• Title/Summary/Keyword: Ion channels

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[$Ca^{2+}$ Signalling in Endothelial Cells: Role of Ion Channels

  • Nilius, Bernd;Viana, Felix;Kamouchi, Masahiro;Fasolato, Cristina;Eggermont, Jan;Droogmans, Guy
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.133-145
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    • 1998
  • $Ca^{2+}-signals$ in endothelial cells are determined by release from intracellular stores and entry through the plasma membrane. In this review, the nature of $Ca^{2+}$ entry and mechanisms of its control are reviewed. The following ion channels play a pivotal role in regulation of the driving force for $Ca^{2+}$ entry: an inwardly rectifying $K^+$ channel, identified as Kir2.1, a big-conductance, $Ca^{2+}-activated$ $K^+$ channel (hslo) and at least two $Cl^-$ channels (a volume regulated $Cl^-$ channel, VRAC, and a $Ca^{2+}$ activated $Cl^-$ channel, CaCC). At least two different types of $Ca^{2+}$-entry channels exist: 1. A typical CRAC-like, highly selective $Ca^{2+}$ channel is described. Current density for this $Ca^{2+}$ entry is approximately 0.1pA/pF at 0 mV and thus 10 times smaller than in Jurkat or mast cells. 2. Another entry pathway for $Ca^{2+}$ entry is a more non-selective channel, which might be regulated by intracellular $Ca^{2+}$. Although detected in endothelial cells, the functional role of trp1,3,4 as possible channel proteins is unclear. Expression of trp3 in macrovascular endothelial cells from bovine pulmonary artery induced non-selective cation channels which are probably not store operated or failed to induce any current. Several features as well as a characterisation of $Ca^{2+}$-oscillations in endothelial cells is also presented.

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Antidepressant drug paroxetine blocks the open pore of Kv3.1 potassium channel

  • Lee, Hyang Mi;Chai, Ok Hee;Hahn, Sang June;Choi, Bok Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.1
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    • pp.71-80
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    • 2018
  • In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to high-frequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an $IC_{50}$ value of $9.43{\mu}M$ and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding ($k_{+1}$) and unbinding ($k_{-1}$) rate constants for the paroxetine effect were $4.5{\mu}M^{-1}s^{-1}$ and $35.8s^{-1}$, respectively, yielding a calculated $K_D$ value of $7.9{\mu}M$. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a use-dependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.

Influence of $1{\alpha}$, 25-dihydroxyvitamin $D_3$ [1, $25(OH)_2D_3$] on the expression of Sox 9 and the transient receptor potential vanilloid 5/6 ion channels in equine articular chondrocytes

  • Hdud, Ismail M.;Loughna, Paul T.
    • Journal of Animal Science and Technology
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    • v.56 no.8
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    • pp.33.1-33.8
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    • 2014
  • Background: Sox 9 is a major marker of chondrocyte differentiation. When chondrocytes are cultured in vitro they progressively de-differentiate and this is associated with a decline in Sox 9 expression. The active form of vitamin D, 1, 25 $(OH)_2D_3$ has been shown to be protective of cartilage in both humans and animals. In this study equine articular chondrocytes were grown in culture and the effects of 1, 25 $(OH)_2D_3$ upon Sox 9 expression examined. The expression of the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine chondrocytes in vitro, we have previously shown, is inversely correlated with de-differentiation. The expression of these channels in response to 1, 25 $(OH)_2D_3$ administration was therefore also examined. Results: The active form of vitamin D (1, 25 $(OH)_2D_3$ when administered to cultured equine chondrocytes at two different concentrations significantly increased the expression of Sox 9 at both. In contrast 1, 25 $(OH)_2D_3$ had no significant effect upon the expression of either TRPV 5 or 6 at either the protein or the mRNA level. Conclusions: The increased expression of Sox 9, in equine articular chondrocytes in vitro, in response to the active form of vitamin D suggests that this compound could be utilized to inhibit the progressive de-differentiation that is normally observed in these cells. It is also supportive of previous studies indicating that $1{\alpha}$, 25-dihydroxyvitamin $D_3$ can have a protective effect upon cartilage in animals in vivo. The previously observed correlation between the degree of differentiation and the expression levels of TRPV 5/6 had suggested that these ion channels may have a direct involvement in, or be modulated by, the differentiation process in vitro. The data in the present study do not support this.

Hydrophobicity and Nanotribological Properties of Silicon Channels coated by Diamond-like Carbon Films

  • Pham, Duc Cuong;Na, Kyung-Hwan;Pham, Van Hung;Yoon, Eui-Sung
    • KSTLE International Journal
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    • v.10 no.1_2
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    • pp.1-5
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    • 2009
  • This paper reports an investigation on nanotribological properties of silicon nanochannels coated by a diamond-like carbon (DLC) film. The nanochannels were fabricated on Si (100) wafers by using photolithography and reactive ion etching (RIE) techniques. The channeled surfaces (Si channels) were then further modified by coating thin DLC film. Water contact angle of the modified and unmodified Si surfaces was examined by an anglemeter using the sessile-drop method. Nanotribological properties, namely friction and adhesion forces, of the Si channels coated with DLC (DLC-coated Si channels) were investigated in comparison with those of the flat Si, DLC-coated flat Si (flat DLC), and Si channels, using an atomic force microscope (AFM). Results showed that the DLC-coated Si channels greatly increased hydrophobicity of silicon surfaces. The DLC coating and Si channels themselves individually reduced adhesion and friction forces of the flat Si. Further, the DLC-coated Si channels exhibited the lowest values of these forces, owing to the combined effect of reduced contact area through the channeling and low surface energy of the DLC. This combined modification could prove a promising method for tribological applications at small scales.

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.

Effect of Propofol on Ion Channels in Acutely Dissociated Dorsal Raphe Neuron of Sprague-Dawley Rats

  • Lee, Bong-Jae;Kwon, Moo-ll;Shin, Min-Chul;Kim, Youn-Jung;Kim, Chang-Ju;Kim, Soon-Ae;Kim, Ee-Hwa;Chung, Joo-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.2
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    • pp.189-197
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    • 2001
  • To investigate propofol's effects on ionic currents induced by ${\gamma}-aminobutyric$ acid (GABA) and glycine as well as on those produced by the nicotinic acetylcholine- and glutamate-responsive channels, rat dorsal raphe neurons were acutely dissociated and the nystatin-perforated patch-clamp technique under voltage-clamp conditions was used to observe their responses to the administration of propofol. Propofol evoked ion currents in a dose-dependent manner, and propofol $(10^{-4}\;M)$ was used to elicit ion currents through the activation of $GABA_A,$ glycine, nicotinic acetylcholine and glutamate receptors. Propofol at a clinically relevant concentration $(10^{-5}\;M)$ potentiated $GABA_A-,$ glycine- and NMDA receptor-mediated currents. The potentiating action of propofol on $GABA_A-,$ glycine- and NMDA receptor-mediated responses involved neither opioid receptors nor G-proteins. Apparently, propofol modulates inhibitory and excitatory neurotransmitter-activated ion channels either by acting directly on the receptors or by potentiating the effects of the neurotransmitters, and this modulation appears to be responsible for the majority of the anaesthetic and/or adverse effects.

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Electroconvective vortex on an Ion Exchange Membrane under Shear Flow (전단흐름 하에 이온교환막 위에서 발생하는 전기수력학적 와류)

  • Kwak, Rhokyun
    • Journal of the Korean Society of Visualization
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    • v.16 no.1
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    • pp.61-69
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    • 2018
  • Ion exchange membrane can transfer only cation or anion in electrically conductive fluids. Recent studies have revealed that such selective ion transport can initiate electroconvective instability, resulting vortical fluid motions on the membrane. This so-called electroconvective vortex (a.k.a. electroconvection (EC)) has been in the spotlight for enhancing an ion flux in electrochemical systems. However, EC under shear flow has not been investigated yet, although most related systems operate under pressure-driven flows. In this study, we present the direct visualization platform of EC under shear flow. On the transparent silicone rubber, microscale channels were fabricated between ion exchange membranes, while allowing microscopic visualization of fluid flow and ion concentration changes on the membranes. By using this platform, not only we visualize the existence of EC under shear flow, its unique characteristics are also identified: i) unidirectional vortex pattern, ii) its advection along the shear flow, and iii) shear-sheltering of EC vortices.