Electrophysiological properties and calcium handling of embryonic stem cell-derived cardiomyocytes

염재범 한국한의학연구원 2016 Integrative Medicine Research Vol.5 No.1

Embryonic stem cell-derived cardiomyocytes (ESC-CMs) hold great interest in many fields of research including clinical applications such as stem cell and gene therapy for cardiac repair or regeneration. ESC-CMs are also used as a platform tool for pharmacological tests or for investigations of cardiac remodeling. ESC-CMs have many different aspects of morphology, electrophysiology, calcium handling, and bioenergetics compared with adult cardiomyocytes. They are immature in morphology, similar to sinus nodal-like in the electrophysiology, higher contribution of trans-sarcolemmal Ca2+ influx to Ca2+ handling, and higher dependence on anaerobic glycolysis. Here, I review a detailed electrophysiology and Ca2+ handling features of ESC-CMs during differentiation into adult cardiomyocytes to gain insights into how all the developmental changes are related to each other to display cardinal features of developing cardiomyocytes.

Role of Stretch-Activated Channels in Stretch-Induced Changes of Electrical Activity in Rat Atrial Myocytes

염재범,조수현,임채헌,호원경,엄융의 대한약리학회 2004 The Korean Journal of Physiology & Pharmacology Vol.8 No.1

We developed a cardiac cell model to explain the phenomenon of mechano-electric feedback (MEF), based on the experimental data with rat atrial myocytes. It incorporated the activity of ion channels, pumps, exchangers, and changes of intracellular ion concentration. Changes in membrane excitability and Ca2+ transients could then be calculated. In the model, the major ion channels responsible for the stretch-induced changes in electrical activity were the stretch-activated channels (SACs). The relationship between the extent of stretch and activation of SACs was formulated based on the experimental findings. Then, the effects of mechanical stretch on the electrical activity were reproduced. The shape of the action potential (AP) was significantly changed by stretch in the model simulation. The duration was decreased at initial fast phase of repolarization (AP duration at 20% repolarization level from 3.7 to 2.5 ms) and increased at late slow phase of repolarization (AP duration at 90% repolarization level from 62 to 178 ms). The resting potential was depolarized from -75 to -61 mV. This mathematical model of SACs may quantitatively predict changes in cardiomyocytes by mechanical stretch.

Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes

염재범,임재훈,Yin Hua Zhang,김나리,한진,Yung E. Earm 대한약리학회 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.5

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, Ca²+ 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+/Ca²+ exchange current secondary to the accumulation of Na+ and Ca²+ 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.

A Computational Model of Cytosolic and Mitochondrial [Ca^(2+)] in Paced Rat Ventricular Myocytes

염재범,최성우,Chang Han Jang,김형규,Chae Hun Leem,김나리,한진 대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.4

We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca^(2+) transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1∼3 Hz) made both the diastolic and systolic [Ca^(2+)] bigger in mitochondria as well as in cytosol. As L-type Ca^(2+) channel has key influence on the amplitude of Ca^(2+)-induced Ca^(2+) release, the relation between stimulus frequency and the amplitude of Ca^(2+) transients was examined under the low density (1/10 of control) of L-type Ca^(2+) channel in model simulation, where the relation was reversed. In experiment, block of Ca^(2+) uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca^(2+) transients, while it failed to affect the cytosolic Ca^(2+) transients. In computer simulation, the amplitude of cytosolic Ca^(2+) transients was not affected by removal of Ca^(2+) uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca^(2+)] in cytosol and eventually abolished the Ca^(2+) transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca^(2+) channel to total transsarcolemmal Ca^(2+) flux could determine whether the cytosolic Ca^(2+) transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca^(2+) affects mitochondrial Ca^(2+) in a beat-to-beat manner, however, removal of Ca^(2+) influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca^(2+) transients.

STRETCH-ACTIVATED CHANNEL IN THE HEART

염재범,임채헌,한진,설창안,엄융의 한국산업응용수학회 2008 한국산업응용수학회 학술대회 논문집 Vol.4 No.3

Since their first discovery 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 such as ionic selectivity and stretch-dependence have been studied both in the single-channel and at the whole-cell level. There is growing evidence that major stretch-induced changes in electrical activity are mediated by activation of these channels. The involvement of SACs in stretch-induced arrhythmias and diastolic depolarization was demonstrated using a specific blocker. Noma's group has created a cardiac cell model (Kyoto-Model) to describe various cellular activities such as the action potential, Ca²? transients and contractile force. We focus on the possible contribution of SACs to the generation of atrial rhythm disturbances by combining the Kyoto-Model and experimental findings on SACs in rat atrial myocytes. The simulation shows that the SACs trigger the firing of action potentials by depolarizing the cell membrane to reach the threshold for the activation of voltage-gated sodium channel and that the firing ceases when a significant rise in intracellular sodium concentration develops. The simulation also shows that the delayed increase in the intracellular calcium concentration triggers the calcium-induced calcium release and that the subsequent activation of Na?/Ca²? exchanger drives spontaneous firing of action potentials. These simulation results successfully demonstrate how the SACs can drive the generation of stretch-induced arrhythmias such as atrial tachycardia and atrial fibrillation.

4차 산업혁명 시대에서 지역혁신 환경이 지역발전 성과에 미치는 영향에 관한 연구

홍재범,염창선,전재균,김하균 사단법인 미래융합기술연구학회 2021 아시아태평양융합연구교류논문지 Vol.7 No.11

It can be said that the 4th industrial revolution is essential for regional development as it has a profound impact on society, economy and business. This 4th industry can innovatively develop the region. Various start-up companies around the world are growing into global companies and there is a lot of interest in wanting to become leaders of these companies. Analysis of society as a whole using big data has been attempted from a different perspective and is becoming an issue. Services founded on the artificial intelligence and Internet of Things are being introduced worldwide. As this paradigm shift is rapidly increasing, the speed of change is rapidly increasing. In order to achieve regional development results, changes in the local innovation environment will have a profound impact. The purpose of this research is to investigate the association between regional growth creation and regional development performance on the regional innovation environment. For questionnaire analysis, SPSS 22.0, a statistical package, was used for basic statistical analysis. Hypothesis testing was performed using the structural equation package Smart PLS 2.0. Factors that determine the regional innovation environment are divided into startup discovery, big data connection, and IOT technology infrastructure creation. A summary of the study follows. First, the discovery of startups had a significant effect on the creation of regional growth. Second, big data linkage had a significant effect on regional growth creation. Third, the establishment of the IOT technology base had a significant effect on the creation of regional growth. Fourth, regional growth creation had a significant effect on regional development performance. 제4차 산업혁명은 주요 산업, 경제, 사회의 변화를 의미하며, 그 의미가 지속해서 확장되고 있다. 지역발전을 위해서는 4차산업의 도입이 필수적이라고 할 수 있다. 이는 벌써 사회, 경제 및 기업에 지대한 영향을 주고 있다. 이러한 4차산업은 지역을 혁신적으로 발전시킬 수 있다. 세계적으로 다양한 스타트업 기업이 글로벌기업으로 성장하고 이러한 기업의 리더십에 지대한 관심이 쏠리고 있다. 빅데이터를 이용한 사회 전체의 분석은 다른 시야에서 시도되어 이슈가 되고 있다. 사물인터넷과 인공지능을 기반으로 하는 서비스들이 세계적으로 도입되고 있다. 이러한 패러다임의 전환이 급격해지면서 변화의 속도가 급속도로 증가하고 있다. 지역발전성과를 이루기 위해서는 지역혁신환경의 변화가 지대한 영향을 미칠 것이다. 연구의 목적은 지역혁신환경에서 지역성장창출과 지역발전성과의 영향관계를 분석하고자 한다. 설문지 분석을 위해 기본통계분석을 위해 통계패키지인 SPSS 22.0을 사용하였다. 구조방정식 패키지 Smart PLS 2.0을 사용하여 가설검정을 실시하였다. 지역혁신환경을 결정하는 요인으로 스타트업 발굴, 빅데이터 연계, IOT 기술기반조성으로 나누었다. 연구의 요약은 다음과 같다. 첫째, 스타트업 발굴은 지역성장창출에 유의한 영향을 미쳤다. 둘째, 빅데이터 연계는 지역성장창출에 유의한 영향을 미쳤다. 셋째, IOT 기술기반조성은 지역성장창출에 유의한 영향을 미쳤다. 넷째, 지역성장창출은 지역발전성과에 유의한 영향을 미쳤다.

창업이후 중소기업의 생존율 변화 분석

염창선,홍재범 한국자료분석학회 2008 Journal of the Korean Data Analysis Society Vol.10 No.5

The objectives of this paper are to analyze the survival probability of small-business companies by the Kaplan-Meier survival analysis based on KIBO databse. KIBO is the pubic institution to support then small-business companies. The result is as follows. Individual startup was much more risk than business start-up. Manufacture start-up was much more risk than Service and Retail. The general start-up was much more risk than the high-tech based start-up. The hazard function illustrated an inverse_u shape except high-tech start-up. The hazard of high-tech start-up was increasing. 본 연구는 기술신용보증기금의 자료를 바탕으로 생존분석을 통해 중소기업 생존율을 추정하고 나아가 창업유형, 참여산업, 사업형태가 생존율에 미치는 영향을 분석하였다. 분석기업의 생존율은 개인으로 창업하는 경우보다는 기업으로 창업하는 경우 생존율이 높고 서비스업이 유통업이나 제조업보다는 생존율이 높으며 기술혁신형이 일반형에 비해 생존율이 높으며 중소기업의 해저드 함수는 대부분 기간이 지남에 따라 계속 상승하고 있다.

인터넷뱅킹의 고객만족에 영향을 미치는 요인에 대한 실증적 연구

염창선,홍재범 대한산업공학회 2004 산업공학 Vol.17 No.3

Protein Kinase C Activates ATP-sensitive Potassium Channels in Rabbit Ventricular Myocytes

김나리,염재범,주현,김형규,김의용,한진 대한약리학회 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.4

Several signal transduction pathways have been implicated in ischemic preconditioning induced by the activation of ATP-sensitive K+ (KATP) channels. We examined whether protein kinase C (PKC) modulated the activity of KATP channels by recording KATP channel currents in rabbit ventricular myocytes using patch-clamp technique and found that phorbol 12,13-didecanoate (PDD) enhanced pinacidil-induced KATP channel activity in the cell-attached configuration; and this effect was prevented by bisindolylmaleimide (BIM). KATP channel activity was not increased by 4α-PDD. In excised inside- out patches, PKC stimulated KATP channels in the presence of 1 mM ATP, and this effect was abolished in the presence of BIM. Heat-inactivated PKC had no effect on channel activity. PKC-induced activation of KATP channels was reversed by PP2A, and this effect was not detected in the presence of okadaic acid. These results suggest that PKC activates KATP channels in rabbit ventricular myocytes.

운동방법에 따른 스쿼트 운동이 넙다리곧은근, 넙다리두갈래근, 장딴지근의 iEMG, MEF에 미치는 영향

김기홍,염재범 대한운동학회 2015 아시아 운동학 학술지 Vol.17 No.1

[PURPOSE] The purpose of this study was to evaluate the effects of different squat exercises on iEMG and MEF on Rectus femoris, biceps femoris and gastrocnemius. [METHODS] In this study, 12 male college students who had more than two years of weight trainingexperience were recruited, and conducted3 sets of three different squat exercises (isometric, isotonic, and jump squats) with 60 seconds rest between sets. The iEMG and MEF were analyzed on three different muscles during these exercises(Rectus femoris, biceps femoris, and gastrocnemius). Two way repeated ANOVA was used to find out statistical significance at the level of alpha = .05. [RESULTS] Rectus femoris'siEMG during isotonic and jump squats was greater than that of isometric squat (p<.01, p<.001). iEMG on biceps femoris when performing isotonic and jump squats was significant different from that of isometric squat (p<.01, p<.001). iEMG on gastrocnemius was the highest during jump squat and that of isotonic squat was the second highest, and so on (p<.001). As sets in squat exercises proceeded, iEMG of gastrocnemius during isotonic and jump squats decreased (p<.001). The MEF of bicepsfemoris during isometric squat was the highest and that of jump squat was the second highest. MEF of gastrocnemius during isometric squat was greater than isotonic and jump squats (p<.001). As sets proceeded, MEF of gastrocnemius was increasedduring isotonic and jump squats(p<.001). [CONCLUSIONS] As a result, it is concluded that iEMG during isotonic and jump squats was greater and MEF during isometric squat was higher than the other exercise types, and iEMG during isotonic and jump squats tended to be lower as MEF increased.