Ionic Dependence and Modulatory Factors of the Background Current Activated by Isoprenaline in Rabbit Ventricular Cells

Leem. Chae-Hun,Lee. Suk-Ho,So. In-Suk,Ho. Won-Kyung,Earm. Yung-E 대한생리학회 1992 대한생리학회지 Vol.26 No.1

In order to elucidate the properties of the background current whole cell patch clamp studies were performed in rabbit ventricular cells. Ramp pulses of ±80 mV from holding potential of 40 mV(or 20 mV) at the speed of 0.8 V/sec were given every 30 sec(or 10 sec) and current-voltage diagrams(I-V curve) were obtained. For the activation of the background current isoprenaline, adenosine 3 ,5 -cyclic monophosphate(dBcAMP), guanosine 3 ,5 -cyclic monophosphate(cGMP), and N⁶-2 -o-dibutyryladenosine 3 ,5 -cyclic monophosphate(dBcAMP) were applied after all known current systems were blocked with 2mM Ba, 1 mM Cd ,5 mM Ni, 10 μM diltiazem, 10 μm ouabain, and 20 mM tetraethylammonium(TEA). The conductance of background current in control was 0.65±0.69 nS at 0 mV, its I-V curves was almost linear and reversed near 50 mV. When there was no taurine in pipette solution, isoprenaline hardly activated the background current but when taurine existed in pipette solution, isoprenaline activated the larger background current. Cyclic AMP or cyclic GMP alone had little effect on the activation of the background current, while cGMP potentiated cGMP effect. When the background current was activated with cGMP and cAMP, isoprenaline could not further increased the background current. The background current activated by isoprenaline depended on extracellular Cl^- concentration and its reversal potential was shifted according to chloride equilibrium potential. The change of extracellular Na<Sup>+</sup> concentration had little effect on reversal potential of the background current activated by isoprenaline.

Frontier Symposium 4 : System Biology Symposium ; Modelling electrical activity of cardiocyte in pulmonary vein of rabbit

( Chae Hun Leem ),( Jae Boum Youm ),( Won Tae Kim ),( Han Choe ),( Yeon Jin Jang ),( Chun Sik Park ) 한국생화학분자생물학회 (구 한국생화학회) 2004 생화학분자생물학회 춘계학술발표논문집 Vol.2004 No.-

알코올성 간경변 환자에서 위대망 정맥류 출혈로 인한 자발성 혈복강 1 예

채희복,윤세진,박선미,성노현,배일헌,임정묵,장이찬,최기원,신종성,지정훈 대한간학회 2001 Clinical and Molecular Hepatology(대한간학회지) Vol.7 No.3

Portal hypertension often leads to the development of several collateral vessels that shunt blood flow from the portal to the systemic circulation. The rupture of intra-abdominal varix is an unusual complication of portal hypertension that can lead to life-threatening hemoperitoneum of the patient is herrmdynamically unstable due to massive intra-abdominal bleeding, exploratory laparotomy should be performed on the patient. There are several reported cases of intra-abdominal variceal bleeding such as paraumbilical varix, the varix from the small intestine and proximal colon etc. Spontaneous hemoperitoneum caused by the rupture of gastroepiploic vein varix, however, has not been repzted in Korm, to the best of our knowledge. We wiU discuss a patient with portal hypnsion due to liver cirrhosis who pnmented with acute intra-abdominal bleeding. During the laparotomy, he was found to have a rupture of the gastnxpiploic vein. 'Ihe vessel was ligated, and the patient recovered uneventfully by operative variceal ligation. (Korean J Hepatol 2001;7:336-340)

Effect of Cyclic GMP on the Calcium Current in Rabbit Ventricular Myocytes

Han, Jin,Leem, Chae-Hun,Ahn, Chul-Soo,So, In-Suk,Kim, Eui-Yong,Ho, Won-Kyung,Earm, Yung-E The Korean Physiological Society 1993 대한생리학회지 Vol.27 No.2

In order to investigate the effect of intracellular cyclic GMP on calcium current the whole-cell patch clamp technique with internal perfusion method was used in isolated ventricular myocytes of the rabbit. Cyclic GMP, 8-bromo-cyclic GMP, cyclic AMP, isoprenaline and forskolin were perfused into cells and their effects on calcium current were analysed by applying depolarizing step pulses of + 10 mV in amplitude far 300 msec from holding potential of - 40 mV. Not only cyclic AMP $(100\;{\mu}M)$ but also cyclic GMF $(100\;{\mu}M)$ increased the basal calcium current. 8-Bromo-cyclic GMP $(100\;{\mu}M)$, a good stimulator of the cyclic GMP-dependent protein kinase, also increased the basal calcium current and its peak amplitude of calcium current was larger than that in the presence of cyclic AMP or cyclic GMP alone. In the presence of $100\;{\mu}M$ cyclic GMP or $100\;{\mu}M$ 8-bromo-cyclic GMP, already augmented calcium current was potentiated by intracellular application of $100\;{\mu}M$ cyclic AMP or $1\;{\mu}M$ isoprenaline or $1\;{\mu}M$ forskolin. In the presence of cyclic GMP, acetylcholine reduced the calcium current only when the calcium current was increased by isoprenaline. From the above results it could be concluded that intracellular perfusion with cyclic GMP increases the basal calcium current via a mechanism involving a cyclic GMP-dependent protein kinase.

Effect of Various Divalent Ions on the Calcium Current of Adrenal Medullary Chromaffin Cells in the Rat

Kim, Jun,Leem, Chae-Hun,Kim, Sang-Jeong The Korean Physiological Society 1992 대한생리학회지 Vol.26 No.2

It is well known that chromaffin cells of adrenal medulla secrete catecholamine in response to sympathetic nerve activation and the influx of $Ca^{2+}$ through the voltage dependent $Ca^{2+}$ channels (VDCC) in the cell membrane do a major role in this secretory process. In this study, we explored the effect of divalent cations on VDCC of rat chromaffin cells. Rat (Sprague-Dawley rat, 150-250 gm) chromaffin cells were isolated and cultured. Standard giga seal, whole cell recording techniques were employed to study $Ca^{2+}$ current with external and internal solutions that could effectively isolate VDCC currents $(NMG\;in\;external\;and\;TEA\;and\;Cs^{2+}\;in\;internal\;solution)$. The voltage dependence and the inactivation time course of VDCC in our cells were identical to those of bovine chromaffin cells. A persistent inward current was first activated by depolarizing step pulse from the holding potential (H.P.) of -80 mV to -40 mV, increased to maximum amplitude at around +10 mV, and became smaller with progressively higher depolarizing pulses to reverse at around +60 mV. The inactivation time constant $(\tau)$, fitted from the long duration test potential (2 sec) was $1295.2{\pm}126.8$ msec $(n=20,\;1\;day\;of\;culture,\;mean\;{\pm}S.E.M.)$ and the kinetic parameters were not altered along the culture duration. Nicardipine $(10\;{\mu}M)$ blocked the current almost completely. Among treated divalent cations such as $Cd^{2+},\;Co^{2+},\;Ni^{2+},\;Zn^{2+}\;and\;,Mn^{2+},\;Cd^{2+}$ was the most potent blocker on VDCC. When the depolarizing step pulse from -80 mV to 10 mV was applied, the equilibrium dissociation constant $(K_d)$ of $Cd^{2+}\;was\;39\;{\mu}M,\;K_d\;of\;Co^{2+}\;was\;100\;{\mu}M\;and\;K_d\;of\;Ni^{2+}];was];780{\mu}M.$ The principal findings of this study are as follows. First, the majority of $Ca^{2+}$ channels in rat chromaffin cells are well classified to L-type $Ca^{2+}$ channel in the view of kinetics and pharmacology. Second, all divalent cations tested could block the $Ca^{2+}$ current and the most potent blocker among the tested was $Cd^{2+}$.

Pulmonary Function Difference in Sasang Constitutional Types

Yoon, Jiwon,Leem, Chae Hun,Kim, Jong Yeol Hindawi 2018 Evidence-based Complementary and Alternative Medic Vol.2018 No.-

<P>The purpose of this study was to determine the differences in pulmonary function among Sasang constitutional types in young adults. The Sasang Constitutional Analysis Tool (SCAT), pulmonary function tests (PFTs), and cardiopulmonary exercise tests were conducted in 417 participants from 2009 to 2015. Subjects with the Tae-Eum (TE) type had significantly higher inspiratory capacity (IC) and inspiratory reserve volume (IRV) values than those with the So-Yang (SY) and So-Eum (SE) types (<I>P</I> < 0.0001). The TE and SY types showed higher forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV<SUB>1</SUB>) values than the SE type (<I>P</I> < 0.0001). An increase in IRV and a decrease in expiratory reserve volume (ERV) in TE type males remained even after adjusting for covariate factors. These results indicate that young adults with the TE type have weaker lung function than those with the other constitutional types, suggesting its innate physiological pulmonary features.</P>

Toward a grey box approach for cardiovascular physiome

Hwang, Minki,Leem, Chae Hun,Shim, Eun Bo The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5

The physiomic approach is now widely used in the diagnosis of cardiovascular diseases. There are two possible methods for cardiovascular physiome: the traditional mathematical model and the machine learning (ML) algorithm. ML is used in almost every area of society for various tasks formerly performed by humans. Specifically, various ML techniques in cardiovascular medicine are being developed and improved at unprecedented speed. The benefits of using ML for various tasks is that the inner working mechanism of the system does not need to be known, which can prove convenient in situations where determining the inner workings of the system can be difficult. The computation speed is also often higher than that of the traditional mathematical models. The limitations with ML are that it inherently leads to an approximation, and special care must be taken in cases where a high accuracy is required. Traditional mathematical models are, however, constructed based on underlying laws either proven or assumed. The results from the mathematical models are accurate as long as the model is. Combining the advantages of both the mathematical models and ML would increase both the accuracy and efficiency of the simulation for many problems. In this review, examples of cardiovascular physiome where approaches of mathematical modeling and ML can be combined are introduced.

Toward a grey box approach for cardiovascular physiome

Minki Hwang,Chae Hun Leem,Eun Bo Shim 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5

The physiomic approach is now widely used in the diagnosis of cardiovascular diseases. There are two possible methods for cardiovascular physiome: the traditional mathematical model and the machine learning (ML) algorithm. ML is used in almost every area of society for various tasks formerly performed by humans. Specifically, various ML techniques in cardiovascular medicine are being developed and improved at unprecedented speed. The benefits of using ML for various tasks is that the inner working mechanism of the system does not need to be known, which can prove convenient in situations where determining the inner workings of the system can be difficult. The computation speed is also often higher than that of the traditional mathematical models. The limitations with ML are that it inherently leads to an approximation, and special care must be taken in cases where a high accuracy is required. Traditional mathematical models are, however, constructed based on underlying laws either proven or assumed. The results from the mathematical models are accurate as long as the model is. Combining the advantages of both the mathematical models and ML would increase both the accuracy and efficiency of the simulation for many problems. In this review, examples of cardiovascular physiome where approaches of mathematical modeling and ML can be combined are introduced.

Modeling of Arrhythmogenic Automaticity Induced by Stretch in Rat Atrial Myocytes

Youm, Jae-Boum,Leem, Chae-Hun,Zhang, Yin Hua,Kim, Na-Ri,Han, Jin,Earm, Yung-E. The Korean Society of Pharmacology 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, $Ca^{2+}$ 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 $Na^+/Ca^{2+}$ exchange current secondary to the accumulation of $Na^+$ and $Ca^{2+}$ 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.

Body temperature regulation: Sasang typology-based perspective

Duong Duc Pham,Chae Hun Leem 한국한의학연구원 2015 Integrative Medicine Research Vol.4 No.4

Global warming induces a dramatic elevation of heat-related morbidity and mortality worldwide. Individual variation of heat stress vulnerability depends on various factors such as age, gender, living area and conditions, health status, and individual innate characteristics. Sasang typology is a unique form of Korean traditional medicine, which is based on the hypothesis that constitution-specific traits of an individual determine the particular distinctive tendency in various aspects, including responses to the external environment. Recent scientific evidence shows that Sasang types differ in body composition, metabolic profile, susceptibility to certain disease patterns, and perspiration. This review aims to interpret these findings under the context of heat balance consisting of heat production (Hprod), heat loss (Hloss), and heat load (Hload). Based on the published data, at a given body mass, the TaeEum type tended to have a lower Hprod at rest and at the exhaustion state, which may indicate the lower metabolic efficiency of this type. Meanwhile, the surface-to-mass ratio and heat capacity of the TaeEum type appear to be lower, implying a lower heat dissipation capacity and heat storage tolerance. Thus, because of these characteristics, the TaeEum type seems to be more vulnerable to heat stress than the other constitutions. Differences in temperature regulation across constitutional types should be taken into account in daily physical activity, health management, and medical research.