• Molecules and Cells
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• 제39권10호
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• pp.722-727
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• 2016

Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions.

• The Korean Journal of Physiology
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• 제17권1호
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• pp.45-54
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• 1983

Contractile responses of myocardium and vascular smooth muscle to angiotensin II were studied in isolated rabbit papillary muscles and aortic helical strips, with respect to the sensitivity and the mechanism of action. All experiments were performed in $HCO-_3\;-buffered Tyrode solution which was aerated with $3%\;CO_2-97%\;O_2$ and kept pH 7.35 at $35^{\circ}C$. Action potentials were measured by conventional microelectrode technique in the papillary muscles. Helical strips of vascular smooth muscle were prepared from the descending thoracic aorta of the rabbit. Angiotensin II elicited a positive inotropic effect in doses from $10^{-8}$ to $10^{-6}\;M$, and this effect was dose-dependent and characterized by a symmetrical increase of maximum dP/dt during contraction and relaxation phase. Slow responses (or slow action potentials) were induced by A. II $(10^{-6}\;M)$ in the papillary muscle hypopolarized by 27 mM $K^+$. These A. II-induced slow action potentials were eliminated by verapamil (2 mg/l), but not affected by propranolol $(10^{-5}\;M)$. In aortic helical strips, contractile force was increased dose-dependently in the range of $10^{-10}{\sim}10^{-7}\;M$ A. II. $ED_{50}$ in aorta was $3{\times}10^{-9}\;M$ A. II, whereas that in paillary muscle was $2.5{\times}10^{-7}\;M$ A. II. A. II contracted vascular smooth muscle in depolarizing concentration of $K^+$ (100 mM $K^+$), and also produced a sustained contraction even in the presence of verapamil and regitine. The results of this experiment suggest that the primarily important physiological role of A. II is the action on the blood vessel, and the positive inotropic effect of A. II in papillary muscle results from the increase of slow inward $Ca^{++}$ current, and that A. II-induced contraction of aorta is independent of transmembrane potential and associated with promoting bet transmembrane $Ca^{++}\;-influx$ and the mobilization of cellular $Ca^{++}$.

• 약학회지
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• 제43권2호
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• pp.237-250
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• 1999

In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

• 대한의생명과학회지
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• 제13권1호
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• pp.1-10
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• 2007

Nebulin, a giant modular protein from muscle, is thought to act as molecular ruler in sarcomere assembly. In skeletal muscle, the C-terminal ${\sim}50 kDa$ region of nebulin extends into the Z-line lattice. The most recent studies implicated highlighting its extensive isoform diversity and exciting reports revealed its expression in cardiac and non-muscle tissues containing brain. Also these novel findings are indicating that nebulin is actually a multifunctional filament system, perhaps playing roles in signal transduction, contractile regulation, and myofibril force generation, as well as other not yet defined functions. However the binding protein of nebulin and function in brain is still unknown. A novel binding partner of nebulin C-terminal region was identified by screening a human brain cDNA library using yeast two-hybrid system. Nebulin C-terminus binding protein 51 (NCBP51) was contained a RING-finger domain and identified a new isoform of RING finger protein 125 (RNF125). The interaction was confirmed using the GST pull-down assay. NCBP51 belongs to a family of the RING finger proteins and its function remains to be identified in brain. The role of nebulin and NCBP51 will be studied by loss-of-function using siRNA technique in brain.

• 대한약리학회지
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• 제17권1호
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• pp.9-15
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• 1981

부자성분중 강심효과를 나타내는 부자부타놀분획의 작용기전을 심근수축기전이 있어서 중심적인 역활을 하는 칼슘이온과의 상호관계에서 검토하였으며 아울러 동물생체내 혈동력학에 대한 영향을 관찰하였다. 부자부타놀분획 적출 고양이 유두근표본의 수축력증가작용에 있어서 심근외칼슘과 상승적이었으며 부자부타놀분획 $10^{-4}g/ml$는 칼슘 0.06mM과 동등한 심근수측증강 효과를 나타내었다. 심근세포막의 칼슘통로 억제약물인 verapamil 존재하에서 저하된 유두근 수축력은 부자부타놀분획에 의하여 용량의존적으로 회복되었으며, 이로부터 부자부타놀분획의 강심작용기전의 일부는 심근세포막의 완만내향성 칼슘통로를 통한 칼슘유입을 측진하는 것과 관계가 있을 것으로 추측하였다. 정상가토의 혈동력학에 있어서 부자부타놀분획은 디지탈리스배당체와는 달리 용량의존적으로 전신동맥압을 저하시키고, 경동맥혈류량을 증가시켰으며, 심박동수에는 크게 의미있는 변화를 보이지 않았다.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.31-41
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• 1986

The sufficient myoplasmic $Ca^{++}$ to react with the contractile proteins is necessary to induce contraction of a cardiac muscle. These $Ca^{++}$ for the production of muscle contraction are supplied from the three recognized $Ca^{++}$ sources; internal $Ca^{++}$ release via the sarcoplasmic reticulum(SR), $Ca^{++}$ influx through a gated Ca-channel in the membrane as a Isi, and $Ca^{++}$ transport by the mechanism of Na/ca exchange. However, it is still controversial which $Ca^{++}$ sources act as a main contributor for myoplasmic $Ca^{++}$, Therefore, this study was undertaken in order to examine the $Ca^{++}$ sources for the contraction of frog ventricle. There is evidence that the SR is sparse in frog ventricular fibers, and that T-tubules are absent. Isolated ventricular strips of frog, Rana nigromaculata, were used in this experiment. Isometric tension was recorded by force transducer, and membrane potentials of ventricular muscles were measured through the intracellular glass microelectrodes, which were filled with 3M KCI and had resistance of $30{\pm}50M{\Omega}$. All experiments were performed at room temperature in a tris·buffered Ringer solution which was aerated with 100% $O_2$. Isotonic high K, low Na solution was used to induce K-contracture, K-contracture appeared at the concentration of 20 to 30mM-KCI and was potentiated in parallel with the increase in KCI concentration. The contracture had two components: an initial rapid phasic and a subsequent slow tonic contractile responses. Membrane Potentials measured at normal Ringer solution(2.5mM KCI) was -90 to -100 mV, and decreased linearly as the KCI concentration increased; -55mV at 20mM.KCI, -45mV at 30 mM.KCI, -30 mY at 50 mM.KCI, and -12 mV at 100 mM.KCI. K-contracture was evoked firstly at the membrane potential of -45 mV. The contracture was potentiated by the increase of bathing extracellular $Ca^{++}$ concentration. However, in the absence of $Ca^{++}$ the contracture was almost not induced by 50 mM.KCI solution. Caffeine(20mM) in normal Ringer solution, which is known to release $Ca^{++}$ from SR without substantial effects on the $Ca^{++}$ fluxes across the surface membrane, did not affect membrane potential and also not initiate contracture, but the caffeine in 20 mM-KCI Ringer solution produced a contracture. Above results suggest that the main $Ca^{++}$ source for the K·contracture of frog ventricle is $Ca^{++}$ influx through the voltage-dependent Ca-channel, and that in the K-contracture at the concentration of 100 mM-KCI, the mechanism of Na/ca exchange also partly contributs, in addition to the $Ca^{++}$ influx.

• 약학회지
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• 제41권6호
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• pp.802-816
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• 1997

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine ($10^{-6}$M) without regard to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.

• 대한약리학회지
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• 제26권1호
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• pp.7-12
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• 1990

흰쥐로 부터 심장을 적출하여 Langendorff 관류장치에 현수하여 Krebs-Hensleit 영양액으로 분당 12ml속도로 30분간 관류시킨 후 관류 속도를 분당 1ml로 줄여(ischemia)60분간 관류시키면, 적출심장의 수축력이 현저히 감소되었고, resting tension이 현저히 증가되었다. 또 적출심장으로부터 유출되는 관류액의 250nm에서의 UV흡광치는 증가되었으며, 좌심실내의 칼슘의 농도는 대조군보다 상당히 증가되었다. 본 실험에서는 흰쥐에서 항염증작용, 혈압강하 및 서맥 작용, 평활근 및 심장근에서 근이완작용을 나타내는 cyclobuxine D의 ischemia에 의해 유도된 심장손상에 대한 보호효과를 관찰하였다. Cyclobuxine D(100ng/ml)는 ischemia에 의해 유발된 적출심장의 수축력 감소와 resting tension의 증가를 유의하게 억제하였으며, 심장으로부터의 ATP metabolites의 유출과 좌심실내의 칼슘 축적을 억제시켰다. 이상의 결과는 Cyclobuxine D가 ischemia에 의해 유발된 손상으로 부터 심장을 보호할 수 있음을 나타내며, 이는 cyclobuxine D의 심장세포내의 칼슘 유입 억제작용에 기인하는 것으로 사려된다.

• 대한약리학회지
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• 제13권2호
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• pp.1-9
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• 1977

최근 강심작용 약물로 보고된 부자 부타놀 분획의 가토 심방근에서의 자극빈도에 따른 강심효과를 분석한 결과는 다음과 같다. 1) 가토 심방근의 수축력은 자극빈도에 따라 polyphasic한 수축양상을 보였으며 rested-state contraction은 $120{\sim}400sec$의 interval에서 나타났으며 이후 10sec의 간격까지는 급격한 수축력의 감소를 보이는, 축적NIEA가 PIEA의 양을 능가하는 양상을 보였으며 이 이하의 자극 빈도에서는 수축력의 증가를 보였고 대부분 0.25 sec이하의 빈도의 자극으로는 수축력의 감소를 보였다. 2) Ouabain은 저 농도에서는 interval-strength curve에 대하여 rested-state contraction의 증가와 전 자극빈도에서 비슷한 수축력의 증가를 나타내었으며, 고농도에서는 rested-state contraction의 증가와 축적 NIEA의 소멸 속도를 증가시켰으나 이는 rested-state contraction을 나타내는 시간의 단축에 따른 이차적 효과로 판정하였다. 또한 ouabain 자극빈도에 따른 강심 효과의 양상은 세포외 calcium 농도를 증가시킨 때와 유사한 양상이었다. 3) Norepinerhrine은, rested-state contraction에는 거의 영향을 주지 않았으며, 고 빈도에서 더욱 현저한 강심 작용을 나타내었고 축적 PIEA의 양의 증가와 매 beat 당 산출하는 PIEA의 양의 증가를 나타내었다. 4) 부자 부타놀 분획은 norepinephrine과 유사하고 빈도에서 수축력의 증가가 현저 하였으며, 수축력의 증가는 용량 반응 상관을 보였으며, PIEA 축적량 및 매 beat 당 산출하는 PIEA를 증가 시켰다. 따라서 고빈도에서의 강력한 수축력의 증가는 PIEA에 대한 효과에 의할 것으로 사료하였다.

• Journal of Acupuncture Research
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• 제19권5호
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• pp.92-111
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• 2002

Objective : Carthami Flos has been used as a herb to promote blood circulation to remove blood stasis in oriental medicine for many centuries, and Amun(GV15) has been used as a meridian point to treat apoplexy etc. To investigate treatment of cerevral vascular disease(CVA) by promoting blood circulation and removing blood stasis(活血化瘀法), we observed the experimental effects and mechanism of auqa-acupunture of Carthami Flos(ACF) injected into GV15 on cerevral hemodynamics and cardiovascular system of rats. Method : Aqua-acupuncture of Carthami Flos(ACF) was injected into GV15, and then we investigated experimental effects and mechanism of ACF on the cerebral hemodynamics[regional cerebral blood flow(rCBF), pial arterial diameter(PAD), meal arterial blood pressure(MABP)] and cardiovascular system[cardiac muscle contractile force(CMF), heart rate(HR)I by pretreatment with methylene blue(MTB) and indomethacin(IDN). The changes in rCBF, MABP, CMF and HR were tested by Laser Doppler Flowmetry(LDF), and the changes in PAD was determinated by video microscopy methods and video analyzer. Results :The results were as follows in normal rats ; The changes of rCBF and PAD were significantly increased by ACF($120{\mu}{\ell}/kg$) in a injected time-dependent manner, but MABP was not changed by ACF. The changes of cardiovascular system were increased by ACF in a injected time-dependent manner. And pretreatment with MTB was significantly inhibited ACE induced increase of rCBF and PAD, and was decreased ACF induced increase of HR. And pretreatment with IDN was increased ACF induced MABP and CMF. And the results were as follows in cerebral ischemic rats ; The changes of rCBF was increased stabilizly by treatment with ACF($120{\mu}{\ell}/kg$) in during the period of cerebral reperfusion, but pretreatment with MTB was increased ACF induced increase of rCBF during the period of cerebral reperfusion. The results were as follows in normal rats ; The changes of rCBF and PAD were significantly increased by ACF($120{\mu}{\ell}/kg$) in a injected time-dependent manner, but MABP was not changed by ACF. The changes of cardiovascular system were increased by ACF in a injected time-dependent manner. And pretreatment with MTB was significantly inhibited ACF induced increase of rCBF and PAD, and was decreased ACF induced increase of HR. And pretreatment with IDN was increased ACF induced MABP and CMF. And the results were as follows in cerebral ischemic rats ; The changes of rCBF was increased stabilizly by treatment with ACF($120{\mu}{\ell}/kg$) in during the period of cerebral reperfusion, but pretreatment with MTB was increased ACF induced increase of rCBF during the period of cerebral reperfusion Conclusions : In conclusion, ACF causes a diverse response of rCBF, PAD an HR, and action of ACF is mediated by cyclic GMP. I suggested that ACF has an anti-ischemic effect through the improvement of crebral hemodynamics in a transient cerebral ischemia.