scholarly journals The current-voltage relation of a pore and its asymptotic behavior in a Nernst-Planck model

2019 ◽  
Vol 3 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Nicolae Marius Bîrlea ◽  
Sînziana Iulia Bîrlea
Keyword(s):  
Potential Energy ◽  
Energy Barrier ◽  
Relative Size ◽  
Linear Current ◽  
Energy Gradient ◽  
Current Voltage ◽  
Starting Point ◽  
Triangular Profile ◽  
Good Starting Point ◽  
Current Voltage Relationship

Abstract A model for current-voltage nonlinearity and asymmetry is a good starting point for explaining the electrical behavior of nanopores in synthetic or biological membranes. Using a Nernst-Planck model, we found three behaviors for the calculated current density in a membrane's pore as a function of voltage: a quasi-ohmic, slow rising linear current at low voltages; a nonlinear current at intermediate voltages; and a non-ohmic, fast rising linear current at large voltages. The slope of the quasi-ohmic current depends mainly on the height of the energy barrier inside the pore, w, through an exponential term, ew. The magnitude of the non-ohmic linear current is controlled by the potential energy gradient at the pore entrance, w/r. The current-voltage relationship is asymmetric if the ion's potential energy inside the pore has an asymmetric triangular profile. The model has only two assumed parameters, the energy barrier height, w, and the relative size of the entrance region of the pore, r, which is a useful feature for fitting and interpreting experimental data.

scholarly journals Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Shigetomo Suyama ◽  
Alexandra Ralevski ◽  
Zhong-Wu Liu ◽  
Marcelo O Dietrich ◽  
Toshihiko Yada ◽  
...  
Keyword(s):  
Food Deprivation ◽  
High Fat Diet ◽  
Receptor Complex ◽  
High Fat ◽  
Fasted State ◽  
Linear Current ◽  
Current Voltage ◽  
Relationship Of ◽  
Current Voltage Relationship ◽  
Voltage Relationship

POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state. Ten days of high-fat diet exposure, which was accompanied by elevated leptin levels and increased POMC neuronal activity, resulted in increased expression of Cp-AMPARs on POMC neurons. Altogether, our results show that entry of calcium via Cp-AMPARs is inherent to activation of POMC neurons, which may underlie a vulnerability of these neurons to calcium overload while activated in a sustained manner during over-nutrition.

More than One Type of Conductance is Activated During Responses of Blowfly Monopolar Neurones

1989 ◽  
Vol 144 (1) ◽  
pp. 147-154 ◽  
Author(s):  
M. WECKSTRÖM ◽  
E. KOUVALAINEN ◽  
K. DJUPSUND ◽  
M. JÄRVILEHTO
Keyword(s):  
Compound Eye ◽  
Reversal Potential ◽  
Input Resistance ◽  
Current Clamp ◽  
Voltage Range ◽  
Continuous Release ◽  
Linear Current ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

The principal second-order neurones in the blowfly compound eye, the large monopolar neurones (LMCs), were studied using intracellular recording and discontinuous current-clamp techniques, in combination with measurement of dynamic input resistance. The LMCs had resting potentials of −35 to −45 mV and showed a linear current-voltage relationship in the lamina in the physiological voltage range. The hyperpolarizing light-on transient was associated with a drop in input resistance from 17 ± 5 to 3 ± 1MΩ, and had a reversal potential between −60 and −90 mV. The dynamic input resistance of saturated responses and the properties of reversed responses suggested that more than one conductance was activated during the response of the LMCs. In lamina recordings, the input resistance increased beyond the resting level during repolarization, which can be interpreted in terms of a continuous release of transmitter by the photoreceptor terminals, even in darkness. The input resistance of LMCs in axon recordings in darkness and during the light-on response was generally higher than in the lamina recordings. The responses to light in axons also differed from those recorded in lamina by showing regenerative properties.

scholarly journals Atomic-level simulation of current–voltage relationships in single-file ion channels

2013 ◽  
Vol 141 (5) ◽  
pp. 619-632 ◽  
Author(s):  
Morten Ø. Jensen ◽  
Vishwanath Jogini ◽  
Michael P. Eastwood ◽  
David E. Shaw
Keyword(s):  
Interaction Strength ◽  
Permeation Rate ◽  
Gramicidin A ◽  
Direct Simulation ◽  
Single File ◽  
Linear Current ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship ◽  
Insight Into

The difficulty in characterizing ion conduction through membrane channels at the level of individual permeation events has made it challenging to elucidate the mechanistic principles underpinning this fundamental physiological process. Using long, all-atom simulations enabled by special-purpose hardware, we studied K+ permeation across the KV1.2/2.1 voltage-gated potassium channel. At experimentally accessible voltages, which include the physiological range, the simulated permeation rate was substantially lower than the experimentally observed rate. The current–voltage relationship was also nonlinear but became linear at much higher voltages. We observed permeation consistent with a “knock-on” mechanism at all voltages. At high voltages, the permeation rate was in accordance with our previously reported KV1.2 pore-only simulations, after the simulated voltages from the previous study were recalculated using the correct method, new insight into which is provided here. Including the voltage-sensing domains in the simulated channel brought the linear current–voltage regime closer to the experimentally accessible voltages. The simulated permeation rate, however, still underestimated the experimental rate, because formation of the knock-on intermediate occurred too infrequently. Reducing the interaction strength between the ion and the selectivity filter did not increase conductance. In complementary simulations of gramicidin A, similar changes in interaction strength did increase the observed permeation rate. Permeation nevertheless remained substantially below the experimental value, largely because of infrequent ion recruitment into the pore lumen. Despite the need to apply large voltages to simulate the permeation process, the apparent voltage insensitivity of the permeation mechanism suggests that the direct simulation of permeation at the single-ion level can provide fundamental physiological insight into ion channel function. Notably, our simulations suggest that the knock-on permeation mechanisms in KV1.2 and KcsA may be different.

scholarly journals Lack of negative slope in I-V plots for BK channels at positive potentials in the absence of intracellular blockers

2013 ◽  
Vol 141 (4) ◽  
pp. 493-497 ◽  
Author(s):  
Yanyan Geng ◽  
Xiaoyu Wang ◽  
Karl L. Magleby
Keyword(s):  
Single Channel ◽  
Bk Channels ◽  
Negative Slope ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Linear Current ◽  
Joint Application ◽  
Current Voltage ◽  
Α Subunits

Large-conductance, voltage- and Ca2+-activated K+ (BK) channels display near linear current–voltage (I-V) plots for voltages between −100 and +100 mV, with an increasing sublinearity for more positive potentials. As is the case for many types of channels, BK channels are blocked at positive potentials by intracellular Ca2+ and Mg2+. This fast block progressively reduces single-channel conductance with increasing voltage, giving rise to a negative slope in the I-V plots beyond about +120 mV, depending on the concentration of the blockers. In contrast to these observations of pronounced differences in the magnitudes and shapes of I-V plots in the absence and presence of intracellular blockers, Schroeder and Hansen (2007. J. Gen. Physiol. http://dx.doi.org/10.1085/jgp.200709802) have reported identical I-V plots in the absence and presence of blockers for BK channels, with both plots having reduced conductance and negative slopes, as expected for blockers. Schroeder and Hansen included both Ca2+ and Mg2+ in the intracellular solution rather than a single blocker, and they also studied BK channels expressed from α plus β1 subunits, whereas most previous studies used only α subunits. Although it seems unlikely that these experimental differences would account for the differences in findings between previous studies and those of Schroeder and Hansen, we repeated the experiments using BK channels comprised of α plus β1 subunits with joint application of 2.5 mM Ca2+ plus 2.5 mM Mg2+, as Schroeder and Hansen did. In contrast to the findings of Schroeder and Hansen of identical I-V plots, we found marked differences in the single-channel I-V plots in the absence and presence of blockers. Consistent with previous studies, we found near linear I-V plots in the absence of blockers and greatly reduced currents and negative slopes in the presence of blockers. Hence, studies of conductance mechanisms for BK channels should exclude intracellular Ca2+/Mg2+, as they can reduce conductance and induce negative slopes.

scholarly journals Discovery and Optimization of Selective Inhibitors of Meprin α (Part I)

2021 ◽  
Vol 14 (3) ◽  
pp. 203 ◽  
Author(s):  
Shurong Hou ◽  
Juan Diez ◽  
Chao Wang ◽  
Christoph Becker-Pauly ◽  
Gregg B. Fields ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
De Novo ◽  
Selective Inhibitors ◽  
Preclinical Development ◽  
Starting Point ◽  
Good Starting Point ◽  
Parallel Screening ◽  
Low Cytotoxicity

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in preclinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultrahigh-throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified five selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These selective inhibitors of meprin α provide a good starting point for further optimization.

scholarly journals Advances on the Implementation of Circular Economy Techniques in Rural Areas in Colombia under a Sustainable Development Framework

2021 ◽  
Vol 13 (7) ◽  
pp. 3816
Author(s):  
Javier Rodrigo-Ilarri ◽  
Camilo-A. Vargas-Terranova ◽  
María-Elena Rodrigo-Clavero ◽  
Paula-A. Bustos-Castro
Keyword(s):  
Sustainable Development ◽  
Waste Management ◽  
Circular Economy ◽  
Rural Areas ◽  
Development Framework ◽  
Starting Point ◽  
Management Plans ◽  
Good Starting Point ◽  
Depressed Regions ◽  
First Time

For the first time in the scientific literature, this research shows an analysis of the implementation of circular economy techniques under sustainable development framework in six municipalities with a depressed economy in Colombia. The analysis is based on solid waste data production at a local scale, the valuation of the waste for subsequent recycling, and the identification and quantification of the variables associated with the treatment and final disposal of waste, in accordance with the Colombian regulatory framework. Waste generation data are obtained considering three different scenarios, in which a comparison between the simulated values and those established in the management plans are compared. Important differences have been identified between the waste management programs of each municipality, specifically regarding the components of waste collection, transportation and disposal, participation of environmental reclaimers, and potential use of materials. These differences are fundamentally associated with the different administrative processes considered for each individual municipality. This research is a good starting point for the development of waste management models based on circular economy techniques, through the subsequent implementation of an office tool in depressed regions such as those studied.

scholarly journals Development of Highly Sensitive Strain Sensor Using Area-Arrayed Graphene Nanoribbons

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1701
Author(s):  
Ken Suzuki ◽  
Ryohei Nakagawa ◽  
Qinqiang Zhang ◽  
Hideo Miura
Keyword(s):  
Graphene Nanoribbons ◽  
Strain Sensor ◽  
Strain Sensors ◽  
Sensitive Strain ◽  
Bending Test ◽  
Gauge Factor ◽  
Four Point Bending ◽  
Current Voltage ◽  
Highly Sensitive ◽  
Current Voltage Relationship

In this study, a basic design of area-arrayed graphene nanoribbon (GNR) strain sensors was proposed to realize the next generation of strain sensors. To fabricate the area-arrayed GNRs, a top-down approach was employed, in which GNRs were cut out from a large graphene sheet using an electron beam lithography technique. GNRs with widths of 400 nm, 300 nm, 200 nm, and 50 nm were fabricated, and their current-voltage characteristics were evaluated. The current values of GNRs with widths of 200 nm and above increased linearly with increasing applied voltage, indicating that these GNRs were metallic conductors and a good ohmic junction was formed between graphene and the electrode. There were two types of GNRs with a width of 50 nm, one with a linear current–voltage relationship and the other with a nonlinear one. We evaluated the strain sensitivity of the 50 nm GNR exhibiting metallic conduction by applying a four-point bending test, and found that the gauge factor of this GNR was about 50. Thus, GNRs with a width of about 50 nm can be used to realize a highly sensitive strain sensor.

Industry-Sponsored Medical Education — In the Quest for Professional Integrity and Legal Certainty

2007 ◽  
Vol 14 (4) ◽  
pp. 313-319
Author(s):  
Benedikt Buchner
Keyword(s):  
Medical Education ◽  
Self Regulation ◽  
State Regulation ◽  
General Question ◽  
Legal Certainty ◽  
European Directive ◽  
Starting Point ◽  
Good Starting Point ◽  
Advertising Law ◽  
The Right

AbstractIndustry-sponsored medical education is a much disputed issue. So far, there has been no regulatory framework which provides clear and definite rules as to whether and under what circumstances the sponsorship of medical education is acceptable. State regulation does not exist, or confines itself to a very general principle. Professional regulation, even though applied frequently, is rather vague and indefinite, raising the general question as to whether self-regulation is the right approach at all. Certainly, self-regulation by industry cannot and should not replace other regulatory approaches. Ultimately, advertising law in general and the European Directive 2001/83/EC specifically, might be a good starting point in providing legal certainty and ensuring the independence of medical education. Swiss advertising law illustrates how the principles of the European Directive could be implemented clearly and unambiguously.

ZINC OXIDE NANOPARTICLES FOR ULTRAVIOLET PHOTODETECTION

2011 ◽  
Vol 20 (01) ◽  
pp. 183-194 ◽  
Author(s):  
SHAYLA SAWYER ◽  
LIQIAO QIN ◽  
CHRISTOPHER SHING
Keyword(s):  
Zinc Oxide ◽  
Gallium Nitride ◽  
Zno Nanoparticles ◽  
Green Emission ◽  
Synthesis Process ◽  
Voltage Response ◽  
Zno Nanoparticle ◽  
Linear Current ◽  
Current Voltage ◽  
Lift Off

Zinc Oxide ( ZnO ) nanoparticles were created by a top-down wet-chemistry synthesis process ( ZnO - A ) and then coated with polyvinyl-alcohol (PVA) ( ZnO - U ). In ZnO - U , strong UV emission was apparent while the parasitic green emission, which normally appears in ZnO suspensions, was suppressed. A standard lift-off process via e-beam lithography was used to fabricate a detector by evaporating Aluminum ( Al ) as ohmic electrodes on the ZnO nanoparticle film. Photoconductivity experiments showed that linear current-voltage response were achieved and the ZnO - U nanoparticles based detector had a ratio of UV photo-generated current more than 5 times better than that of the ZnO - A based detector. In addition, non-linear current-voltage responses were observed when interdigitated finger Gold ( Au ) contacts were deposited on ZnO - U . The UV generated current to dark current ratios were between 4 and 7 orders of magnitude, showing better performance than the photodetector with Al contacts. ZnO - U were also deposited on Gallium Nitride ( GaN ) and Aluminum Gallium Nitride ( AlGaN ) substrates to create spectrally selective photodetectors. The responsivity of detector based on AlGaN is twice that of commercial UV enhanced Silicon photodiodes. These results confirmed that ZnO nanoparticles coating with PVA is a good material for small-signal, visible blind, and wavelength selective UV detection.

PKC-sensitive Cl- channels associated with ciliary epithelial homologue of pICln

1995 ◽  
Vol 268 (3) ◽  
pp. C572-C579 ◽  
Author(s):  
M. Coca-Prados ◽  
J. Anguita ◽  
M. L. Chalfant ◽  
M. M. Civan
Keyword(s):  
Northern Analysis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Current Voltage ◽  
Cl Channels ◽  
Polymerase Chain ◽  
Reaction Cloning ◽  
Cystic Fibrosis Transmembrane ◽  
Nonpigmented Ciliary Epithelial ◽  
Current Voltage Relationship

Swelling activates and protein kinase C (PKC) downregulates Cl- channels in cultured nonpigmented ciliary epithelial (NPE) cells. We now report that the PKC inhibitor staurosporine upregulates whole cell Cl- currents isosmotically. The kinetics and current-voltage relationship are similar to those of volume-activated Cl- channels of these cells. These properties are inconsistent with cloned ClC-0, ClC-1, ClC-2, and MDR1 channels but could reflect the cystic fibrosis transmembrane conductance regulator (CFTR) channel or the Cl- channel regulator pICln. CFTR mRNA was undetectable by Northern analysis of cultured NPE cells or ciliary body tissue. In contrast, a human pICln probe obtained by polymerase chain reaction cloning and showing 90% identity with the rat cDNA clone detected high levels of transcripts in NPE cells. The level was low in tissue, where the NPE message was diluted by RNA from other cells. We conclude that NPE cells display staurosporine-activated Cl- channels [gSt(Cl)] likely identical with the volume-activated channels. The same cells expressing gSt(Cl) transcribe mRNA for a novel homologue (pHCBICln) of pICln that may regulate Cl- transport into the aqueous humor.

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