Effective Activation of BKCa Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4H)-one), Known to Be an Opener of KCNQ2/Q3 Channels

QO-40 (5-(chloromethyl)-3-(naphthalene-1-yl)-2-(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-7(4H)-one) is a novel and selective activator of KCNQ2/KCNQ3 K+ channels. However, it remains largely unknown whether this compound can modify any other type of plasmalemmal ionic channel. The effects of QO-40 on ion channels in pituitary GH3 lactotrophs were investigated in this study. QO-40 stimulated Ca2+-activated K+ current (IK(Ca)) with an EC50 value of 2.3 μM in these cells. QO-40-stimulated IK(Ca) was attenuated by the further addition of GAL-021 or paxilline but not by linopirdine or TRAM-34. In inside-out mode, this compound added to the intracellular leaflet of the detached patches stimulated large-conductance Ca2+-activated K+ (BKCa) channels with no change in single-channel conductance; however, there was a decrease in the slow component of the mean closed time of BKCa channels. The KD value required for the QO-40-mediated decrease in the slow component at the mean closure time was 1.96 μM. This compound shifted the steady-state activation curve of BKCa channels to a less positive voltage and decreased the gating charge of the channel. The application of QO-40 also increased the hysteretic strength of BKCa channels elicited by a long-lasting isosceles-triangular ramp voltage. In HEK293T cells expressing α-hSlo, QO-40 stimulated BKCa channel activity. Overall, these findings demonstrate that QO-40 can interact directly with the BKCa channel to increase the amplitude of IK(Ca) in GH3 cells.

High Capability of Pentagalloylglucose (PGG) in Inhibiting Multiple Types of Membrane Ionic Currents

Pentagalloyglucose (PGG, penta-O-galloyl-β-d-glucose; 1,2,3,4,6-pentagalloyl glucose), a pentagallic acid ester of glucose, is recognized to possess anti-bacterial, anti-oxidative and anti-neoplastic activities. However, to what extent PGG or other polyphenolic compounds can perturb the magnitude and/or gating of different types of plasmalemmal ionic currents remains largely uncertain. In pituitary tumor (GH3) cells, we found out that PGG was effective at suppressing the density of delayed-rectifier K+ current (IK(DR)) concentration-dependently. The addition of PGG could suppress the density of proton-activated Cl− current (IPAC) observed in GH3 cells. The IC50 value required for the inhibitory action of PGG on IK(DR) or IPAC observed in GH3 cells was estimated to be 3.6 or 12.2 μM, respectively, while PGG (10 μM) mildly inhibited the density of the erg-mediated K+ current or voltage-gated Na+ current. The presence of neither chlorotoxin, hesperetin, kaempferol, morin nor iberiotoxin had any effects on IPAC density, whereas hydroxychloroquine or 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5yl)oxy] butanoic acid suppressed current density effectively. The application of PGG also led to a decrease in the area of voltage-dependent hysteresis of IPAC elicited by long-lasting isosceles-triangular ramp voltage command, suggesting that hysteretic strength was lessened in its presence. In human cardiac myocytes, the exposure to PGG also resulted in a reduction of ramp-induced IK(DR) density. Taken literally, PGG-perturbed adjustment of ionic currents could be direct and appears to be independent of its anti-oxidative property.

Inhibitory Effectiveness of Gomisin A, a Dibenzocyclooctadiene Lignan Isolated from Schizandra chinensis, on the Amplitude and Gating of Voltage-Gated Na+ Current

Gomisin A (Gom A), a lignan isolated from Schisandra chinensis, has been reported produce numerous biological activities. However, its action on the ionic mechanisms remains largely unanswered. The present experiments were undertaken to investigate the possible perturbations of Gom A or other related compounds on different types of membrane ionic currents in electrically excitable cells (i.e., pituitary GH3 and pancreatic INS-1 cells). The exposure to Gom A led to the differential inhibition of peak and end-pulse components of voltage-gated Na+ current (INa) in GH3 cells with effective IC50 of 6.2 and 0.73 μM, respectively. The steady-state inactivation curve of INa in the presence of Gom A was shifted towards a more hyperpolarized potential. However, neither changes in the overall current-voltage relationship nor those for the gating charge of the current were demonstrated. The application of neither morin (10 μM) nor hesperidin (10 μM) perturbed the strength of INa, while sesamine could suppress it. However, in the continued presence of Gom A, the addition of sesamine failed to suppress INa further. Gom A also effectively suppressed the strength of persistent INa activated by long ramp voltage command, and further application of tefluthrin effectively attenuated Gom A-mediated inhibition of the current. The presence of Gom A mildly inhibited erg-mediated K+ current, while a lack of change in the amplitude of hyperpolarization-activated cation current was observed in its presence. Under cell-attached current recordings, the exposure to Gom A resulted in the decreased firing of spontaneous action currents with a minimal change in AC amplitude. In pancreatic INS-1 cells, the presence of Gom A was also noticed to inhibit peak and end-pulse components of INa differentially with the IC50 of 5.9 and 0.84 μM, respectively. Taken together, the emerging results presented herein provide the evidence that Gom A can differentially inhibit peak and sustained INa in endocrine cells (e.g., GH3 and INS-1 cells).

Diamond-like carbon as gate dielectric for metal–insulator–semiconductor applications

Diamond-like carbon (DLC) has been studied as a dielectric material for future metal–insulator–semiconductor (MIS) technology. In this paper, ultrathin DLC films were deposited on silicon substrates by using the dc magnetron sputtering technique at various deposition voltages. The current–voltage characteristics indicated that the leakage currents of the MIS devices decreased with an increase in deposition voltages, and that a low leakage current ([Formula: see text] A/cm2) was achieved at −2 V bias voltage. The deposition voltage effects on the structures of films were investigated through Raman spectroscopy, which indicated that the sp3 bonding fraction decreased with an increase in the deposition voltage. The ramp-voltage breakdown test revealed high effective breakdown electric field ([Formula: see text]85 MV/cm) for the MIS device with the DLC film deposited at 1100-V deposition. Stress-induced leakage current measurement indicated that the DLC film exhibited excellent reliability.

Study of the optimizing karyotype by applying AC voltage

Background: The main problem in the conventional karyotype slide is twisted and folded chromosomes that make it challenging to analyze the karyotype slide. Most of the time karyotype sorting software mistake chromosome with each order. In this study, the alternating current (AC) voltage conducted in order to drag the chromosome on karyotype slides. This method can facilitate the analysis of chromosomes structure by researchers, and karyotype sorting software can perform better and show a more accurate result. Methods: In this study, the AC ramp voltage has been applied to drag the chromosome on karyotype slides. AC voltage interacts with chromosomes in the slide so the force of electric charge can untwist and unfold chromosomes partially. Results: Karyotype chromosomes that were under AC voltage showed somewhat lined, and arranged chromosomes compare to conventional karyotype chromosomes. Conclusions: This method makes the study of the chromosomes structure very easy and more reliable. Hopefully, with the design and development of custom signal generators, the results of the study will be better and more accurate.

Study of the optimizing karyotype by applying AC voltage

Background: The main problem in the conventional karyotype slide is twisted and folded chromosomes that make it challenging to analyze the karyotype slide. Most of the time karyotype sorting software mistake chromosome with each order. In this study, the alternating current (AC) voltage conducted in order to drag the chromosome on karyotype slides. This method can facilitate the analysis of chromosomes structure by researchers, and karyotype sorting software can perform better and show a more accurate result. Methods: In this study, the AC ramp voltage has been applied to drag the chromosome on karyotype slides. AC voltage interacts with chromosomes in the slide so the force of electric charge can untwist and unfold chromosomes partially. Results: Karyotype chromosomes that were under AC voltage showed somewhat lined, and arranged chromosomes compare to conventional karyotype chromosomes. Conclusions: This method makes the study of the chromosomes structure very easy and more reliable. Hopefully, with the design and development of custom signal generators, the results of the study will be better and more accurate.

A Proposed Resistance-to-Time Converter with Switching Impulse Calibrators for Application in Resistive Bridge Sensors

This paper presents a simple resistance-to-time converter. It consists of two voltage comparators, a ramp voltage generator, two logic gates and impulse voltage calibrators. A square-wave generator circuit is suggested in this paper. The design is simple and independent of the OPAMP offset issues. The resulting square-wave is rectified to get its DC equivalent and to a triangular output; the two outputs are applied to a comparator for generating a digital output with a duty cycle proportional to a change in resistance upon which is dependent the DC.

Comparative Assessment on Linearity Test based V2π and Vπ/2 Voltage Variations of Closed Loop IFOG

Interferometric Fiber Optic Gyroscope (IFOG) has to operate in closed loop condition to achieve inertial grade performance. The closed loop system is mainly depends upon the amplitude of the ramp signal (V2π of IOC) and bias (square wave) signal frequency (f_bias). The digital phase ramp function is given as feedback to the optical system and makes gyro to null condition. The peak-to-peak amplitude (Vπ/2) of biasing signal is one-fourth of the ramp amplitude (V2π). If there are any variations in the amplitude of the ramp and biasing signals, then it introduces variations in the gyro performance. In this paper, a comparative discussion made in the gyro parameters for three cases: (i) V2π (vary) & Vπ/2 (constant), (ii) Vπ/2 (vary) & V2π (constant) and (iii) both V2π and Vπ/2 are varying simultaneously. The effects on gyroscope are described with the derived values in terms of linearity. From the experimental results, it was observed that the gyro output is very sensitive with respect to V2π variations and obtained the percentage error of 10% in gyro output, but very less effect due to Vπ/2 variations. So, the proper resetting of ramp voltage (V2π) is required to avoid nonlinearities and instabilities in gyro output.