• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.112-112
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• 2003

Voltage-gated $K^{+}$ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. These channels play an important role in determining the length of the cardiac action potential and are the targets for antiarrhythmic drugs. Many $K^{+}$ channel genes have been cloned from human myocardium and functionally contribute to its electrical activity. One of these channels, Kv1.5, is one of the more cardiovascular-specific $K^{+}$ channel isoforms identified to date and forms the molecular basis for an ultra-rapid delayed rectifier $K^{＋}$ current found in human atrium. Thus, the blocker of hKv1.5 is expected to be an ideal antiarrhythmic drug for atrial fibrillation. Chelidonine was isolated from Chelidonium majus L. We examined the effect of chelidonine on the hKv1.5 current expressed in Ltk-cells using whole cell mode of patch clamp techniques. Chelidonine selectively inhibited the hKv1.5 current expressed in Ltk-cells in a concentration-dependent manner, whereas did not affect the HERG current expressed in HEK-293 cells. Additionally, chelidonine reduced the tail current amplitude recorded at -50 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a 'crossover' phenomenon when the tail currents recorded under control conditions and in the presence of chelidonine were superimposed. We found that chelidonine also inhibited the $K^{+}$ current in isolated human atrial myocytes where hKv1.5 channels were predominantly expressed. Furthermore, we examined the effects of chelidonine on the action potentials in rabbit hearts using conventional microelectrode technique. Chelidonine prolonged the action potential durations (APD) of atrial, ventricular myocytes and Purkinje fibers in a dose-dependent manner. However, the effect of chelidonine on atrial APD was frequency-dependent whereas the effect of chelidonine on the APDs of ventricular myocytes and Purkinje fibers was not frequency- dependent. Also, the selective action of chelidonine on heart was more potent than dofetilide, $K^{+}$ channel blocker.

• The Korean Journal of Physiology and Pharmacology
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• 제16권5호
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• pp.327-332
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• 2012

Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In these experiments, we have used the whole cell patch clamp technique to examine the effects of sertraline on the major cardiac ion channels expressed in HEK293 cells and the native voltage-gated $Ca^{2+}$ channels in rat ventricular myocytes. According to the results, sertraline is a potent blocker of cardiac $K^+$ channels, such as hERG, $I_{Ks}$ and $I_{K1}$. The rank order of inhibitory potency was hERG > $I_{K1}$ > $I_{Ks}$ with $IC_{50}$ values of 0.7, 10.5, and 15.2 ${\mu}M$, respectively. In addition to $K^+$ channels, sertraline also inhibited $I_{Na}$ and $I_{Ca}$, and the $IC_{50}$ values are 6.1 and 2.6 ${\mu}M$, respectively. Modification of these ion channels by sertraline could induce changes of the cardiac action potential duration and QT interval, and might result in cardiac arrhythmia.

• 대한영상의학회지
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• 제81권2호
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• pp.302-309
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• 2020

파브리병(Fabry disease)은 매우 드문 X-연관 유전 대사 질환으로 알파 갈락토시다아제(alpha galactosidase A)의 결핍으로 인하여 다양한 세포 및 기관에 글리코스핑고지질(glycosphingolipid)의 축적을 초래하는 질환이다. 심장 침범이 비교적 흔하며 비정상적인 지질침착으로 인한 심근 염증, 좌심실 비대 및 심근 섬유증을 일으킨다. 심장 침범은 환자 예후를 결정하는 중요한 요인이므로 이를 진단하는 것은 매우 중요하다. 심장 자기공명영상은 심실의 기능, 부피 측정을 위한 표준기법으로 알려져 있으며 심근의 조직 변화를 볼 수 있는 유용한 기법이다. 특히 최근 많이 쓰이는 T1 지도화 기법을 통한 심근 조영 전 T1 수치를 이용하여 파브리병의 심장 침범을 조기 진단할 수 있으며 자기공명영상을 이용한 심근 질량 측정으로 치료 모니터링을 할 수 있다. 심장 자기공명영상은 파브리병 환자에서 다양한 역할을 할 수 있을 것으로 생각되며 이에 대해 정리해보고자 한다.

• Applied Microscopy
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• 제33권4호
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• pp.299-313
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• 2003

본 연구는 피부화상으로 유도된 심근손상에서 protein kinase C (PKC)의 역할을 알아보고자 하였다. 수컷 흰 쥐(SD계)에 15%의 피부전층화상을 유도한 뒤, PKC activator인 phorbol 12-myristate 13-acetate (PMA)와 PKC inhibitor인 bisindolylmaleimide (BIS)를 투여하여 5시간, 24시간 후에 심장을 적출하여 생화학적 미세구조적 입체해석학적 방법을 실시하였다. 혈청 AST와 creatinine 은 화상 후 5시간군과 화상 후 5시간+BIS 투여군에서 높게 나타났고, KC와 MPO 활성은 PMA 투여군이 BIS 투여군보다 낮게 나타났다. 미세구조적 관찰 결과 PMA 투여군에서는, 화상으로 인한 핵의 분열, 과수축대 형성, 사이원반의 분리 현상이 다소 완화된 형태로 관찰되었고, BIS 투여군에서는 화상 단독군에서 나타나는 형태적 변화 뿐만 아니라 비정상적인 형태의 사립체도 일부 관찰되었다. 전체적으로 5시간에서 24시간군으로 가면서 손상이 완화된 양상을 나타내었다. 입체해석학적 결과에서는 화상으로 인한 근원섬유의 체적밀도 감소가 PMA와 BIS 투여로 인해 증가되었고, 사립체의 체적밀도와 수밀도의 증가는 BIS군에서 가장 높게 나타났다. 결론적으로 PKC의 활성화는 화상으로 인해 손상된 심근에서 염증반응을 감소시켜 심근 손상을 보호한다고 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.129-143
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• 2024

Sulfur dioxide (SO₂), a novel endogenous gas signaling molecule, is involved in the regulation of cardiac function. Exerting a key role in progression of hyperthyroidism-induced cardiomyopathy (HTC), myocardial fibrosis is mainly caused by myocardial apoptosis, leading to poor treatment outcomes and prognoses. This study aimed to investigate the effect of SO₂ on the hyperthyroidism-induced myocardial fibrosis and the underlying regulatory mechanisms. Elisa, Masson staining, Western-Blot, transmission electron microscope, and immunofluorescence were employed to evaluate the myocardial interstitial collagen deposition, endoplasmic reticulum stress (ERS), apoptosis, changes in endogenous SO₂, and Hippo pathways from in vitro and in vivo experiments. The study results indicated that the hyperthyroidism-induced myocardial fibrosis was accompanied by decreased cardiac function, and down-regulated ERS, apoptosis, and endogenous SO₂-producing enzyme aspartate aminotransferase (AAT)1/2 in cardiac myocytes. In contrast, exogenous SO₂ donors improved cardiac function, reduced myocardial interstitial collagen deposition, up-regulated AAT1/2, antagonized ERS and apoptosis, and inhibited excessive activation of Hippo pathway in hyperthyroid rats. In conclusion, the results herein suggested that SO₂ inhibited the overactivation of the Hippo pathway, antagonized ERS and apoptosis, and alleviated myocardial fibrosis in hyperthyroid rats. Therefore, this study was expected to identify intervention targets and new strategies for prevention and treatment of HTC.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.30-30
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• 2003

Without a definitive resolution of stoichiometry of cardiac Na$^{+}$-Ca$^{2+}$exchange (NCX), we cannot proceed to any quantitative analysis of exchange function as well as cardiac excitation-contraction coupling. The stoichiometry of cardiac NCX, however, is presently in doubt because reversal potentials determined by various groups range between those expected for a 3-to-1 and a 4-to-1 flux coupling. For a new perspective on this problem, we have used ion-selective microelectrodes to quantify directly exchanger-mediated fluxes of $Ca^{2+}$and Na$^{+}$in giant membrane patches. $Ca^{2+}$- and Na$^{+}$-selective microelectrodes, fabricated from quartz capillaries, are placed inside of the patch pipettes to detect extracellular ion transients associated with exchange activity. Ion changes are monitored at various distances from the membrane, and the absolute ion fluxes through NCX are determined via simulations of ion diffusion and compared with standard ion fluxes (Ca$^{2+}$ fluxes mediated by $Ca^{2+}$ ionophore, and Na$^{+}$ fluxes through gramicidin channels and Na$^{+}$/K$^{+}$pumps). Both guinea pig myocytes and NCX1-expressing BHK cells were employed, and for both systems the calculated stoichiometries for inward and outward exchange currents range between 3.2- and 3.4-to-1. The coupling ratios do not change significantly when currents are varied by changing cytoplasmic [Ca$^{2+}$] or by adding cytoplasmic Na$^{+}$. The exchanger reversal potentials, measured in both systems under several ionic conditions, range from 3.1- to 3.3-to-1. Taken together, a clear discrepancy from a NCX stoichiometry of 3-to-1 was obtained. Further definitive experiments are required to acquire a fixed number, and the present working hypothesis is that NCX current has an extra current via ‘conduction mode’.ent via ‘conduction mode’.

• 대한수의학회지
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• 제44권1호
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• pp.125-129
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• 2004

A 2-year-old, female, American cocker spaniel dog presented for a 1-year history of severe ascites, exercise intolerance, tachypnea. At that time, she was in an emergency state. First, the dog was stabilized with oxygen therapy. A diagnosis of cardiac problem was made from history, auscultation, radiograph, ECG, and echocardiography. Jugular pulsation was palpated and a harsh, systolic murmur of tricuspid regurgitation was prominent at the right cardiac apex. Tricuspid valve dysplasia (TVD) was confirmed with echocardiography, accompanying enormous myocardial hypertrophy. The clinical signs had been improved for 8 months with careful therapy and periodic abdominocentesis, and ascites was well controlled. The situation, however, became worse quickly in a week because the client did not follow our management schedule. Finally, she died due to dyspnea and shock. After the spontaneous death, necropsy and histopathological examination were performed and when we opened the thorax, a significantly large heart was observed. On histopathological findings, grossly myocardium appeared pale initially, then progressed to yellow and white. Microscopically, there was an extensive hemorrhage along with loss of myocardial striations. Interstitial fibrosis and various degenerative alterations in myocytes were also present.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.305-313
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• 1999

To explore whether $Cl^-$ channel blockers interact with the ATP-sensitive $K^+\;(K_{ATP})$ channel, I have examined the effect of two common $Cl^-$ channel blockers on the $K_{ATP}$ channel activity in isolated rat ventricular myocytes using patch clamp techniques. In inside-out patches, 4,4'-diisothio-cyanatostilbene- 2,2'-disulfonic acid (DIDS) and niflumic acid applied to bath solution inhibited the $K_{ATP}$ channel activity in a concentration-dependent manner with $IC_{50}$ of 0.24 and 927 ${\mu}M,$ respectively. The inhibitory action of DIDS was irreversible whereas that of niflumic acid was reversible. Furthermore, DIDS-induced block was not recovered despite exposure to ATP (1 mM). In cell-attached and inside-out patches, DIDS blocked the pinacidil- or 2,4-dinitrophenol (DNP)-induced $K_{ATP}$ channel openings. In contrast, niflumic acid did not block the pinacidil-induced $K_{ATP}$ channel openings in inside-out patches, but inhibited it in cell-attached patches. DIDS and niflumic acid produced additional block in the presence of ATP and did not affect current-voltage relationship and channel kinetics. All these results indicate that DIDS among $Cl^-$ channel blockers specifically blocks the cardiac $K_{ATP}$ channel.

• Journal of Chest Surgery
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• 제36권4호
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• pp.277-279
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• 2003

15세 남아가 경도의 운동 시 호흡곤란, 우연히 발견된 심잡음을 주소로 내원하였다. 심초음파 소견에서 주로 심실중격을 침범한 종양에 의한 좌심실유출로 협착을 보였고, 심도자에서 측정한 좌심실유출로 평균 압력차는 20 mmHg였다. 체외순환하에 대동맥절개를 통해 종양의 부분절제를 시행하였고, 병리검사 결과 심근이형종으로 진단되었다. 병변은 중증비대를 보이는 성숙한 심근세포와 주변부 섬유화가 주를 이루었다. 술 후 5년간의 외래추적관찰에서 부정맥 발생이나 종양 재발의 증거는 관찰되지 않았다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1996년도 정기총회 및 학술발표회
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• pp.40-40
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• 1996

Abnormally high $Ca^{2+}$ concentrations have been reported in the cardiac myocytes of diabetic mellitus (DM). In order to elucidate the molecular mechanisms of the intracellular $Ca^{2+}$ overload, the activities of $^{45}$ Ca$^{2+}$ uptake and $^{45}$ Ca$^{2+}$ release were measured from the vesicles of junctional SR (Heavy SR, HSR). (omitted)omitted)