• Title/Summary/Keyword: Sodium channel

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The Sedative Effects of Ethanol Extract from Cimicifugae Rhizoma (승마 에탄올 추출물의 진정 효과)

  • Choi, Yun-Jung;Yoon, Seo-Young;Choi, Ji-Young;Woo, Tae-Seon;Son, Kun-Ho;Lee, Yong-Soo;Cheong, Jae-Hoon
    • YAKHAK HOEJI
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    • v.55 no.3
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    • pp.213-218
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    • 2011
  • The aim of this study is to evaluate the sedative effects of ethanol extract and the three major constituents of Cimicifugae Rhizoma. They decreased locomotor activity significantly, and enhanced sleeping duration induced by thiopental sodium. The ethanol extract of Cimicifugae rhizoma and 24-epi-7,8-didehydrocimigenol-3-xyloside (24-epi.) increased the $Cl^-$ influx into the intracellular area of SH-SY5Y neuroblastoma cells significantly. The present results demonstrate that the sedative effects of Cimicifugae rhizoma are mediated via the GABA-gated $Cl^-$ channel, partly by 24-epi.

Insecticide Targets: Learning to Keep Up with Resistance and Changing Concepts of Safety

  • Casida, John E.;Quistad, Gary B.
    • Journal of Applied Biological Chemistry
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    • v.43 no.4
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    • pp.185-191
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    • 2000
  • Pest insect control is dependent on about 200 insecticides that work by relatively few mechanisms. The targets they disrupt are mostly involved in the nervous system, respiratory chain, growth and development, or the gut. The major nerve targets are: acetylcholinesterase for the organophosphates and methylcarbamates; the nicotinic acetylcholine receptor for the neonicotinoids; the $\gamma$-aminobutyric acid receptor for several chlorinated hydrocarbons and fipronil; the voltage-gated sodium channel for DDT and pyrethroids. Selection of resistant strains often confers cross-resistance to some or all other insecticides working at the same site. The toxicological properties of different compounds acting on the same target are increasingly considered together, summating the risk even though the compounds are of quite diverse chemical types. Continuing attention is also being given to secondary targets not involved in the primary mechanism of toxicity but instead in side effects that must be considered in the overall safety evaluation. Research on insecticide targets is important in learning to keep up with resistance and changing concepts and policies on safety. These relationships are illustrated by recent studies in the Environmental Chemistry and Toxicology Laboratory of the University of California at Berkeley.

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Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

  • Jin, Yun-Ju;Kim, Jun;Kwak, Ji-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.211-217
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    • 2012
  • Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents ($I_{cap}$). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on $I_{cap}$. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on $I_{cap}$. The PKG inhibitor KT5823 prevented the inhibition of $I_{cap}$ by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

Experimental study of turbulent flow in a scaled RPV model by PIV technology

  • Luguo Liu;Wenhai Qu;Yu Liu;Jinbiao Xiong;Songwei Li;Guangming Jiang
    • Nuclear Engineering and Technology
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    • v.56 no.7
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    • pp.2458-2473
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    • 2024
  • The turbulent flow in reactor pressure vessel (RPV) of pressurized water reactor (PWR) is important for the flow rate distribution at core inlet. Thus, it is vital to study the turbulent flow phenomena in RPV. However, the complicated fluid channel consisted of inner structures of RPV will block or refract the laser sheet of particle image velocimetry (PIV). In this work, the matched index of refraction (MIR) of sodium iodide (NaI) solution and acrylic was applied to support optical path for flow field measurements by PIV in the 1/10th scaled-down RPV model. The experimental results show detailed velocity field at different locations inside the scaled-down RPV model. Some interesting phenomena are obtained, including the non-negligible counterflow at the corner of nozzle edge, the high downward flowing stream in downcomer, large vortices above vortex suppression plate in lower plenum. And the intensity of counterflow and the strength of vortices increase as inlet flow rate increasing. Finally, the case of asymmetry flow was also studied. The turbulent flow has different pattern compared with the case of symmetrical inlet flow rate, which may affect the uniformity of flow distribution at the core inlet.

An Arg1239His mutation of the CACNL1A3 gene in a Korean family with hypokalemic periodic paralysis (가족성 저칼륨성 주기성 마비 1예)

  • Yeo, Chae Young;Kim, Young Ok;Kim, Myeong Kyu;Kim, Ji Youn;Cho, Young Kuk;Kim, Chan Jong;Woo, Young Jong
    • Clinical and Experimental Pediatrics
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    • v.51 no.7
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    • pp.771-774
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    • 2008
  • Familial hypokalemic periodic paralysis (hypoPP) is a rare inherited channelopathy that often presents with episodic weakness accompanied by hypokalemia. Thus far, mutations in the gene encoding two ion channels (CACNL1A3, L-type calcium channel alpha-1 subunit and SCN4A, a sodium channel type IV alpha subunit) have been identified. Several cases of familial hypoPP in children have been reported in Koreans, but there are only a few cases with identified mutations. We report a 12-year-old boy and his affected mother with hypoPP who has a heterozygous G to A substitution at codon 1239 in exon 30 of the CACNL1A3 gene that causes a change from arginine to histidine (Arg1239His, CACNL1A3). This mutation is common among Caucasians; however, it has not yet been reported in Koreans. The patients were treated with oral acetazolamide and potassium replacement and were instructed to avoid precipitating factors. After the medication and lifestyle modification, the paralytic attacks significantly decreased.

The Effects of Magnoliae officinalis Cortex and Machili thunbergii Cortex on Small Intestinal Motility (후박(厚朴)과 토후박(土厚朴)의 소장운동에 미치는 영향에 대한 연구)

  • Lee, Kyung-Jin;Park, Geun-Yong;Park, Gyu-Ha;Liu, Kwang-Hyeon;Kim, Tae-Wan;Ham, In-Hye;Bu, Young-Min;Choi, Ho-Young
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.75-81
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    • 2011
  • Objectives : Magnoliae officinalis Cortex (MOC) has been used in traditional medicine for digestive diseases in Korea, China and Japan. However, Machili thunbergii Cortex (MTC) also has been used as a substitute of MOC in Korea sometimes. Thus, this study was carried out to investigate and compare the effects of MOC and MTC on intestinal motility of isolated small intestinal segments from ICR mouse. Methods : Changes in motility were recorded via isometric transducers connected to a data acquisition system and amplitude, frequency and area under the curve (AUC) of intestinal spontaneous phasic contraction were compared. Results : The MOC extracts ($1{\sim}{\mu}g/mL$) dose-dependently decreased both amplitudes and frequencies of the spontaneous phasic contraction, but not AUC. However, high concentration of MOC (100 ${\mu}g$/mL) evoked tonic contraction. And it was not inhibited by tetrodotoxin, a sodium channel blocker, and nifedipine, a L-type $Ca^{2+}$ channel antagonist. These results suggested that MOC (100 ${\mu}g$/mL)-induced tonic contraction is not mediated by nerve or L-type $Ca^{2+}$ channel. On the other hand, the MTC extracts dose-dependently inhibited amplitude and AUC, but not the frequency. Conclusions : Although both MOC and MTC affected intestinal motility, MOC is more effective on intestinal motility than MTC. And MOC has been used as a traditional medicine for a long time but not MTC. Thus, we suggested that MTC should not be used in Korea as a substitute of MOC and MOC might be useful traditional medicine for gastrointestinal disease. The mechanism of MOC is still remained to elucidate.

Effect of Thyroid Hormone on the Electrical Activity of Rabbit Heart (토끼심장의 전기적 활동에 대한 갑상선 호르몬의 영향)

  • Hong, Seong-Geun;Kwun, Jong-Kuk;Chung, Soon-Il
    • The Korean Journal of Physiology
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    • v.20 no.1
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    • pp.17-29
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    • 1986
  • The present study was carried out to observe the effect of triiodothyronine on heart, one of the target organ of thyroid hormone. There are many reports that tachycardia, arrythmia, and agumentation of sodium, potassium pump activity are caused in hyperthyroid animal. To examine these cardiac positive chronotropic effects on sinoatrial (SA) node and atrial muscle, hyperthyroid state was induced experimentally by the injecion of 3,3',5-1-triiodothyronine $(T_3)$ in $3{\sim}6$ month-old rabbits. Then intracellular recordings by inserting glass microelectrode into cell were obtained in SA node and atrial muscle. The results can be summarized as follows : 1) Heartbeat was increased from $169.6{\pm}28.0\;to\;264.2{\pm}18.0$ beats per minute, while body weight was decreased to 68f of the initial body weight (Day 1). 2) In experimental group, the duration of action potential at 80% repolarization was decreased from $148.0{\pm}29.1\;to\;107{\pm}13.6msec$. This suggested the increase heartbeat. 3) The firing rate in hyperthyroid group markedly reduced under the 15 mM potassium Tyrode (p<0.005). 4) In hyperthyroid group, depolarization of atrial muscle cell was lowered significantly in 15 mM (p<0.05), 20 mM (p<0.05) potassium Tyrode solution. 5) Sodium-potassium pump activities in experimental group were higher than those in control group in both SA node (p<0. 1) and atrial muscle (p<0.025). 6) In lower concentration of $MnCl_2$, the excitability of SA node in hyperthyroid group was decreased more than that in control group. Effective inhibitory dose $(ID_{50})$ as 0.6 mM in hyperthyroid statd and 1.1 mM in control group.

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The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

  • Parajuli, Shankar Prasad;Choi, Seok;Lee, Jun;Kim, Young-Dae;Park, Chan-Guk;Kim, Man-Yoo;Kim, Hyun-Il;Yeum, Cheol-Ho;Jun, Jae-Yeoul
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.2
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    • pp.83-89
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    • 2010
  • In this study, we studied whether hydrogen sulfide ($H_2S$) has an effect on the pacemaker activity of interstitial cells of Cajal (ICC), in the small intestine of mice. The actions of $H_2S$ on pacemaker activity were investigated using whole-cell patch-clamp technique, intracellular $Ca^{2+}$ analysis at $30^{\circ}C$ and RT-PCR in cultured mouse intestinal ICC. Exogenously applied sodium hydrogen sulfide (NaHS), a donor of hydrogen sulfide, caused a slight tonic inward current on pacemaker activity in ICC at low concentrations (50 and $100{\mu}m$), but at high concentration ($500{\mu}m$ and 1 mM) it seemed to cause light tonic inward currents and then inhibited pacemaker amplitude and pacemaker frequency, and also an increase in the resting currents in the outward direction. Glibenclamide or other potassium channel blockers (TEA, $BaCl_2$, apamin or 4-aminopydirine) did not have an effect on NaHS-induced action in ICC. The exogenous application of carbonilcyanide p-triflouromethoxyphenylhydrazone (FCCP) and thapsigargin also inhibited the pacemaker activity of ICC as NaHS. Also, we found NaHS inhibited the spontaneous intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) oscillations in cultured ICC. In doing an RT-PCR experiment, we found that ICC enriched population lacked mRNA for both CSE and CBS, but was prominently detected in unsorted muscle. In conclusion, $H_2S$ inhibited the pacemaker activity of ICC by modulating intracellular $Ca^{2+}$. These results can serve as evidence of the physiological action of $H_2S$ as acting on the ICC in gastrointestinal (GI) motility.

$Ca^{2+}$ is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line

  • Park, Soonhong;Ku, Sang Kyun;Ji, Hye Won;Choi, Jong-Hoon;Shin, Dong Min
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.249-255
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    • 2015
  • Wnk kinase maintains cell volume, regulating various transporters such as sodium-chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium-chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and specific conditions is broadly unclear. In the present study, we used a human salivary gland (HSG) cell line as a model and showed that $Ca^{2+}$ may have a role in regulating Wnk kinase in the HSG cell line. Through this study, we found that the HSG cell line expressed molecules participating in the WNK-OSR1-NKCC pathway, such as Wnk1, Wnk4, OSR1, SPAK, and NKCC1. The HSG cell line showed an intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increase in response to hypotonic stimulation, and the response was synchronized with the phosphorylation of OSR1. Interestingly, when we inhibited the hypotonically induced $[Ca^{2+}]_i$ increase with nonspecific $Ca^{2+}$ channel blockers such as 2-aminoethoxydiphenyl borate, gadolinium, and lanthanum, the phosphorylated OSR1 level was also diminished. Moreover, a cyclopiazonic acid-induced passive $[Ca^{2+}]_i$ elevation was evoked by the phosphorylation of OSR1, and the amount of phosphorylated OSR1 decreased when the cells were treated with BAPTA, a $Ca^{2+}$ chelator. Finally, through that process, NKCC1 activity also decreased to maintain the cell volume in the HSG cell line. These results indicate that $Ca^{2+}$ may regulate the WNK-OSR1 pathway and NKCC1 activity in the HSG cell line. This is the first demonstration that indicates upstream $Ca^{2+}$ regulation of the WNK-OSR1 pathway in intact cells.

Dose-Related Prolongation of Ropivacaine Epidural Anesthesia by Epidural Ketamine (로피바카인 경막외 마취 시 케타민첨가 용량에 따른 마취시간의 연장)

  • Joo, Jin Deok;Jeon, Yeon Su;Choi, Jin Woo;In, Jang Hyeok;Kim, Yong Shin;Kang, Yoo Jin;Kim, Dae Woo;Lim, Yong Gul;Kim, Ghi Hyun
    • The Korean Journal of Pain
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    • v.18 no.1
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    • pp.39-42
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    • 2005
  • Background: Besides its general anesthetic effect, ketamine interacts with sodium channels in a local anesthetic-like fashion, including the sharing of binding sites with those commonly used by clinical local anesthetics. This study evaluated the dose related effects of ketamine during epidural anesthesia with 0.5% ropivacaine. Methods: Sixty ASA physical status I II patients, scheduled for minor elective surgery under epidural anesthesia using 0.5% ropivacaine, were randomly divided into three groups (n = 20 each). The patients initially received either 0.5% ropivacaine (group 1), ketamine (0.1 mg/kg) in addition to the epidural 0.5% ropivacaine (group 2) or ketamine (0.2 mg/kg) in addition to the epidural 0.5% ropivacaine (group 3). The regression of sensory block was assessed by transcutaneous electric stimulation (TES), equivalent to a surgical incision. Motor block was assessed using the Modified Bromage's scale. Episodes of bradycardia, hypotension and sedation were also recorded. Results: There were no significant differences among the three groups in the maximal levels of sensory block or the times taken for these levels to be reached. The mean times for the block to regress to two and four segments below the maximal level were significantly prolonged by epidural ketamine. Conclusions: Epidural ketamine prolongs the duration of ropivacaine epidural anesthesia. These results suggest that ketamine has local anesthetic-like actions.