we present a technique that involves inserting a noise function into a standard voltage step protocol, which allows one to characterize the unique frequency response of an ion channel at different step potentials. Specifically, we compute the fast Fourier transform for a family of current traces at different step potentials for the inward rectifying potassium channel, K(ir)2.1, and the channel encoding the cardiac fast sodium current, Na(v)1.5. Each individual frequency magnitude, as a function of voltage step, is correlated to the peak current produced by each channel. The correlation coefficient vs. frequency relationship reveals that these two channels are associated with some unique frequencies with high absolute correlation. The individual IV relationship can then be recreated using only the unique frequencies with magnitudes of high absolute correlation. Thus, this study demonstrates that ion channels may exhibit unique frequency responses.

Unusual Voltage-Gated Sodium Currents as Targets for Pain.

PubMed

Barbosa, C; Cummins, T R

2016-01-01

Pain is a serious health problem that impacts the lives of many individuals. Hyperexcitability of peripheral sensory neurons contributes to both acute and chronic pain syndromes. Because voltage-gated sodium currents are crucial to the transmission of electrical signals in peripheral sensory neurons, the channels that underlie these currents are attractive targets for pain therapeutics. Sodium currents and channels in peripheral sensory neurons are complex. Multiple-channel isoforms contribute to the macroscopic currents in nociceptive sensory neurons. These different isoforms exhibit substantial variations in their kinetics and pharmacology. Furthermore, sodium current complexity is enhanced by an array of interacting proteins that can substantially modify the properties of voltage-gated sodium channels. Resurgent sodium currents, atypical currents that can enhance recovery from inactivation and neuronal firing, are increasingly being recognized as playing potentially important roles in sensory neuron hyperexcitability and pain sensations. Here we discuss unusual sodium channels and currents that have been identified in nociceptive sensory neurons, describe what is known about the molecular determinants of the complex sodium currents in these neurons. Finally, we provide an overview of therapeutic strategies to target voltage-gated sodium currents in nociceptive neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

4-channels coherent perfect absorption (CPA)-type demultiplexer using plasmonic nano spheres

NASA Astrophysics Data System (ADS)

Soltani, Mohamadreza; Keshavarzi, Rasul

2017-10-01

The current research represents a nanoscale and compact 4-channels plasmonic demultiplexer. It includes eight coherent perfect absorption (CPA) - type filters. The operation principle is based on the absorbable formation of a conductive path in the dielectric layer of a plasmonic nano-spheres waveguide. Since the CPA efficiency depends strongly on the number of plasmonic nano-spheres and the nano spheres location, an efficient binary optimization method based on the Particle Swarm Optimization algorithm is used to design an optimized array of the plasmonic nano-sphere in order to achieve the maximum absorption coefficient in the 'off' state.

High performance thin film transistor with ZnO channel layer deposited by DC magnetron sputtering.

PubMed

Moon, Yeon-Keon; Moon, Dae-Yong; Lee, Sang-Ho; Jeong, Chang-Oh; Park, Jong-Wan

2008-09-01

Research in large area electronics, especially for low-temperature plastic substrates, focuses commonly on limitations of the semiconductor in thin film transistors (TFTs), in particular its low mobility. ZnO is an emerging example of a semiconductor material for TFTs that can have high mobility, while a-Si and organic semiconductors have low mobility (<1 cm2/Vs). ZnO-based TFTs have achieved high mobility, along with low-voltage operation low off-state current, and low gate leakage current. In general, ZnO thin films for the channel layer of TFTs are deposited with RF magnetron sputtering methods. On the other hand, we studied ZnO thin films deposited with DC magnetron sputtering for the channel layer of TFTs. After analyzing the basic physical and chemical properties of ZnO thin films, we fabricated a TFT-unit cell using ZnO thin films for the channel layer. The field effect mobility (micro(sat)) of 1.8 cm2/Vs and threshold voltage (Vth) of -0.7 V were obtained.

Visualization of the meridian of traditional Chinese medicine with electrical impedance tomography: An initial experience

NASA Astrophysics Data System (ADS)

Cao, Yanli; Lu, Xiaozuo; Wang, Xuemin

2010-04-01

The meridian is a concept central to traditional Chinese medical techniques such as acupuncture. There is no physically verifiable anatomical or histological basis for the existence of meridians. In Chinese medicine, the meridians are channels along which the energy of the psychological system is considered to flow. It has been proven that the resistance along the meridian channels is lower compared to other paths. Based on this knowledge, we proposed using electrical impedance tomography (EIT) to visualize the meridians of human being. A simplified three dimensional (3D) mathematical model of the forearm developed. Current was injected in the direction perpendicular to the cross-section where eight electrodes were equally placed around the surface of the forearm for the voltage measurements. The model was solved using Finite Element Method (FEM) and dynamic image was reconstructed using truncated singular value decomposition (TSVD) regularization method. The conductivity distributions were compared with different current injections, along the meridian channel and channels around respectively. We also conducted experiments on models and the meridians were shown in final reconstructed images.

Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

PubMed Central

Naranjo, David; Wen, Hua; Brehm, Paul

2015-01-01

The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

High-current discharge channel contraction in high density gas

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

Rutberg, Ph. G.; Bogomaz, A. A.; Pinchuk, M. E.

Research results for discharges at current amplitudes of 0.5-1.6 MA and current rise rate of {approx}10{sup 10} A/s are presented. The discharge is performed in the hydrogen environment at the initial pressure of 5-35 MPa. Initiation is implemented by a wire explosion. The time length of the first half-period of the discharge current is 70-150 {mu}s. Under such conditions, discharge channel contraction is observed; the contraction is followed by soft x-ray radiation. The phenomena are discussed, which are determined by high density of the gas surrounding the discharge channel. These phenomena are increase of the current critical value, where themore » channel contraction begins and growth of temperature in the axis region of the channel, where the initial density of the gas increases.« less

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.

Acoustic Imaging of a Turbidity Current Flowing along a Channel

NASA Astrophysics Data System (ADS)

Hughes Clarke, J. E.; Hiroji, A.; Cahill, L.; Fedele, J. J.

2017-12-01

As part of a 3 month sequence of repetitive surveys and ADCP monitoring, more than 30 turbidity currents have been identified modifying a lobe channel in 130 to 190m of water on the Squamish prodelta. For a 6 day period, daily surveys at low tide tried to capture the change resulting from a single flow. On the 8thof June three flows occurred within a half hour. Along channel multibeam images of the seabed and water column were obtained from a moving vessel immediately before, during and after the passage of the third flow. In this manner the spatial extent of the in-channel and overbank flow could be constrained. By following the flow, the spatial pattern of scattering from the flow upper surface could be examined over a 2 km length of the channel. Along channel bands of high scattering appear related to enhanced release of gas along the channel flanks. Notably, no signature of the underlying across-channel bedform modulations were evident, suggesting that the upper surface of the flow does not feel the influence of the channel floor. Overbank spillage of the flow could be detected by perturbation of a plankton scattering layer just above the seabed. Additionally, evidence of enhanced overbank deposition due to flow stripping on the outer corner of a bend was identified from backscatter changes. The specific seabed alteration due to this flow could be identified and compared with the cumulative change over three months in the channel and adjacent channel-lobe transition zone. As the flow passed under the ADCP, it had a peak velocity of over 2 m/s, a thickness of 4-5m and duration of 35 minutes. Based on the timing of the flow head when in view of the surface vessel, it was decelerating as it exited the mouth of the channel.

Morphodynamics of submarine channel inception revealed by new experimental approach

PubMed Central

de Leeuw, Jan; Eggenhuisen, Joris T.; Cartigny, Matthieu J. B.

2016-01-01

Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and only in one instance on the modern seafloor. Previous experimental flows did not show channel inception, because flow conditions were not appropriately scaled to sustain suspended sediment transport. Here we introduce and apply new scaling constraints for similarity between natural and experimental turbidity currents. The scaled currents initiate a leveed channel from an initially featureless slope. Channelization commences with deposition of levees in some slope segments and erosion of a conduit in other segments. Channel relief and flow confinement increase progressively during subsequent flows. This morphodynamic evolution determines the architecture of submarine channel deposits in the stratigraphic record and efficiency of sediment bypass to the basin floor. PMID:26996440

Role of Cyclic Nucleotide-Gated Channels in the Modulation of Mouse Hippocampal Neurogenesis

PubMed Central

Podda, Maria Vittoria; Piacentini, Roberto; Barbati, Saviana Antonella; Mastrodonato, Alessia; Puzzo, Daniela; D’Ascenzo, Marcello; Leone, Lucia; Grassi, Claudio

2013-01-01

Neural stem cells generate neurons in the hippocampal dentate gyrus in mammals, including humans, throughout adulthood. Adult hippocampal neurogenesis has been the focus of many studies due to its relevance in processes such as learning and memory and its documented impairment in some neurodegenerative diseases. However, we are still far from having a complete picture of the mechanism regulating this process. Our study focused on the possible role of cyclic nucleotide-gated (CNG) channels. These voltage-independent channels activated by cyclic nucleotides, first described in retinal and olfactory receptors, have been receiving increasing attention for their involvement in several brain functions. Here we show that the rod-type, CNGA1, and olfactory-type, CNGA2, subunits are expressed in hippocampal neural stem cells in culture and in situ in the hippocampal neurogenic niche of adult mice. Pharmacological blockade of CNG channels did not affect cultured neural stem cell proliferation but reduced their differentiation towards the neuronal phenotype. The membrane permeant cGMP analogue, 8-Br-cGMP, enhanced neural stem cell differentiation to neurons and this effect was prevented by CNG channel blockade. In addition, patch-clamp recording from neuron-like differentiating neural stem cells revealed cGMP-activated currents attributable to ion flow through CNG channels. The current work provides novel insights into the role of CNG channels in promoting hippocampal neurogenesis, which may prove to be relevant for stem cell-based treatment of cognitive impairment and brain damage. PMID:23991183

A three-dimensional stratigraphic model for aggrading submarine channels based on laboratory experiments, numerical modeling, and sediment cores

NASA Astrophysics Data System (ADS)

Limaye, A. B.; Komatsu, Y.; Suzuki, K.; Paola, C.

2017-12-01

Turbidity currents deliver clastic sediment from continental margins to the deep ocean, and are the main driver of landscape and stratigraphic evolution in many low-relief, submarine environments. The sedimentary architecture of turbidites—including the spatial organization of coarse and fine sediments—is closely related to the aggradation, scour, and lateral shifting of channels. Seismic stratigraphy indicates that submarine, meandering channels often aggrade rapidly relative to lateral shifting, and develop channel sand bodies with high vertical connectivity. In comparison, the stratigraphic architecture developed by submarine, braided is relatively uncertain. We present a new stratigraphic model for submarine braided channels that integrates predictions from laboratory experiments and flow modeling with constraints from sediment cores. In the laboratory experiments, a saline density current developed subaqueous channels in plastic sediment. The channels aggraded to form a deposit with a vertical scale of approximately five channel depths. We collected topography data during aggradation to (1) establish relative stratigraphic age, and (2) estimate the sorting patterns of a hypothetical grain size distribution. We applied a numerical flow model to each topographic surface and used modeled flow depth as a proxy for relative grain size. We then conditioned the resulting stratigraphic model to observed grain size distributions using sediment core data from the Nankai Trough, offshore Japan. Using this stratigraphic model, we establish new, quantitative predictions for the two- and three-dimensional connectivity of coarse sediment as a function of fine-sediment fraction. Using this case study as an example, we will highlight outstanding challenges in relating the evolution of low-relief landscapes to the stratigraphic record.

Role of ion channels and subcellular Ca2+ signaling in arachidonic acid-induced dilation of pressurized retinal arterioles.

PubMed

Kur, Joanna; McGahon, Mary K; Fernández, Jose A; Scholfield, C Norman; McGeown, J Graham; Curtis, Tim M

2014-05-02

To investigate the mechanisms responsible for the dilatation of rat retinal arterioles in response to arachidonic acid (AA). Changes in the diameter of isolated, pressurized rat retinal arterioles were measured in the presence of AA alone and following pre-incubation with pharmacologic agents inhibiting Ca(2+) sparks and oscillations and K(+) channels. Subcellular Ca(2+) signals were recorded in arteriolar myocytes using Fluo-4-based confocal imaging. The effects of AA on membrane currents of retinal arteriolar myocytes were studied using whole-cell perforated patch clamp recording. Arachidonic acid dilated pressurized retinal arterioles under conditions of myogenic tone. Eicosatetraynoic acid (ETYA) exerted a similar effect, but unlike AA, its effects were rapidly reversible. Arachidonic acid-induced dilation was associated with an inhibition of subcellular Ca(2+) signals. Interventions known to block Ca(2+) sparks and oscillations in retinal arterioles caused dilatation and inhibited AA-induced vasodilator responses. Arachidonic acid accelerated the rate of inactivation of the A-type Kv current and the voltage dependence of inactivation was shifted to more negative membrane potentials. It also enhanced voltage-activated and spontaneous large-conductance calcium-activated K(+) (BK) currents, but only at positive membrane potentials. Pharmacologic inhibition of A-type Kv and BK currents failed to block AA-induced vasodilator responses. Arachidonic acid suppressed L-type Ca(2+) currents. These results suggest that AA induces retinal arteriolar vasodilation by inhibiting subcellular Ca(2+)-signaling activity in retinal arteriolar myocytes, most likely through a mechanism involving the inhibition of L-type Ca(2+)-channel activity. Arachidonic acid actions on K(+) currents are inconsistent with a model in which K(+) channels contribute to the vasodilator effects of AA.

Top-Contact Self-Aligned Printing for High-Performance Carbon Nanotube Thin-Film Transistors with Sub-Micron Channel Length.

PubMed

Cao, Xuan; Wu, Fanqi; Lau, Christian; Liu, Yihang; Liu, Qingzhou; Zhou, Chongwu

2017-02-28

Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed thin-film transistors due to their excellent electrical performance and intrinsic printability with solution-based deposition. However, limited by resolution and registration accuracy of current printing techniques, previously reported fully printed nanotube transistors had rather long channel lengths (>20 μm) and consequently low current-drive capabilities (<0.2 μA/μm). Here we report fully inkjet printed nanotube transistors with dramatically enhanced on-state current density of ∼4.5 μA/μm by downscaling the devices to a sub-micron channel length with top-contact self-aligned printing and employing high-capacitance ion gel as the gate dielectric. Also, the printed transistors exhibited a high on/off ratio of ∼10 5 , low-voltage operation, and good mobility of ∼15.03 cm 2 V -1 s -1 . These advantageous features of our printed transistors are very promising for future high-definition printed displays and sensing systems, low-power consumer electronics, and large-scale integration of printed electronics.

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.

Non-equilibrium Green's functions study of discrete dopants variability on an ultra-scaled FinFET

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

Valin, R., E-mail: r.valinferreiro@swansea.ac.uk; Martinez, A., E-mail: a.e.Martinez@swansea.ac.uk; Barker, J. R., E-mail: john.barker@glasgow.ac.uk

In this paper, we study the effect of random discrete dopants on the performance of a 6.6 nm channel length silicon FinFET. The discrete dopants have been distributed randomly in the source/drain region of the device. Due to the small dimensions of the FinFET, a quantum transport formalism based on the non-equilibrium Green's functions has been deployed. The transfer characteristics for several devices that differ in location and number of dopants have been calculated. Our results demonstrate that discrete dopants modify the effective channel length and the height of the source/drain barrier, consequently changing the channel control of the charge. Thismore » effect becomes more significant at high drain bias. As a consequence, there is a strong effect on the variability of the on-current, off-current, sub-threshold slope, and threshold voltage. Finally, we have also calculated the mean and standard deviation of these parameters to quantify their variability. The obtained results show that the variability at high drain bias is 1.75 larger than at low drain bias. However, the variability of the on-current, off-current, and sub-threshold slope remains independent of the drain bias. In addition, we have found that a large source to drain current by tunnelling current occurs at low gate bias.« less

OmpF, a nucleotide-sensing nanoprobe, computational evaluation of single channel activities

NASA Astrophysics Data System (ADS)

Abdolvahab, R. H.; Mobasheri, H.; Nikouee, A.; Ejtehadi, M. R.

2016-09-01

The results of highthroughput practical single channel experiments should be formulated and validated by signal analysis approaches to increase the recognition precision of translocating molecules. For this purpose, the activities of the single nano-pore forming protein, OmpF, in the presence of nucleotides were recorded in real time by the voltage clamp technique and used as a means for nucleotide recognition. The results were analyzed based on the permutation entropy of current Time Series (TS), fractality, autocorrelation, structure function, spectral density, and peak fraction to recognize each nucleotide, based on its signature effect on the conductance, gating frequency and voltage sensitivity of channel at different concentrations and membrane potentials. The amplitude and frequency of ion current fluctuation increased in the presence of Adenine more than Cytosine and Thymine in milli-molar (0.5 mM) concentrations. The variance of the current TS at various applied voltages showed a non-monotonic trend whose initial increasing slope in the presence of Thymine changed to a decreasing one in the second phase and was different from that of Adenine and Cytosine; e.g., by increasing the voltage from 40 to 140 mV in the 0.5 mM concentration of Adenine or Cytosine, the variance decreased by one third while for the case of Thymine it was doubled. Moreover, according to the structure function of TS, the fractality of current TS differed as a function of varying membrane potentials (pd) and nucleotide concentrations. Accordingly, the calculated permutation entropy of the TS, validated the biophysical approach defined for the recognition of different nucleotides at various concentrations, pd's and polarities. Thus, the promising outcomes of the combined experimental and theoretical methodologies presented here can be implemented as a complementary means in pore-based nucleotide recognition approaches.

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 ) .

Thin membrane sensor with biochemical switch

NASA Technical Reports Server (NTRS)

Worley, III, Jennings F. (Inventor); Case, George D. (Inventor)

1994-01-01

A modular biosensor system for chemical or biological agent detection utilizes electrochemical measurement of an ion current across a gate membrane triggered by the reaction of the target agent with a recognition protein conjugated to a channel blocker. The sensor system includes a bioresponse simulator or biochemical switch module which contains the recognition protein-channel blocker conjugate, and in which the detection reactions occur, and a transducer module which contains a gate membrane and a measuring electrode, and in which the presence of agent is sensed electrically. In the poised state, ion channels in the gate membrane are blocked by the recognition protein-channel blocker conjugate. Detection reactions remove the recognition protein-channel blocker conjugate from the ion channels, thus eliciting an ion current surge in the gate membrane which subsequently triggers an output alarm. Sufficiently large currents are generated that simple direct current electronics are adequate for the measurements. The biosensor has applications for environmental, medical, and industrial use.

Interactions among DIV voltage-sensor movement, fast inactivation, and resurgent Na current induced by the NaVβ4 open-channel blocking peptide

PubMed Central

Lewis, Amanda H.

2013-01-01

Resurgent Na current flows as voltage-gated Na channels recover through open states from block by an endogenous open-channel blocking protein, such as the NaVβ4 subunit. The open-channel blocker and fast-inactivation gate apparently compete directly, as slowing the onset of fast inactivation increases resurgent currents by favoring binding of the blocker. Here, we tested whether open-channel block is also sensitive to deployment of the DIV voltage sensor, which facilitates fast inactivation. We expressed NaV1.4 channels in HEK293t cells and assessed block by a free peptide replicating the cytoplasmic tail of NaVβ4 (the “β4 peptide”). Macroscopic fast inactivation was disrupted by mutations of DIS6 (L443C/A444W; “CW” channels), which reduce fast-inactivation gate binding, and/or by the site-3 toxin ATX-II, which interferes with DIV movement. In wild-type channels, the β4 peptide competed poorly with fast inactivation, but block was enhanced by ATX. With the CW mutation, large peptide-induced resurgent currents were present even without ATX, consistent with increased open-channel block upon depolarization and slower deactivation after blocker unbinding upon repolarization. The addition of ATX greatly increased transient current amplitudes and further enlarged resurgent currents, suggesting that pore access by the blocker is actually decreased by full deployment of the DIV voltage sensor. ATX accelerated recovery from block at hyperpolarized potentials, however, suggesting that the peptide unbinds more readily when DIV voltage-sensor deployment is disrupted. These results are consistent with two open states in Na channels, dependent on the DIV voltage-sensor position, which differ in affinity for the blocking protein. PMID:23940261

Characteristics of single Ca(2+) channel kinetics in feline hypertrophied ventricular myocytes.

PubMed

Yang, Xiangjun; Hui, Jie; Jiang, Tingbo; Song, Jianping; Liu, Zhihua; Jiang, Wenping

2002-04-01

To explore the mechanism underlying the prolongation of action potential and delayed inactivation of the L-type Ca(2+) (I(Ca, L)) current in a feline model of left ventricular system hypertension and concomitant hypertrophy. Single Ca(2+) channel properties in myocytes isolated from normal and pressure overloaded cat left ventricles were studied, using patch-clamp techniques. Left ventricular pressure overload was induced by partial ligation of the ascending aorta for 4 - 6 weeks. The amplitude of single Ca(2+) channel current evoked by depolarizing pulses from -40 mV to 0 mV was 1.02 +/- 0.03 pA in normal cells and 1.05 +/- 0.03 pA in hypertrophied cells, and there was no difference in single channel current-voltage relationships between the groups since slope conductance was 26.2 +/- 1.0 pS in normal and hypertrophied cells, respectively. Peak amplitudes of the ensemble-averaged single Ca(2+) channel currents were not different between the two groups of cells. However, the amplitude of this averaged current at the end of the clamp pulse was significantly larger in hypertrophied cells than in normal cells. Open-time histograms revealed that open-time distribution was fitted by a single exponential function in channels of normal cells and by a two exponential function in channels of hypertrophied cells. The number of long-lasting openings was increased in channels of hypertrophied cells, and therefore the calculated mean open time of the channel was significantly longer compared to normal controls. Kinetic changes in the Ca(2+) channel may underlie both hypertrophy-associated delayed inactivation of the Ca(2+) current and, in part, the pressure overload-induced action potential lengthening in this cat model of ventricular left systolic hypertension and hypertrophy.

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

PubMed Central

Puopolo, Michelino; Binshtok, Alexander M.; Yao, Gui-Lan; Oh, Seog Bae; Woolf, Clifford J.

2013-01-01

QX-314 (N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of “pore dilation” previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50–100 μM. We conclude that QX-314 is directly permeant in the “standard” pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry. PMID:23303863

47 CFR 90.355 - LMS operations below 512 MHz.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PRIVATE LAND MOBILE RADIO SERVICES Intelligent Transportation Systems Radio Service § 90.355 LMS... LMS station and the nearest co-channel base station of another licensee operating a voice system is 75... MHz, 150-170 MHz, and 450-512 MHz bands may use either base-mobile frequencies currently assigned the...

Theory and simulation of multi-channel interference (MCI) widely tunable lasers.

PubMed

Chen, Quanan; Lu, Qiaoyin; Guo, Weihua

2015-07-13

A novel design of an InP-based monolithic widely tunable laser, multi-channel interference (MCI) laser, is proposed and presented for the first time. The device is comprised of a gain section, a common phase section and a multi-channel interference section. The multi-channel interference section contains a 1x8 splitter based on cascaded 1 × 2 multi-mode interferometers (MMIs) and eight arms with unequal length difference. The rear part of each arm is integrated with a one-port multi-mode interference reflector (MIR). Mode selection of the MCI laser is realized by the constructive interference of the lights reflected back by the eight arms. Through optimizing the arm length difference, a tuning range of more than 40 nm covering the whole C band, a threshold current around 11.5 mA and an side-mode-suppression-ratio (SMSR) up to 48 dB have been predicted for this widely tunable laser. Detailed design principle and numerical simulation results are presented.

MUSIC: An 8 channel readout ASIC for SiPM arrays

NASA Astrophysics Data System (ADS)

Gómez, Sergio; Gascón, David; Fernández, Gerard; Sanuy, Andreu; Mauricio, Joan; Graciani, Ricardo; Sanchez, David

2016-04-01

This paper presents an 8 channel ASIC for SiPM anode readout based on a novel low input impedance current conveyor (under patent1). This Multiple Use SiPM Integrated Circuit (MUSIC) has been designed to serve several purposes, including, for instance, the readout of SiPM arrays for some of the Cherenkov Telescope Array (CTA) cameras. The current division scheme at the very front end part of the circuit splits the input current into differently scaled copies which are connected to independent current mirrors. The circuit contains a tunable pole zero cancellation of the SiPM recovery time constant to deal with sensors from different manufacturers. Decay times up to 100 ns are supported covering most of the available SiPM devices in the market. MUSIC offers three main features: (1) differential output of the sum of the individual input channels; (2) 8 individual single ended analog outputs and; (3) 8 individual binary outputs. The digital outputs encode the amount of collected charge in the duration of the digital signal using a time over threshold technique. For each individual channel, the user must select the analog or digital output. Each functionality, the signal sum and the 8 A/D outputs, include a selectable dual-gain configuration. Moreover, the signal sum implements dual-gain output providing a 15 bit dynamic range. Full die simulation results of the MUSIC designed using AMS 0.35 µm SiGe technology are presented: total die size of 9 mm2, 500 MHz bandwidth for channel sum and 150 MHz bandwidth for A/D channels, low input impedance (≍32 Ω), single photon output pulse width at half maximum (FWHM) between 5 and 10 ns and with a power consumption of ≍ 30 mW/ch plus ≍ 200 mW for the 8 ch sum. Encapsulated prototype samples of the MUSIC are expected by March 2016.

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

M Current-Based Therapies for Nerve Agent Seizures

DTIC Science & Technology

2012-07-01

2012.235820. Third goal was to test whether drugs that open M channels wouterminate status epilepticus induced by an organophosphate and cholinergic...agonist (Li/Pilocarpine). Two modelof organophasphate-induced seizures were characterized and published: Characterization of status epilepticus induced...terminates refractory status epilepticus in two models. . 15. SUBJECT TERMS- Seizures, status epilepticus Cholinergic, M Current, Synaptoic

A perspective on paper-based microfluidics: Current status and future trends

PubMed Central

Li, Xu; Ballerini, David R.; Shen, Wei

2012-01-01

“Paper-based microfluidics” or “lab on paper,” as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors’ point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system may take in its development. PMID:22662067

Numerical Simulation of Multiphase Magnetohydrodynamic Flow and Deformation of Electrolyte-Metal Interface in Aluminum Electrolysis Cells

NASA Astrophysics Data System (ADS)

Hua, Jinsong; Rudshaug, Magne; Droste, Christian; Jorgensen, Robert; Giskeodegard, Nils-Haavard

2018-06-01

A computational fluid dynamics based multiphase magnetohydrodynamic (MHD) flow model for simulating the melt flow and bath-metal interface deformation in realistic aluminum reduction cells is presented. The model accounts for the complex physics of the MHD problem in aluminum reduction cells by coupling two immiscible fluids, electromagnetic field, Lorentz force, flow turbulence, and complex cell geometry with large length scale. Especially, the deformation of bath-metal interface is tracked directly in the simulation, and the condition of constant anode-cathode distance (ACD) is maintained by moving anode bottom dynamically with the deforming bath-metal interface. The metal pad deformation and melt flow predicted by the current model are compared to the predictions using a simplified model where the bath-metal interface is assumed flat. The effects of the induced electric current due to fluid flow and the magnetic field due to the interior cell current on the metal pad deformation and melt flow are investigated. The presented model extends the conventional simplified box model by including detailed cell geometry such as the ledge profile and all channels (side, central, and cross-channels). The simulations show the model sensitivity to different side ledge profiles and the cross-channel width by comparing the predicted melt flow and metal pad heaving. In addition, the model dependencies upon the reduction cell operation conditions such as ACD, current distribution on cathode surface and open/closed channel top, are discussed.

The What and Where of Adding Channel Noise to the Hodgkin-Huxley Equations

PubMed Central

Goldwyn, Joshua H.; Shea-Brown, Eric

2011-01-01

Conductance-based equations for electrically active cells form one of the most widely studied mathematical frameworks in computational biology. This framework, as expressed through a set of differential equations by Hodgkin and Huxley, synthesizes the impact of ionic currents on a cell's voltage—and the highly nonlinear impact of that voltage back on the currents themselves—into the rapid push and pull of the action potential. Later studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional) description than the original Hodgkin-Huxley equations or their counterparts. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the equations of Hodgkin-Huxley type. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic equations of Hodgkin-Huxley type as well as to more modern models of ion channel dynamics. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly MATLAB simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950) and http://www.amath.washington.edu/~etsb/tutorials.html. PMID:22125479

Endogenous channels in HEK cells and potential roles in HCN ionic current measurements.

PubMed

Varghese, Anthony; Tenbroek, Erica M; Coles, James; Sigg, Daniel C

2006-01-01

A transformed line of human embryonic kidney epithelial cells (HEK 293) is commonly used as an expression system for exogenous ion channel genes. Previously, it has been shown that these cells contain mRNAs for a variety of ion channels. Expression of some of these genes has been confirmed at the protein level. Patch-clamp electrophysiology experiments confirm the presence of multiple ion channels and molecular data agree with pharmacological profiles of identified channels. In this work, we show that endogenous voltage-gated potassium channels in HEK cells are a significant source of outward current at positive potentials. We show that both non-transfected HEK cells and HEK cells transfected with hyperpolarization-activated cyclic-nucleotide gated (HCN) channels have a significant amount of voltage-gated potassium (K(V)) current when certain tail current voltage-clamp protocols are used to assay HCN current activation. Specifically, tail current protocols that use a depolarized holding potential of -40 mV followed by hyperpolarizing pulses (-80 to -140 mV) and then a tail pulse potential of +20 mV indicate K(V) channels undergo closed-state inactivation at the more depolarized holding potential of -40 mV, followed by recovery from inactivation (but no activation) at hyperpolarizing potentials and high amount of activation at the positive tail potential. Our results indicate that pulse protocols with positive tail pulses are inaccurate assays for HCN current in certain HEK cells. Surprisingly, HEK-293 cells were found to contain mRNA for HCN2 and HCN3 although we have not detected a significant and consistent endogenous I(f)-like current in these cells.

[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.

Performance enhancement of pentacene-based organic thin-film transistors using 6,13-pentacenequinone as a carrier injection interlayer

NASA Astrophysics Data System (ADS)

Fan, Ching-Lin; Lin, Wei-Chun; Chen, Hao-Wei

2018-06-01

This work demonstrates pentacene-based organic thin-film transistors (OTFTs) fabricated by inserting a 6,13-pentacenequinone (PQ) carrier injection layer between the source/drain (S/D) metal Au electrodes and pentacene channel layer. Compared to devices without a PQ layer, the performance characteristics including field-effect mobility, threshold voltage, and On/Off current ratio were significantly improved for the device with a 5-nm-thick PQ interlayer. These improvements are attributed to significant reduction of hole barrier height at the Au/pentacene channel interfaces. Therefore, it is believed that using PQ as the carrier injection layer is a good candidate to improve the pentacene-based OTFTs electrical performance.

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.

Monolithic single mode interband cascade lasers with wide wavelength tunability

NASA Astrophysics Data System (ADS)

von Edlinger, M.; Weih, R.; Scheuermann, J.; Nähle, L.; Fischer, M.; Koeth, J.; Kamp, M.; Höfling, S.

2016-11-01

Monolithic two-section interband cascade lasers offering a wide wavelength tunability in the wavelength range around 3.7 μm are presented. Stable single mode emission in several wavelength channels was realized using the concept of binary superimposed gratings and two-segment Vernier-tuning. The wavelength selective elements in the two segments were based on specially designed lateral metal grating structures defined by electron beam lithography. A dual-step dry etch process provided electrical separation between the segments. Individual current control of the segments allowed wavelength channel selection as well as continuous wavelength tuning within channels. A discontinuous tuning range extending over 158 nm in up to six discrete wavelength channels was achieved. Mode hop free wavelength tuning up to 14 nm was observed within one channel. The devices can be operated in continuous wave mode up to 30 °C with the output powers of 3.5 mW around room temperature.

Measuring kinetics of complex single ion channel data using mean-variance histograms.

PubMed Central

Patlak, J B

1993-01-01

The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean-variance histogram technique provided a more credible analysis of the open, closed, and subconductance times for the patch. I also show that the method produces accurate results on simulated data in a wide variety of conditions, whereas the half-amplitude method, when applied to complex simulated data shows the same errors as were apparent in the real data. The utility and the limitations of this new method are discussed. Images FIGURE 2 FIGURE 4 FIGURE 8 FIGURE 9 PMID:7690261

Volume-dependent ATP-conductive large-conductance anion channel as a pathway for swelling-induced ATP release.

PubMed

Sabirov, R Z; Dutta, A K; Okada, Y

2001-09-01

In mouse mammary C127i cells, during whole-cell clamp, osmotic cell swelling activated an anion channel current, when the phloretin-sensitive, volume-activated outwardly rectifying Cl(-) channel was eliminated. This current exhibited time-dependent inactivation at positive and negative voltages greater than around +/-25 mV. The whole-cell current was selective for anions and sensitive to Gd(3)+. In on-cell patches, single-channel events appeared with a lag period of approximately 15 min after a hypotonic challenge. Under isotonic conditions, cell-attached patches were silent, but patch excision led to activation of currents that consisted of multiple large-conductance unitary steps. The current displayed voltage- and time-dependent inactivation similar to that of whole-cell current. Voltage-dependent activation profile was bell-shaped with the maximum open probability at -20 to 0 mV. The channel in inside-out patches had the unitary conductance of approximately 400 pS, a linear current-voltage relationship, and anion selectivity. The outward (but not inward) single-channel conductance was suppressed by extracellular ATP with an IC(50) of 12.3 mM and an electric distance (delta) of 0.47, whereas the inward (but not outward) conductance was inhibited by intracellular ATP with an IC(50) of 12.9 mM and delta of 0.40. Despite the open channel block by ATP, the channel was ATP-conductive with P(ATP)/P(Cl) of 0.09. The single-channel activity was sensitive to Gd(3)+, SITS, and NPPB, but insensitive to phloretin, niflumic acid, and glibenclamide. The same pharmacological pattern was found in swelling-induced ATP release. Thus, it is concluded that the volume- and voltage-dependent ATP-conductive large-conductance anion channel serves as a conductive pathway for the swelling-induced ATP release in C127i cells.

Direct demonstration of persistent Na+ channel activity in dendritic processes of mammalian cortical neurones

PubMed Central

Magistretti, Jacopo; Ragsdale, David S; Alonso, Angel

1999-01-01

Single Na+ channel activity was recorded in patch-clamp, cell-attached experiments performed on dendritic processes of acutely isolated principal neurones from rat entorhinal-cortex layer II. The distances of the recording sites from the soma ranged from ≈20 to ≈100 μm.Step depolarisations from holding potentials of −120 to −100 mV to test potentials of −60 to +10 mV elicited Na+ channel openings in all of the recorded patches (n= 16).In 10 patches, besides transient Na+ channel openings clustered within the first few milliseconds of the depolarising pulses, prolonged and/or late Na+ channel openings were also regularly observed. This ‘persistent’ Na+ channel activity produced net inward, persistent currents in ensemble-average traces, and remained stable over the entire duration of the experiments (≈9 to 30 min).Two of these patches contained <= 3 channels. In these cases, persistent Na+ channel openings could be attributed to the activity of one single channel.The voltage dependence of persistent-current amplitude in ensemble-average traces closely resembled that of whole-cell, persistent Na+ current expressed by the same neurones, and displayed the same characteristic low threshold of activation.Dendritic, persistent Na+ channel openings had relatively high single-channel conductance (≈20 pS), similar to what is observed for somatic, persistent Na+ channels.We conclude that a stable, persistent Na+ channel activity is expressed by proximal dendrites of entorhinal-cortex layer II principal neurones, and can contribute a significant low-threshold, persistent Na+ current to the dendritic processing of excitatory synaptic inputs. PMID:10601494

Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches

PubMed Central

Joseph, Biny K.; Thakali, Keshari M.; Moore, Christopher L.; Rhee, Sung W.

2013-01-01

Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells (VSMCs). The dynamic interplay of Ca2+ and K+ channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles. The abnormally-elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca2+ and K+ channels in the VSMCs. In this short review, we focus on the three well-studied ion channels in VSMCs, namely the L-type Ca2+ (CaV1.2) channels, the voltage-gated K+ (KV) channels, and the large-conductance Ca2+-activated K+ (BK) channels. First, we provide a brief overview on the physiological role of vascular CaV1.2, KV and BK channels in regulating arterial tone. Second, we discuss the current understanding of the expression changes and regulation of CaV1.2, KV and BK channels in the vasculature during hypertension. Third, based on available proof-of-concept studies, we describe the potential therapeutic approaches targeting these vascular ion channels in order to restore blood pressure to normotensive levels. PMID:23376354

A microprocessor-based multichannel subsensory stochastic resonance electrical stimulator.

PubMed

Chang, Gwo-Ching

2013-01-01

Stochastic resonance electrical stimulation is a novel intervention which provides potential benefits for improving postural control ability in the elderly, those with diabetic neuropathy, and stroke patients. In this paper, a microprocessor-based subsensory white noise electrical stimulator for the applications of stochastic resonance stimulation is developed. The proposed stimulator provides four independent programmable stimulation channels with constant-current output, possesses linear voltage-to-current relationship, and has two types of stimulation modes, pulse amplitude and width modulation.

Flavonoid Regulation of HCN2 Channels*

PubMed Central

Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.

2013-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

Dual-channel current valve in a three terminal zigzag graphene nanoribbon junction

NASA Astrophysics Data System (ADS)

Zhang, L.

2017-02-01

We theoretically propose a dual-channel current valve based on a three terminal zigzag graphene nanoribbon (ZGNR) junction driven by three asymmetric time-dependent pumping potentials. By means of the Keldysh Green’s function method, we show that two asymmetric charge currents can be pumped in the different left-right terminals of the device at a zero bias, which mainly stems from the single photon-assisted pumping approximation and the valley valve effect in a ZGNR p-n junction. The ON and OFF states of pumped charge currents are crucially dependent on the even-odd chain widths of the three electrodes, the pumping frequency, the lattice potential and the Fermi level. Two-tunneling spin valves are also considered to spatially separate and detect 100% polarized spin currents owing to the combined spin pump effect and the valley selective transport in a three terminal ZGNR ferromagnetic junction. Our investigations might be helpful to control the spatial and spin degrees of freedom of electrons in graphene pumping devices.

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.

Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain.

PubMed

Miceli, Francesco; Vargas, Ernesto; Bezanilla, Francisco; Taglialatela, Maurizio

2012-03-21

Changes in voltage-dependent gating represent a common pathogenetic mechanism for genetically inherited channelopathies, such as benign familial neonatal seizures or peripheral nerve hyperexcitability caused by mutations in neuronal K(v)7.2 channels. Mutation-induced changes in channel voltage dependence are most often inferred from macroscopic current measurements, a technique unable to provide a detailed assessment of the structural rearrangements underlying channel gating behavior; by contrast, gating currents directly measure voltage-sensor displacement during voltage-dependent gating. In this work, we describe macroscopic and gating current measurements, together with molecular modeling and molecular-dynamics simulations, from channels carrying mutations responsible for benign familial neonatal seizures and/or peripheral nerve hyperexcitability; K(v)7.4 channels, highly related to K(v)7.2 channels both functionally and structurally, were used for these experiments. The data obtained showed that mutations affecting charged residues located in the more distal portion of S(4) decrease the stability of the open state and the active voltage-sensing domain configuration but do not directly participate in voltage sensing, whereas mutations affecting a residue (R4) located more proximally in S(4) caused activation of gating-pore currents at depolarized potentials. These results reveal that distinct molecular mechanisms underlie the altered gating behavior of channels carrying disease-causing mutations at different voltage-sensing domain locations, thereby expanding our current view of the pathogenesis of neuronal hyperexcitability diseases. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Microglial K+ Channel Expression in Young Adult and Aged Mice

PubMed Central

Schilling, Tom; Eder, Claudia

2015-01-01

The K+ channel expression pattern of microglia strongly depends on the cells' microenvironment and has been recognized as a sensitive marker of the cells' functional state. While numerous studies have been performed on microglia in vitro, our knowledge about microglial K+ channels and their regulation in vivo is limited. Here, we have investigated K+ currents of microglia in striatum, neocortex and entorhinal cortex of young adult and aged mice. Although almost all microglial cells exhibited inward rectifier K+ currents upon membrane hyperpolarization, their mean current density was significantly enhanced in aged mice compared with that determined in young adult mice. Some microglial cells additionally exhibited outward rectifier K+ currents in response to depolarizing voltage pulses. In aged mice, microglial outward rectifier K+ current density was significantly larger than in young adult mice due to the increased number of aged microglial cells expressing these channels. Aged dystrophic microglia exhibited outward rectifier K+ currents more frequently than aged ramified microglia. The majority of microglial cells expressed functional BK-type, but not IK- or SK-type, Ca2+-activated K+ channels, while no differences were found in their expression levels between microglia of young adult and aged mice. Neither microglial K+ channel pattern nor K+ channel expression levels differed markedly between the three brain regions investigated. It is concluded that age-related changes in microglial phenotype are accompanied by changes in the expression of microglial voltage-activated, but not Ca2+-activated, K+ channels. PMID:25472417

An Experimental Evaluation of Blockage Corrections for Current Turbines

NASA Astrophysics Data System (ADS)

Ross, Hannah; Polagye, Brian

2017-11-01

Flow confinement has been shown to significantly alter the performance of turbines that extract power from water currents. These performance effects are related to the degree of constraint, defined by the ratio of turbine projected area to channel cross-sectional area. This quantity is referred to as the blockage ratio. Because it is often desirable to adjust experimental observations in water channels to unconfined conditions, analytical corrections for both wind and current turbines have been derived. These are generally based on linear momentum actuator disk theory but have been applied to turbines without experimental validation. This work tests multiple blockage corrections on performance and thrust data from a cross-flow turbine and porous plates (experimental analogues to actuator disks) collected in laboratory flumes at blockage ratios ranging between 10 and 35%. To isolate the effects of blockage, the Reynolds number, Froude number, and submergence depth were held constant while the channel width was varied. Corrected performance data are compared to performance in a towing tank at a blockage ratio of less than 5%. In addition to examining the accuracy of each correction, underlying assumptions are assessed to determine why some corrections perform better than others. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1256082 and the Naval Facilities Engineering Command (NAVFAC).

Controllable transport of a skyrmion in a ferromagnetic narrow channel with voltage-controlled magnetic anisotropy

NASA Astrophysics Data System (ADS)

Wang, Junlin; Xia, Jing; Zhang, Xichao; Zhao, G. P.; Ye, Lei; Wu, Jing; Xu, Yongbing; Zhao, Weisheng; Zou, Zhigang; Zhou, Yan

2018-05-01

Magnetic skyrmions have potential applications in next-generation spintronic devices with ultralow energy consumption. In this work, the current-driven skyrmion motion in a narrow ferromagnetic nanotrack with voltage-controlled magnetic anisotropy (VCMA) is studied numerically. By utilizing the VCMA effect, the transport of skyrmion can be unidirectional in the nanotrack, leading to a one-way information channel. The trajectory of the skyrmion can also be modulated by periodically located VCMA gates, which protects the skyrmion from destruction by touching the track edge. In addition, the location of the skyrmion can be controlled by adjusting the driving pulse length in the presence of the VCMA effect. Our results provide guidelines for practical realization of the skyrmion-based information channel, diode, and skyrmion-based electronic devices such as racetrack memory.

Dynamics of Braided Channels, Bars, and Associated Deposits Under Experimental Density Currents

NASA Astrophysics Data System (ADS)

Limaye, A. B. S.; Jean-Louis, G.; Paola, C.

2015-12-01

Turbidity currents are the principal agents that transfer clastic sediment from continental margins to the deep ocean. The extensive sedimentary deposits that result can record influences from fluvial transport, ocean currents, and seafloor bathymetry; decoding these controls is key to understanding long-term continental denudation and the formation of hydrocarbon reservoirs. Experimental turbidity currents often use pre-formed, single-thread channels, but more recent experiments and seafloor observations suggest that braided channels also develop in submarine environments. Yet controls on the formation of submarine braided channels and relationships between these channels and stratigraphic evolution remain largely untested. We have conducted a series of experiments to determine the conditions conducive to forming braided submarine channels, and to relate channel geometry and kinematics to deposit architecture. Dissolved salt supplies the excess density of the experimental turbidity currents, which transport plastic, sand-sized sediment as bedload across a test section two meters long and one meter wide. Our experiments indicate that braided channels can form as constructional features without prior erosion for a range of input water and sediment fluxes. Channel migration, avulsion, and aggradation construct sedimentary deposits with bars at a variety of scales. Bar geometry and channel kinematics are qualitatively similar under subaerial and subaqueous experiments with other parameters fixed. We will present quantitative analyses of the relationships between channel geometry and mobility and deposit architecture, at scales from individual bars to the entire deposit, and compare these results to control experiments with subaerial braiding. These experimental results suggest parallels between subaerial and subaqueous braiding, and help to constrain forward models for stratigraphic evolution and inverse methods for estimating flow conditions from turbidites.

Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum.

PubMed Central

Arispe, N; Rojas, E; Pollard, H B

1993-01-01

Amyloid beta protein (A beta P) is the 40- to 42-residue polypeptide implicated in the pathogenesis of Alzheimer disease. We have incorporated this peptide into phosphatidylserine liposomes and then fused the liposomes with a planar bilayer. When incorporated into bilayers the A beta P forms channels, which generate linear current-voltage relationships in symmetrical solutions. A permeability ratio, PK/PCl, of 11 for the open A beta P channel was estimated from the reversal potential of the channel current in asymmetrical KCl solutions. The permeability sequence for different cations, estimated from the reversal potential of the A beta P-channel current for each system of asymmetrical solutions, is Pcs > PLi > PCa > or = PK > PNa. A beta P-channel current (either CS+ or Ca2+ as charge carriers) is blocked reversibly by tromethamine (millimolar range) and irreversibly by Al3+ (micromolar range). The inhibition of the A beta P-channel current by these two substances depends on transmembrane potential, suggesting that the mechanism of blockade involves direct interaction between tromethamine (or Al3+) and sites within the A beta P channel. Hitherto, A beta P has been presumed to be neurotoxic. On the basis of the present data we suggest that the channel activity of the polypeptide may be responsible for some or all of its neurotoxic effects. We further propose that a useful strategy for drug discovery for treatment of Alzheimer disease may include screening compounds for their ability to block or otherwise modify A beta P channels. PMID:8380642

A pharmacokinetic-pharmacodynamic model for the quantitative prediction of dofetilide clinical QT prolongation from human ether-a-go-go-related gene current inhibition data.

PubMed

Jonker, Daniël M; Kenna, Leslie A; Leishman, Derek; Wallis, Rob; Milligan, Peter A; Jonsson, E Niclas

2005-06-01

QT prolongation is an important biomarker of the arrhythmia torsades de pointes and appears to be related mainly to blockade of delayed inward cardiac rectifier potassium currents. The aim of this study was to quantify the relationship between in vitro human ether-a-go-go-related gene (hERG) potassium channel blockade and the magnitude of QT prolongation in humans for the class III antiarrhythmic dofetilide. The in vitro affinity and activity of dofetilide were determined in recombinant cell cultures expressing the hERG channel, and the QT-prolonging effect of dofetilide was assessed in 5 clinical studies (80 healthy volunteers and 17 patients with ischemic heart disease). A population pharmacokinetic-pharmacodynamic analysis of the in vitro and in vivo data was performed in NONMEM by use of the operational model of pharmacologic agonism to estimate the efficiency of transduction from ion channel binding to Fridericia-corrected QT response. A 3-compartment pharmacokinetic model with first-order absorption characterized the time course of dofetilide concentrations. On the basis of an in vitro potency of 5.13 ng/mL for potassium current inhibition and predicted unbound dofetilide concentrations, the estimated transducer ratio (tau) of 6.2 suggests that the QT response plateaus before currents are fully blocked. In our study population, 10% hERG blockade corresponds to a QT prolongation of 20 ms (95% confidence interval, 12-32 ms). With long-term dofetilide administration, tolerance develops with a half-life of 4.7 days. The current mechanism-based pharmacokinetic-pharmacodynamic model quantified the relationship between in vitro hERG channel blockade and clinical QT prolongation for dofetilide. This model may prove valuable for assessing the risk of QT prolongation in humans for other drugs that selectively block the hERG channel on the basis of in vitro assays and pharmacokinetic properties.

Microfluidics-based, time-resolved mechanical phenotyping of cells using high-speed imaging

NASA Astrophysics Data System (ADS)

Belotti, Yuri; Conneely, Michael; Huang, Tianjun; McKenna, Stephen; Nabi, Ghulam; McGloin, David

2017-07-01

We demonstrate a single channel hydrodynamic stretching microfluidic device that relies on high-speed imaging to allow repeated dynamic cell deformation measurements. Experiments on prostate cancer cells suggest richer data than current approaches.

Mathematical modeling of electrical activity of uterine muscle cells.

PubMed

Rihana, Sandy; Terrien, Jeremy; Germain, Guy; Marque, Catherine

2009-06-01

The uterine electrical activity is an efficient parameter to study the uterine contractility. In order to understand the ionic mechanisms responsible for its generation, we aimed at building a mathematical model of the uterine cell electrical activity based upon the physiological mechanisms. First, based on the voltage clamp experiments found in the literature, we focus on the principal ionic channels and their cognate currents involved in the generation of this electrical activity. Second, we provide the methodology of formulations of uterine ionic currents derived from a wide range of electrophysiological data. The model is validated step by step by comparing simulated voltage-clamp results with the experimental ones. The model reproduces successfully the generation of single spikes or trains of action potentials that fit with the experimental data. It allows analyzing ionic channels implications. Likewise, the calcium-dependent conductance influences significantly the cellular oscillatory behavior.

Proton and non-proton activation of ASIC channels

PubMed Central

Gautschi, Ivan; van Bemmelen, Miguel Xavier; Schild, Laurent

2017-01-01

The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization. PMID:28384246

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

PubMed

Tuluc, Petronel; Flucher, Bernhard E

2011-12-01

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

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.

Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques

PubMed Central

Yue, Jin-feng; Qiao, Guan-hua; Liu, Ni; Nan, Fa-jun; Gao, Zhao-bing

2016-01-01

Aim: To establish an improved, high-throughput screening techniques for identifying novel KCNQ2 channel activators. Methods: KCNQ2 channels were stably expressed in CHO cells (KCNQ2 cells). Thallium flux assay was used for primary screening, and 384-well automated patch-clamp IonWorks Barracuda was used for hit validation. Two validated activators were characterized using a conventional patch-clamp recording technique. Results: From a collection of 80 000 compounds, the primary screening revealed a total of 565 compounds that potentiated the fluorescence signals in thallium flux assay by more than 150%. When the 565 hits were examined in IonWorks Barracuda, 38 compounds significantly enhanced the outward currents recorded in KCNQ2 cells, and were confirmed as KCNQ2 activators. In the conventional patch-clamp recordings, two validated activators ZG1732 and ZG2083 enhanced KCNQ2 currents with EC50 values of 1.04±0.18 μmol/L and 1.37±0.06 μmol/L, respectively. Conclusion: The combination of thallium flux assay and IonWorks Barracuda assay is an efficient high-throughput screening (HTS) route for discovering KCNQ2 activators. PMID:26725738

Molecular sensing using monolayer floating gate, fully depleted SOI MOSFET acting as an exponential transducer.

PubMed

Takulapalli, Bharath R

2010-02-23

Field-effect transistor-based chemical sensors fall into two broad categories based on the principle of signal transduction-chemiresistor or Schottky-type devices and MOSFET or inversion-type devices. In this paper, we report a new inversion-type device concept-fully depleted exponentially coupled (FDEC) sensor, using molecular monolayer floating gate fully depleted silicon on insulator (SOI) MOSFET. Molecular binding at the chemical-sensitive surface lowers the threshold voltage of the device inversion channel due to a unique capacitive charge-coupling mechanism involving interface defect states, causing an exponential increase in the inversion channel current. This response of the device is in opposite direction when compared to typical MOSFET-type sensors, wherein inversion current decreases in a conventional n-channel sensor device upon addition of negative charge to the chemical-sensitive device surface. The new sensor architecture enables ultrahigh sensitivity along with extraordinary selectivity. We propose the new sensor concept with the aid of analytical equations and present results from our experiments in liquid phase and gas phase to demonstrate the new principle of signal transduction. We present data from numerical simulations to further support our theory.

A novel gate and drain engineered charge plasma tunnel field-effect transistor for low sub-threshold swing and ambipolar nature

NASA Astrophysics Data System (ADS)

Yadav, Dharmendra Singh; Raad, Bhagwan Ram; Sharma, Dheeraj

2016-12-01

In this paper, we focus on the improvement of figures of merit for charge plasma based tunnel field-effect transistor (TFET) in terms of ON-state current, threshold voltage, sub-threshold swing, ambipolar nature, and gate to drain capacitance which provides better channel controlling of the device with improved high frequency response at ultra-low supply voltages. Regarding this, we simultaneously employ work function engineering on the drain and gate electrode of the charge plasma TFET. The use of gate work function engineering modulates the barrier on the source/channel interface leads to improvement in the ON-state current, threshold voltage, and sub-threshold swing. Apart from this, for the first time use of work function engineering on the drain electrode increases the tunneling barrier for the flow of holes on the drain/channel interface, it results into suppression of ambipolar behavior. The lowering of gate to drain capacitance therefore enhanced high frequency parameters. Whereas, the presence of dual work functionality at the gate electrode and over the drain region improves the overall performance of the charge plasma based TFET.

A physically based compact I-V model for monolayer TMDC channel MOSFET and DMFET biosensor.

PubMed

Rahman, Ehsanur; Shadman, Abir; Ahmed, Imtiaz; Khan, Saeed Uz Zaman; Khosru, Quazi D M

2018-06-08

In this work, a compact transport model has been developed for monolayer transition metal dichalcogenide (TMDC) channel MOSFET. The analytical model solves the Poisson's equation for the inversion charge density to get the electrostatic potential in the channel. Current is then calculated by solving the drift-diffusion equation. The model makes gradual channel approximation to simplify the solution procedure. The appropriate density of states obtained from the first principle density functional theory simulation has been considered to keep the model physically accurate for monolayer TMDC channel FET. The outcome of the model has been benchmarked against both experimental and numerical quantum simulation results with the help of a few fitting parameters. Using the compact model, detailed output and transfer characteristics of monolayer WSe 2 FET have been studied, and various performance parameters have been determined. The study confirms excellent ON and OFF state performances of monolayer WSe 2 FET which could be viable for the next generation high-speed, low power applications. Also, the proposed model has been extended to study the operation of a biosensor. A monolayer MoS 2 channel based dielectric modulated FET is investigated using the compact model for detection of a biomolecule in a dry environment.

A physically based compact I–V model for monolayer TMDC channel MOSFET and DMFET biosensor

NASA Astrophysics Data System (ADS)

Rahman, Ehsanur; Shadman, Abir; Ahmed, Imtiaz; Zaman Khan, Saeed Uz; Khosru, Quazi D. M.

2018-06-01

In this work, a compact transport model has been developed for monolayer transition metal dichalcogenide (TMDC) channel MOSFET. The analytical model solves the Poisson’s equation for the inversion charge density to get the electrostatic potential in the channel. Current is then calculated by solving the drift–diffusion equation. The model makes gradual channel approximation to simplify the solution procedure. The appropriate density of states obtained from the first principle density functional theory simulation has been considered to keep the model physically accurate for monolayer TMDC channel FET. The outcome of the model has been benchmarked against both experimental and numerical quantum simulation results with the help of a few fitting parameters. Using the compact model, detailed output and transfer characteristics of monolayer WSe2 FET have been studied, and various performance parameters have been determined. The study confirms excellent ON and OFF state performances of monolayer WSe2 FET which could be viable for the next generation high-speed, low power applications. Also, the proposed model has been extended to study the operation of a biosensor. A monolayer MoS2 channel based dielectric modulated FET is investigated using the compact model for detection of a biomolecule in a dry environment.

Comparisons of the hydraulics of water flows in Martian outflow channels with flows of similar scale on earth

NASA Technical Reports Server (NTRS)

Komar, P. D.

1979-01-01

The hydraulics of channelized water flows on Mars and the resulting sediment transport rates are calculated, and similar computations are performed for such terrestrial analogs as the Mississippi River and the catastrophic Lake Missoula floods that formed the Channeled Scabland in eastern Washington State. The morphologies of deep-sea channels formed by catastrophic turbidity currents are compared with the Martian channels, many similarities are pointed out, and the hydraulics of the various flows are compared. The results indicate that the velocities, discharges, bottom shear stresses, and sediment-transport capacity of water flows along the Martian channels would be comparable to those of the oceanic turbidity currents and the Lake Missoula floods. It is suggested that the submarine canyons from which turbidity currents originate are the terrestrial counterparts to the chaotic-terrain areas or craters that serve as sources for many of the Martian channels.

Modulation of Kv7 channels and excitability in the brain.

PubMed

Greene, Derek L; Hoshi, Naoto

2017-02-01

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits.

Modulation of Kv7 channels and excitability in the brain

PubMed Central

Greene, Derek L; Hoshi, Naoto

2016-01-01

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits. PMID:27645822

Simulation modeling to explore the effects of length-based harvest regulations for Ictalurus fisheries

USGS Publications Warehouse

Stewart, David R.; Long, James M.; Shoup, Daniel E.

2016-01-01

Management of Blue Catfish Ictalurus furcatus and Channel Catfish I. punctatus for trophy production has recently become more common. Typically, trophy management is attempted with length-based regulations that allow for the moderate harvest of small fish but restrict the harvest of larger fish. However, the specific regulations used vary considerably across populations, and no modeling efforts have evaluated their effectiveness. We used simulation modeling to compare total yield, trophy biomass (Btrophy), and sustainability (spawning potential ratio [SPR] > 0.30) of Blue Catfish and Channel Catfish populations under three scenarios: (1) current regulation (typically a length-based trophy regulation), (2) the best-performing minimum length regulation (MLRbest), and (3) the best-performing length-based trophy catfish regulation (LTRbest; “best performing” was defined as the regulation that maximized yield, Btrophy, and sustainability). The Btrophy produced did not differ among the three scenarios. For each fishery, the MLRbest and LTRbest produced greater yield (>22% more) than the current regulation and maintained sustainability at higher finite exploitation rates (>0.30) than the current regulation. The MLRbest and LTRbest produced similar yields and SPRs for Channel Catfish and similar yields for Blue Catfish; however, the MLRbest for Blue Catfish produced more resilient fisheries (higher SPR) than the LTRbest. Overall, the variation in yield, Btrophy, and SPR among populations was greater than the variation among regulations applied to any given population, suggesting that population-specific regulations may be preferable to regulations applied to geographic regions. We conclude that LTRs are useful for improving catfish yield and maintaining sustainability without overly restricting harvest but are not effective at increasing the Btrophy of catfish.

FHF2 isoforms differentially regulate Nav1.6 mediated resurgent sodium currents in dorsal root ganglion neurons

PubMed Central

Barbosa, Cindy; Xiao, Yucheng; Johnson, Andrew J.; Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming; Cummins, Theodore R.

2017-01-01

Nav1.6 and Nav1.6 mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6 mediated resurgent currents by isoforms of Fibroblast growth Factor Homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas, FHF2B enhances resurgent currents. Overall our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies. PMID:27999940

Regulation of Connexin-Based Channels by Fatty Acids

PubMed Central

Puebla, Carlos; Retamal, Mauricio A.; Acuña, Rodrigo; Sáez, Juan C.

2017-01-01

In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood. PMID:28174541

Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents

PubMed Central

2016-01-01

Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between −30 and −40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli. PMID:26936982

Zonal variations in K+ currents in vestibular crista calyx terminals

PubMed Central

Meredith, Frances L.

2014-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na+ but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K+ currents were observed at potentials above −60 mV. K+ currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K+ channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K+ channel blocker 4-aminopyridine (10–50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K+ conductances may contribute to different firing responses in calyx afferents. PMID:25343781

Zonal variations in K+ currents in vestibular crista calyx terminals.

PubMed

Meredith, Frances L; Rennie, Katherine J

2015-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na(+) but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K(+) currents were observed at potentials above -60 mV. K(+) currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K(+) channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K(+) channel blocker 4-aminopyridine (10-50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K(+) conductances may contribute to different firing responses in calyx afferents. Copyright © 2015 the American Physiological Society.

The Fibroblast Growth Factor 14·Voltage-gated Sodium Channel Complex Is a New Target of Glycogen Synthase Kinase 3 (GSK3)*

PubMed Central

Shavkunov, Alexander S.; Wildburger, Norelle C.; Nenov, Miroslav N.; James, Thomas F.; Buzhdygan, Tetyana P.; Panova-Elektronova, Neli I.; Green, Thomas A.; Veselenak, Ronald L.; Bourne, Nigel; Laezza, Fernanda

2013-01-01

The FGF14 protein controls biophysical properties and subcellular distribution of neuronal voltage-gated Na+ (Nav) channels through direct binding to the channel C terminus. To gain insights into the dynamic regulation of this protein/protein interaction complex, we employed the split luciferase complementation assay to screen a small molecule library of kinase inhibitors against the FGF14·Nav1.6 channel complex and identified inhibitors of GSK3 as hits. Through a combination of a luminescence-based counter-screening, co-immunoprecipitation, patch clamp electrophysiology, and quantitative confocal immunofluorescence, we demonstrate that inhibition of GSK3 reduces the assembly of the FGF14·Nav channel complex, modifies FGF14-dependent regulation of Na+ currents, and induces dissociation and subcellular redistribution of the native FGF14·Nav channel complex in hippocampal neurons. These results further emphasize the role of FGF14 as a critical component of the Nav channel macromolecular complex, providing evidence for a novel GSK3-dependent signaling pathway that might control excitability through specific protein/protein interactions. PMID:23640885

Effect of oscillator strength and intermediate resonance on the performance of resonant phonon-based terahertz quantum cascade lasers

NASA Astrophysics Data System (ADS)

Fathololoumi, S.; Dupont, E.; Wasilewski, Z. R.; Chan, C. W. I.; Razavipour, S. G.; Laframboise, S. R.; Huang, Shengxi; Hu, Q.; Ban, D.; Liu, H. C.

2013-03-01

We experimentally investigated the effect of oscillator strength (radiative transition diagonality) on the performance of resonant phonon-based terahertz quantum cascade lasers that have been optimized using a simplified density matrix formalism. Our results show that the maximum lasing temperature (Tmax) is roughly independent of laser transition diagonality within the lasing frequency range of the devices under test (3.2-3.7 THz) when cavity loss is kept low. Furthermore, the threshold current can be lowered by employing more diagonal transition designs, which can effectively suppress parasitic leakage caused by intermediate resonance between the injection and the downstream extraction levels. Nevertheless, the current carrying capacity through the designed lasing channel in more diagonal designs may sacrifice even more, leading to electrical instability and, potentially, complete inhibition of the device's lasing operation. We propose a hypothesis based on electric-field domain formation and competition/switching of different current-carrying channels to explain observed electrical instability in devices with lower oscillator strengths. The study indicates that not only should designers maximize Tmax during device optimization but also they should always consider the risk of electrical instability in device operation.

Inhibition of cardiac inward rectifier currents by cationic amphiphilic drugs.

PubMed

van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A

2013-09-01

Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.

One-channel Cell-attached Patch-clamp Recording

PubMed Central

Maki, Bruce A.; Cummings, Kirstie A.; Paganelli, Meaghan A.; Murthy, Swetha E.; Popescu, Gabriela K.

2014-01-01

Ion channel proteins are universal devices for fast communication across biological membranes. The temporal signature of the ionic flux they generate depends on properties intrinsic to each channel protein as well as the mechanism by which it is generated and controlled and represents an important area of current research. Information about the operational dynamics of ion channel proteins can be obtained by observing long stretches of current produced by a single molecule. Described here is a protocol for obtaining one-channel cell-attached patch-clamp current recordings for a ligand gated ion channel, the NMDA receptor, expressed heterologously in HEK293 cells or natively in cortical neurons. Also provided are instructions on how to adapt the method to other ion channels of interest by presenting the example of the mechano-sensitive channel PIEZO1. This method can provide data regarding the channel’s conductance properties and the temporal sequence of open-closed conformations that make up the channel’s activation mechanism, thus helping to understand their functions in health and disease. PMID:24961614

Currents through Hv1 channels deplete protons in their vicinity.

PubMed

De-la-Rosa, Víctor; Suárez-Delgado, Esteban; Rangel-Yescas, Gisela E; Islas, León D

2016-02-01

Proton channels have evolved to provide a pH regulatory mechanism, affording the extrusion of protons from the cytoplasm at all membrane potentials. Previous evidence has suggested that channel-mediated acid extrusion could significantly change the local concentration of protons in the vicinity of the channel. In this work, we directly measure the proton depletion caused by activation of Hv1 proton channels using patch-clamp fluorometry recordings from channels labeled with the Venus fluorescent protein at intracellular domains. The fluorescence of the Venus protein is very sensitive to pH, thus behaving as a genetically encoded sensor of local pH. Eliciting outward proton currents increases the fluorescence intensity of Venus. This dequenching is related to the magnitude of the current and not to channel gating and is dependent on the pH gradient. Our results provide direct evidence of local proton depletion caused by flux through the proton-selective channel. © 2016 De-la-Rosa et al.

Emerging role of the KCNT1 Slack channel in intellectual disability.

PubMed

Kim, Grace E; Kaczmarek, Leonard K

2014-01-01

The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed I KNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the fragile X mental retardation protein (FMRP) and I KNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal I KNa currents.

Statistics of Stacked Strata on Experimental Shelf Margins

NASA Astrophysics Data System (ADS)

Fernandes, A. M.; Straub, K. M.

2015-12-01

Continental margin deposits provide the most complete record on Earth of paleo-landscapes, but these records are complex and difficult to interpret. To a seismic geomorphologist or stratigrapher, mapped surfaces often present a static diachronous record of these landscapes through time. We present data that capture the dynamics of experimental shelf-margin landscapes at high-temporal resolution and define internal hierarchies within stacked channelized and weakly channelized deposits from the shelf to the slope. Motivated by observations from acoustically-imaged continental margins offshore Brunei and in the Gulf of Mexico, we use physical experiments to quantify stratal patterns of sub-aqueous slope channels and lobes that are linked to delta-top channels. The data presented here are from an experiment that was run for 26 hours of experimental run time. Overhead photographs and topographic scans captured flow dynamics and surface aggradation/degradation every ten minutes. Currents rich in sediment built a delta that prograded to the shelf-edge. These currents were designed to plunge at the shoreline and travel as turbidity currents beyond the delta and onto the continental slope. Pseudo-subsidence was imposed by a slight base-level rise that generated accommodation space and promoted the construction of stratigraphy on the delta-top. Compensational stacking is a term that is frequently applied to deposits that tend to fill in topographic lows in channelized and weakly channelized systems. The compensation index, a metric used to quantify the strength of compensation, is used here to characterize deposits at different temporal scales on the experimental landscape. The compensation timescale is the characteristic time at which the accumulated deposits begins to match the shape of basin-wide subsidence rates (uniform for these experiments). We will use the compensation indices along strike transects across the delta, proximal slope and distal slope to evaluate the degree of compensation and the trends in the compensation time-scale, tied to a reduced degree of channelization in the down-slope direction.

Functional properties of internalization-deficient P2X4 receptors reveal a novel mechanism of ligand-gated channel facilitation by ivermectin.

PubMed

Toulmé, Estelle; Soto, Florentina; Garret, Maurice; Boué-Grabot, Eric

2006-02-01

Although P2X receptors within the central nervous system mediate excitatory ATP synaptic transmission, the identity of central ATP-gated channels has not yet been elucidated. P2X(4), the most widely expressed subunit in the brain, was previously shown to undergo clathrin-dependent constitutive internalization by direct interaction between activator protein (AP)2 adaptors and a tyrosine-based sorting signal specifically present in the cytosolic C-terminal tail of mammalian P2X(4) sequences. In this study, we first used internalization-deficient P2X(4) receptor mutants to show that suppression of the endocytosis motif significantly increased the apparent sensitivity to ATP and the ionic permeability of P2X(4) channels. These unique properties, observed at low channel density, suggest that interactions with AP2 complexes may modulate the function of P2X(4) receptors. In addition, ivermectin, an allosteric modulator of several receptor channels, including mammalian P2X(4), did not potentiate the maximal current of internalization-deficient rat or human P2X(4) receptors. We demonstrated that binding of ivermectin onto wild-type P2X(4) channels increased the fraction of plasma membrane P2X(4) receptors, whereas surface expression of internalization-deficient P2X(4) receptors remained unchanged. Disruption of the clathrin-mediated endocytosis with the dominant-negative mutants Eps15 or AP-50 abolished the ivermectin potentiation of wild-type P2X(4) channel currents. Likewise, ivermectin increased the membrane fraction of nicotinic alpha7 acetylcholine (nalpha7ACh) receptors and the potentiation of acetylcholine current by ivermectin was suppressed when the same dominant-negative mutants were expressed. These data showed that potentiation by ivermectin of both P2X(4) and nalpha7ACh receptors was primarily caused by an increase in the number of cell surface receptors resulting from a mechanism dependent on clathrin/AP2-mediated endocytosis.

Simulation model for electron irradiated IGZO thin film transistors

NASA Astrophysics Data System (ADS)

Dayananda, G. K.; Shantharama Rai, C.; Jayarama, A.; Kim, Hyun Jae

2018-02-01

An efficient drain current simulation model for the electron irradiation effect on the electrical parameters of amorphous In-Ga-Zn-O (IGZO) thin-film transistors is developed. The model is developed based on the specifications such as gate capacitance, channel length, channel width, flat band voltage etc. Electrical parameters of un-irradiated IGZO samples were simulated and compared with the experimental parameters and 1 kGy electron irradiated parameters. The effect of electron irradiation on the IGZO sample was analysed by developing a mathematical model.

[Dependence of the concentration of the demi-maximal action of a channel blocker on the agonist concentration].

PubMed

Skorinkin, A I; Valeev, N V; Shaĭkhutdinova, A R

2005-01-01

Based on the analysis of kinetic scheme of blocking of open channels at any number of blocker binding sites, the dependence of current on blocker concentration was found. A variant of this dependence for a trapping blocker was also found. The restrictions of the applicability of the Hill equation and the necessity of taking into account the dependence of the concentration of demi-maximal blocker action (IC50) on the concentration of agonist were shown.

Giga-seal formation alters properties of sodium channels of human myoballs.

PubMed

Fahlke, C; Rüdel, R

1992-03-01

The influence of giga-seal formation on the properties of the Na+ channels within the covered membrane patch was investigated with a whole-cell pipette and a patch pipette applied to the same cell. Current kinetics, current/voltage relation and channel densities were determined in three combinations: (i) voltage-clamping and current recording with the whole-cell pipette, (ii) voltage-clamping with the whole-cell pipette and current recording with the patch pipette and, (iii) voltage-clamping and current recording with the patch pipette. The Hodgkin-Huxley (1952) parameters tau m and tau h were smaller for the patch currents than for the whole cell, and the h infinity curve was shifted in the negative direction. The channel density was of the order of 10 times smaller. All effects were independent of the extracellular Ca2+ concentration. The capacitive current generated in the patch by the whole-cell Na+ current and its effect on the transmembrane voltage of the patch were evaluated. The kinetic parameters of the Na+ channels in the patch did not depend on whether the voltage was clamped with the whole-cell pipette or the patch pipette. Thus, the results are not due to spurious voltage.

Impact of uniform electrode current distribution on ETF. [Engineering Test Facility MHD generator

NASA Technical Reports Server (NTRS)

Bents, D. J.

1982-01-01

A basic reason for the complexity and sheer volume of electrode consolidation hardware in the MHD ETF Powertrain system is the channel electrode current distribution, which is non-uniform. If the channel design is altered to provide uniform electrode current distribution, the amount of hardware required decreases considerably, but at the possible expense of degraded channel performance. This paper explains the design impacts on the ETF electrode consolidation network associated with uniform channel electrode current distribution, and presents the alternate consolidation designs which occur. They are compared to the baseline (non-uniform current) design with respect to performance, and hardware requirements. A rational basis is presented for comparing the requirements for the different designs and the savings that result from uniform current distribution. Performance and cost impacts upon the combined cycle plant are discussed.

Translocation of double strand DNA into a biological nanopore

NASA Astrophysics Data System (ADS)

Chatkaew, Sunita; Mlayeh, Lamia; Leonetti, Marc; Homble, Fabrice

2009-03-01

Translocation of double strand DNA across a unique mitochondrial biological nanopore (VDAC) is observed by an electrophysiological method. Characteristics of opened and sub-conductance states of VDAC are studied. When the applied electric potential is beyond ± 20 mV, VDAC transits to a sub-conductance state. Plasmids (circular double strand DNA) with a diameter greater than that of the channel shows the current reduction into the channel during the interaction but the state with zero-current is not observed. On the contrary, the interaction of linear double strand DNA with the channel shows the current reduction along with the zero-current state. These show the passages of linear double strand DNA across the channel and the electrostatic effect due to the surface charges of double strand DNA and channel for circular and linear double strand DNA.

The Current Collapse in AlGaN/GaN High-Electron Mobility Transistors Can Originate from the Energy Relaxation of Channel Electrons?

PubMed Central

Mao, Ling-Feng; Ning, Huan-Sheng; Wang, Jin-Yan

2015-01-01

Influence of the energy relaxation of the channel electrons on the performance of AlGaN/GaN high-electron mobility transistors (HEMTs) has been investigated using self-consistent solution to the coupled Schrödinger equation and Poisson equation. The first quantized energy level in the inversion layer rises and the average channel electron density decreases when the channel electric field increases from 20 kV/cm to 120 kV/cm. This research also demonstrates that the energy relaxation of the channel electrons can lead to current collapse and suggests that the energy relaxation should be considered in modeling the performance of AlGaN/GaN HEMTs such as, the gate leakage current, threshold voltage, source-drain current, capacitance-voltage curve, etc. PMID:26039589

The Current Collapse in AlGaN/GaN High-Electron Mobility Transistors Can Originate from the Energy Relaxation of Channel Electrons?

PubMed

Mao, Ling-Feng; Ning, Huan-Sheng; Wang, Jin-Yan

2015-01-01

Influence of the energy relaxation of the channel electrons on the performance of AlGaN/GaN high-electron mobility transistors (HEMTs) has been investigated using self-consistent solution to the coupled Schrödinger equation and Poisson equation. The first quantized energy level in the inversion layer rises and the average channel electron density decreases when the channel electric field increases from 20 kV/cm to 120 kV/cm. This research also demonstrates that the energy relaxation of the channel electrons can lead to current collapse and suggests that the energy relaxation should be considered in modeling the performance of AlGaN/GaN HEMTs such as, the gate leakage current, threshold voltage, source-drain current, capacitance-voltage curve, etc.

Single Pore Translocation of Folded, Double-Stranded, and Tetra-stranded DNA through Channel of Bacteriophage Phi29 DNA Packaging Motor

PubMed Central

Haque, Farzin; Wang, Shaoying; Stites, Chris; Chen, Li; Wang, Chi; Guo, Peixuan

2015-01-01

The elegant architecture of the channel of bacteriophage phi29 DNA packaging motor has inspired the development of biomimetics for biophysical and nanobiomedical applications. The reengineered channel inserted into a lipid membrane exhibits robust electrophysiological properties ideal for precise sensing and fingerprinting of dsDNA at the single-molecule level. Herein, we used single channel conduction assays to quantitatively evaluate the translocation dynamics of dsDNA as a function of the length and conformation of dsDNA. We extracted the speed of dsDNA translocation from the dwell time distribution and estimated the various forces involved in the translocation process. A ~35-fold slower speed of translocation per base pair was observed for long dsDNA, a significant contrast to the speed of dsDNA crossing synthetic pores. It was found that the channel could translocate both dsDNA with ~32% of channel current blockage and ~64% for tetra-stranded DNA (two parallel dsDNA). The calculation of both cross-sectional areas of the dsDNA and tetra-stranded DNA suggested that the blockage was purely proportional to the physical space of the channel lumen and the size of the DNA substrate. Folded dsDNA configuration was clearly reflected in their characteristic current signatures. The finding of translocation of tetra-stranded DNA with 64% blockage is in consent with the recently elucidated mechanism of viral DNA packaging via a revolution mode that requires a channel larger than the dsDNA diameter of 2 nm to provide room for viral DNA revolving without rotation. The understanding of the dynamics of dsDNA translocation in the phi29 system will enable us to design more sophisticated single pore DNA translocation devices for future applications in nanotechnology and personal medicine. PMID:25890769

Analysis on RF parameters of nanoscale tunneling field-effect transistor based on InAs/InGaAs/InP heterojunctions.

PubMed

Woo, Sung Yun; Yoon, Young Jun; Cho, Seongjae; Lee, Jung-Hee; Kang, In Man

2013-12-01

Tunneling field-effect transistors (TFETs) based on the quantum mechanical band-to-band tunneling (BTBT) have advantages such as low off-current and subthreshold swing (S) below 60 mV/dec at room temperature. For these reasons, TFETs are considered as promising devices for low standby power (LSTP) applications. On the other hand, silicon (Si)-based TFETs have a drawback in low on-state current (lon) drivability. In this work, we suggest a gate-all-around (GAA) TFET based on compound semiconductors to improve device performances. The proposed device materials consist of InAs (source), InGaAs (channel), and InP (drain). According to the composition (x) of Ga in In1-xGa(x)As layer of the channel region, simulated devices have been investigated in terms of both direct-current (DC) and RF parameters including tunneling rate, transconductance (g(m)), gate capacitance (Cg), intrinsic delay time (tau), cut-off frequency (fT) and maximum oscillation frequency (f(max)). In this study, the obtained maximum values of tau, fT, and f(max) for GAA InAs/In0.9Ga0.1As/InP heterojunction TFET were 21.2 fs, 7 THz, and 18 THz, respectively.

Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

PubMed

Shin, Hyewon; Song, Jin-Ho

2014-09-05

Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumour mast cell line.

PubMed

Wischmeyer, E; Lentes, K U; Karschin, A

1995-04-01

The basophilic leucaemia cell line RBL-2H3 exhibits a robust inwardly rectifying potassium current, IKIR, which is likely to be modulated by G proteins. We examined the physiological and molecular properties of this KIR conductance to define the nature of the underlying channel species. The macroscopic conductance revealed characteristics typical of classical K+ inward rectifiers of the IRK type. Channel gating was rapid, first order (tau approximately 1 ms at -100 mV) and steeply voltage dependent. Both activation potential and slope conductance were dependent on extracellular K+ concentration ([K+]o) and inward rectification persisted in the absence of internal Mg2+. The current was susceptible to a concentration- and voltage-dependent block by extracellular Na+, Cs+ and Ba2+. Initial IKIR whole-cell amplitudes as well as current rundown were dependent on the presence of 1 mM internal ATP. Perfusion of intracellular guanosine 5'-Q-(3-thiotriphosphate) (GTP[gamma S]) suppressed IKIR with an average half-time of decline of approximately 400 s. It was demonstrated that the dominant IRK-type 25 pS conductance channel was indeed suppressed by 100 microM preloaded GTP[gamma S]. Reverse transcriptase-polymerase chain reactions (RT-PCR) with RBL cell poly(A)+ RNA identified a full length K+ inward rectifier with 94% base pair homology to the recently cloned mouse IRK1 channel. It is concluded that RBL cells express a classical voltage-dependent IRK-type K+ inward rectifier RBL-IRK1 which is negatively controlled by G proteins.

The operation principle of the well in quantum dot stack infrared photodetector

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

Lee, Jheng-Han; Wu, Zong-Ming; Liao, Yu-Min

2013-12-28

The well in the quantum dot stack infrared photodetector (WD-QDIP) is proposed which can be operated at high temperature ∼230 K. The operation principle of this device is investigated, including the carrier transport and the enhancement in the photocurrent. The WD-QDIPs with different well numbers are fabricated to study the mechanisms. It is realized that the carrier transport from the emitter to the collector in traditional quantum dot infrared photodetectors consists of two channels deduced from current-voltage characteristics and dark current activation energy at different temperatures. At temperatures below 77 K, the current transports through the InAs quantum dot channel, whereas atmore » temperatures higher than 77 K, the current is dominated by the GaAs leakage channel. In addition, the non-equilibrium situation at low temperatures is also observed owing to the presence of photovoltaic phenomenon. The carrier distribution inside the QDs is simulated to investigate the reasons for the increase of photocurrent. Based on the simulation and the photocurrent response, the hot carrier (electron) scattering effect by the insertion of a quantum well layer is inferred as the most probable reason that lead to the enhancement of the response and regarded as the key factor to achieve high- temperature operation.« less

Electrical transport and low-frequency noise in chemical vapor deposited single-layer MoS2 devices.

PubMed

Sharma, Deepak; Amani, Matin; Motayed, Abhishek; Shah, Pankaj B; Birdwell, A Glen; Najmaei, Sina; Ajayan, Pulickel M; Lou, Jun; Dubey, Madan; Li, Qiliang; Davydov, Albert V

2014-04-18

We have studied temperature-dependent (77-300 K) electrical characteristics and low-frequency noise (LFN) in chemical vapor deposited (CVD) single-layer molybdenum disulfide (MoS2) based back-gated field-effect transistors (FETs). Electrical characterization and LFN measurements were conducted on MoS2 FETs with Al2O3 top-surface passivation. We also studied the effect of top-surface passivation etching on the electrical characteristics of the device. Significant decrease in channel current and transconductance was observed in these devices after the Al2O3 passivation etching. For passivated devices, the two-terminal resistance variation with temperature showed a good fit to the activation energy model, whereas for the etched devices the trend indicated a hopping transport mechanism. A significant increase in the normalized drain current noise power spectral density (PSD) was observed after the etching of the top passivation layer. The observed channel current noise was explained using a standard unified model incorporating carrier number fluctuation and correlated surface mobility fluctuation mechanisms. Detailed analysis of the gate-referred noise voltage PSD indicated the presence of different trapping states in passivated devices when compared to the etched devices. Etched devices showed weak temperature dependence of the channel current noise, whereas passivated devices exhibited near-linear temperature dependence.

New technologies for HWIL testing of WFOV, large-format FPA sensor systems

NASA Astrophysics Data System (ADS)

Fink, Christopher

2016-05-01

Advancements in FPA density and associated wide-field-of-view infrared sensors (>=4000x4000 detectors) have outpaced the current-art HWIL technology. Whether testing in optical projection or digital signal injection modes, current-art technologies for infrared scene projection, digital injection interfaces, and scene generation systems simply lack the required resolution and bandwidth. For example, the L3 Cincinnati Electronics ultra-high resolution MWIR Camera deployed in some UAV reconnaissance systems features 16MP resolution at 60Hz, while the current upper limit of IR emitter arrays is ~1MP, and single-channel dual-link DVI throughput of COTs graphics cards is limited to 2560x1580 pixels at 60Hz. Moreover, there are significant challenges in real-time, closed-loop, physics-based IR scene generation for large format FPAs, including the size and spatial detail required for very large area terrains, and multi - channel low-latency synchronization to achieve the required bandwidth. In this paper, the author's team presents some of their ongoing research and technical approaches toward HWIL testing of large-format FPAs with wide-FOV optics. One approach presented is a hybrid projection/injection design, where digital signal injection is used to augment the resolution of current-art IRSPs, utilizing a multi-channel, high-fidelity physics-based IR scene simulator in conjunction with a novel image composition hardware unit, to allow projection in the foveal region of the sensor, while non-foveal regions of the sensor array are simultaneously stimulated via direct injection into the post-detector electronics.

Estimates of the location of L-type Ca2+ channels in motoneurons of different sizes: a computational study.

PubMed

Grande, Giovanbattista; Bui, Tuan V; Rose, P Ken

2007-06-01

In the presence of monoamines, L-type Ca(2+) channels on the dendrites of motoneurons contribute to persistent inward currents (PICs) that can amplify synaptic inputs two- to sixfold. However, the exact location of the L-type Ca(2+) channels is controversial, and the importance of the location as a means of regulating the input-output properties of motoneurons is unknown. In this study, we used a computational strategy developed previously to estimate the dendritic location of the L-type Ca(2+) channels and test the hypothesis that the location of L-type Ca(2+) channels varies as a function of motoneuron size. Compartmental models were constructed based on dendritic trees of five motoneurons that ranged in size from small to large. These models were constrained by known differences in PIC activation reported for low- and high-conductance motoneurons and the relationship between somatic PIC threshold and the presence or absence of tonic excitatory or inhibitory synaptic activity. Our simulations suggest that L-type Ca(2+) channels are concentrated in hotspots whose distance from the soma increases with the size of the dendritic tree. Moving the hotspots away from these sites (e.g., using the hotspot locations from large motoneurons on intermediate-sized motoneurons) fails to replicate the shifts in PIC threshold that occur experimentally during tonic excitatory or inhibitory synaptic activity. In models equipped with a size-dependent distribution of L-type Ca(2+) channels, the amplification of synaptic current by PICs depends on motoneuron size and the location of the synaptic input on the dendritic tree.

Pharmacological Targeting Of Neuronal Kv7.2/3 Channels: A Focus On Chemotypes And Receptor Sites.

PubMed

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; Manocchio, Laura; Medoro, Alessandro; Mosca, Ilaria; Taglialatela, Maurizio

2017-10-12

The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing a characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for development of new drugs for neuronal, cardiac and metabolic diseases. In the present manuscript, we focus on describing the pharmacological relevance and the potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different modulator chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and we express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ion channel mechanisms underlying frequency-firing patterns of the avian nucleus magnocellularis: A computational model

PubMed Central

Lu, Ting; Wade, Kirstie; Sanchez, Jason Tait

2017-01-01

ABSTRACT We have previously shown that late-developing avian nucleus magnocellularis (NM) neurons (embryonic [E] days 19–21) fire action potentials (APs) that resembles a band-pass filter in response to sinusoidal current injections of varying frequencies. NM neurons located in the mid- to high-frequency regions of the nucleus fire preferentially at 75 Hz, but only fire a single onset AP to frequency inputs greater than 200 Hz. Surprisingly, NM neurons do not fire APs to sinusoidal inputs less than 20 Hz regardless of the strength of the current injection. In the present study we evaluated intrinsic mechanisms that prevent AP generation to low frequency inputs. We constructed a computational model to simulate the frequency-firing patterns of NM neurons based on experimental data at both room and near physiologic temperatures. The results from our model confirm that the interaction among low- and high-voltage activated potassium channels (KLVA and KHVA, respectively) and voltage dependent sodium channels (NaV) give rise to the frequency-firing patterns observed in vitro. In particular, we evaluated the regulatory role of KLVA during low frequency sinusoidal stimulation. The model shows that, in response to low frequency stimuli, activation of large KLVA current counterbalances the slow-depolarizing current injection, likely permitting NaV closed-state inactivation and preventing the generation of APs. When the KLVA current density was reduced, the model neuron fired multiple APs per sinusoidal cycle, indicating that KLVA channels regulate low frequency AP firing of NM neurons. This intrinsic property of NM neurons may assist in optimizing response to different rates of synaptic inputs. PMID:28481659

Electrical characterization of single cells using polysilicon wire ion sensor in an isolation window.

PubMed

Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Wang, Chih-Cheng; Lee, Li-Wen; Lin, Jing-Jenn

2011-10-01

A polysilicon wire (PSW) sensor can detect the H(+) ion density (pH value) of the medium coated on its surface, and different cells produce different extracellular acidification and hence different H(+) ion densities. Based on this, we used a PSW sensor in combination with a mold-cast polydimethylsiloxane (PDMS) isolation window to detect the adhesion, apoptosis and extracellular acidification of single normal cells and single cancer cells. Single living human normal cells WI38, MRC5, and BEAS-2B as well as non-small-cell lung cancer (NSCLC) cells A549, H1299, and CH27 were cultivated separately inside the isolation window. The current flowing through the PSW channel was measured. From the PSW channel current change as a function of time, we determined the cell adhesion time by observing the time required for the current change to saturate, since a stable extracellular ion density was established after the cells were completely adhered to the PSW surface. The apoptosis of cells can also be determined when the channel current change drops to zero. We found that all the NSCLC cells had a higher channel current change and hence a lower pH value than the normal cells anytime after they were seeded. The corresponding average pH values were 5.86 for A549, 6.00 for H1299, 6.20 for CH27, 6.90 for BEAS-2B, 6.96for MRC5, and 7.02 for WI38, respectively, after the cells were completely adhered to the PSW surface. Our results show that NSCLC cells have a stronger cell-substrate adhesion and a higher extracellular acidification rate than normal cells.

Comparison of sarcolemmal calcium channel current in rabbit and rat ventricular myocytes.

PubMed Central

Yuan, W; Ginsburg, K S; Bers, D M

1996-01-01

1. Fundamental properties of Ca2+ channel currents in rat and rabbit ventricular myocytes were measured using whole cell voltage clamp. 2. In rat, as compared with rabbit myocytes, Ca2+ channel current (ICa) was half-activated at about 10 mV more negative potential, decayed slower, was half-inactivated (in steady state) at about 5 mV more positive potential, and recovered faster from inactivation. 3. These features result in a larger steady-state window current in rat, and also suggest that under comparable voltage clamp conditions, including action potential (AP) clamp, more Ca2+ influx would be expected in rat myocytes. 4. Ca2+ channel current carried by Na+ and Cs+ in the absence of divalent ions (Ins) also activated at more negative potential and decayed more slowly in rat. 5. The reversal potential for Ins was 6 mV more positive in rabbit, consistent with a larger permeability ratio (PNa/PCs) in rabbit than in rat. ICa also reversed at slightly more positive potentials in rabbit (such that PCa/PCs might also be higher). 6. Ca2+ influx was calculated by integration of ICa evoked by voltage clamp pulses (either square pulses or pulses based on recorded rabbit or rat APs). For a given clamp waveform, the Ca2+ influx was up to 25% greater in rat, as predicted from the fundamental properties of ICa and Ins. 7. However, the longer duration of the AP in rabbit myocytes compensated for the difference in influx, such that the integrated Ca2+ influx via ICa in response to the species-appropriate waveform was about twice as large as that seen in rat. PMID:8799895

Low Noise Amplifiers Based on Lattice Engineered Substrates

DTIC Science & Technology

2004-11-01

the base contacts. To overcome this deficiency, a current aperture must be adopted in the emitter to properly channel the carriers. Appendix V is a...Appendix V "Design and Fabrication of Collector-up Heterojunction BipolarTransistors with Oxide Confined Current Apertures," James G. Champlain and Umesh K...a consequence of the [110] elimination of steps which were produced during plastic re- o, .A,,A A A A’YAL , V IA VP ’ \\P4 laxation of the misfit strain

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.

Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons.

PubMed

Amarillo, Yimy; De Santiago-Castillo, Jose A; Dougherty, Kevin; Maffie, Jonathon; Kwon, Elaine; Covarrubias, Manuel; Rudy, Bernardo

2008-04-15

Kv4 channels mediate most of the somatodendritic subthreshold operating A-type current (I(SA)) in neurons. This current plays essential roles in the regulation of spike timing, repetitive firing, dendritic integration and plasticity. Neuronal Kv4 channels are thought to be ternary complexes of Kv4 pore-forming subunits and two types of accessory proteins, Kv channel interacting proteins (KChIPs) and the dipeptidyl-peptidase-like proteins (DPPLs) DPPX (DPP6) and DPP10. In heterologous cells, ternary Kv4 channels exhibit inactivation that slows down with increasing depolarization. Here, we compared the voltage dependence of the inactivation rate of channels expressed in heterologous mammalian cells by Kv4.2 proteins with that of channels containing Kv4.2 and KChIP1, Kv4.2 and DPPX-S, or Kv4.2, KChIP1 and DPPX-S, and found that the relation between inactivation rate and membrane potential is distinct for these four conditions. Moreover, recordings from native neurons showed that the inactivation kinetics of the I(SA) in cerebellar granule neurons has voltage dependence that is remarkably similar to that of ternary Kv4 channels containing KChIP1 and DPPX-S proteins in heterologous cells. The fact that this complex and unique behaviour (among A-type K(+) currents) is observed in both the native current and the current expressed in heterologous cells by the ternary complex containing Kv4, DPPX and KChIP proteins supports the hypothesis that somatically recorded native Kv4 channels in neurons include both types of accessory protein. Furthermore, quantitative global kinetic modelling showed that preferential closed-state inactivation and a weakly voltage-dependent opening step can explain the slowing of the inactivation rate with increasing depolarization. Therefore, it is likely that preferential closed-state inactivation is the physiological mechanism that regulates the activity of both ternary Kv4 channel complexes and native I(SA)-mediating channels.

Ca2+ current vs. Ca2+ channel cooperativity of exocytosis

PubMed Central

Matveev, Victor; Bertram, Richard; Sherman, Arthur

2009-01-01

Recently there has been significant interest and progress in the study of spatio-temporal dynamics of Ca2+ that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca2+ influx. While varying extracellular or intracellular Ca2+ concentration assesses the intrinsic biochemical Ca2+ cooperativity of neurotransmitter release, varying the number of open Ca2+ channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca2+ channels in triggering exocytosis. Despite the wide use of these Ca2+ sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca2+ sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca2+ current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca2+ current magnitude, and the underlying Ca2+ channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use 3D computational modeling of buffered Ca2+ diffusion to analyze these distinct Ca2+ cooperativity measures, and demonstrate the role of endogenous Ca2+ buffers on such measures. We show that buffers can either increase or decrease the Ca2+ current cooperativity of exocytosis, depending on their concentration and the single-channel Ca2+ current. PMID:19793978

A Predictive Model for Submarine Canyon Type Based on the Relative Influence of Rivers, Waves and Tides.

NASA Astrophysics Data System (ADS)

Sumner, E.; Paull, C. K.

2017-12-01

In recent years progress has been achieved in directly measuring turbidity currents in submarine canyons and channels. It is useful to consider how representative these observations are of the diversity that potentially exists in the dynamics of turbidity currents among different canyons and channels. Firstly, we integrate sediment core, bathymetric and (in a limited number of cases) direct observations of turbidity current dynamics from 20 submarine canyons on the northern California Margin. We use this dataset to construct a diagram that explains canyon type, and thus turbidity current characteristics (grain-size carried, flow power, relative frequency of flows), based on the relative influence of rivers, waves and tides at the canyon head. This diagram enables prediction of canyon type and thus processes using three easily measurable characteristics: (i) distance of the canyon head from the shoreline; (ii) distance of the canyon head from the nearest river mouth; and (iii) local shelf width. Secondly, we test and refine the diagram using published data on submarine canyons from around the world. We also discuss the influence of outsized events such as earthquakes on submarine canyons. Finally, we demonstrate the location within the diagram of current monitoring studies and thus suggest where it might be fruitful to focus future monitoring efforts.

In vivo voltammetry: from wire to wireless measurements.

PubMed

Crespi, Francesco; Dalessandro, Davide; Annovazzi-Lodi, Valerio; Heidbreder, Christian; Norgia, Michele

2004-12-30

A novel telemetric system based on either differential pulse voltammetry (DPV) or direct current amperometry (DCA) by using a diffused infrared transmission channel is presented. Unlike similar pre-existing instruments based on infrared transmission, the present system works on a single-way communication, thus avoiding problems related to cross-talking between two-way channels. The infrared channel is also immune from electromagnetic interferences from the surrounding environment. Further advancement is the development of an original miniaturised system (dimension 1cm x 1.2 cm x 0.5 cm) with reduced weight (5-6 g), suitable for affixing to the rat head and allowing real time telemetric monitoring using DCA sampling of neurotransmitters such as dopamine or serotonin every 100 ms. The set-up is based on a transmitter (TX) circuit mounted on the animal's head and connected to the electrodes inserted into its brain. The TX circuit generates the proper electrical signals for DPV or DCA, collects the electrical response of the brain and transmits it, via an infrared channel, to a receiving station (RX) interfaced with a personal computer. The PC performs the sampling and elaboration of polarographic traces in a flexible and programmable way.

Nonselective Currents and Channels in Plasma Membranes of Protoplasts from Coats of Developing Seeds of Bean1

PubMed Central

Zhang, Wen-Hao; Skerrett, Martha; Walker, N. Alan; Patrick, John W.; Tyerman, Stephen D.

2002-01-01

In developing bean (Phaseolus vulgaris) seeds, phloem-imported nutrients move in the symplast from sieve elements to the ground parenchyma cells where they are transported across the plasma membrane into the seed apoplast. To study the mechanisms underlying this transport, channel currents in ground parenchyma protoplasts were characterized using patch clamp. A fast-activating outward current was found in all protoplasts, whereas a slowly activating outward current was observed in approximately 25% of protoplasts. The two currents had low selectivity for univalent cations, but the slow current was more selective for K+ over Cl− (PK:PCl = 3.6–4.2) than the fast current (PK:PCl = 1.8–2.5) and also displayed Ca2+ selectivity. The slow current was blocked by Ba2+, whereas both currents were blocked by Gd3+ and La3+. Efflux of K+ from seed coat halves was inhibited 25% by Gd3+ and La3+ but was stimulated by Ba2+ and Cs+, suggesting that only the fast current may be a component in the pathway for K+ release. An “instantaneous” inward current observed in all protoplasts exhibited similar pharmacology and permeability for univalent cations to the fast outward current. In outside-out patches, two classes of depolarization-activated cation-selective channels were observed: one slowly activating of low conductance (determined from nonstationary noise to be 2.4 pS) and another with conductances 10-fold higher. Both channels occurred at high density. The higher conductance channel in 10 mm KCl had PK:PCl = 2.8. Such nonselective channels in the seed coat ground parenchyma cell could function to allow some of the efflux of phloem-imported univalent ions into the seed apoplast. PMID:11842143

Functional reconstitution of the voltage-regulated sodium channel purified from electroplax of Electrophorus electricus

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

Rosenberg, R.L.

1985-01-01

The voltage-regulated NA channel is responsible for the depolarization of the excitable cell membrane during the normal action potential. This research has focused on the functional properties of the Na channel, purified from detergent extracts of electroplax membranes of the electric eel, and reconstituted into vesicles of defined phospholipid. These properties were assessed by measuring neurotoxin-modulated ion flux into the reconstituted membrane vesicles and by recording the single-channel currents of the purified channel by the patch-clamp method. The binding of tritiated tetrodotoxin (TTX) was employed as a marker for the purification of the channel. Two high-resolution fractionation steps, based onmore » molecular charge and protein size, were used to obtain a preparation that is 80% homogeneous for a large peptide of 270,000 daltons. Radiotracer /sup 22/Na/sup +/ influx into the vesicles was stimulated by veratridine and by batrachotoxin (BTX) at concentrations of 100 ..mu..M and 5 ..mu..M, respectively. The stimulation by BTX was greater than that by veratridine, and can be as much as 16-fold over control influx levels. The stimulated influx is blocked by TTX with a K/sub i/ of 35 nM, and by local anesthetics in the normal pharmacological range. Large multilamellar vesicles prepared with a freeze-thaw step are suitable for single-channel recording techniques. When excised patches of the reconstituted membranes were voltage-clamped in the absence of activating neurotoxins, voltage-dependent single-channel currents were recorded. These displayed properties similar to those from native membranes of nerve and muscle. These results indicate that the protein purified on the basis of TTX binding is a functional Na channel possessing these functional domains: the ion-selective channel, the voltage sensors controlling activation and inactivation, and the sites of action of TTX, alkaloid neurotoxins, and local anesthetics.« less

Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages.

PubMed

Gao, Ya-dong; Hanley, Peter J; Rinné, Susanne; Zuzarte, Marylou; Daut, Jurgen

2010-07-01

STIM1 'senses' decreases in endoplasmic reticular (ER) luminal Ca(2+) and induces store-operated Ca(2+) (SOC) entry through plasma membrane Orai channels. The Ca(2+)/calmodulin-activated K(+) channel K(Ca)3.1 (previously known as SK4) has been implicated as an 'amplifier' of the Ca(2+)-release activated Ca(2+) (CRAC) current, especially in T lymphocytes. We have previously shown that human macrophages express K(Ca)3.1, and here we used the whole-cell patch-clamp technique to investigate the activity of these channels during Ca(2+) store depletion and store-operated Ca(2+) influx. Using RT-PCR, we found that macrophages express the elementary CRAC channel components Orai1 and STIM1, as well as Orai2, Orai3 and STIM2, but not the putatively STIM1-activated channels TRPC1, TRPC3-7 or TRPV6. In whole-cell configuration, a robust Ca(2+)-induced outwardly rectifying K(+) current inhibited by clotrimazole and augmented by DC-EBIO could be detected, consistent with K(Ca)3.1 channel current (also known as intermediate-conductance IK1). Introduction of extracellular Ca(2+) following Ca(2+) store depletion via P2Y(2) receptors induced a robust charybdotoxin (CTX)- and 2-APB-sensitive outward K(+) current and hyperpolarization. We also found that SOC entry induced by thapsigargin treatment induced CTX-sensitive K(+) current in HEK293 cells transiently expressing K(Ca)3.1. Our data suggest that SOC and K(Ca)3.1 channels are tightly coupled, such that a small Ca(2+) influx current induces a much large K(Ca)3.1 channel current and hyperpolarization, providing the necessary electrochemical driving force for prolonged Ca(2+) signaling and store repletion. Copyright 2010 Elsevier Ltd. All rights reserved.

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

Correction of clipped pixels in color images.

PubMed

Xu, Di; Doutre, Colin; Nasiopoulos, Panos

2011-03-01

Conventional images store a very limited dynamic range of brightness. The true luma in the bright area of such images is often lost due to clipping. When clipping changes the R, G, B color ratios of a pixel, color distortion also occurs. In this paper, we propose an algorithm to enhance both the luma and chroma of the clipped pixels. Our method is based on the strong chroma spatial correlation between clipped pixels and their surrounding unclipped area. After identifying the clipped areas in the image, we partition the clipped areas into regions with similar chroma, and estimate the chroma of each clipped region based on the chroma of its surrounding unclipped region. We correct the clipped R, G, or B color channels based on the estimated chroma and the unclipped color channel(s) of the current pixel. The last step involves smoothing of the boundaries between regions of different clipping scenarios. Both objective and subjective experimental results show that our algorithm is very effective in restoring the color of clipped pixels. © 2011 IEEE

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.

Modulation of Kv4.2 channels by a peptide isolated from the venom of the giant bird-eating tarantula Theraphosa leblondi.

PubMed

Ebbinghaus, Jan; Legros, Christian; Nolting, Andreas; Guette, Catherine; Celerier, Marie-Louise; Pongs, Olaf; Bähring, Robert

2004-06-15

In order to find new peptide inhibitors for voltage-dependent potassium (Kv) channels, we examined the effects of venom from Theraphosa leblondi on Kv channel-mediated currents with the whole-cell patch-clamp technique. Both A-type currents in cultured hippocampal neurons and A-type currents recorded from HEK 293 cells transiently expressing recombinant Kv4.2 channels were selectively inhibited by T. leblondi venom. No venom activity was observed on recombinant Kv1.3, Kv1.4, Kv2.1 or Kv3.4 channels. We purified and sequenced three novel homologous peptides from this venom, which are related to previously identified Kv4 channel-specific peptide inhibitors and were named T. leblondi toxin (TLTx) 1, 2 and 3. The mode of action of TLTx1 on recombinant Kv4.2 channels was studied in more detail. TLTx1 inhibited Kv4.2-mediated currents with an IC50 of approximately 200 nM, and macroscopic current inactivation was slowed in the presence of TLTx1. Notably, TLTx1 also caused a shallower voltage dependence of Kv4.2 peak conductance and a shift of the activation midpoint to more positive potentials (DeltaV1/2 = +35 mV). TLTx1 caused a noticable slowing of Kv4.2 activation kinetics, and Kv4.2 deactivation kinetics were accelerated by TLTx1 as infered from Rb+ tail current measurements. Chimeric Kv2.1(4.2L3-4) channels, in which the linker region between S3 and S4 of the TLTx1-insensitive Kv2.1 channel was replaced by the corresponding Kv4.2 domain, were sensitive to TLTx1. Apparently, TLTx1 can act as a gating modifier of Kv4.2 channels. Copyright 2004 Elsevier Ltd.

Optimal feedback control of turbulent channel flow

NASA Technical Reports Server (NTRS)

Bewley, Thomas; Choi, Haecheon; Temam, Roger; Moin, Parviz

1993-01-01

Feedback control equations were developed and tested for computing wall normal control velocities to control turbulent flow in a channel with the objective of reducing drag. The technique used is the minimization of a 'cost functional' which is constructed to represent some balance of the drag integrated over the wall and the net control effort. A distribution of wall velocities is found which minimizes this cost functional some time shortly in the future based on current observations of the flow near the wall. Preliminary direct numerical simulations of the scheme applied to turbulent channel flow indicates it provides approximately 17 percent drag reduction. The mechanism apparent when the scheme is applied to a simplified flow situation is also discussed.

Single channel recording of a mitochondrial calcium uniporter.

PubMed

Wu, Guangyan; Li, Shunjin; Zong, Guangning; Liu, Xiaofen; Fei, Shuang; Shen, Linda; Guan, Xiangchen; Yang, Xue; Shen, Yuequan

2018-01-29

Mitochondrial calcium uniporter (MCU) is the pore-forming subunit of the entire uniporter complex and plays an important role in mitochondrial calcium uptake. However, the single channel recording of MCU remains controversial. Here, we expressed and purified different MCU proteins and then reconstituted them into planar lipid bilayers for single channel recording. We showed that MCU alone from Pyronema omphalodes (pMCU) is active with prominent single channel Ca 2+ currents. In sharp contrast, MCU alone from Homo sapiens (hMCU) is inactive. The essential MCU regulator (EMRE) activates hMCU, and therefore, the complex (hMCU-hEMRE) shows prominent single channel Ca 2+ currents. These single channel currents are sensitive to the specific MCU inhibitor Ruthenium Red. Our results clearly demonstrate that active MCU can conduct large amounts of calcium into the mitochondria. Copyright © 2018 Elsevier Inc. All rights reserved.

Interaction between permeation and gating in a putative pore domain mutant in the cystic fibrosis transmembrane conductance regulator.

PubMed Central

Zhang, Z R; McDonough, S I; McCarty, N A

2000-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel with distinctive kinetics. At the whole-cell level, CFTR currents in response to voltage steps are time independent for wild type and for the many mutants reported so far. Single channels open for periods lasting up to tens of seconds; the openings are interrupted by brief closures at hyperpolarized, but not depolarized, potentials. Here we report a serine-to-phenylalanine mutation (S1118F) in the 11th transmembrane domain that confers voltage-dependent, single-exponential current relaxations and moderate inward rectification of the macroscopic currents upon expression in Xenopus oocytes. At steady state, the S1118F-CFTR single-channel conductance rectifies, corresponding to the whole-cell rectification. In addition, the open-channel burst duration is decreased 10-fold compared with wild-type channels. S1118F-CFTR currents are blocked in a voltage-dependent manner by diphenylamine-2-carboxylate (DPC); the affinity of S1118F-CFTR for DPC is similar to that of the wild-type channel, but blockade exhibits moderately reduced voltage dependence. Selectivity of the channel to a range of anions is also affected by this mutation. Furthermore, the permeation properties change during the relaxations, which suggests that there is an interaction between gating and permeation in this mutant. The existence of a mutation that confers voltage dependence upon CFTR currents and that changes kinetics and permeation properties of the channel suggests a functional role for the 11th transmembrane domain in the pore in the wild-type channel. PMID:10866956

Chloride channel blockers activate an endogenous cationic current in oocytes of Bufo arenarum.

PubMed

Cavarra, M S; del Mónaco, S M; Kotsias, B A

2004-07-01

A two-electrode, voltage-clamp technique was used to measure the effect of the Cl(-) channel blockers, 9-anthracene carboxylic acid and niflumic acid, upon the ionic currents of oocytes of the South American toad Bufo arenarum. The main results were: (1) both blockers produced a reversible increase of the outward currents on a dose-dependent manner; (2) the activated outward current was voltage dependent; (3) the 9-anthracene carboxylic acid-sensitive current was blocked with barium; and (4) the effect of 9-anthracene carboxylic acid was more pronounced in a zero-K(+) solution than in standard (2 mmol l(-1)) or high (20 mmol l(-1)) K(+) solutions, indicating that a K(+) conductance is activated. The effect of the Cl(-) channel blockers could be due to a direct interaction with endogenous cationic channels. Another possible explanation is that Cl(-) that enter the cell during depolarizing steps in control solution inhibit this cationic conductance; thus, the blockade of Cl(-) channels by 9-anthracene carboxylic acid and niflumic acid would remove this inhibition, allowing the cationic current to flow freely.

Statistical variability study of random dopant fluctuation on gate-all-around inversion-mode silicon nanowire field-effect transistors

NASA Astrophysics Data System (ADS)

Yoon, Jun-Sik; Rim, Taiuk; Kim, Jungsik; Kim, Kihyun; Baek, Chang-Ki; Jeong, Yoon-Ha

2015-03-01

Random dopant fluctuation effects of gate-all-around inversion-mode silicon nanowire field-effect transistors (FETs) with different diameters and extension lengths are investigated. The nanowire FETs with smaller diameter and longer extension length reduce average values and variations of subthreshold swing and drain-induced barrier lowering, thus improving short channel immunity. Relative variations of the drain currents increase as the diameter decreases because of decreased current drivability from narrower channel cross-sections. Absolute variations of the drain currents decrease critically as the extension length increases due to decreasing the number of arsenic dopants penetrating into the channel region. To understand variability origins of the drain currents, variations of source/drain series resistance and low-field mobility are investigated. All these two parameters affect the variations of the drain currents concurrently. The nanowire FETs having extension lengths sufficient to prevent dopant penetration into the channel regions and maintaining relatively large cross-sections are suggested to achieve suitable short channel immunity and small variations of the drain currents.

High performance multi-finger MOSFET on SOI for RF amplifiers

NASA Astrophysics Data System (ADS)

Adhikari, M. Singh; Singh, Y.

2017-10-01

In this paper, we propose structural modifications in the conventional planar metal-oxide-semiconductor field-effect transistor (MOSFET) on silicon-on-insulator by utilizing trenches in the epitaxial layer. The proposed multi-finger MOSFET (MF-MOSFET) has dual vertical-gates placed in separate trenches to form multiple channels in the p-base which carry the drain current in parallel. The proposed device uses TaN as gate electrode and SiO2 as gate dielectric. Simultaneous conduction of multiple channels enhances the drain current (ID) and provides higher transconductance (gm) leading to significant improvement in cut-off frequency (ft). Two-dimensional simulations are performed to evaluate and compare the performance of the MF-MOSFET with the conventional MOSFET. At a gate length of 60 nm, the proposed device provides 4 times higher ID, 3 times improvement in gm and 1.25 times increase in ft with better control over the short channel effects as compared with the conventional device.

Nanowire size dependence on sensitivity of silicon nanowire field-effect transistor-based pH sensor

NASA Astrophysics Data System (ADS)

Lee, Ryoongbin; Kwon, Dae Woong; Kim, Sihyun; Kim, Sangwan; Mo, Hyun-Sun; Kim, Dae Hwan; Park, Byung-Gook

2017-12-01

In this study, we investigated the effects of nanowire size on the current sensitivity of silicon nanowire (SiNW) ion-sensitive field-effect transistors (ISFETs). The changes in on-current (I on) and resistance according to pH were measured in fabricated SiNW ISFETs of various lengths and widths. As a result, it was revealed that the sensitivity expressed as relative I on change improves as the width decreases. Through technology computer-aided design (TCAD) simulation analysis, the width dependence on the relative I on change can be explained by the observation that the target molecules located at the edge region along the channel width have a stronger effect on the sensitivity as the SiNW width is reduced. Additionally, the length dependence on the sensitivity can be understood in terms of the resistance ratio of the fixed parasitic resistance, including source/drain resistance, to the varying channel resistance as a function of channel length.

Cryptographic robustness of practical quantum cryptography: BB84 key distribution protocol

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

Molotkov, S. N.

2008-07-15

In real fiber-optic quantum cryptography systems, the avalanche photodiodes are not perfect, the source of quantum states is not a single-photon one, and the communication channel is lossy. For these reasons, key distribution is impossible under certain conditions for the system parameters. A simple analysis is performed to find relations between the parameters of real cryptography systems and the length of the quantum channel that guarantee secure quantum key distribution when the eavesdropper's capabilities are limited only by fundamental laws of quantum mechanics while the devices employed by the legitimate users are based on current technologies. Critical values are determinedmore » for the rate of secure real-time key generation that can be reached under the current technology level. Calculations show that the upper bound on channel length can be as high as 300 km for imperfect photodetectors (avalanche photodiodes) with present-day quantum efficiency ({eta} {approx} 20%) and dark count probability (p{sub dark} {approx} 10{sup -7})« less

On the applicability of the Natori formula to realistic multi-layer quantum well III-V FETs

NASA Astrophysics Data System (ADS)

Gili, A.; Xanthakis, J. P.

2017-10-01

We investigated the validity of the Natori formalism for realistic multi-layer quantum well FETs. We show that the assumption of a single layer (the channel) carrying all of the current density is far from reality in the sub-threshold region, where in fact most of the current density resides below the channel. Our analysis is based on comparing results of Natori calculations with experimental ones and on comparing with other first-principles calculations. If the Natori calculations are employed in the subthreshold region then a misleadingly small subthreshold slope would be obtained. We propose a way to remedy this inefficiency of this formulation so that it can be applicable to realistic many-layer devices. In particular we show that if the 1-dimensional quantum well of the Natori method enclosing the electron gas is expanded to include the supply layer-usually below the channel- and a proper ab initio potential is used to obtain its eigenvalues, then the Natori formula regains its validity.

Comprehensive analysis of sub-20 nm black phosphorus based junctionless-recessed channel MOSFET for analog/RF applications

NASA Astrophysics Data System (ADS)

Kumar, Ajay; Tripathi, M. M.; Chaujar, Rishu

2018-04-01

In this work, a comprehensive analog and RF performance of a novel Black Phosphorus-Junctionless-Recessed Channel (BP-JL-RC) MOSFET has been explored at 45 nm technology node (Gate length = 20 nm). The integration of black phosphorus with junctionless recessed channel MOSFET, leads to higher drain current of about 0.3 mA and excellent switching ratio (of the order of 1011) due to reduced off-current which leads to improvement in sub-threshold slope (SS) (67mV/dec). Further, RF performance metrics have also been studied with an aim to analyze high-frequency performance. The following FOMs have been evaluated: cut-off frequency (fT), maximum oscillator frequency (fMAX), stern stability factor, various power gains and parasitic capacitances at THz frequency range. Thus, in addition to the high packing density offered by RC MOSFET, the proposed design finds numerous application at THz frequency making it a promising candidate at wafer scale integration level.

The overview of channels, transporters, and calcium signaling molecules during amelogenesis.

PubMed

Kim, Hee-Eun; Hong, Jeong Hee

2018-05-20

Enamel is a highly calcified tissue. Its formation requires a progressive and dynamic system for the regulation of electrolyte concentration by enamel epithelia. A critical function of enamel epithelial cells, ameloblasts, is the secretion and movement of electrolytes via various channels and transporters to develop the enamel tissue. Enamel formation generates protons, which need to be neutralised. Thus, ameloblasts possess a buffering system to sustain mineral accretion. Normal tooth formation involves stage-dependent net fluctuations in pH during amelogenesis. To date, all of our information about ion transporters in dental enamel tissue is based solely on immunostaining-expression techniques. This review critically evaluates the current understanding and recent discoveries and physiological role of ion channels and transporters, Mg 2+ transporters, and Ca 2+ regulatory proteins during amelogenesis in enamel formation. The ways in which ameloblasts modulate ions are discussed in the context of current research for developing a novel morphologic-functional model of enamel maturation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cryptographic robustness of practical quantum cryptography: BB84 key distribution protocol

NASA Astrophysics Data System (ADS)

Molotkov, S. N.

2008-07-01

In real fiber-optic quantum cryptography systems, the avalanche photodiodes are not perfect, the source of quantum states is not a single-photon one, and the communication channel is lossy. For these reasons, key distribution is impossible under certain conditions for the system parameters. A simple analysis is performed to find relations between the parameters of real cryptography systems and the length of the quantum channel that guarantee secure quantum key distribution when the eavesdropper’s capabilities are limited only by fundamental laws of quantum mechanics while the devices employed by the legitimate users are based on current technologies. Critical values are determined for the rate of secure real-time key generation that can be reached under the current technology level. Calculations show that the upper bound on channel length can be as high as 300 km for imperfect photodetectors (avalanche photodiodes) with present-day quantum efficiency (η ≈ 20%) and dark count probability ( p dark ˜ 10-7).

Analysis of the role of the low threshold currents IT and Ih in intrinsic delta oscillations of thalamocortical neurons.

PubMed

Amarillo, Yimy; Mato, Germán; Nadal, Marcela S

2015-01-01

Thalamocortical neurons are involved in the generation and maintenance of brain rhythms associated with global functional states. The repetitive burst firing of TC neurons at delta frequencies (1-4 Hz) has been linked to the oscillations recorded during deep sleep and during episodes of absence seizures. To get insight into the biophysical properties that are the basis for intrinsic delta oscillations in these neurons, we performed a bifurcation analysis of a minimal conductance-based thalamocortical neuron model including only the IT channel and the sodium and potassium leak channels. This analysis unveils the dynamics of repetitive burst firing of TC neurons, and describes how the interplay between the amplifying variable mT and the recovering variable hT of the calcium channel IT is sufficient to generate low threshold oscillations in the delta band. We also explored the role of the hyperpolarization activated cationic current Ih in this reduced model and determine that, albeit not required, Ih amplifies and stabilizes the oscillation.

Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act

PubMed Central

Tucker, Kristal R.; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.

2012-01-01

Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (NaV) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density and gating of NaV currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment (AIS) and NaV channels are distributed in multiple dendrites, selective reduction of NaV channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic NaV current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when NaV currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold NaV current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic NaV channels. More generally, we conclude that the somatodendritic distribution of NaV channels is a major determinant of repetitive spiking frequency. PMID:23077037

Study on the influences of ionization region material arrangement on Hall thruster channel discharge characteristics

NASA Astrophysics Data System (ADS)

Xiang, HU; Ping, DUAN; Jilei, SONG; Wenqing, LI; Long, CHEN; Xingyu, BIAN

2018-02-01

There exists strong interaction between the plasma and channel wall in the Hall thruster, which greatly affects the discharge performance of the thruster. In this paper, a two-dimensional physical model is established based on the actual size of an Aton P70 Hall thruster discharge channel. The particle-in-cell simulation method is applied to study the influences of segmented low emissive graphite electrode biased with anode voltage on the discharge characteristics of the Hall thruster channel. The influences of segmented electrode placed at the ionization region on electric potential, ion number density, electron temperature, ionization rate, discharge current and specific impulse are discussed. The results show that, when segmented electrode is placed at the ionization region, the axial length of the acceleration region is shortened, the equipotential lines tend to be vertical with wall at the acceleration region, thus radial velocity of ions is reduced along with the wall corrosion. The axial position of the maximal electron temperature moves towards the exit with the expansion of ionization region. Furthermore, the electron-wall collision frequency and ionization rate also increase, the discharge current decreases and the specific impulse of the Hall thruster is slightly enhanced.

Gate engineered heterostructure junctionless TFET with Gaussian doping profile for ambipolar suppression and electrical performance improvement

NASA Astrophysics Data System (ADS)

Aghandeh, Hadi; Sedigh Ziabari, Seyed Ali

2017-11-01

This study investigates a junctionless tunnel field-effect transistor with a dual material gate and a heterostructure channel/source interface (DMG-H-JLTFET). We find that using the heterostructure interface improves device behavior by reducing the tunneling barrier width at the channel/source interface. Simultaneously, the dual material gate structure decreases ambipolar current by increasing the tunneling barrier width at the drain/channel interface. The performance of the device is analyzed based on the energy band diagram at on, off, and ambipolar states. Numerical simulations demonstrate improvements in ION, IOFF, ION/IOFF, subthreshold slope (SS), transconductance and cut-off frequency and suppressed ambipolar behavior. Next, the workfunction optimization of dual material gate is studied. It is found that if appropriate workfunctions are selected for tunnel and auxiliary gates, the JLTFET exhibits considerably improved performance. We then study the influence of Gaussian doping distribution at the drain and the channel on the ambipolar performance of the device and find that a Gaussian doping profile and a dual material gate structure remarkably reduce ambipolar current. Gaussian doped DMG-H-JLTFET, also exhibits enhanced IOFF, ION/IOFF, SS and a low threshold voltage without degrading IOFF.

Mechanosensitive Piezo Channels in the Gastrointestinal Tract

PubMed Central

Alcaino, C.; Farrugia, G.; Beyder, A.

2017-01-01

Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types—epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling. Several mechanosensitive ionic conductances have been identified in the mechano-sensory GI cells, ranging from mechanosensitive voltage-gated sodium and calcium channels to the mechanogated ion channels, such as the two-pore domain potassium channels K2P (TREK-1) and nonselective cation channels from the transient receptor potential family. The recently discovered Piezo channels are increasingly recognized as significant contributors to cellular mechanosensitivity. Piezo1 and Piezo2 are nonselective cationic ion channels that are directly activated by mechanical forces and have well-defined biophysical and pharmacologic properties. The role of Piezo channels in the GI epithelium is currently under investigation and their role in the smooth muscle syncytium and enteric neurons is still not known. In this review, we outline the current state of knowledge on mechanosensitive ion channels in the GI tract, with a focus on the known and potential functions of the Piezo channels. PMID:28728818

A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels.

PubMed

Maffie, Jonathon; Blenkinsop, Timothy; Rudy, Bernardo

2009-01-16

The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.

Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference

PubMed Central

Santi, C. M.; Yuan, A.; Fawcett, G.; Wang, Z.-W.; Butler, A.; Nonet, M. L.; Wei, A.; Rojas, P.; Salkoff, L.

2003-01-01

GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances. PMID:14612577

Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow.

PubMed

Hannah, Rachael M; Dunn, Kathryn M; Bonev, Adrian D; Nelson, Mark T

2011-05-01

Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK(Ca)) and intermediate-conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and IK(Ca) channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents were not detected in PA SMCs. In contrast, BK(Ca) currents were prominent in PA SMCs (~154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK(Ca) (~16%) and IK(Ca) (~16%) channels, but were only modestly affected by inhibition of BK(Ca) channels (~5%). Blockade of SK(Ca) and IK(Ca) channels decreased resting cortical cerebral blood flow (CBF) by ~15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SK(Ca)/IK(Ca) channel opener, hyperpolarized PA SMCs by ~27 mV, maximally dilated pressurized PAs, and increased CBF by ~40%. In conclusion, these data show that SK(Ca) and IK(Ca) channels in ECs profoundly modulate PA tone and CBF, whereas BK(Ca) channels in SMCs only modestly influence PA diameter.

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.

A comparative TCAD assessment of III-V channel materials for future high speed and low power logic applications

NASA Astrophysics Data System (ADS)

Gomes, U. P.; Takhar, K.; Ranjan, K.; Rathi, S.; Biswas, D.

2015-02-01

In this work, by means physics based drift-diffusion simulations, three different narrow band gap semiconductors; InAs, InSb and In0.53Ga0.47As, and their associated heterostructures have been studied for future high speed and low power logic applications. It is observed that In0.53Ga0.47As has higher immunity towards short channel effects with low DIBL and sub-threshold slope than InSb and InAs. Also it is observed that for the same device geometry InSb has the highest drive current and lower intrinsic delay but its ION/IOFF figure of merit is deteriorated due to excess leakage current.

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.

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.

Stencil Nano Lithography Based on a Nanoscale Polymer Shadow Mask: Towards Organic Nanoelectronics

PubMed Central

Yun, Hoyeol; Kim, Sangwook; Kim, Hakseong; Lee, Junghyun; McAllister, Kirstie; Kim, Junhyung; Pyo, Sengmoon; Sung Kim, Jun; Campbell, Eleanor E. B.; Hyoung Lee, Wi; Wook Lee, Sang

2015-01-01

A stencil lithography technique has been developed to fabricate organic-material-based electronic devices with sub-micron resolution. Suspended polymethylmethacrylate (PMMA) membranes were used as shadow masks for defining organic channels and top electrodes. Arrays of pentacene field effect transistors (FETs) with various channel lengths from 50 μm down to 500 nm were successfully produced from the same batch using this technique. Electrical transport measurements showed that the electrical contacts of all devices were stable and the normalized contact resistances were much lower than previously studied organic FETs. Scaling effects, originating from the bulk space charge current, were investigated by analyzing the channel-length-dependent mobility and hysteresis behaviors. This novel lithography method provides a reliable means for studying the fundamental transport properties of organic materials at the nanoscale as well as enabling potential applications requiring the fabrication of integrated organic nanoelectronic devices. PMID:25959389

Stencil nano lithography based on a nanoscale polymer shadow mask: towards organic nanoelectronics.

PubMed

Yun, Hoyeol; Kim, Sangwook; Kim, Hakseong; Lee, Junghyun; McAllister, Kirstie; Kim, Junhyung; Pyo, Sengmoon; Sung Kim, Jun; Campbell, Eleanor E B; Hyoung Lee, Wi; Wook Lee, Sang

2015-05-11

A stencil lithography technique has been developed to fabricate organic-material-based electronic devices with sub-micron resolution. Suspended polymethylmethacrylate (PMMA) membranes were used as shadow masks for defining organic channels and top electrodes. Arrays of pentacene field effect transistors (FETs) with various channel lengths from 50 μm down to 500 nm were successfully produced from the same batch using this technique. Electrical transport measurements showed that the electrical contacts of all devices were stable and the normalized contact resistances were much lower than previously studied organic FETs. Scaling effects, originating from the bulk space charge current, were investigated by analyzing the channel-length-dependent mobility and hysteresis behaviors. This novel lithography method provides a reliable means for studying the fundamental transport properties of organic materials at the nanoscale as well as enabling potential applications requiring the fabrication of integrated organic nanoelectronic devices.

Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

PubMed

Bigiani, Albertino

2017-05-01

Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels. In heterologous expression systems, these channels mediate outwardly rectifying membrane currents with distinct biophysical and pharmacological properties. I therefore tested whether also salt-detecting taste cells were endowed with these currents. To this aim, I applied the patch-clamp techniques to single cells in isolated taste buds from rat fungiform papillae. Salt-detecting cells were functionally identified by exploiting the effect of amiloride, which induces a current response by shutting down ENaCs. I looked for the presence of outwardly rectifying currents by using appropriate voltage-clamp protocols and specific pharmacological tools. I found that indeed salt-detecting cells possessed these currents with properties consistent with the presence, at least in part, of CALHM1 channels. Unexpectedly, CALHM1-like currents in taste cells were potentiated by known blockers of pannexin, suggesting a possible inhibitory action of this protein on CALMH1. These findings indicate that communication between salt-detecting cells and nerve endings might involve ATP release by CALMH1 channels. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Generation of a constitutive Na+-dependent inward-rectifier current in rat adult atrial myocytes by overexpression of Kir3.4.

PubMed

Mintert, Elisa; Bösche, Leif I; Rinne, Andreas; Timpert, Mathias; Kienitz, Marie-Cécile; Pott, Lutz; Bender, Kirsten

2007-11-15

Apart from gating by interaction with betagamma subunits from heterotrimeric G proteins upon stimulation of appropriate receptors, Kir.3 channels have been shown to be gated by intracellular Na+. However, no information is available on how Na+-dependent gating affects endogenous Kir3.1/Kir3.4 channels in mammalian atrial myocytes. We therefore studied how loading of adult atrial myocytes from rat hearts via the patch pipette filling solution with different concentrations of Na+ ([Na+]pip) affects Kir3 current. Surprisingly, in a range between 0 and 60 mm, Na+ neither had an effect on basal inward-rectifier current nor on the current activated by acetylcholine. Overexpression of Kir3.4 in adult atrial myocytes forced by adenoviral gene transfer results in formation of functional homomeric channels that interact with betagamma subunits upon activation of endogenous muscarinic receptors. These channels are activated at [Na+]pip >or= 15 mm, resulting in a receptor-independent basal inward rectifier current (I bir). I bir was neither affected by pertussis toxin nor by GDP-beta-S, suggesting G-protein-independent activation. PIP(2) depletion via endogenous PLC-coupled alpha1 adrenergic receptors causes inhibition of endogenous Kir3.1/3.4 channel currents by about 75%. In contrast, inhibition of Na+-activated I bir amounts to < 20%. The effect of the Kir3 channel blocker tertiapin-Q can be described using an IC50 of 12 nm (endogenous I K(ACh)) and 0.61 nm (I bir). These data clearly identify I bir as a homotetrameric Kir3.4 channel current with novel properties of regulation and pharmacology. Ibir shares some properties with a basal current recently described in atrial myocytes from an animal model of atrial fibrillation (AF) and AF patients.

A comparative study of n-channel low temperature poly-Si thin-film transistors with a body terminal or a lightly-doped-drain structure

NASA Astrophysics Data System (ADS)

Wu, Yanwen; Wang, Mingxiang; Wang, Huaisheng; Zhang, Dongli

2018-02-01

Hot-carrier (HC) induced degradation is a critical reliability issue of n-channel low temperature poly-Si thin-film transistors (TFTs) in TFT-based circuits. In this work, a kind of four-terminal TFT, which has an additional p+-doped lateral body terminal connecting to the floating channel, is systematically compared to conventional n-channel TFT and lightly-doped-drain (LDD) TFT. We demonstrate that the four-terminal TFT can provide similar advantages to that of the LDD TFT such as kink current suppression and DC HC degradation immunity, much superior immunity to the dynamic HC degradation, but without any tradeoffs in device performance and process complexity of the LDD TFT. It has high performance, as well as excellent reliability under both DC and AC conditions.

NIFLUMIC ACID BLOCKS NATIVE AND RECOMBINANT T-TYPE CHANNELS

PubMed Central

Balderas, E; Arteaga-Tlecuitl, R; Rivera, M; Gomora, JC; Darszon, A

2012-01-01

Voltage-dependent calcium channels are widely distributed in animal cells, including spermatozoa. Calcium is fundamental in many sperm functions such as: motility, capacitation and the acrosome reaction, all essential for fertilization. Pharmacological evidence has suggested T-type calcium channels participate in the acrosome reaction. Niflumic acid (NA), a non-steroidal anti-inflammatory drug commonly used as chloride channel blocker, blocks T-currents in mouse spermatogenic cells and Cl− channels in testicular sperm. Here we examine the mechanism of NA blockade and explore if it can be used to separate the contribution of different CaV3 members previously detected in these cells. Electrophysiological patch-clamp recordings were performed in isolated mouse spermatogenic cells and in HEK cells heterologously expressing CaV3 channels. NA blocks mouse spermatogenic cell T-type currents with an IC50 of 73.5 µM, without major voltage-dependent effects. The NA blockade is more potent in the open and in the inactivated state than in the closed state of the T-type channels. Interestingly, we found that heterologously expressed CaV3.1 and CaV3.3 channels were more sensitive to NA than CaV3.2 channels, and this drug substantially slowed the recovery from inactivation of the three isoforms. Molecular docking modeling of drug-channel binding predicts that NA binds preferentially to the extracellular face of CaV3.1 channels. The biophysical characteristics of mouse spermatogenic cell T-type currents more closely resemble those from heterologously expressed CaV3.1 channels, including their sensitivity to NA. As CaV3.1 null mice maintain their spermatogenic cell T-currents, it is likely that a novel CaV3.2 isoform is responsible for them. PMID:21898399

An empirical study of the nuclear explosion-induced lightning seen on IVY-MIKE

NASA Astrophysics Data System (ADS)

Colvin, J. D.; Mitchell, C. K.; Greig, J. R.; Murphy, D. P.; Pechacek, R. E.; Raleigh, M.

1987-05-01

We report the results of a unique study of the lightninglike phenomena that were seen to accompany the MIKE shot of operation IVY on October 31 1952. MIKE was a thermonuclear surface burst yielding 10.4 MT, which took place on Enewetak Atoll. During the period of approximately 10 ms after detonation, five discrete luminous channels were seen to start from the ground or sea surface at a distance of approximately 1 km from the burst point and to grow up into the clouds. We have reexamined the original photographic records of IVY-MIKE, obtaining effective brightnesses (optical powers per unit length) for the luminous channels at different altitudes as functions of time. The absolute calibration for the MIKE records was deduced by comparison with the photographic records of other events of that era, laboratory measurements of film sensitivity, and use of atmospheric transmission data taken just prior to the MIKE event. Errors in this analysis lead to an uncertainty of a factor of ˜2 in the brightnesses of the luminous channels. In the laboratory we have used laser-guided electric discharges to create long (100 cm), arclike plasma channels to simulate the observed luminous channels and to allow determination of an empirical relation between the brightness of the channel and the electric current flowing in the channel. These laboratory discharges had peak currents up to 100 kA and periods of ˜2 ms. Spectroscopic analysis showed that the luminous channels consisted primarily of normal air plasma with typical ground-level contaminants. Photographic studies showed that these long-duration discharges are unstable to the m = 1 magnetohydrodynamic (MHD) instability and become severely distorted in less than 1 ms. By direct comparison of the luminous channels seen at MIKE and the laboratory discharges, we deduce: (1) the peak current in the prominent (brightest) channel at MIKE was between 200 and 600 kA. Here the most likely value of the peak current was 250±50 kA, but potential systematic errors in the film calibration and the comparison of MIKE and laboratory data make higher currents possible. (2) The rapid decline in the brightness of the luminous channels seen at MIKE is caused by a combination of the effects of the MHD instability, which eventually leads to a broadening of the current-carrying channel, and channel cooling by turbulent convective mixing.

A Voltage Dependent Non-Inactivating Na+ Channel Activated during Apoptosis in Xenopus Oocytes

PubMed Central

Englund, Ulrika H.; Gertow, Jens; Kågedal, Katarina; Elinder, Fredrik

2014-01-01

Ion channels in the plasma membrane are important for the apoptotic process. Different types of voltage-gated ion channels are up-regulated early in the apoptotic process and block of these channels prevents or delays apoptosis. In the present investigation we examined whether ion channels are up-regulated in oocytes from the frog Xenopus laevis during apoptosis. The two-electrode voltage-clamp technique was used to record endogenous ion currents in the oocytes. During staurosporine-induced apoptosis a voltage-dependent Na+ current increased three-fold. This current was activated at voltages more positive than 0 mV (midpoint of the open-probability curve was +55 mV) and showed almost no sign of inactivation during a 1-s pulse. The current was resistant to the Na+-channel blockers tetrodotoxin (1 µM) and amiloride (10 µM), while the Ca2+-channel blocker verapamil (50 µM) in the bath solution completely blocked the current. The intracellular Na+ concentration increased in staurosporine-treated oocytes, but could be prevented by replacing extracellular Na+ whith either K+ or Choline+. Prevention of this influx of Na+ also prevented the STS-induced up-regulation of the caspase-3 activity, suggesting that the intracellular Na+ increase is required to induce apoptosis. Taken together, we have found that a voltage dependent Na+ channel is up-regulated during apoptosis and that influx of Na+ is a crucial step in the apoptotic process in Xenopus oocytes. PMID:24586320

Redox regulation of neuronal voltage-gated calcium channels.

PubMed

Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

2014-08-20

Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain.

A three-wavelength multi-channel brain functional imager based on digital lock-in photon-counting technique

NASA Astrophysics Data System (ADS)

Ding, Xuemei; Wang, Bingyuan; Liu, Dongyuan; Zhang, Yao; He, Jie; Zhao, Huijuan; Gao, Feng

2018-02-01

During the past two decades there has been a dramatic rise in the use of functional near-infrared spectroscopy (fNIRS) as a neuroimaging technique in cognitive neuroscience research. Diffuse optical tomography (DOT) and optical topography (OT) can be employed as the optical imaging techniques for brain activity investigation. However, most current imagers with analogue detection are limited by sensitivity and dynamic range. Although photon-counting detection can significantly improve detection sensitivity, the intrinsic nature of sequential excitations reduces temporal resolution. To improve temporal resolution, sensitivity and dynamic range, we develop a multi-channel continuous-wave (CW) system for brain functional imaging based on a novel lock-in photon-counting technique. The system consists of 60 Light-emitting device (LED) sources at three wavelengths of 660nm, 780nm and 830nm, which are modulated by current-stabilized square-wave signals at different frequencies, and 12 photomultiplier tubes (PMT) based on lock-in photon-counting technique. This design combines the ultra-high sensitivity of the photon-counting technique with the parallelism of the digital lock-in technique. We can therefore acquire the diffused light intensity for all the source-detector pairs (SD-pairs) in parallel. The performance assessments of the system are conducted using phantom experiments, and demonstrate its excellent measurement linearity, negligible inter-channel crosstalk, strong noise robustness and high temporal resolution.

Temporal Large-Eddy Simulation

NASA Technical Reports Server (NTRS)

Pruett, C. D.; Thomas, B. C.

2004-01-01

In 1999, Stolz and Adams unveiled a subgrid-scale model for LES based upon approximately inverting (defiltering) the spatial grid-filter operator and termed .the approximate deconvolution model (ADM). Subsequently, the utility and accuracy of the ADM were demonstrated in a posteriori analyses of flows as diverse as incompressible plane-channel flow and supersonic compression-ramp flow. In a prelude to the current paper, a parameterized temporal ADM (TADM) was developed and demonstrated in both a priori and a posteriori analyses for forced, viscous Burger's flow. The development of a time-filtered variant of the ADM was motivated-primarily by the desire for a unifying theoretical and computational context to encompass direct numerical simulation (DNS), large-eddy simulation (LES), and Reynolds averaged Navier-Stokes simulation (RANS). The resultant methodology was termed temporal LES (TLES). To permit exploration of the parameter space, however, previous analyses of the TADM were restricted to Burger's flow, and it has remained to demonstrate the TADM and TLES methodology for three-dimensional flow. For several reasons, plane-channel flow presents an ideal test case for the TADM. Among these reasons, channel flow is anisotropic, yet it lends itself to highly efficient and accurate spectral numerical methods. Moreover, channel-flow has been investigated extensively by DNS, and a highly accurate data base of Moser et.al. exists. In the present paper, we develop a fully anisotropic TADM model and demonstrate its utility in simulating incompressible plane-channel flow at nominal values of Re(sub tau) = 180 and Re(sub tau) = 590 by the TLES method. The TADM model is shown to perform nearly as well as the ADM at equivalent resolution, thereby establishing TLES as a viable alternative to LES. Moreover, as the current model is suboptimal is some respects, there is considerable room to improve TLES.

Optimal Performance Monitoring of Hybrid Mid-Infrared Wavelength MIMO Free Space Optical and RF Wireless Networks in Fading Channels

NASA Astrophysics Data System (ADS)

Schmidt, Barnet Michael

An optimal performance monitoring metric for a hybrid free space optical and radio-frequency (RF) wireless network, the Outage Capacity Objective Function, is analytically developed and studied. Current and traditional methods of performance monitoring of both optical and RF wireless networks are centered on measurement of physical layer parameters, the most common being signal-to-noise ratio, error rate, Q factor, and eye diagrams, occasionally combined with link-layer measurements such as data throughput, retransmission rate, and/or lost packet rate. Network management systems frequently attempt to predict or forestall network failures by observing degradations of these parameters and to attempt mitigation (such as offloading traffic, increasing transmitter power, reducing the data rate, or combinations thereof) prior to the failure. These methods are limited by the frequent low sensitivity of the physical layer parameters to the atmospheric optical conditions (measured by optical signal-to-noise ratio) and the radio frequency fading channel conditions (measured by signal-to-interference ratio). As a result of low sensitivity, measurements of this type frequently are unable to predict impending failures sufficiently in advance for the network management system to take corrective action prior to the failure. We derive and apply an optimal measure of hybrid network performance based on the outage capacity of the hybrid optical and RF channel, the outage capacity objective function. The objective function provides high sensitivity and reliable failure prediction, and considers both the effects of atmospheric optical impairments on the performance of the free space optical segment as well as the effect of RF channel impairments on the radio frequency segment. The radio frequency segment analysis considers the three most common RF channel fading statistics: Rayleigh, Ricean, and Nakagami-m. The novel application of information theory to the underlying physics of the gamma-gamma optical channel and radio fading channels in determining the joint hybrid channel outage capacity provides the best performance estimate under any given set of operating conditions. It is shown that, unlike traditional physical layer performance monitoring techniques, the objective function based upon the outage capacity of the hybrid channel at any combination of OSNR and SIR, is able to predict channel degradation and failure well in advance of the actual outage. An outage in the information-theoretic definition occurs when the offered load exceeds the outage capacity under the current conditions of OSNR and SIR. The optical channel is operated at the "long" mid-infrared wavelength of 10000 nm. which provides improved resistance to scattering compared to shorter wavelengths such as 1550 nm.

Modeling and simulation of enhancement mode p-GaN Gate AlGaN/GaN HEMT for RF circuit switch applications

NASA Astrophysics Data System (ADS)

Panda, D. K.; Lenka, T. R.

2017-06-01

An enhancement mode p-GaN gate AlGaN/GaN HEMT is proposed and a physics based virtual source charge model with Landauer approach for electron transport has been developed using Verilog-A and simulated using Cadence Spectre, in order to predict device characteristics such as threshold voltage, drain current and gate capacitance. The drain current model incorporates important physical effects such as velocity saturation, short channel effects like DIBL (drain induced barrier lowering), channel length modulation (CLM), and mobility degradation due to self-heating. The predicted I d-V ds, I d-V gs, and C-V characteristics show an excellent agreement with the experimental data for both drain current and capacitance which validate the model. The developed model was then utilized to design and simulate a single-pole single-throw (SPST) RF switch.

Activation by intracellular GDP, metabolic inhibition and pinacidil of a glibenclamide-sensitive K-channel in smooth muscle cells of rat mesenteric artery.

PubMed Central

Zhang, H; Bolton, T B

1995-01-01

1. Single-channel recordings were made from cell-attached and isolated patches, and whole-cell currents were recorded under voltage clamp from single smooth muscle cells obtained by enzymic digestion of a small branch of the rat mesenteric artery. 2. In single voltage-clamped cells 1 mM uridine diphosphate (UDP) or guanidine diphosphate (GDP) added to the pipette solution, or pinacidil (100 microM) a K-channel opener (KCO) applied in the bathing solution, evoked an outward current of up to 100pA which was blocked by glibenclamide (10 microM). In single cells from which recordings were made by the 'perforated patch' (nystatin pipette) technique, metabolic inhibition by 1 mM NaCN and 10 mM 2-deoxy-glucose also evoked a similar glibenclamide-sensitive current. 3. Single K-channel activity was observed in cell-attached patches only infrequently unless the metabolism of the cell was inhibited, whereupon channel activity blocked by glibenclamide was seen; pinacidil applied to the cell evoked similar glibenclamide-sensitive channel activity. If the patch was pulled off the cell to form an isolated inside-out patch, similar glibenclamide-sensitive single-channel currents were observed in the presence of UDP and/or pinacidil to those seen in cell-attached mode; channel conductance was 20 pS (60:130 K-gradient) and openings showed no voltage-dependence and noisy inward currents, typical of the nucleoside diphosphate (NDP) activated K-channel (KNDP) seen previously in rabbit portal vein. 4. Formation of an isolated inside-out patch into an ATP-free solution did not increase the probability of channel opening which declined with time even when some single-channel activity had occurred in the cell-attached mode before detachment. However, application of 1 mM UDP or GDP, but not ATP, to inside-out patches evoked single-channel activity. Application of ATP-free solution to isolated patches, previously exposed to ATP and in which channel activity had been seen, did not evoke channel activity. 5. It is concluded that small conductance K-channels (KNDP) open in smooth muscle cells from this small artery in response to UDP or GDP acting from the inside, or pinacidil acting from the outside; the same channels open during inhibition of metabolism presumably mainly due to the rise in nucleoside diphosphates, but a fall in the ATP concentration on the inside of the channel did not by itself evoke channel activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7735693

Label Free Detection of Biomolecules Using Charge-Plasma-Based Gate Underlap Dielectric Modulated Junctionless TFET

NASA Astrophysics Data System (ADS)

Wadhwa, Girish; Raj, Balwinder

2018-05-01

Nanoscale devices are emerging as a platform for detecting biomolecules. Various issues were observed during the fabrication process such as random dopant fluctuation and thermal budget. To reduce these issues charge-plasma-based concept is introduced. This paper proposes the implementation of charge-plasma-based gate underlap dielectric modulated junctionless tunnel field effect transistor (DM-JLTFET) for the revelation of biomolecule immobilized in the open cavity gate channel region. In this p+ source and n+ drain regions are introduced by employing different work function over the intrinsic silicon. Also dual material gate architecture is implemented to reduce short channel effect without abandoning any other device characteristic. The sensitivity of biosensor is studied for both the neutral and charge-neutral biomolecules. The effect of device parameters such as channel thickness, cavity length and cavity thickness on drain current have been analyzed through simulations. This paper investigates the performance of charge-plasma-based gate underlap DM-JLTFET for biomolecule sensing applications while varying dielectric constant, charge density at different biasing conditions.

Mechanism-Based Mathematical Model for Gating of Ionotropic Glutamate Receptors.

PubMed

Dai, Jian; Wollmuth, Lonnie P; Zhou, Huan-Xiang

2015-08-27

We present a mathematical model for ionotropic glutamate receptors (iGluR's) that is built on mechanistic understanding and yields a number of thermodynamic and kinetic properties of channel gating. iGluR's are ligand-gated ion channels responsible for the vast majority of fast excitatory neurotransmission in the central nervous system. The effects of agonist-induced closure of the ligand-binding domain (LBD) are transmitted to the transmembrane channel (TMC) via interdomain linkers. Our model demonstrates that, relative to full agonists, partial agonists may reduce either the degree of LBD closure or the curvature of the LBD free energy basin, leading to less stabilization of the channel open state and hence lower channel open probability. A rigorous relation is derived between the channel closed-to-open free energy difference and the tension within the linker. Finally, by treating LBD closure and TMC opening as diffusive motions, we obtain gating trajectories that resemble stochastic current traces from single-channel recordings and calculate the rate constants for transitions between the channel open and closed states. Our model can be implemented by molecular dynamics simulations to realistically depict iGluR gating and may guide functional experiments in gaining deeper insight into this essential family of channel proteins.

A Tale of Two Inlets: Tidal Currents at Two Adjacent Inlets in the Indian River Lagoon

NASA Astrophysics Data System (ADS)

Webb, B. M.; Weaver, R. J.

2012-12-01

The tidal currents and hydrography at two adjacent inlets of the Indian River Lagoon estuary (Florida) were recently measured using a personal watercraft-based coastal profiling system. Although the two inlets—Sebastian Inlet and Port Canaveral Inlet—are separated by only 60 km, their characteristics and dynamics are quite unique. While Sebastian Inlet is a shallow (~4 m), curved inlet with a free connection to the estuary, Port Canaveral Inlet is dominated by a deep (~13 m), straight ship channel and has limited connectivity to the Banana River through a sector gate lock. Underway measurements of tidal currents were obtained using a bottom tracking acoustic Doppler current profiler; vertical casts of hydrography were obtained with a conductivity-temperature-depth profiling instrument; and continuous underway measurements of surface water hydrography were made using a Portable SeaKeeper system. Survey transects were performed to elucidate the along-channel variability of tidal flows, which appears to be significant in the presence of channel curvature. Ebb and flood tidal currents in Sebastian Inlet routinely exceeded 2.5 m/s from the surface to the bed, and an appreciable phase lag exists between tidal stage and current magnitude. The tidal currents at Port Canaveral Inlet were much smaller (~0.2 m/s) and appeared to be sensitive to meteorological forcing during the study period. Although the lagoon has free connections to the ocean 145 km to the north and 45 km to the south, Sebastian Inlet likely drains much of the lagoon to its north, an area of ~550 sq. km.

Relationship among side channels, fish assemblages, and environmental gradients in the unimpounded Upper Mississippi River

USGS Publications Warehouse

Barko, V.A.; Herzog, D.P.

2003-01-01

We analyzed fish abundance and environmental data collected over nine years from six side channels of the unimpounded upper Mississippi River between river km 46.7 and 128.7. A partial canonical correspondence analysis revealed differences in fish assemblages and environmental factors correlated with the six side channels. Fishes correlated with open side channels represented large river species tolerant of current and/or turbidity. Fishes correlated with closed side channels represented assemblages preferring either moderate to low turbidity/current or pools.

Conductivity noise in transmembrane ion channels due to ion concentration fluctuations via diffusion.

PubMed

Mak, D O; Webb, W W

1997-03-01

A Green's function approach is developed from first principles to evaluate the power spectral density of conductance fluctuations caused by ion concentration fluctuations via diffusion in an electrolyte system. This is applied to simple geometric models of transmembrane ion channels to obtain an estimate of the magnitude of ion concentration fluctuation noise in the channel current. Pure polypeptide alamethicin forms stable ion channels with multiple conductance states in artificial phospholipid bilayers isolated onto tips of micropipettes with gigaohm seals. In the single-channel current recorded by voltage-clamp techniques, excess noise was found after the background instrumental noise and the intrinsic Johnson and shot noises were removed. The noise que to ion concentration fluctuations via diffusion was isolated by the dependence of the excess current noise on buffer ion concentration. The magnitude of the concentration fluctuation noise derived from experimental data lies within limits estimated using our simple geometric channel models. Variation of the noise magnitude for alamethicin channels in various conductance states agrees with theoretical prediction.

Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents.

PubMed

Mani, Bharath K; Robakowski, Christina; Brueggemann, Lyubov I; Cribbs, Leanne L; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L

2016-03-01

Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K(+) currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 > Kv7.4/Kv7.5 > Kv7.4. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents

PubMed Central

Mani, Bharath K.; Robakowski, Christina; Brueggemann, Lyubov I.; Cribbs, Leanne L.; Tripathi, Abhishek; Majetschak, Matthias

2016-01-01

Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K+ currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4. PMID:26700561

Local anaesthetics transiently block currents through single acetylcholine-receptor channels.

PubMed Central

Neher, E; Steinbach, J H

1978-01-01

1. Single channel currents through acetylcholine receptor channels (ACh channels) were recorded at chronically denervated frog muscle extrajunctional membranes in the absence and presence of the lidocaine derivatives QX-222 and QX-314. 2. The current wave forms due to the opening and closing of single ACh channels (activated by suberyldicholine) normally are square pulses. These single pulses appear to be chopped into bursts of much shorter pulses, when the drug QX-222 is present in addition to the agonist. 3. The mean duration of the bursts is comparable to or longer than the normal channel open time, and increases with increasing drug concentration. 4. The duration of the short pulses within a burst decreases with increasing drug concentration. 5. It is concluded that drug molecules reversibly block open end-plate channels and that the flickering within a burst represents this fast, repeatedly occurring reaction. 6. The voltage dependence of the reaction rates involved, suggested that the site of the blocking reaction is in the centre of the membrane, probably inside the ionic channel. PMID:306437

Kv7 potassium channel subunits and M currents in cultured hippocampal interneurons.

PubMed

Grigorov, Alexej; Moskalyuk, Anastasia; Kravchenko, Mykola; Veselovsky, Nikolai; Verkhratsky, Alexei; Fedulova, Svetlana

2014-09-01

Potassium channels of the Kv7 family that mediate the non-inactivating M current regulate the excitability of many types of neurons in the central nervous system, including some in the hippocampus. We report here that individual interneurons from newborn rat hippocampi in long-term culture strongly express messenger RNA specific for Kv7.2 and Kv7.3 and, to a lesser extent, Kv7.5 channel subunits but not for the Kv7.4 subunit. An M-like current was electrophysiologically identified in two subpopulations of interneurons distinct in their spiking behaviour (regular or fast spiking). The M-channel enhancer retigabine reduced interneuronal excitability by constraining the number of action potentials generated during imposed depolarisations; this effect was inhibited by specific the M-channel blocking drugs. In paired synaptically connected interneuron-target cell recordings, anatomically localised applications of retigabine indicated that M channels were present in both the interneuron soma and its GABA-ergic inhibitory axon. We conclude that M-channel subunits and functional M channels are broadly expressed in hippocampal interneurons and their axons and are potentially capable of strongly regulating their firing properties.

Properties of voltage-activated Na+ and K+ currents in mouse hippocampal glial cells in situ and after acute isolation from tissue slices.

PubMed

Steinhäuser, C; Kressin, K; Kuprijanova, E; Weber, M; Seifert, G

1994-10-01

In the present study, we were interested in a quantitative analysis of voltage-activated channels in a subpopulation of hippocampal glial cells, termed "complex" cells. The patch-clamp technique in the whole-cell mode was applied to identified cells in situ and to glial cells acutely isolated from tissue slices. The outward current was composed of two components: a sustained and a transient current. The transient K+ channel had electrophysiological and pharmacological properties resembling those of the channel through which the A-currents pass. In addition, this glial A-type current possessed a significant Ca2+ dependence. The current parameters determined in situ or in isolated cells corresponded well. Due to space clamp problems in situ, properties of voltage-dependent Na+ currents were only analysed in suspended glial cells. The tetrodotoxin (TTX) sensitivity and the stationary and kinetic characteristics of this current were similar to corresponding properties of hippocampal neurons. These quantitative data demonstrate that at an early postnatal stage of central nervous system maturation, glial cells in situ express a complex pattern of voltage-gated ion channels. The results are compared to findings in other preparations and the possible consequences of transmitter-mediated channel modulation in glial cells are discussed.

External K+ dependence of strong inward rectifier K+ channel conductance is caused not by K+ but by competitive pore blockade by external Na.

PubMed

Ishihara, Keiko

2018-06-15

Strong inward rectifier K + (sKir) channels determine the membrane potentials of many types of excitable and nonexcitable cells, most notably the resting potentials of cardiac myocytes. They show little outward current during membrane depolarization (i.e., strong inward rectification) because of the channel blockade by cytoplasmic polyamines, which depends on the deviation of the membrane potential from the K + equilibrium potential ( V - E K ) when the extracellular K + concentration ([K + ] out ) is changed. Because their open - channel conductance is apparently proportional to the "square root" of [K + ] out , increases/decreases in [K + ] out enhance/diminish outward currents through sKir channels at membrane potentials near their reversal potential, which also affects, for example, the repolarization and action-potential duration of cardiac myocytes. Despite its importance, however, the mechanism underlying the [K + ] out dependence of the open sKir channel conductance has remained elusive. By studying Kir2.1, the canonical member of the sKir channel family, we first show that the outward currents of Kir2.1 are observed under the external K + -free condition when its inward rectification is reduced and that the complete inhibition of the currents at 0 [K + ] out results solely from pore blockade caused by the polyamines. Moreover, the noted square-root proportionality of the open sKir channel conductance to [K + ] out is mediated by the pore blockade by the external Na + , which is competitive with the external K + Our results show that external K + itself does not activate or facilitate K + permeation through the open sKir channel to mediate the apparent external K + dependence of its open channel conductance. The paradoxical increase/decrease in outward sKir channel currents during alternations in [K + ] out , which is physiologically relevant, is caused by competition from impermeant extracellular Na . © 2018 Ishihara.

Liposomal quercetin potentiates maxi-K channel openings in smooth muscles and restores its activity after oxidative stress.

PubMed

Melnyk, Mariia I; Dryn, Dariia O; Al Kury, Lina T; Zholos, Alexander V; Soloviev, Anatoly I

2018-04-19

The effects of quercetin-loaded liposomes (PCL-Q) and their constituents, that is, free quercetin (Q) and 'empty' phosphatidylcholine vesicles (PCL), on maxi-K channel activity were studied in single mouse ileal myocytes before and after H 2 O 2 -induced oxidative stress. Macroscopic Maxi-K channel currents were recorded using whole-cell patch clamp techniques, while single BK Ca channel currents were recorded in the cell-attached configuration. Bath application of PCL-Q (100 μg/ml of lipid and 3 μg/ml of quercetin) increased single Maxi-K channel activity more than threefold, from 0.010 ± 0.003 to 0.034 ± 0.004 (n = 5; p < 0.05), whereas single-channel conductance increased non-significantly from 138 to 146 pS. In the presence of PCL-Q multiple simultaneous channel openings were observed, with up to eight active channels in the membrane patch. Surprisingly, 'empty' PCL (100 μg/ml) also produced some channel activation, although it was less potent compared to PCL-Q, that is, these increased NPo from 0.010 ± 0.003 to 0.019 ± 0.003 (n = 5; p < 0.05) and did not affect single-channel conductance (139 pS). Application of PCL-Q restored macroscopic Maxi-K currents suppressed by H 2 O 2 -induced oxidative stress in ileal smooth muscle cells. We conclude that PCL-Q can activate Maxi-K channels in ileal myocytes mainly by increasing channel open probability, as well as maintain Maxi-K-mediated whole-cell current under the conditions of oxidative stress. While fusion of the 'pure' liposomes with the plasma membrane may indirectly activate Maxi-K channels by altering channel's phospholipids environment, the additional potentiating action of quercetin may be due to its better bioavailability.

Coxsackievirus and adenovirus receptor (CAR) mediates trafficking of acid sensing ion channel 3 (ASIC3) via PSD-95.

PubMed

Excoffon, Katherine J D A; Kolawole, Abimbola O; Kusama, Nobuyoshi; Gansemer, Nicholas D; Sharma, Priyanka; Hruska-Hageman, Alesia M; Petroff, Elena; Benson, Christopher J

2012-08-17

We have previously shown that the Coxsackievirus and adenovirus receptor (CAR) can interact with post-synaptic density 95 (PSD-95) and localize PSD-95 to cell-cell junctions. We have also shown that activity of the acid sensing ion channel (ASIC3), a H(+)-gated cation channel that plays a role in mechanosensation and pain signaling, is negatively modulated by PSD-95 through a PDZ-based interaction. We asked whether CAR and ASIC3 simultaneously interact with PSD-95, and if so, whether co-expression of these proteins alters their cellular distribution and localization. Results indicate that CAR and ASIC3 co-immunoprecipitate only when co-expressed with PSD-95. CAR also brings both PSD-95 and ASIC3 to the junctions of heterologous cells. Moreover, CAR rescues PSD-95-mediated inhibition of ASIC3 currents. These data suggest that, in addition to activity as a viral receptor and adhesion molecule, CAR can play a role in trafficking proteins, including ion channels, in a PDZ-based scaffolding complex. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Liau, Leo Chau-Kuang, E-mail: lckliau@saturn.yzu.edu.tw; Hsu, Tzu-Hsien; Lo, Pei-Hsuan

We report the characteristics of p-channel thin film transistors (p-TFTs) with ZnO/hydrated polyvinyl alcohol (PVA) (ZnO/PVA) conducting channels. The metal-oxide-semiconductor structure of the p-TFTs was composed of indium tin oxide (ITO)/SiO{sub 2}/ZnO/PVA layers. The TFT was assembled using PVA gel, which was glued to ITO substrates patterned to form source and drain electrodes. The ZnO/PVA composite film acted as an effective conducting film because of the chemisorption reaction at the film interface where free electrons can be generated. The formation of the conducting channel was also affected by V{sub G} applied to the TFT. The ZnO/PVA-based TFTs demonstrated p-channel transistormore » performance, shown by current-voltage (I-V) data analysis. The electrical parameters of the device were evaluated, including the on/off ratio (∼10{sup 3}), threshold voltage (V{sub th}, −1 V), and subthreshold swing (−2.2 V/dec). The PVA/ZnO-based p-TFTs were fabricated using simple and cost-effective approaches instead of doping methods.« less

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

El Tor hemolysin of Vibrio cholerae O1 forms channels in planar lipid bilayer membranes.

PubMed

Ikigai, H; Ono, T; Iwata, M; Nakae, T; Shimamura, T

1997-05-15

We investigated the channel formation by El Tor hemolysin (molecular mass, 65 kDa) of Vibrio cholerae O1 biotype El Tor in planar lipid bilayers. The El Tor hemolysin channel exhibited asymmetric and hyperbolic membrane current with increasing membrane potential, meaning that the channel is voltage dependent. The zero-current membrane potential measured in KCI solution showed that permeability ratio PK+/PCl- was 0.16, indicating that the channel is 6-fold more anion selective over cation. The hemolysin channel frequently flickered in the presence of divalent cations, suggesting that the channel spontaneously opens and closes. These data imply that the El Tor hemolysin damages target cells by the formation of transmembrane channels and, consequently, is the cause of osmotic cytolysis.

Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion

PubMed Central

García-Delgado, Neivys; Velasco, Myrian; Sánchez-Soto, Carmen; Díaz-García, Carlos Manlio; Hiriart, Marcia

2018-01-01

Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells. We observed that the percentage of detection of T-type current increased with the stage of development. T-type calcium current density in adult cells was higher than in neonatal and P20 beta cells. Mean HVA current density also increased with age. Calcium current behavior in P20 beta cells was heterogeneous; almost half of the cells had HVA current densities higher than the adult cells, and this was independent of the presence of T-type current. We detected the presence of α1G, α1H, and α1I subunits of LVA channels at all ages. The Cav 3.1 subunit (α1G) was the most expressed. T-type channel blockers mibefradil and TTA-A2 significantly inhibited insulin secretion at 5.6 mM glucose, which suggests a physiological role for T-type channels at basal glucose conditions. Both, nifedipine and TTA-A2, drastically decreased the beta-cell subpopulation that secretes more insulin, in both basal and stimulating glucose conditions. We conclude that changes in expression and activity of VGCC during the development play an important role in physiological maturation of beta cells. PMID:29556214

Dynamics of 30 large channel bars in the Lower Mississippi River in response to river engineering from 1985 to 2015

NASA Astrophysics Data System (ADS)

Wang, Bo; Xu, Y. Jun

2018-01-01

Channel bars are a major depositional feature in alluvial rivers and their morphodynamics has been investigated intensively in the past several decades. However, relatively less is known about how channel bars in alluvial rivers respond to river engineering and regulations. In this study, we assessed 30-yr morphologic changes of 30 large emerged bars located in a 223 km reach of the highly regulated Lower Mississippi River from Vicksburg, Mississippi, to the Mississippi-Atchafalaya River diversion. Landsat imagery and river stage data between 1985 and 2015 were utilized to characterize bar morphologic features and quantify decadal changes. Based on bar surface areas estimated with the satellite images at different river stages, a rating curve was developed for each of the 30 bars to determine their volumes. Results from this study show that the highly regulated river reach favored the growth of mid-channel and attached bars, while more than half of the point bars showed degradation. Currently, the mid-channel and attached bars accounted for 38% and 34% of the total volume of the 30 bars. The average volume of a single mid-channel bar is over two times that of an attached bar and over four times that of a point bar. Overall, in the past three decades, the total volume of the studied 30 bars increased by 110,118,000 m3 (41%). Total dike length in a dike field was found mostly contributing to the bar volume increase. Currently, the emerged volume of the 30 bars was estimated approximately 378,183,000 m3. The total bar volume is equivalent to 530 million metric tons of coarse sand, based on an average measured bulk density of 1.4 t/m3 for the bar sediment. The findings show that these bars are large sediment reservoirs.

A simplified simulation model for a HPDC die with conformal cooling channels

NASA Astrophysics Data System (ADS)

Frings, Markus; Behr, Marek; Elgeti, Stefanie

2017-10-01

In general, the cooling phase of the high-pressure die casting process is based on complex physical phenomena: so-lidification of molten material; heat exchange between cast part, die and cooling fluid; turbulent flow inside the cooling channels that needs to be considered when computing the heat flux; interdependency of properties and temperature of the cooling liquid. Intuitively understanding and analyzing all of these effects when designing HPDC dies is not feasible. A remedy that has become available is numerical design, based for example on shape optimization methods. However, current computing power is not sufficient to perform optimization while at the same time fully resolving all physical phenomena. But since in HPDC suitable objective functions very often lead to integral values, e.g., average die temperature, this paper identifies possible simplifications in the modeling of the cooling phase. As a consequence, the computational effort is reduced to an acceptable level. A further aspect that arises in the context of shape optimization is the evaluation of shape gradients. The challenge here is to allow for large shape deformations without remeshing. In our approach, the cooling channels are described by their center lines. The flow profile of the cooling fluid is then estimated based on experimental data found in literature for turbulent pipe flows. In combination, the heat flux throughout cavity, die, and cooling channel can be described by one single advection-diffusion equation on a fixed mesh. The parameters in the equation are adjusted based on the position of cavity and cooling channel. Both results contribute towards a computationally efficient, yet accurate method, which can be employed within the frame of shape optimization of cooling channels in HPDC dies.

Molecular basis of activation of the arachidonate-regulated Ca2+ (ARC) channel, a store-independent Orai channel, by plasma membrane STIM1

PubMed Central

Thompson, Jill L; Shuttleworth, Trevor J

2013-01-01

Currently, Orai proteins are known to encode two distinct agonist-activated, highly calcium-selective channels: the store-operated Ca2+ release-activated Ca2+ (CRAC) channels, and the store-independent, arachidonic acid-activated ARC channels. Surprisingly, whilst the trigger for activation of these channels is entirely different, both depend on stromal interacting molecule 1 (STIM1). However, whilst STIM1 in the endoplasmic reticulum membrane is the critical sensor for the depletion of this calcium store that triggers CRAC channel activation, it is the pool of STIM1 constitutively resident in the plasma membrane that is essential for activation of the ARC channels. Here, using a variety of approaches, we show that the key domains within the cytosolic part of STIM1 identified as critical for the activation of CRAC channels are also key for activation of the ARC channels. However, examination of the actual steps involved in such activation reveal marked differences between these two Orai channel types. Specifically, loss of calcium from the EF-hand of STIM1 that forms the key initiation point for activation of the CRAC channels has no effect on ARC channel activity. Secondly, in marked contrast to the dynamic and labile nature of interactions between STIM1 and the CRAC channels, STIM1 in the plasma membrane appears to be constitutively associated with the ARC channels. Finally, specific mutations in STIM1 that induce an extended, constitutively active, conformation for the CRAC channels actually prevent activation of the ARC channels by arachidonic acid. Based on these findings, we propose that the likely role of arachidonic acid lies in inducing the actual gating of the channel. PMID:23690558

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

PubMed Central

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

2012-01-01

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

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.

Evaluation of Open Cell Foam Heat Transfer Enhancement for Liquid Rocket Engine

NASA Technical Reports Server (NTRS)

Chung, J. N.; Tully, Landon; Kim, Jung Hwan; Jones, Gregg W.; Watkins, William

2006-01-01

As NASA pursues the exploration mission, advanced propulsion for the next generation of spacecraft will be needed. These new propulsion systems will require higher performance and increased durability, despite current limitations on materials. A break-through technology is needed in the thrust chamber. In this paper the idea of using a porous metallic foam is examined for its potential cooling enhancement capabilities. The goal is to increase the chamber wall cooling without creating an additional pressure drop penalty. A feasibility study based on experiments at laboratory-scale conditions was performed and analysis at rocket conditions is underway. In the experiment, heat transfer and pressure drop data were collected using air as the coolant in a copper or nickel foam filled annular channel. The foam-channel performance was evaluated based on comparison with conventional microchannel cooling passages under equal pressure drop conditions. The heat transfer enhancement of the foam channel over the microchannel ranges from 130% to 172%. The enhancement is relatively independent of the pressure drop and increases with decreasing pore size. A direct numerical simulation model of the foam heat exchange has been built. The model is based on the actual metal foam microstructure of thin ligaments (0.2- 0.3 mm in diameter) that form a network of interconnected open-cells. The cell dimension is around 2 mm. The numerical model was built using the FLUENT CFD code. Comparison of the pressure drop results predicted by the current model with those experimental data of Leong and Jin [8] shows favorable comparisons. Pressure drop predictions have been made using hydrogen as a coolant at typical rocket conditions. Conjugate heat transfer analysis using the foam filled channel is planned for the future.

ATP-sensitive potassium currents from channels formed by Kir6 and a modified cardiac mitochondrial SUR2 variant

PubMed Central

Aggarwal, Nitin T; Shi, Nian-Qing; Makielski, Jonathan C

2013-01-01

Cardiac ATP-sensitive potassium channels (KATP) are found in both the sarcoplasmic reticulum (sarcKATP) and the inner membrane of mitochondria (mitoKATP). SarcKATP are composed of a pore containing subunit Kir6.2 and a regulatory sulfonylurea receptor subunit (SUR2), but the composition of mitoKATP remains unclear. An unusual intra-exonic splice variant of SUR2 (SUR2A-55) was previously identified in mitochondria of mammalian heart and brain, and by analogy with sarcKATP we proposed SUR2A-55 as a candidate regulatory subunit of mitoKATP. Although SUR2A-55 lacks the first nucleotide binding domain (NBD) and 2 transmembrane domains (TMD), it has a hybrid TMD and retains the second NBD. It resembles a hemi-ABC transporter suggesting it could multimerize to function as a regulatory subunit. A putative mitochondrial targeting signal in the N-terminal domain of SUR2A-55 was removed by truncation and when co-expressed with Kir6.1 and Kir6.2 it targeted to the plasma membrane and yielded KATP currents. Single channel conductance, mean open time, and burst open time of SUR2A-55 based KATP was similar to the full-length SUR2A based KATP. However, the SUR2A-55 KATP were 70-fold less sensitive to block by ATP, and twice as resistant to intracellular Ca2+ inhibition compared with the SUR2A KATP, and were markedly insensitive to KATP drugs, pinacidil, diazoxide, and glybenclamide. These results suggest that the SUR2A-55 based channels would tend to be open under physiological conditions and in ischemia, and could account for cardiac and mitochondrial phenotypes protective for ischemia. PMID:24037327

A new safety channel based on ¹⁷N detection in research reactors.

PubMed

Seyfi, Somayye; Gharib, Morteza

2015-10-01

Tehran research reactor (TRR) is a representative of pool type research reactors using light water, as coolant and moderator. This reactor is chosen as a prototype to demonstrate and prove the feasibility of (17)N detection as a new redundant channel for reactor power measurement. In TRR, similar to other pool type reactors, neutron detectors are immersed in the pool around the core as the main power measuring devices. In the present article, a different approach, using out of water neutron detector, is employed to measure reactor power. This new method is based on (17)O (n,p) (17)N reaction taking place inside the core and subsequent measurement of delayed neutrons emitted due to (17)N disintegration. Count and measurement of neutrons around outlet water pipe provides a reliable redundant safety channel to measure reactor power. Results compared with other established channels indicate a good agreement and shows a linear interdependency with true thermal power. Safety of reactor operation is improved with installation & use of this new power measuring channel. The new approach may equally serve well as a redundant channel in all other types of reactors having coolant comprised of oxygen in its molecular constituents. Contrary to existing channels, this one is totally out of water and thus is an advantage over current instrumentations. It is proposed to employ the same idea on other reactors (nuclear power plants too) to improve safety criteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of Ancillary Subunits on Ventricular Repolarization

PubMed Central

Abbott, Geoffrey W.; Xu, Xianghua; Roepke, Torsten K.

2007-01-01

Voltage-gated potassium (Kv) channels generate the outward K+ ion currents that constitute the primary force in ventricular repolarization. Kv channels comprise tetramers of pore-forming α subunits and, in probably the majority of cases in vivo, ancillary or β subunits that help define the properties of the Kv current generated. Ancillary subunits can be broadly categorized as cytoplasmic or transmembrane, and can modify Kv channel trafficking, conductance, gating, ion selectivity, regulation and pharmacology. Because of their often profound effects on Kv channel function, studies of the molecular correlates of ventricular repolarization must take into account ancillary subunits as well as α subunits. Cytoplasmic ancillary subunits include the Kvβ subunits, which regulate a range of Kv channels and may link channel gating to redox potential; and the KChIPs, which appear most often associated with Kv4 subfamily channels that generate the ventricular Ito current. Transmembrane ancillary subunits include the MinK-related proteins (MiRPs) encoded by KCNE genes, which modulate members of most Kv α subunit subfamilies; and the putative 12-transmembrane domain KCR1 protein which modulates hERG. In some cases, such as the ventricular IKs channel complex, it is well-established that the KCNQ1 α subunit must co-assemble with the MinK (KCNE1) single transmembrane domain ancillary subunit for recapitulation of the characteristic, unusually slowly-activating IKs current. In other cases it is not so clear-cut, and in particular the roles of the other MinK-related proteins (MiRPs 1–4) in regulating cardiac Kv channels such as KCNQ1 and hERG in vivo are under debate. MiRP1 alters hERG function and pharmacology, and inherited MiRP1 mutations are associated with inherited and acquired arrhythmias, but controversy exists over the native role of MiRP1 in regulating hERG (and therefore ventricular IKr) in vivo. Some ancillary subunits may exhibit varied expression to shape spatial Kv current variation, e.g. KChIP2 and the epicardial-endocardial Ito current density gradient. Indeed, it is likely that most native ventricular Kv channels exhibit temporal and spatial heterogeneity of subunit composition, complicating both modeling of their functional impact on the ventricular action potential and design of specific current-targeted compounds. Here, we discuss current thinking and lines of experimentation aimed at resolving the complexities of the Kv channel complexes that repolarize the human ventricular myocardium. PMID:17993327

Conservation of cardiac L-type Ca2+ channels and their regulation in Drosophila: A novel genetically-pliable channelopathic model.

PubMed

Limpitikul, Worawan B; Viswanathan, Meera C; O'Rourke, Brian; Yue, David T; Cammarato, Anthony

2018-04-21

Dysregulation of L-type Ca 2+ channels (LTCCs) underlies numerous cardiac pathologies. Understanding their modulation with high fidelity relies on investigating LTCCs in their native environment with intact interacting proteins. Such studies benefit from genetic manipulation of endogenous channels in cardiomyocytes, which often proves cumbersome in mammalian models. Drosophila melanogaster, however, offers a potentially efficient alternative as it possesses a relatively simple heart, is genetically pliable, and expresses well-conserved genes. Fluorescence in situ hybridization confirmed an abundance of Ca-α1D and Ca-α1T mRNA in fly myocardium, which encode subunits that specify hetero-oligomeric channels homologous to mammalian LTCCs and T-type Ca 2+ channels, respectively. Cardiac-specific knockdown of Ca-α1D via interfering RNA abolished cardiac contraction, suggesting Ca-α1D (i.e. A1D) represents the primary functioning Ca 2+ channel in Drosophila hearts. Moreover, we successfully isolated viable single cardiomyocytes and recorded Ca 2+ currents via patch clamping, a feat never before accomplished with the fly model. The profile of Ca 2+ currents recorded in individual cells when Ca 2+ channels were hypomorphic, absent, or under selective LTCC blockage by nifedipine, additionally confirmed the predominance of A1D current across all activation voltages. T-type current, activated at more negative voltages, was also detected. Lastly, A1D channels displayed Ca 2+ -dependent inactivation, a critical negative feedback mechanism of LTCCs, and the current through them was augmented by forskolin, an activator of the protein kinase A pathway. In sum, the Drosophila heart possesses a conserved compendium of Ca 2+ channels, suggesting that the fly may serve as a robust and effective platform for studying cardiac channelopathies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata

PubMed Central

Benton, Mark D.; Lewis, Amanda H.; Bant, Jason S.

2013-01-01

Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17–21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias. PMID:23446695

Crystal Structure of a Fibroblast Growth Factor Homologous Factor (FHF) Defines a Conserved Surface on FHFs for Binding and Modulation of Voltage-gated Sodium Channels

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

Goetz, R.; Dover, K; Laezza, F

2009-01-01

Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel bindingmore » in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.« less

Stretch-activated TRPV2 channels: Role in mediating cardiopathies.

PubMed

Aguettaz, Elizabeth; Bois, Patrick; Cognard, Christian; Sebille, Stéphane

2017-11-01

Transient receptor potential vanilloid type 2, TRPV2, is a calcium-permeable cation channel belonging to the TRPV channel family. Although this channel has been first characterized as a noxious heat sensor, its mechanosensor property recently gained importance in various physiological functions. TRPV2 has been described as a stretch-mediated channel and a regulator of calcium homeostasis in several cell types and has been shown to be involved in the stretch-dependent responses in cardiomyocytes. Hence, several studies in the last years support the idea that TRPV2 play a key role in the function and structure of the heart, being involved in the cardiac compensatory mechanisms in response to pathologic or exercise-induced stress. We present here an overview of the current literature and concepts of TRPV2 channels involvement (i) in the mechanical coupling mechanisms in heart and (ii) in the mechanisms that lead to cardiomyopathies. All these studies lead us to think that TRPV2 may also be an important cardiac drug target based on its major physiological roles in heart. Copyright © 2017 Elsevier Ltd. All rights reserved.

DNA Origami Scaffolds as Templates for Functional Tetrameric Kir3 K+ Channels.

PubMed

Kurokawa, Tatsuki; Kiyonaka, Shigeki; Nakata, Eiji; Endo, Masayuki; Koyama, Shohei; Mori, Emiko; Tran, Nam Ha; Dinh, Huyen; Suzuki, Yuki; Hidaka, Kumi; Kawata, Masaaki; Sato, Chikara; Sugiyama, Hiroshi; Morii, Takashi; Mori, Yasuo

2018-03-01

In native systems, scaffolding proteins play important roles in assembling proteins into complexes to transduce signals. This concept is yet to be applied to the assembly of functional transmembrane protein complexes in artificial systems. To address this issue, DNA origami has the potential to serve as scaffolds that arrange proteins at specific positions in complexes. Herein, we report that Kir3 K + channel proteins are assembled through zinc-finger protein (ZFP)-adaptors at specific locations on DNA origami scaffolds. Specific binding of the ZFP-fused Kir3 channels and ZFP-based adaptors on DNA origami were confirmed by atomic force microscopy and gel electrophoresis. Furthermore, the DNA origami with ZFP binding sites nearly tripled the K + channel current activity elicited by heterotetrameric Kir3 channels in HEK293T cells. Thus, our method provides a useful template to control the oligomerization states of membrane protein complexes in vitro and in living cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Permeation and gating properties of the L-type calcium channel in mouse pancreatic beta cells

PubMed Central

1993-01-01

Ba2+ currents through L-type Ca2+ channels were recorded from cell- attached patches on mouse pancreatic beta cells. In 10 mM Ba2+, single- channel currents were recorded at -70 mV, the beta cell resting membrane potential. This suggests that Ca2+ influx at negative membrane potentials may contribute to the resting intracellular Ca2+ concentration and thus to basal insulin release. Increasing external Ba2+ increased the single-channel current amplitude and shifted the current-voltage relation to more positive potentials. This voltage shift could be modeled by assuming that divalent cations both screen and bind to surface charges located at the channel mouth. The single- channel conductance was related to the bulk Ba2+ concentration by a Langmuir isotherm with a dissociation constant (Kd(gamma)) of 5.5 mM and a maximum single-channel conductance (gamma max) of 22 pS. A closer fit to the data was obtained when the barium concentration at the membrane surface was used (Kd(gamma) = 200 mM and gamma max = 47 pS), which suggests that saturation of the concentration-conductance curve may be due to saturation of the surface Ba2+ concentration. Increasing external Ba2+ also shifted the voltage dependence of ensemble currents to positive potentials, consistent with Ba2+ screening and binding to membrane surface charge associated with gating. Ensemble currents recorded with 10 mM Ca2+ activated at more positive potentials than in 10 mM Ba2+, suggesting that external Ca2+ binds more tightly to membrane surface charge associated with gating. The perforated-patch technique was used to record whole-cell currents flowing through L-type Ca2+ channels. Inward currents in 10 mM Ba2+ had a similar voltage dependence to those recorded at a physiological Ca2+ concentration (2.6 mM). BAY-K 8644 (1 microM) increased the amplitude of the ensemble and whole-cell currents but did not alter their voltage dependence. Our results suggest that the high divalent cation solutions usually used to record single L-type Ca2+ channel activity produce a positive shift in the voltage dependence of activation (approximately 32 mV in 100 mM Ba2+). PMID:7687645

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.

The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells

PubMed Central

Shao, Li-Rong; Halvorsrud, Ragnhild; Borg-Graham, Lyle; Storm, Johan F

1999-01-01

The role of large-conductance Ca2+-dependent K+ channels (BK-channels; also known as maxi-K- or slo-channels) in spike broadening during repetitive firing was studied in CA1 pyramidal cells, using sharp electrode intracellular recordings in rat hippocampal slices, and computer modelling. Trains of action potentials elicited by depolarizing current pulses showed a progressive, frequency-dependent spike broadening, reflecting a reduced rate of repolarization. During a 50 ms long 5 spike train, the spike duration increased by 63·6 ± 3·4% from the 1st to the 3rd spike. The amplitude of the fast after-hyperpolarization (fAHP) also rapidly declined during each train. Suppression of BK-channel activity with (a) the selective BK-channel blocker iberiotoxin (IbTX, 60 nM), (b) the non-peptidergic BK-channel blocker paxilline (2–10 μM), or (c) calcium-free medium, broadened the 1st spike to a similar degree (≈60%). BK-channel suppression also caused a similar change in spike waveform as observed during repetitive firing, and eliminated (occluded) most of the spike broadening during repetitive firing. Computer simulations using a reduced compartmental model with transient BK-channel current and 10 other active ionic currents, produced an activity-dependent spike broadening that was strongly reduced when the BK-channel inactivation mechanism was removed. These results, which are supported by recent voltage-clamp data, strongly suggest that in CA1 pyramidal cells, fast inactivation of a transient BK-channel current (ICT), substantially contributes to frequency-dependent spike broadening during repetitive firing. PMID:10562340

Non-selective cation channels in plasma and vacuolar membranes and their contribution to K+ transport.

PubMed

Pottosin, Igor; Dobrovinskaya, Oxana

2014-05-15

Both in vacuolar and plasma membranes, in addition to truly K(+)-selective channels there is a variety of non-selective channels, which conduct K(+) and other ions with little preference. Many non-selective channels in the plasma membrane are active at depolarized potentials, thus, contributing to K(+) efflux rather than to K(+) uptake. They may play important roles in xylem loading or contribute to a K(+) leak, induced by salt or oxidative stress. Here, three currents, expressed in root cells, are considered: voltage-insensitive cation current, non-selective outwardly rectifying current, and low-selective conductance, activated by reactive oxygen species. The latter two do not only poorly discriminate between different cations (like K(+)vs Na(+)), but also conduct anions. Such solute channels may mediate massive electroneutral transport of salts and might be involved in osmotic adjustment or volume decrease, associated with cell death. In the tonoplast two major currents are mediated by SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually impermeable for anions. SV channels conduct mono- and divalent cations indiscriminately and are activated by high cytosolic Ca(2+) and depolarized voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and polyamines, and conduct a variety of monovalent cations, including K(+). Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which modulates their voltage dependence, and in case of SV, also alleviates channel's inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)-sensing valves, controlling K(+) distribution between the vacuole and the cytosol. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

Down-regulation of CaV1.2 channels during hypertension: how fewer CaV1.2 channels allow more Ca2+ into hypertensive arterial smooth muscle

PubMed Central

Tajada, Sendoa; Cidad, Pilar; Colinas, Olaia; Santana, L Fernando; López-López, José R; Pérez-García, M Teresa

2013-01-01

Hypertension is a clinical syndrome characterized by increased arterial tone. Although the mechanisms are varied, the generally accepted view is that increased CaV1.2 channel function is a common feature of this pathological condition. Here, we investigated the mechanisms underlying vascular dysfunction in a mouse model of genetic hypertension. Contrary to expectation, we found that whole-cell CaV1.2 currents (ICa) were lower in hypertensive (BPH line) than normotensive (BPN line) myocytes. However, local CaV1.2 sparklet activity was higher in BPH cells, suggesting that the relatively low ICa in these cells was produced by a few hyperactive CaV1.2 channels. Furthermore, our data suggest that while the lower expression of the pore-forming α1c subunit of CaV1.2 currents underlies the lower ICa in BPH myocytes, the increased sparklet activity was due to a different composition in the auxiliary subunits of the CaV1.2 complexes. ICa currents in BPN cells were produced by channels composed of α1c/α2δ/β3 subunits, while in BPH myocytes currents were probably generated by the opening of channels formed by α1c/α2δ/β2 subunits. In addition, Ca2+ sparks evoked large conductance, Ca2+-activated K+ (BK) currents of lower magnitude in BPH than in BPN myocytes, because BK channels were less sensitive to Ca2+. Our data are consistent with a model in which a decrease in the global number of CaV1.2 currents coexist with the existence of a subpopulation of highly active channels that dominate the resting Ca2+ influx. The decrease in BK channel activity makes the hyperpolarizing brake ineffective and leads BPH myocytes to a more contracted resting state. PMID:24167226

Hippocampal A-type current and Kv4.2 channel modulation by the sulfonylurea compound NS5806.

PubMed

Witzel, Katrin; Fischer, Paul; Bähring, Robert

2012-12-01

We examined the effects of the sulfonylurea compound NS5806 on neuronal A-type channel function. Using whole-cell patch-clamp we studied the effects of NS5806 on the somatodendritic A-type current (I(SA)) in cultured hippocampal neurons and the currents mediated by Kv4.2 channels coexpressed with different auxiliary β-subunits, including both Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-related proteins (DPPs), in HEK 293 cells. The amplitude of the I(SA) component in hippocampal neurons was reduced in the presence of 20 μM NS5806. I(SA) decay kinetics were slowed and the recovery kinetics accelerated, but the voltage dependence of steady-state inactivation was shifted to more negative potentials by NS5806. The peak amplitudes of currents mediated by ternary Kv4.2 channel complexes, associated with DPP6-S (short splice-variant) and either KChIP2, KChIP3 or KChIP4, were potentiated and their macroscopic inactivation slowed by NS5806, whereas the currents mediated by binary Kv4.2 channels, associated only with DPP6-S, were suppressed, and the NS5806-mediated slowing of macroscopic inactivation was less pronounced. Neither potentiation nor suppression and no effect on current decay kinetics in the presence of NS5806 were observed for Kv4.2 channels associated with KChIP3 and the N-type inactivation-conferring DPP6a splice-variant. For all recombinant channel complexes, NS5806 slowed the recovery from inactivation and shifted the voltage dependence of steady-state inactivation to more negative potentials. Our results demonstrate the activity of NS5806 on native I(SA) and possible molecular correlates in the form of recombinant Kv4.2 channels complexed with different KChIPs and DPPs, and they shed some light on the mechanism of NS5806 action. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dynamic reciprocity of sodium and potassium channel expression in a macromolecular complex controls cardiac excitability and arrhythmia.

PubMed

Milstein, Michelle L; Musa, Hassan; Balbuena, Daniela Ponce; Anumonwo, Justus M B; Auerbach, David S; Furspan, Philip B; Hou, Luqia; Hu, Bin; Schumacher, Sarah M; Vaidyanathan, Ravi; Martens, Jeffrey R; Jalife, José

2012-07-31

The cardiac electrical impulse depends on an orchestrated interplay of transmembrane ionic currents in myocardial cells. Two critical ionic current mechanisms are the inwardly rectifying potassium current (I(K1)), which is important for maintenance of the cell resting membrane potential, and the sodium current (I(Na)), which provides a rapid depolarizing current during the upstroke of the action potential. By controlling the resting membrane potential, I(K1) modifies sodium channel availability and therefore, cell excitability, action potential duration, and velocity of impulse propagation. Additionally, I(K1)-I(Na) interactions are key determinants of electrical rotor frequency responsible for abnormal, often lethal, cardiac reentrant activity. Here, we have used a multidisciplinary approach based on molecular and biochemical techniques, acute gene transfer or silencing, and electrophysiology to show that I(K1)-I(Na) interactions involve a reciprocal modulation of expression of their respective channel proteins (Kir2.1 and Na(V)1.5) within a macromolecular complex. Thus, an increase in functional expression of one channel reciprocally modulates the other to enhance cardiac excitability. The modulation is model-independent; it is demonstrable in myocytes isolated from mouse and rat hearts and with transgenic and adenoviral-mediated overexpression/silencing. We also show that the post synaptic density, discs large, and zonula occludens-1 (PDZ) domain protein SAP97 is a component of this macromolecular complex. We show that the interplay between Na(v)1.5 and Kir2.1 has electrophysiological consequences on the myocardium and that SAP97 may affect the integrity of this complex or the nature of Na(v)1.5-Kir2.1 interactions. The reciprocal modulation between Na(v)1.5 and Kir2.1 and the respective ionic currents should be important in the ability of the heart to undergo self-sustaining cardiac rhythm disturbances.

Physical and functional interactions between a glioma cation channel and integrin-β1 require α-actinin

PubMed Central

Rooj, Arun K.; Liu, Zhiyong; McNicholas, Carmel M.

2015-01-01

Major plasma membrane components of the tumor cell, ion channels, and integrins play crucial roles in metastasis. Glioma cells express an amiloride-sensitive nonselective cation channel composed of acid-sensing ion channel (ASIC)-1 and epithelial Na+ channel (ENaC) α- and γ-subunits. Inhibition of this channel is associated with reduced cell migration and proliferation. Using the ASIC-1 subunit as a reporter for the channel complex, we found a physical and functional interaction between this channel and integrin-β1. Short hairpin RNA knockdown of integrin-β1 attenuated the amiloride-sensitive current, which was due to loss of surface expression of ASIC-1. In contrast, upregulation of membrane expression of integrin-β1 increased the surface expression of ASIC-1. The link between the amiloride-sensitive channel and integrin-β1 was mediated by α-actinin. Downregulation of α-actinin-1 or -4 attenuated the amiloride-sensitive current. Mutation of the putative binding site for α-actinin on the COOH terminus of ASIC-1 reduced the membrane localization of ASIC-1 and also resulted in attenuation of the amiloride-sensitive current. Our data suggest a novel interaction between the amiloride-sensitive glioma cation channel and integrin-β1, mediated by α-actinin. This interaction may form a mechanism by which channel activity can regulate glioma cell proliferation and migration. PMID:26108662

Mechanosensitive Piezo Channels in the Gastrointestinal Tract.

PubMed

Alcaino, C; Farrugia, G; Beyder, A

2017-01-01

Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types-epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling. Several mechanosensitive ionic conductances have been identified in the mechanosensory GI cells, ranging from mechanosensitive voltage-gated sodium and calcium channels to the mechanogated ion channels, such as the two-pore domain potassium channels K2P (TREK-1) and nonselective cation channels from the transient receptor potential family. The recently discovered Piezo channels are increasingly recognized as significant contributors to cellular mechanosensitivity. Piezo1 and Piezo2 are nonselective cationic ion channels that are directly activated by mechanical forces and have well-defined biophysical and pharmacologic properties. The role of Piezo channels in the GI epithelium is currently under investigation and their role in the smooth muscle syncytium and enteric neurons is still not known. In this review, we outline the current state of knowledge on mechanosensitive ion channels in the GI tract, with a focus on the known and potential functions of the Piezo channels. Copyright © 2017 Elsevier Inc. All rights reserved.

Cockpit display of hazardous wind shear information

NASA Technical Reports Server (NTRS)

Wanke, Craig; Hansman, R. John, Jr.

1990-01-01

Information on cockpit display of wind shear information is given in viewgraph form. Based on the current status of windshear sensors and candidate data dissemination systems, the near-term capabilities for windshear avoidance will most likely include: (1) Ground-based detection: TDWR (Terminal Doppler Weather Radar), LLWAS (Low-Level Windshear Alert System), Automated PIREPS; (2) Ground-Air datalinks: Air traffic control voice channels, Mode-S digital datalink, ACARS alphanumeric datalink. The possible datapaths for integration of these systems are illustrated in a diagram. In the future, airborne windshear detection systems such as lidars, passive IR detectors, or airborne Doppler radars may also become available. Possible future datalinks include satellite downlink and specialized en route weather channels.

Electrical characteristics of silicon percolating nanonet-based field effect transistors in the presence of dispersion

NASA Astrophysics Data System (ADS)

Cazimajou, T.; Legallais, M.; Mouis, M.; Ternon, C.; Salem, B.; Ghibaudo, G.

2018-05-01

We studied the current-voltage characteristics of percolating networks of silicon nanowires (nanonets), operated in back-gated transistor mode, for future use as gas or biosensors. These devices featured P-type field-effect characteristics. It was found that a Lambert W function-based compact model could be used for parameter extraction of electrical parameters such as apparent low field mobility, threshold voltage and subthreshold slope ideality factor. Their variation with channel length and nanowire density was related to the change of conduction regime from direct source/drain connection by parallel nanowires to percolating channels. Experimental results could be related in part to an influence of the threshold voltage dispersion of individual nanowires.

Multichannel photonic Hilbert transformers based on complex modulated integrated Bragg gratings.

PubMed

Cheng, Rui; Chrostowski, Lukas

2018-03-01

Multichannel photonic Hilbert transformers (MPHTs) are reported. The devices are based on single compact spiral integrated Bragg gratings on silicon with coupling coefficients precisely modulated by the phase of each grating period. MPHTs with up to nine wavelength channels and a single-channel bandwidth of up to ∼625  GHz are achieved. The potential of the devices for multichannel single-sideband signal generation is suggested. The work offers a new possibility of utilizing wavelength as an extra degree of freedom in designing radio-frequency photonic signal processors. Such multichannel processors are expected to possess improved capacities and a potential to greatly benefit current widespread wavelength division multiplexed systems.

Template-based synthesis and magnetic properties of Mn-Zn ferrite nanotube and nanowire arrays

NASA Astrophysics Data System (ADS)

Guo, Limin; Wang, Xiaohui; Zhong, Caifu; Li, Longtu

2012-01-01

Template-based electrophoretic deposition of Mn-Zn ferrite nanotubes (NTs) and nanowires (NWs) were achieved using anodic alumina oxide (AAO) membranes. The effect of electrophoretic current and deposition time on the morphology of the tubes was investigated. The samples show cubic spinel structure with no preferred orientation. Room-temperature magnetic properties of the Mn-Zn ferrite NT/NW arrays were studied. The magnetic easy axis parallels the NT/NW's channel axis attributing to the large shape anisotropy in this direction, especially for the NTs with a small wall thickness. Magnetocrystalline anisotropy and magnetostatic interactions were found dominant in the samples when applied field was perpendicular to the channel axis.

The Prevention Disaster Program of Flood in 2013 for the 4th Grade Students of Kawatanaka Primary School, Tokushima Prefecture, Japan and Underflow Channels Revealed in 2016

NASA Astrophysics Data System (ADS)

Kawamata, Sanae; Murata, Mamoru

2017-12-01

The Typhoon No. 18 caused flood on September 15, 2013 in the Kawata River basin, Yoshinogawa City, Tokushima Prefecture. The Kawata River is a raised river bed of 36.7 m with banks to 40.5 m above sea level. The heavy rain did not destroy the banks but made the river level 39.4 m high and then pressed the underflow channel. As the Kawatanaka primary school is located at 36.2 m height, it was not submerged although the underflow channel overbanked the adjacent playground. An educational program on the prevention and reduction for natural disaster, which consists of science, social studies and presentation, was conducted to 18 students of the 4th grade in the period of integrated study in the Kawatanaka primary school from September 17, 2013. On the first day, flow current markings from 625 holes, 30 cm to 1 mm in diameter, on the playground were observed. The flow currents showed direction from SE to NW. On the basis of their observations on the flow currents that water runs from high to low, the students considered the phenomena as a result of tilting of the ground. They conducted activity as their homework to confirm their hypothesis to know if there is any tilt in the ground. They took plastic bottle filled with water and reviled that the ground had 1 to 2 degrees’ tilt to the NW during the experiment. On the bases of the difference between E to W flow of the Kawata River and their SE to NW estimated current flow on the playground and the fact that the bank of the river was not destroyed, the students suggested that the heavy rain had pressed the underflow channels. The suggested channels were found on the playground, where new school buildings were constructed in 2016, by one of the students who studied the program in 2013.

Pacemaker channels produce an instantaneous current.

PubMed

Proenza, Catherine; Angoli, Damiano; Agranovich, Eugene; Macri, Vincenzo; Accili, Eric A

2002-02-15

Spontaneous rhythmic activity in mammalian heart and brain depends on pacemaker currents (I(h)), which are produced by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well characterized, slowly activating I(h). I(inst(HCN2)) was specific to expression of HCN2 on the plasma membrane and its amplitude was correlated with that of I(h). The two currents had similar reversal potentials, and both were modulated by changes in intracellular Cl(-) and cAMP. A mutation in the S4 domain of HCN2 (S306Q) decreased I(h) but did not alter I(inst(HCN2)), and instantaneous currents in cells expressing either wild type HCN2 or mutant S306Q channels were insensitive to block by Cs(+). Co-expression of HCN2 with the accessory subunit, MiRP1, decreased I(h) and increased I(inst(HCN2)), suggesting a mechanism for modulation of both currents in vivo. These data suggest that expression of HCN channels may be accompanied by a background conductance in native tissues and are consistent with at least two open states of HCN channels: I(inst(HCN2)) is produced by a Cs(+)-open state; hyperpolarization produces an additional Cs(+)-sensitive open state, which results in I(h).

Fibromodulin modulates myoblast differentiation by controlling calcium channel.

PubMed

Lee, Eun Ju; Nam, Joo Hyun; Choi, Inho

2018-06-16

Fibromodulin (FMOD) is a proteoglycan present in extracellular matrix (ECM). Based on our previous findings that FMOD controls myoblast differentiation by regulating the gene expressions of collagen type I alpha 1 (COL1α1) and integral membrane protein 2 A (Itm2a), we undertook this study to investigate relationships between FMOD and calcium channels and to understand further the mechanism by which they control myoblast differentiation. Gene expression studies and luciferase reporter assays showed FMOD affected calcium channel gene expressions by regulating calcium channel gene promoter, and patch-clamp experiments showed both L- and T-type calcium channel currents were almost undetectable in FMOD knocked down cells. In addition, gene knock-down studies demonstrated the COL1α1 and Itm2a genes both regulate the expressions of calcium channel genes. Studies using a cardiotoxin-induced mouse muscle injury model demonstrated calcium channels play important roles in the regeneration of muscle tissue, possibly by promoting the differentiation of muscle stem cells (MSCs). Summarizing, the study demonstrates ECM components secreted by myoblasts during differentiation provide an essential environment for muscle differentiation and regeneration. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line.

PubMed

Ishihara, Keiko; Ehara, Tsuguhisa

2004-04-01

The strong inward rectifier K(+) current, I(K1), shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward I(K1) is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K(+) channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current-voltage (I-V) relationships of Kir2.1, obtained with 5-10 microm spermine or 10-100 microm spermidine, were similar to the steady-state outward I-V relationship of I(K1), showing a peak at a level that is approximately 20 mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1 microm spermine/spermidine or 0.1 microm spermine, respectively. In the chord conductance-voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5-10 microm spermine or 10-100 microm spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1-10 microm spermine, 0.75 with 1-100 microm spermidine, and between 0.75 and 0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine with the channel at an intracellular site appeared to modify the equilibrium of the two conformational channel states that allow different modes of blockage. Our results suggest that the outward I(K1) is primarily generated by channels with lower affinities for polyamines. Polyamines may regulate the amplitude of the outward I(K1), not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block.

Three-dimensional model of hydro acoustic channel for research MIMO systems

NASA Astrophysics Data System (ADS)

Fedosov, V. P.; Lomakina, A. V.; Legin, A. A.; Voronin, V. V.

2017-05-01

Currently, wireless hydroacoustic modems are actively being developed, which are used to provide efficient data transmission in the hydroacoustic channel. Such kind of developments are relevant for today, as they are used in various fields of science and fields of activity. An example is the connection with underwater vehicles for scientific, research, search and rescue purposes. Development of this kind of communication systems (modems) is a difficult task, as signal propagation is affected by various factors. As a result, the transfer characteristic changes with time, thereby imposing restrictions on the acoustic communication channel. In this regard, the researchers began the task of further study sonar environment and get a detailed mathematical description of the underwater channel. For this, a huge number of field tests were conducted, aimed at studying the underwater acoustic environment. However, the results of the research are always limited by the conditions in which the test took place. Therefore, it is not always possible to apply these results to the required conditions. All of the above features do not allow you to create some kind of a commonly accepted model for the acoustic channel, as studies based on experiments, collected in localized environments without generalizations. This paper presents, the three-dimensional model of the sonar channel for MIMO systems in the coastal zone, based on the acoustic signal propagation characteristics in the presence of multiple paths, the influence of the Doppler effect (as a result of mobile and / or base station traffic), in terms of signal attenuation, receiver characteristics influence and Transmitting antenna, etc.

Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent mechanism.

PubMed

Choi, Shinkyu; Kim, Moon Young; Joo, Ka Young; Park, Seonghee; Kim, Ji Aee; Jung, Jae-Chul; Oh, Seikwan; Suh, Suk Hyo

2012-07-01

Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K(Ca)3.1 channels and vascular smooth muscle contraction. K(Ca)3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of K(Ca)3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit K(Ca)3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC(50)) of modafinil for the current inhibition was 6.8 ± 0.7 nM. The protein kinase A (PKA) activator forskolin also inhibited K(Ca)3.1 currents. The inhibitory effects of modafinil and forskolin on K(Ca)3.1 currents were blocked by the PKA inhibitors PKI(14-22) or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated K(Ca)3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of K(Ca)3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits K(Ca)3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K(Ca)3.1 channel blocker and vasodilator. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polydisperse particle-driven gravity currents in non-rectangular cross section channels

NASA Astrophysics Data System (ADS)

Zemach, T.

2018-01-01

We consider a high-Reynolds-number gravity current generated by polydisperse suspension of n types of particles distributed in a fluid of density ρi. Each class of particles in suspension has a different settling velocity. The current propagates along a channel of non-rectangular cross section into an ambient fluid of constant density ρa. The bottom and top of the channel are at z = 0, H, and the cross section is given by the quite general form -f1(z) ≤ y ≤ f2(z) for 0 ≤ z ≤ H. The flow is modeled by the one-layer shallow-water equations obtained for the time-dependent motion. We solve the problem by a finite-difference numerical code to present typical height h, velocity u, and mass fractions of particle (concentrations) (ϕ( j), j = 1, …, n) profiles. The runout length of suspensions in channels of power-law cross sections is analytically predicted using a simplified depth-averaged "box" model. We demonstrate that any degree of polydispersivity adds to the runout length of the currents, relative to that of equivalent monodisperse currents with an average settling velocity. The theoretical predictions are supported by the available experimental data. The present approach is a significant generalization of the particle-driven gravity current problem: on the one hand, now the monodisperse current in non-rectangular channels is a particular case of n = 1. On the other hand, the classical formulation of polydisperse currents for a rectangular channel is now just a particular case, f(z) = const., in the wide domain of cross sections covered by this new model.

Modulation of A-type potassium channels by a family of calcium sensors.

PubMed

An, W F; Bowlby, M R; Betty, M; Cao, J; Ling, H P; Mendoza, G; Hinson, J W; Mattsson, K I; Strassle, B W; Trimmer, J S; Rhodes, K J

2000-02-03

In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes. Although pore-forming alpha-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells, these differ significantly from native A-type currents. Here we describe three Kv channel-interacting proteins (KChIPs) that bind to the cytoplasmic amino termini of Kv4 alpha-subunits. We find that expression of KChIP and Kv4 together reconstitutes several features of native A-type currents by modulating the density, inactivation kinetics and rate of recovery from inactivation of Kv4 channels in heterologous cells. All three KChIPs co-localize and co-immunoprecipitate with brain Kv4 alpha-subunits, and are thus integral components of native Kv4 channel complexes. The KChIPs have four EF-hand-like domains and bind calcium ions. As the activity and density of neuronal A-type currents tightly control responses to excitatory synaptic inputs, these KChIPs may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium.

Stochastic nonlinear electrical characteristics of graphene

NASA Astrophysics Data System (ADS)

Jun Shin, Young; Gopinadhan, Kalon; Narayanapillai, Kulothungasagaran; Kalitsov, Alan; Bhatia, Charanjit S.; Yang, Hyunsoo

2013-01-01

A stochastic nonlinear electrical characteristic of graphene is reported. Abrupt current changes are observed from voltage sweeps between the source and drain with an on/off ratio up to 103. It is found that graphene channel experiences the topological change. Active radicals in an uneven graphene channel cause local changes of electrostatic potential. Simulation results based on the self-trapped electron and hole mechanism account well for the experimental data. Our findings illustrate an important issue of reliable electron transports and help for the understanding of transport properties in graphene devices.

Toxins That Affect Voltage-Gated Sodium Channels.

PubMed

Ji, Yonghua

2017-10-26

Voltage-gated sodium channels (VGSCs) are critical in generation and conduction of electrical signals in multiple excitable tissues. Natural toxins, produced by animal, plant, and microorganisms, target VGSCs through diverse strategies developed over millions of years of evolutions. Studying of the diverse interaction between VGSC and VGSC-targeting toxins has been contributing to the increasing understanding of molecular structure and function, pharmacology, and drug development potential of VGSCs. This chapter aims to summarize some of the current views on the VGSC-toxin interaction based on the established receptor sites of VGSC for natural toxins.

Large current modulation and tunneling magnetoresistance change by a side-gate electric field in a GaMnAs-based vertical spin metal-oxide-semiconductor field-effect transistor.

PubMed

Kanaki, Toshiki; Yamasaki, Hiroki; Koyama, Tomohiro; Chiba, Daichi; Ohya, Shinobu; Tanaka, Masaaki

2018-05-08

A vertical spin metal-oxide-semiconductor field-effect transistor (spin MOSFET) is a promising low-power device for the post scaling era. Here, using a ferromagnetic-semiconductor GaMnAs-based vertical spin MOSFET with a GaAs channel layer, we demonstrate a large drain-source current I DS modulation by a gate-source voltage V GS with a modulation ratio up to 130%, which is the largest value that has ever been reported for vertical spin field-effect transistors thus far. We find that the electric field effect on indirect tunneling via defect states in the GaAs channel layer is responsible for the large I DS modulation. This device shows a tunneling magnetoresistance (TMR) ratio up to ~7%, which is larger than that of the planar-type spin MOSFETs, indicating that I DS can be controlled by the magnetization configuration. Furthermore, we find that the TMR ratio can be modulated by V GS . This result mainly originates from the electric field modulation of the magnetic anisotropy of the GaMnAs ferromagnetic electrodes as well as the potential modulation of the nonmagnetic semiconductor GaAs channel layer. Our findings provide important progress towards high-performance vertical spin MOSFETs.

Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

PubMed Central

Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.

2015-01-01

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

PubMed

Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G

2015-05-01

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.

Proposal for a graphene-based all-spin logic gate

NASA Astrophysics Data System (ADS)

Su, Li; Zhao, Weisheng; Zhang, Yue; Querlioz, Damien; Zhang, Youguang; Klein, Jacques-Olivier; Dollfus, Philippe; Bournel, Arnaud

2015-02-01

In this work, we present a graphene-based all-spin logic gate (G-ASLG) that integrates the functionalities of perpendicular anisotropy magnetic tunnel junctions (p-MTJs) with spin transport in graphene-channel. It provides an ideal integration of logic and memory. The input and output states are defined as the relative magnetization between free layer and fixed layer of p-MTJs. They can be probed by the tunnel magnetoresistance and controlled by spin transfer torque effect. Using lateral non-local spin valve, the spin information is transmitted by the spin-current interaction through graphene channels. By using a physics-based spin current compact model, the operation of G-ASLG is demonstrated and its performance is analyzed. It allows us to evaluate the influence of parameters, such as spin injection efficiency, spin diffusion length, contact area, the device length, and their interdependence, and to optimize the energy and dynamic performance. Compared to other beyond-CMOS solutions, longer spin information transport length (˜μm), higher data throughput, faster computing speed (˜ns), and lower power consumption (˜μA) can be expected from the G-ASLG.

N channel JFET based digital logic gate structure

NASA Technical Reports Server (NTRS)

Krasowski, Michael J. (Inventor)

2010-01-01

A circuit topography is presented which is used to create usable digital logic gates using N (negatively doped) channel Junction Field Effect Transistors (JFETs) and load resistors, level shifting resistors, and supply rails whose values are based on the direct current (DC) parametric distributions of those JFETs. This method has direct application to the current state of the art in high temperature, for example 300.degree. C. to 500.degree. C. and higher, silicon carbide (SiC) device production. The ability to produce inverting and combinatorial logic enables the production of pulse and edge triggered latches. This scale of logic synthesis would bring digital logic and state machine capabilities to devices operating in extremely hot environments, such as the surface of Venus, near hydrothermal vents, within nuclear reactors (SiC is inherently radiation hardened), and within internal combustion engines. The basic logic gate can be configured as a driver for oscillator circuits allowing for time bases and simple digitizers for resistive or reactive sensors. The basic structure of this innovation, the inverter, can be reconfigured into various analog circuit topographies through the use of feedback structures.

Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes’ hearing problem: an innovation in multi-channel-array skin-hearing technology

PubMed Central

Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong

2014-01-01

The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes’ hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized. PMID:25317171

Wafer-scale, massively parallel carbon nanotube arrays for realizing field effect transistors with current density exceeding silicon and gallium arsenide

NASA Astrophysics Data System (ADS)

Arnold, Michael

Calculations have indicated that aligned arrays of semiconducting carbon nanotubes (CNTs) promise to outperform conventional semiconducting materials in short-channel, aggressively scaled field effect transistors (FETs) like those used in semiconductor logic and high frequency amplifier technologies. These calculations have been based on extrapolation of measurements of FETs based on one CNT, in which ballistic transport approaching the quantum conductance limit of 2Go = 4e2/h has been achieved. However, constraints in CNT sorting, processing, alignment, and contacts give rise to non-idealities when CNTs are implemented in densely-packed parallel arrays, which has resulted in a conductance per CNT far from 2Go. The consequence has been that it has been very difficult to create high performance CNT array FETs, and CNT array FETs have not outperformed but rather underperformed channel materials such as Si by 6 x or more. Here, we report nearly ballistic CNT array FETs at a density of 50 CNTs um-1, created via CNT sorting, wafer-scale alignment and assembly, and treatment. The on-state conductance in the arrays is as high as 0.46 Go per CNT, and the conductance of the arrays reaches 1.7 mS um-1, which is 7 x higher than previous state-of-the-art CNT array FETs made by other methods. The saturated on-state current density reaches 900 uA um-1 and is similar to or exceeds that of Si FETs when compared at equivalent gate oxide thickness, off-state current density, and channel length. The on-state current density exceeds that of GaAs FETs, as well. This leap in CNT FET array performance is a significant advance towards the exploitation of CNTs in high-performance semiconductor electronics technologies.

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.

Implementation of controlled quantum teleportation with an arbitrator for secure quantum channels via quantum dots inside optical cavities.

PubMed

Heo, Jino; Hong, Chang-Ho; Kang, Min-Sung; Yang, Hyeon; Yang, Hyung-Jin; Hong, Jong-Phil; Choi, Seong-Gon

2017-11-02

We propose a controlled quantum teleportation scheme to teleport an unknown state based on the interactions between flying photons and quantum dots (QDs) confined within single- and double-sided cavities. In our scheme, users (Alice and Bob) can teleport the unknown state through a secure entanglement channel under the control and distribution of an arbitrator (Trent). For construction of the entanglement channel, Trent utilizes the interactions between two photons and the QD-cavity system, which consists of a charged QD (negatively charged exciton) inside a single-sided cavity. Subsequently, Alice can teleport the unknown state of the electron spin in a QD inside a double-sided cavity to Bob's electron spin in a QD inside a single-sided cavity assisted by the channel information from Trent. Furthermore, our scheme using QD-cavity systems is feasible with high fidelity, and can be experimentally realized with current technologies.

NB-PLC channel modelling with cyclostationary noise addition & OFDM implementation for smart grid

NASA Astrophysics Data System (ADS)

Thomas, Togis; Gupta, K. K.

2016-03-01

Power line communication (PLC) technology can be a viable solution for the future ubiquitous networks because it provides a cheaper alternative to other wired technology currently being used for communication. In smart grid Power Line Communication (PLC) is used to support communication with low rate on low voltage (LV) distribution network. In this paper, we propose the channel modelling of narrowband (NB) PLC in the frequency range 5 KHz to 500 KHz by using ABCD parameter with cyclostationary noise addition. Behaviour of the channel was studied by the addition of 11KV/230V transformer, by varying load location and load. Bit error rate (BER) Vs signal to noise ratio SNR) was plotted for the proposed model by employing OFDM. Our simulation results based on the proposed channel model show an acceptable performance in terms of bit error rate versus signal to noise ratio, which enables communication required for smart grid applications.

A Source for Fuel Supply to a Fusion Reactor Core

NASA Astrophysics Data System (ADS)

Voronin, A. V.; Bakharev, N. N.; Gusev, V. K.; Novokhatskii, A. N.; Ponyaev, S. A.

2018-05-01

We present the results of studies of the plasma source based on the coaxial accelerator with the slothole channel geometry for plasma acceleration and working gas inlet into the accelerator via the electrodynamic valve. The plasma parameters at the output of the accelerator are measured. The slot-hole channel of the accelerator created higher jet pressure, as compared to the coaxial channel, especially at large distances from the source. The jet pressure reached 106 N/m2 at a distance of 0.7 m. The source created moderately pure plasma for a current below 80 kA. The density was (2.5-5) × 1022 m-3, which was higher than the density obtained with the coaxial gun.

Silicon-compatible high-hole-mobility transistor with an undoped germanium channel for low-power application

NASA Astrophysics Data System (ADS)

Cho, Seongjae; Man Kang, In; Rok Kim, Kyung; Park, Byung-Gook; Harris, James S.

2013-11-01

In this work, Ge-based high-hole-mobility transistor with Si compatibility is designed, and its performance is evaluated. A 2-dimensional hole gas is effectively constructed by a AlGaAs/Ge/Si heterojunction with a sufficiently large valence band offset. Moreover, an intrinsic Ge channel is exploited so that high hole mobility is preserved without dopant scattering. Effects of design parameters such as gate length, Ge channel thickness, and aluminum fraction in the barrier material on device characteristics are thoroughly investigated through device simulations. A high on-current above 30 μA/μm along with a low subthreshold swing was obtained from an optimized planar device for low-power applications.

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.

Properties of glutamate-gated ion channels in horizontal cells of the perch retina.

PubMed

Schmidt, K F

1997-08-01

The effect of two different concentrations of L-glutamate and kainate on the gating kinetics of amino acid-sensitive non-NMDA channels were studied in cultured teleost retinal horizontal cells by single-channel recording and by noise analysis of whole-cell currents. When the glutamate agonist kainate was applied clearly parabolic mean-variance relations of whole-cell membrane currents (up to 3000 pA) indicated that this agonist was acting on one type of channels with a conductance of 5-10 pS. The cells were less sensitive when L-glutamate was used as the agonist and in most cases whole-cell currents amounted to less than 200 pA. The mean-variance relation of glutamate induced currents was complex, indicating that more than one type of channel opening could be involved. Power spectra of whole-cell currents were fitted with two Lorentzians with time constants of approx. 1 and 5-20 msec. Effects on amplitudes and time constants of agonist concentrations are demonstrated. Two categories of unitary events with mean open times of approx. 1 and 7 msec and conductances of approx. 7 and 12 pS, respectively, were obtained in single-channel recordings from cell-attached patches at different concentrations of glutamate in the pipette.

A nonlinear model of flow in meandering submarine and subaerial channels

NASA Astrophysics Data System (ADS)

Imran, Jasim; Parker, Gary; Pirmez, Carlos

1999-12-01

A generalized model of flow in meandering subaqueous and subaerial channels is developed. The conservation equations of mass and momentum are depth/layer integrated, normalized, and represented as deviations from a straight base state. This allows the determination of integrable forms which can be solved at both linear and nonlinear levels. The effects of various flow and geometric parameters on the flow dynamics are studied. Although the model is not limited to any specific planform, this study focuses on sine-generated curves. In analysing the flow patterns, the turbidity current of the subaqueous case is simplified to a conservative density flow with water entrainment from above neglected. The subaqueous model thus formally corresponds to a subcritical or only mildly supercritical mud-rich turbidity current. By extension, however the analysis can be applied to a depositional or erosional current carrying sand that is changing only slowly in the streamwise direction. By bringing the subaqueous and subaerial cases into a common form, flow behaviour in the two environments can be compared under similar geometric and boundary conditions. A major difference between the two cases is the degree of superelevation of channel flow around bends, which is modest in the subaerial case but substantial in the subaqueous case. Another difference concerns Coriolis effects: some of the largest subaqueous meandering systems are so large that Coriolis effects can become important. The model is applied to meander bends on the youngest channel in the mid-fan region of the Amazon Fan and a mildly sinuous bend of the North-West Atlantic Mid-Ocean Channel. In the absence of specific data on the turbid flows that created the channel, the model can be used to make inferences about the flow, and in particular the range of values of flow velocity and sediment concentration that would allow the growth and downfan migration of meander bends.

Slack, Slick, and Sodium-Activated Potassium Channels

PubMed Central

Kaczmarek, Leonard K.

2013-01-01

The Slack and Slick genes encode potassium channels that are very widely expressed in the central nervous system. These channels are activated by elevations in intracellular sodium, such as those that occur during trains of one or more action potentials, or following activation of nonselective cationic neurotransmitter receptors such as AMPA receptors. This review covers the cellular and molecular properties of Slack and Slick channels and compares them with findings on the properties of sodium-activated potassium currents (termed KNa currents) in native neurons. Human mutations in Slack channels produce extremely severe defects in learning and development, suggesting that KNa channels play a central role in neuronal plasticity and intellectual function. PMID:24319675

Potassium Channels Mediate Killing by Human Natural Killer Cells

NASA Astrophysics Data System (ADS)

Schlichter, Lyanne; Sidell, Neil; Hagiwara, Susumu

1986-01-01

Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. However, no direct evidence exists for ion channels in NK cells or in their target cells. Using the whole-cell variation of the patch-clamp technique, we found a voltage-dependent potassium (K+) current in NK cells. The K+ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd2+. We tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard 51Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd2+, and 4-aminopyridine at concentrations comparable to those that blocked the K+ current in NK cells. In K562 target cells only a voltage-dependent Na+ current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K+ current was found that was similar to the one in NK cells. We could not find any evidence of a Ca2+ current in target cells or in NK cells; therefore, our results cannot explain the Ca dependence of killing. Our findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process. In contrast, the endogenous channel type in the target cell is probably not a factor in determining target cell sensitivity to natural killing.

Folding similarity of the outer pore region in prokaryotic and eukaryotic sodium channels revealed by docking of conotoxins GIIIA, PIIIA, and KIIIA in a NavAb-based model of Nav1.4

PubMed Central

Korkosh, Viacheslav S.; Zhorov, Boris S.

2014-01-01

Voltage-gated sodium channels are targets for many drugs and toxins. However, the rational design of medically relevant channel modulators is hampered by the lack of x-ray structures of eukaryotic channels. Here, we used a homology model based on the x-ray structure of the NavAb prokaryotic sodium channel together with published experimental data to analyze interactions of the μ-conotoxins GIIIA, PIIIA, and KIIIA with the Nav1.4 eukaryotic channel. Using Monte Carlo energy minimizations and published experimentally defined pairwise contacts as distance constraints, we developed a model in which specific contacts between GIIIA and Nav1.4 were readily reproduced without deformation of the channel or toxin backbones. Computed energies of specific interactions between individual residues of GIIIA and the channel correlated with experimental estimates. The predicted complexes of PIIIA and KIIIA with Nav1.4 are consistent with a large body of experimental data. In particular, a model of Nav1.4 interactions with KIIIA and tetrodotoxin (TTX) indicated that TTX can pass between Nav1.4 and channel-bound KIIIA to reach its binding site at the selectivity filter. Our models also allowed us to explain experimental data that currently lack structural interpretations. For instance, consistent with the incomplete block observed with KIIIA and some GIIIA and PIIIA mutants, our computations predict an uninterrupted pathway for sodium ions between the extracellular space and the selectivity filter if at least one of the four outer carboxylates is not bound to the toxin. We found a good correlation between computational and experimental data on complete and incomplete channel block by native and mutant toxins. Thus, our study suggests similar folding of the outer pore region in eukaryotic and prokaryotic sodium channels. PMID:25156117

Complex role of STIM1 in the activation of store-independent Orai1/3 channels

PubMed Central

Zhang, Wei; González-Cobos, José C.; Jardin, Isaac; Romanin, Christoph; Matrougui, Khalid

2014-01-01

Orai proteins contribute to Ca2+ entry into cells through both store-dependent, Ca2+ release–activated Ca2+ (CRAC) channels (Orai1) and store-independent, arachidonic acid (AA)-regulated Ca2+ (ARC) and leukotriene C4 (LTC4)-regulated Ca2+ (LRC) channels (Orai1/3 heteromultimers). Although activated by fundamentally different mechanisms, CRAC channels, like ARC and LRC channels, require stromal interacting molecule 1 (STIM1). The role of endoplasmic reticulum–resident STIM1 (ER-STIM1) in CRAC channel activation is widely accepted. Although ER-STIM1 is necessary and sufficient for LRC channel activation in vascular smooth muscle cells (VSMCs), the minor pool of STIM1 located at the plasma membrane (PM-STIM1) is necessary for ARC channel activation in HEK293 cells. To determine whether ARC and LRC conductances are mediated by the same or different populations of STIM1, Orai1, and Orai3 proteins, we used whole-cell and perforated patch-clamp recording to compare AA- and LTC4-activated currents in VSMCs and HEK293 cells. We found that both cell types show indistinguishable nonadditive LTC4- and AA-activated currents that require both Orai1 and Orai3, suggesting that both conductances are mediated by the same channel. Experiments using a nonmetabolizable form of AA or an inhibitor of 5-lipooxygenase suggested that ARC and LRC currents in both cell types could be activated by either LTC4 or AA, with LTC4 being more potent. Although PM-STIM1 was required for current activation by LTC4 and AA under whole-cell patch-clamp recordings in both cell types, ER-STIM1 was sufficient with perforated patch recordings. These results demonstrate that ARC and LRC currents are mediated by the same cellular populations of STIM1, Orai1, and Orai3, and suggest a complex role for both ER-STIM1 and PM-STIM1 in regulating these store-independent Orai1/3 channels. PMID:24567509

Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

PubMed Central

Liu, Pin W.

2014-01-01

Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

The inward rectifier potassium channel Kir2.1 is expressed in mouse neutrophils from bone marrow and liver.

PubMed

Masia, Ricard; Krause, Daniela S; Yellen, Gary

2015-02-01

Neutrophils are phagocytic cells that play a critical role in innate immunity by destroying bacterial pathogens. Channels belonging to the inward rectifier potassium channel subfamily 2 (Kir2 channels) have been described in other phagocytes (monocytes/macrophages and eosinophils) and in hematopoietic precursors of phagocytes. Their physiological function in these cells remains unclear, but some evidence suggests a role in growth factor-dependent proliferation and development. Expression of functional Kir2 channels has not been definitively demonstrated in mammalian neutrophils. Here, we show by RT-PCR that neutrophils from mouse bone marrow and liver express mRNA for the Kir2 subunit Kir2.1 but not for other subunits (Kir2.2, Kir2.3, and Kir2.4). In electrophysiological experiments, resting (unstimulated) neutrophils from mouse bone marrow and liver exhibit a constitutively active, external K(+)-dependent, strong inwardly rectifying current that constitutes the dominant current. The reversal potential is dependent on the external K(+) concentration in a Nernstian fashion, as expected for a K(+)-selective current. The current is not altered by changes in external or internal pH, and it is blocked by Ba(2+), Cs(+), and the Kir2-selective inhibitor ML133. The single-channel conductance is in agreement with previously reported values for Kir2.1 channels. These properties are characteristic of homomeric Kir2.1 channels. Current density in short-term cultures of bone marrow neutrophils is decreased in the absence of growth factors that are important for neutrophil proliferation [granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF)]. These results demonstrate that mouse neutrophils express functional Kir2.1 channels and suggest that these channels may be important for neutrophil function, possibly in a growth factor-dependent manner. Copyright © 2015 the American Physiological Society.

A 200-Channel Area-Power-Efficient Chemical and Electrical Dual-Mode Acquisition IC for the Study of Neurodegenerative Diseases.

PubMed

Guo, Jing; Ng, Waichiu; Yuan, Jie; Li, Suwen; Chan, Mansun

2016-06-01

Microelectrode array (MEA) can be used in the study of neurodegenerative diseases by monitoring the chemical neurotransmitter release and the electrical potential simultaneously at the cellular level. Currently, the MEA technology is migrating to more electrodes and higher electrode density, which raises power and area constraints on the design of acquisition IC. In this paper, we report the design of a 200-channel dual-mode acquisition IC with highly efficient usage of power and area. Under the constraints of target noise and fast settling, the current channel design saves power by including a novel current buffer biased in discrete time (DT) before the TIA (transimpedance amplifier). The 200 channels are sampled at 20 kS/s and quantized by column-wise SAR ADCs. The prototype IC was fabricated in a 0.18 μm CMOS process. Silicon measurements show the current channel has 21.6 pArms noise with cyclic voltammetry (CV) and 0.48 pArms noise with constant amperometry (CA) while consuming 12.1 μW . The voltage channel has 4.07 μVrms noise in the bandwidth of 100 kHz and 0.2% nonlinearity while consuming 9.1 μW. Each channel occupies 0.03 mm(2) area, which is among the smallest.

Changes in Inward Rectifier K+ Channels in Hepatic Stellate Cells During Primary Culture

PubMed Central

Lee, Dong Hyeon; Kong, In Deok; Lee, Joong-Woo

2008-01-01

Purpose This study examined the expression and function of inward rectifier K+ channels in cultured rat hepatic stellate cells (HSC). Materials and Methods The expression of inward rectifier K+ channels was measured using real-time RT-PCR, and electrophysiological properties were determined using the gramicidin-perforated patch-clamp technique. Results The dominant inward rectifier K+ channel subtypes were Kir2.1 and Kir6.1. These dominant K+ channel subtypes decreased significantly during the primary culture throughout activation process. HSC can be classified into two subgroups: one with an inward-rectifying K+ current (type 1) and the other without (type 2). The inward current was blocked by Ba2+ (100 µM) and enhanced by high K+ (140 mM), more prominently in type 1 HSC. There was a correlation between the amplitude of the Ba2+-sensitive current and the membrane potential. In addition, Ba2+ (300 µM) depolarized the membrane potential. After the culture period, the amplitude of the inward current decreased and the membrane potential became depolarized. Conclusion HSC express inward rectifier K+ channels, which physiologically regulate membrane potential and decrease during the activation process. These results will potentially help determine properties of the inward rectifier K+ channels in HSC as well as their roles in the activation process. PMID:18581597

Multiple modes of a-type potassium current regulation.

PubMed

Cai, Shi-Qing; Li, Wenchao; Sesti, Federico

2007-01-01

Voltage-dependent potassium (K+) channels (Kv) regulate cell excitability by controlling the movement of K+ ions across the membrane in response to changes in the cell voltage. The Kv family, which includes A-type channels, constitute the largest group of K+ channel genes within the superfamily of Na+, Ca2+ and K+ voltage-gated channels. The name "A-type" stems from the typical profile of these currents that results form the opposing effects of fast activation and inactivation. In neuronal cells, A-type currents (I(A)), determine the interval between two consecutive action potentials during repetitive firing. In cardiac muscle, A-type currents (I(to)), control the initial repolarization of the myocardium. Structurally, A-type channels are tetramers of alpha-subunits each containing six putative transmembrane domains including a voltage-sensor. A-type channels can be modulated by means of protein-protein interactions with so-called beta-subunits that control inactivation voltage sensitivity and other properties, and by post-transcriptional modifications such as phosphorylation or oxidation. Recently a new mode of A-type regulation has been discovered in the form of a class of hybrid beta-subunits that posses their own enzymatic activity. Here, we review the biophysical and physiological properties of these multiple modes of A-type channel regulation.

Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

NASA Astrophysics Data System (ADS)

Gulothungan, G.; Malathi, R.

2018-04-01

Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.

Watch what you say, your computer might be listening: A review of automated speech recognition

NASA Technical Reports Server (NTRS)

Degennaro, Stephen V.

1991-01-01

Spoken language is the most convenient and natural means by which people interact with each other and is, therefore, a promising candidate for human-machine interactions. Speech also offers an additional channel for hands-busy applications, complementing the use of motor output channels for control. Current speech recognition systems vary considerably across a number of important characteristics, including vocabulary size, speaking mode, training requirements for new speakers, robustness to acoustic environments, and accuracy. Algorithmically, these systems range from rule-based techniques through more probabilistic or self-learning approaches such as hidden Markov modeling and neural networks. This tutorial begins with a brief summary of the relevant features of current speech recognition systems and the strengths and weaknesses of the various algorithmic approaches.

The status of membrane bioreactor technology.

PubMed

Judd, Simon

2008-02-01

In this article, the current status of membrane bioreactor (MBR) technology for wastewater treatment is reviewed. Fundamental facets of the MBR process and membrane and process configurations are outlined and the advantages and disadvantages over conventional suspended growth-based biotreatment are briefly identified. Key process design and operating parameters are defined and their significance explained. The inter-relationships between these parameters are identified and their implications discussed, with particular reference to impacts on membrane surface fouling and channel clogging. In addition, current understanding of membrane surface fouling and identification of candidate foulants is appraised. Although much interest in this technology exists and its penetration of the market will probably increase significantly, there remains a lack of understanding of key process constraints such as membrane channel clogging, and of the science of membrane cleaning.

Channel bed particle size distribution procedure used to evaluate watershed cumulative effects for range permit re-issuance on the Santa Fe National Forest

Treesearch

Bruce Sims; Jim Piatt; Lee Johnson; Carol Purchase; John Phillips

1996-01-01

Personnel on the Santa Fe National Forest used methodologies adapted from Bevenger and King (1995) to collect base line particle size data on streams within grazing allotments currently scheduled for permit reissuance. This information was used to determine the relative current health of the watersheds as well as being used in the development of potential alternatives...

Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine.

PubMed

Thurner, Patrick; Stary-Weinzinger, Anna; Gafar, Hend; Gawali, Vaibhavkumar S; Kudlacek, Oliver; Zezula, Juergen; Hilber, Karlheinz; Boehm, Stefan; Sandtner, Walter; Koenig, Xaver

2014-02-01

Ibogaine is a psychoactive indole alkaloid. Its use as an antiaddictive agent has been accompanied by QT prolongation and cardiac arrhythmias, which are most likely caused by human ether a go-go-related gene (hERG) potassium channel inhibition. Therefore, we studied in detail the interaction of ibogaine with hERG channels heterologously expressed in mammalian kidney tsA-201 cells. Currents through hERG channels were blocked regardless of whether ibogaine was applied via the extracellular or intracellular solution. The extent of inhibition was determined by the relative pH values. Block occurred during activation of the channels and was not observed for resting channels. With increasing depolarizations, ibogaine block grew and developed faster. Steady-state activation and inactivation of the channel were shifted to more negative potentials. Deactivation was slowed, whereas inactivation was accelerated. Mutations in the binding site reported for other hERG channel blockers (Y652A and F656A) reduced the potency of ibogaine, whereas an inactivation-deficient double mutant (G628C/S631C) was as sensitive as wild-type channels. Molecular drug docking indicated binding within the inner cavity of the channel independently of the protonation of ibogaine. Experimental current traces were fit to a kinetic model of hERG channel gating, revealing preferential binding of ibogaine to the open and inactivated state. Taken together, these findings show that ibogaine blocks hERG channels from the cytosolic side either in its charged form alone or in company with its uncharged form and alters the currents by changing the relative contribution of channel states over time.

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.

Characterization of a novel 132-bp exon of the human maxi-K channel.

PubMed

Korovkina, V P; Fergus, D J; Holdiman, A J; England, S K

2001-07-01

The large-conductance Ca2+-activated voltage-dependent K+ channel (maxi-K channel) induces a significant repolarizing current that buffers cell excitability. This channel can derive its diversity by alternative splicing of its transcript-producing isoforms that differ in their sensitivity to voltage and intracellular Ca2+. We have identified a novel 132-bp exon of the maxi-K channel from human myometrial cells that encodes 44 amino acids within the first intracellular loop of the channel protein. Distribution analysis reveals that this exon is expressed predominantly in human smooth muscle tissues with the highest abundance in the uterus and aorta and resembles the previously reported distribution of the total maxi-K channel transcript. Single-channel K+ current measurements in fibroblasts transfected with the maxi-K channel containing this novel 132-bp exon demonstrate that the presence of this insert attenuates the sensitivity to voltage and intracellular Ca2+. Alternative splicing to introduce this 132-bp exon into the maxi-K channel may elicit another mode to modulate cell excitability.

Conductance of Ion Channels - Theory vs. Experiment

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Wilson, Michael; Mijajlovic, Milan

2013-01-01

Transmembrane ion channels mediate a number of essential physiological processes in a cell ranging from regulating osmotic pressure to transmission of neural signals. Kinetics and selectivity of ion transport is of critical importance to a cell and, not surprisingly, it is a subject of numerous experimental and theoretical studies. In this presentation we will analyze in detail computer simulations of two simple channels from fungi - antiamoebin and trichotoxin. Each of these channels is made of an alpha-helical bundle of small, nongenomically synthesized peptides containing a number of rare amino acids and exhibits strong antimicrobial activity. We will focus on calculating ionic conductance defined as the ratio of ionic current through the channel to applied voltage. From molecular dynamics simulations, conductance can be calculated in at least two ways, each involving different approximations. Specifically, the current, given as the number of charges transferred through the channel per unit of time, can be obtained from the number of events in which ions cross the channel during the simulation. This method works well for large currents (high conductance values and/or applied voltages). If the number of crossing events is small, reliable estimates of current are difficult to achieve. Alternatively, conductance can be estimated assuming that ion transport can be well approximated as diffusion in the external potential given by the free energy profile. Then, the current can be calculated by solving the one-dimensional diffusion equation in this external potential and applied voltage (the generalized Nernst-Planck equation). To do so three ingredients are needed: the free energy profile, the position-dependent diffusion coefficient and the diffusive flux of ions into the channel. All these quantities can be obtained from molecular dynamics simulations. An important advantage of this method is that it can be used equally well to estimating large and small currents. In addition, once the free energy profile becomes available the full current-voltage dependence can be readily obtained. For both channels we carried out calculations using both approaches. We also tested the main assumptions underlying the diffusive model, such as uncorrelated nature of individual crossing events and Fickian diffusion. The accuracy and consistency of different methods will be discussed. Finally we will discuss how comparisons between calculated and measured ionic conductance and selectivity of transport can be used for determining structural models of the channels.

Characteristics of camel-gate structures with active doping channel profiles

NASA Astrophysics Data System (ADS)

Tsai, Jung-Hui; Lour, Wen-Shiung; Laih, Lih-Wen; Liu, Rong-Chau; Liu, Wen-Chau

1996-03-01

In this paper, we demonstrate the influence of channel doping profile on the performances of camel-gate field effect transistors (CAMFETs). For comparison, single and tri-step doping channel structures with identical doping thickness products are employed, while other parameters are kept unchanged. The results of a theoretical analysis show that the single doping channel FET with lightly doping active layer has higher barrier height and drain-source saturation current. However, the transconductance is decreased. For a tri-step doping channel structure, it is found that the output drain-source saturation current and the barrier height are enhanced. Furthermore, the relatively voltage independent performances are improved. Two CAMFETs with single and tri-step doping channel structures have been fabricated and discussed. The devices exhibit nearly voltage independent transconductances of 144 mS mm -1 and 222 mS mm -1 for single and tri-step doping channel CAMFETs, respectively. The operation gate voltage may extend to ± 1.5 V for a tri-step doping channel CAMFET. In addition, the drain current densities of > 750 and 405 mA mm -1 are obtained for the tri-step and single doping CAMFETs. These experimental results are inconsistent with theoretical analysis.

Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

PubMed

Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

2017-06-15

TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Redox Regulation of Neuronal Voltage-Gated Calcium Channels

PubMed Central

Jevtovic-Todorovic, Vesna

2014-01-01

Abstract Significance: Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Recent Advances: Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. Critical Issues: A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Future Directions: Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain. Antioxid. Redox Signal. 21, 880–891. PMID:24161125

Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization.

PubMed

Han, Sung Il; Hwang, Kyo Seon; Kwak, Rhokyun; Lee, Jeong Hoon

2016-06-21

Microfluidic paper-based analytical devices (μPADs) for molecular detection have great potential in the field of point-of-care diagnostics. Currently, a critical problem being faced by μPADs is improving their detection sensitivity. Various preconcentration processes have been developed, but they still have complicated structures and fabrication processes to integrate into μPADs. To address this issue, we have developed a novel paper-based preconcentrator utilizing ion concentration polarization (ICP) with minimal addition on lateral-flow paper. The cation selective membrane (i.e., Nafion) is patterned on adhesive tape, and this tape is then attached to paper-based channels. When an electric field is applied across the Nafion, ICP is initiated to preconcentrate the biomolecules in the paper channel. Departing from previous paper-based preconcentrators, we maintain steady lateral fluid flow with the separated Nafion layer; as a result, fluorescent dyes and proteins (FITC-albumin and bovine serum albumin) are continuously delivered to the preconcentration zone, achieving high preconcentration performance up to 1000-fold. In addition, we demonstrate that the Nafion-patterned tape can be integrated with various geometries (multiplexed preconcentrator) and platforms (string and polymer microfluidic channel). This work would facilitate integration of various ICP devices, including preconcentrators, pH/concentration modulators, and micro mixers, with steady lateral flows in paper-based platforms.

Double gaps along Shaker S4 demonstrate omega currents at three different closed states.

PubMed

Gamal El-Din, Tamer M; Heldstab, Hansjakob; Lehmann, Claudia; Greeff, Nikolaus G

2010-01-01

The aim of the present study was to investigate in detail how the voltage sensor in the Shaker potassium channel moves during the gating process. After the publication of the open channel structure from the crystallized K(V)AP channel in 2003, an alternative so-called "paddle" model was put forward in contrast to the existing helical screw model. The voltage sensor S4 contains 4 arginine residues relevant for gating, R1(362), R2(365), R3(368) and R4(371), each separated by 2 neutral residues. These charged residues coil as one of three threads on the S4-alpha-helix. Based on a previous finding that the mutation R1S leads to the so-called omega leak current through a "gating-pore" in the closed state, we introduced gaps systematically along the arginine thread substituting long arginines by short serines. Mutations R2S or R3S did neither create transient nor steady leaks. The fact that the native residue A359, which is located three amino acids in front of R1, is a short one, motivated us to check its role. Mutation of A359 to arginine blocked the omega current in the R1S mutant indicating that the omega pore is occupied by A359 and R1. Introducing further double gaps (RR to SS) at sequential positions (0 + 1, 1 + 2, 2 + 3), produced clear leak currents which were remarkably stable over a wide voltage range. These leaks contradict that S4 would swing together with S3 in lipid according to the paddle hypothesis. Rather, our results show that during gating the S4 segment moves in 3 helical steps through a fixed pore formed by the channel protein.

Basolateral K channels in an insect epithelium. Channel density, conductance, and block by barium

PubMed Central

Hanrahan, JW; Wills, NK; Phillips, JE; Lewis, SA

1986-01-01

K channels in the basolateral membrane of insect hindgut were studied using current fluctuation analysis and microelectrodes. Locust recta were mounted in Ussing-type chambers containing Cl-free saline and cyclic AMP (cAMP). A transepithelial K current was induced by raising serosal [K] under short-circuit conditions. Adding Ba to the mucosal (luminal) side under these conditions had no effect; however, serosal Ba reversibly inhibited the short-circuit current (Isc), increased transepithelial resistance (Rt), and added a Lorentzian component to power density spectra of the Isc. A nonlinear relationship between corner frequency and serosal [Ba] was observed, which suggests that the rate constant for Ba association with basolateral channels increased as [Ba] was elevated. Microelectrode experiments revealed that the basolateral membrane hyperpolarized when Ba was added: this change in membrane potential could explain the nonlinearity of the 2 pi fc vs. [Ba] relationship if external Ba sensed about three-quarters of the basolateral membrane field. Conventional microelectrodes were used to determine the correspondence between transepithelially measured current noise and basolateral membrane conductance fluctuations, and ion-sensitive microelectrodes were used to measure intracellular K activity (acK). From the relationship between the net electrochemical potential for K across the basolateral membrane and the single channel current calculated from noise analysis, we estimate that the conductance of basolateral K channels is approximately 60 pS, and that there are approximately 180 million channels per square centimeter of tissue area. PMID:2420918

Side-information-dependent correlation channel estimation in hash-based distributed video coding.

PubMed

Deligiannis, Nikos; Barbarien, Joeri; Jacobs, Marc; Munteanu, Adrian; Skodras, Athanassios; Schelkens, Peter

2012-04-01

In the context of low-cost video encoding, distributed video coding (DVC) has recently emerged as a potential candidate for uplink-oriented applications. This paper builds on a concept of correlation channel (CC) modeling, which expresses the correlation noise as being statistically dependent on the side information (SI). Compared with classical side-information-independent (SII) noise modeling adopted in current DVC solutions, it is theoretically proven that side-information-dependent (SID) modeling improves the Wyner-Ziv coding performance. Anchored in this finding, this paper proposes a novel algorithm for online estimation of the SID CC parameters based on already decoded information. The proposed algorithm enables bit-plane-by-bit-plane successive refinement of the channel estimation leading to progressively improved accuracy. Additionally, the proposed algorithm is included in a novel DVC architecture that employs a competitive hash-based motion estimation technique to generate high-quality SI at the decoder. Experimental results corroborate our theoretical gains and validate the accuracy of the channel estimation algorithm. The performance assessment of the proposed architecture shows remarkable and consistent coding gains over a germane group of state-of-the-art distributed and standard video codecs, even under strenuous conditions, i.e., large groups of pictures and highly irregular motion content.

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

Sancho Pitarch, Jose Carlos; Kerbyson, Darren; Lang, Mike

Increasing the core-count on current and future processors is posing critical challenges to the memory subsystem to efficiently handle concurrent memory requests. The current trend to cope with this challenge is to increase the number of memory channels available to the processor's memory controller. In this paper we investigate the effectiveness of this approach on the performance of parallel scientific applications. Specifically, we explore the trade-off between employing multiple memory channels per memory controller and the use of multiple memory controllers. Experiments conducted on two current state-of-the-art multicore processors, a 6-core AMD Istanbul and a 4-core Intel Nehalem-EP, for amore » wide range of production applications shows that there is a diminishing return when increasing the number of memory channels per memory controller. In addition, we show that this performance degradation can be efficiently addressed by increasing the ratio of memory controllers to channels while keeping the number of memory channels constant. Significant performance improvements can be achieved in this scheme, up to 28%, in the case of using two memory controllers with each with one channel compared with one controller with two memory channels.« less

The styryl dye FM1-43 suppresses odorant responses in a subset of olfactory neurons by blocking cyclic nucleotide-gated (CNG) channels.

PubMed

Breunig, Esther; Kludt, Eugen; Czesnik, Dirk; Schild, Detlev

2011-08-12

Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.

A novel muscarinic receptor-independent mechanism of KCNQ2/3 potassium channel blockade by Oxotremorine-M.

PubMed

Zwart, Ruud; Reed, Hannah; Clarke, Sophie; Sher, Emanuele

2016-11-15

Inhibition of KCNQ (Kv7) potassium channels by activation of muscarinic acetylcholine receptors has been well established, and the ion currents through these channels have been long known as M-currents. We found that this cross-talk can be reconstituted in Xenopus oocytes by co-transfection of human recombinant muscarinic M1 receptors and KCNQ2/3 potassium channels. Application of the muscarinic acetylcholine receptor agonist Oxotremorine-methiodide (Oxo-M) between voltage pulses to activate KCNQ2/3 channels caused inhibition of the subsequent KCNQ2/3 responses. This effect of Oxo-M was blocked by the muscarinic acetylcholine receptor antagonist atropine. We also found that KCNQ2/3 currents were inhibited when Oxo-M was applied during an ongoing KCNQ2/3 response, an effect that was not blocked by atropine, suggesting that Oxo-M inhibits KCNQ2/3 channels directly. Indeed, also in oocytes that were transfected with only KCNQ2/3 channels, but not with muscarinic M1 receptors, Oxo-M inhibited the KCNQ2/3 response. These results show that besides the usual muscarinic acetylcholine receptor-mediated inhibition, Oxo-M also inhibits KCNQ2/3 channels by a direct mechanism. We subsequently tested xanomeline, which is a chemically distinct muscarinic acetylcholine receptor agonist, and oxotremorine, which is a close analogue of Oxo-M. Both compounds inhibited KCNQ2/3 currents via activation of M1 muscarinic acetylcholine receptors but, in contrast to Oxo-M, they did not directly inhibit KCNQ2/3 channels. Xanomeline and oxotremorine do not contain a positively charged trimethylammonium moiety that is present in Oxo-M, suggesting that such a charged moiety could be a crucial component mediating this newly described direct inhibition of KCNQ2/3 channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Three homologous subunits form a high affinity peptide-gated ion channel in Hydra.

PubMed

Dürrnagel, Stefan; Kuhn, Anne; Tsiairis, Charisios D; Williamson, Michael; Kalbacher, Hubert; Grimmelikhuijzen, Cornelis J P; Holstein, Thomas W; Gründer, Stefan

2010-04-16

Recently, three ion channel subunits of the degenerin (DEG)/epithelial Na(+) channel (ENaC) gene family have been cloned from the freshwater polyp Hydra magnipapillata, the Hydra Na(+) channels (HyNaCs) 2-4. Two of them, HyNaC2 and HyNaC3, co-assemble to form an ion channel that is gated by the neuropeptides Hydra-RFamides I and II. The HyNaC2/3 channel is so far the only cloned ionotropic receptor from cnidarians and, together with the related ionotropic receptor FMRFamide-activated Na(+) channel (FaNaC) from snails, the only known peptide-gated ionotropic receptor. The HyNaC2/3 channel has pore properties, like a low Na(+) selectivity and a low amiloride affinity, that are different from other channels of the DEG/ENaC gene family, suggesting that a component of the native Hydra channel might still be lacking. Here, we report the cloning of a new ion channel subunit from Hydra, HyNaC5. The new subunit is closely related to HyNaC2 and -3 and co-localizes with HyNaC2 and -3 to the base of the tentacles. Coexpression in Xenopus oocytes of HyNaC5 with HyNaC2 and -3 largely increases current amplitude after peptide stimulation and affinity of the channel to Hydra-RFamides I and II. Moreover, the HyNaC2/3/5 channel has altered pore properties and amiloride affinity, more similarly to other DEG/ENaC channels. Collectively, our results suggest that the three homologous subunits HyNaC2, -3, and -5 form a peptide-gated ion channel in Hydra that could contribute to fast synaptic transmission.

Muscle length-dependent contribution of motoneuron Cav1.3 channels to force production in model slow motor unit.

PubMed

Kim, Hojeong

2017-07-01

Persistent inward current (PIC)-generating Ca v 1.3 channels in spinal motoneuron dendrites are thought to be actively recruited during normal behaviors. However, whether and how the activation of PIC channels influences force output of motor unit remains elusive. Here, building a physiologically realistic model of slow motor unit I demonstrated that force production induced by the PIC activation is much smaller for short than lengthened muscles during the regular firing of the motoneuron that transitions from the quiescent state by either a brief current pulse at the soma or a brief synaptic excitation at the dendrites. By contrast, the PIC-induced force potentiation was maximal for short muscles when the motoneuron switched from a stable low-frequency firing state to a stable high-frequency firing state by the current pulse at the soma. Under the synaptic excitation at the dendrites, however, the force could not be potentiated by the transitioning of the motoneuron from a low- to a high-frequency firing state due to the simultaneous onset of PIC at the dendrites and firing at the soma. The strong dependency of the input-output relationship of the motor unit on the neuromodulation and Ia afferent inputs for the PIC channels was further shown under static variations in muscle length. Taken together, these findings suggest that the PIC activation in the motoneuron dendrites may differentially affect the force production of the motor unit, depending not only on the firing state history of the motoneuron and the variation in muscle length but also on the mode of motor activity. NEW & NOTEWORTHY Ca v 1.3 channels in motoneuron dendrites are actively involved during normal motor activities. To investigate the effects of the activation of motoneuron Ca v 1.3 channels on force production, a model motor unit was built based on best-available data. The simulation results suggest that force potentiation induced by Ca v 1.3 channel activation is strongly modulated not only by firing history of the motoneuron but also by length variation of the muscle as well as neuromodulation inputs from the brainstem. Copyright © 2017 the American Physiological Society.

Investigation of defect-induced abnormal body current in fin field-effect-transistors

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

Liu, Kuan-Ju; Tsai, Jyun-Yu; Lu, Ying-Hsin

2015-08-24

This letter investigates the mechanism of abnormal body current at the linear region in n-channel high-k/metal gate stack fin field effect transistors. Unlike body current, which is generated by impact ionization at high drain voltages, abnormal body current was found to increase with decreasing drain voltages. Notably, the unusual body leakage only occurs in three-dimensional structure devices. Based on measurements under different operation conditions, the abnormal body current can be attributed to fin surface defect-induced leakage current, and the mechanism is electron tunneling to the fin via the defects, resulting in holes left at the body terminal.

Stimulation of the BKCa channel in cultured smooth muscle cells of human trachea by magnolol

PubMed Central

Wu, S; Chen, C; Li, H; Lo, Y; Chen, S; Chiang, H

2002-01-01

Background: Magnolol, a compound isolated from the cortex of Magnolia officinalis, has been found to possess anti-allergic and anti-asthmatic activity. Methods: The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique. Results: In whole cell current recordings magnolol reversibly increased the amplitude of K+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 µM) but not by glibenclamide (10 µM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BKCa) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1.5 µM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BKCa channels to less positive membrane potentials. The change in the kinetic behaviour of BKCa channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants. Conclusions: These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BKCa channel activity in tracheal smooth muscle cells. The direct stimulation of these BKCa channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound. PMID:11809993

Upregulation of an inward rectifying K+ channel can rescue slow Ca2+ oscillations in K(ATP) channel deficient pancreatic islets.

PubMed

Yildirim, Vehpi; Vadrevu, Suryakiran; Thompson, Benjamin; Satin, Leslie S; Bertram, Richard

2017-07-01

Plasma insulin oscillations are known to have physiological importance in the regulation of blood glucose. In insulin-secreting β-cells of pancreatic islets, K(ATP) channels play a key role in regulating glucose-dependent insulin secretion. In addition, they convey oscillations in cellular metabolism to the membrane by sensing adenine nucleotides, and are thus instrumental in mediating pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically depolarizes the β-cell plasma membrane and terminates islet oscillations. Surprisingly, when K(ATP) channels are genetically knocked out, oscillations in islet activity persist, and relatively normal blood glucose levels are maintained. Compensation must therefore occur to overcome the loss of K(ATP) channels in K(ATP) knockout mice. In a companion study, we demonstrated a substantial increase in Kir2.1 protein occurs in β-cells lacking K(ATP) because of SUR1 deletion. In this report, we demonstrate that β-cells of SUR1 null islets have an upregulated inward rectifying K+ current that helps to compensate for the loss of K(ATP) channels. This current is likely due to the increased expression of Kir2.1 channels. We used mathematical modeling to determine whether an ionic current having the biophysical characteristics of Kir2.1 is capable of rescuing oscillations that are similar in period to those of wild-type islets. By experimentally testing a key model prediction we suggest that Kir2.1 current upregulation is a likely mechanism for rescuing the oscillations seen in islets from mice deficient in K(ATP) channels.