• Archives of Pharmacal Research
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• 제28권4호
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• pp.405-412
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• 2005

A vanilloid receptor (VR1, now known as TRPV1) is an ion channel activated by vanilloids, including capsaicin (CAP) and resiniferatoxin (RTX), which are pungent ingredients of plants. Putative endogenous activators (anandamide and metabolites of arachidonic acid) are weak activators of VR1 compared to capsaicin and RTX, and the concentrations of the physiological condition of those activators are not sufficient to induce significant activation of VR1. One way to overcome the weak activation of endogenous activators would be the sensitization of VR1, with the phosphorylation of the channel being one possibility. The phosphorylation of VR1 by several kinases has been reported, mostly by indirect evidence. Here, using an in vivo phosphorylation method, the VR1 channel was shown to be sensitized by phosphorylation of the channel itself by multiple pathways involving PKA, PKC and acid. Also, in sensitizing VR1, BK appeared to show activation of PKC for the sensitization of VR1 by phosphorylation of the channel.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.1-9
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• 2010

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

• 한국결정학회지
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• 제15권1호
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• pp.5-8
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• 2004

Copper(I) bromide(CuBr) 와 pyrazine($C_4H_4N_2$, pyz)의 수열 반응으로 2차원 배위 고분자 [CuBr(pyz)] (1)이 얻어졌다. X-ray 구조 결정 결과, 고분자 1은 4.0${\times}$5.7 ${\AA}$ 크기를 갖는 직사각형 격자들을 토대로 한 2차원 그물 망 구조를 갖고 있었다. 고분자 1은 b-축 방향으로 통로(channel)를 갖고 있다.

• International Journal of Oral Biology
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• 제40권4호
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• pp.211-216
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• 2015

Nitric Oxide (NO) is an important signaling molecule in the nociceptive process. Our previous study suggested that high concentrations of sodium nitroprusside (SNP), a NO donor, induce a membrane hyperpolarization and outward current through large conductances calcium-activated potassium ($BK_{ca}$) channels in substantia gelatinosa (SG) neurons. In this study, patch clamp recording in spinal slices was used to investigate the sources of $Ca^{2+}$ that induces $Ca^{2+}$-activated potassium currents. Application of SNP induced a membrane hyperpolarization, which was significantly inhibited by hemoglobin and 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO), NO scavengers. SNP-induced hyperpolarization was decreased in the presence of charybdotoxin, a selective $BK_{Ca}$ channel blocker. In addition, SNP-induced response was significantly blocked by pretreatment of thapsigargin which can remove $Ca^{2+}$ in endoplasmic reticulum, and decreased by pretreatment of dentrolene, a ryanodine receptors (RyR) blocker. These data suggested that NO induces a membrane hyperpolarization through $BK_{ca}$ channels, which are activated by intracellular $Ca^{2+}$ increase via activation of RyR of $Ca^{2+}$ stores.

• Korean Chemical Engineering Research
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• 제50권4호
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• pp.738-742
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• 2012

본 연구에서는 알루미나 나노 템플레이트(anodic alumina oxide; AAO)를 이용하여 신속하면서도 효과적으로 나노입자 및 바이오물질을 분리, 농축할 수 있는 나노필터 소자를 개발하였다. 본 연구에서 사용한 나노필터 소자는 유체의 주입 및 흐름이 가능한 미세유체채널(microfluidic channel)을 PDMS에 패터닝하였다. 위아래로 형성된 PDMS 미세유체채널 사이로, 다양한 크기의 나노 다공을 형성하고 있는 AAO 막을 삽입하여 크기에 따른 나노입자 및 바이오 물질을 분리할 수 있었다. 위아래로 PDMS 유체채널과 AAO 분리막을 집적하고, 최종적으로 아크릴레이트 플락스틱(acrylic plastic)으로 전체 소자를 고정하여 나노필터유체소자를 제작하였다. 완성된 나노필터소자를 이용하여 나노입자의 농축효율 및 은나노입자가 뭉쳐져있는 필터존(filtration zone)으로부터 뎅기 바이러스(dengue virus)를 표면증강라만(surface enhanced Raman scattering)분석법에 의해 검출할 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.241-249
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• 2017

Plasma membrane hyperpolarization associated with activation of $Ca^{2+}$-activated $K^+$ channels plays an important role in sperm capacitation during fertilization. Although Slo3 (slowpoke homologue 3), together with the auxiliary ${\gamma}^2$-subunit, LRRC52 (leucine-rich-repeat-containing 52), is known to mediate the pH-sensitive, sperm-specific $K^+$ current KSper in mice, the molecular identity of this channel in human sperm remains controversial. In this study, we tested the classical $BK_{Ca}$ activators, NS1619 and LDD175, on human Slo3, heterologously expressed in HEK293 cells together with its functional interacting ${\gamma}^2$ subunit, hLRRC52. As previously reported, Slo3 $K^+$ current was unaffected by iberiotoxin or 4-aminopyridine, but was inhibited by ~50% by 20 mM TEA. Extracellular alkalinization potentiated hSlo3 $K^+$ current, and internal alkalinization and $Ca^{2+}$ elevation induced a leftward shift its activation voltage. NS1619, which acts intracellularly to modulate hSlo1 gating, attenuated hSlo3 $K^+$ currents, whereas LDD175 increased this current and induced membrane potential hyperpolarization. LDD175-induced potentiation was not associated with a change in the half-activation voltage at different intracellular pHs (pH 7.3 and pH 8.0) in the absence of intracellular $Ca^{2+}$. In contrast, elevation of intracellular $Ca^{2+}$ dramatically enhanced the LDD175-induced leftward shift in the half-activation potential of hSlo3. Therefore, the mechanism of action does not involve pH-dependent modulation of hSlo3 gating; instead, LDD175 may modulate $Ca^{2+}$-dependent activation of hSlo3. Thus, LDD175 potentially activates native KSper and may induce membrane hyperpolarization-associated hyperactivation in human sperm.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2012년도 제42회 동계 정기 학술대회 초록집
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• pp.427-427
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• 2012

Ferroelectric-gate field effect transistor based memory using a nanowire as a conducting channel offers exceptional advantages over conventional memory devices, like small cell size, low-voltage operation, low power consumption, fast programming/erase speed and non-volatility. We successfully fabricated ferroelectric nonvolatile memory devices using both n-type and p-type Si nanowires coated with organic ferroelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] via a low temperature fabrication process. The devices performance was carefully characterized in terms of their electrical transport, retention time and endurance test. Our p-type Si NW ferroelectric memory devices exhibit excellent memory characteristics with a large modulation in channel conductance between ON and OFF states exceeding $10^5$; long retention time of over $5{\times}10^4$ sec and high endurance of over 105 programming cycles while maintaining ON/OFF ratio higher $10^3$. This result offers a viable way to fabricate a high performance high-density nonvolatile memory device using a low temperature fabrication processing technique, which makes it suitable for flexible electronics.

• Bulletin of the Korean Chemical Society
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• 제34권2호
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• pp.482-488
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• 2013

Two piperazine-containing 3,4-dihyroquinazolines (BK10007S/8S) have been synthesized, based on our previous work on the synthesis and antitumoral activity of 3,4-dihyroquinazolines. After evaluating them for T-type calcium channel blocking effect and in vitro anti-cancer effect, they were profiled for acute and repeat dose toxicity (40 mg/kg, 2 weeks) to BALB/c mice. BK10007S/8S were further in vivo evaluated against human pancreatic MIA PaCa-2 carcinoma in $BALB/c^{nu/nu}$ nude mice, which exhibited 54 and 61% tumor growth inhibition through 57-day oral administration of 2 mg/kg of body weight, respectively.

• KSII Transactions on Internet and Information Systems (TIIS)
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• 제16권12호
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• pp.4099-4113
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• 2022

In this paper, we propose improved maximum access delay time, noise variance, and power delay profile (PDP) estimation schemes for orthogonal frequency division multiplexing (OFDM) system in multipath fading channels. To this end, we adopt the approximate maximum likelihood (ML) estimation strategy. For the first step, the log-likelihood function (LLF) of the received OFDM symbols is derived by utilizing only the cyclic redundancy induced by cyclic prefix (CP) without additional information. Then, the set of the initial path powers is sub-optimally obtained to maximize the derived LLF. In the second step, we can select a subset of the initial path power set, i.e. the maximum access delay time, so as to maximize the modified LLF. Through numerical simulations, the benefit of the proposed method is verified by comparison with the existing methods in terms of normalized mean square error, erroneous detection, and good detection probabilities.

• Biomolecules & Therapeutics
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• 제14권4호
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• pp.253-258
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• 2006

LDD175(4-choloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-l-carboxylic acid) is one of benzofuroindole derivatives that act as a potent $BK_{Ca}$ channel openers. In the process of testing LDD175 as a new drug candidate, an acute toxicity study was carried out in mice. The mice were administered LDD175 intraperitoneally at dose of 0.2, 1, 10, 50, 100, 200, 400, 800mg/kg and orally at dose of 10, 100, 400, 800mg/kg body weight. After administering LDD175, the vital organs such as the liver, kidney and spleen were carefully observed for any significant pathological features or differences from the norm over a l4-day period. LDD175 did not induce any short-term toxicity at doses less than 100mg/kg. A $LD_{50}$ of LDD175 was 2493mg/kg in male mice and 4908mg/kg in female mice. Weight reduction was observed at a dose of 800mg/kg in male, and 400 and 800mg/kg in female. The kidney weight decreased in females after an intraperitoneal injection of LDD175 high dose(>400mg/kg, i.p.), and the spleen weight increased in the male(800mg/kg, i.p.) and female(400mg/kg, i.p.) mice. Inspite of the change in organ weights, there were neither histopathological changes nor any gross morphological abnormalities detected in any organ. LDD175 did not produce significant changes in the general behavior at doses of <200mg/kg, but decreased locomotor activity was observed at an intraperitoneal dose of 400mg/kg. Its effects on the locomotor activity and activity on the rotarod were tested and compared with the effects of diazepam 5mg/kg. The decrement in the locomotor activity and the activity on the rotarod induced by LDD175 was less serious than it by diazepam.