• The Korean Journal of Physiology and Pharmacology
• /
• 제15권5호
• /
• pp.291-297
• /
• 2011

The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $3.17{\mu}m$ and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.

• Journal of information and communication convergence engineering
• /
• 제16권1호
• /
• pp.43-47
• /
• 2018

The existing modeling of avalanche dominated breakdown in double gate MOSFETs (DGMOSFETs) is not relevant for 10 nm gate lengths, because the avalanche mechanism does not occur when the channel length approaches the carrier scattering length. This paper focuses on the punch through mechanism to analyze the breakdown characteristics in 10 nm DGMOSFETs. The analysis is based on an analytical model for the thermionic-emission and tunneling currents, which is based on two-dimensional distributions of the electric potential, obtained from the Poisson equation, and the Wentzel-Kramers-Brillouin (WKB) approximation for the tunneling probability. The analysis shows that corresponding flat-band-voltage for fixed threshold voltage has a significant impact on the breakdown voltage. To investigate ambiguousness of number of dopants in channel, we compared breakdown voltages of high doping and undoped DGMOSFET and show undoped DGMOSFET is more realistic due to simple flat-band-voltage shift. Given that the flat-band-voltage is a process dependent parameter, the new model can be used to quantify the impact of process-parameter fluctuations on the breakdown voltage.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권2호
• /
• pp.215-223
• /
• 2017

The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent $K^+$ and $Ca^{2+}$ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent $K^+$currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent $K^+$ currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker $Cs^+$ (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent $Ca^{2+}$ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권2호
• /
• pp.193-200
• /
• 2016

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has been reported to lead to cardiac toxicity even at therapeutic doses including sudden cardiac death and ventricular arrhythmia. And in a SSRI-independent manner, sertraline has been known to inhibit various voltage-dependent channels, which play an important role in regulation of cardiovascular system. In the present study, we investigated the action of sertraline on Kv1.5, which is one of cardiac ion channels. The effect of sertraline on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Sertraline reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $0.71{\mu}M$ and 1.29, respectively. Sertraline accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -20 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +10 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance ${\delta}$ of 0.16. Sertraline slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of sertraline, were superimposed. Inhibition of Kv1.5 by sertraline was use-dependent. The present results suggest that sertraline acts on Kv1.5 currents as an open-channel blocker.

• The Korean Journal of Physiology and Pharmacology
• /
• 제10권2호
• /
• pp.71-77
• /
• 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.

• 생명과학회지
• /
• 제14권5호
• /
• pp.882-890
• /
• 2004

간극결합(gap junction)은 이웃하는 두 세포사이에 형성된 막 구조물로 이를 통하여 각종 이온들과 여러 가지 분자들이 통과한다. 일반적으로 알려진 세포의 이온채널(예를 들어 $Na^{+}$ 이온채널과$K^+$이온채널)과 구별하여 두 세포사이에 형성된 간극결합을 세포간 채널(intercellular channel)이라고도 부른다. 간극결합채널(gap junction channel)은 단순히 수동적으로 열려있는 통로가 아니라 여러 가지 자극 즉 pH, 칼슘이온(calcium ion), 전압(voltage), 그리고 화학적인 변형(주로 인산화, phosphorylation)에 의해서 개폐(gating, opening and closing)가 조절되는 이온채널이다. 그 가운데서도 전압에 의한 간극결합채널 개폐 변화가 가장 많이 연구되었다. 세포안과 바깥에 형성된 전압차이(membrane potential, $V_m$) 보다는 주로 두 세포 사이에 형성된 전압차이(transjunctional voltage, $V_j$)에 의해서 간극결합채널은 민감하게 반응한다. 본 총설에서는 간극결합채널의 일반적인 특성을 정리해보고 전압-의존적인(voltage-dependent) 채널개폐에 관한 기전을 논의하고자 한다.

• 한국정보통신학회논문지
• /
• 제18권9호
• /
• pp.2183-2188
• /
• 2014

본 연구에서는 비대칭 이중게이트(double gate; DG) MOSFET의 채널 도핑농도 변화에 따른 문턱전압이동 현상에 대하여 분석하였다. 비대칭 DGMOSFET는 일반적으로 저 농도로 채널을 도핑하여 완전결핍상태로 동작하도록 제작한다. 불순물산란의 감소에 의한 고속 동작이 가능하므로 고주파소자에 응용할 수 있다는 장점이 있다. 미세소자에서 필연적으로 발생하고 있는 단채널 효과 중 문턱전압이동현상이 비대칭 DGMOSFET의 채널도핑농도의 변화에 따라 관찰하고자 한다. 문턱전압을 구하기 위하여 해석학적 전위분포를 포아송방정식으로부터 급수형태로 유도하였다. 채널길이와 두께, 산화막 두께 및 도핑분포함수의 변화 등을 파라미터로 하여 도핑농도에 따라 문턱전압의 이동현상을 관찰하였다. 결과적으로 도핑농도가 증가하면 문턱전압이 증가하였으며 채널길이가 감소하면 문턱전압이 크게 감소하였다. 또한 채널두께와 하단게이트 전압이 감소하면 문턱전압이 크게 증가하는 것을 알 수 있었다. 마지막으로 산화막 두께가 감소하면 문턱전압이 증가하는 것을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제9권6호
• /
• pp.353-361
• /
• 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.

• The Korean Journal of Physiology
• /
• 제27권1호
• /
• pp.107-114
• /
• 1993

Most of voltage operated $Ca^{2+}$ channels can be divided into three types (T-, N-, and L-type), according to the electrical and pharmacological properties. Their distribution is closely related to cell specific functions. Properties of the voltage activated $Ca^{2+}$ current in mouse eggs were examined to classify channel types and to deduce the function by using whole cell voltage clamp technique. $Ca^{2+}$ currents appeared below -40 mV and reached a maximum at -15 mV (half maximum was -31 mV), then decayed rapidly (inactivation time constant ${\tau}=28.2{\pm}9.59$ ms at -10 mV within 50 ms after the onset of step depolarization. Activation and inactivation of the $Ca^{2+}$ channel was steeply dependent on voltage, in a relatively low range of $-70\;mV{\sim}-10 mV,$ half maximum of activation was -31 mV and that of inactivation was -39 mV, respectively. This current was not decreased significantly by nifedipine, a specific dihydropyridine $Ca^{2+}$ channel blocker in the range of $1\;{\mu}M\;to\;100{\mu}M.$ The inhibitory effect of $Ni^{2+}\;on\;Ca^{2+}$ current was greater than that of $Cd^{2+}.$ The conductance of $Ba^{2+}$ through the channel was equal to or lower than that of $Ca^{2+}$ These results implied that $Ca^{2+}$ current activated at a lower voltage in the mouse egg is carried via a $Ca^{2+}$ channel with similar properties that of the T-type channel.

• JSTS:Journal of Semiconductor Technology and Science
• /
• 제11권4호
• /
• pp.278-286
• /
• 2011

In this paper, we present a compact model of gate-voltage-dependent quantum effects in short-channel surrounding-gate (SG) metal-oxide-semiconductor field-effect transistors (MOSFETs). We based the model on a two-dimensional (2-D) analytical solution of Poisson's equation using cylindrical coordinates. We used the model to investigate the electrostatic potential and current sensitivities of various gate lengths ($L_g$) and radii (R). Schr$\ddot{o}$dinger's equation was solved analytically for a one-dimensional (1-D) quantum well to include quantum effects in the model. The model takes into account quantum effects in the inversion region of the SG MOSFET using a triangular well. We show that the new model is in excellent agreement with the device simulation results in all regions of operation.