• 제목/요약/키워드: $Na^+$ channel

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Requirement of β subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A

  • Na Kyeong Park;Seong Woo Choi;Soon-Jung Park;JooHan Woo;Hyun Jong Kim;Woo Kyung Kim;Sung-Hwan Moon;Hun-Jun Park;Sung Joon Kim
    • The Korean Journal of Physiology and Pharmacology
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    • 제28권4호
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    • pp.313-322
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    • 2024
  • Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the co-expression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.

Triclinic Na3.12Co2.44(P2O7)2 as a High Redox Potential Cathode Material for Na-Ion Batteries

  • Ha, Kwang-Ho;Kwon, Mi-Sook;Lee, Kyu Tae
    • Journal of Electrochemical Science and Technology
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    • 제11권2호
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    • pp.187-194
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    • 2020
  • Two types of sodium cobalt pyrophosphates, triclinic Na3.12Co2.44(P2O7)2 and orthorhombic Na2CoP2O7, are compared as high-voltage cathode materials for Na-ion batteries. Na2CoP2O7 shows no electrochemical activity, delivering negligible capacity. In contrast, Na3.12Co2.44(P2O7)2 exhibits good electrochemical performance, such as high redox potential at ca. 4.3 V (vs. Na/Na+) and stable capacity retention over 50 cycles, although Na3.12Co2.44(P2O7)2 delivered approximately 40 mA h g-1. This is attributed to the fact that Na2CoP2O7 (~3.1 Å) has smaller diffusion channel size than Na3.12Co2.44(P2O7)2 (~4.2 Å). Moreover, the electrochemical performance of Na3.12Co2.44(P2O7)2 is examined using Na cells and Li cells. The overpotential of Na cells is smaller than that of Li cells. This is due to the fact that Na3.12Co2.44(P2O7)2 has a smaller charge transfer resistance and higher diffusivity for Na+ ions than Li+ ions. This implies that the large channel size of Na3.12Co2.44(P2O7)2 is more appropriate for Na+ ions than Li+ ions. Therefore, Na3.12Co2.44(P2O7)2 is considered a promising high-voltage cathode material for Na-ion batteries, if new electrolytes, which are stable above 4.5 V vs. Na/Na+, are introduced.

Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes

  • Youm, Jae-Boum;Leem, Chae-Hun;Zhang, Yin Hua;Kim, Na-Ri;Han, Jin;Earm, Yung-E.
    • The Korean Journal of Physiology and Pharmacology
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    • 제12권5호
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    • pp.267-274
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    • 2008
  • Since first discovered in chick skeletal muscles, stretch-activated channels (SACs) have been proposed as a probable mechano-transducer of the mechanical stimulus at the cellular level. Channel properties have been studied in both the single-channel and the whole-cell level. There is growing evidence to indicate that major stretch-induced changes in electrical activity are mediated by activation of these channels. We aimed to investigate the mechanism of stretch-induced automaticity by exploiting a recent mathematical model of rat atrial myocytes which had been established to reproduce cellular activities such as the action potential, $Ca^{2+}$ transients, and contractile force. The incorporation of SACs into the mathematical model, based on experimental results, successfully reproduced the repetitive firing of spontaneous action potentials by stretch. The induced automaticity was composed of two phases. The early phase was driven by increased background conductance of voltage-gated $Na^+$ channel, whereas the later phase was driven by the reverse-mode operation of $Na^+/Ca^{2+}$ exchange current secondary to the accumulation of $Na^+$ and $Ca^{2+}$ through SACs. These results of simulation successfully demonstrate how the SACs can induce automaticity in a single atrial myocyte which may act as a focus to initiate and maintain atrial fibrillation in concert with other arrhythmogenic changes in the heart.

Effects of ${\alpha}_1-Adrenergic$ Stimulation on Contractility and Intracellular $Na^+$ Activity of Guinea Pig Ventricular Muscles (기니픽 심근의 수축력과 세포내 $Na^+$ 활성도에 미치는 ${\alpha}_1-Adrenergic$ 수용체 자극효과)

  • Kim, Jin-Sang;Kang, Hyung-Sub;Chae, Soo-Wan;Lee, Chin-Ok
    • The Korean Journal of Pharmacology
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    • 제32권2호
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    • pp.189-199
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    • 1996
  • Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

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Evaluation of an Efficient Channel Estimator for the STTD Schemes

  • Kim, Seong-Hwan;Na, Cheol-Hun;Ryoo, Sang-Jin;Hwang, In-Tae
    • Journal of information and communication convergence engineering
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    • 제5권3호
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    • pp.185-193
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    • 2007
  • This paper evaluates the performance combining space-time transmit diversity (STTD) and an efficient channel estimator (ECE) for wideband code division multiple access (WCDMA) systems in various mobile channels. Using decision variable (DV), we also derive the analytic bit error rate (BER) and mean square error (MSE) for WCDMA applying ECE for STTD schemes. The simulation results show that the ECE performance is superior to the previous works in [1] as because we use additional pilot diversity which is so called secondary common control physical channel (S-CCPCH). The performance in case of the channel estimator using only one-channel or two-channel is worse than that of an ECE as about the maximum 4 dB at BER 1.0E-3 satisfying voice service over Rician fading channel. Our results show that, even with ICE, an ECE algorithm are effective in improving the output SNR and significantly reduce the error floor. In addition, the simulation results investigated in this paper also reveal that WCDMA combining an ECE and the STTD scheme could provide appreciable performance improvements in Rayleigh fading channel.

Characterization of an Ion Channel Prepared from Tomato Roots and Inhibitory Effects by Heavy Metal Ions (토마토 뿌리조직에서 분리한 이온채널의 중금속에 의한 저해)

  • Shin, Dae-Seop;Han, Min-Woo;Kim, Young-Kee
    • Applied Biological Chemistry
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    • 제47권4호
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    • pp.390-395
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    • 2004
  • In order to characterize ion channels present in tomato roots, microsomes were incorporated into an artificial lipid bilayer arranged for electrophysiological analysis. Of the five different ion channels that could be found, a channel of 450 pS conductance was found most frequently. This channel displayed subconductance states of 450, 257 and 105 pS. All subconductance states showed linear current-voltage relationships. At positive holding potentials, high frequency of transient channel openings was observed; however, at negative potentials, the open times were long and open probability high. Po was 0.83 at -40 mV. When an additional 50 mM $K^+\;or\;Na^+$ was added to the cis side of bilayer, the reversal potentials shifted in the negative direction to near -10 mV. Thus, the 450 pS cation channel selects poorly between $K^+\;and\;Na^+$. In the presence of $100\;{\mu}M$ metal ions, the channel activity was severely inhibited by $La^{3+},\;Ba^{2+},\;and\;Zn^{2+}$, and Po was decreased to 0.2 or even less. However, $Al^{3+}\;and\;Cd^{2+}$ decreased the activity by only 20%. Interestingly, each metal ion showed different kinetics of channel inhibition. While $500\;{\mu}M\;La^{3+}$ inhibited the activities of all subconductance state, 1 mM $Zn^{2+}$ inhibited all except the 105 pS state. $Cd^{2+}$ changed the gating of the channel from a long-opening state to brief transient openings even at negative holding potentials. These data represent that the metal ions may have different binding sites on the channel protein and could be useful modulators and probes to investigate structural characteristics as well as the functional roles of the 450 pS channel on the root physiology.

Dependence of Na+ leakage on intrinsic properties of cation exchange resin in simulated secondary environment for nuclear power plants

  • Hyun Kyoung Ahn;Chi Hyun An;Byung Gi Park;In Hyoung Rhee
    • Nuclear Engineering and Technology
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    • 제55권2호
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    • pp.640-647
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    • 2023
  • Material corrosion in nuclear power plant (NPP) is not controlled only by amine injection but also by ion exchange (IX) which is the best option to remove trace Na+. This study was conducted to understand the Na+ leakage characteristics of IX beds packed with ethanolamine-form (ETAH-form) and hydrogen-form (H-form) resins in the simulated water-steam cycle in terms of intrinsic behaviors of four kinds of cation-exchange resins through ASTM test and Vanselow mass action modeling. Na+ was inappreciably escaped throughout the channel created in resin layer. Na+ leakage from IX bed was non-linearly raised because of its decreasing selectivity with increasing Na+ capture and with increasing the fraction of ETAH-form resin. Na+ did not reach the breakthrough earlier than ETAH+ and NH4+ due to the increased selectivity of Na+ to the cation-exchange resin (H+ < ETAH+ < NH4+ ≪ Na+) at the feed composition. Na+ leakage from the resin bed filled with small particles was decreased due to the enhanced dynamic IX processes, regardless of its low selectivity. Thus, the particle size is a predominant factor among intrinsic properties of IX resin to reduce Na+ leakage from the condensate polishing plant (CPP) in NPPs.

The Shaker Type Potassium Channel, GORK, Regulates Abscisic Acid Signaling in Arabidopsis

  • Lim, Chae Woo;Kim, Sang Hee;Choi, Hyong Woo;Luan, Sheng;Lee, Sung Chul
    • The Plant Pathology Journal
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    • 제35권6호
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    • pp.684-691
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    • 2019
  • Evolution of adaptive mechanisms to abiotic stress is essential for plant growth and development. Plants adapt to stress conditions by activating the abscisic acid (ABA) signaling pathway. It has been suggested that the ABA receptor, clade A protein phosphatase, SnRK2 type kinase, and SLAC1 anion channel are important components of the ABA signaling pathway. In this study, we report that the shaker type potassium (K+) channel, GORK, modulates plant responses to ABA and abiotic stresses. Our results indicate that the full length of PP2CA is needed to interact with the GORK C-terminal region. We identified a loss of function allele in gork that displayed ABA-hyposensitive phenotype. gork and pp2ca mutants showed opposite responses to ABA in seed germination and seedling growth. Additionally, gork mutant was tolerant to the NaCl and mannitol treatments, whereas pp2ca mutant was sensitive to the NaCl and mannitol treatments. Thus, our results indicate that GORK enhances the sensitivity to ABA and negatively regulates the mechanisms involved in high salinity and osmotic stresses via PP2CA-mediated signals.