• Journal of Ginseng Research
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• v.39 no.4
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• pp.314-321
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• 2015

Background: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on GI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. Methods: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. Results: Ginsenoside Re ($20-40{\mu}M$) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 50-[${\beta}-thio$]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive $K^{+}$ channel blocker]. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester ($100{\mu}M$), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. Conclusion: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium ($K^{+}$) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction.

• Journal of Life Science
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• v.29 no.9
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• pp.1010-1015
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• 2019

The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of olanzapine, an atypical antipsychotic agent, on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole-cell patch-clamp configuration was used to record pacemaker potentials from cultured ICCs. Olanzapine produced pacemaker depolarizations in a concentration-dependent manner in current clamp mode. Methoctramine, a muscarinic $M_2$ receptor antagonist, did not inhibit olanzapine-induced pacemaker depolarizations, whereas 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) muscarinic $M_3$ receptor antagonist did inhibit it. When guanosine 5'-[${\beta}$-thio] diphosphate (GDP-${\beta}$-S; 1 mM) was in the pipette solution, olanzapine-induced pacemaker depolarization was blocked. Also, low $Na^+$ solution externally eliminated the generation of pacemaker potentials and inhibited the olanzapine-induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the olanzapine-induced pacemaker depolarizations. Pretreatment with U-73122, an active phospholipase C (PLC) inhibitor, also eliminated the generation of pacemaker potentials and suppressed the olanzapine-induced pacemaker depolarizations. These results suggested that olanzapine modulates the pacemaker potentials through muscarinic $M_3$ receptor activation by G protein-dependent external $Na^+$ and PLC pathway in the ICCs. Therefore, olanzapine could affect intestinal motility through ICCs.

• The Transactions of the Korean Institute of Electrical Engineers P
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• v.66 no.4
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• pp.188-193
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• 2017

In this paper, a ZVS-PWM high-frequency inverter with a PWM control function is applied to commercial system 220[Vrms], and a resonator type ZVS-PWM high-frequency inverter circuit with a fixed-two methods were proposed. The parameters of the transformer model equivalent circuit of a copier fixing device, which is an essential element in the parameter optimization of the proposed circuit, are obtained by using a high-frequency amplifier and its frequency characteristics are described. The proposed method compared to the existing single-ended ZVS-PFM high frequency inverter can suppress the voltage and current peak value of the power semiconductor switching device and reduce the switching loss. The efficiency of the proposed method itself is 98[%] at rated power output. Also, the efficiency of 96[%] can be obtained even at low output, so that the proposed high frequency inverter is very efficient inverter. The total efficiency from the commercial AC input to the inverter output is 93[%] at rated, which is considered efficient for use in copying machines. In addition, the diode bridge loss accounts for the largest portion of the overall system efficiency distribution. On the other hand, the nonparallel filter has a very low loss.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.28-33
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant $GABA_A$ receptor (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, $Rb_1$, $Rb_2$, Rc, Rd, Re, Rf, $Rg_1$ and $Rg_2$, we found that Rc most potently enhanced the GABA-induced inward peak current ($I_{GABA}$). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the $GABA_A$ receptor. The effect of ginsenoside Rc on $I_{GABA}$ was both dose-dependent and reversible. The half-stimulatory concentration ($EC_{50}$) of ginsenoside Rc was 53.2$\pm$12.3 $\mu$M. Both bicuculline, a $GABA_A$ receptor antagonist, and picrotoxin, a $GABA_A$ channel blocker, blocked the stimulatory effect of ginsenoside Rc on $I_{GABA}$. Niflumic acid (NFA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), both $CI^{-1}$ channel blockers, attenuated the effect of ginsenoside Rc on I$I_{GABA}$. This study suggests that ginsenosides regulated $GABA_A$ receptor expressed in Xenopus oocytes and implies that this regulation might be one of the pharmacological actions of Panax ginseng.

• Journal of Power Electronics
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• v.5 no.3
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• pp.233-239
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• 2005

In this paper, a new conceptual circuit configuration of a 3-phase voltage source, soft switching AC-DC-AC converter using an IGBT module, which has one ARCPL circuit and one ARDCL circuit, is presented. In actuality, the ARCPL circuit is applied in the 3-phase voltage source rectifier side, and the ARDCL circuit is in the inverter side. And more, each power semiconductor device has a novel clamp snubber circuit, which can save the power semiconductor device from voltage and current across each power device. The proposed soft switching circuits have only two active power semiconductor devices. These ARCPL and ARDCL circuits consist of fewer parts than the conventional soft switching circuit. Furthermore, the proposed 3-phase voltage source soft switching AC-DC-AC power conversion system needs no additional sensor for complete soft switching as compared with the conventional 3-phase voltage source AC-DC-AC power conversion system. In addition to this, these soft switching circuits operate only once in one sampling term. Therefore, the power conversion efficiency of the proposed AC-DC-AC converter system will get higher than a conventional soft switching converter system because of the reduced ARCPL and ARDCL circuit losses. The operation timing and terms for ARDCL and ARCPL circuits are calculated and controlled by the smoothing DC capacitor voltage and the output AC current. Using this control, the loss of the soft switching circuits are reduced owing to reduced resonant inductor current in ARCPL and ARDCL circuits as compared with the conventional controlled soft switching power conversion system. The operating performances of proposed soft switching AC-DC-AC converter treated here are evaluated on the basis of experimental results in a 50kVA setup in this paper. As a result of experiment on the 50kVA system, it was confirmed that the proposed circuit could reduce conduction noise below 10 MHz and improve the conversion efficiency from 88. 5% to 90.5%, when compared with the hard switching circuit.

• The Transactions of the Korean Institute of Power Electronics
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• v.10 no.4
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• pp.380-387
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• 2005

We report the performance of an open-frame type low-voltage high-current DC-DC converter module developed using an active clamp forward converter circuit and single ended rectifier. The converter module is designed with the specifications of an 3.3V output voltage, 30A output current, 100W output power and 36-75V input voltage. The synchronous rectifier is used to reduce the conduction loss at high current level and constant current control using precision PCB resistance is adapted to enhance the over current protection function in the system configuration. A prototype converter module is successfully implemented within 8mm height and quarter brick size (58x37mm) and recorded an $95W/in^3$ power density, 90.6$\%$ efficiency and 0.07$\%$ voltage regulation for the entire Input voltage range, thereby demonstrating its application potentials to future telecommunication electronics.

• The Transactions of the Korean Institute of Power Electronics
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• v.16 no.3
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• pp.242-249
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• 2011

The proposed converter has easy device selection for high step-up and high power applications since boost half bridge and voltage doubler cells are connected, respectively, in parallel and series in order to increase output power and voltage. Especially, optimized design of high frequency transformers is possible owing to reduced turn ratio and eliminated dc offset, and distributed power through three cores is beneficial to low profile and thermal distribution. The proposed converter does not necessitate start-up circuit and additional clamp circuit due to the use of whole duty range between 0 and 1 and is suitable for applications with wide input voltage range. Also, high efficiency can be achieved since ZVS turn on of switches are achieved in wide duty cycle range and ZCS turn on and off of diodes are achieved. The proposed converter was validated through 5 kW prototype.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.545-553
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• 2020

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K⁺ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC₅₀ value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC₅₀ value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC₅₀ value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.381-392
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• 2019

Sperm function and male fertility are closely related to pH dependent $K^+$ current (KSper) in human sperm, which is most likely composed of Slo3 and its auxiliary subunit leucine-rich repeat-containing protein 52 (LRRC52). Onion peel extract (OPE) and its major active ingredient quercetin are widely used as fertility enhancers; however, the effect of OPE and quercetin on Slo3 has not been elucidated. The purpose of this study is to investigate the effect of quercetin on human Slo3 channels. Human Slo3 and LRRC52 were co-transfected into HEK293 cells and pharmacological properties were studied with the whole cell patch clamp technique. We successfully expressed and measured pH sensitive and calcium insensitive Slo3 currents in HEK293 cells. We found that OPE and its key ingredient quercetin inhibit Slo3 currents. Inhibition by quercetin is dose dependent and this degree of inhibition decreases with elevating internal alkalization and internal free calcium concentrations. Functional moieties in the quercetin polyphenolic ring govern the degree of inhibition of Slo3 by quercetin, and the composition of such functional moieties are sensitive to the pH of the medium. These results suggest that quercetin inhibits Slo3 in a pH and calcium dependent manner. Therefore, we surmise that quercetin induced depolarization in spermatozoa may enhance the voltage gated proton channel (Hv1), and activate non-selective cation channels of sperm (CatSper) dependent calcium influx to trigger sperm capacitation and acrosome reaction.