• 제목/요약/키워드: Sodium channel

검색결과 144건 처리시간 0.023초

Molecular Mechanism of Action of Local Anesthetics: A Review

  • Yun, Il;Kang, Jung-Sook
    • 생명과학회지
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    • 제2권2호
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    • pp.97-107
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    • 1992
  • 비록 국소마취제가 신경세포막 당단백질중의 하나인 sodium channel과의 직접적인 상호작용에 의하여 그 특유의 국소마취제를 나타낸다고 할지라도 신경세포막의 골격을 형성하고 있는 지질과 국소마취제와의 상호작용을 분자적 국소마취제 작용기전을 설명함에 있어 배제할 수는 없다. 왜냐하면 sodium channel은 지질과의 공유 또는 비공유결합을 통해 단단하게 결합되어 있기 때문이다. 따라서 국소마취제가 직접 sodium channel과 결합, 상호작용하여 Na+의 유입을 차단할 뿐만 아니라 직접 지질의 측방 및 회전확산 운동을 증가시킴으로써 간접적으로 sodium channel의 conformational change가 유발되어 Na+의 유입이 차단되는 등의 복합적인 기전에 의하여 그 특유의 국소마취작용이 나타나는 것이다.

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Paeonol의 잠재적인 항부정맥 효과의 컴퓨터 시뮬레이션 연구 (Computer Simulation Study of the Potential Anti-arrhythmic Properties of Paeonol)

  • 이수진
    • 동의생리병리학회지
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    • 제29권4호
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    • pp.305-312
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    • 2015
  • Paeonol is a major component found in the Paeoniaceae family such as Paeonia suffruticosa Andrews. Paeonia suffruticosa Andrews has traditionally been used to enhance blood flow and relieve joint pain in east Asian countries including China, Korea and Japan. Current research has shown that paeonol blocked the voltage-gated sodium channel and L-type calcium channel. However, there is a lack of research to reveal the relation between cardiac function and blockade of ion channels by paeonol. Therefore, the aim of this study is to investigate whether paeonol has anti-arrhythmic effects via modulating cardiac ion channels. It is collected that the effects of paeonol on multiple ion channels such as the fast sodium channel and L-type calcium channel from published papers. To incorporate the information on multi-channel block, we computed the effects using the mathematical cardiac model of the guinea-pig and rat ventricular cells (Noble 1998 and 1991 model) and induced early after-depolarizations (EADs) to generate an arrhythmia in the whole heart. Paeonol slightly shortened the action potential duration in the normal cardiac ventricular action potential by the inhibition of sodium channel and L-type calcium channel. Paeonol presented the protective effect from EADs by the inactivation of sodium channel but not L-type calcium channel. Paeonol did not show any changes when it treated on normal ventricular cells through the inhibition of sodium channel, but the protective effect of paeonol through sodium channel on EADs was dose-dependent. These findings suggest that paeonol and its original plant may possess anti-arrhythmic activity, which implies their cardioprotective effects.

Application of the H Infinity Control Principle to the Sodium Ion Selective Gating Channel on Biological Excitable Membranes

  • Hirayama, Hirohumi
    • International Journal of Control, Automation, and Systems
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    • 제2권1호
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    • pp.23-38
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    • 2004
  • We proposed the infinity control principle to evaluate the Biological function. The H infinity control was applied to the Sodium (Na) ion selective gating channel on the excitable cellular membrane of the neural system. The channel opening, closing and inactivation processes were expressed by movements of three gates and one inactivation blocking particle in the channel pore. The rate constants of the channel state transition were set to be voltage dependent. The temporal changes in amounts per unit membrane area of the channel states were expressed by means of eight differential equations. The biochemical mimetic used to complete the Na ion selective channel was regarded as noise. The control inputs for ejecting the blocking particle with plugging in the channel pore were set for the active transition from inactivated states to a closed or open state. By applying the H infinity control, we computed temporal changes in the channel states, observers, control inputs and the worst case noises. The present paper will be available for evaluating the noise filtering function of the biological signal transmission system.

Development of Sodium Voiding Model for the KALIMER Analysis

  • Chang, Won-Pyo;Dohee Hahn
    • Nuclear Engineering and Technology
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    • 제34권4호
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    • pp.286-300
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    • 2002
  • An algorithm for the sodium boiling model has been developed for calculation of the void reactivity feedback as well as the fuel and cladding temperatures in the KALIMER core after onset of sodium boiling. Modeling of sodium boiling in liquid metal reactors using sodium as a coolant is necessary because of phenomenon difference comparing with that observed generally in light water reactor systems. The applied model to the algorithm is the multiple-bubble slug ejection model. It allows a finite number of bubbles in a channel at any time. Voiding is assumed to result from formation of bubbies that (ill the whole cross section of the coolant channel except for the liquid film left on the cladding surface. The vapor pressure, currently, is assumed to be uniform within a bubble The present study is focused on not only demonstration of the vapor bubble behavior predicted by the developed model, but also confirmation of a qualitative acceptance for the model. As a result, the model can represent important phenomena in the sodium boiling, but it is found that further effort is also needed for its completition.

An atypical phenotype of hypokalemic periodic paralysis caused by a mutation in the sodium channel gene $SCN4A$

  • Park, Yang-Hee;Kim, June-Bum
    • Clinical and Experimental Pediatrics
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    • 제53권10호
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    • pp.909-912
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    • 2010
  • Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene $SCN4A$, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications.

Tramadol as a Voltage-Gated Sodium Channel Blocker of Peripheral Sodium Channels Nav1.7 and Nav1.5

  • Chan-Su, Bok;Ryeong-Eun, Kim;Yong-Yeon, Cho;Jin-Sung, Choi
    • Biomolecules & Therapeutics
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    • 제31권2호
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    • pp.168-175
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    • 2023
  • Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Nav1.7 or the cardiac sodium channel Nav1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Nav1.7 and 0.43 mM for Nav1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Nav1.7 and Nav1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Nav1.7 and Nav1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Nav1.7 or show cardiotoxicity by blocking Nav1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

Evaluation of thermal-hydraulic performance and economics of Printed Circuit Heat Exchanger (PCHE) for recuperators of Sodium-cooled Fast Reactors (SFRs) using CO2 and N2 as working fluids

  • Lee, Su Won;Shin, Seong Min;Chung, SungKun;Jo, HangJin
    • Nuclear Engineering and Technology
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    • 제54권5호
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    • pp.1874-1889
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    • 2022
  • In this study, we evaluate the thermal-hydraulic performance and economics of Printed Circuit Heat Exchanger (PCHE) according to the channel types and associated shape variables for the design of recuperators with Sodium-cooled Fast Reactors (SFRs). To perform the evaluations with variables such as the Reynolds number, channel types, tube diameter, and shape variables, a code for the heat exchanger is developed and verified through a comparison with experimental results. Based on the code, the volume and pressure drop are calculated, and an economic assessment is conducted. The zigzag type, which has bending angle of 80° and a tube diameter of 1.9 mm, is the most economical channel type in a SFR using CO2 as the working fluid. For a SFR using N2, we recommend the airfoil type with vertical and horizontal numbers of 1.6 and 1.1, respectively. The airfoil type is superior when the mass flow rate is large because the operating cost changes significantly. When the mass flow rate is small, volume is a more important design parameter, therefore, the zigzag type is suitable. In addition, we conduct a sensitivity analysis based on the production cost of the PCHE to identify changes in optimal channel types.

Pancreatic Polypeptide Family의 심혈관계 근육 수축성에 대한 약리학적 작용: I. 개의 뇌혈관에서 cyclic nucleotide활성제와 칼륨통로개방제와의 상호작용 (Effect of Pancreatic Polypeptide Family on Cardiovascular Muscle Contractility: 1. Interactions with cyclic nucleotide activators and $K^+$ channel openers in canine cerebral arteries)

  • 김원준;이광윤;하정희;권오철
    • 대한약리학회지
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    • 제28권2호
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    • pp.147-162
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    • 1992
  • Pancreatic polypeptide family펩타이드들의 뇌혈관 평활근 수축성에 미치는 효과를 관찰하고, cyclic nucleotide 활성제 및 칼륨통로개방제와의 상호작용을 관찰하기 위하여 다음과 같은 실험을 하였다. 체중 $20{\sim}30\;g$의 개를 사혈 희생시켜 두개골을 절개한 후 뇌저동맥과 중뇌동맥을 적출하였다. 적출된 동맥편은 $4^{\circ}C$의 생리적식염수 내에서 나선형 절편으로 만들어 0.3%의 CHAPS 용액에 침잠시킴으로써 내피세포층을 제거한 후 95% $O_2$와 5% $CO_2$의 혼합기체로 포화된 $37^{\circ}C$의 Krebs-Henseleit 용액을 포함한 적출근편실험조에서 등척성 장력을 측정하였다. 1. PP, PYY 및 NPY는 뇌동맥 나선형절편을 농도의존적으로 수축시켰으며, 그 효력과 효능은 PYY가 가장 강하였고, 그 다음이 NPY, 그리고 PP의 순이었다. 이들의 효력은 노르아드레날린보다 20내지 200배 강하였으며, 그 중 PYY는 5-HT 보다도 강한 효력을 보였다. 2. Cyclic AMP 활성제인 forskolin과 cyclic GMP 활성제인 sodium nitroprusside는 뇌동맥절편의 기본장력을 감소시켰으며, PP, PYY 및 NPY 유발수축 역시 농도의존적으로 억제하였다. 이 때 forskolin의 기본장력억제작용이 sodium nitroprusside보다 강한 효력을 나타내었다. 3. 칼륨통로 개방제인 RP 49356, P 1060 및 BRL 38227은 기본장력에 대해서는 공히 농도의존적으로 억제하였으나, PP, PYY 및 NPY 유발수축에 대해서는 P 1060만이 농도의존적으로 억제하였고, RP 49356 및 BRL 38227은 약간 억제하는 경향만을 보였는데, 특기할 것은 저농도의$(0.1\;{\mu}M)$ BRL 38227이 이들 펩타이드 유발수축을 오히려 증가 시켰다는 것이다. 4. 기본장력에 대해서, 칼륨통로개방제들은 forskolin의 이완작용에 유의한 영향을 미치지 못하였으나, 그중 P 1060과 BRL 38227은 sodium nitroprusside의 이완작용을 상승적으로 강화하였다. PYY$(0.1\;{\mu}M)$유발 수축작용에 대해서, 칼륨통로 개방제들은 forskolin의 수축억제작용에 대해서는 약간 길항하는 경향만을 보였고, sodium nitroprusside의 수축억제작용은 유의하게 길항하였다. 이상의 결과들을 종합하면, 개의 뇌혈관에서는 NPY 뿐만 아니라 PYY도 혈관수축기전에 중요한 역할을 한다고 볼 수 있으며, 그 수축작용의 기전에는 세포내 cAMP 및 cGMP 활성도의 변화가 포함된다고 사료된다. 또 칼륨통로개방제들은 pancreatic polypeptide family의 뇌혈관수축작용에 대하여 제제 및 농도에 따라 다양한 영향을 미치므로 이에 대한 향후의 더욱 세밀한 연구가 요구된다.

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기니 픽 장관 평활근에서 Sodium Nitroprusside가 장력에 미치는 영향 (The Eeffect of Sodium Nitroprusside on Muscle Tension in Guinea-pig Ileum)

  • 권성춘;김시연;김은주;강복순
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권6호
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    • pp.797-808
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    • 1997
  • Nitric oxide (NO) has been 3mown as a mediator of nonadrenergic, noncholinergic inhibitory neurotransmitter in intestinal smooth muscles. It has been suggested that NO donor such as sodium nitroprusside (SNP) produces relaxation of smooth muscle via activation of guanylate cyclase and elevation of cGMP levels. We have therefore investigated the effects of NO, using SNP, on muscle tension in the longitudinal smooth muscle of guinea-pig ileum. The possible role of cGMP was also investigated as well as the involvement of $K^+$ channel on SNP-induced inhibitory effect. The results are summarized as follows; high KCI-or CCh-activated contractions were inhibited by SNP in a concentration-dependent manner. 8-Br-cGMP also showed a similar effect in that of SNP TEA (1 mM) significantly reduced the SNP-induced inhibitory effect. SNP-induced effect was forther reduced by the presence of 10 mM TEA. On the other hand, 4-AP (0.1 mM), glibenclamide $(10\;{\mu}M)$ and apinain $(0.1\;{\mu}M)$ showed little effects on SNP-induced relaxation. Zaprinast significantly potentiated the SNP-induced inhibitory effect in all ranges. ODQ also significantly decreased the SNP-induced inhibitory effect. Pretreatment with CPA $(10\;{\mu}M)$ slightly reduced the SNP-induced inhibitory effect. From the above results, both effect mediated by NO and cGMP might be responsible for the activation of $Ca^{2+}$-activated $K^+$ channel by SNP in guinea-rig ileum. And this $K^+$ channel activation by SNP also contributes to the SNP-induced membrane hyperpolarization and relaxation.

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