Time Constant Of Current Decay Research Articles

Synergistic Enhancement of Electron Dynamics and Optical Properties in Zeolitic Imidazolate Framework-8-Derived Zinc Oxide via Surface Plasmon Resonance Effects of Silver Nanoparticles under UV Irradiation.

This study investigates the surface plasmon resonance (SPR)-induced UV photoresponse of zinc oxide (ZnO) derived from zeolitic imidazolate framework-8 (ZIF-8) to assess the influence of silver nanoparticles (Ag NPs) on the photoresponse behavior of metal-organic framework (MOF)-derived ZnO. The initial synthesis involved a thermal treatment in air to convert ZIF-8 into ZnO. We noted enhanced optical absorption both in the UV and visible spectra with the deposition of Ag NPs onto the ZIF-8-derived ZnO. Additionally, the presence of Ag NPs in the ZnO resulted in a substantial increase in current, even without any light exposure. This increase is attributed to the transfer of electrons from the Ag NPs to the ZnO. Photocurrent measurements under UV illumination revealed that the photocurrent with Ag NPs was significantly higher-by two orders of magnitude-compared with that without Ag NPs. This demonstrates that SPR-induced absorption markedly boosted the photocurrent, although the current rise and decay time constants remained comparable to those observed with ZnO alone. Although Ag NPs contribute electrons to ZnO, creating a "pre-doping" effect that heightens baseline conductivity (even in the absence of light), this does not necessarily alter the recombination dynamics of the photogenerated carriers, as indicated by the similar rise and decay time constants. The electron transfer from Ag to ZnO increases the density of charge carriers but does not significantly influence their recombination.

The residence of synaptically released dopamine on D2 autoreceptors.

SUMMARYNeuromodulation mediated by synaptically released endogenous transmitters acting in G-protein-coupled receptors (GPCRs) is slow primarily because of multistep downstream signaling. What is less well understood is the spatial and temporal kinetics of transmitter and receptor interaction. The present work uses the combination of the dopamine sensor, dLight, to detect the spatial release and diffusion of dopamine and a caged form of a D2-dopamine receptor antagonist, CyHQ-sulpiride, to rapidly block the D2 autoreceptors. Photoactivation of the CyHQ-sulpiride blocks receptors in milliseconds such that the time course of dopamine/receptor interaction is mapped onto the downstream signaling. The results show that highly localized release, but not dopamine diffusion, defines the time course of the functional interaction between dopamine and D2 autoreceptors, which determines downstream inhibition.

1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth muscle.

1,8-Cineole is a cyclic monoterpenoid used in folk medicine for treatment of numerous respiratory diseases and other infections. 1,8-Cineole has anti-inflammatory, antioxidant, and myorelaxant effects, as well as low toxicity. In the present study, the effects of 1,8-cineole on contractility and voltage-gated calcium channels (VGCC) in tracheal smooth muscle were investigated. Intact and dissociated tracheal smooth muscle were used for muscle contraction and patch-clamp recordings, respectively. In experiments involving muscle contraction, 1,8-cineole potentiated contractions at low concentrations and relaxed contractions induced by isotonic K+ at high concentrations. AMTB (a TRPM8 channel blocker) reduced the potentiation induced by 1,8-cineole while indomethacin (a COX inhibitor) did not block this effect. In dissociated myocytes, 1,8-cineole partially blocked Ba2+ currents through VGCC in a concentration-dependent manner. 1,8-Cineole shifted the steady-state activation and inactivation curves to the left and also reduced the current decay time constant. In conclusion, 1,8-cineole has a dual effect on tracheal smooth muscle contraction resulting in a biphasic effect. Our data suggest that the potentiation effect is mediated by activation of TRPM8 channels and the relaxation effect is mediated by the blockage of L-type VGCC.

Study on Quench Protection of Coil Wound of Bi/Ag-Sheathed Wire

Sure quench protection of HTS coils is essential for their sustainable operations in their real applications to HTS power devices. The authors investigate conditions to safely protect HTS coils from quench damages by a detect-and-dump-type active method. In the previous work, the safe area in the V qs versus τ plane was identified by experiment using test coils wound of Bi/Ag-sheathed wires, where V qs is the quench detection voltage, and τ is the decay time constant of the coil current in the active protection method. In this work, the safe area is obtained by numerical calculation, making a simulation model of a winding pack of a coil wound of Bi/Ag-sheathed wires. The analytical results well agree with those of the experimental results, and it is shown analytically that condition to safely protect a coils wound of Bi/Ag-sheathed wires from a quench damage can be analytically predicted.

Quench Protection Characteristics of Coil Wound of Bi/Ag-Sheathed Wire

The most probable cause of quenches of a coil wound of Bi/Ag-sheathed wires is the appearance of a long resistive zone caused by the temperature rise of the long part of the conductor due to, for example, ac losses and the malfunction of the cryogenic system. Protection characteristics of quenches by this cause are experimentally and analytically investigated. In the experiment, the operating temperature of a coil wound of a Bi/Ag-sheathed wire is gradually increased until the resistive voltage of the coil exceeds a given threshold to start a quench dump sequence. Damages in the test coils are examined by changing the decay time constant of the coil current. Based on those results, conditions to protect coils from damages are investigated. Analysis is conducted to simulate quench events, and conditions for quench protection are obtained. The analytical results well explain the quench behaviors of the test coils.

Fast and slow interactions of n-alkanols with human 5-HT3A receptors: Implications for anesthetic mechanisms

This is part of a continuing patch-clamp study exploring molecular actions of anesthetics and systematically varied related substances on 5-HT3A receptors as prototypes of ligand-gated ion channels. Specifically, n-alkanols, related to but simpler in structure than propofol, were studied to explore the complex actions of this leading intravenous anesthetic.Outside-out patches excised from HEK 293 cells heterologously expressing human 5-HT3A receptors were superfused with even-numbered n-alkanols (ethanol through n-tetradecanol) of different concentrations. Fast solution exchange for varying durations allowed separation of drug actions by their kinetics.Compared with propofol the electrophysiological responses to n-alkanols were not much simpler. n-Alkanols produced fast and slow inhibition or potentiation of current amplitudes, and acceleration of current rise and decay time constants, depending on exposure time, concentration, and chain-length of the drug. Inhibition dominated, characterized by fast and slow processes with time constants separated by two orders of magnitude which were similar for different n-alkanols and for propofol. Absolute interaction energies for ethanol to n-dodecanol (relative to xenon) ranged from −10.8 to −37.3kJmol−1.No two n-alkanols act completely alike. Potency increases with chain length (until cutoff) mainly because of methylene groups interacting with protein sites rather than because of their tendency to escape from the aqueous phase. Similar wash-in time constants for n-alkanols and propofol suggest similar mechanisms, dominated by the kinetics of conformational state changes rather than by binding reactions.

Quench Protection of DI-BSCCO Coil

Quench protection is one of the most important requirements for the practical application of high-temperature-superconducting (HTS) coils. Quench protection requires that early detection of a developing quench event is followed by rapid reduction of the operating current. However, such quench detection is very difficult because HTS wire produces heat only locally due to the very slow propagation velocity of a normal zone. Excellent high voltage insulation performance is required if the current is to be reduced rapidly in a large-scale superconducting application with very large inductance. Thus it is important to investigate the behavior of coils with various decay time constants, and to detect voltages on very short time scales. This goal remains to be achieved. In the present study we built test coil and a full-scale pole coil for a 20 MW motor for use in experiments on quench protection, and parameterized the relation between the decay time constant and the detecting voltage, using a conventional balance circuit to detect the quench, which was generated by gradually raising the temperature of the coils. The results verify that a balance circuit can be used for quench detection. For example, when the current decay time constant is 4seconds, the test coil can be protected even with a detecting voltage of 0.15 volts, despite a significant heat production rate of 126W. We also confirmed that the full-scale pole coil, with a decay time constant of 20seconds, can be protected with a detecting voltage of 0.06V.

Desensitization of functional µ-opioid receptors increases agonist off-rate.

Desensitization of µ-opioid receptors (MORs) develops over 5-15 minutes after the application of some, but not all, opioid agonists and lasts for tens of minutes after agonist removal. The decrease in function is receptor selective (homologous) and could result from 1) a reduction in receptor number or 2) a decrease in receptor coupling. The present investigation used photolysis of two caged opioid ligands to examine the kinetics of MOR-induced potassium conductance before and after MOR desensitization. Photolysis of a caged antagonist, carboxynitroveratryl-naloxone (caged naloxone), blocked the current induced by a series of agonists, and the time constant of decline was significantly decreased after desensitization. The increase in the rate of current decay was not observed after partial blockade of receptors with the irreversible antagonist, β-chlornaltrexamine (β-CNA). The time constant of current decay after desensitization was never more rapid than 1 second, suggesting an increased agonist off-rate rather than an increase in the rate of channel closure downstream of the receptor. The rate of G protein-coupled K(+) channel (GIRK) current activation was examined using photolysis of a caged agonist, carboxynitrobenzyl-tyrosine-[Leu(5)]-enkephalin. After acute desensitization or partial irreversible block of MORs with β-CNA, there was an increase in the time it took to reach a peak current. The decrease in the rate of agonist-induced GIRK conductance was receptor selective and dependent on receptor number. The results indicate that opioid receptor desensitization reduced the number of functional receptor and that the remaining active receptors have a reduced agonist affinity.

Anxiolytic drugs and altered hippocampal theta rhythms: The quantitative systems pharmacological approach

The spirit of systems pharmacology was adopted to study the possible mechanisms of anxiolytic drugs on hippocampal electric patterns. The frequency of the hippocampal theta rhythm increases linearly with the intensity of electrical stimulation to the brainstem. The reduction of mean theta frequency in this paradigm predicts the clinical efficacy of anxiolytic drugs. The purpose of this study was to investigate the mechanisms by which anxiolytics produce their characteristic effects on the slope and intercept of the stimulus-frequency relationship of hippocampal theta. A network of neuron populations that generates septo-hippocampal theta rhythm was modeled using a compartmental modeling technique. The influence of cellular and synaptic parameters on network frequency was studied. Results show that halving the rate of rise and fall of pyramidal hyperpolarization-activated (Ih) conductance lowers nPO elicited theta frequency at low levels of stimulation. Results also suggest that increasing the decay time constant of inhibitory post-synaptic current can reduce the frequency of low nPO stimulation elicited theta rhythm, while maximal synaptic conductance of GABA-mediated synapses has little effect on frequency. Given their similar effect on network dynamics as by known anxiolytics, these parameter manipulations may mimic or predict the biophysical manifestations of anxiolytic action within the septo-hippocampal system.

Effects of a Non-Hydrolyzable ADP-Ribose Analog on the Gating of the TRPM2 Channel

TRPM2 is a non-selective Ca2+ permeable cation channel co-activated by intracellular Ca2+ and ADP-ribose (ADPR). ADPR binds to the C-terminal NUDT9-H domain. Intriguingly, when expressed in isolation, the NUDT9-H domain functions as an active ADPR hydrolase which breaks ADPR into AMP and ribose-5-phosphate. To exploit the relevance of this putative activity for channel gating, we examined the effect of AMPCPR-, a non-hydrolyzable ADPR analogue, on TRPM2 channel gating using macroscopic measurements and steady-state single-channel kinetic analysis. In biochemical experiments purified NUDT9, a mitochondrial ADPR-pyrophosphatase, showed efficient hydrolysis of ADPR, but completely failed to cleave AMPCPR.When applied to inside-out patches the apparent affinity of AMPCPR for TRPM2 activation was two orders of magnitude lower compared to ADPR (K1/2ADPR≈1μM, K1/2AMPCPR≈80μM), and even at a saturating concentration, it could only partially stimulate TRPM2 activity.We also compared macroscopic current relaxation time courses in response to sudden removal of ADPR or AMPCPR. The current decay time constant was almost four times shorter after AMPCPR removal than following ADPR withdrawal.In steady-state single-channel measurements TRPM2 shows bursting behaviour when gated by either nucleotide. We compared mean open times and mean burst durations in the presence of ADPR or AMPCPR. These parameters were independent of the concentrations of the agonists, but both were significantly shorter in the presence of AMPCPR.Our results identify AMPCPR as a low-affinity partial agonist. The fact that channel closing rate is not slowed in the presence of a non-hydrolyzable ligand suggests either that the NUDT9-H domain has no ADPR hydrolase activity, or that the latter is not required for channel closure.

Digenic inheritance novel mutations in SCN5a and SNTA1 increase late INa contributing to LQT syndrome

SCN5A and SNTA1 are reported susceptible genes for long QT syndrome (LQTS). This study was designed to elucidate a plausible pathogenic arrhythmia mechanism for the combined novel mutations R800L-SCN5A and A261V-SNTA1 on cardiac sodium channels. A Caucasian family with syncope and marginally prolonged QT interval was screened for LQTS-susceptibility genes and found to harbor the R800L mutation in SCN5A and A261V mutation in SNTA1, and those with both mutations had the strongest clinical phenotype. The mutations were engineered into the most common splice variant of human SCN5A and SNTA1 cDNA, respectively, and sodium current (INa) was characterized in human embryonic kidney 293 cells cotransfected with neuronal nitric oxide synthase (nNOS) and the cardiac isoform of the plasma membrane Ca-ATPase (PMCA4b). Peak INa densities were unchanged for wild-type (WT) and for mutant channels containing R800L-SCN5A, A261V-SNTA1, or R800L-SCN5A plus A261V-SNTA1. However, late INa for either single mutant was moderately increased two- to threefold compared with WT. The combined mutations of R800L-SCN5A plus A261V-SNTA1 significantly enhanced the INa late/peak ratio by 5.6-fold compared with WT. The time constants of current decay of combined mutant channel were markedly increased. The gain-of-function effect could be blocked by the N(G)-monomethyl-l-arginine, a nNOS inhibitor. We conclude that novel mutations in SCN5A and SNTA1 jointly exert a nNOS-dependent gain-of-function on SCN5A channels, which may consequently prolong the action potential duration and lead to LQTS phenotype.

SYNERGISTIC EFFECT OF THE NOVEL MUTATIONS IN SCN5A AND SNTA1 ON LATE INA CONTRIBUTING TO LQT SYNDROME

ObjectivesSCN5A and SNTA1 are reported susceptible genes for long QT syndrome (LQTS). This study was designed to elucidate a plausible pathogenic arrhythmiamechanism for the combined novel mutations R800L-SCN5Aand A261V-SNTA1 on...

Protecting the Leads of a Powered Magnet That is Protected With Diodes and Resistors

MRI magnets and other magnets that have a low current and high self-inductance are passively quench-protected with a system that includes sub-divided coils with resistors and diodes that are in parallel with sections of the coils. The primary purpose of coil sub-division is to protect the coil from the high voltages that can occur during a quench. In the event of a lead failure (conventional or superconducting) between the coil and its power supply or its persistent switch, the total current in the coil flows through the diodes and resistors in parallel with the coil. When a lead fails, the current decay time constant for the coil current can be quite long. It is desirable that the coil quench in a time that is short compared to the coil current decay time constant. Experience shows that the heating from the resistors and diodes will eventually quench the magnet. This paper presents methods for shortening the time between a lead failure or a persistent switch failure and the eventual magnet quench.

Abstract 472: Calcium Current by Somatostatin Leads to Vasoconstriction in Rabbit Cerebral Artery

Somatostatin-containing neurons have a widespread distribution in the central nervous system. Moreover, the level of somatostatin in bloody cerebrospinal fluid and plasma is elevated patients with stroke. However, there is little evidence to support that somatostatin is a possible factor of vasopasm after stroke. This experiment was to undertaken to evaluate the effects of somatostatin on Ca 2+ currents using the whole-cell voltage-clamp techniques and on Ca 2+ transients using whole-cell fluorescence in cerebral arteries of the rabbit. During rectangular pulses, both peak and steady-state Ca 2+ currents were significantly increased by the application of somatostatin. Somatostatin had little effect on the steady-state activation kinetics, however, significant effect on the time constants for current decay. τ increased monotonically with voltage and was slightly slower in somatostatin-treated cells between 0 and +30 mV. The half maximal concentration of somatostatin was 8.5±1.3 pM in dose-response relation. Moreover, Ca 2+ transients by somatostatin were significantly increased in cells. From these results, the activation of Ca 2+ currents by somatostatin could be involved in pathogenesis of vasospasm after stroke.

The Two Different Effects of the Potential Neuroprotective Compound Minocycline on AMPA-Type Glutamate Receptors

Background: Minocycline has demonstrated neuroprotective effects in experimental neurodegenerative diseases. The aim of this study was to investigate if there is any direct interaction between minocycline and the AMPA-type receptor channels, and to elucidate the underlying molecular pharmacological mechanisms. Methods: The patch-clamp technique was used combined with an ultrafast solution exchange system to investigate the interaction of minocycline with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y). Results: Dose-dependent decreases in the relative peak current amplitude (rAmp) and the relative steady-state current (rC_des) were found in coapplication experiments with GluR2L504Y receptors, but not in preincubation experiments. Furthermore, coapplication of 1 or 3 mmol/l minocycline showed a decrease in the fast time constant of current decay, and reopening currents were observed. But in the test with GluR2flipGQ receptors, rAmp, relative area under the curve and rC_des increased with increasing concentrations of minocycline, and the steady-state time constant also increased when 3 µmol/l glutamate were used as agonist. Conclusion: Minocycline modulates AMPA-type receptor channels in a combination of a weaker open-channel block effect and a stronger potentiation effect, and the latter effect arises mainly from attenuating the extent of receptor desensitization.

Different effects of α-chloralose on spontaneous and evoked GABA release in rat hippocampal CA1 neurons

The effects of α-chloralose on presynaptic GABA A receptors were investigated with respect to spontaneous and evoked GABAergic transmission (sIPSCs and eIPSCs) in rat hippocampal CA1 pyramidal neurons. sIPSCs were recorded in mechanically dissociated CA1 neurons with intact GABAergic terminals, namely the “synaptic bouton preparation.” eIPSCs were elicited by focal electrical stimuli of a single GABAergic bouton on an isolated CA1 neuron using the whole-cell patch recording configurations under voltage-clamp condition. We found that α-chloralose potentiated the exogenous GABA-induced Cl − response in a concentration dependent manner, and the drug itself induced Cl − response at high concentrations (>100 μM). α-Chloralose at low concentrations (3–10 μM) increased sIPSC frequency without affecting the current amplitude and kinetics, but prolonged the slow current decay time constant ( τ s) at concentrations greater than 30 μM without changing either current amplitude or frequency. α-Chloralose at 10 μM enhanced amplitude of eIPSCs and decreased the failure rate (Rf), but at 30 μM decreased the amplitude and increased the Rf. Pretreatment with bumetanide, a blocker of NKCC-1, completely prevented the 30 μM α-chloralose-induced inhibition on eIPSC amplitude and Rf. These results suggest that α-chloralose activates GABA A receptors on GABAergic presynaptic nerve terminals and depolarizes the terminals, mediating presynaptic inhibition or autoregulation, in a concentration-dependent manner. In addition, α-chloralose at high concentrations activates not only extrasynaptic GABA A receptors on the postsynaptic soma membrane but also synaptic GABA A receptors resulting in prolongation of current decay phase. Thus α-chloralose induces complex and differential modulation of sIPSCs and eIPSCs in a concentration dependent manner.

Biophysical Properties of a Human Disease-Causing Mutation in Ca V1.3 L-Type Calcium Channels

Mice lacking functional Cav1.3 L-type Ca2+-channels show sinoatrial node dysfunction and are congenitally deaf. Here we investigated the functional consequences of a homozygote mutation (insertion of an amino acid residue in a pore-forming S6-helix) in the alpha1-subunit encoding the CACNA1D gene which causes bradycardia and deafness in humans.We expressed human wildtype (WT) and mutant channel complexes (MUT) in tsA-201 cells (with alpha2delta and beta3-subunits) and recorded ON-gating (Qon) and ionic Ca2+-currents (ICa) using the whole-cell patch-clamp technique. Full length WT and MUT channel alpha1 subunit proteins were expressed at equal levels in tsA-201 membranes. In contrast to WT, MUT channels did not conduct significant ICa, but gave clear rise to Qon. WT and MUT Qon exhibited a typical nonlinear voltage-dependence of activation. Under identical experimental conditions (block of ICa by replacing Ca2+ with Mg2+ and addition of La3+ and Cd2+ in the recording solution) the half maximal activation voltage (Vh) of MUT Qon was significantly shifted by 16.2±2.8 mV (n=6-8, p<0.0001) to more negative voltages compared to WT. Inward ICa of WT activated 11.5±2.9 mV more positive than WT Qon (n=7-8; p=0.0016). In addition, MUT Qon kinetics were significantly faster than for WT evident e.g. as shorter time constants for gating current decay over a large voltage range (−10 to +50 mV).The presence of charge movement in the absence of ionic currents implies that voltage-sensors in MUT channels move, but either fail to trigger pore opening or prevent conduction through opened channels. The mutation is not located within voltage-sensing S4-helices, but within a region of S6 predicted to interact with the voltage-sensor. Compromising this functional module may uncouple voltage-sensor function from pore opening and allow voltage-sensor movements to occur faster and at more negative voltages.

Temperature Dependence of Acetylcholine Receptor Channels Activated by Different Agonists

The temperature dependence of agonist binding and channel gating were measured for wild-type adult neuromuscular acetylcholine receptors activated by acetylcholine, carbamylcholine, or choline. With acetylcholine, temperature changed the gating rate constants (Q 10 ≈ 3.2) but had almost no effect on the equilibrium constant. The enthalpy change associated with gating was agonist-dependent, but for all three ligands it was approximately equal to the corresponding free-energy change. The equilibrium dissociation constant of the resting conformation (K d), the slope of the rate-equilibrium free-energy relationship (Φ), and the acetylcholine association and dissociation rate constants were approximately temperature-independent. In the mutant αG153S, the choline association and dissociation rate constants were temperature-dependent (Q 10 ≈ 7.4) but K d was not. By combining two independent mutations, we were able to compensate for the catalytic effect of temperature on the decay time constant of a synaptic current. At mouse body temperature, the channel-opening and -closing rate constants are ∼400 and 16 ms −1. We hypothesize that the agonist dependence of the gating enthalpy change is associated with differences in ligand binding, specifically to the open-channel conformation of the protein.

Population Models of Temporal Differentiation

Temporal derivatives are computed by a wide variety of neural circuits, but the problem of performing this computation accurately has received little theoretical study. Here we systematically compare the performance of diverse networks that calculate derivatives using cell-intrinsic adaptation and synaptic depression dynamics, feedforward network dynamics, and recurrent network dynamics. Examples of each type of network are compared by quantifying the errors they introduce into the calculation and their rejection of high-frequency input noise. This comparison is based on both analytical methods and numerical simulations with spiking leaky-integrate-and-fire (LIF) neurons. Both adapting and feedforward-network circuits provide good performance for signals with frequency bands that are well matched to the time constants of postsynaptic current decay and adaptation, respectively. The synaptic depression circuit performs similarly to the adaptation circuit, although strictly speaking, precisely linear differentiation based on synaptic depression is not possible, because depression scales synaptic weights multiplicatively. Feedback circuits introduce greater errors than functionally equivalent feedforward circuits, but they have the useful property that their dynamics are determined by feedback strength. For this reason, these circuits are better suited for calculating the derivatives of signals that evolve on timescales outside the range of membrane dynamics and, possibly, for providing the wide range of timescales needed for precise fractional-order differentiation.

The Interaction of the Neuroprotective Compounds Riluzole and Phenobarbital with AMPA-Type Glutamate Receptors: A Patch-Clamp Study

Background: Blockade of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors is a promising pharmacological strategy in the treatment of neurodegenerative diseases. The aim of the study is to elucidate if there are direct interactions of riluzole and phenobarbital with AMPA-type receptor channels and to determinethe molecular pharmacological mechanisms. Methods: The patch-clamp technique was used combining an ultrafast solution exchange system to investigate the interaction of riluzole and phenobarbital with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y). Results: A dose-dependent decrease in the relative peak current amplitude (rAmp) and the relative area-under-the-current curve (rAUC) were found after preincubation with 0.1 mmol/l or higher concentrations of riluzole. Furthermore, in coapplication experiments with GluR2L504Y, the application of 1 or 3 mmol/l riluzole showed a decrease in the current decay time constant, and a reopening current was observed at 3 mmol/l riluzole. Phenobarbital blocks AMPA receptor channels dose-dependently in the coapplication experiments, and reopening currents after removing glutamate and blocker were observed. A slight block effect after preincubation should indicate an additional competitive block effect. Conclusion: Riluzole and phenobarbital modulate AMPA-type receptor channels separately, which could be both characterized as a combination of open-channel block and competitive-block mechanism.