• Title/Summary/Keyword: $K^+$ currents

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Effects of hydrogen peroxide on voltage-dependent K+ currents in human cardiac fibroblasts through protein kinase pathways

  • Bae, Hyemi;Lee, Donghee;Kim, Young-Won;Choi, Jeongyoon;Lee, Hong Jun;Kim, Sang-Wook;Kim, Taeho;Noh, Yun-Hee;Ko, Jae-Hong;Bang, Hyoweon;Lim, Inja
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.3
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    • pp.315-324
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    • 2016
  • Human cardiac fibroblasts (HCFs) have various voltage-dependent $K^+$ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide ($H_2O_2$) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether $H_2O_2$ could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of $H_2O_2$ stimulated $Ca^{2+}-activated$ $K^+$ ($K_{Ca}$) currents but not delayed rectifier $K^+$ or transient outward $K^+$ currents, all of which are VDKCs. $H_2O_2-stimulated$ $K_{Ca}$ currents were blocked by iberiotoxin (IbTX, a large conductance $K_{Ca}$ blocker). The $H_2O_2-stimulating$ effect on large-conductance $K_{Ca}$ ($BK_{Ca}$) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated $BK_{Ca}$ currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the $H_2O_2-stimulating$ effect on $BK_{Ca}$ currents. Using RT-PCR and western blot analysis, three subtypes of $K_{Ca}$ channels were detected in HCFs: $BK_{Ca}$ channels, small-conductance $K_{Ca}$ ($SK_{Ca}$) channels, and intermediate-conductance $K_{Ca}$ ($IK_{Ca}$) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to $H_2O_2$, but IbTX decreased $H_2O_2$-induced apoptosis. These data suggest that among the VDKCs of HCFs, $H_2O_2$ only enhances $BK_{Ca}$ currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through $BK_{Ca}$ channels.

ATP-Sensitive $K^+$ Currents in Gastric Myocytes Isolated from Guinea-pig

  • Jun, Jae-Yeoul;Yeum, Cheol-Ho;Yun, Pyung-Jin;Park, Jong-Seong;Kim, Sung-Joon;So, In-Suk;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.1
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    • pp.85-93
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    • 1998
  • ATP-sensitive $K^+$ channels ($K_{ATP}$) were not identified in gastric smooth muscle cells. However, in tension recording of intact gastric circular muscle, lemakalim of $K_{ATP}$ channels opener in other tissues suppressed mechanical contractions and this effect was blocked by glibenclamide, a specific inhibitor of $K_{ATP}$ channels. The aims of this study were to investigate whether $K_{ATP}$ channels exist in gastric smooth muscle of guinea-pig and to know its physiological role. Whole cell $K^+$ currents activated by lemakalim were recorded from freshly isolated cells with a 0.1 mM ATP, 140 mM KCl pipette solutions. Lemakalim (10 ${\mu}M$) increased inward currents of $-224{\pm}34$ pA (n=13) at -80 mV of holding potential in bath solution contained 90 mM $K^+$. Bath-applied glibenclamide (10 ${\mu}M$) inhibited the lemakalim-activated inward currents by $91{\pm}6%$ (n=5). These lemakalim-activated inward currents were reduced by increased intracellular ATP from 0.1 to 3 mM ($-41{\pm}12$ pA) (n=5). The reversal potential of the glibenclamide- sensitive inward currents was $-5.2{\pm}2.4$ mV (n=3) in external 90 mM $K^+$ and shifted to $-14.8{\pm}3.6$ mV (n=3) in external 60 mM $K^+$, which close to equilibrium potential of $K^+$ ($E_K$). External barium and cesium inhibited the lemakalim-activated inward currents dose-dependently. The half-inhibitory dose ($IC_{50}$) of barium and cesium were 2.3 ${\mu}M$ (n=5) and 0.38 mM (n=4), respectively. 10 mM tetraethylammonium (TEA) also inhibited the lemakalim-activated inward currents by $66{\pm}15%$ (n=5). Both substance P (SP) (5 ${\mu}M$) and acetylcholine (ACh) (5 ${\mu}M$) inhibited lemakalim-activated inward currents. These results suggest that $K_{ATP}$ channels exist in the gastric smooth muscle and its modulation by neurotransmitters may play an important role in regulating gastric motility.

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Internal Perfusion of ADP in Mouse Oocytes Increases Outward $K^+$ Currents (ADP에 의한 생쥐 난자의 외향전류 증가 효과)

  • 한재희;박홍기;강다원;이상미;이상호;배인하;홍성근
    • Development and Reproduction
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    • v.4 no.2
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    • pp.243-250
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    • 2000
  • To find the mechanism underlying the ADP-induced increase in the outward current in ovulated mouse oocytes, we examined changes in voltage-dependent currents using the whole cell voltage clamp technique and the internal perfusion technique. Eggs were collected from the oviduct of superovulated mice with PMSG and hCG. Membrane potential was held at -60 mV (or -80 mV in the case of recording $Ca^{2+}$ currents) and step depolarizations or hyperpolarizations were applied for 300 ms. By step depolarizations, outward currents comprising steady-state and time-dependent components were elicited. They were generated in response to the positive potential more than 20 mV with severe outward rectification and were blocked by external TEA, a specific $K^{+}$ channel blocker, suggesting that they be carried via $K^{+}$ channels. Internally-perused 5 mM ADP gradually increased outward $K^{+}$ currents (IK) 1 min after perfusion of ADP and reached slowly to maximum (150~170%) 5 min later over the positive potential range, implying that ADP might not be acted directly to the $K^{+}$ channels. IK were decreased by 5 mM ATP without affecting the steady-state component of outward current. In contrast to the effect of ADP and ATP on IK, both effect of ATP and ADP on inward $Ca^{2+}$ currents (ICa) could not be detected due to the continuous decrease in current amplitudes with time-lapse ("run-down" phenomena). To check if there is a G protein-involved regulation in the ionic current of mouse oocytes, 1 mM GTP was applied to the cytoplasmic side, and the outward current and inward currents were recorded. ICa was promptly increased in the presence of GTP whereas IK was not changed. from these results, it is concluded that the ATP-dependent regulation is likely linked in the ADP-induced increase in the outward $K^{+}$ current, and G protein-involved cellular signalling might affect ion channels carrying $Ca^{2+}$ and $K^{+}$ in mouse oocytes.

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The Influence of Medium Frequency Currents According to Frequency on Sensory Threshold (중주파 전류의 주파수가 감각 역치에 미치는 영향)

  • Yu, Jin-Ho;Hwang, Tae-Yeon;Jeong, Jin-Gyu
    • Journal of the Korean Academy of Clinical Electrophysiology
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    • v.7 no.1
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    • pp.23-27
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    • 2009
  • Purpose : The purpose of this study was to examine the effects of different medium frequency currents on afferent fibers. Methods : Thirty healthy volunteers who had no known history of neurological disorders were equally assigned to one of three groups; 2500Hz, 4000Hz, and control and each group was applied to the left wrist in palmer cutaneous branch of radial nerve by different medium frequency currents for 15 min. We measured the changes of thresholds for tactile, two-point discrimination, and thresholds for pain. Results : The results showed that the medium frequency currents stimulation increased thresholds for tactile, two-point discrimination, and thresholds for pain. However, there is no statistically significant difference between group 2500Hz and group 4000Hz. Conclusion : This may explain thresholds for tactile, two-point discrimination, and thresholds for pain plain medium frequency currents stimulation inhibits the excitability of afferent fibers, but the effect of the frequency difference within medium frequency currents is not demonstrated.

Bisphenol A and 4-tert-Octylphenol Inhibit Cx46 Hemichannel Currents

  • Oh, Seunghoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.1
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    • pp.73-79
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    • 2015
  • Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ) channels. Cx46 and Cx50 are also known to function as conductive hemichannels. As part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors were used to examine their effect on Cx46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, $1{\mu}M$) reversibly reduced outward hemichannel currents up to ~28% (n=4). However, overall shapes of Cx46 hemichannel current traces (outward and inward currents) were not changed by these drugs. These results suggest that BPA and OP are likely to occupy the pore of Cx46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.

Lamotrigine, an antiepileptic drug, inhibits 5-HT3 receptor currents in NCB-20 neuroblastoma cells

  • Kim, Ki Jung;Jeun, Seung Hyun;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.169-177
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    • 2017
  • Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine $(5-HT)_3$ receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine ($1{\sim}300{\mu}M$) resulted in a concentration-dependent reduction in peak amplitude of currents induced by $3{\mu}m$ of 5-HT for an $IC_{50}$ value of $28.2{\pm}3.6{\mu}M$ with a Hill coefficient of $1.2{\pm}0.1$. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, $5-HT_3$-mediated currents evoked by 1 mM dopamine, a partial $5-HT_3$ receptor agonist, were inhibited by lamotrigine co-application. The $EC_{50}$ of 5-HT for $5-HT_3$ receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate $5-HT_3$ receptor desensitization, inhibited $5-HT_3$ receptor currents in a concentration-dependent manner. The deactivation of $5-HT_3$ receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of $5-HT_3$ receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the $5-HT_3$ receptor currents. These results indicate that lamotrigine inhibits $5-HT_3$-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

The Calculation of Reflection Coefficients of Water Waves over Various Shear Currents with a Uniform Depth Topography (다양한 외부흐름에 대한 평탄한 지형을 통과하는 파랑의 반사율 산정)

  • Lee, Jun-Whan;Cho, Yong-Sik
    • Journal of Korea Water Resources Association
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    • v.46 no.3
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    • pp.245-252
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    • 2013
  • The reflection coefficients of monochromatic water waves over various shear currents flowing on a constant topography are estimated analytically in this study. The region of varying shear currents is represented by a finite number of tiny steps with a uniform depth topography. The proper numbers of steps and evanescent modes needed for the analysis are proposed by a series of convergence tests. The characteristics of reflection coefficients for various shear currents conditions are also examined.

A Control Strategy to Obtain Sinusoidal Input Currents of Matrix Converter under Unbalanced Input Voltages

  • Nguyen, Thanh-Luan;Lee, Hong-Hee
    • Proceedings of the KIPE Conference
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    • 2018.07a
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    • pp.114-116
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    • 2018
  • This paper presents a control strategy to achieve the balanced sinusoidal output currents, as well as sinusoidal input currents for the matrix converter (MC) under unbalanced input voltages. By regulating the modulation index of the converter according to the instantaneous input voltages, the output currents are kept balanced and sinusoidal. In order to obtain sinusoidal input currents, the input power factor angle should be dynamically calculated based on the positive and negative sequence components of the input voltages. This paper proposes a simple method to construct the expected input power factor angle without the complicated sequence component extraction of input voltages. Simulation results are given to validate the effectiveness of the proposed control strategy.

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New High-Voltage Generator with Several mA Output Currents using Low Temperature Poly Silicon (LTPS) Technology for TFT-LCD Panel

  • Akiyama, Yuuki;Suzuki, Yasoji;Ishii, Noriyuki;Murata, Shinichi
    • 한국정보디스플레이학회:학술대회논문집
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    • 2006.08a
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    • pp.218-221
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    • 2006
  • In this paper, a high-voltage generator with several mA draw output currents using LTPS-TFT technology is proposed. The new generator can be efficiently boosted about +18V output voltages with 5mA draw output currents and power efficiency ${\eta}$ is around 84% under the conditions of +5V power-supply voltage and 250kHz frequency.

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Degradation properties of ZnO surge arrester due to lightning impulse current (뇌임펄스 전류에 의한 ZnO 배전용 피뢰기의 열화특성)

  • Lee, Seung-Ju;Lee, Bok-Hee;Lee, Su-Bong;Kim, Dong-Soung;Shin, Hee-Kyung;Jung, Dong-Cheol
    • Proceedings of the KIEE Conference
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    • 2008.07a
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    • pp.1305-1306
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    • 2008
  • In this work, in order to investigate the effect of lightning impulse currents on ZnO surge arrester. and the deterioration characteristics of ZnO surge arrester, 8/20 [${\mu}s$], 2.5 [kA] impulse currents were applied to the ZnO surge arrester under test. The leakage currents of ZnO surge arrester were measured and ZnO element was analyzed by X-ray photoelectron spectroscopy. As a result, the resistive leakage current of ZnO surge arrester was increased with the injection number of lightning impulse currents.

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