• 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.

• BMB Reports
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• v.43 no.11
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• pp.756-760
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• 2010

Recent studies have reported that delayed-rectifier Kv channels regulate apoptosis in the nervous system. Herein, we investigated changes in the expression of the delayed-rectifier Kv channels Kv1.2, Kv2.1, and Kv3.1 after acute spinal cord injury (SCI) in rats. We performed RT-PCR analysis and found an increase in the level of Kv2.1 mRNA after SCI but no significant changes in the levels of Kv1.2 and Kv3.1 mRNA. Western blot analysis revealed that Kv2.1 protein levels rapidly decreased and then dramatically increased from 1 day, whereas Kv3.1b protein levels gradually and sharply decreased at 5 days. Kv1.2 protein levels did not change significantly. In addition, Kv2.1 clusters were disrupted in the plasma membranes of motor neurons after SCI. Interestingly, the expressional changes and translocation of Kv2.1 were consistent with the apoptotic changes on day 1. Therefore, these results suggest that Kv2.1 channels probably contribute to neuronal cell responses to SCI.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.6
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• pp.353-361
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• 2005

The interaction of cyclosporine A (CsA), an immunosuppressant, with rat brain Kv1.5 (Kv1.5) channels, which were stably expressed in Chinese hamster ovary cells, was investigated using the whole-cell patch-clamp technique. CsA reversibly blocked Kv1.5 currents at +50 mV in a reversible concentrationdependent manner with an apparent $IC_{50}$ of 1.0μM. Other calcineurin inhibitors (cypermethrin, autoinhibitory peptide) had no effect on Kv1.5 and did not prevent the inhibitory effect of CsA. Fast application of CsA led to a rapid and reversible block of Kv1.5, and the onset time constants of the CsA-induced block were decreased in a concentration-dependent manner. The CsA-induced block of Kv1.5 channels was voltage-dependent, with a steep increase over the voltage range of channel opening. However, the block exhibited voltage independence over the voltage range in which channels were fully activated. The rate constants for association and dissociation of CsA were $7.0{\mu}M{-1}s^{-1}$ and $8.1s^{-1}$, respectively. CsA slowed the deactivation time course, resulting in a tail crossover phenomenon. Block of Kv1.5 by CsA was use-dependent. CsA also blocked Kv1.3 currents at +50 mV in a reversible concentration-dependent manner with an apparent $IC_{50}$ of $1.1{\mu}M$. The same effects of CsA on Kv1.3 were also observed in excised inside-out patches when applied to the internal surface of the membrane. The present results suggest that CsA acts directly on Kv1.5 currents as an open-channel blocker, independently of the effects of CsA on calcineurin activity.

• International Journal of Oral Biology
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• v.44 no.3
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• pp.115-123
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• 2019

Among the environmental chemicals that may be able to disrupt the endocrine systems of animals and humans are polychlorinated biphenyls (PCBs), a chemical class of considerable concern. PCB consists of two six-carbon rings linked by a single carbon bond, and theoretically, 209 congeners can form, depending on the number of chlorines and their location on the biphenyl rings. Furthermore, 3,3',4,4',5-pentachlorobiphenyl (PCB126) exposure also increases nitric oxide production and nuclear factor kappa-light-chain-enhancer of activated B cells binding activity in chondrocytes, thus contributing as an initiator of chondrocyte apoptosis and resulting in thymic atrophy and immunosuppression. This study identified whether cardiac and immune abnormalities from PCB126 were caused by the Kv1.3 and Kv1.5 channels. PCB126 did not affect either the steady-state current or peak current of the Kv1.3 and Kv1.5 channels. However, PCB126 right-shifted the steady-state activation curves of human Kv1.3 channels. These results suggest that PCBs can affect the heart in a way that does not block voltage-dependent potassium channels including Kv1.3 and Kv1.5 directly.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• BMB Reports
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• v.42 no.8
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• pp.535-539
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• 2009

Voltage-gated $K^+$ (Kv) channels are widely expressed in the plasma membranes of numerous cells such as epithelial cells. Recently, it has been demonstrated that Kv channels are associated with the proliferation of several types of cancer cells. Specifically, Kv1.3 seems to be involved in cancer cell proliferation and apoptosis. In the present study, we examined the expression of Kv1.3 in immortalized and tumorigenic human mammary epithelial cells. We also evaluated the expression level of Kv1.3 in each stage of breast cancer using mRNA isolated from breast cancer patients. In addition, treatment with tetraethylammonium, a Kv channel blocker, suppressed tumorigenic human mammary epithelial cell proliferation. Therefore, Kv1.3 may serve as a novel molecular target for breast cancer therapy while its stage-specific expression pattern may provide a potential diagnostic marker for breast cancer development.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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• pp.71-77
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• 2006

The goal of this study was to analyze the effects of genistein, a widely used tyrosine kinase inhibitor, on cloned Shaw-type $K^+$ currents, Kv3.1 which were stably expressed in Chinese hamster ovary (CHO) cells, using the whole-cell configuration of patch-clamp techniques. In whole-cell recordings, genistein at external concentrations from 10 to $100{\mu}M$ accelerated the rate of inactivation of Kv3.1 currents, thereby concentration-dependently reducing the current at the end of depolarizing pulse with an $IC_{50}$ value of $15.71{\pm}0.67{\mu}M$ and a Hill coefficient of $3.28{\pm}0.35$ (n=5). The time constant of activation at a 300 ms depolarizing test pulses from -80 mV to +40 mV was $1.01{\pm}0.04$ ms and $0.90{\pm}0.05$ ms (n=9) under control conditions and in the presence of $20{\mu}M$ genistein, respectively, indicating that the activation kinetics was not significantly modified by genistein. Genistein $(20{\mu}M)$ slowed the deactivation of the tail current elicited upon repolarization to -40 mV, thus inducing a crossover phenomenon. These results suggest that drug unbinding is required before Kv3.1 channels can close. Genistein-induced block was voltage-dependent, increasing in the voltage range $(-20\'mV{\sim}0\'mV)$ for channel opening, suggesting an open channel interaction. Genistein $(20{\mu}M)$ produced use-dependent block of Kv3.1 at a stimulation frequency of 1 Hz. The voltage dependence of steady-state inactivation of Kv3.1 was not changed by $20{\mu}M$ genistein. Our results indicate that genistein blocks directly Kv3.1 currents in concentration-, voltage-, time-dependent manners and the action of genistein on Kv3.1 is independent of tyrosine kinase inhibition.

• 전기의세계
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• v.20 no.6
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• pp.37-43
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• 1971

본고에서는 한전 345KV 초고압설비의 절연협조에 대해서 개관하여 보았으며 다음과 같이 요약할 수 있다. 1. 절연협조에서는 충격전압, 개폐과도전압 및 상용주파전압을 고찰해야 한다. 2. 이들 전압의 기대치는 다음과 같다. 충격전압: 1500KV, 개폐과도전압: 890KV(3.0 P.U.), 상용주파과전압: 1.2배, 3. 한전이 선정한 절연수준은 다소 유도의 폭이 큰 편이다. 4. 송전선로의 절연은 개폐과도전압치를 2.3 P.U로 압제 상대적으로 높게하고 있으며, 일연 17개의 애자로서 충분한 것으로 보인다.

• Clinical and Experimental Reproductive Medicine
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• v.18 no.1
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• pp.35-40
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• 1991

To find out the suitable method for blastomeres fusion of mouse 2-cell embryo using electric stimuli, these studies were carried out with various voltages (1.0 KV, 1.2 KV, 1.5 KV, 1.7 KV and 2.0KV), pulse duration times($50{\mu}\;sec$, $75/{\mu}\;sec$, $100{\mu}\;sec$) and different fusion solutions. In addition, the fused embryos were cultured for 72-80hr to observe their subsequent development. These results were summarized as follows: 1. The proportion of the fused embryos were 50.8%(34/67), 60.7%(34/56), 70.6%(48/68), 66.7% (48/72) and 85.3% (58/68) after stimuli of 1.0KV, 1.2KV, 1.5KV, 1.7KV and 2.0KV for $100{\mu}\;sec$ with 2 times, and the electric stimulation at 2.0KV(85.3%) was the most effective voltage on the blastomere fusion. 2. For in vitro development, blastocysts of the fused embryos were cultured for 72-80hrs in $M_{16}$ medium. The group(52.1%) treated with 1.5KV for $100{\mu}\;sec$ with 2 times showd higher development rates than those any other group. However, these results were not corresponded to those of the rates of blastomere fusion. 3. There were no significant differences among the rates of blastomeres fusion to 50(70.6%), 75(71.9%), and 100(78.0%) ${\mu}sec$ stimulation at 1.5KV with two times. However, the development rates of the fused embryo in vitro were 52.1%(25/48), 28.3%(13/46) and 9.4%(3/32) at the above conditions, and the development rates of fused embryo increased as the pulse duration times increased. 4. The rates of the blastomeres fusion were 38.9% (28/72) or 70.6% (48/68) in electrolyte (PBS) or non-electrolyte(0.3M mannitol) solution. The development rates of the fused embryo were 32.1% (9/28) or 52.1%(25/48) in the above fusion solutions, and non-electrolyte-treated group showed higher development rates of embryo than that of electrolyte-treated group.

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.22-23
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• 1999

Voltage-gated $K^{＋}$ channels represent the most complex group of ion channel genes expressed in cardiovascular system. The human Kv1.5 channel (hKv1.5) represents the $I_{Kur}$ repolarizing current in atrial myocytes. The hKv1.5 channel is functionally modulated by the Kv$\beta$1.3 subunit, which converts it from a delayed rectifier to a channel with rapid inactivation and enhanced voltage sensitivity.(omitted)d)