• Title/Summary/Keyword: $K_{2p}$ channels

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Theoretical Studies on Mechanism and Kinetics of the Hydrogen-Abstraction Reaction of CF3CH2CHO with OH Radicals

  • Ci, Cheng-Gang;Yu, Hong-Bo;Wan, Su-Qin;Liu, Jing-Yao;Sun, Chia-Chung
    • Bulletin of the Korean Chemical Society
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    • v.32 no.4
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    • pp.1187-1194
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    • 2011
  • The hydrogen abstraction reaction of $CF_3CH_2CHO$ + OH has been studied theoretically by dual-level direct dynamics method. Two stable conformers, trans- and cis-$CF_3CH_2CHO$, have been located, and there are four distinct OH hydrogen-abstraction channels from t-$CF_3CH_2CHO$ and two channels from c-$CF_3CH_2CHO$. The required potential energy surface information for the kinetic calculation was obtained at the MCG3-MPWB//M06-2X/aug-cc-pVDZ level. The rate constants, which were calculated using improved canonical transitionstate theory with small-curvature tunneling correction (ICVT/SCT) were fitted by a four-parameter Arrhenius equation. It is shown that the reaction proceeds predominantly via the H-abstraction from the -CHO group over the temperature range 200-2000 K. The calculated rate constants were in good agreement with the experimental data between 263 and 358 K.

Purinoceptor and Intracellular $Ca^{2+}$ Regulation in Rat Prostate N euronencocrine Cells

  • Kim, Jun-Hee;Nam, Joo-Hyun;Uhm, Dae-Yong;Kim, Sung-Joon
    • Proceedings of the Korean Biophysical Society Conference
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    • 2002.06b
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    • pp.45-45
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    • 2002
  • Extracellular ATP regulates a wide range of cellular function including the growth of prostate gland. Purinoceptors (ATP receptors) are divided into P2X (ligand-gated ion channels) and P2Y (G-protein-coupled receptor) subfamilies. In the present study, we investigated the types of purinoceptors in rat prostate neuroendocrine (RPNE) cells using whole-cell patch clamp technique, intracellular $Ca^{2+}$ measurement and RT-PCR analysis.(omitted)d)

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Syntheses and Structures of Two Reduced Open-framework Titanophosphates

  • Zhao, Yongnan;Yu, Jianguo;Kwon, Young-Uk
    • Bulletin of the Korean Chemical Society
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    • v.29 no.4
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    • pp.805-810
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    • 2008
  • Using metallic Ti powder as raw materials and 1,2-diaminocyclohexane (DACH) as the trial template, two novel reduced titanophosphate open-structures were hydrothermally isolated by varying the $H_3PO_4/H_2O$ ratio to adjust the pH value. TiPO-1 crystallizes in orthorhombic Pbca space group with cell parameters a = 21.956(3) $\AA$, b = 8.6268(11) $\AA$, c = 7.2883(9) $\AA$, V = 1380.5(3) $\AA^3$, Z = 4. TiPO-2 crystallizes in triclinic space group P$\bar{1}$ with parameters a = 5.1620(10) $\AA$, b = 8.815(2) $\AA$, c = 10.655(3) $\AA$, $\alpha$ = $99.45^{\circ}$, $\beta$ = $102.94^{\circ}$, $\gamma$ = $91.06^{\circ}$, V = 465.34 $\AA^3$. TiPO-1 is constructed by infinite -Ti-O-Ti-O- linkage that is capped by $PO_4$ groups to form a chain structure with protonated DACH molecules occupying the interchain spaces. TiPO-2 represents a rare 3-D reduced titanophosphate with 12-MR channels. The structure of TiPO-2 is a neutral framework with water molecules located in the channels.

The TREK2 Channel Is Involved in the Proliferation of 253J Cell, a Human Bladder Carcinoma Cell

  • Park, Kyung-Sun;Han, Min Ho;Jang, Hee Kyung;Kim, Kyung-A;Cha, Eun-Jong;Kim, Wun-Jae;Choi, Yung Hyun;Kim, Yangmi
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.6
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    • pp.511-516
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    • 2013
  • Bladder cancer is the seventh most common cancer in men that smoke, and the incidence of disease increases with age. The mechanism of occurrence has not yet been established. Potassium channels have been linked with cell proliferation. Some two-pore domain $K^+$ channels (K2P), such as TASK3 and TREK1, have recently been shown to be overexpressed in cancer cells. Here we focused on the relationship between cell growth and the mechanosensitive K2P channel, TREK2, in the human bladder cancer cell line, 253J. We confirmed that TREK2 was expressed in bladder cancer cell lines by Western blot and quantitative real-time PCR. Using the patch-clamp technique, the mechanosensitive TREK2 channel was recorded in the presence of symmetrical 150 mM KCl solutions. In 253J cells, the TREK2 channel was activated by polyunsaturated fatty acids, intracellular acidosis at -60 mV and mechanical stretch at -40 mV or 40 mV. Furthermore, small interfering RNA (siRNA)-mediated TREK2 knockdown resulted in a slight depolarization from $-19.9mV{\pm}0.8$ (n=116) to $-8.5mV{\pm}1.4$ (n=74) and decreased proliferation of 253J cells, compared to negative control siRNA. 253J cells treated with TREK2 siRNA showed a significant increase in the expression of cell cycle boundary proteins p21 and p53 and also a remarkable decrease in protein expression of cyclins D1 and D3. Taken together, the TREK2 channel is present in bladder cancer cell lines and may, at least in part, contribute to cell cycle-dependent growth.

Eugenol Inhibits ATP-induced P2X Currents in Trigeminal Ganglion Neurons

  • Li, Hai Ying;Lee, Byung-Ky;Kim, Joong-Soo;Jung, Sung-Jun;Oh, Seog-Bae
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.6
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    • pp.315-321
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    • 2008
  • Eugenol is widely used in dentistry to relieve pain. We have recently demonstrated voltage-gated $Na^+$ and $Ca^{2+}$ channels as molecular targets for its analgesic effects, and hypothesized that eugenol acts on $P2X_3$, another pain receptor expressed in trigeminal ganglion (TG), and tested the effects of eugenol by whole-cell patch clamp and $Ca^{2+}$ imaging techniques. In the present study, we investigated whether eugenol would modulate 5'-triphosphate (ATP)-induced currents in rat TG neurons and $P2X_3$-expressing human embryonic kidney (HEK) 293 cells. ATP-induced currents in TG neurons exhibited electrophysiological properties similar to those in HEK293 cells, and both ATP- and $\alpha$, $\beta$-meATP-induced currents in TG neurons were effectively blocked by TNP-ATP, suggesting that $P2X_3$ mediates the majority of ATP-induced currents in TG neurons. Eugenol inhibited ATP-induced currents in both capsaicin-sensitive and capsaicin-insensitive TG neurons with similar extent, and most ATP-responsive neurons were IB4-positive. Eugenol inhibited not only $Ca^{2+}$ transients evoked by $\alpha$, $\beta$-meATP, the selective $P2X_3$ agonist, in capsaicin-insensitive TG neurons, but also ATP-induced currents in $P2X_3$-expressing HEK293 cells without co-expression of transient receptor potential vanilloid 1 (TRPV1). We suggest, therefore, that eugenol inhibits $P2X_3$ currents in a TRPV1-independent manner, which contributes to its analgesic effect.

Effects of green tea or $Sasa$ $quelpaertensis$ bamboo leaves on plasma and liver lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats

  • Ryou, Sung-Hee;Kang, Min-Sook;Kim, Kyu-Il;Kang, Young-Hee;Kang, Jung-Sook
    • Nutrition Research and Practice
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    • v.6 no.2
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    • pp.106-112
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    • 2012
  • This study was conducted to investigate the effects of $Sasa$ $quelpaertensis$ bamboo and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX, and ten female rats were sham-operated at the age of 6 weeks. The rats were divided into four groups at the age of 10 weeks and fed the experiment diets: sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%) for four weeks. Final body weight increased significantly in the OVX groups compared with that in the sham-control, whereas body weight in the OVX-green tea group decreased significantly compared with that in the OVX-control ($P$ < 0.01). High density lipoprotein (HDL)-cholesterol level decreased in all OVX groups compared with that in the sham-control rats ($P$ < 0.05) but without a difference in plasma total cholesterol. Plasma triglycerides in the OVX-green tea group were significantly lower than those in the sham-control or OVX-control group ($P$ < 0.05). Liver triglycerides increased significantly in the OVX-control compared with those in the sham-control ($P$ < 0.01) but decreased significantly in the OVX-green tea group compared with those in the OVX-control or OVX-bamboo group ($P$ < 0.01). Platelet aggregation in both maximum and initial slope tended to be lower in all OVX rats compared with that in the sham-control rats but was not significantly different. Na-K ATPase tended to increase and Na-K cotransport tended to decrease following ovariectomy. Na-K ATPase decreased significantly in the OVX-green tea group compared with that in the OVX-control group ($P$ < 0.01), and Na-K cotransport increased significantly in the OVX-bamboo and OVX-green tea groups compared with that in the OVX-control ($P$ < 0.05). Femoral bone mineral density tended to be lower in OVX rats than that in the sham-control, whereas the green tea and bamboo leaves groups recovered bone density to some extent. The results show that ovariectomy caused an increase in body weight and liver triglycerides, and that green tea was effective for lowering body weight and triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption of green tea and bamboo leaves affected Na efflux channels, controlling electrolyte and body water balance.

Caffeine and 2-Aminoethoxydiphenyl Borate (2-APB) Have Different Ability to Inhibit Intracellular Calcium Mobilization in Pancreatic Acinar Cell

  • Choi, Kyung-Jin;Kim, Kab-Sung;Kim, Se-Hoon;Kim, Dong-Kwan;Park, Hyung-Seo
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.2
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    • pp.105-111
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    • 2010
  • Inositol 1,4,5-trisphosphate receptors ($InsP_3Rs$) modulate $Ca^{2+}$ release from intracellular $Ca^{2+}$ store and are extensively expressed in the membrane of endoplasmic/sarcoplasmic reticulum and Golgi. Although caffeine and 2-aminoethoxydiphenyl borate (2-APB) have been widely used to block $InsP_3Rs$, the use of these is limited due to their multiple actions. In the present study, we examined and compared the ability of caffeine and 2-APB as a blocker of $Ca^{2+}$ release from intracellular $Ca^{2+}$ stores and $Ca^{2+}$ entry through store-operated $Ca^{2+}$ (SOC) channel in the mouse pancreatic acinar cell. Caffeine did not block the $Ca^{2+}$ entry, but significantly inhibited carbamylcholine (CCh)-induced $Ca^{2+}$ release. In contrast, 2-APB did not block CCh-induced $Ca^{2+}$ release, but remarkably blocked SOC-mediated $Ca^{2+}$ entry at lower concentrations. In permeabilized acinar cell, caffeine had an inhibitory effect on InsP3-induced $Ca^{2+}$ release, but 2-APB at lower concentration, which effectively blocked $Ca^{2+}$ entry, had no inhibitory action. At higher concentrations, 2-APB has multiple paradoxical effects including inhibition of Ins$P_3$-induced $Ca^{2+}$ release and direct stimulation of $Ca^{2+}$ release. Based on the results, we concluded that caffeine is useful as an inhibitor of $InsP_3R$, and 2-APB at lower concentration is considered a blocker of $Ca^{2+}$ entry through SOC channels in the pancreatic acinar cell.

Hypokalemic periodic paralysis: two different genes responsible for similar clinical manifestations

  • Kim, Hun-Min;Hwang, Hee;Cheong, Hae-Il;Park, Hye-Won
    • Clinical and Experimental Pediatrics
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    • v.54 no.11
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    • pp.473-476
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    • 2011
  • Primary hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder manifesting as recurrent periodic flaccid paralysis and concomitant hypokalemia. HOKPP is divided into type 1 and type 2 based on the causative gene. Although 2 different ion channels have been identified as the molecular genetic cause of HOKPP, the clinical manifestations between the 2 groups are similar. We report the cases of 2 patients with HOKPP who both presented with typical clinical manifestations, but with mutations in 2 different genes ($CACNA1S$ p.Arg528His and $SCN4A$ p.Arg672His). Despite the similar clinical manifestations, there were differences in the response to acetazolamide treatment between certain genotypes of $SCN4A$ mutations and $CACNA1S$ mutations. We identified p.Arg672His in the $SCN4A$ gene of patient 2 immediately after the first attack through a molecular genetic testing strategy. Molecular genetic diagnosis is important for genetic counseling and selecting preventive treatment.

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.

Effects of Dangkwisoo-San, Ginger and Curcumin on Transient Receptor Potential Melastatin 7 Channels (당귀수산, 생강, 커큐민의 대사성 질환과 관련된 일과성 수용체 전압 이온통로조절에 관한 연구)

  • Kim, Byung Joo
    • Journal of Korean Medicine for Obesity Research
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    • v.18 no.1
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    • pp.10-18
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    • 2018
  • Objectives: Metabolic syndrome is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential (TRP) melastatin 7 (TRPM7) channels have been associated with the development of cardiovascular diseases. The purpose of this study was to investigate the effects of Dangkwisoo-san, ginger and curcumin on TRPM7 channel. Methods: Human embryonic kidney (HEK) 293 cells stably transfected with the TRPM7 expression vectors were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin/streptomycin, $5{\mu}g/mL$ blasticidin, and 0.4 mg/mL zeocin in a humidified 20% $O_2$/10% $CO_2$ atmosphere at $37^{\circ}C$. Whole-cell patch clamp recordings were obtained using an Axopatch 700B amplifier and pClamp v.10.4 software, and signals were digitalized at 5 kHz using Digidata 1422A. Results: Dangkwisoo-san extract (100, 200, 300, 400, and $500{\mu}g/mL$) inhibited the outward and inward TRPM7 whole-cell currents at dose dependent manner and the half maximal inhibitory concentration $(IC)_{50}$ of Dangkwisoo-san was $218.3{\mu}g/mL$. Also, ginger extract (100, 200, 300, 400, and $500{\mu}g/mL$) inhibited the outward and inward of TRPM7 whole-cell currents in a dose dependent manner and the $IC_{50}$ of ginger was $877.2{\mu}g/mL$. However, curcumin had no effects on TRPM7 whole-cell currents. Conclusions: These results suggest that both Dangkwisoo-san and ginger have good roles to inhibit the TRPM7 channel, suggesting that Dangkwisoo-san and ginger are considered one of the candidate agents for the treatment of metabolic syndrome such as cardiovascular disease.