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1.
An overflow-type wetted-wall MFC (WWMFC) was developed to generate a stable voltage from acetate-based substrates. The maximum power density of 18.21 W/m3 was obtained. The power generation showed a saturation-type relationship as a function of initial COD, with a maximum power density (Pmax) of 18.82 W/m3 and a saturation constant (Ks) of 227.4 mg/l. Forced air flowing through the cathode chamber had a negligible effect on power generation. Influent flow rate could greatly affect the power generation. The maximum power density was increased by 72.8% when the influent flow rate increased from 5 to 30 ml/min. In addition, increasing ionic strength did not affect the power density and internal resistance. Oxygen could be restrained to diffuse into the anode chamber effectively in the overflow-type WWMFC. And the overflow-type WWMFC could be scaled up conveniently in practical application.  相似文献   

2.
As an emerging biotechnology capable of removing contaminants and producing electricity, microbial fuel cells (MFCs) hold a promising future in wastewater treatment. However, several main problems, including the high internal resistance (Rin), low power output, expensive material, and complicated configuration have severely hindered the large-scale application of MFCs. The study targeted these challenges by developing a novel MFC system, granular activated carbon single-chamber MFC, termed as GAC-SCMFC. The batch tests showed that GAC was a good substitute for carbon cloth and GAC-SCMFCs generated high and stable power outputs compared with the traditional two-chamber MFCs (2CMFCs). Critical operational parameters (i.e. wastewater substrate concentrations, GAC amount, electrode distance) affecting the performance of GAC-SCMFCs were examined at different levels. The results showed that the Rin gradually decreased from 60 Ω to 45 Ω and the power output increased from 0.2 W/m3 to 1.2 W/m3 when the substrate concentrations increased from 100 mg/L to 850 mg/L. However, at high concentrations of 1000–1500 mg/L, the power output leveled off. The Rin of MFCs decreased 50% when the electrode distance was reduced from 7.5 cm to 1 cm. The highest power was achieved at the electrode distance of 2 cm. The power generation increased with more GAC being added in MFCs due to the higher amount of biomass attached. Finally, the multi-anode GAC-SCMFCs were developed to effectively collect the electrons generated in the GAC bed. The results showed that the current was split among the multiple anodes, and the cathode was the limiting factor in the power production of GAC-SCMFCs.  相似文献   

3.
Summary The steady-state, current-voltage (I–V) characteristics of stomatal guard cells fromVicia faba L. were explored by voltage clamp using conventional electrophysiological techniques, but with double-barrelled microelectrodes containing 50mm K+-acetate. Attention was focused, primarily, on guard cell response to metabolic blockade. Exposures to 0.3–1.0mm NaCN and 0.4mm salicylhydroxamic acid (SHAM) lead consistently to depolarizing (positive-going) shifts in guard cell potentials (V m ), as large as +103 mV, which were generally complete within 60–90 sec (mean response half-time, 10.3±1.7 sec); values forV m in NaCN plus SHAM were close or positive to –100 mV and well removed from the K+ equilibrium potential. Guard cell ATP content, which was followed in parallel experiments, showed a mean half-time for decay of 10.8±1.9 ([ATP] t=0, 1.32±0.28mm; [ATP] t=60–180sec, 0.29±0.40mm). In respiring cells, theI–V relations were commonly sigmoid aboutV m or gently concave to the voltage axis positive toV m . Inward- and outward-rectifying currents were also observed, especially near the voltage extremes (nominally –350 and +50 mV). Short-circuit currents (atV=0 mV) were typically about 200–500 mA m–2. The principal effect of cyanide early on was to linearize theI–V characteristic while shifting it to the right along the voltage axis, to decrease the membrane conductance, and to reduce the short-circuit current by approx. 50–75%. The resulting difference-current-voltage (dI–V) curves (±cyanide) showed a marked sensitivity to voltages negative from –100 mV and, when clamp scans had been extended sufficiently, they revealed a distinct minimum near –300 mV before rising at still more negative potentials. The difference currents, along with changes in guard cell potential, conductance and ATP content are interpreted in context of a primary, ATP-consuming ion pump. FittingdI–V curves to reaction kinetic model for the pump [Hansen, U.-P., et al. (1981)J. Membrane Biol. 63:165; Blatt, M.R. (1986)J. Membrane Biol. 92:91] implicates a stoichiometry of one (+) charge transported outward for each ATP hydrolyzed, with pump currents as high as 200 mA m–2 at the free-running potential. The analysis indicates that the pump can comprise more than half of the total membrane conductance and argues against modulations of pump activity alone, as an effective means to controlling K+ transport for stomatal movements.  相似文献   

4.
The discovery of ductile Ag2(S, Se, Te) materials opens a new avenue toward high-performance flexible/hetero-shaped thermoelectrics. Specifically, the cubic-structured materials are quite attractive by combining remarkable plasticity, decent thermoelectric figure of merit (zT), and no phase transition above room temperature. However, such materials are quite few and the understanding is inadequate on their mechanical and thermoelectric properties. Enlightened by the high-entropy principles, a series of pseudo-ternary Ag2S-Ag2Se-Ag2Te alloys is designed and comprehensive diagrams of composition-structure-plasticity-zT are compiled. Subsequently, the compositional region for the cubic phase is outlined. As a high-entropy example featuring with anion-site alloying and disordered Ag ions, Ag2-xS1/3Se1/3Te1/3 materials exhibit impressively large elongations of 60–97%, ultralow lattice thermal conductivities of ≈0.2 W m−1 K−1, and decent zT values of 0.45 at 300 K, 0.8 at 460 K. The materials can be readily rolled into thin foils, showing excellent flexibility. Finally, a six-leg in-plane device is fabricated, achieving an output voltage of 13.6 mV, a maximal power of 12.8 µW, and a power density of 14.3 W m−2 under the temperature difference of 30 K, much higher than the organic counterparts. This study largely enriches the members of cubic ductile inorganic materials for the applications in flexible and hetero-shaped energy and electronic devices.  相似文献   

5.
The anion channel protein from Clavibacter michiganense ssp. nebraskense (Schürholz, Th. et al. 1991, J. Membrane Biol. 123: 1-8) was analyzed at different concentrations of KCl and KF. At 0.8 M KCl the conductance G(Vm) increases exponentially from 21 pS at 50 mV up to 53 pS at Vm = 200 mV, 20°C. The concentration dependence of G(Vm) corresponds to a Michaelis-Menten type saturation function at all membrane voltage values applied (0-200 mV). The anion concentration K0.5, where G(Vm) has its half-maximum value, increases from 0.12 M at 50 mV to 0.24 M at 175 mV for channels in a soybean phospholipid bilayer. The voltage dependence of the single channel conductance, which is different for charged and neutral lipid bilayers, can be described either by a two-state flicker (2SF) model and the Nernst-Planck continuum theory, or by a two barrier, one-site (2B1S) model with asymmetric barriers. The increase in the number of open channels after a voltage jump from 50 mV to 150 mV has a time constant of 0.8 s. The changes of the single-channel conductance are much faster (<1 ms). The electric part of the gating process is characterized by the (reversible) molar electrical work ΔGθel = ρZgFVm ≈ -1.3 RT, which corresponds to the movement of one charge of the gating charge number |Zg| = 1 across the fraction ρ = ΔVm/Vm = 0.15 of the membrane voltage Vm = 200 mV. Unlike with chloride, the single channel conductance of fluoride has a maximum at about 150 mV in the presence of the buffer PIPES (≥5 mM, pH 6.8) with K0.5 ≈ 1 M. It is shown that the decrease in conductance is due to a blocking of the channel by the PIPES anion. In summary, the results indicate that the anion transport by the Clavibacter anion channel (CAC) does not require a voltage dependent conformation change of the CAC.  相似文献   

6.
Bioelectricity production from a phytoplankton, Chlorella vulgaris, and a macrophyte, Ulva lactuca was examined in single chamber microbial fuel cells (MFCs). MFCs were fed with the two algae (as powders), obtaining differences in energy recovery, degradation efficiency, and power densities. C. vulgaris produced more energy generation per substrate mass (2.5 kWh/kg), but U. lactuca was degraded more completely over a batch cycle (73 ± 1% COD). Maximum power densities obtained using either single cycle or multiple cycle methods were 0.98 W/m2 (277 W/m3) using C. vulgaris, and 0.76 W/m2 (215 W/m3) using U. lactuca. Polarization curves obtained using a common method of linear sweep voltammetry (LSV) overestimated maximum power densities at a scan rate of 1 mV/s. At 0.1 mV/s, however, the LSV polarization data was in better agreement with single‐ and multiple‐cycle polarization curves. The fingerprints of microbial communities developed in reactors had only 11% similarity to inocula and clustered according to the type of bioprocess used. These results demonstrate that algae can in principle, be used as a renewable source of electricity production in MFCs. Biotechnol. Bioeng. 2009;103: 1068–1076. © 2009 Wiley Periodicals, Inc.  相似文献   

7.
A good understanding of cell membrane properties is crucial for better controlled and reproducible experiments, particularly for cell electroporation where the mechanism of pore formation is not fully elucidated. In this article we study the influence on that process of several constituents found in natural membranes using bilayer lipid membranes. This is achieved by measuring the electroporation threshold (Vth) defined as the potential at which pores appear in the membrane. We start from highly stable 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) membranes (Vth ∼ 200 mV), and subsequently add therein other phospholipids, cholesterol and a channel protein. While the phospholipid composition has a slight effect (100 mV ≤ Vth ≤ 290 mV), cholesterol gives a concentration-dependent effect: a slight stabilization until 5% weight (Vth ∼ 250 mV) followed by a noticeable destabilization (Vth ∼ 100 mV at 20%). Interestingly, the presence of a model protein, α-hemolysin, dramatically disfavours membrane poration and Vth shows a 4-fold increase (∼ 800 mV) from a protein density in the membrane of 24 × 10− 3 proteins/μm2. In general, we find that pore formation is affected by the molecular organization (packing and ordering) in the membrane and by its thickness. We correlate the resulting changes in molecular interactions to theories on pore formation.  相似文献   

8.
Bio (microbial) fuel cell (microbial fuel cell) with Saccharomyces cerevisiae as anodic biocatalyst was evaluated in terms of power generation and substrate degradation at three redox conditions (5.0, 6.0 and 7.0). Fuel cell was operated in single chamber (open-air cathode) configuration without mediators using non-catalyzed graphite as electrodes. The performance was further studied with increasing loading rate (OLRI, 0.91 kg COD/m3-day; OLRII, 1.43 kg COD/m3). Higher current density was observed at pH 6.0 [160.36 mA/m2 (OLRI); 282.83 mA/m2 (OLRII)] than pH 5.0 (137.24 mA/m2) and pH 7.0 (129.25 mA/m2). Bio-electrochemical behavior of fuel cell was evaluated using cyclic voltammetry which showed the presence of redox mediators (NADH/NAD+; FADH/FAD+). Higher electron discharge was observed at pH 6.0, suggesting higher proton shuttling through the involvement of different redox mediators. The application of yeast based fuel cell can be extended to treat high strength wastewaters with simultaneous power generation.  相似文献   

9.
Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations.  相似文献   

10.
Simultaneous carbon and nitrogen removal using loop configuration microbial fuel cell (MFC) with relatively large size of 5 L was investigated in this study. Four MFC reactors were constructed with a loop configuration to eliminate the pH gradient, and the reactor performance was examined with different separators and cathode materials. The performance of the reactors in terms of electricity generation and contaminant removal rate was examined. Results showed that a maximum power density of 1415.6 mW/m3 (The empty bed volume of anode chamber) was obtained at a current density of 3258.5 mA/m3 with cation exchange membrane as separator and graphite felt (Pt coated) as cathode using the piggery wastewater as feed, and the organic removal rate obtained was approximately 0.523 kg COD/m3/d (total anode chamber) with nitrogen removal rate of 0.194 kg N/m3/d (total cathode chamber).  相似文献   

11.
Combining Voltage and Calcium Imaging from Neuronal Dendrites   总被引:2,自引:0,他引:2  
The ability to monitor membrane potential (V m) and calcium (Ca2+) transients at multiple locations on the same neuron can facilitate further progress in our understanding of neuronal function. Here we describe a method to combine V m and Ca2+ imaging using styryl voltage sensitive dyes and Fura type UV-excitable Ca2+ indicators. In all cases V m optical signals are linear with membrane potential changes, but the calibration of optical signals on an absolute scale is presently possible only in some neurons. The interpretation of Ca2+ optical signals depends on the indicator Ca2+ buffering capacity relative to the cell endogenous buffering capacity. In hippocampal CA1 pyramidal neurons, loaded with JPW-3028 and 300 μM Bis-Fura-2, V m optical signals cannot be calibrated and the physiological Ca2+ dynamics are compromised by the presence of the indicator. Nevertheless, at each individual site, relative changes in V m and Ca2+ fluorescence signals under different conditions can provide meaningful new information on local dendritic integration. In cerebellar Purkinje neurons, loaded with JPW-1114 and 1 mM Fura-FF, V m optical signals can be calibrated in terms of mV and Ca2+ optical signals quantitatively reveal the physiological changes in free Ca2+. Using these two examples, the method is explained in detail.  相似文献   

12.
The Ca2+-activated maxi K+ channel was found in the apical membrane of everted rabbit connecting tubule (CNT) with a patch-clamp technique. The mean number of open channels (NP o ) was markedly increased from 0.007 ± 0.004 to 0.189 ± 0.039 (n= 7) by stretching the patch membrane in a cell-attached configuration. This activation was suggested to be coupled with the stretch-activation of Ca2+-permeable cation channels, because the maxi K+ channel was not stretch-activated in both the cell-attached configuration using Ca2+-free pipette and in the inside-out one in the presence of 10 mm EGTA in the cytoplasmic side. The maxi K+ channel was completely blocked by extracellular 1 μm charybdotoxin (CTX), but was not by cytoplasmic 33 μm arachidonic acid (AA). On the other hand, the low-conductance K+ channel, which was also found in the same membrane, was completely inhibited by 11 μm AA, but not by 1 μm CTX. The apical K+ conductance in the CNT was estimated by the deflection of transepithelial voltage (ΔV t ) when luminal K+ concentration was increased from 5 to 15 mEq. When the tubule was perfused with hydraulic pressure of 0.5 KPa, the ΔV t was only −0.7 ± 0.4 mV. However, an increase in luminal fluid flow by increasing perfusion pressure to 1.5 KPa markedly enhanced ΔV t to −9.4 ± 0.9 mV. Luminal application of 1 μm CTX reduced the ΔV t to −1.3 ± 0.6 mV significantly in 6 tubules, whereas no significant change of ΔV t was recorded by applying 33 μm AA into the lumen of 5 tubules (ΔV t =−7.2 ± 0.5 mV in control vs.ΔV t =−6.7 ± 0.6 mV in AA). These results suggest that the Ca2+-activated maxi K+ channel is responsible for flow-dependent K+ secretion by coupling with the stretch-activated Ca2+-permeable cation channel in the rabbit CNT. Received: 21 August 1997/Revised: 20 March 1998  相似文献   

13.
Human HeLa cells transfected with mouse connexin Cx45 were used to examine the conductive and kinetic properties of Cx45 hemichannels. The experiments were carried out on single cells using a voltage-clamp method. Lowering the [Ca2+]o revealed an extra current. Its sensitivity to extracellular Ca2+ and gap junction channel blockers (18α-glycyrrhetinic acid, palmitoleic acid, heptanol), and its absence in non-transfected HeLa cells suggested that it is carried by Cx45 hemichannels. The conductive and kinetic properties of this current, I hc, were determined adopting a biphasic pulse protocol. I hc activated at positive V m and deactivated partially at negative V m. The analysis of the instantaneous I hc yielded a linear function g hc,inst = f(V m) with a hint of a negative slope (g hc,inst: instantaneous conductance). The analysis of the steady-state I hc revealed a sigmoidal function g hc,ss = f(V m) best described with the Boltzmann equation: V m,0 = −1.08 mV, g hc,min = 0.08 (g hc,ss: steady-state conductance; V m, 0:V m at which g hc,ss is half-maximally activated; g hc,min: minimal conductance; major charge carriers: K+ and Cl). The g hc was minimal at negative V m and maximal at positive V m. This suggests that Cx45 connexons integrated in gap junction channels are gating with negative voltage. I hc deactivated exponentially with time, giving rise to single time constants, τd. The function τd = f(V m) was exponential and increased with positive V md = 7.6 s at V m = 0 mV). The activation of I hc followed the sum of two exponentials giving rise to the time constants, τa1 and τa2. The function τa1 = f(V m) and τa2 = f(V m) were bell-shaped and yielded a maximum of ≅ 0.6 s at V m ≅ −20 mV and ≅ 4.9 s at V m ≅ 15 mV, respectively. Neither τa1 = f(V m) nor τa2 = f(V m) coincided with τd = f(V m). These findings conflict with the notion that activation and deactivation follow a simple reversible reaction scheme governed by first-order voltage-dependent processes.  相似文献   

14.
Neuronal membrane potential (Em) regulates the activity of excitatory voltage-sensitive channels. Anoxic insults lead to a severe loss of Em and excitotoxic cell death (ECD) in mammalian neurons. Conversely, anoxia-tolerant freshwater turtle neurons depress energy usage during anoxia by altering ionic conductance to reduce neuronal excitability and ECD is avoided. This wholesale alteration of ion channel and pump activity likely has a significant effect on Em. Using the whole-cell patch clamp technique we recorded changes in Em from turtle cortical neurons during a normoxic to anoxic transition in the presence of various ion channel/pump modulators. Em did not change with normoxic perfusion but underwent a reversible, mild depolarization of 8.1 ± 0.2 mV following anoxic perfusion. This mild anoxic depolarization (MAD) was not prevented by the manipulation of any single ionic conductance, but was partially reduced by pre-treatment with antagonists of GABAA receptors (5.7 ± 0.5 mV), cellular bicarbonate production (5.3 ± 0.2 mV) or K+ channels (6.0 ± 0.2 mV), or by perfusion of reactive oxygen species scavengers (5.2 ± 0.3 mV). Furthermore, all of these treatments induced depolarization in normoxic neurons. Together these data suggest that the MAD may be due to the summation of numerous altered ion conductance states during anoxia.  相似文献   

15.
We used ion-sensitive, double-barrel microelectrodes to measure changes in hepatocyte transmembrane potential (V m), intracellular K+, Cl-, and Na+ activities (a i k, a Cl i and a Na i ), and water volume during l-alanine uptake. Mouse liver slices were superfused with control and experimental Krebs physiological salt solutions. The experimental solution contained 20 m l-alanine, and the control solution was adjusted to the same osmolality (305 mOsm) with added sucrose. Hepatocytes also were loaded with 50 mm tetramethylammonium ion (TMA+) for 10 min. Changes in cell water volume during l-alanine uptake were determined by changes in intracellular, steady-state TMA+ activity measured with the K+ electrode. Hepatocyte control V m was -33±1 mV. l-alanine uptake first depolarized V m by 2±0.2 mV and then hyperpolarized V m by 5 mV to-38±1 mV (n = 16) over 6 to 13 min. During this hyperpolarization, a Na i increased by 30% from 19±2 to 25±3 mm (P < 0.01), and a K i did not change significantly from 83±3 mm. However, with added ouabain (1 mm) l-alanine caused only a 2-mV increase in V m, but now a K i decreased from 61±3 to 54±5 mm (P < 0.05). Hyperpolarization of V m by l-alanine uptake also resulted in a 38% decrease of a Cl i from 20±2 to 12±3 mm (P < 0.001). Changes in V m and V ClV m voltage traces were parallel during the time of l-alanine hyperpolarization, which is consistent with passive distribution of intracellular Cl with the V m in hepatocytes. Added Ba2+ abolished the l-alanineinduced hyperpolarization, and a Cl i remained unchanged. Hepatocyte water volume during l-alanine uptake increased by 12±3%. This swelling did not account for any changes in ion activities following l-alanine uptake. We conclude that hepatocyte a K i is regulated by increased Na+-K+ pump activity during l-alanine uptake in spite of cell swelling and increased V m due to increased K+ conductance. The hyperpolarization of V m during l-alanine uptake provides electromotive force to decrease a Cl i . The latter may contribute to hepatocyte volume regulation during organic solute transport.This work was supported by grant AA-08867 from the Alcohol, Drug Abuse, and Mental Health Association.  相似文献   

16.
Production of hydrogen and organic compounds by an electrosynthetic microbiome using electrodes and carbon dioxide as sole electron donor and carbon source, respectively, was examined after exposure to acidic pH (∼5). Hydrogen production by biocathodes poised at −600 mV vs. SHE increased>100-fold and acetate production ceased at acidic pH, but ∼5–15 mM (catholyte volume)/day acetate and>1,000 mM/day hydrogen were attained at pH ∼6.5 following repeated exposure to acidic pH. Cyclic voltammetry revealed a 250 mV decrease in hydrogen overpotential and a maximum current density of 12.2 mA/cm2 at −765 mV (0.065 mA/cm2 sterile control at −800 mV) by the Acetobacterium-dominated community. Supplying −800 mV to the microbiome after repeated exposure to acidic pH resulted in up to 2.6 kg/m3/day hydrogen (≈2.6 gallons gasoline equivalent), 0.7 kg/m3/day formate, and 3.1 kg/m3/day acetate ( = 4.7 kg CO2 captured).  相似文献   

17.
As an emerging biotechnology capable of removing contaminants and producing electricity, microbial fuel cells (MFCs) hold a promising future in wastewater treatment. However, several main problems, including the high internal resistance (Rin), low power output, expensive material, and complicated configuration have severely hindered the large-scale application of MFCs. The study targeted these challenges by developing a novel MFC system, granular activated carbon single-chamber MFC, termed as GAC-SCMFC. The batch tests showed that GAC was a good substitute for carbon cloth and GAC-SCMFCs generated high and stable power outputs compared with the traditional two-chamber MFCs (2CMFCs). Critical operational parameters (i.e. wastewater substrate concentrations, GAC amount, electrode distance) affecting the performance of GAC-SCMFCs were examined at different levels. The results showed that the Rin gradually decreased from 60 Ω to 45 Ω and the power output increased from 0.2 W/m3 to 1.2 W/m3 when the substrate concentrations increased from 100 mg/L to 850 mg/L. However, at high concentrations of 1000–1500 mg/L, the power output leveled off. The Rin of MFCs decreased 50% when the electrode distance was reduced from 7.5 cm to 1 cm. The highest power was achieved at the electrode distance of 2 cm. The power generation increased with more GAC being added in MFCs due to the higher amount of biomass attached. Finally, the multi-anode GAC-SCMFCs were developed to effectively collect the electrons generated in the GAC bed. The results showed that the current was split among the multiple anodes, and the cathode was the limiting factor in the power production of GAC-SCMFCs.  相似文献   

18.
Phoneutria nigriventer toxin Tx1 (PnTx1, also referred to in the literature as Tx1) exerts inhibitory effect on neuronal (NaV1.2) sodium channels in a way dependent on the holding potential, and competes with μ-conotoxins but not with tetrodotoxin for their binding sites. In the present study we investigated the electrophysiological properties of the recombinant toxin (rPnTx1), which has the complete amino acid sequence of the natural toxin with 3 additional residues: AM on the N-terminal and G on the C-terminal. At the concentration of 1.5 μM, the recombinant toxin inhibits Na+ currents of dorsal root ganglia neurons (38.4 ± 6.1% inhibition at −80 mV holding potential) and tetrodotoxin-resistant Na+ currents (26.2 ± 4.9% at the same holding potential). At −50 mV holding potential the inhibition of the total current reached 71.3 ± 2.3% with 1.5 μM rPnTx1. The selectivity of rPnTx1 was investigated on ten different isoforms of voltage-gated sodium channels expressed in Xenopus oocytes. The order of potency for rPnTx1 was: rNaV1.2 > rNaV1.7 ≈ rNaV1.4 ≥ rNaV1.3 > mNaV1.6 ≥ hNaV1.8. No effect was seen on hNaV1.5 and on the arthropods isoforms (DmNaV1, BGNaV1.1a and VdNaV1). The IC50 for NaV1.2 was 33.7 ± 2.9 nM with a maximum inhibition of 83.3 ± 1.9%. The toxin did not alter the voltage-dependence of channel gating and was effective on NaV1.2 channels devoid of inactivation. It was ineffective on neuronal calcium channels. We conclude that rPnTx1 has a promising selectivity, and that it may be a valuable model to achieve pharmacological activities of interest for the treatment of channelopathies and neuropathic pain.  相似文献   

19.
We explored the ability of a two-site, three-barrier (2S3B) Eyring model to describe recently reported data on current flow through open CaV3.1 T-type calcium channels, varying Ca2+ and Ba2+ over a wide range (100 nm–110 mm) while recording whole-cell currents over a wide voltage range (−150 mV to +100 mV) from channels stably expressed in HEK 293 cells. Effects on permeation were isolated using instantaneous current–voltage relationships (IIV) after strong, brief depolarizations to activate channels with minimal inactivation. Most experimental results were reproduced by a 2S3B model. The model described the IIV relationships, apparent affinities for permeation and block for Ca2+ and Ba2+, and shifts in reversal potential between Ca2+ and Ba2+. The fit to block by 1 mm  \textMg2+\texti {\text{Mg}}^{2+}_{\text{i}} was reasonable, but block by \textMg2+\texto {\text{Mg}}^{2+}_{\text{o}} was described less well. Surprisingly, fits were comparable with strong ion–ion repulsion, with no repulsion, or with intermediate values. With weak repulsion, there was a single high-affinity site, with a low-affinity site near the cytoplasmic side of the pore. With strong repulsion, the net charge of ions in the pore was near +2 over a relatively wide range of concentration and voltage, suggesting a knockoff mechanism. With strong repulsion, Ba2+ preferred the inner site, while Ca2+ preferred the outer site, potentially explaining faster entry of Ni2+ and other pore blockers when Ba2+ is the charge carrier.  相似文献   

20.
This study explores the relationship between impact severity and resulting pulmonary contusion (PC) for four impact conditions using a rat model of the injury. The force–deflection response from a Finite Element (FE) model of the lung was simultaneously matched to experimental data from distinct impacts via a genetic algorithm optimization. Sprague-Dawley rats underwent right-side thoracotomy prior to impact. Insults were applied directly to the lung via an instrumented piston. Five cohorts were tested: a sham group and four groups experiencing lung insults of varying degrees of severity. The values for impact velocity (V) and penetration depth (D) of the cohorts were Group 1, (V = 6.0 m · s−1, D = 5.0 mm), Group 2, (V = 1.5 m · s−1,D = 5.0 mm), Group 3, (V = 6 m · s−1, D = 2.0 mm), and Group 4, (V = 1.5 m · s−1, D = 2.0 mm). CT scans were acquired at 24 h, 48 h, and 1 week post-insult. Contusion volume was determined through segmentation. FE-based injury metrics for PC were determined at 24 h and 1 week post-impact, based on the observed volume of contusion and first principal strain. At 24 h post-impact, the volume of high radiopacity lung (HRL) was greatest for the severe impact group (mean HRL = 9.21 ± 4.89) and was significantly greater than all other cohorts but Group 3. The concurrent optimization matched simulated and observed impact energy within one standard deviation for Group 1 (energy = 3.88 ± 0.883 mJ, observed vs. 4.47 mJ, simulated) and Group 2 (energy = 1.46 ± 0.403 mJ, observed vs. 1.50 mJ, simulated) impacts. Statistically significant relationships between HRL and impact energy are presented. The FEA-based injury metrics at 24 h post-contusion are emax·[(e)\dot]max{\varepsilon_{\max}\cdot \dot {\varepsilon}_{\max}} exceeding 94.5 s−1, ε max exceeding 0.284 and [(e)\dot]max{\dot{\varepsilon}_{\max}} exceeding 470 s−1. Thresholds for injury to the lung still present at 1 week post-impact were also determined. They are emax·[(e)\dot]max{\varepsilon_{\max}\cdot \dot {\varepsilon}_{\max}} exceeding 149 s−1, ε max exceeding 0.343 and [(e)\dot]max{\dot{\varepsilon}_{\max}} exceeding 573 s−1. A mesh sensitivity study found that thresholds based on strain rate were more sensitive to changes to mesh density than the threshold based on strain only.  相似文献   

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