• 전자공학회논문지
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• 제50권5호
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• pp.242-250
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• 2013

본 논문에서는 심장의 심근세포의 탈분극과 재분극을 반영하는 불응기(Refractory Period)를 이용한 R-파 검출 알고리즘을 제안한다. 제안 알고리즘은 R-파의 특징과 가변 불응기를 이용하여 R-정점을 검출한다. 먼저 상대적으로 높은 전위 점을 R-정점 후보로 추출하고, 그 후보 점에 대해 첨도와 전위를 고려한 불응기를 구한다. 다음으로 불응기내에서 R-파의 형태학적 특징을 이용하여 R-정점을 검출한다. 제안 알고리즘은 적은 연산을 가지므로 실시간 처리가 가능하다. 제안한 알고리즘을 MIT-BIH 부정맥 데이터베이스의 모든 레코드에 적용한 결과 99.7% 이상의 매우 우수한 검출율을 보였다.

• 한국컴퓨터정보학회논문지
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• 제18권1호
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• pp.93-101
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• 2013

심전도 신호에서 R-파는 다른 특징 점을 구하는데 중요한 역할을 할 뿐만 아니라 심장에 대한 많은 의학적인 정보를 가지고 있다. 지금까지의 연구는 심전도 신호 형태에 대한 분석을 통하여 R-파를 검출하였으나, R-파와 비슷한 형태의 P-파가 나타날 경우 정확한 R-파 검출이 어려웠다. 본 논문에서는 세포막이 흥분 후에 탈분극과 재 분극 기간인 불응기와 불응기내 파형의 첨도 형태를 이용하여 R-파를 검출하는 방식을 제시하였다. MIT-BIH 부정맥 데이터베이스에 있는 심전도 신호 대한 실험을 통하여 R-파와 유사한 형태의 P-파를 가진 105번과 108번 레코드뿐만 아니라 다른 레코드에서도 기존의 방식보다 비교적 우수한 검출율을 확인하였다.

• International Journal of Oral Biology
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• 제43권1호
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• pp.43-51
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• 2018

$K^+$ channels are key components of the primary and secondary basolateral $Cl^-$ pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human $K^+$ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier $K^+$ channel ($I_{Kr}$) in the heart. Mutations in hERG reduce $I_{Kr}$ and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at $36^{\circ}C$, treatment with $0.4{\mu}M$ paroxetine for 5 min decreased the action potential duration at 90% of repolarization ($APD_{90}$) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

• 한국정보통신학회논문지
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• 제21권2호
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• pp.450-460
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• 2017

T파는 심장의 심실의 재분극을 나타내는 파라미터로써 부정맥 진단에 있어 매우 중요하다. T 파를 검출하기 위한 기존 연구방법으로는 주파수 분석과 비선형 접근방법 등이 제안되어 왔지만 검출 정확도가 낮다는 문제점이 있다. 이는 T파의 경우 P파와 중복되는 경우가 발생하기 때문이다. 본 연구에서는 QRS 구간을 제거한 후, 이동평균을 통한 P파와 T파의 대상 영역을 추출하여 정확히 T파를 검출하는 알고리즘을 제안한다. 이를 위해 전처리를 통해 잡음이 제거된 심전도 신호에서 Q, R, S를 검출한다. 이후 검출된 QRS 구간을 제거, 이동평균을 통해 4개의 PAC 패턴과 기타부정맥에 대한 판단규칙을 적용하여 P, T파의 대상 영역을 추출하고, 이를 대상으로 RR 간격과 RT 간격의 문턱치를 적용하여 T파를 검출하였다. 제안한 방법의 우수성을 입증하기 위해 MIT-BIH 부정맥 데이터베이스 48개의 레코드를 대상으로 한 T파의 평균 검출율은 95.32%의 성능을 나타내었다.

• 한국통신학회논문지
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• 제41권2호
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• pp.244-253
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• 2016

ECG 신호에서 QRS군은 매우 중요한 심실의 탈분극 상태 정보를 제공한다. 자동으로 심전도 신호를 분석하기 위해서는 $QRS_{onset}$ 과 $QRS_{offset}$ 에 대한 정확한 정보가 중요하다. 본 연구에서는 먼저 QRS군의 전위값 변화량 및 $R_{peak}$ 와의 거리를 이용하여 Q파와 R파의 접속 부분 그리고 R파와 S파의 접속 부분을 구하였다. 다음 단계에서는 이를 기준으로 적분연산을 이용하여 $QRS_{onset}$ 과 $QRS_{offset}$ 을 검출하였다. 알고리즘의 성능을 평가하기위해 PhysioNet QT database를 사용하여 심장 전문의가 수작업으로 표시한 결과에 대한 평균과 표준편차를 계산하였다. 실험결과에서 제안한 알고리즘의 표준편차는 전문의사가 수용할 수 있는 허용치 범위 안에 속하며, 다른 알고리즘보다 더 우수함을 나타낸다.

• The Korean Journal of Physiology
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• 제24권2호
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• pp.377-388
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• 1990

Ca movements during the late plateau phase in rabbit atrium implicate Na-Ca exchange. In single atrial cells isolated from the rabbit the properties of the inward current of Na-Ca exchange were investigated using the whole cell voltage clamp technique. The inward currents were recorded during repolarization following brief 2 ms depolarizing pulse to +40 mV from a holding potential of -70 mV. Followings are the results obtained: 1) When stimulated every 30 sec, the inward currents were activated and reached peak values $6{\sim}12\;ms$ after the beginning of depolarizing pulse. The mean current amplitude was 342 pA/cell. 2) The current decayed spontaneously from the peak activation and the timecourse of the relaxation showed two different phases: fast and slow phase. 3) The recovery of the inward current was tested by paired pulse of various interval. The peak current recovered exponentialy with a time course similar to that of Ca current recovery. 4) Relaxation timecourse was also affected by pulse interval and time constant was reduced almost linearly according to the decrease of pulse interval between 30 sec and 1 sec. 5) The peak inward current was increased by long prepulse stimulation, Bay K, isoprenaline or c-AMP. 6) The relaxation time constant of the inward current was prolonged by Bay K or c-AMP, and shortened by isoprenaline. From the above results, it could be concluded that increase of the calcium current potentiates and prolongs intracellular calcium transients, while shortening of the timecourse by isoprenaline or short interval stimulations might be due to the facilitation of Ca uptake by SR.

• The Korean Journal of Physiology and Pharmacology
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• 제10권2호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.1-8
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• 2000

To investigate the contributions of intrinsic membrane properties to the spontaneous activity of medial vestibular nucleus (MVN) neurons, we assessed the effects of blocking large and small calcium-activated potassium channels by means of patch clamp recordings. Almost all the MVN neurons recorded in neonatal $(P13{\sim}P17)$ rat were shown to have either a single deep after-hyperpolarization (AHP; type A cells), or an early fast and a delayed slow AHP (type B cells). Among the recorded MVN cells, immature action potential shapes were found. Immature type A cell showed single uniform AHP and immature B cell showed a lack of the early fast AHP, and the delayed AHP was separated from the repolarization phase of the spike by a period of isopotentiality. Application of apamin and charybdotoxin (CTX), which selectively block the small and large calcium-activated potassium channels, respectively, resulted in significant changes in spontaneous firings. In both type A and type B cells, CTX (20 nM) resulted in a significant increase in spike frequency but did not induce bursting activity. By contrast, apamin (300 nM) selectively abolished the delayed slow AHP and induced bursting activity in type B cells. Apamin had no effect on the spike frequency of type A cells. These data suggest that there are differential roles of apamin and CTX sensitive potassium conductances in spontaneous firing patterns of MVN neurons, and these conductances are important in regulating the intrinsic rhythmicity and excitability.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.545-553
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• 2020

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K⁺ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC₅₀ value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC₅₀ value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC₅₀ value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

• 분석과학
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• 제24권6호
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• pp.533-543
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• 2011

hERG (human ether-a-go-go related gene) 이온채널은 심장 재분극의 중요 요소이며 이 채널의 저해제는 부정맥과 돌연사를 유발할 수 있다. 따라서, 신약개발과정에서 후보물질이 hERG 이온채널의 잠재적인 저해제일 경우에는 심장독성 부작용을 유발하므로, 이를 최소화하고자 많은 노력이 집중되고 있다. 본 연구는 HEK(인간 배아 신장)세포에서 얻은 202개 유기화합물의 $IC_{50}$ 데이터를 이용하여 2차원 구조-활성의 정량적 관계(2D-QSAR)방법으로 예측하는 모델을 개발하였다. hERG이온채널 저해제의 기계 학습방법으로는 다중선형회귀(Multiple Linear Regression), 서포트 벡터 머신(Support Vector Machine: SVM)방법과 인공신경망(Artificial Neural Network)방법이며, 교차검증을 적용한 모집단 기반 전진선택(forward selection)방법과 결합하여 각 학습모델에 적합한 최적의 표현자들을 결정하였다. 가장 우수한 방법은 14종의 표현자를 사용한 인공신경망방법($R^2_{CV}$=0.617, RMSECV=0.762, MAECV=0.583)이었고, 다중선형회귀방법을 통해서 hERG이온채널 저해물질의 구조적 특징과 수용체와의 상호작용을 설명할 수 있다. QSAR모델의 검증은 교차검증과 Y-scrambling test방법으로 수행하였다.