• Title/Summary/Keyword: Activation Channels

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3,3',4,4'-tetrachlorobiphenyl (PCB77) enhances human Kv1.3 channel currents and alters cytokine production

  • Jong-Hui Kim;Soobeen Hwang;Seo-In Park;Hyo-Ji Lee;Yu-Jin Jung;Su-Hyun Jo
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.4
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    • pp.323-333
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    • 2024
  • Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.

A Sensing Channel Scheduling Scheme for Improving the Cognition Ability in Cognitive Radio Systems (인지 라디오 시스템에서 주파수 상황인지 능력 향상을 위한 감지 채널 스케줄링 기법)

  • Han, Jeong-Ae;Jeon, Wha-Sook
    • Journal of KIISE:Information Networking
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    • v.35 no.2
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    • pp.130-138
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    • 2008
  • The scheme for recognizing the channel availability is one of the most important research issues in cognitive radio systems utilizing unused frequency bands. In this paper, we propose a novel scheme of selecting sensing channel in order to improve the sensing ability of frequency status in cognitive radio ad hoc networks. To fully exploit the sensing ability of each cognitive radio user, we adopt a master for a cluster which is made of several cognitive radio users. By gathering and analyzing the sensing information from cognitive radio users in the cluster, the cooperative sensing is realized. Since the transmission range of a licensed user is limited, it is possible that a master determines different sensing channels to each cognitive radio users based on their location. By making cognitive radio users sense different channels, the proposed scheme can recognize the state of wireless spectrum fast and precisely. Using the simulation, we compare the performance of the proposed scheme with those of two different compared schemes that one makes cognitive radio users recognize the frequency status based on their own sensing results and the other shares frequency status information but does not utilize the location information of licensed user. Simulation results show that the proposed scheme provides available channels as many as possible while detecting the activation of licensed user immediately.

Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse

  • Hong, Seung Hwa;Sung, Rohyun;Kim, Young Chul;Suzuki, Hikaru;Choi, Woong;Park, Yeon Jin;Ji, Ill Woon;Kim, Chan Hyung;Myung, Sun Chul;Lee, Moo Yeol;Kang, Tong Mook;You, Ra Young;Lee, Kwang Ju;Lim, Seung Woon;Yun, Hyo-Yung;Song, Young-Jin;Xu, Wen-Xie;Kim, Hak Soon;Lee, Sang Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.4
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    • pp.359-365
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    • 2013
  • Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of $K^+$ channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, $K^+$ conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.

Activation of K+ channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca2+ ionophore-induced cell death

  • Yin, Ming Zhe;Park, Seok-Woo;Kang, Tae Wook;Kim, Kyung Soo;Yoo, Hae Young;Lee, Junho;Hah, J. Hun;Sung, Myung Hun;Kim, Sung Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.25-33
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    • 2016
  • Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$)-dependent signaling affects the fate of cancer cells. Here we investigate the role of $Ca^{2+}$-activated $K^+$ channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of dif-ferent cell lines; SNU-1076, OSC-19 and HN5. Treatment with $1{\mu}M$ ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of $Ca^{2+}$-activated $Cl^-$ channels (Ano-1) and $Ca^{2+}$-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward $K^+$ current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Con-sistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the $Ca^{2+}$ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.

A Study on the Determinants of Purchasing Decision Making for Effective Branding Strategy: Focusing the Medicine Treatment in Infantile Obesity (효과적인 브랜딩 전략을 위한 소비자 구매의사 결정 요인 분석: 소아비만 치료제 유통시장을 중심으로)

  • Park, Mun-Seo;Kim, Hyung-Joon;Lee, Sang-Youn
    • Journal of Distribution Science
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    • v.9 no.3
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    • pp.55-64
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    • 2011
  • This study is important in its focus to find key clues in the marketing strategy, consumer behavior, and communication processes that define the infantile obesity market. The study, the first of its kind, surveyed a target audience, purchasing group, and housewives in their quest to determine purchasing decisions and effective branding strategy planning for the infantile obesity market. Another key component of the study was to focus on the key direct and/or indirect distribution channels for the subject market. Recently, obesity has emerged as a major social concern; some studies show that the onslaught of an adverse eating culture in Korea emanates from the prevalence of fast-food dining establishments. Obesity among children leads to adult obesity, especially if the young people's parents are overweight; notably, if either one or both of the parents are obese, the percentage of young people eventually being obese is approximately 80 to 85 percent. Because obesity is the cause of many major health concerns later in life, the struggle for a healthy life is considerably adversely affected by parents' consumer behavior. Infantile obesity, resulting in adult obesity, is also an important national economic and social issue. The sizable direct and indirect economic costs, as well as the tremendous social costs of obesity, cannot be overstated. Effective food branding and advertising centered on food preferences and dietary behaviors, especially to children, creates an effective marketing effort that, ultimately, leads to positive results. Thus, the purpose of this study is to demonstrate that the treatment of childhood obesity in Korea, through the activation of a brand and retail market, can effectively solve social and economic problems that result from infantile and childhood obesity. In this study, obesity markets and distribution channels in the purchase decision-making factors determining factor based on it effective inspection and branding strategies and brand marketing communications strategy proposed measures contribute to the obesity drug market and further enable the childhood obesity problem is intended to assist in solving.

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Vasorelaxant Effect of Prunus yedoensis leaf on Rat Aortic Rings (앵엽(櫻葉) 에탄올 추출물의 혈관이완 효능 및 작용기전에 대한 연구)

  • Lee, Kyungjin;Kim, Kwang-Woo;Heo, Heeseung;Ham, Inhye;Lee, Mi-Hwa;Kim, Bumjung;Bu, Youngmin;Kim, Hocheol;Choi, Ho-Young
    • The Korea Journal of Herbology
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    • v.28 no.4
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    • pp.63-69
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    • 2013
  • Objectives : The purpose of present study was to investigate the vasorelaxant activities and mechanisms of action of the ethanol extract of P. yedoensis leaf (PYL) on isolated rat aortic rings. Methods : Dried P. yedoensis leaves were extracted 3 times with 100% ethanol for 3 h in a reflux apparatus. Isolated rat aortic rings were suspended in organ chambers containing 10 ml Krebs-Henseleit (K-H) solution. The rings were maintained at $37^{\circ}C$ and aerated with a mixture of 95% $O_2$ and 5% $CO_2$. Changes in their tension were recorded via isometric transducers connected to a data acquisition system. Results : PYL relaxed the contraction of aortic rings induced by phenylephrine (PE, 1 ${\mu}M$) or KCl (60 mM) in a concentration dependent manner. However, the vasorelaxant effects of PYL on endothelium-denuded aortic rings were lower than endothelium-intact aortic rings. And the vasorelaxant effects of PYL on endothelium-intact aortic rings were reduced by pre-treatment with $N{\omega}$-Nitro-L-arginine methyl ester (10 ${\mu}M$), methylene blue (10 ${\mu}M$), 1-H-[1,2,4]-oxadiazolo-[4,3-${\alpha}$]-quinoxalin-1-one (10 ${\mu}M$), tetraethylammonium (5 mM). In addition, PYL inhibited the contraction induced by extracellular $Ca^{2+}$ in endothelium-denuded aortic rings pre-contracted by PE or KCl in $Ca^{2+}$-free K-H solution. Conclusions : These results suggest that PYL exerts its vasorelaxant effects via the activation of Nitric Oxide (NO) formation by means of L-arginine and NO-cGMP pathways and via the blockage of receptor operated calcium channels, voltage dependent calcium channels and calcium-activated potassium channels.

Hesperetin Stimulates Cholecystokinin Secretion in Enteroendocrine STC-1 Cells

  • Kim, Hye Young;Park, Min;Kim, Kyong;Lee, Yu Mi;Rhyu, Mee Ra
    • Biomolecules & Therapeutics
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    • v.21 no.2
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    • pp.121-125
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    • 2013
  • Hesperetin (3',5,7-trihydroxy 4'-methoxyflavanone) and its glycoside hesperidin (hesperetin 7-rhamnoglucoside) in oranges have been reported to possess pharmacological effects related to anti-obesity. However, hesperetin and hesperidin have not been studied on suppressive effects on appetite. This study examined that hesperetin and hesperidin can stimulate the release of cholecystokinin (CCK), one of appetite-regulating hormones, from the enteroendocrine STC-1 cells, and then examined the mechanisms involved in the CCK release. Hesperetin significantly and dose-dependently stimulated CCK secretion with an $EC_{50}$ of 0.050 mM and increased the intracellular $Ca^{2+}$ concentrations ($[Ca^{2+}]_i$) compared to the untreated control. The stimulatory effect by hesperetin was mediated via the entry of extracellular $Ca^{2+}$ and the activation of TRP channels including TRPA1. These results suggest that hesperetin can be a candidate biomolecule for the suppression of appetite and eventually for the therapeutics of obesity.

TRPC-Mediated Current Is Not Involved in Endocannabinoid-Induced Short-Term Depression in Cerebellum

  • Chang, Won-Seok;Kim, Jun;Kim, Sang-Jeong
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.2
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    • pp.139-144
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    • 2012
  • It has been reported that activation of metabotropic glutamate receptor 1 (mGluR1) can mediate endocannabinoid-induced short-term depression of synaptic transmission in cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse. mGluR1 has signaling pathways involved in intracellular calcium increase which may contribute to endocannabinoid release. Two major mGluR1-evoked calcium signaling pathways are known: (1) slow-kinetic inward current carried by transient receptor potential canonical (TRPC) channel which is permeable to $Ca^{2+}$; (2) $IP_3$-induced calcium release from intracellular calcium store. However, it is unclear how much each calcium source contributes to endocannabinoid signaling. Here, we investigated whether calcium influx through mGluR1-evoked TRPC channel contributes to endocannabinoid signaling in cerebellar Purkinje cells. At first, we applied SKF96365 to inhibit TRPC, which blocked endocannabinoid-induced short-term depression completely. However, an alternative TRP channel inhibitor, BTP2 did not affect endocannabinoid-induced short-term depression although it blocked mGluR1-evoked TRPC currents. Endocannabinoid signaling occurred normally even though the TRPC current was mostly blocked by BTP2. Our data imply that TRPC current does not play an important role in endocannabinoid signaling. We also suggest precaution in applying SKF96365 to inhibit TRP channels and propose BTP2 as an alternative TRPC inhibitor.

Role of Recombinant PnTx2-6 Protein as a Mediator of Vasodilation in Blood Vessels

  • Park, Seung-Won;Kim, Seong Ryul;Goo, Tae-Won;Choi, Kwang-Ho
    • International Journal of Industrial Entomology and Biomaterials
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    • v.35 no.1
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    • pp.39-44
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    • 2017
  • The venome of Phoneutria nigriventer spider has been shown to have side effects including severe painful erections that last for hours. PnTx2-6, a toxin from P. nigriventer spider venom, modulates voltage gated $Na^+$ channels and activation of nitric oxide (NO) production. NO is essential for the regulation of blood flow and pressure. Therefore, PnTx2-6 is expected to be effective not only for erectile dysfunction but also for cardiovascular diseases. A previously has reported cDNA clone for PnTx2-6 toxin, which was expressed in E. coli cytoplasm. We created the same clone and expressed it in a bacterial expression system. PnTx2-6 increased the genes expression of superoxide dismutase 1, glutathione peroxidase 1, and sulfiredoxin 1. We hypothesized that recombinant PnTx2-6 may indirectly regulate blood flow and pressure, resulting in NO production in human umbilical vein endothelial cells (HUVEC). These data suggest differential regulation of the vascular ageing process, which may contribute to the anatomic heterogeneity of atherosclerosis. The results of this study may be used for the emergency treatment of sudden cardiovascular disease caused by ageing.

Analysis of temperature-dependent abnormal bursting patterns of neurons in Aplysia

  • Hyun, Nam Gyu;Hyun, Kwangho;Oh, Saecheol;Lee, Kyungmin
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.4
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    • pp.349-362
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    • 2020
  • Temperature affects the firing pattern and electrical activity of neurons in animals, eliciting diverse responses depending on neuronal cell type. However, the mechanisms underlying such diverse responses are not well understood. In the present study, we performed in vitro recording of abdominal ganglia cells of Aplysia juliana, and analyzed their burst firing patterns. We identified atypical bursting patterns dependent on temperature that were totally different from classical bursting patterns observed in R15 neurons of A. juliana. We classified these abnormal bursting patterns into type 1 and type 2; type 1 abnormal single bursts are composed of two kinds of spikes with a long interspike interval (ISI) followed by short ISI regular firing, while type 2 abnormal single bursts are composed of complex multiplets. To investigate the mechanism underlying the temperature dependence of abnormal bursting, we employed simulations using a modified Plant model and determined that the temperature dependence of type 2 abnormal bursting is related to temperature-dependent scaling factors and activation or inactivation of potassium or sodium channels.