Search

The direction of overflow in the rotary mechanism of a screw vacuum pump and the shapes of the channels through which it occurs are considered. Calculation formulas for each type of channel are given. The conductance of a triangular slot, i.e., the gap with the largest overflow, is calculated using the slope coefficient method in the COMSOL Multiphysics software. The dependence of the conductance on the screw pitch is obtained for a different assignment of the computational domain. Based on the data obtained, the mass flow coefficient was calculated, which can be used to create a mathematical model of a screw vacuum pump. [ABSTRACT FROM AUTHOR]

AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain AMPAR properties. Here we have found that AMPARs show a clear stoichiometry-dependent modulation by the prototypical TARP γ2 although the receptor still needs to be fully saturated with γ2 to show some typical TARP-induced characteristics (i.e. an increase in channel conductance). We also uncovered important differences in the stoichiometric modulation between calcium-permeable and calcium-impermeable AMPARs. Moreover, in heteromeric AMPARs, γ2 positioning in the complex is important to exert certain TARP-dependent features. Finally, by comparing data from recombinant receptors with endogenous AMPAR currents from mouse cerebellar granule cells, we have determined a likely presence of two γ2 molecules at somatic receptors in this cell type.

We have developed a 2-dimensional analytical model to study the subthreshold swing and channel conductance of a gate and channel engineered double gate MOSFET. Basic diffusion equation has been considered to model the drain to source current of the device in subthreshold region and expressions of the device parameters like subthreshold swing and channel conductance have been derived. Subthreshold swing variations of the device with varied materials, channel, and effective oxide layer thickness and channel length have also been investigated. Changes in subthreshold swing owing to different doping profile concentrations have been explored. Effect of similar device parameters on the channel conductance of the device has been examined as well. Another important observation of the work is the pseudo flat band condition of the device structure based on the intersecting point of body potentials of the device at different thickness of the channel. The analytical results of the proposed model have been validated with the numerical results from commercially available 2-dimensional device simulator. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium (Na V ) channels are critical in the signal transduction of excitable cells. In this work, we modeled the open conformation for the pore domain of a prokaryotic Na V channel (Na V Rh), and used molecular dynamics simulations to track the translocation of dozens of Na + ions through the channel in the presence of a physiological transmembrane ion concentration gradient and a transmembrane electrical field that was closer to the physiological one than previous studies. Channel conductance was then estimated from simulations on the wide-type and DEKA mutant of Na V Rh. Interestingly, the conductivity predicted from the DEKA mutant agrees well with experimental measurement on eukaryotic Na V 1.4 channel. Moreover, the wide-type and DEKA mutant of Na V Rh exhibited markedly distinct ion permeation patterns, which thus implies the mechanistic difference between prokaryotic and eukaryotic Na V channels. [ABSTRACT FROM AUTHOR]

The viroporin p7 of the hepatitis C virus forms multimeric channels eligible for ion transport across the endoplasmic reticulum membrane. Currently the subject of many studies and discussion, the molecular assembly of the ion channel and the structural characteristics of the p7 monomer are not yet fully understood. Structural investigation of p7 has been carried out only in detergent environments, making the interpretation of the experimental results somewhat questionable. Here, we analyze by means of molecular dynamics simulations the structure of the p7 monomer as a function of its sequence, initial conformation and environment. We investigate the conductance properties of three models of a hexameric p7 ion channel by examining ion translocation in a pure lipid bilayer. It is noteworthy that although none of the models reflects the experimentally observed trend to conduct preferentially cations, we were able to identify the position and orientation of titratable acidic or basic residues playing a crucial role in ion selectivity and in the overall conductance of the channel. In addition, too compact a packing of the monomers leads to channel collapse rather than formation of a reasonable pore, amenable to ion translocation. The present findings are envisioned to help assess the physiological relevance of p7 ion channel models consisting of multimeric structures obtained in non-native environments. [ABSTRACT FROM AUTHOR]

As the principal receptor that mediates both synaptic and tonic inhibition of neurons in the brain, the A-type gamma-aminobutyric acid receptor (GABA A R) is functionally important for maintaining the balance between neuronal excitation and inhibition. Here, we report the identification of netrin-1 as an endogenous allosteric modulator of GABA A Rs. Following increased neuronal excitability, netrin-1 is secreted and binds to the extracellular domains of GABA A R subunits, thereby inducing homeostatic upscaling of GABA A R-mediated synaptic efficacy and currents. Surprisingly, this homeostatic plasticity is primarily mediated by increasing GABA A R single-channel conductance. Our study reveals an important role of netrin-1 as an endogenous GABA A R allosteric modulator in maintaining neuronal excitation-inhibition balance, a fundamental process for brain function and dysfunction. [Display omitted] • Endogenous netrin-1 is secreted during neuronal excitation and binds to GABA A Rs • Netrin-1 mediates homeostatic upscaling of the GABA A R synaptic efficacy • Netrin-1 allosterically potentiates GABA A R single-channel conductance Chan et al. reveal an important role of netrin-1 as an endogenous GABA A receptor allosteric modulator in fine-tuning neuronal excitation-inhibition balance through a mechanism of potentiating GABA A receptor single-channel conductance during excitation-induced inhibitory synaptic homeostasis. [ABSTRACT FROM AUTHOR]

The transition process from the low resistance state into the high resistance state in a Pt/NiO/Pt memory switching structure has been studied by numerical modeling. Detailed analysis shows, that thermally induced diffusion oxidation by nickel vacancies is the key factor for distortion of the channel metallic conductivity. Spatial dynamics of the process of oxidation defines channel narrowing mainly in its central part, and also sets the critical current through the structure sufficient for final rupture of the channel and the transition to high resistance state. The increase in critical current above the limit even by 10% reduces the switching time by an order of magnitude, which is in agreement with experiments. The developed radial diffusion model of conductive channel (or filaments) oxidation may be suitable for the analysis of switching effect a number of other ReRAM oxide structures. [ABSTRACT FROM AUTHOR]

As the principal receptor that mediates both synaptic and tonic inhibition of neurons in the brain, the A-type gamma-aminobutyric acid receptor (GABA A R) is functionally important for maintaining the balance between neuronal excitation and inhibition. Here, we report the identification of netrin-1 as an endogenous allosteric modulator of GABA A Rs. Following increased neuronal excitability, netrin-1 is secreted and binds to the extracellular domains of GABA A R subunits, thereby inducing homeostatic upscaling of GABA A R-mediated synaptic efficacy and currents. Surprisingly, this homeostatic plasticity is primarily mediated by increasing GABA A R single-channel conductance. Our study reveals an important role of netrin-1 as an endogenous GABA A R allosteric modulator in maintaining neuronal excitation-inhibition balance, a fundamental process for brain function and dysfunction., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many properties of fast synaptic transmission in the brain are influenced by transmembrane AMPAR regulatory proteins (TARPs) that modulate the pharmacology and gating of AMPA-type glutamate receptors (AMPARs). Although much is known about TARP influence on AMPAR pharmacology and kinetics through their modulation of the extracellular ligand-binding domain (LBD), less is known about their regulation of the ion channel region. TARP-induced modifications in AMPAR channel behavior include increased single-channel conductance and weakened block of calcium-permeable AMPARs (CP-AMPARs) by endogenous intracellular polyamines. To investigate how TARPs modify ion flux and channel block, we examined the action of у-2 (stargazin) on GluA1 and GluA4 CP-AMPARs. First, we compared the permeation of organic cations of different sizes. We found that у-2 increased the permeability of several cations but not the estimated AMPAR pore size, suggesting that TARP-induced relief of polyamine block does not reflect altered pore diameter. Second, to determine whether residues in the TARP intracellular C-tail regulate polyamine block and channel conductance, we examined various y-у C-tail mutants. We identified the membrane proximal region of the C terminus as crucial for full TARP-attenuation of polyamine block, whereas complete deletion of the C-tail markedly enhanced the TARP-induced increase in channel conductance;thus, the TARP C-tail influences ion permeation. Third, we identified a site in the pore-lining region of the AMPAR, close to its Q/R site, that is crucial in determining the TARP-induced changes in single-channel conductance. This conserved residue represents a site of TARP action, independent of the AMPAR LBD. [ABSTRACT FROM AUTHOR]

Abstract: Mutations of Cx40 (GJA5) have been identified in people with lone chronic atrial fibrillation including G38D and M163V which were found in the same patient. We used dual whole cell patch clamp procedures to examine the transjunctional voltage (V j) gating and channel conductance properties of these two rare mutants. Each mutant exhibited slight alterations of V j gating properties and increased the gap junction channel conductance (γ j) by 20–30pS. While co-expression of the two mutations had similar effects on V j gating, it synergistically increased γ j by 50%. Unlike WTCx40 or M163V, G38D induced activity of a dominant 271pS hemichannel. [Copyright &y& Elsevier]

In this paper, a physical model of gas flows through the channels is refined. The influence of gas absorbed by the walls of a channel on its conductance is shown. The experimentally obtained minimum on the channel conductance-pressure dependence (as the Knudsen paradox) is interpreted. [ABSTRACT FROM AUTHOR]

Structural studies place the VDAC1 (voltage-dependent anion channel 1) N-terminal region within the channel pore. Biochemical and functional studies, however, reveal that the N-terminal domain is cytoplasmically exposed. In the present study, the location and translocation of the VDAC1 N-terminal domain, and its role in voltage-gating and as a target for antiapoptotic proteins, were addressed. Site-directed mutagenesis and cysteine residue substitution, together with a thiol-specific cross-linker, served to show that the VDAC1 N-terminal region exists in a dynamic equilibrium, located within the pore or exposed outside the ß-barrel. Using a single cysteine-residuebearing VDAC1, we demonstrate that the N-terminal region lies inside the pore. However, the same region can be exposed outside the pore, where it dimerizes with the N-terminal domain of a second VDAC1 molecule. When the N-terminal region a-helix structure was perturbed, intra-molecular cross-linking was abolished and dimerization was enhanced. This mutant also displays reduced voltage-gating and reduced binding to hexokinase, but not to the anti-apoptotic proteins Bcl-2 and BclxL. Replacing glycine residues in the N-terminal domain GRS (glycine-rich sequence) yielded less intra-molecular cross-linked product but more dimerization, suggesting that GRS provides the flexibility needed for N-terminal translocation from the internal pore to the channel face. N-terminal mobility may thus contribute to channel gating and interaction with anti-apoptotic proteins. [ABSTRACT FROM AUTHOR]

Abstract: A comparative analysis of chemosensory systems in invertebrates and vertebrates reveals that different animals use similar strategies when sensing CO2 to control respiration. A variety of animals possess neurons that respond to changes in pH. These respiratory chemoreceptor neurons seem to rely largely on pH-dependent inhibition of potassium channels, but the channels do not appear to be uniquely adapted to detect pH. The ‘chemosensory’ potassium channels identified thus far are widely distributed, common potassium channels. The pH-sensitivity is a common feature of the channels whether the channels are in chemosensory neurons or not. Thus, the pattern of synaptic connectivity and the mix of potassium channels expressed seem to determine whether a neuron is chemosensory or not, rather than any special adaptation of a channel for pH-sensitivity. Moreover, there are often multiple pH-sensitive channels in each chemosensory neuron. These ionic mechanisms may, however, be only part of the chemosensory process, and pH-dependent modulation of synaptic activity seems to contribute to central chemosensitivity as well. In addition, the exploration of the mechanisms of pH-dependent modulation of ion channel activity in chemosensory cells is incomplete: additional mechanisms of pH modulation of channel activity may be found, and addition conductances, other than potassium channels, may participate in the chemosensory process. [ABSTRACT FROM AUTHOR]

Almost all spintronic transistors (e.g., spin field-effect transistors, spin bipolar transistors, and spin-enhanced MOSFETs) require high efficiency of spin injection from a ferromagnetic contact into a semiconductor channel for proper operation. In this paper, we calculate the efficiency of spin injection from a realistic nonideal ferromagnetic contact into the semiconductor quantum wire channel of a spintronic transistor, taking into account the presence of an axial magnetic field (caused by either the ferromagnetic contact or external agents) and spin orbit interaction. In our calculations, the temperature is assumed to be low enough that phonon scattering is weak and transport is phase-coherent, although not ballistic because of elastic scattering caused by impurities and defects. We consider a single impurity in the channel and show that the conductance depends strongly on the exact location of this impurity because of quantum mechanical interference effects. This is a nuisance since it exacerbates device variability. The ldquosignrdquo of the impurity potential, i.e., whether it is attractive or repulsive, also influences the channel conductance. Surprisingly, at absolute zero temperature, the spin injection efficiency can reach 100% at certain gate biases, even though the ferromagnetic injector is nonideal. However, this efficiency drops rapidly with increasing temperature. [ABSTRACT FROM PUBLISHER]

A self-assembled film of gold nanoparticles is integrated into the gate dielectric of an organic thin-film transistor to produce memory effects. The transistor is fabricated on a heavily doped n-type silicon (n+-Si) substrate with a thermally grown oxide layer of 100 nm thick. n+-Si serves as the gate electrode while the oxide layer functions as the gate dielectric. Gold nanoparticles as the floating gate for charge storage are deposited on the gate oxide by electrostatic layer-by-layer self-assembly method. A self-assembled multilayer of polyelectrolytes, together with a thin spin-coated poly(4-vinyl phenol) layer, covers the gold nanoparticles and separates them from the poly(3-hexyl thiophene) channel. Gold nanoparticles are charged or discharged with different gate bias so that the channel conductance is modulated. The memory transistor has an on/off ratio over 1500 and data retention time of about 200 s. The low-temperature solution-based process is especially suitable for plastic-based circuits. Therefore, the results of this study could accelerate achievement of cheap and flexible organic nonvolatile memories [ABSTRACT FROM PUBLISHER]

Because of high electrical impedance of cell membrane, when living cells are exposed to an external electric field, the field-induced voltage drops will mainly occur on the cell membrane. In addition to Joule heating damage and electroporation of the cell membrane, the electric field-induced supraphysiological transmembrane potential may inevitably damage the membrane proteins, especially the voltage-dependent membrane proteins. That is because the charged particles in the amino acid of the membrane proteins and, in particular, the voltage-sensors in the voltage-dependent membrane proteins are vulnerable to the membrane potential. An intensive, brief electric shock may induce electroconformational damage or denaturation in the membrane proteins. As a result, the cell functions are significantly reduced. This electric field-induced denaturation in the membrane proteins strongly suggests a new underlying mechanism involved in electrical injury. [ABSTRACT FROM AUTHOR]

The access resistance (AR) of a channel is an important component of the conductance of ion channels, particularly in wide and short channels, where it accounts for a substantial fraction of the total resistance to the movement of ions. The AR is usually calculated by using a classical and simple expression derived by Hall from electrostatics (J.E. Hall 1975J. Gen. Phys.66:531-532), though other expressions, both analytical and numerical, have been proposed. Here we report some numerical results for the AR of a channel obtained by solving the Poisson-Nernst-Planck equations at the entrance of a circular pore. Agreement is found between numerical calculations and analytical results from Hall’s equation for uncharged pores in neutral membranes. However, for channels embedded in charged membranes, Hall’s expression overestimates the AR, which is much lower and can even be neglected in some cases. The weak dependence of AR on the pore radius for charged membranes at low salt concentration can be exploited to separate the channel and the access contributions to the measured conductance. [ABSTRACT FROM AUTHOR]

The semimicroscopic (SMC) approach to modeling the energetics of ion permeation through biological channels provides an alternative perspective to standard molecular dynamics methods. It exploits the timescale separation between electronic and structural contributions to dielectric stabilization and accounts for electronic polarization by embedding the channel in a milieu that, on average, describes this polarization. Ions, water, and selected peptide moieties are mobile and comprise the reorganizational contribution to dielectric stabilization. The conceptual advantages and limitations of the technique are described. Methodological details are outlined, stressing three convenient electrical geometries. Practical aspects of the SMC procedure are explained, highlighting the areas ripe for further development. Finally, some specific applications are considered. [ABSTRACT FROM PUBLISHER]

E1/E3-deleted adenoviral vectors expressing an N-terminal green fluorescent protein (GFP) reporter gene fused to either wtCFTR (H5.040CMVEGFP-wtCFTR) or ?F508-CFTR (H5.040CMVEGFP-?F508CFTR) were generated. To characterize the expression and activity, A549 cells were infected with vectors expressing GFP-tagged and non-tagged forms of CFTR and ?F508CFTR. CFTR activity was assayed in cell-attached and excised patches. For H5.040CMVEGFP-wtCFTR, forskolin-dependent outward current was observed in cell-attached patches from 56 of 67 GFP-positive cells. Single-channel conductances, open probability, mean open and mean closed time values for GFP-CFTR and CFTR were not significantly different. After excision, GFP-CFTR activity required ATP and exhibited a linearI-Vrelationship. For H5.040CMVEGFP-?F508CFTR, media were supplemented with 5 mM butyrate 16 h after infection. Forskolin-dependent outward current was observed in cell-attached patches from 21 of 30 butyrate-treated GFP-positive cells and 0 of 8 GFP-positive cells without butyrate. Single-channel conductances, open probability, mean open and mean closed time values for GFP-?F508CFTR and ?F508CFTR were not significantly different. However, the increase in open probability with genistein was significantly smaller for GFP-?F508CFTR than for ?F508CFTR. In excised patches, GFP-?F508CFTR activity required ATP and exhibited a linearI-Vrelationship. Despite the consistent detection of GFP-CFTR and GFP-?F508CFTR channels in the plasma membrane by patch clamping, GFP fluorescence was observed only in intracellular regions and was not altered by butyrate. The data show that high levels of functional GFP-tagged CFTR channels can be expressed with these adenoviral vector constructs. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that short lasting hypoxia induces an increase of Ca2+ influx into the cell through high voltage-activated Ca2+ channels in hippocampal neurons. This effect was abolished by removing of free Ca2+ from intracellular solution. The aim of this study was to compare hypoxic responses at different extracellular Ca2+ concentrations ([Ca2+]e) in hippocampal neurons to ascertain whether the hypoxic sensitivity is restricted to Ca2+ ions. Whole-cell patch-clamp recordings were made from acutely dissociated CA1 hippocampal neurons of rats. Polarographic method for measurements of O2 partial pressure was used. Here we found that at 2 mM [Ca2+]e the hypoxic effect was significant (up to ∼94%), whereas [Ca2+]e elevations to 5 and 15 mM resulted in gradual decreasing of the effect. We found, that total Ca2+ charge carried into the cell under the hypoxia was similar at all [Ca2+]e, whereas Ca2+ charge carried at normoxia was different for different [Ca2+]e, being larger at higher [Ca2+]e. These data indicated a saturation of the hypoxic effect due to limitation in the channel conductance. Therefore, we suggested that the hypoxic effect can be connected with increase of channel conductance, and the level of channel conductance at normoxia can determine the amplitude of hypoxic effect. [Copyright &y& Elsevier]

Commercial metal-semiconductor-field-effect transistors (MESFET's) have opaque gate. We present here the frequency-dependent characteristics of an ion-implanted GaAs MESFET with opaque gate under illumination. The incident light enters the device through the gate-source and gate-drain spacings. Two photovoltages are developed: one across the Schottky junction due to generation in the side walls of the depletion layer below the gate and the other across the channel-substrate junction due to generation in the channel-substrate depletion region. The frequency dependence of the two photovoltages along with channel charge, drain-source current, transconductance and channel conductance of the device have been studied analytically and compared with the published theoretical results. For the first time, a commercially available GaAs optically illuminated field-effect transistor (OPFET) has been analyzed for frequency dependent characteristics instead of the transparent/semitransparent gate OPFET [ABSTRACT FROM PUBLISHER]

A cloned inwardly rectifying potassium channel, IRK1, expressed in Xenopus oocytes was found to be sensitive to an extracellular acidic pH level of below 6, achieved by buffering with a membrane-impermeable buffer, phthalate. The voltage dependency of the suppressive effect of pH on the macroscopic current suggested that the location of the proton-sensitive site was at ≈ 5% of the distance from the outer entrance to the pore. The single-channel conductance was reduced by protonation of the channel on the extracellular side. The external proton-binding site appears to consist of a single class of negatively charged groups with a p K of around 4.6. An intracellular acidic pH, buffered with membrane-permeable acetate, was found to inhibit, in a voltage-independent manner, the macroscopic IRK1 current with an approximate apparent p K of 5.6 and an approximate apparent Hill coefficient of 2.3. The single-channel activity was abolished by intracellular acidification down to pH 5.0. [ABSTRACT FROM AUTHOR]

The paradigm that nucleocytoplasmic transport of ions occurs without a diffusional barrier has been challenged by the recent demonstration with patch-clamp techniques of the existence of ion channels in the nuclear envelope of murine zygotes and hepatocytes. This report demonstrates the existence of nuclear ion channels (NIC) in murine ventricular cardiac myocytes. NIC conductance ( γ), calculated from current histogram peaks, was 106-532 pS at 22-36°C. In nucleus-attached patches, replacement of cytoplasmic K with Na reduced NIC activity within 30 s, suggesting that intranuclear-delimited mechanisms mediate this phenomenon. In excised, inside-out patches K was as permeable as Na through NIC. NIC activity was observed in 0-4 mM Mg and/or ATP, with or without 0-1 mM Ca, indicating a minor direct role of these ions. However, in non-responsive excised inside-out patches, NIC activity appeared when the catalytic subunit of the cAMP-dependent protein kinase was applied to the nucleoplasmic side of the patch, in the presence of Mg and ATP, indicating an important role for phosphorylation-dependent process(es) in NIC function - an observation supported by the depressing effects of protein kinase inhibitor on responsive NIC. The concept that nucleopore complexes are solely responsible for nucleocytoplamic transport leads to the speculation that these structures are the physical substrate for NIC. [ABSTRACT FROM AUTHOR]

Prevalent nucleocytoplasmic transport theory views flow of monoatomic ions as completely unrestricted, resulting from the presence of large diameter pore complexes (NPCs) that perforate, but hold together, the two separate membranes of the nuclear envelope (NE). However, three lines of investigations indicate that, at least in some cell types, monoatomic ion flow is restricted. (i) Patch clamp reveals quantized, ion channel-like activity in several NE preparations; activity thought to result from nuclear ion channels (NICs) connected to NPCs. (ii) Ratiometric fluorescence microscopy demonstrates that ions, as well as small molecules relevant to signal transduction, do distribute as if there is a NE barrier. (iii) Electron microscopy shows that NPCs contain material that behaves like a plug. NICs' large conductance (up to 1,000 pS) makes them a major determinant of nuclear ion concentrations which, in turn, influence nuclear processes. Therefore, NICs are an important modulating force of gene and transcriptional activities-two major determinants of gene expression. As nuclear processes may take from seconds (e.g., signaling) to minutes (e.g., transcription), the time the channels dwell in the ion-conducting open state is relevant to understanding NICs' role in nuclear function. Consequently, dwell-times and lifetimes of open NIC states were studied in 61 patch-clamped adult mouse cardiac myocyte nuclei. Upon voltage stimulation, NICs opened to main states of large conductance (281 ± 198 pS, range = 120-490 pS, n = 55) and wide-range mean dwell-times (∼100 msec, 1-10 sec, and min). Closed states (0 pS) also had widely distributed mean dwell-times (∼100 msec, 1-10 sec, and min). Putative open substates (37 ±11 pS, range = 25-50, pS, n = 6) of high bursting frequency (<1 msec) were observed without intervening main states (≈5% of patches). Fast (∼0.1 msec) and slow (∼10 msec) statetransitions were also detected. These observations suggest a role for NICs in mediating cytoplasmic signal control of cardiomyocyte gene expression. [ABSTRACT FROM AUTHOR]

We examined the interactions of cAMP-dependent protein kinase and varying aqueous Cl concentrations in modulating the activity of Cl channels obtained by fusing basolaterally enriched renal outer medullary vesicles into planar lipid bilayers. Under the present experimental conditions, the cis and trans solutions face the extracellular and intracellular aspects of these Cl channels, respectively. Raising the trans Cl concentration from 2 to 50 mm increased the channel open-time probability, raised the unit channel conductance, and affected the voltage-independent determinant (Δ G) of channel activity but not the gating charge (Winters, C.J., Reeves, W.B., Andreoli, T.E. 1990. J. Membrane Biol. 118:269-278). With 2 mm trans KCl, trans addition of the catalytic subunit of PKA (C-PKA) plus ATP increased channel open-time probability and altered the voltage-independent determinant of channel activity without affecting either unit channel conductance or gating charge. The effect was ATP specific, did not occur with (C-PKA plus ATP) addition to cis solutions, and was abolished by denaturing C-PKA. Finally, (C-PKA plus ATP) activation of channel activity was not detected with relatively high (50 mm) trans Cl concentrations. These data indicate that (C-PKA plus ATP) might modulate Cl channel activity by phosphorylation at or near the Cl-sensitive site on the intracellular face of these channels. [ABSTRACT FROM AUTHOR]

This paper provides the results of studies which characterized conductive 36Cl- flux in basolaterally enriched membrane vesicles prepared from rabbit renal outer medulla. Conductive 36Cl- uptake was studied under two different experimental conditions. In the first, 36Cl- flux was driven by an inside positive voltage created with oppositely directed Cl- and gluconate gradients. In the second, an inwardly direct K+ gradient was used to drive 36Cl- uptake. By these two methods, voltage-sensitive 36Cl- uptake was shown to comprise about 45 and 65%, respectively, of the initial rates of total 36Cl- flux. Separate paired studies demonstrated that the conductive 36Cl- uptake was inhibited by the Cl- channel blocker diphenylamine-2-carboxylate (DPC) with an IC50 for DPC of 154 microM. The voltage-dependent 36Cl- uptake had an activation energy of 6.4 kcal/mole. This 36Cl- conductance had an anion selectivity sequence of I- greater than Cl- greater than or equal to NO3- much greater than gluconate. [ABSTRACT FROM AUTHOR]

The present studies examined some of the properties of Cl- channels in renal outer medullary membrane vesicles incorporated into planar lipid bilayers. The predominant channel was anion selective having a PCl/PK ratio of 10 and a unit conductance of 93 pS in symmetric 320 mM KCl. In asymmetric KCl solutions, the I-V relations conformed to the Goldman-Hodgkin-Katz equation. Channel activity was voltage-dependent with a gating charge of unity. This voltage dependence of channel activity may account, at least in part, for the striking voltage dependence of the basolateral membrane Cl- conductance of isolated medullary thick ascending limb segments. The Cl- channels incorporated into the planar bilayers were asymmetrical: the trans surface was sensitive to changes in ionized Ca2+ concentrations and insensitive to reducing KCl concentrations to 10 mM, while the cis side was insensitive to changes in ionized Ca2+ concentrations, but was inactivated by reducing KCl concentrations to 50 mM. [ABSTRACT FROM AUTHOR]

A model based on the solution of the electrostatic potential for a geometry of three dielectric regions associated with a gramicidin A channel (GA) is presented. The model includes a cylindrical dielectric layer to represent the peptide backbone and dipole rings to account for dipolar side chains. Image potential and dipolar contributions for different orientations and positions along the channel are analyzed. The conductance of GA and two analogues obtained by substituting the amino acid at position 1 are studied. The numerical simulation reproduces experimental results (Barrett et al. 1986, Biophys J 49, 673-686) and supports the idea that electrostatic dipole-ion interactions are of primary importance in gramicidin channel function. [ABSTRACT FROM AUTHOR]

With two independent patch electrodes sealed to small clusters of electrically coupled chick embryo cardiac cells, we have measured four parameters: true seal and patch resistance, channel conductance, and membrane potential. One electrode was in the cell-attached mode, and recorded current flowing in parallel through the membrane patch and seal. The second electrode, sealed on a different cell in the cluster, was in the whole cell recording configuration, and served to record or control the membrane potential of the cluster. We fit the four measured parameters to a simple electrical model to reveal errors not usually recognized in the patch-clamp technique. Among these are the following: (1) The apparent seal resistance, determined by changing the potential in a patch electrode, may be a poor estimate of true seal resistance, since it includes the parallel combination of seal- and patch-resistance. (2) Patch resistance may be influenced by the electrode filling solution, and is often much lower than is usually assumed. (3) With a small cell preparation that has an input resistance in the gigaohm range, measurements of single-channel conductance using a cell-attached patch electrode may be inaccurate because cell membrane potential does not remain constant as electrode potential is varied. [ABSTRACT FROM AUTHOR]

Voltage fluctuations associated with the sodium system were measured upon elimination of the potassium current in the nodal membrane by internal application of cesium-ions. The intensity of this noise reaches a maximal value at a membrane potential in the vicinity of −40 mV. Here the power spectrum consists of two additive components: a 1/ f component and a Lorentzian. The Lorentzian is associated with h-gate kinetics and is consistent with the binary state conduction model. On the basis of this model the sodium-channel conductance is calculated to be 2 to 5·10 S. The analysis is complicated by the existence of an incomplete slow sodium inactivation process. [ABSTRACT FROM AUTHOR]

The intense downscaling of a Metal Oxide Semiconductor Field Effect Transistor (MOSFET) to nano range for improving the device performance requires a high-k dielectric material instead of conventional silica (SiO2) as to avoid Quantum Mechanical Tunneling towards the gate terminal which leads to unnecessary gate current. Out of all the rare earth oxide materials, since lanthana (La2O3) has significantly high dielectric constant (k) and bandgap, we've chosen it as oxide layer for one of the MOSFETs. In this work, we simulated two MOSFETs - one with nano SiO2 oxide layer and other with nano La2O3 oxide layer in the atomic level to analyze and compare the transmission spectra, I-V characteristics and Channel conductance of both the MOSFETs. [ABSTRACT FROM AUTHOR]

We report that the channel activities of gramicidin A in a supported lipid bilayer (SLB) were modulated by membrane fusion with exosomes. The mechanism of the modulation was an increase in the number of exosomes inserting into the SLB membrane, rather than enhancements of the single channel activity of gramicidin A. The modulation of apparent channel activities was applicable to the exosome fusion assay. This assay revealed that the membrane fusion of HEK-293 and MCF-7 exosomes was enhanced at pH 6.0, and the initial rates of membrane fusion for MCF-7 exosomes were higher than those for HEK-293 cells. • Exosome membrane fusion increases the number of gramicidin A inserting into the SLB membrane. • Assay for exosome membrane fusion assay based on changes in the conductance values of gramicidin A. • The fusion rate increased at pH 6.0 for both HEK-293 and MCF-7 exosomes. • The fusion rate of MCF-7 exosomes was higher than that of HEK-293 exosomes. [ABSTRACT FROM AUTHOR]

The glycine receptor (GlyR) is by far the best-characterized pentameric ligand-gated ion channel, with several high-resolution structures from X-ray crystallography, cryoelectron microscopy (cryo-EM), and modeling. Nonetheless, the significance of the currently available open-pore conformations is debated due to their diversity in the pore geometry. Here, we discuss the physiological significance of existing models of the GlyR active state based on conductance and selectivity measurements by computational electrophysiology. The results support the conclusion that the original cryo-EM reconstruction of the active state obtained in detergents as well as its subsequent refinement by molecular dynamics simulations are likely to be non-physiological as they feature artificially dilated ion pores. In addition, the calculations indicate that a physiologically relevant open pore should be constricted within a radius of 2.5 and 2.8 Å, which is consistent with previous modeling, electrophysiology measurements, and the most recent cryo-EM structures obtained in a native lipid membrane environment., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)