• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.95-101
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• 2005

In the heart, $Na^{+}-Ca^{2+}$ exchange (NCX) is the major $Ca^{2+}$ extrusion mechanism. NCX has been considered as a relaxation mechanism, as it reduces global $[Ca^{2+}]_i$ raised during activation. However, if NCX locates in the close proximity to the ryanodine receptor, then NCX would curtail $Ca^{2+}$ before its diffusion to global $Ca^{2+}_i$ This will result in a global $[Ca^{2+}]_i$ decrease especially during its ascending phase rather than descending phase. Therefore, NCX would decrease the myocardial contractility rather than inducing relaxation in the heart. This possibility was examined in this study by comparing NCX-induced extrusion of $Ca^{2+}$ after its release from SR in the presence and absence of global $Ca^{2+}_i$ transient in the isolated single rat ventricular myocytes by using patch-clamp technique in a whole-cell configuration. Global $Ca^{2+}_i$ transient was controlled by an internal dialysis with different concentrations of BAPTA added in the pipette. During stimulation with a ramp pulse from +100 mV to -100 mV for 200 ms, global $Ca^{2+}_i$ transient was suppressed only mildly, and completely at 1 mmol/L, and 10 mmol/L BAPTA, respectively. In these situations, ryanodine-sensitive inward NCX current was compared using $100{\mu}mol/L$ ryanodine, $Na^+$ depletion, 5 mmol/L $NaCl_2$ and $1{\mu}mol/L$ nifedipine. Surprisingly, the result showed that the ryanodine-sensitive inward NCX current was well preserved after 10 mmol/L BAPTA to 91 % of that obtained after 1 mmol/L BAPTA. From this result, it is concluded that most of the NCX-induced $Ca^{2+}$ extrusion occurs before the $Ca^{2+}$ diffuses to global $Ca^{2+})i$ in the rat ventricular myocyte.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.313-322
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• 1998

In a myocyte freshly isolated from rabbit cerebral artery, the characteristics of $Ca^{2+}$ release by histamine or caffeine were studied by microspectrofluorimetry using a $Ca^{2+}-binding$ fluorescent dye, fura-2. Histamine (5 ${\mu}M$) or caffeine (10 mM) induced a phasic rise of cytoplasmic free $Ca^{2+}$ concentration $([Ca^{2+}]_C)$ which could occur repetitively with extracellular $Ca^{2+}$ but only once or twice in $Ca^{2+}-free$ bathing solution. Also, the treatment with inhibitor of sarcoplasmic reticulum $Ca^{2+}-ATPase$ suppressed the rise of $[Ca^{2+}]_C$ by histamine or caffeine. In $Ca^{2+}-free$ bathing solution, short application of caffeine in advance markedly attenuated the effect of histamine, and vice versa. In normal $Ca^{2+}-containing$ solution with ryanodine (2 ${\mu}M$), the caffeine-induced rise of $[Ca^{2+}]_C$ occurred only once and in this condition, the response to histamine was also suppressed. On the other hand, in the presence of ryanodine, histamine could induce repetitive rise of $[Ca^{2+}]_C$ while the amplitude of peak rise became stepwisely decreased and eventually disappeared. These results suggest that two different $Ca^{2+}-release$ mechanisms (caffeine-sensitive and histamine-sensitive) are present in rabbit cerebral artery myocyte and the corresponding pools overlap each other functionally. Increase of $[Ca^{2+}]_C$ by histamine seems to partially activate ryanodine receptors present in caffeine-sensitive pool.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.507-515
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• 1996

Background : Potassium channel opener (K-opener) opens ATP-sensitive K'-channel located at cell membrane and induces potassium efflux from cytosol, resulting in intracellular hyperpolarization. Newly synthesized K-opener is currently examined for pharmacologic potency by means of rubidium release test from smooth muscle strip pre-incubated with Rb-86. Since in-vivo behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter T1-201 kinetics in vivo. Purpose : This study was prepared to investigate the effects of pinacidil (one of potent K-openers) on the T1-201 uptake and clearance in cultured myocyte, and in-vivo biodistribution in mice. Methods : Spontaneous contracting myocytes were prepared to imitate in-vivo condition from 20 hearts of 3-5 days old Sprague-Dawley rat and cultured for 3-5 days before use ($5{\times}10^5$ cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or l0uM and was co-incubated with T1-201 in HBSS buffer for 20-min to evaluate its effect on cellular T1-uptake, or challenged to cell preparation pre-incubated with T1-201 for washout study. Two, 40 or $100{\mu}g$ of pinacidil was injected intravenously into ICR mice at 10 min after $5{\mu}Ci$ T1-201 injection, and organ uptake and whole body retention rate were measured at different time points. Results : Co-incubation of pinacidil with T1-201 resulted in a decrease in T1-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced T1-201 washout by 1.6-3.1 times from myocyte preparations pre-incubated with T1-201. Pinacidil treatment appears to be resulted in mild decreases in blood and liver activity in normal mice, in contrast, renal and cardiac uptake were mildly decreased in a dose dependent manner. Whole body retention ratios of T1-201 were lower at 24 hour after injection with $100{\mu}g$ of pinacidil than control. Conclusion : These results suggest that treatment with K-opener may affect the interpretation of T1-201 myocardial images, due to decreasing thallium accumulation and enhancing washout from myocardium.

• Journal of Korean Biological Nursing Science
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• v.14 no.2
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• pp.129-138
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• 2012

Purpose: Cachexia is a complex metabolic syndrome associated with wasting of skeletal muscle which contributes to nearly one-third of all cancer deaths. Cachexia lowers the frequency of response to chemotherapy and radiation and ultimately can impact survival as well as quality of life during treatment. NF-kappa B is one of the most important molecular mediators of cachexia. In this study, therefore, possible candidates for inhibitors of NF-kappa B were searched. Methods: Amino acids that regulate cellular redox potential by adjusting the level of NAD/NADH ratio, such as aspartate, pyruvate, and isocitrate were selected. Results: Pyruvate effectively inhibited luciferase activity in TNF-stimulated 293T cells transfect with an NF-kB dependent luciferase reporter vector. Pyruvate also showed protective effect on muscle atrophy of differentiated C2C12 myocyte induced by TNF/IFN. Conclusion: We might be able to develop the nutritional management strategy for cancer cachexia patients with pyruvate supplementation.

• 제어로봇시스템학회:학술대회논문집
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• 2005.06a
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• pp.1179-1182
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• 2005

To facilitate the cell based robot research, we presented a micro-mechanical force measurement system for the biological muscle actuators, which utilize glucose as a power source for potential application in a human body or blood vessels. The system is composed of a micro-manipulator, a force transducer with a glass probe, a signal processor, an inverted microscope and video recoding system. Using this measurement system, the contractile force and frequency of the cardiac myocytes were measured in real time and the magnitude of the contractile force of each cardiac myocyte on a different condition was compared. From the quantitative experimental results, we estimated that the force of cardiac myocytes is about $20{\sim}40\;{\mu}$N, and showed that there is difference between the control cells and the micro-patterned cells.

• Journal of Mechanical Science and Technology
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• v.20 no.5
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• pp.668-674
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• 2006

In order to develop a cell based robot, we present a micro-mechanical force measurement system for the biological muscle actuators, which utilize glucose as a power source. The proposed measurement system is composed of a micro-manipulator, a force transducer with a glass probe, a signal processor, an inverted microscope and video recording system. Using this measurement system, the contractile force and frequency of the cardiac myocytes were measured in real time and the magnitudes of the contractile force of each cardiac myocyte under different conditions were compared. From the quantitative experimental results, we could estimate that the force of cardiac myocytes is about $20\sim40{\mu}N$, and show that there are differences between the control cells and the micro-patterned cells.

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1674-1678
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• 2008

본 연구에서는 심장의 세포 변화에서부터 혈류 순환의 시스템 변화까지 일련의 과정을 시뮬레이션 할 수 있는 통합모델을 개발하였다. 본 통합 모델을 이용하여 대동맥의 탄성도 변화 따른 Pulse Wave Velocity를 추정하였으며 심근의 수축 Mechanics의 변화를 시뮬레이션 하였다. 심장은 단순한 구 형상으로 모델링 되었다. 특히 동맥순환의 특성인 Wave propagation 과 Wave deflection의 현상을 모델링하기 위해 기존 모델에서 사용된 동맥계 순환 모델을 수정하였다. 즉 기존의 동맥 모델을 1차원의 운동방정식과 연속방정식을 기반으로 하는 Distributed arterial model로 대체하였다. Distributed arterial model은 혈액의 점성에 의한 에너지 손실, 혈관의 점탄성 효과 그리고 분지 되는 혈관에서의 에너지 손실을 포함하는 정교한 동맥 순환 모델이다. 정교한 동맥계 순환 모델의 동맥 탄성도 값을 조절함으로써 탄성도 변화에 대한 PWV를 계산 할 수 있었다. 이러한 수치적 방법을 사용하여 노화에 따른 동맥벽 탄성도의 저하가 심근세포의 Cross-bridge 동역학에 미치는 영향을 시뮬레이션 하였다.

• Molecules and Cells
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• v.28 no.1
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• pp.1-5
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• 2009

Vascular endothelial growth factor (VEGF) is essential for many angiogenic processes both in normal and pathological conditions. However, the signaling pathways involved in VEGF-induced angiogenesis are incompletely understood. The protein kinase D1 (PKD1), a newly described calcium/calmodulin-dependent serine/threonine kinase, has been implicated in cell migration, proliferation and membrane trafficking. Increasing evidence suggests critical roles for PKD1-mediated signaling pathways in endothelial cells, particularly in the regulation of VEGF-induced angiogenesis. Recent studies show that class IIa histone deacetylases (HDACs) are PKD1 substrates and VEGF signal-responsive repressors of myocyte enhancer factor-2 (MEF2) transcriptional activation in endothelial cells. This review provides a guide to PKD1 signaling pathways and the direct downstream targets of PKD1 in VEGF signaling, and suggests important functions of PKD1 in angiogenesis.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.40-40
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• 2002

Altered intracellular $Ca^{2＋}$ homeostasis is presumably the primary mechanism of the diastolic impairment in diabetic cardiomyopathy. However, causal relations of numerous environmental changes observed in the diabetic heart have been left unresolved. In the present study, we sought to establish an in vitro model of diabetic cardiomyopathy using H9c2 cardiac myocyte cell line.(omitted)

• Genomics & Informatics
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• v.18 no.3
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• pp.26.1-26.6
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• 2020

Single-cell RNA sequencing (scRNA-seq) has been widely applied to provide insights into the cell-by-cell expression difference in a given bulk sample. Accordingly, numerous analysis methods have been developed. As it involves simultaneous analyses of many cell and genes, efficiency of the methods is crucial. The conventional cell type annotation method is laborious and subjective. Here we propose a semi-automatic method that calculates a normalized score for each cell type based on user-supplied cell type-specific marker gene list. The method was applied to a publicly available scRNA-seq data of mouse cardiac non-myocyte cell pool. Annotating the 35 t-stochastic neighbor embedding clusters into 12 cell types was straightforward, and its accuracy was evaluated by constructing co-expression network for each cell type. Gene Ontology analysis was congruent with the annotated cell type and the corollary regulatory network analysis showed upstream transcription factors that have well supported literature evidences. The source code is available as an R script upon request.