• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.53-53
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• 1999

We have investigated whether alterations in the expression levels of sarcoplasmic reticulum (SR) $Ca^{2＋}$ regulatory proteins in heart and mesenteric arteries from different models of hypertension would occur. Nephrectomied diabetic-hypertensive rats (DM-HT) and spontaneously hypertensive rats (SHR) were used as models of hypertension.(omitted)

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1997년도 학술발표회
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• pp.18-18
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• 1997

Chronic treatment with cyclosporin A (CsA) were shown to induce reversible alterations of contractile properties in rat heart. To define the molecular mechanisms underlying the physiological alterations, the $Ca^{2＋}$ release channel (CRC) and $Ca^{2＋}$-ATPase in rat sarcoplasmic reticulum (SR) were examined.(omitted)

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1997년도 학술발표회
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• pp.30-30
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• 1997

Dysfunctions of skeletal muscles have been frequently reported in chronic diabetic mellitus (DM). In order to investigate the molecular mechanisms of abnormal function, the junctional sarcoplasmic reticulum (HSR) vesicles of skeletal muscles were prepared from the control and the streptozotocin-induced diabetic rats.(omitted)

• Molecules and Cells
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• 제20권1호
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• pp.51-56
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• 2005

Excitation-contraction coupling (ECC) proteins in the human heart were characterized using human atrial tissues from different age groups. The samples were classified into one infant group (Group A: 0.2-7 years old) and three adult groups (Group B: 21-30; Group C: 41-49; Group D: 60-66). Whole homogenates (WH) of atrial tissues were assayed for ligand binding, $^{45}Ca^{2+}$ uptake and content of ECC proteins by Western blotting. Equilibrium [$^3H$]ryanodine binding to characterize the ryanodine receptor (RyR) of the sarcoplasmic reticulum (SR) showed that the maximal [$^3H$]ryanodine binding ($B_{max}$) to RyR was similar in all the age groups, but the dissociation constant ($k_d$) of ryanodine was higher in the infant group than the adult groups. Oxalate-supported $^{45}Ca^{2+}$ uptake into the SR, a function of the SR SERCA2a activity, was lower in the infant group than in the adult groups. Similarly, [$^3H$]PN200-110 binding, an index of dihydropyridine receptor (DHPR) density, was lower in the infant group. Expression of calsequestrin and triadin assessed by Western blotting was similar in the infant and adult groups, but junctin expression was considerably higher in the adult groups. These differences in key ECC proteins could underlie the different $Ca^{2+}$ handling properties and contractility of infant hearts.

• The Korean Journal of Physiology and Pharmacology
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• 제9권4호
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• pp.195-201
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• 2005

High extracellular glucose concentration was reported to suppress intracellular $Ca^{2+}$ clearing through altered sarcoplasmic reticulum (SR) function. In the present study, we attempted to elucidate the effects of pyruvate and fatty acid on SR function and reveal the mechanistic link with glucose-induced SR dysfunction. For this purpose, SR $Ca^{2+}$-uptake rate was measured in digitonin-permeabilized H9c2 cardiomyocytes cultured in various conditions. Exposure of these cells to 5 mM pyruvate for 2 days induced a significant suppression of SR $Ca^{2+}$-uptake, which was comparable to the effects of high glucose. These effects were accompanied with decreased glucose utilization. However, pyruvate could not further suppress SR $Ca^{2+}$-uptake in cells cultured in high glucose condition. Enhanced entry of pyruvate into mitochondria by dichloroacetate, an activator of pyruvate dehydrogenase complex, also induced suppression of SR $Ca^{2+}$-uptake, indicating that mitochondrial uptake of pyruvate is required in the SR dysfunction induced by pyruvate or glucose. On the other hand, augmentation of fatty acid supply by adding 0.2 to 0.8 mM oleic acid resulted in a dose-dependent suppression of SR $Ca^{2+}$-uptake. However, these effects were attenuated in high glucose-cultured cells, with no significant changes by oleic acid concentrations lower than 0.4 mM. These results demonstrate that (1) increased pyruvate oxidation is the key mechanism in the SR dysfunction observed in high glucose-cultured cardiomyocytes; (2) exogenous fatty acid also suppresses SR $Ca^{2+}$-uptake, presumably through a mechanism shared by glucose.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.707-716
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• 1997

Recent reports revealed that the $Na^+-Ca^{2+}$ exchangers and feet structures of sarcoplasmic reticulum(SR) are located in close vicinity in the specific compartment. Therefore, we investigated the possibility that the $Na^+-Ca^{2+}$ exchanger may decrease the tension development by transporting the $Ca^{2+}$ out of the cell right after it released from SR, on the basis of this anatomical proximity. We exammined the negative force-frequency relationship of the developed tension in the electrically field stimulated left atria of postnatal developing rat(1, 3 day, 1 week and 4 week old after birth). Cyclopiazonic $acid(3{\times}10^{-5}\;M)$ treatment decreased the developed tension further according to postnatal age. $Monensin(3{\times}10^{-6}\;M)$ treatment did not increase the maximal tension in 4 week-old rat, preserving negative staircase, while the negative staircase in the younger rat were flattened. $Ca^{2+}$ depletion in the buffer elicited more suppression of the maximal tension according to the frequency in all groups except the 4 week-old group. The % decrease of the maximal developed tension of 4 week-old group at 1 Hz to that of 0.1 Hz after $Na^+$ and $Ca^{2+}$ depletion was only a half of those of the yonger groups. Taken together, it is concluded that the $Na^+-Ca^{2+}$ exchange transports more $Ca^{2+}$ released from SR out of the cell in proportion to the frequency, and this is responsible for the negative staircase effect of the rat heart.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.725-732
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• 1998

In order to elucidate the molecular mechanism of the intracellular $Ca^{2+}$ overload frequently reported from diabetic heart, diabetic rats were induced by the administration of streptozotocin, the membrane vesicles of junctional SR (heavy SR, HSR) were isolated from the ventricular myocytes, and SR $Ca^{2+}$ uptake and SR $Ca^{2+}$ release were measured. The activity of SR $Ca^{2+}-ATPase$ was $562{\pm}14$ nmol/min/mg protein in control heart. The activity was decreased to $413{\pm}30$ nmol/min/mg protein in diabetic heart and it was partially recovered to $485{\pm}18$ nmol/min/mg protein in insulin-treated diabetic heart. A similar pattern was observed in SR $^{45}Ca^{2+}$ uptakes; the specific uptake was the highest in control heart and it was the lowest in diabetic heart. In SR $^{45}Ca^{2+}$ release experiment, the highest release, 45% of SR $^{45}Ca^{2+}$, was observed in control heart. The release of diabetic heart was 20% and it was 30% in insulin-treated diabetic heart. Our results showed that the activities of both SR $Ca^{2+}-ATPase$ and SR $Ca^{2+}$ release channel were decreased in diabetic heart. In order to evaluate how these two factors contribute to SR $Ca^{2+}$ storage, the activity of SR $Ca^{2+}-ATPase$ was measured in the uncoupled leaky vesicles. The uncoupling effect which is able to increase the activity of SR $Ca^{2+}-ATPase$ was observed in control heart; however, no significant increments of SR $Ca^{2+}-ATPase$ activities were measured in both diabetic and insulin-treated diabetic rats. These results represent that the $Ca^{2+}$ storage in SR is significantly depressed and, therefore, $Ca^{2+}-sequestering$ activity of SR may be also depressed in diabetic heart.

• 대한약리학회지
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• 제26권2호
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• pp.113-120
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• 1990

전기장 자극으로 수축을 유발한 흰쥐 좌심방에서, 자극 빈도 변경에 따른 수축 운동의 변동에 미치는, 여러 경로를 통한 수축 유발 calcium의 영향을 검색하므로, 각 경로가 심근 수축에 미치는 영향을 추구하였다. 흰쥐 좌심방은 자극 빈도를 급격하게 낮추므로, 특징적인 삼단계 변동을 나타내었다. 즉, 처음의 급격한 수축 장력증가와, 두번째 일시적인 빠른 장력감소, 이어서 세번째로 수축장력의 유지단계로 나타났으며, 이때 수축장력은 고빈도 자극시의 2배 정도가 되었다. Caffeine처치는 이와같은 자극빈도 하강에 따른 수축 장력의 증가를 현저하게 억압하였다. Verapamil은 고빈도 자극시 수축 운동을 완전히 소실시켰으나, 저빈도 자극으로 변경시에는 verapamil 존재하에서도 수축 운동이 소생되었다. 한편 ouabain처치나 영양액내 sodium 배제시에는 저빈도 자극으로 나타나는 특징적인 두번째 단계의 변동이 소실되었다. 이러한 결과로 보아, 심근막의 calcium통로는 세포내 유지에 필수불가결한 경로이며, 심근 수축 유발 calcium의 주된 기원은 근 소포체로 부터 유리되는 것으로 믿어진다. 또한 sodium-calcium교환은 세포내 sodium농도의 변동에 따라 수축 유발 calcium양 형성에 조절 인자로서의 기능을 갖는 것으로 추측된다.

• Applied Microscopy
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• 제20권2호
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• pp.127-159
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• 1990

This study was investigated to elucidate the effect of chlorambucil on the heart in aging rats. Male rat ranging in age from 3 to 36 months were used. Each age groups(3, 6, 12, 18, 24, 36 months) included control and chlorambucil treated rats. As a part of the study, the ultrastructural changes in the left ventricular myocardial cells were described by using the qualitative and morphometric techniques. The results are summarized as follows. Age associated ultrastructural changes included: an increase in vacuoles, protrusion of plasma membranes, lipid droplets, and lipofuscins in myocardium of control groups. These changes which begin to occur at 12 months and continue through 36 months. At the 36 months some instance of unusual formation of contraction band and separation of intercalated discs were encountered. Morever, these changes and contents with chlorambucil treatment were remarkably increased in comparison with control groups. Age-dependent changes of control group measured with morphometry were not observed in the volume densities of mitochondria and myofibrils. But there was increase in interstitium. On the other hand decrease in sarcoplasmic reticulum and T-tubule system. In chlorambucil treated groups, volume densities of mitochondria and interstitium were increased in comparison with those of the control groups. But sarcoplasmic reticulum and T-tubule system were remarkably decreased.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.101-107
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• 2002

In the present study, the postnatal developmental changes in the expressional levels of cardiac sarcoplasmic reticulum (SR) $Ca^{2+}$ regulatory proteins, i.e. $Ca^{2+}-ATPase,$ phospholamban, and $Ca^{2+}$ release channel, were investigated. Both SR $Ca^{2+}-ATPase$ and phospholamban mRNA levels were about 35% of adult levels at birth and gradually increased to adult levels. Protein levels of both SR $Ca^{2+}-ATPase$ and phospholamban, which were measured by quantitative immunoblotting, were closely correlated with the mRNA levels. The initial rates of $Ca^{2+}$ uptake at birth were about 40% of adult rates and also increased gradually during the myocardial development. Consequently, the relative phospholamban/$Ca^{2+}-ATPase$ ratio was 1 in developmental hearts. $Ca^{2+}$ release channel (ryanodine receptor) mRNA was about $50{\sim}60%$ at birth and increased gradually to adult level throughout the postnatal rat heart development. $^3[H]ryanodine$ binding increased gradually during postnatal myocardial development, which was closely correlated with ryanodine mRNA expression levels during the development except the ryanodine mRNA level at birth. These findings indicate that cardiac SR $Ca^{2+}-ATPase,$ phospholamban, and $Ca^{2+}$ release channel are expressed coordinately, which may be necessary for intracellular $Ca^{2+}$ regulation during the rat heart development.