Electrophysiological Properties from Computations at a Single Voltage: Testing Theory with Stochastic Simulations

We use stochastic simulations to investigate the performance of two recently developed methods for calculating the free energy profiles of ion channels and their electrophysiological properties, such as current–voltage dependence and reversal potential, from molecular dynamics simulations at a single applied voltage. These methods require neither knowledge of the diffusivity nor simulations at multiple voltages, which greatly reduces the computational effort required to probe the electrophysiological properties of ion channels. They can be used to determine the free energy profiles from either forward or backward one-sided properties of ions in the channel, such as ion fluxes, density profiles, committor probabilities, or from their two-sided combination. By generating large sets of stochastic trajectories, which are individually designed to mimic the molecular dynamics crossing statistics of models of channels of trichotoxin, p7 from hepatitis C and a bacterial homolog of the pentameric ligand-gated ion channel, GLIC, we find that the free energy profiles obtained from stochastic simulations corresponding to molecular dynamics simulations of even a modest length are burdened with statistical errors of only 0.3 kcal/mol. Even with many crossing events, applying two-sided formulas substantially reduces statistical errors compared to one-sided formulas. With a properly chosen reference voltage, the current–voltage curves can be reproduced with good accuracy from simulations at a single voltage in a range extending for over 200 mV. If possible, the reference voltages should be chosen not simply to drive a large current in one direction, but to observe crossing events in both directions.     

Effects of fractal gating of potassium channels on neuronal behaviours

The classical model of voltage-gated ion channels assumes that according to a Markov process ion channels switch among a small number of states without memory, but a bunch of experimental papers show that some ion channels exhibit significant memory effects, and this memory effects can take the form of kinetic rate constant that is fractal. Obviously the gating character of ion channels will affect generation and propagation of action potentials, furthermore, affect generation, coding and propagation of neural information. However, there is little previous research on this series of interesting issues. This paper investigates effects of fractal gating of potassium channel subunits switching from closed state to open state on neuronal behaviours. The obtained results show that fractal gating of potassium channel subunits switching from closed state to open state has important effects on neuronal behaviours, increases excitability, rest potential and spiking frequency of the neuronal membrane, and decreases threshold voltage and threshold injected current of the neuronal membrane. So fractal gating of potassium channel subunits switching from closed state to open state can improve the sensitivity of the neuronal membrane, and enlarge the encoded strength of neural information.     

随机中毒对神经元网络时空动力学行为的影响

神经元细胞膜上的离子通道能够被一些有毒的化学物质阻断. 离子通道阻断会降低离子通道的电导率和激活通道数, 影响神经元的放电活动, 进而影响神经网络时空模式的动力学行为. 本文采用具有周期边界的近邻耦合Hodgkin-Huxley神经元网络, 数值研究了钠离子和钾离子通道随机中毒时神经网络时空模式的演化过程. 发现钠离子和钾离子通道随机中毒可以导致螺旋波破裂. 通过分析网络的放电概率, 发现钠离子通道随机中毒降低了神经网络的兴奋性, 且其对中毒的敏感程度与噪声强度有关; 钾离子通道随机中毒增强了神经网络的兴奋性. 与均匀的通道中毒相比, 随机通道中毒的神经网络具有更丰富的动力学行为. 最后, 采用无流边界条件对神经网络进行数值仿真, 得到了类似的结果. 该研究更真实地反映神经系统中毒时整体兴奋性的变化, 从另一个方面揭示离子通道中毒对网络时空行为的影响, 有利于更进一步理解离子通道在网络整体行为中的作用. 关键词： 神经网络 离子通道 随机中毒 时空动力学     

Raman spectroscopy of bromine chains inside the one‐dimensional channels of AlPO4‐5 single crystals

Raman spectroscopy of the one‐dimensional atomic or molecular chains, which are the attractive building blocks of advanced nanoscale materials, is crucial in understanding the physical properties of the one‐dimensional atomic or molecular chains. Here, we introduce the bromine into the one‐dimensional channels of AlPO₄‐5 single crystals through a physical vapor diffusion method. Raman spectroscopy indicates that the confined bromine structures mainly exist as (Br₂)_n chains, individual Br₂ molecules, and a small amount of Br₃⁻ chains inside the channels of AlPO₄‐5 single crystals. Polarized Raman spectra demonstrate that the bromine molecular chains are approximately parallel to the channel direction of AlPO₄‐5 single crystals. Copyright © 2015 John Wiley & Sons, Ltd.     

Experiment on the electromagnetic radiation excited in an electron beam‐ion channel system

An experimental study on electromagnetic (EM) radiation in an electron beam‐ion channel system is reported, which indicates the same result predicted by our previous theory. The system is formed in an arc plasma jet with a plasma density of 10¹⁷m^?3 , and the electron beam is driven by a voltage pulse of 20 kV. The result shows that the system can excite EM radiation in the range of the plasma frequency. The scheme is also hopeful to be used for generating high‐frequency and wide‐band EM radiation up to terahertz by enhancing the plasma density.     

Calculation of the conductance and selectivity of an ion-selective potassium channel (IRK1) from simulation of atomic scale models

We present the equations and methodology for the theoretical prediction of the conductance, permeability and selectivity of a K⁺ channel on the basis of atomic scale models for it. The methodology involves the use of Langevin dynamics and activated trajectories in order to obtain translocation free energies, rate constants and transmission coefficients for an ion going through the channel. The models are for the Inward Rectifier K⁺ channel (IRK1) which is a member of a family of ion-selective K⁺ channels. The IRK1 channel is biologically important because of its role in cardiac pacemaker function. The models we use for the IRK1 channel are developed from a model of the Shaker voltage-gated K⁺ channel. We find that the theoretically predicted conductance is too low by three orders of magnitude. We attribute this underestimate to a specific structural defect in the model used. Perhaps our most significant result is that the computed conductance is tremendously sensitive to the structural details of the so-called ‘P-loop’ that lines the outer half of the permeation pathway of the channel. This sensitivity may be useful in future studies on ion channel proteins for which the structure is not known from X-ray crystallography. In addition, this sensitivity may help determine whether X-ray structures of these proteins correspond to open or closed conformations.     

Electron-impact dissociation and transient properties of a stored LiH2 - beam

The fragmentation of LiH₂ ^- anions after electron impact was investigated at the heavy-ion storage ring TSR. The main reaction channel was found to be electron detachment followed by a breakup into LiH + H. In the first ms after production of the molecular ions in a cesium sputtering ion source, additional contributions were observed in the Li + H₂ and Li^- + H₂ channels, hinting at an initial population of a short-lived state of the anion. To gain a better understanding of the mechanisms underlying the observed behavior of the system, ab initio calculations of relevant potential energy surfaces were performed at selected geometries. The experimental findings are discussed in the light of these calculations.     

The Transport Properties of the Cell Membrane Ion Channels in Electric Fields: Bethe Lattice Treatment

The interactive two-state model of cell membrane ion channels in an electric field is formulated on the Bethe lattice by means of the exact recursion relations. The probability of channel opening or maximum fractions of open potassium and sodium channels are obtained by solving a non-linear algebraic equation. Using known parameters for the conventional mean-field theory the model gives a good agreement with the experiment both at low and high trans-membrane potential values. For intermediate voltages, the numerical results imply that collective effects are introduced by trans-membrane voltage.     

Carbon‐Coated Supraballs of Randomly Packed LiFePO4 Nanoplates for High Rate and Stable Cycling of Li‐Ion Batteries

One of the key strategies used to obtain high‐rate Li‐ion battery is the reduction of the Li‐ion path length inside the active materials and the enhancement of the ionic diffusion outside the active materials. It is demonstrated that electrochemical performance can be improved significantly at high C‐rates using carbon‐coated spherical aggregates or “supraballs” of randomly packed olivine LiFePO₄ (LFP) nanoplates as cathode active materials. 258 nm LFP nanoplates with 30 nm thickness are synthesized through a high‐temperature solvothermal method, in which short lithium‐ion channels are formed perpendicular to the top or bottom planes. These thin nanoplates are formed into carbon‐coated “supraballs” through a spray‐drying and thermal annealing process, in which nanoplates are not stacked but randomly packed due to relatively fast drying. Internal and external nanoplate ion diffusion is therefore enhanced simultaneously due to the optimal molecular crystalline structure and interparticle pore structures of the nanoplates. Indeed, the initial capacity of the carbon‐coated supraballs is 162 mAh g^?1 (173.34 mAh cm^?3) at 0.1 C and more than 80% is retained (≈130.91 mAh g^?1) at 50 C. Furthermore, they offer durable cycling stability (>500 cycles) at 1 C without compromising their capacity.     

Study on the Relation Between Discharge Voltage and Magnetic Field Topography in a Hall Thruster Discharge Channel

The relation between magnetic field topography and operating voltage is investigated in a 1kW Hall thruster discharge channel in order to focus the ion beam effectively and optimize the performance. The curvature of magnetic field line (α) is introduced to characterize the differences of topologies. The optimized magnetic field distribution under each operating voltage is obtained by experiment. Through the curvature transformation, we find that the area of (α > 1) in the channel gradually decreases with the increase of the operating voltage. In response to the results above, two dimensional plasma flows are simulated employing Particle‐in‐Cell method. The distributions of the electric potential, ion density and ion radial velocity are calculated to understand the important influence of the relation above on ion beam focusing. The numerical results indicate that magnetic field curvature and thermal electric field control the ion beam in the ionization and acceleration zone, respectively. The magnetic field topography and discharge voltage interact with each other and together form the focusing electric field. The ion radial mobility is suppressed effectively and the ion beam is focused to the channel centerline. In addition, for a given voltages, when the area of (α > 1) is larger than the optimal scope, the electric potential lines excessively bend to the anode causing ion over focus; contrarily, the electric potential lines will bend to the exit and defocus ions. All these results suggest the relation between magnetic field topography and discharge voltage is important to the ion radial flow control and performance optimization of the Hall thruster (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Two-colour mid-infrared absorption in InAs/GaSb type II and broken-gap quantum wells under gated electric field

We present a detailed theoretical study on optical properties of an InAs/GaSb-based type II and broken-gap quantum well (QW) in the presence of gated electric voltage. Two absorption peaks were observed through intraband transitions within the same material layer. The intensity of optical absorption induced by inter-layer transition is relatively weak due to a small overlap of electron and hole wavefunctions at InAs/GaSb interface. The applied electric field can open up new channels for optical transition and thus affect significantly the optical absorption by changing the overlap of the electron and hole wavefunctions as well as the transition channels. The obtained results suggest that InAs/GaSb-based type II and broken-gap QWs can be employed as two-colour photodetectors working at mid-infrared bandwidth at relatively high temperatures. More over, the bandwidth of the optical absorption can be tuned by the gated electric field.     

Evolution of NMDA receptor cytoplasmic interaction domains: implications for organisation of synaptic signalling complexes

Background  

Glutamate gated postsynaptic receptors in the central nervous system (CNS) are essential for environmentally stimulated behaviours including learning and memory in both invertebrates and vertebrates. Though their genetics, biochemistry, physiology, and role in behaviour have been intensely studied in vitro and in vivo, their molecular evolution and structural aspects remain poorly understood. To understand how these receptors have evolved different physiological requirements we have investigated the molecular evolution of glutamate gated receptors and ion channels, in particular the N-methyl-D-aspartate (NMDA) receptor, which is essential for higher cognitive function. Studies of rodent NMDA receptors show that the C-terminal intracellular domain forms a signalling complex with enzymes and scaffold proteins, which is important for neuronal and behavioural plasticity     

A naturally occurring omega current in a Kv3 family potassium channel from a platyhelminth

Background  

Voltage-gated ion channels are membrane proteins containing a selective pore that allows permeable ions to transit the membrane in response to a change in the transmembrane voltage. The typical selectivity filter in potassium channels is formed by a tetrameric arrangement of the carbonyl groups of the conserved amino-acid sequence Gly-Tyr-Gly. This canonical pore is opened or closed by conformational changes that originate in the voltage sensor (S4), a transmembrane helix with a series of positively charged amino acids. This sensor moves through a gating pore formed by elements of the S1, S2 and S3 helices, across the plane of the membrane, without allowing ions to pass through the membrane at that site. Recently, synthetic mutagenesis studies in the Drosophila melanogaster Shaker channel and analysis of human disease-causing mutations in sodium channels have identified amino acid residues that are integral parts of the gating-pore; when these residues are mutated the proteins allow a non-specific cation current, known as the omega current, to pass through the gating-pore with relatively low selectivity.     

DFT studies on the cascade rearrangement reactions of the cubylcarbinyl radical

DFT (U)B3LYP calculations with the 6‐311 + G** basis set were carried out to investigate the mechanisms of cascade rearrangement reactions (involving eight reaction channels) of the cubylcarbinyl radical (radical 1 ). The rate constant for each reaction step was calculated on the basis of the conventional transition state theory. The reaction channel from radical 1 to the 4‐(4‐methylenecyclobut‐2‐enyl) radical is preferred kinetically, while the reaction channel from radical 1 to the 1‐homocubyl radical is unfavorable. The mechanism of the conversion from radical 1 to the tricyclic dienes radical, which is experimentally uncertain, is predicted to be a stepwise process with the methylenesecocubyl radical as an intermediate instead of a concerted reaction. The energy barrier and rate constant of the initial reaction step are evaluated to be 2.8 kcal/mol and 3.0 × 10¹⁰ s^?1, respectively, in excellent agreement with the corresponding experimental values. Copyright © 2010 John Wiley & Sons, Ltd.     

NIR‐Raman spectrum and DFT calculations of okadaic acid DSP marine biotoxin microprobe

Commercially available diarrhetic shellfish poisoning (DSP) marine toxins are limited to micrograms samples invisible to the naked eye or in small amounts of micromole concentration solutions that are not suitable for normal Raman spectroscopy. As the Raman‐derived techniques are increasingly employed in various detection schemes of harmful substances, Raman spectra of the target compounds are essential for molecular recognition, detection and sensing reasons. Using a new μ‐RIM™ stainless steel hydrophobic substrate, we recorded near‐infrared micro‐Raman spectrum of okadaic acid (OA), a DSP marine biotoxin from 75 µg recrystallized toxin after drop coating deposition. Excitation with the 785‐nm line allowed the recovery and assembling of the Raman spectrum over the 100–3200 cm⁻¹ spectral range on several OA microparticles, while the 532‐nm line excited the fluorescence emission that hampered the Raman signal. Density functional theory calculations were conducted on the isolated species both in gas phase and in ethanol solution to accurately assess and interpret the experimentally observed Raman bands. A good correlation between the experimental and theoretical Raman bands allowed for a reliable vibrational Raman assignment. Owing to the molecular geometry with intramolecular hydrogen bonds, the CC conjugated systems together with the methyl groups exhibited dominant OA Raman bands. Unlike domoic acid, an amnesic shellfish poisoning toxin whose carboxyl group showed the most intense Raman band, OA Raman characteristic band was not assigned to carboxyl group. Copyright © 2016 John Wiley & Sons, Ltd.     

Tunable anticrossing of gated and ungated plasma resonances and enhancement of interlayer terahertz electric field in an asymmetric bilayer of density-modulated two-dimensional electron gases

We study theoretically the terahertz (THz) response of a bilayer of density-modulated two-dimensional electron gases, which we employ to model the actual double-quantum-well electron channel of a grid-gated field-effect transistor in which strong THz photoresponse was recently observed. We have shown that such a system can be driven into the anticrossing regime between gated and ungated plasma resonances by tuning the gate voltage. The amplitude of the interlayer THz electric field in the ungated (double-layered) portions of the channel increases dramatically in the anticrossing regime. This strong interlayer THz electric field may strongly affect interlayer electron tunneling which, in turn, may contribute to the physical mechanism underlying the strong THz photoresponse observed in recent experiments.     

Sodium channel Na<Subscript>v</Subscript>1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

Background  

Voltage gated sodium channels Na_v1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders.     

Energy transfer over long distances by means of electron beams

It is suggested that the effect of multiple contactless rotation of electrons in an electrified ring, which has been recently discovered by our group, be used for energy transfer over long distances. In experiments with the ring, electrons travel very long distances, ≥10⁷ km. Electron losses due to radiation and losses in a residual gas are analyzed. It is shown that these losses are much lower than 10^?4 % over a distance of ≥10⁴ km. Analysis is performed with regard to the complicated profile of the track. The electrical power that can be transmitted through such a channel is estimated. It exceeds 10¹³ W at a channel diameter of several millimeters. If channels have the form of a solenoid or toroid, high magnetic fields arise in them, which may find different applications including magnetic plasma confinement.     

Langevin approach for stochastic Hodgkin–Huxley dynamics with discretization of channel open fraction

The random opening and closing of ion channels establishes channel noise, which can be approximated and included into stochastic differential equations (Langevin approach). The Langevin approach is often incorporated to model stochastic ion channel dynamics for systems with a large number of channels. Here, we introduce a discretization procedure of a channel-based Langevin approach to simulate the stochastic channel dynamics with small and intermediate numbers of channels. We show that our Langevin approach with discrete channel open fractions can give a good approximation of the original Markov dynamics even for only 10 K⁺$10{\text{K}}^{+}$ channels. We suggest that the better approximation by the discretized Langevin approach originates from the improved representation of events that trigger action potentials.