• Natural Product Sciences
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• 제19권4호
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• pp.290-296
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• 2013

In preliminary tests, we examined the effect of several fractions isolated from fermented pine needle extract on pacemaker potentials in cultured interstitial cells of Cajal (ICCs) from the mouse colon using a whole cell patch clamp technique. Among these fractions, Fraction 3 (F3) elicited the most powerful depolarization of membrane. Therefore, the aim of the present study was to investigate the effect of F3 obtained from fermented extract of Pinus densiflora needle on pacemaker potentials in ICCs and to establish its mechanism of action. Colonic ICCs generated spontaneous periodic pacemaker potentials in the current-clamp mode. F3 depolarized the membrane and decreased the frequency and amplitude of pacemaker potentials in a dose-dependent fashion. The F3-induced effects on pacemaker potentials were blocked by methoctramine, a muscarinic $M_2$ receptor antagonist, and by glycopyrrolate, a muscarinic $M_3$ receptor antagonist. The F3-induced effects on pacemaker potentials were blocked by external $Na^+$-free solution and by flufenamic acid, a non-selective cation channel blocker, as well as by the removal of external $Ca^{2+}$ and in the presence of thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum. Taken together, these results suggest that F3 of pine needle extract modulates the pacemaker activity of colonic ICCs by the activation of non-selective cation channels via muscarinic $M_2$ and $M_3$ receptors. And external $Ca^{2+}$ influx and intracellular $Ca^{2+}$ release are involved in F3 actions on ICCs.

• 대한한의학방제학회지
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• 제28권1호
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• pp.71-80
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• 2020

Obejectives : The purpose of this study was to investigate the effects of Yijin-tang on pacemaker potentials of small intestinal interstitial Cells of Cajal (ICC). Methods : To dissociate the ICC, we used enzymatic digestions from the small intestine in mice. The electrophysiological whole-cell patch-clamp configuration was used to record pacemaker potentials in the cultured ICC and the in vivo effects of Yijin-tang on GI motility were investigated by calculating percent intestinal transit rates (ITR). Results : 1. The ICC generated pacemaker potentials in the murine small intestine. Yijin-tang produced membrane depolarization with concentration-dependent manners in the current clamp mode. 2. Pretreatment with a Ca²⁺ free solution and thapsigargin, a Ca²⁺-ATPase inhibitor in the endoplasmic reticulum, stopped the pacemaker potentials. In the case of Ca²⁺-free solutions and thapsigargin, Yijin-tang did not induce membrane potential depolarizations. 3. U73122, a phospholipase C (PLC) inhibitors, blocked the Yijin-tang-induced membrane potential depolarizations. However, U73343, an inactive PLC inhibitors, did not block. 4. In the presence of protein kinase C (PKC) inhibitors, staurosporine or Rottlerin, Yijin-tang depolarized the pacemaker potentials. However, in the presence of Go6976, Yijin-tang did not depolarize the pacemaker potentials. 5. In mice, intestinal transit rate (ITR) values were significantly and dose-dependently increased by the intragastric administration of Yijin-tang. Conclusions : These results suggest that Yijin-tang can modulate the pacemaker activity of ICC through an internal/external Ca²⁺ and PLC/PKC-dependent pathway in ICC. In addition, Yijin-tang is a good candidate for the development of a prokinetic agent.

• The Korean Journal of Physiology and Pharmacology
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• 제4권2호
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• pp.81-90
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• 2000

The types of $K^+$ channel which determine the pattern of spontaneous action potential (SAP) were investigated using whole-cell variation of patch clamp techniques under current- and voltage-clamp recording conditions in rat clonal pituitary $GH_3$ cells. Heterogeneous pattern of SAP activities was changed into more regular mode with elongation of activity duration and afterhyperpolarization by treatment of TEA (10 mM). Under this condition, exposure of the class III antiarrhythmic agent E-4031 $(5\;{\mu}M)$ to $GH_3$ cells hardly affected SAP activities. On the other hand, the main $GH_3$ stimulator thyrotropin-releasing hormone (TRH) still produced its dual effects (transient hyperpolarization and later increase in SAP frequency) in the presence of TEA. However, addition of $BaCl_2$ (2 mM) in the presence of TEA completely blocked SAP repolarization process and produced membrane depolarization in all tested cells. This effect was observed even in TEA-untreated cells and was not mimicked by higher concentration of TEA (30 mM). Also this barium-induced membrane depolarization effect was still observed after L-type $Ca^{2+}$ channel was blocked by nicardipine $(10\;{\mu}M).$ These results suggest that barium-sensitive current is important in SAP repolarization process and barium itself may have some depolarizing effect in $GH_3$ cells.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.585-595
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• 2018

Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 ($5-HT_3$) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with $5-HT_3$ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the $5-HT_3$ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. To elucidate the mechanism of amitriptyline, we simulated the $5-HT_3$ receptor currents using Berkeley $Madonna^{(R)}$ software and calculated the rate constants of the agonist binding and receptor transition steps. The $5-HT_3$ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the $5-HT_3$ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the $5-HT_3$ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a $5-HT_3$ receptor, a potential target of neurologic and psychiatric diseases through this study.

• Molecules and Cells
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• 제27권3호
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• pp.307-312
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• 2009

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by $GDP-{\beta}-S$, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external $Ca^{2+}$ influx, phospholipase C activation, and $Ca^{2+}$ release from internal storage in a G protein-independent and protein kinase C-independent manner.

• The Korean Journal of Physiology and Pharmacology
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• 제7권1호
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• pp.25-28
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• 2003

Ion channel inhibitors are widely used for pharmacological discrimination between the different channel types as well as for determination of their functional role. In the present study, we tested the hypothesis that 4-aminopyridine (4-AP) could affect the large conductance $Ca^{2+}$-activated $K^+$ channel ($BK_{Ca}$) currents using perforated-patch or cell-attached configuration of patch-clamp technique in the rabbit pulmonary arterial smooth muscle. Application of 4-AP reversibly inhibited the spontaneous transient outward currents (STOCs). The reversal potential and the sensitivity to charybdotoxin indicated that the STOCs were due to the activation of $BK_{Ca}$. The $BK_{Ca}$ currents were recorded in single channel resolution under the cell-attached mode of patch-clamp technique for minimal perturbation of intracellular environment. Application of 4-AP also inhibited the single $BK_{Ca}$ currents reversibly and dose-dependently. The membrane potential of rabbit pulmonary arterial smooth muscle cells showed spontaneous transient hyperpolarizations (STHPs), presumably due to the STOC activities, which was also inhibited by 4-AP. These results suggest that 4-AP can inhibit $BK_{Ca}$ currentsin the intact rabbit vascular smooth muscle. The use of 4-AP as a selective voltage-dependent $K^+$ (KV) channel blocker in vascular smooth muscle, therefore, must be reevaluated.

• 전력전자학회논문지
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• 제4권6호
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• pp.539-546
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• 1999

본 논문에서는 역률개선용 단일 수위치 부수투 플라이백 결합형 ZCS 준공진 컨버터(quasi-resonant converter(QRC))를 제안한다. 제안된 컨버터는 입력전류를 불연속 모드로 동작과 zero-crossing-point에서의 왜곡을 개선함으로써 고조파를 감소시켜 역률을 향상시켰으며 좋은 출력전압의 레귤레이션 성능을 가지고 있다. 또한 능동 클램프회로를 제안된 회로의 동작특성에 맞게 스위칭 시간을 조절해 줌으로써 ZCS-QR의 일잔적인 특성인 스위치 차단시의 스위치 양단전압의 공진현상을 제거하여 스위치의 전압스트레스를 줄였다. 체계적인 설계를 위하여 설계식을 제안하였으며 제안된 설계식을 통하여 프로토타입 컨버터를 설계하였다. 실험결과 효율은 약 87%, 역률은 약0.985이상을 얻었다. 따라서 본 컨버터는 스위칭 주파수가 수백kHz이상이고 높은 레귤레이션 성능을 요구하는 낮은 전압의 소용량 컨버터에 적합하다.

• 전기학회논문지
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• 제67권2호
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• pp.233-238
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• 2018

This paper proposes a seamless MPPT operation mode transfer method of photovoltaic system. The photovoltaic system consists of a DC-DC boost converter, a DC-Link, and a 3-level neutral point clamp (NPC) type inverter. The PV voltage fluctuates due to the output characteristics of the solar pane1 depending on the irradiation amount and the temperature. The photovoltaic system requires seamless MPPT mode transfer method that the discontinuity does not occur in order to supply the stable power to system without affecting the fluctuation of the PV voltage. MPPT operation is divided into two modes by the voltage reference. Under the condition that the PV voltage is below 650V, the DC-DC boost converter performs MPPT through duty control based on perturb & observe (P&O) method, and the inverter conducts DC-link voltage and grid current controls in synchronous reference frame. On the other hand, when the PV voltage exceeds above 650V, inverter performs MPPT in accordance with the variation of DC-link voltage control while the converter stops operating. Two MPPT operation modes is smoothly transferred through the proposed method that DC-link voltage or grid current commands are appropriately adjusted from the certain criteria. The feasibility of the MPPT operation mode transfer method is verified using a 10kW solar photovoltaic system, experimental results have good performances that the fluctuation of PV current is reduced to 100%.

• 전력전자학회논문지
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• 제11권3호
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• pp.258-265
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• 2006

풍력, 태양광, 연료전지와 같은 신 재생 에너지에 관한 연구가 활발해 지면서 컨버터, 인버터와 같은 PCS (Power Conditioning System)의 연구가 활발히 진행되고 있다. 그러나, 부하에 따라 가변되는 저전압, 대전류, 출력특성을 갖는 연료전지 발전 시스템에서는 PCS의 연구 및 개발이 어려운 실정이다. 본 논문에서는 연료전지를 이용한 발전시스템에 알맞은 능동 클램프 sepic-flyback 컨버터를 제안한다. 제안된 컨버터는 중간 탭 변압기를 이용하여 sepic, flyback 컨버터를 결합한 구조를 가진다. 변압기를 이용하는 종래의 토폴로지에 비해 변압기 이용률을 높일 수 있고, 변압기의 변환 비 및 파워 스위치 소자의 수를 줄일 수 있으며, 고효율 운전특성을 갖는다. 본 논문에서는 시뮬레이션과 실험을 통하여 컨버터의 동작특성을 비교 분석하였으며, PEMFC (Proton Exchange Membrane Fuel Cell)을 이용하여 제안된 컨버터의 타당성을 검증하였다.

• Steel and Composite Structures
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• 제31권3호
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• pp.261-276
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• 2019

The study investigates the free vibration of a nano-scale sandwich beam by an extended high order approach, which has not been reported in the existing literature. First-order shear deformation theory for steel skins and so-called high-order sandwich panel theory for the core are applied. Next, the modified couple stress theory is used for both skins and cores. The Hamilton principle is utilized for deriving equations and corresponding boundary conditions. First, in the study the three-mode shapes natural frequencies for various material parameters are investigated. Also, obtained results are evaluated for two types of stiff and soft cores and isotropic, homogenous steel skins. In the research since the governing equations and also the boundary conditions are nonhomogeneous, therefore some closed-form solutions are not applicable. So, to obtain natural frequencies, the boundary conditions are converted to initial conditions called the shooting method as the numerical one. This method is one of the most robust approaches to solve complex equations and boundary conditions. Moreover, three types of simply supported on both sides of the beam (S-S), simply on one side and clamp supported on the other one (S-C) and clamped supported on both sides (C-C) are scrutinized. The parametric study is followed to evaluate the effect of nano-size scale, geometrical configurations for skins, core and material property change for cores as well. Results show that natural frequencies increase by an increase in skins thickness and core Young modulus and a decrease in beam length, core thickness as well. Furthermore, differences between obtained frequencies for soft and stiff cores increase in higher mode shapes; while, the more differences are evaluated for the stiff one.