• Title/Summary/Keyword: Ion Channel

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Short-term activation of synaptic transmission by acute KCl application significantly reduces somatic A-type K+ current

  • Song, Jung-Yop;Kim, Hye-Ji;Jung, Sung-Cherl;Kang, Moon-Seok
    • Journal of Medicine and Life Science
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    • v.15 no.2
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    • pp.62-66
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    • 2018
  • A-type $K^+$ ($I_A$) channels are transiently activated in the suprathreshold membrane potential and then rapidly inactivated. These channels play roles to control the neuronal excitability in pyramidal neurons in hippocampi. We here electrophysiologically tested if regulatory functions of $I_A$ channels might be targeted by acute activation of glutamatergic synaptic transmission in cultured hippocampal neurons(DIV 6~8). The application of high KCl in recording solutions(10 mM, 2 min) to increase presynaptic glutamate release, significantly reduced the peak of somatic $I_A$ without changes of gating kinetics. This indicates that neuronal excitation induced by the enhancement of synaptic transmission may process with distinctive signaling cascades to affect voltage-dependent ion channels in hippocampal neurons. Therefore, it is possible that short-lasting enhancement of synaptic transmission is functionally restricted in local synapses without effects on intracellular signaling cascades affecting a whole neuron, efficiently and rapidly enhancing synaptic functions in hippocampal network.

Sub-Ciliary Segregation of Two Drosophila Transient Receptor Potential Channels Begins at the Initial Stage of Their Pre-Ciliary Trafficking

  • Kwon, Youngtae;Lee, Jeongmi;Chung, Yun Doo
    • Molecules and Cells
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    • v.43 no.12
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    • pp.1002-1010
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    • 2020
  • Cilia are important eukaryotic cellular compartments required for diverse biological functions. Recent studies have revealed that protein targeting into the proper ciliary subcompartments is essential for ciliary function. In Drosophila chordotonal cilium, where mechano-electric transduction occurs, two transient receptor potential (TRP) superfamily ion channels, TRPV and TRPN, are restricted to the proximal and distal subcompartments, respectively. To understand the mechanisms underlying the sub-ciliary segregation of the two TRPs, we analyzed their localization under various conditions. In developing chordotonal cilia, TRPN was directly targeted to the ciliary tip from the beginning of its appearance and was retained in the distal subcompartment throughout development, whereas the ciliary localization of TRPV was considerably delayed. Lack of intraflagella transport-related proteins affected TRPV from the initial stage of its pre-ciliary trafficking, whereas it affected TRPN from the ciliary entry stage. The ectopic expression of the two TRP channels in both ciliated and non-ciliated cells revealed their intrinsic properties related to their localization. Taken together, our results suggest that sub-ciliary segregation of the two TRP channels relies on their distinct intrinsic properties, and begins at the initial stage of their pre-ciliary trafficking.

N-4-Substituted-benzyl-N'-tert-butylbenzyl Thioureas as Vanilloid Receptor Ligands: Investigation on the Role of Methanesulfonamido group in Antagonistic Activity

  • Park, Hyeung-Geun;Choi, Je-Yeon;Choi, Sea-Hoon;Park, Mi-Kyung;Lee, Ji-Hye;Suh, Young-Ger;Cho, Ha-Won;Oh, Uh-Taek;Lee, Ji-Youn;Kang, Sang-Uk;Lee, Jee-Woo;Kim, Hee-Doo;Park, Young-Ho;Jeong, Yeon-Su;Choi, Jin-Kyu;Jew, Sang-Sup
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.173.2-173.2
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    • 2003
  • Vanilloid receptor I (VR1) is a nonselective cation ion channel placed in the plasma membrane of peripheral sensory neurons that is potential target for analgesia A series of N-4-substituted-benzyl-N'-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG. Their structure-activity relationship in reveals that not only the two oxygens and amide hydrogen of sulfonamido group but also the optimal size of methyl in methanesulfonamido group play an integral role for the antagonistic activity on vanilloid receptor.

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Fabrication of Paper-based Biosensor Chip Using Polydimethylsiloxane Blade Coating Method (PDMS 블레이드 코팅법을 이용한 종이-기반 바이오센서칩 제작)

  • Jeong, Heon-Ho;Park, Chami
    • Korean Chemical Engineering Research
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    • v.59 no.1
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    • pp.100-105
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    • 2021
  • This paper proposes the polydimethylsiloxane (PDMS) blade coating method for fabrication of paper-based analytical device (PAD) that is able to monitor the disease diagnosis and progress without special analytical equipment. The mold that has PAD design is easily modified by using laser cutting technique. And the fabricated mold is used for hydrophobic barrier formation by blade coating. We have optimized the stable formation of PDMS hydrophobic barrier as blade coating condition, which is established by analyzing the structure of the PDMS hydrophobic barrier and change of hydrophilic channel size as thickness of the ink and contact time with the chromatography paper. Based on optimal condition, we demonstrate that PAD as biosensor can apply to detect protein, glucose, and metal ion without special analysis equipment.

Fabrication of the FET-based SPM probe by CMOS standard process and its performance evaluation (CMOS 표준 공정을 통한 SPM 프로브의 제작 및 그 성능 평가)

  • Lee, Hoontaek;Kim, Junsoo;Shin, Kumjae;Moon, Wonkyu
    • Journal of Sensor Science and Technology
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    • v.30 no.4
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    • pp.236-242
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    • 2021
  • In this paper, we report the fabrication of the tip-on-gate of a field-effect-transistor (ToGoFET) probe using a standard complementary metal-oxide-semiconductor (CMOS) process and the performance evaluation of the fabricated probe. After the CMOS process, I-V characteristic measurement was performed on the reference MOSFET. We confirmed that the ToGoFET probe could be operated at a gate voltage of 0 V due to channel ion implantation. The transconductance at the operating point (Vg = 0 V, Vd = 2 V) was 360 ㎂/V. After the fabrication process was completed, calibration was performed using a pure metal sample. For sensitivity calibration, the relationship between the input voltage of the sample and the output current of the probe was determined and the result was consistent with the measurement result of the reference MOSFET. An oxide sample measurement was performed as an example of an application of the new ToGoFET probe. According to the measurement, the ToGoFET probe could spatially resolve a hundred nanometers with a height of a few nanometers in both the topographic image and the ToGoFET image.

Microstructure characterization technique of spacer garter spring coil X-750 material (스페이서 가터 스프링 코일 X-750 소재 정밀 조직 분석 방법)

  • Hyung-Ha Jin;I Seol Ryu;Gyeng-Geun Lee
    • Transactions of the Korean Society of Pressure Vessels and Piping
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    • v.17 no.2
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    • pp.109-118
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    • 2021
  • In the periodic surveillance material test for the spacer component of fuel channel assembly in CANDU, a microstructural characterization analysis is required in addition to the mechanical property evaluation test. In this study, detailed microstructure analysis and simple mechanical property evaluation of archive spacer parts were conducted to indirectly support the surveillance test and assist in the study of spacer material degradation. We investigated the microstructural characteristics of the spacer garter spring coil through comparative analysis with the plate material. The main microstructure characteristics of the garter spring coil X-750 are represented by the fine grain size distribution, the ordering phase distribution developed inside the matrix, the high dislocation density inside the grains, and the arrangement of coarse carbides. In addition, the yield strength of the garter spring coil X-750 was indirectly evaluated to be approximately 1 GPa. We also established an analytical method to elucidate the microstructural evolution of the radioactive spacer garter spring coil X-750 based on Canadian research experiences. Finally, we confirmed the measurement technique for helium bubble formation through TEM examination on the helium implanted X-750 material.

Closed-Loop Cooling System for High Field Mangets (고자기장용 자석을 위한 밀폐순환형 냉각장치)

  • Choi, Y.S.;Kim, D.L.;Lee, B.S.;Yang, H.S.;Painter, T.A.;Miller, J.R.
    • Progress in Superconductivity and Cryogenics
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    • v.8 no.1
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    • pp.59-64
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    • 2006
  • A closed-loop cryogenic cooling system for high field magnets is presented. This design is motivated by our recent development of cooling system for 21 tesla Fourier Transform ion Cyclotron Resonance (FT-ICR) superconducting magnets without any replenishment of cryogen. The low temperature superconducting magnets are immersed in a subcooled 1.8 K bath, which is connected hydraulically to the 4.2 K reservoir through a narrow channel. Saturated liquid helium is cooled by Joule-Thomson heat exchanger and flows through the JT valve, isenthalpically dropping its pressure to approximately 1 6 kPa, corresponding saturation temperature of 1.8 K. Helium gas exhausted from pump is now recondensed by two-stage cryocooler located after vapor purify system. The amount of cryogenic Heat loads and required mass flow rate through closed-loop are estimated by a relevant heat transfer analysis, from which dimensions of JT heat exchanger and He II heat exchanger are determined. The detailed design of cryocooler heat exchanger for helium recondensing is performed. The effect of cryogenic loads, especially superfluid heat leak through the gap of weight load relief valve, on the dimensions of cryogenic system is also investigated.

Effect of $Ca^{++}$ Ionophore and $Ca^{++}$-Channel Blocker on the Mouse Oocyte Maturation (생쥐 난자성숙에 미치는 $Ca^{++}$ Ionophore와 $Ca^{++}$ Channel Blocker의 영향)

  • Bae, In-Ha;Kim, Hyun-Sook;Kim, Moon-Kyoo
    • Clinical and Experimental Reproductive Medicine
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    • v.19 no.2
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    • pp.105-116
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    • 1992
  • The present study was examined to clarify the role of calcium ion as a factor for the maturation of mouse oocytes. Follicles and cumulus-enclosed oocytes were isolated with two sharp needles under a stereomicroscope from female mouse (ICR) ovaries which were treated PMSG 5 IU 45-46 hours previously. Isolated follicles and cumulus-enclosed oocytes were cultured for 14-16 hours in an organ culture system at $37^{\circ}C$, 5% $CO_2$ in air and 100% humudified in incubator. MHBS was the basic medium used from which A23187, verapamil, $NiCl_{2.}$ $6H_2O$ and $LaCl_{3.}$ $7H_2O$ were added depending on the experimental groups. In follicle- or cumulus-enclosed oocytes wre cultured in these differently treated media. Following results were obtained from the present study. 1. The calcium ionophore A23187 directly or indirectly seems to stimulate GVBD of follicle-enclosed mouse oocytes. Increasing concentration of ionophore A23187 1ed to an increase in oocytes degeneration from the cumulus-enclosed mouse oocytes. 2. The organic $Ca^{++}$ channel blocker, verapamil does not induce GVBD of follicle-enclosed mouse oocytes. Specially, higher dose of 1 mM verapamil induced GVBD of follicle-enclosed mouse oocytes. However, cytoplasm of GVBD oocytes in 1 mM verapamil treated groups appeared shrunk. In the cumulus-enclosed oocytes, polar body formation was reduced in verapamil treated groups and degeneration increased. Verapamil inhibit oocyte maturation (polar body formation). 3. The $Ca^{++}$ inhibitor, Nickel ($NiCl_{2.}$ $6H_2O$) inhibits maturation of the follicle-enclosed oocytes. In the cumulus-enclosed oocytes the progression to MII (PB formation) was reduced and degeneration of mouse oocytes increased as the concentration of $Ni^{++}$ increase. The results indicates that nickel act as an inhibitor of calcium. 4. The $Ca^{++}$ inhibitors, Lanthanum ($LaCl_{3.}$ $7H_2O$) has shown different effect from that of nickel. In follicle-enclosed oocytes, 0.01mM lanthanum induced maturation of mouse oocytes. Polar body formation was reduced in the cumulus-enclosed oocytes all lanthanum treated group.

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Magnesium-induced Relaxation in Rat Aorta (Magnesium에 의한 흰쥐 대동맥 이완)

  • Oh, Sung-suck;Lee, Sang-woo;Kang, Hyung-sub;Kim, Jin-shang
    • Korean Journal of Veterinary Research
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    • v.43 no.3
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    • pp.373-382
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    • 2003
  • Magnesium ion ($Mg^{2+}$) is a vasodilator, but little is known about its mechanism of action on vascular system. In vitro, extracellular magnesium sulfate ($MgSO_4$) produced relaxation in phenylephrine (PE) or high KCl-precontracted isolated rat thorocic aorta with (+E) or without (-E) endothelium in a concentration-dependent manner. The $MgSO_4$-induced relaxations were not affected by removal of the endothelium. Pretreatment of +E or -E aortic rings with nitric oxide synthase (NOS) inhibitors ($20{\mu}M$ L-NNA, $100{\mu}M$ L-NAME, $1{\mu}M$ dexamethasone and $400{\mu}M$ aminoguanidine), cyclooxygenase inhibitor ($10{\mu}M$ indomethacin), guanylate cyclase inhibitors ($10{\mu}M$ ODQ and $30{\mu}M$ methylene blue) and $Ca^{2+}$ transport blocker ($10{\mu}M$ ryanodine) did not affect the relaxant effects of $MgSO_4$. $Ca^{2+}$ channel blockers ($0.3{\mu}M$ nifedipine and $0.5{\mu}M$ veropamil) completely decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. However, in $Ca^{2+}$-free medium, $MgSO_4$-induced vasorelaxation was potentiated and this response was inhibited by nifedipine. Protein kinase C (PKC) inhibitors ($1.0{\mu}M$ staurosporine, $0.5{\mu}M$ tamoxifen and $0.1{\mu}M$ H7) or PLC inhibitor ($100{\mu}M$ NCDC) markedly decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. In vivo, infusion of $MgSO_4$ elicited significant decreases in arterial blood pressure. After intravenous injection of nifedipine ($150{\mu}g/kg$) and NCDC (3 mg/kg), infusion of $MgSO_4$ inhibited the $MgSO_4$-lowered blood pressure markedly. However, after introvenous injection of saponin (15 mg/kg), L-NNA (3 mg/kg), L-NAME (5 mg/kg), indomethacin (2 mg/kg), methylene blue (15 mg/kg) and aminoguanidine (10 mg/kg) failed to inhibit it. These results suggest that endothelial NQ-cGMP or prostaglandin pathway is not involved in vasorelaxant or hypotensive action of $Mg^{2+}$ and that these effects are due to the inhibitory action of $Mg^{2+}$ on the $Ca^{2+}$ channel or PLC-PKC pathway, and are due to the competitive influx of $Mg^{2+}$ and $Ca^{2+}$ through the $Ca^{2+}$ channel.

Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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