• Title/Summary/Keyword: $K^{+}$ channels

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The Downregulation of Somatic A-Type $K^+$ Channels Requires the Activation of Synaptic NMDA Receptors in Young Hippocampal Neurons of Rats

  • Kang, Moon-Seok;Yang, Yoon-Sil;Kim, Seon-Hee;Park, Joo-Min;Eun, Su-Yong;Jung, Sung-Cherl
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.2
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    • pp.135-141
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    • 2014
  • The downregulation of A-type $K^+$ channels ($I_A$ channels) accompanying enhanced somatic excitability can mediate epileptogenic conditions in mammalian central nervous system. As $I_A$ channels are dominantly targeted by dendritic and postsynaptic processings during synaptic plasticity, it is presumable that they may act as cellular linkers between synaptic responses and somatic processings under various excitable conditions. In the present study, we electrophysiologically tested if the downregulation of somatic $I_A$ channels was sensitive to synaptic activities in young hippocampal neurons. In primarily cultured hippocampal neurons (DIV 6~9), the peak of $I_A$ recorded by a whole-cell patch was significantly reduced by high KCl or exogenous glutamate treatment to enhance synaptic activities. However, the pretreatment of MK801 to block synaptic NMDA receptors abolished the glutamate-induced reduction of the $I_A$ peak, indicating the necessity of synaptic activation for the reduction of somatic $I_A$. This was again confirmed by glycine treatment, showing a significant reduction of the somatic $I_A$ peak. Additionally, the gating property of $I_A$ channels was also sensitive to the activation of synaptic NMDA receptors, showing the hyperpolarizing shift in inactivation kinetics. These results suggest that synaptic LTP possibly potentiates somatic excitability via downregulating $I_A$ channels in expression and gating kinetics. The consequential changes of somatic excitability following the activity-dependent modulation of synaptic responses may be a series of processings for neuronal functions to determine outputs in memory mechanisms or pathogenic conditions.

A study on the Transmutation among Six-channels in Shanghanlun (『상한론(傷寒論)』 육경병(六經病) 전변(傳變)에 관한 연구(硏究))

  • Lee, Sang-Hyup;Kim, Hoon
    • Journal of Korean Medical classics
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    • v.28 no.3
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    • pp.27-43
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    • 2015
  • Objectives : Zhang Zhong-jing's Shanghanlun is based on Six-channels system to classified a disease. This paper is planning to describe the Transmutation among Six-channels system. Six-channels change not fixed in either direction and each is relative to each other. Methods : I will try to describe the Transmutation among Six channels system, through the letter of the Shanghanlun. First, I will find letters related to a disease transmission. Second, It will be described through the analysis of the past medical scientists. Results : Six-Meridian Pattern is the categorization of syndromes according to the theory of the six meridians, applied to the diagnosis of acute febrile diseases at different stages, but also useful for the pattern syndrome differentiation of other diseases. Transmutation among Six channels system is not fixed in a certain order and it each affects one another. Conclusions : We can see that Zhong-jing's medical treatment from syndrome differentiation is associated with a Mutual transmission(相互傳變).

Analyzing Customer Feedback Differences between VOCs and External Channels (VOC와 외부채널간의 고객 피드백 차이 분석)

  • Ahn, Sang Hyeon;Baek, Dong Hyun
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.41 no.3
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    • pp.129-137
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    • 2018
  • VOCs have been used as the most definitive resource to reflect customer feedback when developing products and services. However, due to the development of the Internet and the emergence of SNS, VOC is no longer the only channel that represents customer opinions. There are also a number of studies showing that many customers express complaints through channels other than VOCs. In this paper, we analyze the difference between the official VOC data and the data collected through the external channel, and suggest ways to reflect the various opinions of customers. To do this, this study uses keyword analysis that can identify differences according to frequency through social network, modular analysis to distinguish topics according to centrality and similarity, and emotional analysis to confirm word polarity (positive and negative). The results of this study show that the opinions of the customers were different depending on channels such as VOCs and external channels. Therefore, the collected data through VOC as well as external channels should be used in order to reflect the opinions of customers. In particular, this paper confirms that the results of one channel may vary depending on the channel characteristics even for the same channel. This confirms that collecting voc only on certain channels may differ from what real customers require. Therefore, data collected through VOCs as well as external channels must be used to reflect various customer feedback.

Design of Conformal Cooling Channels for the Mould of a Plastic Drawer of a Refrigerator by Analysis of Three-Dimensional Injection Moulding (3 차원 사출성형 해석을 통한 냉장고 플라스틱 서랍 제작용 사출 성형 금형의 형상적응형 냉각수로 설계)

  • Ahn, Dong-Gyu;Park, Min-Woo;Park, Seung-Hwa;Kim, Hyung-Su
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.34 no.10
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    • pp.1487-1492
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    • 2010
  • The objective of this study is to design the conformal cooling channels for the mould of a plastic drawer of a refrigerator by analysis of three-dimensional injection molding. In order to obtain the desired design of the conformal cooling channels, the influence of the diameter and the position of the conformal cooling channels on the moulding characteristics and the product qualities were quantitatively examined. From the results of the examination, an optimal design of the conformal cooling channels, which ensures uniform cooling and minimum potential deformation of the molded drawers, was estimated. By comparing the designed mould and a conventional mould with linear cooling channels from the viewpoints of the product qualities as well as cooling and cycle times, it was shown that the mould with conformal cooling channels can simultaneously improve the productivity of the injection moulding process and the product qualities.

Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells

  • Joo, Young Shin;Lee, Hong Joon;Choi, Jin-Sung;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.75-82
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    • 2017
  • The effects of acepromazine on human ether-$\grave{a}$-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an $IC_{50}$ value of $1.5{\mu}M$ and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV. Before and after application of acepromazine, the half activation potentials of hERG currents changed to hyperpolarizing direction. Acepromazine blocked both the steady-state hERG currents by depolarizing pulse and the peak tail currents by repolarizing pulse; however, the extent of blocking by acepromazine in the repolarizing pulse was more profound than that in the depolarizing pulse, indicating that acepromazine has a high affinity for the open state of the channels, with a relatively lower affinity for the closed state of hERG channels. A fast application of acepromazine during the tail currents inhibited the open state of hERG channels in a concentration-dependent. The steady-state inactivation of hERG currents shifted to the hyperpolarized direction by acepromazine. These results suggest that acepromazine inhibits the hERG channels probably by an open- and inactivated-channel blocking mechanism. Regarding to the fact that the hERG channels are the potential target of drug-induced long QT syndrome, our results suggest that acepromazine can possibly induce a cardiac arrhythmia through the inhibition of hERG channels.

Role of Calcium and Calcium Channels in Progesterone Induced Acrosome Reaction in Caprine Spermatozoa

  • Somanath, P.R.;Gandhi, K.K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.7
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    • pp.949-956
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    • 2002
  • There are several physiological and pharmacological evidences indicating that opening of voltage dependent $Ca^{2+}$ channels play a critical role in induction of acrosome reaction in mammalian sperm. We determined the intracellular free $Ca^{2+}$ concentration in ejaculated goat sperm using a fluorescent, $Ca^{2+}$-specific probe, Fura2/AM, after the suspension of sperm in KRB medium, capable of sustaining capacitation and the acrosome reaction. We used nifedipine, D-600 and diltiazem, the $Ca^{2+}$ channel antagonists belonging to the classes of dihydropyridines, phenylalkylamines and benzothiazepines, to investigate the possibility that L-type voltage gated $Ca^{2+}$ channels play a role in the progesterone-stimulated exocytotic response. Progesterone promoted a rise in intracellular $Ca^{2+}$ in goat sperm and addition of nifedipine (100 nM) just prior to progesterone induction, significantly inhibited both intracellular $Ca^{2+}$ rise and exocytosis suggesting that $Ca^{2+}$ channels are involved in the process. However, the intracellular $Ca^{2+}$ increase during the process of capacitation was not affected with the addition of nifedipine suggesting a role of focal channel for $Ca^{2+}$ during capacitation. Studies using monensin and nigericin, two monovalent cation ionophores showed that an influx of $Na^+$ also may play a role in the opening of $Ca^{2+}$ channels. These results strongly suggests that the entry of $Ca^{2+}$ channels with characteristics similar to those of L-type, voltage-sensitive $Ca^{2+}$ channels found in cardiac and skeletal muscle, is a crucial step in the sequence of events leading to progesterone induced acrosome reaction in goat sperm.

Endothelial Ca2+ signaling-dependent vasodilation through transient receptor potential channels

  • Hong, Kwang-Seok;Lee, Man-Gyoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.4
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    • pp.287-298
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    • 2020
  • Ca2+ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca2+ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca2+ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K+ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca2+ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca2+-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca2+-sensitive K+ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca2+ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca2+ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

Electrophysiological Properties of Ion Channels in Ascaris suum Tissue Incorporated into Planar Lipid Bilayers

  • Park, Kwon Moo;Kim, Sun-Don;Park, Jin Bong;Hong, Sung-Jong;Ryu, Pan Dong
    • Parasites, Hosts and Diseases
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    • v.59 no.4
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    • pp.329-339
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    • 2021
  • Ion channels are important targets of anthelmintic agents. In this study, we identified 3 types of ion channels in Ascaris suum tissue incorporated into planar lipid bilayers using an electrophysiological technique. The most frequent channel was a large-conductance cation channel (209 pS), which accounted for 64.5% of channels incorporated (n=60). Its open-state probability (Po) was ~0.3 in the voltage range of -60~+60 mV. A substate was observed at 55% of the main-state. The permeability ratio of Cl- to K+ (PCl/PK) was ~0.5 and PNa/PK was 0.81 in both states. Another type of cation channel was recorded in 7.5% of channels incorporated (n=7) and discriminated from the large-conductance cation channel by its smaller conductance (55.3 pS). Its Po was low at all voltages tested (~0.1). The third type was an anion channel recorded in 27.9% of channels incorporated (n=26). Its conductance was 39.0 pS and PCl/PK was 8.6±0.8. Po was ~1.0 at all tested potentials. In summary, we identified 2 types of cation and 1 type of anion channels in Ascaris suum. Gating of these channels did not much vary with voltage and their ionic selectivity is rather low. Their molecular nature, functions, and potentials as anthelmintic drug targets remain to be studied further.

Antidepressant drug paroxetine blocks the open pore of Kv3.1 potassium channel

  • Lee, Hyang Mi;Chai, Ok Hee;Hahn, Sang June;Choi, Bok Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.1
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    • pp.71-80
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    • 2018
  • In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to high-frequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an $IC_{50}$ value of $9.43{\mu}M$ and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding ($k_{+1}$) and unbinding ($k_{-1}$) rate constants for the paroxetine effect were $4.5{\mu}M^{-1}s^{-1}$ and $35.8s^{-1}$, respectively, yielding a calculated $K_D$ value of $7.9{\mu}M$. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a use-dependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.

Synthesis and Characterization of Cu2+-Perfluorophthalocyanine Incorporated SBA15

  • Oh, Mi-Ok;Park, Sung Soo;Ha, Chang-Sik
    • Journal of Adhesion and Interface
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    • v.7 no.3
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    • pp.10-15
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    • 2006
  • After anchoring 3-(2-aminoethylamino)propyltriethoxysilane (APTES) onto the surfaces of the channels within ordered mesoporous silica, SBA-15, we dispersed $Cu^{2+}$-perfluorophthalocyanine into the modified SBA-15 channels. From small-angle X-ray scattering (SAXS) patterns and transmission electron microscopy (TEM) images, we confirmed that both the calcined and $Cu^{2+}$-perfluorophthalocyanine-incorporated SBA-15 samples possessed ordered periodic structures and hexagonal symmetry lattices (p6mm). The value of the $d_{100}$ spacing was decreased after the incorporation of $Cu^{2+}$-perfluorophthalocyanine into the modified SBA-15 channels. We used FTIR and UV-Vis spectroscopy and thermogravimetric analysis (TGA) to characterize both the modified SBA-15 and the $Cu^{2+}$-perfluorophthalocyanine-incorporated SBA-15 samples. From scanning electron microscopy (SEM) images and $N_2$ sorption measurements, we found that the $Cu^{2+}$-perfluorophthalocyanine units were incorporated within the modified SBA-15 channels, rather than on the external surfaces of the modified SBA-15 channels.

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