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Carbon monoxide activates large-conductance calcium-activated potassium channels of human cardiac fibroblasts through various mechanisms

  • Bae, Hyemi;Kim, Taeho;Lim, Inja
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.3
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    • pp.227-237
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    • 2021
  • Carbon monoxide (CO) is a cardioprotectant and potential cardiovascular therapeutic agent. Human cardiac fibroblasts (HCFs) are important determinants of myocardial structure and function. Large-conductance Ca2+-activated K+ (BK) channel is a potential therapeutic target for cardiovascular disease. We investigated whether CO modulates BK channels and the signaling pathways in HCFs using whole-cell mode patch-clamp recordings. CO-releasing molecules (CORMs; CORM-2 and CORM-3) significantly increased the amplitudes of BK currents (IBK). The CO-induced stimulating effects on IBK were blocked by pre-treatment with specific nitric oxide synthase (NOS) blockers (L-NG-monomethyl arginine citrate and L-NG-nitroarginine methyl ester). 8-bromo-cyclic GMP increased IBK. KT5823 (inhibits PKG) or ODQ (inhibits soluble guanylate cyclase) blocked the CO-stimulating effect on IBK. Moreover, 8-bromo-cyclic AMP also increased IBK, and pre-treatment with KT5720 (inhibits PKA) or SQ22536 (inhibits adenylate cyclase) blocked the CO effect. Pre-treatment with N-ethylmaleimide (a thiol-alkylating reagent) also blocked the CO effect on IBK, and DL-dithiothreitol (a reducing agent) reversed the CO effect. These data suggest that CO activates IBK through NO via the NOS and through the PKG, PKA, and S-nitrosylation pathways.

A Study on the Operating-Mode Characteristics of Two-Module Thyristor Controlled Series Compensator (Two-Module TCSC의 운전모드 특성 연구)

  • Jeong, Gyo-Beom
    • The Transactions of the Korean Institute of Electrical Engineers A
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    • v.48 no.11
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    • pp.1410-1416
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    • 1999
  • This paper aims at investigating the operating-mode characteristics of two-module Thyristor Controlled Series Compensator (TCSC) as an equivalent of the multi-module TCSC in a simple three-phase power transmission system. The load flow program is developed to analyze the steady-state characteristics of two-module TCSC system and to find the thyristor firing angles for the required real power flow. The stability calculation program is developed with Poincare mapping theory. Simulation studies of the TCSC power transmission system using EMTP are performed to evaluate the transient characteristics of two-module TCSC as a real power flow controller and to rpove the results of the load flow calculation and the stability analysis. In the process of the study, the operating-mode characteristics of two-module TCSC are evaluated and compared to those of single-module TCSC.

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Characterization of Chemical Sludge inside Pipes Using Torsional Guided Waves

  • Park, Kyung-Jo
    • Journal of Power System Engineering
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    • v.18 no.3
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    • pp.29-35
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    • 2014
  • A new method is presented that uses guided wave techniques for sludge and blockage detection in long-range pipelines. Existing techniques have the limitations that the sludge position needs to be known a priori and the area to be inspected needs to be accessible. A novel guided wave technique has been developed that allow the sludge or blockages to be detected remotely without the need to access the specific location where the pipe is blocked, nor to open the pipe. The technique measures the reflection of guided waves by sludge that can be used to accurately locate the blocked region. The effectiveness of the proposed technique is demonstrated and confirmed by experimental measurements.

Liquid Crystal Display Mode with a Single Polarizer based on Switchable Microlens Arrays

  • Kim, Young-Wook;Gwag, Jin-Seog;Lee, Se-Hyun;Jeong, Ji-Won;Kim, Jae-Hoon;Yu, Change-Jae
    • 한국정보디스플레이학회:학술대회논문집
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    • 2009.10a
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    • pp.620-622
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    • 2009
  • We demonstrated a liquid crystal display (LCD) mode with a single polarizer based on the array of a switchable microlens consisting of a circular stop mask and its complementary open mask. The focused beam passed through the open mask and thus the bright state was obtained, while the defocused beam was blocked by the stop mask and the complementary open mask. It is expected that our single-polarizer LCD mode is applicable to low cost displays.

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Carbon monoxide activation of delayed rectifier potassium currents of human cardiac fibroblasts through diverse pathways

  • Bae, Hyemi;Kim, Taeho;Lim, Inja
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.1
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    • pp.25-36
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    • 2022
  • To identify the effect and mechanism of carbon monoxide (CO) on delayed rectifier K+ currents (IK) of human cardiac fibroblasts (HCFs), we used the wholecell mode patch-clamp technique. Application of CO delivered by carbon monoxidereleasing molecule-3 (CORM3) increased the amplitude of outward K+ currents, and diphenyl phosphine oxide-1 (a specific IK blocker) inhibited the currents. CORM3-induced augmentation was blocked by pretreatment with nitric oxide synthase blockers (L-NG-monomethyl arginine citrate and L-NG-nitro arginine methyl ester). Pretreatment with KT5823 (a protein kinas G blocker), 1H-[1,-2,-4] oxadiazolo-[4,-3-a] quinoxalin-1-on (ODQ, a soluble guanylate cyclase blocker), KT5720 (a protein kinase A blocker), and SQ22536 (an adenylate cyclase blocker) blocked the CORM3 stimulating effect on IK. In addition, pretreatment with SB239063 (a p38 mitogen-activated protein kinase [MAPK] blocker) and PD98059 (a p44/42 MAPK blocker) also blocked the CORM3's effect on the currents. When testing the involvement of S-nitrosylation, pretreatment of N-ethylmaleimide (a thiol-alkylating reagent) blocked CO-induced IK activation and DL-dithiothreitol (a reducing agent) reversed this effect. Pretreatment with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)-21H,23H porphyrin manganese (III) pentachloride and manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (superoxide dismutase mimetics), diphenyleneiodonium chloride (an NADPH oxidase blocker), or allopurinol (a xanthine oxidase blocker) also inhibited CO-induced IK activation. These results suggest that CO enhances IK in HCFs through the nitric oxide, phosphorylation by protein kinase G, protein kinase A, and MAPK, S-nitrosylation and reduction/oxidation (redox) signaling pathways.

Deep Learning Machine Vision System with High Object Recognition Rate using Multiple-Exposure Image Sensing Method

  • Park, Min-Jun;Kim, Hyeon-June
    • Journal of Sensor Science and Technology
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    • v.30 no.2
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    • pp.76-81
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    • 2021
  • In this study, we propose a machine vision system with a high object recognition rate. By utilizing a multiple-exposure image sensing technique, the proposed deep learning-based machine vision system can cover a wide light intensity range without further learning processes on the various light intensity range. If the proposed machine vision system fails to recognize object features, the system operates in a multiple-exposure sensing mode and detects the target object that is blocked in the near dark or bright region. Furthermore, short- and long-exposure images from the multiple-exposure sensing mode are synthesized to obtain accurate object feature information. That results in the generation of a wide dynamic range of image information. Even with the object recognition resources for the deep learning process with a light intensity range of only 23 dB, the prototype machine vision system with the multiple-exposure imaging method demonstrated an object recognition performance with a light intensity range of up to 96 dB.

Heterogeneity of the SR-dependent Inward $Na^+-Ca^{2+}$ Exchange Current in the Heavily $Ca^{2+}-buffered$ Rat Ventricular Myocytes

  • Yoon, Kyung-Bong;Ahn, Sung-Wan;Ko, Chang-Mann
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.2
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    • pp.101-110
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    • 2004
  • Voltage-sensitive release mechanism was pharmacologically dissected from the $Ca^{2+}-induced\;Ca^{2+}\;release$ in the SR $Ca^{2+}$ release in the rat ventricular myocytes patch-clamped in a whole-cell mode. SR $Ca^{2+}$ release process was monitored by using forward-mode $Na^+-Ca^{2+}$ exchange after restriction of the interactions between $Ca^{2+}$ from SR and $Na^+-Ca^{2+}$ exchange within micro-domains with heavy cytosolic $Ca^{2+}$ buffering with 10 mM BAPTA. During stimulation every 10 s with a pulse roughly mimicking action potential, the initial outward current gradually turned into a huge inward current of $-12.9{\pm}0.5\;pA/pF$. From the inward current, two different inward $I_{NCX}s$ were identified. One was $10\;{\mu}M$ ryanodine-sensitive, constituting $14.2{\pm}2.3%$. It was completely blocked by $CdCl_2$ (0.1 mM and 0.5 mM) and by $Na^+-depletion$. The other was identified by 5 mM $NiCl_2$ after suppression of $I_{CaL}$ and ryanodine receptor, constituting $14.8{\pm}1.6%$. This latter was blocked by either 10 mM caffeine-induced SR $Ca^{2+}-depletion$ or 1 mM tetracaine. IV-relationships illustrated that the latter was activated until the peak in $30{\sim}35\;mV$ lower voltages than the former. Overall, it was concluded that the SR $Ca^{2+}$ release process in the rat ventricular myocytes is mediated by the voltage-sensitive release mechanism in addition to the $Ca^{2+}-induced-Ca^{2+}\;release$.

Relatoinship between Sarcoplasmic Reticular Calcium Release and $Na^+-Ca^{2+}$ Exchange in the Rat Myocardial Contraction

  • Kim, Eun-Gi;Kim, Soon-Jin;Ko, Chang-Mann
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.3
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    • pp.197-210
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    • 2000
  • Suppressive role of $Na^+-Ca^{2+}$ exchange in myocardial tension generation was examined in the negative frequency-force relationship (FFR) of electric field stimulated left atria (LA) from postnatal developing rat heart and in the whole-cell clamped adult rat ventricular myocytes with high concentration of intracellular $Ca^{2+}$ buffer (14 mM EGTA). LA twitch amplitudes, which were suppressed by cyclopiazonic acid in a postnatal age-dependent manner, elicited frequency-dependent and postnatal age-dependent enhancements after $Na^+-reduced,\;Ca^{2+}-depleted$ (26 Na-0 Ca) buffer application. These enhancements were blocked by caffeine pretreatment with postnatal age-dependent intensities. In the isolated rat ventricular myocytes, stimulation with the voltage protocol roughly mimicked action potential generated a large inward current which was partially blocked by nifedipine or $Na^+$ current inhibition. 0 Ca application suppressed the inward current by $39{\pm}4%$ while the current was further suppressed after 0 Na-0 Ca application by $53{\pm}3%.$ Caffeine increased this inward current by $44{\pm}3%$ in spite of 14 mM EGTA. Finally, the $Na^+$ current-dependent fraction of the inward current was increased in a stimulation frequency-dependent manner. From these results, it is concluded that the $Ca^{2+}$ exit-mode (forward-mode) $Na^+-Ca^{2+}$ exchange suppresses the LA tension by extruding $Ca^{2+}$ out of the cell right after its release from sarcoplasmic reticulum (SR) in a frequency-dependent manner during contraction, resulting in the negative frequency-force relationship in the rat LA.

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Effects of Nitric Oxide on Inhibitory Receptors of Rod Bipolar Cells of Rat Retina

  • Park, No-Gi;Bai, Sun-Ho;Jung, Chang-sub;Chun, Mynng-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.6
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    • pp.347-352
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    • 2005
  • The effects of nitric oxide (NO) on inhibitory neurotransmitter receptors and some types of inhibitory receptors in dissociated rod bipolar cell (RBC) were investigated. In the whole cell voltage-clamping mode, the gamma-aminobutyric acid (GABA) activated current showed both sustained and transient components. GABA activated transient current was fully blocked by bicuculine, a $GABA_A$ receptor antagonist. The cis-4-aminocrotonic acid (CACA), a $GABA_C$ receptor agonist, evoked the sustained current that was not blocked by bicuculline (BIC). Glycine activated the transient current. These results indicate that the RBCs possess $GABA_A$, $GABA_C$, and glycine inhibitory receptors. Sodium nitroprusside (SNP), a NO analogue, reduced the currents activated by $GABA_A$ receptor only, however, did not reduce the currents activated by either $GABA_C$ or glycine receptors. This study signifies further that only NO depresses the fast inhibitory response activated by $GABA_A$ receptor in RBC. We, therefore, postulate that NO might depress the light-on/off transient inhibitory responses in RBCs in the rat retina.

Blockade of Intrinsic Oscillatory Activity of Cerebellar Purkinje Cells by Apamin and Nickel

  • Seo, Wha-Sook;Strahlendorf, Jean-C.;Strahlendorf, Howard-K.
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.477-484
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    • 1997
  • Intracellular recordings of oscillatory firing (bursting activity) were obtained from Purkinje cells (PCs) in rat cerebellar slices. Apamin inhibited post-burst hyperpolarizations (PBHs) progressively and finally terminated oscillatory firing activity of PCs. Apamin did not affect the amplitude or duration of the after-hyperpolarization (AHP) between spikes within the burst. In the voltage clamp mode, apamin shifted the whole-cell, quasi-steady state I/V relationship in an inward direction and abolished the zero slope resistance (ZSR) region by blocking outward current. Nickel ($Ni^{2+}$) terminated oscillatory activity and also abolished the ZSR region. However, $Ni^{2+}$ did not have progressive blocking action on the post-burst hyperpolarization before it blocked oscillatory activity. $Ni^{2+}$ blocked an inward current at potentials positive to approximately -65 mV, which was responsible for the ZSR region and outward current at more negative potentials. These data indicated that oscillatory activity of PCs is sustained by a balance between a slow $Ni^{2+}$-sensitive inward current and an apamin-sensitive outward current in the region of ZSR of the whole-cell I/V curve.

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