• Title/Summary/Keyword: sodium channel

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Molecular Mechanism of Action of Local Anesthetics: A Review

  • Yun, Il;Kang, Jung-Sook
    • Journal of Life Science
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    • v.2 no.2
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    • pp.97-107
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    • 1992
  • Strichartz and Richie have suggested that the mechanism of sodium donductance block of local anesthetics involves their interaction with a specific binding site within the sodium channel. However, there is evidence that local anesthetics can interact electrostatically with membrane proteins as well as membrane lipids. Whether or not all actions of local anesthetics are mediated by common site remains unclear. Thus, it can not be ruled out that local anesthetics concurrently interact with neuronal membrane lipids since sodium channels were found to be tightly associated with membrane lipids through covalent or noncovalent bonds. In summary, it is strongly postulated that local anesthetics, in addition to their direct interaction with sodium channels, concurrently interact with membrane lipids, fluidize the membrane, and thus induce conformational changes of sodium channels, which are known to be tightly associated with membrane lipids.

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

  • Lee, Soojin
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.29 no.4
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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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    • v.2 no.1
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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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    • v.34 no.4
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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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    • v.53 no.10
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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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    • v.31 no.2
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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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    • v.54 no.5
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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.

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

  • Kim, Won-Joon;Lee, Kwang-Youn;Ha, Jeoung-Hee;Kwon, Oh-Cheol
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.147-162
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    • 1992
  • The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.

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

  • Kwon, Seong-Chun;Kim, Si-Yeon;Kim, Eun-Ju;Kang, Bok-Soon
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.6
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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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