ATP-activated chloride channel inhibited by an antibody to P glycoprotein

1994 ◽  
Vol 267 (4) ◽  
pp. C1095-C1102 ◽  
Author(s):  
J. J. Zhang ◽  
T. J. Jacob

In this report, we present the characteristics of a Cl- channel found in lens fiber cells. The single channel has a conductance of 17 pS, a linear current-voltage curve, is activated by ATP or strong depolarization and is blocked by verapamil, quinidine, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 5-nitro-2-(3- phenylpropylamino)benzoate, dideoxyforskolin, and tamoxifen. These properties are similar to those reported for a volume-activated Cl- channel associated with the multidrug resistance (MDR) gene product, P glycoprotein (24). Confirming this connection, we demonstrate that our lens Cl- channel is inhibited by an antibody to P glycoprotein. The data we present here may, therefore, be the first characterization of the single channel activity of the Cl- channel associated with P glycoprotein.

1997 ◽  
Vol 273 (2) ◽  
pp. C384-C393 ◽  
Author(s):  
A. M. Sherry ◽  
K. Stroffekova ◽  
L. M. Knapp ◽  
E. Y. Kupert ◽  
J. Cuppoletti ◽  
...  

A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.


2011 ◽  
Vol 403-408 ◽  
pp. 3411-3417
Author(s):  
Quan Sun ◽  
Zong Fu Jiang ◽  
Edmond Cretu

This paper reports on the simulation and characterization of a microelectromechanical system (MEMS) micromirror fabricated with PolyMUMPs. The overall diameter of the hexagonal micrimirror, including mirror plate and 3 supporting cantilevers fixed around, is 450um. A 3D model is built in finite element method (FEM) with COMSOL. Simulations of the elevated height of mirror plate, pull-in voltage and eigenfrequency of the micromirror are carried out. The static and dynamic performances of the fabricated micromirror are characterized by Veeco Optical Profiler and Polytek MEMS System Analyzer. The comparison between measurement and simulation exhibits good concordance. Surface topography measurement shows the elevated height and stress-induced concave deformation of mirror plate almost the same scale as demonstrated in FEM simulation. The Pull-In voltages are measured to be around 32V in current-voltage curve which is almost the same as in FEM simulation with one electrode biased. The fundamental resonant frequency is measured to be 4.3k Hz in torsional motion and 4.9k Hz in piston motion.


1989 ◽  
Vol 256 (4) ◽  
pp. C902-C912 ◽  
Author(s):  
R. J. Bridges ◽  
R. T. Worrell ◽  
R. A. Frizzell ◽  
D. J. Benos

We studied blockade by 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) of a secretory Cl- channel from colonic enterocyte plasma membrane vesicles incorporated into planar lipid bilayer membranes. Except for intermittent long-lived closed periods (100 ms to several min), the control channel open probability (Po) was greater than 90%. DNDS, added to the cis or vesicle-containing side, which corresponds to the outer membrane side of the channel, caused a dramatic increase in the number of current transitions from the open-to-closed state. DNDS caused a concentration-dependent decrease in Po with a maximum inhibition of 95 +/- 2.0% and a half-maximal inhibitory concentration of 3.3 +/- 1.4 microM. DNDS added to the trans side of the channel had no effect on either the single-channel conductance or kinetic behavior of the channel. Kinetic analysis revealed that DNDS blockade from the cis side could be explained by a linear, closed-open-blocked, kinetic scheme. The estimated DNDS block rate constants were kon = 3.2 X 10(7) M-1.s-1 and koff = 52 s-1, yielding an equilibrium dissociation constant (KD) of 2.1 +/- 0.38 microM, similar to the Ki for inhibition of Po. The effects of DNDS were fully reversible after perfusion of the cis compartment with DNDS-free solution. In contrast, the covalently reactive 4,4'-diisothiocyano-substituted stilbene disulfonate caused an irreversible blockade of the Cl- channel.


1997 ◽  
Vol 467 ◽  
Author(s):  
D. Caputo ◽  
G. De Cesare ◽  
F. Palma

ABSTRACTA novel device based on a-Si:H p+-i-n−-i-p−-i-n+ structure, showing a hysteresis in its current-voltage curve is reported. A numerical device model allows to investigate in detail the fundamental role of the two lightly doped n− and p− layers, where charge trapping determines the bistable behavior of the device. The ON condition is mantained until the ambipolar charge injection overcomes the fixed charge. The transition OFF-ON starts when, increasing the applied voltage, one of the two lightly doped layers becomes completely depleted. The transition ON-OFF is, instead, mainly dependent on the recombination processes occurring in the central doped layers. Devices with hysteresis around 2 V and tum-on voltage around 12 are presented.


Membranes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 22
Author(s):  
Anatoly N. Filippov ◽  
Natalia A. Kononenko ◽  
Natalia V. Loza ◽  
Daria A. Petrova

A novel bilayer cation-exchange membrane—consisting of a thick layer of a pristine perfluorinated membrane MF-4SC (Russian equivalent of Nafion®-117) and a thinner layer (1 μm) of the membrane, on a base of glassy polymer of internal microporosity poly(1-trimethylsilyl-1-propyne) (PTMSP)—was prepared and characterized. Using the physicochemical characteristics of one-layer membranes MF-4SC and PTMSP in 0.05 M HCl and NaCl solutions, the asymmetric current–voltage curves (CVC) of the bilayer composite were described with good accuracy up to the overlimiting regime, based on the “fine-porous membrane” model. The MF-4SC/PTMSP bilayer composite has a significant asymmetry of CVC that is promising for using it in electromembrane devices, such as membrane detectors, sensors, and diodes.


Author(s):  
Jonathan Cooper ◽  
Martin Scharm ◽  
Gary R Mirams

Computational modelling of cardiac cellular electrophysiology has a long history, with many models now available for different species, cell types, and experimental preparations. This success brings with it a challenge: how do we assess and compare the underlying hypotheses and emergent behaviours, in order to choose a model as a suitable basis for a new study, or characterize how a particular model behaves in different scenarios? We have created an online resource for the characterization and comparison of electrophysiological cell models under a wide range of experimental scenarios. The details of the mathematical model (quantitative assumptions and hypotheses formulated as ordinary differential equations) are separated from the experimental protocol being simulated. Each model and protocol is then encoded in computer-readable formats. A simulation tool runs virtual experiments on models, and a website – https://chaste.cs.ox.ac.uk/FunctionalCuration – provides a friendly interface, allowing users to store and compare results. The system currently contains a sample of 36 models and 23 protocols, including current-voltage curve generation, action potential properties under steady pacing at different rates, restitution properties, block of particular channels, and hypo-/hyper-kalaemia. This resource is publicly available, open source, and free; and we invite the community to use it and become involved in future developments. Those interested in comparing competing hypotheses using models can make a more informed decision; those developing new models can upload them for easy evaluation under the existing protocols, and even add their own protocols.


2019 ◽  
Vol 14 (1) ◽  
pp. 1-6
Author(s):  
Li�gia Martins d'Oliveira ◽  
Valeriya Kilchytska ◽  
Denis Flandre ◽  
Michelly De Souza

This paper proposes a curve extraction method for I-V curves and analog figures-of-merit of self-cascode MOSFET associations (SC) using a code that exploits I-V curves of single transistors as input. The method was validated by using experimental measurements of fabricated SC and the very single transistors that compose them. The results indicate a very low error between the SC generated by the code and the measured reference for operation in saturation regime and above threshold voltage, for both the I-V curves and their derivatives. This method is then valid for the assessment of the SC structures in new technologies, avoiding experimental dedicated layouts or complex set-ups.


2018 ◽  
Vol 1 ◽  
pp. 94-98
Author(s):  
Israel Reyes-Ramírez ◽  
◽  
Jorge Fonseca-Campos ◽  
Juan Luis Mata Machuca

2014 ◽  
Vol 1697 ◽  
Author(s):  
Jie Liu ◽  
Xu Xu ◽  
M. P. Anantram

ABSTRACTThe sub-threshold electron transport properties of amorphous (a-) germanium telluride (GeTe) phase change material (PCM) ultra-thin films are investigated by using ab initio molecular dynamics, density function theory, and Green’s function simulations. The simulation results reproduce the trends in measured electron transport properties, e.g. current-voltage curve, intra-bandgap donor-like and acceptor-like defect states, and p-type conductivity. The underlying physical mechanism of electron transport in ultra-scaled a-PCM is unraveled. We find that, though the current-voltage curve of the ultra-scaled a-PCM resembles that of the bulk a-PCM, their physical origins are different. Unlike the electron transport in bulk a-PCM, which is governed by the Poole-Frenkel effect, the electron transport in ultra-scaled a-PCM is largely dominated by tunneling transport via intra-bandgap donor-like and acceptor-like defect states.


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