Voltage-dependent Gating Research Articles

Gate voltage dependence on the density of state of 30° twisted bilayer graphene using Trotter–Suzuki tight-binding time propagation method

Abstract Twisted multilayer structures are considered a helpful framework for exploring strongly correlated many-particle systems, where phenomena of physics correlation emerge. Here, we present the Trotter–Suzuki tight-binding time propagation method for computing the density of states (DOS) in a 30° twisted bilayer graphene (TBG). This method solves the time-dependent Schrödinger equation by decomposing Hamiltonian matrices to derive the correlation function. The Fourier transform of this correlation function yields the DOS of the system up to ≈ 1000 000 atoms. Our calculation proves that geometry makes an outstanding contribution to our final results. Additionally, applying additional gate voltage induces shifts in Van Hove singularities, potentially leading to the emergence of new states at the Fermi energy level. The results demonstrate that TBG systems can be easily adjusted and modified for further investigation of optoelectronic features.

Temperature- and gate voltage-dependent I–V modeling of GaN HEMTs based on ASM-HEMT

Abstract In this paper, a temperature and gate voltage dependent current-voltage (I-V) model for Gallium nitride (GaN) high electron mobility transistors (HEMTs) devices is studied. In order to help researchers and designers simulate devices in the absence of experimental data and improve parameter extraction efficiency, the temperature and gate voltage dependence of mobility are discussed and incorporated into the proposed model which is revised from the standard advanced SPICE model (ASM) for GaN HEMTs. The mobility variations with gate voltage from -2 V to 6 V and temperature from 10 K to 1000 K are analyzed. The simulation results of our model are compared with the standard ASM-HEMT model, and the output and transfer characteristics of the device from 270 K to 420 K are simulated. Thereby, our model may simulate various applications of GaN HEMTs at different gate voltages and temperatures in the early stages of design and research.

A positively charged residue at the Kv1.1 T1 interface is critical for voltage-dependent activation and gating kinetics.

Within the tetramerization domain (T1) of most voltage-gated potassium channels (Kv) are highly conserved charged residues that line the T1-T1 interface. We investigated the Kv1.1 residue R86 located at the narrowest region of the T1 interface. A Kv1.1 R86Q mutation was reported in a child diagnosed with lower limb dyskinesia (Set KK, Ghosh D, Huq AHM, Luat AF. Mov Disord Clin Pract 4: 784-786, 2017). The child did not present with episodic ataxia 1 (EA1) symptoms typically associated with Kv1.1 loss-of-function mutations. We characterized the electrophysiological outcome of the R86Q substitution by expressing Kv1.1 in Xenopus laevis oocytes. Mutated α-subunits were able to form functional channels that pass delayed rectifier currents. Oocytes that expressed only mutated α-subunits produced a significant reduction in Kv1.1 current and showed a positive shift in voltage dependence of activation. In addition, there was substantially slower activation and faster deactivation implying a reduction in the time the channel is in its open state. Oocytes co-injected with both mutated and wild-type cRNA in equal amounts, to mimic the heterozygous condition of the disease, showed a decrease in current amplitude at -10 mV, a positive shift in activation voltage-dependence and faster deactivation kinetics when compared with the wild-type channel. These findings indicate that T1 plays a role in Kv1.1's voltage-dependent activation and in its kinetics of activation and deactivation.NEW & NOTEWORTHY This is the first Kv1.1 study to characterize the electrophysiological and structural phenotype of a tetramerization (T1) domain mutation. Surprisingly, the mutated α-subunits were able to tetramerize, albeit with different gating kinetics and voltage dependence. This novel finding points to a clear role of T1 in the channel's voltage dependence and gating. Mimicking the heterozygous condition resulted in milder alterations in channel function when compared with previously reported mutations. This is in agreement with the child's milder symptoms.

A Feature Selection-Incorporated Simulation Study to Reveal the Effect of Calcium Ions on Cardiac Repolarization Alternans during Myocardial Ischemia

(1) Background: The main factors and their interrelationships contributing to cardiac repolarization alternans (CRA) remain unclear. This study aimed to elucidate the calcium (Ca2+)-related mechanisms underlying myocardial ischemia (MI)-induced CRA. (2) Materials and Methods: CRA was induced using S1 stimuli for pacing in an in silico ventricular model with MI. The standard deviations of nine Ca2+-related subcellular parameters among heartbeats from 100 respective nodes with and without alternans were chosen as features, including the maximum systole and end-diastole and corresponding differences in the Ca2+ concentration in the intracellular region([Ca2+]i) and junctional sarcoplasmic reticulum ([Ca2+]jsr), as well as the maximum opening of the L-type Ca2+ current (ICaL) voltage-dependent activation gate (d-gate), maximum closing of the inactivation gate (ff-gate), and the gated channel opening time (GCOT). Feature selection was applied to determine the importance of these features. (3) Results: The major parameters affecting CRA were the differences in [Ca2+]i at end-diastole, followed by the extent of d-gate activation and GCOT among beats. (4) Conclusions: MI-induced CRA is primarily characterized by functional changes in Ca2+ re-uptake, leading to alternans of [Ca2+]i and subsequent alternans of ICaL-dependent properties. The combination of computational simulation and machine learning shows promise in researching the underlying mechanisms of cardiac electrophysiology.

Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia.

The function of the chloride channel ClC-1 is crucial for the control of muscle excitability. Thus, reduction of ClC-1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not allow in vivo screening of potentially therapeutic drugs, as the zebrafish model does. In this work, we identified and characterized the two zebrafish orthologues (clc-1a and clc-1b) of the ClC-1 channel. Both channels are mostly expressed in the skeletal muscle as revealed by RT-PCR, western blot, and electrophysiological recordings of myotubes, and clc-1a is predominantly expressed in adult stages. Characterization in Xenopus oocytes shows that the zebrafish channels display similar anion selectivity and voltage dependence to their human counterparts. However, they show reduced sensitivity to the inhibitor 9-anthracenecarboxylic acid (9-AC), and acidic pH inverts the voltage dependence of activation. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement, which could be reverted by expression of human ClC-1 but not by some ClC-1 containing myotonia mutations. Treatment of clc-1-depleted zebrafish with mexiletine, a typical drug used in human myotonia, improves the motor behaviour. Our work extends the repertoire of ClC channels to evolutionary structure-function studies and proposes the zebrafish clcn1 crispant model as a simple tool to find novel therapies for myotonia. KEY POINTS: We have identified two orthologues of ClC-1 in zebrafish (clc-1a and clc-1b) which are mostly expressed in skeletal muscle at different developmental stages. Functional characterization of the activity of these channels reveals many similitudes with their mammalian counterparts, although they are less sensitive to 9-AC and acidic pH inverts their voltage dependence of gating. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement which could be reverted by expression of human ClC-1. Myotonia-like symptoms caused by clc-1a/b depletion can be reverted by mexiletine, suggesting that this model could be used to find novel therapies for myotonia.

Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels1 are essential for pacemaking activity and neural signalling2,3. Drugs inhibiting HCN1 are promising candidates for management of neuropathic pain4 and epileptic seizures5. The general anaesthetic propofol (2,6-di-iso-propylphenol) is a known HCN1 allosteric inhibitor6 with unknown structural basis. Here, using single-particle cryo-electron microscopy and electrophysiology, we show that propofol inhibits HCN1 by binding to a mechanistic hotspot in a groove between the S5 and S6 transmembrane helices. We found that propofol restored voltage-dependent closing in two HCN1 epilepsy-associated polymorphisms that act by destabilizing the channel closed state: M305L, located in the propofol-binding site in S5, and D401H in S6 (refs. 7,8). To understand the mechanism of propofol inhibition and restoration of voltage-gating, we tracked voltage-sensor movement in spHCN channels and found that propofol inhibition is independent of voltage-sensor conformational changes. Mutations at the homologous methionine in spHCN and an adjacent conserved phenylalanine in S6 similarly destabilize closing without disrupting voltage-sensor movements, indicating that voltage-dependent closure requires this interface intact. We propose a model for voltage-dependent gating in which propofol stabilizes coupling between the voltage sensor and pore at this conserved methionine-phenylalanine interface in HCN channels. These findings unlock potential exploitation of this site to design specific drugs targeting HCN channelopathies.

Impact of Gate Voltage on Mobility of Charge Carriers in Conductive Channel of Organic Molecular Semiconductors: Transport Landscape Assessed by Alternating and Direct Current Mode Techniques

AbstractThe gate voltage dependence of the charge carrier mobility is investigated by the microwave resonance technique in transport channels at various organic semiconductors‐insulator interfaces. Although the microwave based measurement is free from the Schottky‐barrier, the vertical charge transport, and the minority carrier trapping, which have been regarded as the origin of the nonlinearity in field effect transistor (FET) measurements, the obtained charge carrier mobility is impacted significantly by the applied gate bias. Atomic force microscopy (AFM) and X‐ray diffractometry (XRD) measurements revealed that the observed nonlinearity indeed originates from the surface disorder in even polycrystalline materials including conjugated polymers. The concerted assessment of the microwave resonance and the FET measurements reveals that 1) injected carriers below the threshold voltage are not trapped despite of the absence of the drain current, 2) the only charge carrier mobility at the 1st layer is assessed by FET measurements, and 3) the threshold voltage of conjugated polymers is relatively low due to the intra‐domain connection through tie molecules.

GaAs Cone-Shell Quantum Dots in a Lateral Electric Field: Exciton Stark-Shift, Lifetime, and Fine-Structure Splitting.

Strain-free GaAs cone-shell quantum dots have a unique shape, which allows a wide tunability of the charge-carrier probability densities by external electric and magnetic fields. Here, the influence of a lateral electric field on the optical emission is studied experimentally using simulations. The simulations predict that the electron and hole form a lateral dipole when subjected to a lateral electric field. To evaluate this prediction experimentally, we integrate the dots in a lateral gate geometry and measure the Stark-shift of the exciton energy, the exciton intensity, the radiative lifetime, and the fine-structure splitting (FSS) using single-dot photoluminescence spectroscopy. The respective gate voltage dependencies show nontrivial trends with three pronounced regimes. We assume that the respective dominant processes are charge-carrier deformation at a low gate voltage U, a vertical charge-carrier shift at medium U, and a lateral charge-carrier polarization at high U. The lateral polarization forms a dipole, which can either enhance or compensate the intrinsic FSS induced by the QD shape anisotropy, dependent on the in-plane orientation of the electric field. Furthermore, the data show that the biexciton peak can be suppressed by a lateral gate voltage, and we assume the presence of an additional vertical electric field induced by surface charges.

Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease

Together with its β-subunit OSTM1, ClC-7 performs 2Cl−/H+ exchange across lysosomal membranes. Pathogenic variants in either gene cause lysosome-related pathologies, including osteopetrosis, lysosomal storage, and pigmentation defects. CLCN7 variants can cause recessive or dominant disease. Different variants entail different sets of symptoms. Loss of ClC-7 causes osteopetrosis and mostly neuronal lysosomal storage. A recently reported de novo CLCN7 mutation (p.Tyr715Cys) causes widespread severe lysosome pathology and hypopigmentation (‘HOD syndrome’), but no osteopetrosis. We now describe two additional HOD individuals with the previously described p.Tyr715Cys and a novel p.Lys285Thr mutation, respectively. Both mutations decreased ClC-7 inhibition by PI(3,5)P2 and affected residues lining its binding pocket, and shifted voltage-dependent gating to less positive potentials, an effect partially conferred to WT subunits in WT/mutant heteromers. This shift predicts augmented pH gradient-driven Cl− uptake into vesicles. Overexpressing either mutant induced large lysosome-related vacuoles. This effect depended on Cl−/H+-exchange, as shown using mutants carrying uncoupling mutations. Fibroblasts from the p.Y715C patient also displayed giant vacuoles. This was not observed with p.K285T fibroblasts probably due to some ClC-7K285T-retained PI(3,5)P2 sensitivity. The gain of function caused by the shifted voltage-dependence of either mutant likely is the main cause of their pathogenicity. Their loss of PI(3,5)P2 inhibition will further increase currents, but may not be a general feature of HOD. Overactivity of ClC-7 induces pathologically enlarged vacuoles in many tissues, which is distinct from lysosomal storage observed with the loss of ClC-7 function. Osteopetrosis results from a loss of ClC-7, but osteoclasts remain resilient to increased ClC-7 activity.

Supercurrent in the Presence of Direct Transmission and a Resonant Localized State.

We study the current-phase relation (CPR) of an InSb-Al nanowire Josephson junction in parallel magnetic fields up to 700mT. At high magnetic fields and in narrow voltage intervals of a gate under the junction, the CPR exhibits π shifts. The supercurrent declines within these gate intervals and shows asymmetric gate voltage dependence above and below them. We detect these features sometimes also at zero magnetic field. The observed CPR properties are reproduced by a theoretical model of supercurrent transport via interference between direct transmission and a resonant localized state.

Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

Characterization of Mn5Ge3 Contacts on a Shallow Ge/SiGe Heterostructure.

Mn5Ge3 is a ferromagnetic phase of the Mn-Ge system that is a potential contact material for efficient spin injection and detection. Here, we investigate the creation of Mn5Ge3-based contacts on a Ge/SiGe quantum well heterostructure via solid-state synthesis. X-ray diffraction spectra fitting indicates the formation of Mn5Ge3-based contacts on bulk Ge and Ge/SiGe. High-resolution scanning transmission electron microscopy imaging and energy dispersive X-ray spectroscopy verify the correct Mn5Ge3-based phase formation. Schottky diode measurements, transmission line measurements, and Hall measurements reveal that Mn5Ge3-based contacts serve as good p-type contacts for Ge/SiGe quantum well heterostructures due to having a low Schottky barrier height of 0.10eV (extracted from a Mn5Ge3/n-Ge analogue) and a contact resistance in the order of 1 kΩ. Furthermore, we show that these electrical characteristics have a gate-voltage dependence, thereby providing tunability.

Physical Insight Into Multiple Gate-Voltage Dependencies of Off-State Photocurrent in Amorphous InZnO Thin-Film Transistors

Physical Insight Into Multiple Gate-Voltage Dependencies of Off-State Photocurrent in Amorphous InZnO Thin-Film Transistors

A DFT+U study of carbon nanotubes under influence of a gate voltage

A possibility of appearance of antiferromagnetic ordering in armchair carbon nanotubes and graphene is studied using density functional theory within a DFT+U approach. It is shown that the Coulomb repulsion between electrons in the π-orbitals of graphene would need to reach a threshold value of Uc=3.6eV, in order to stabilize the antiferromagnetic order and an energy gap in an electron spectrum at the Fermi level. In the carbon nanotubes the threshold value Uc for appearance of the antiferromagnetism decreases with the nanotube’s diameter. For an intermediate value of U<Uc the dependence of the energy gap on the diameter of nanotube is well described by a power law in agreement with earlier experimental findings.The antiferromagnetism in the carbon nanotubes is suppressed by departure of the Fermi level from a neutrality point. The latter result can qualitatively explain experimentally observed gate voltage dependence of the energy gap in junctions with the suspended carbon nanotubes as well as the absence of the energy gap in junctions with nanotubes deposited on some substrates.

Propofol rescues HCN1 epilepsy mutants and reveals non-canonical voltage-dependent gating in HCN channels

Propofol rescues HCN1 epilepsy mutants and reveals non-canonical voltage-dependent gating in HCN channels

Hot-Carrier Damage in N-Channel EDMOS Used in Single Photon Avalanche Diode Cell through Quasi-Static Modeling.

A single photon avalanche diode (SPAD) cell using N-channel extended-drain metal oxide semiconductor (N-EDMOS) is tested for its hot-carrier damage (HCD) resistance. The stressing gate-voltage (VGS) dependence is compared to hot-hole (HH) injection, positive bias temperature (PBT) instability and off-mode (VGS = 0). The goal was to check an accurate device lifetime extraction using accelerated DC to AC stressing by applying the quasi-static (QS) lifetime technique. N-EDMOS device is devoted to 3D bonding with CMOS imagers obtained by an optimized process with an effective gate-length Leff = 0.25 µm and a SiO2 gate-oxide thickness Tox = 5 nm. The operating frequency is 10 MHz at maximum supply voltage VDDmax = 5.5 V. TCAD simulations are used to determine the real voltage and timing configurations for the device in a mixed structure of the SPAD cell. AC device lifetime is obtained using worst-case DC accelerating degradation, which is transferred by QS technique to the AC waveforms applied to N-EDMOS device. This allows us to accurately obtain the AC device lifetime as a function of the delay and load for a fixed pulse shape. It shows the predominance of the high energy hot-carriers involved in the first substrate current peak during transients.

Speedy stomata of a C4 plant correlate with enhanced K+ channel gating.

Stomata are microscopic pores at the surface of plant leaves that facilitate gaseous diffusion to support photosynthesis. The guard cells around each stoma regulate the pore aperture. Plants that carry out C4 photosynthesis are usually more resilient than C3 plants to stress, and their stomata operate over a lower dynamic range of CO2 within the leaf. What makes guard cells of C4 plants more responsive than those of C3 plants? We used gas exchange and electrophysiology, comparing stomatal kinetics of the C4 plant Gynandropsis gynandra and the phylogenetically related C3 plant Arabidopsis thaliana. We found, with varying CO2 and light, that Gynandropsis showed faster changes in stomata conductance and greater water use efficiency when compared with Arabidopsis. Electrophysiological analysis of the dominant K+ channels showed that the outward-rectifying channels, responsible for K+ loss during stomatal closing, were characterised by a greater maximum conductance and substantial negative shift in the voltage dependence of gating, indicating a reduced inhibition by extracellular K+ and enhanced capacity for K+ flux. These differences correlated with the accelerated stomata kinetics of Gynandropsis, suggesting that subtle changes in the biophysical properties of a key transporter may prove a target for future efforts to engineer C4 stomatal kinetics.

Molecular basis of ClC-6 function and its impairment in human disease.

ClC-6 is a late endosomal voltage-gated chloride-proton exchanger that is predominantly expressed in the nervous system. Mutated forms of ClC-6 are associated with severe neurological disease. However, the mechanistic role of ClC-6 in normal and pathological states remains largely unknown. Here, we present cryo-EM structures of ClC-6 that guided subsequent functional studies. Previously unrecognized ATP binding to cytosolic ClC-6 domains enhanced ion transport activity. Guided by a disease-causing mutation (p.Y553C), we identified an interaction network formed by Y553/F317/T520 as potential hotspot for disease-causing mutations. This was validated by the identification of a patient with a de novo pathogenic variant p.T520A. Extending these findings, we found contacts between intramembrane helices and connecting loops that modulate the voltage dependence of ClC-6 gating and constitute additional candidate regions for disease-associated gain-of-function mutations. Besides providing insights into the structure, function, and regulation of ClC-6, our work correctly predicts hotspots for CLCN6 mutations in neurodegenerative disorders.

Moiré Synaptic Transistor for Homogeneous-Architecture Reservoir Computing

Reservoir computing has been considered as a promising intelligent computing paradigm for effectively processing complex temporal information. Exploiting tunable and reproducible dynamics in the single electronic device have been desired to implement the “reservoir” and the “readout” layer of reservoir computing system. Two-dimensional moiré materials, with an artificial lattice constant many times larger than the atomic length scale, are one type of most studied artificial quantum materials in community of material science and condensed-matter physics over the past years. These materials are featured with gate-tunable periodic potential and electronic correlation, thus varying the electric field allows the electrons in the moiré potential per unit cell to exhibit distinct and reproducible dynamics, showing great promise in robust reservoir computing. Here, we report that a moiré synaptic transistor can be used to implement the reservoir computing system with a homogeneous reservoir-readout architecture. The synaptic transistor is fabricated based on an h-BN/bilayer graphene/h-BN moiré heterostructure, exhibiting ferroelectricity-like hysteretic gate voltage dependence of resistance. Varying the magnitude of the gate voltage enables the moiré transistor to switch between long-term memory and short-term memory with nonlinear dynamics. By employing the short- and long-term memories as the reservoir nodes and weights of the readout layer, respectively, we construct a full-moiré physical neural network and demonstrate that the classification accuracy of 90.8% can be achieved for the MNIST (Modified National Institute of Standards and Technology) handwritten digits database. Our work would pave the way towards the development of neuromorphic computing based on moiré materials.

A new polymodal gating model of the proton-activated chloride channel.

The proton-activated chloride (PAC) channel plays critical roles in ischemic neuron death, but its activation mechanisms remain elusive. Here, we investigated the gating of PAC channels using its novel bifunctional modulator C77304. C77304 acted as a weak activator of the PAC channel, causing moderate activation by acting on its proton gating. However, at higher concentrations, C77304 acted as a weak inhibitor, suppressing channel activity. This dual function was achieved by interacting with 2 modulatory sites of the channel, each with different affinities and dependencies on the channel's state. Moreover, we discovered a protonation-independent voltage activation of the PAC channel that appears to operate through an ion-flux gating mechanism. Through scanning-mutagenesis and molecular dynamics simulation, we confirmed that E181, E257, and E261 in the human PAC channel serve as primary proton sensors, as their alanine mutations eliminated the channel's proton gating while sparing the voltage-dependent gating. This proton-sensing mechanism was conserved among orthologous PAC channels from different species. Collectively, our data unveils the polymodal gating and proton-sensing mechanisms in the PAC channel that may inspire potential drug development.