• Title/Summary/Keyword: A-type $K^+$ channels

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Functional Abnormalities of HERG Mutations in Long QT Syndrome 2 (LQT2)

  • Hiraoka, Masayasu
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.5
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    • pp.367-371
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    • 2001
  • The chromosome 7-linked long QT syndrome (LQT2) is caused by mutations in the human ether-a- go-go-related gene (HERG) that encodes the rapidly activating delayed rectifier $K^+$ current, $I_{Kr},$ in cardiac myocytes. Different types of mutations have been identified in various locations of HERG channel. One of the mechanisms for the loss of normal channel function is due to membrane trafficking of channel protein. The decreased channel function in some deletion mutants appears to be due to loss of coupling with wild type HERG to form the functional channel as the tetramer. Most of missense mutants with few exceptions could interact with wild type HERG to form functional tetramer and caused dominant negative suppression with co-injection with wild type HERG showing variable effects on current amplitude, voltage dependence, and kinetics of activation and inactivation. Two missense mutants at pore regions of HERG found in Japanese LQT2 (A614V and V630L) showed accentuated inward rectification due to a negative shift in steady-state inactivation and fast inactivation. One mutation in S4 region (R534C) produced a negative shift in current activation, indicating the S4 serving as the voltage sensor and accelerated deactivation. The C-terminus mutation, S818L, could not express the current by mutant alone and did not show dominant negative suppression with co-injection of equal amount of wild type cRNA. Co-injection of excess amount of mutant with wild type produced dominant negative suppression with a shift in voltage dependent activation. Therefore, multiple mechanisms are involved in different mutations and functional abnormality in LQT2. Further characterization with the interactions between various mutants in HERG and the regulatory subunits of the channels (MiRP1 and minK) is to be clarified.

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EXPERIMENTAL STUDY OF CRITICAL HEAT FLUX WITH ALUMINA-WATER NANOFLUIDS IN DOWNWARD-FACING CHANNELS FOR IN-VESSEL RETENTION APPLICATIONS

  • Dewitt, G.;Mckrell, T.;Buongiorno, J.;Hu, L.W.;Park, R.J.
    • Nuclear Engineering and Technology
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    • v.45 no.3
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    • pp.335-346
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    • 2013
  • The Critical Heat Flux (CHF) of water with dispersed alumina nanoparticles was measured for the geometry and flow conditions relevant to the In-Vessel Retention (IVR) situation which can occur during core melting sequences in certain advanced Light Water Reactors (LWRs). CHF measurements were conducted in a flow boiling loop featuring a test section designed to be thermal-hydraulically similar to the vessel/insulation gap in the Westinghouse AP1000 plant. The effects of orientation angle, pressure, mass flux, fluid type, boiling time, surface material, and surface state were investigated. Results for water-based nanofluids with alumina nanoparticles (0.001% by volume) on stainless steel surface indicate an average 70% CHF enhancement with a range of 17% to 108% depending on the specific flow conditions expected for IVR. Experiments also indicate that only about thirty minutes of boiling time (which drives nanoparticle deposition) are needed to obtain substantial CHF enhancement with nanofluids.

Development of New Type of Submerged Breakwater for Reducing Mean Water Level behind Structure (배후수위 저감효과를 가진 신기능 잠제의 개발)

  • Hur, Dong-Soo;Lee, Woo-Dong;Goo, Nam-Heon;Jeon, Ho-Seong;Jeong, Yeon-Myeong
    • Journal of Ocean Engineering and Technology
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    • v.31 no.2
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    • pp.130-140
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    • 2017
  • Typically, a submerged breakwater is one of the good scene-friendly coastal structures used to reduce wave energy and coastal erosion. However, sometimes, a submerged breakwater also has a negative aspect in that a strong rip current occurring around an open inlet due to a difference in mean water levels on the front and rear sides of the structure leads to scouring. Such scouring has a bad effect on its stability. In order to eliminate this kind of demerit, this study investigated four new types of submerged breakwaters with drainage channels. First, hydraulic experiments were performed the typical and new structures. Then, the wave height and mean water level distributions around the structures were examined using the experimental results. Finally, it was revealed that the new type of submerged breakwater could efficiently reduce the mean water level on its rear side. In particular, in the case of new-type submerged breakwater 2, an average reduction efficiency of 71.2% for the difference between the mean water levels at the front and rear sides was shown in comparison with the typical one.

Development of a Linear Stability Analysis Model for Vertical Boiling Channels Connecting with Unheated Risers

  • Hwang, Dae-Hyun;Yoo, Yeon-Jong;Zee, Seong-Quun
    • Nuclear Engineering and Technology
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    • v.31 no.6
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    • pp.572-585
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    • 1999
  • The characteristics of two-phase flow instability in a vertical boiling channel connecting with an unheated riser are investigated through the linear stability analysis model. Various two-phase flow models, including thermal non-equilibrium effects, are taken into account for establishing a physical model in the time domain. A classical approach to the frequency response method is adopted for the stability analysis by employing the D-partition method. The adequacy of the linear model is verified by evaluating experimental data at high quality conditions. It reveals that the flow-pattern-dependent drift velocity model enhances the prediction accuracy while the homogeneous equilibrium model shows the most conservative predictions. The characteristics of density wave oscillations under low-power and low-quality conditions are investigated by devising a simple model which accounts for the gravitational and frictional pressure losses along the channel. The necessary conditions for the occurrences of type-I instability and flow excursion are deduced from the one-dimensional D-partition analysis. The parametric effects of some design variables on low quality oscillations are also investigated.

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Performance and Thermal-Flow Characteristics in a Planar Type Solid oxide Fuel Cell with Single Channel and Multi-Channel (단일채널 및 다채널을 포함한 평판형 고체산화물연료전지의 열유동 해석 및 성능평가)

  • Ahn, Hyo-Jung;Cha, Suk-Won
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.31 no.12
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    • pp.1033-1041
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    • 2007
  • This paper studied the characteristics of performance and temperature in a unit cell of a planar type SOFC under various conditions by employing computational fluid dynamics (CFD). In order to derive thermal stress distribution and performance characteristics, the 3-D model simulation for a single channel was performed in various conditions which include interconnect materials $(LaCrO_3/AISI430)$, gas flow direction (co-flow/counter-flow) and inlet temperature (923 K/1173 K). From these results of a single channel, the most effective conditions were applied to the unit stack with multi-channel and the temperature distribution is displayed. Considering both thermal stress and performance, the best combination is 923 K inlet temperature, counter-flow and interconnector of stainless steel. As the end results, flow, thermal and current density distributions were found in the model with multi-channel applied to the best combination and were concentrated in the middle of channels than in the edge.

Inhibitory Effects of Dihydrexidine on Catecholamine Release from the Rat Adrenal Medulla

  • Lee, Jae-Hwang;Lim, Hyo-Jeong;Lim, Dong-Yoon
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.32-42
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    • 2009
  • The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

Effects of Lemakalim, a Potassium Channel Opener, on the Contractility and Electrical Activity of the Antral Circular Muscle in Guinea-Pig Stomach

  • Kim, Sung-Joon;Jun, Jae-Yeoul;Choi, Youn-Baik;Kim, Ki-Whan;Kim, Woo-Gyeum
    • The Korean Journal of Physiology
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    • v.28 no.1
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    • pp.37-50
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    • 1994
  • Synthetic potassium channel openers (KCOs) are agents capable of opening K-channels in excitable cells. These agents are known to have their maximal potency in the smooth muscle tissue, especially in the vascular smooth muscle. Much attention has been focused on the type of K-channel that is responsible for mediating the effects of KCOs. As the KCO-induced changes are antagonized by glibenclamide, an $K_{ATP}$ (ATP-sensitive K-channel) blocker in the pancreatic ${\beta}-cell,\;K_{ATP}$ was suggested to be the channel responsible. However, there also are many results in favor of other types of K-channel $$(maxi-K,\;small\;conductance\;K_{Ca,}\; SK_{ATP}) mediating the effects of KCOs. Effects of lemakalim, (-)enantiomer of cromakalim (BRL 34915), on the spontaneous contractions and slow waves, were investigated in the antral circular muscle of the guinea-pig stomach. Membrane currents and the effects on membrane currents and single channel activities were also measured in single smooth muscle cells and excised membrane patches by using the patch clamp method. Lemakalim induced hyperpolarization and inhibited spontaneous contractions in a dose-dependent manner. These effects were blocked by glibenclamide and low concentrations of tetraethyl ammonium (< mM). Glibenclamide blocked the effect of lemakalim on the membrane potential and slow waves. The mechanoinhibitory effect of lemakalim was blocked by pretreatment with glibenclamide. In a whole ceIl patch clamp condition, lemakalim largely increased outward K currents. These outward K currents were blocked by TEA, glibenclamide and a high concentration of intracelIular EGTA (10 mM). Volatage-gated Ca currents were not affected by lemakalim. In inside-out patch clamp experiments, lemakalim increased the opening frequency of the large conductance $Ca^{2+}-activated$ K channels $(BK_{Ca},\;Maxi-K).$ From these results, it is suggested that lemakalim induces hyperpolarization by opening K-channels which are sensitive to internal Ca and such a hyperpolarization leads to the inhibition of the spontaneous contraction.

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Study on the Behaivor of Bubbles in Array Type Flow Channels (균일형 유로에서 기포의 거동에 관한 연구)

  • Jung, Youngguan
    • Transactions of the Korean hydrogen and new energy society
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    • v.24 no.1
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    • pp.84-90
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    • 2013
  • The hydrogen or oxygen gas producted by electrolysis become many bubbles in the electrolyte, but exact data on the behavior of these bubbles in the separator of an electrolysis stack didn't become known. In this study, the flow visualization experiment on the behavior of bubbles in the flow pattern of the array type separator is performed by using of a visible alkaline electrolysis stack and a stereoscopic microscope. As the results, a fine size bubbles adhered to the surface of the flow pattern grow to large sized bubbles until each bubble's buoyance is lager than the sum of external force and weight. And then the large bubbles flow into the upper area of the separator. Bubbles adhered to the surface of the vertical flow pattern grow quickly than them adhered to the surface of the horizontal flow pattern. Also, he electrolysis efficiency is declined because many multi-size bubbles occupied the wide volume in the flow pattern.

Involvement of ERK1/2 and JNK Pathways in 17${\beta}-estradiol$ Induced Kir6.2 and SK2 Upregulation in Rat Osteoblast-like Cells

  • Kim, Jung-Wook;Yang, Eun-Kyoung
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.4
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    • pp.199-205
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    • 2006
  • The functional expression of potassium $(K^+)$ channels has electrophysiologically been studied in bone cells from several species, however, their identity and regulation of gene expressions in bone cells are not well known. In the present study, to investigate how $K^+$ channel expressions are regulated by estrogen, we measured changes of transcript levels of various $Ca^{2+}$-activated ($K_{Ca}$) and ATP-sensitive $K^+$ channels in rat osteoblastic ROS 17/2.8 cells after treatment with estrogen. Application of 17${\beta}$-estradiol $(E_2)$ for 24 h and 48 h increased mRNA and protein expressions of inwardly rectifying $K^+$ channel (Kir) 6.2 and type 2 small conductance $K_{Ca}$ channel (SK2), respectively. Combined treatment of cells with 17${\beta}-E_2$ and ICI 182,780, a pure antiestrogen, suppressed 17${\beta}-E_2$-induced alterations of SK2 and Kir6.2 mRNA levels. In addition, treatment of cells with U0126, a specific inhibitor of extracellular receptor kinases (ERK)1/2, and SP600125, a specific inhibitor of c-jun N-terminal kinase (JNK) blocked the enhancing effects of 17${\beta}-E_2$ on SK2 and Kir6.2 protein expressions. On the other hand, blocking of p38 mitogen-activated protein kinase had no effect. Taken together, these results indicate that 17${\beta}-E_2$ modulates SK2 and Kir6.2 expressions through the estrogen receptor, involving ERK1/2 and JNK activations.

Numerical and Experimental Analysis of Pressure Drop in a Bipolar Plate channel of a Proton Exchange Membrane Fuel Cell (연료전지 분리판 압력손실 감소를 위한 수치해석 및 실험적 연구)

  • Kim, Hee-Su;Kang, Kyung-Tae;Choi, Yun-Ki;Lee, Su-Dong
    • Transactions of the Korean hydrogen and new energy society
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    • v.15 no.2
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    • pp.159-165
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    • 2004
  • Fuel cell makes electricity through chemical reaction. Bipolar-plate distribute hydrogen, oxidation using channel geometry condensation of water vapor inside channels of bipolar-plates lowers efficiency of fuel cell. Usually high pressured gas supply is used to solve the water condensation problem with serpentine type channel geometry. In this study, a new channel geometry shows feasible to minimize lowering efficiency due to water condensation through numerical and experimental analysis.