• Archives of Pharmacal Research
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• 제29권10호
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• pp.834-839
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• 2006

Torilin was purified from Torilis japonica (Houtt.) DC., and its effects on a rapidly activating delayed rectifier $K^+$ channel (hKv1.5), cloned from human heart and stably expressed in Ltk cells, as well as the corresponding $K^+$ current (the ultrarapid delayed rectifier, $I_{KUR}$) were assessed in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, torilin was found to inhibit the hKv1.5 current in time and voltage-dependent manners, with an $IC_50$ value of $2.51{\pm}0.34\;{\mu}M$ at +60 mV. Torilin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Additionally, torilin inhibited the hKv1.5 current in a use dependent manner. These results strongly suggest that torilin is a type of open-channel blocker of the hKv1.5 channel.

• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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• pp.333-339
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• 2003

It has been demonstrated that an unidentified cytosolic factor(s) reduces $K_{ACh}$ channel function. Therefore, this study attempted to elucidate the cytosolic factor. Fresh cytosol isolated from normal heart (FC) depressed the $K_{ACh}$ channel activity, but cytosol isolated from the ischemic hearts (IC) did not modulate the channel function. Electrophorectic analysis revealed that a protein of ${\sim}80 kDa was markedly reduced or even lost in IC. By using peptide sequencing analysis and Western blot, this 80 kDa protein was identified as transferrin (receptor-mediated $Fe^{3+}$ transporter, 76 kDa). Direct application of transferrin (100 nM) to the cytoplasmic side of inside-out patches decreased the open probability ($P_o$, 12.7${\pm}6.4%, n=4) without change in mean open time (${\tau}_o$, $98.5{\pm}1.3$%, n=4). However, the equimolar apotransferrin, which is free of $Fe^{3+}$, had no effect on the channel activity (N*$P_o$, $129.1{\pm}13.5$%, n=3). Directly applied $Fe^{3+}$ (100 nM) showed results similar to those of transferrin (N*$P_o$: $21.1{\pm}3.9$%, n=5). However $Fe^{2+}$ failed to reduce the channel function (N*$P_o$, $106.3{\pm}26.8$%, n=5). Interestingly, trivalent cation La3+ inhibited N*$P_o$ of the channel ($6.1{\pm}3.0$%, n=3). Taken together, these results suggest that $Fe^{3+}$ bound to transferrin can modulate the $K_{ACh}$ channel function by its electrical property as a polyvalent cation.

• Journal of Chest Surgery
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• 제40권8호
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• pp.552-557
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• 2007

배경: B-type natriuretic peptide (BNP)는 심실 심근 세포에서 생성되는 심장 호르몬이며, 울혈성 심부전, 심실비대증, 심근염, 심장이식 후 거부반응 때 증가하는 것으로 알려져 있다. 본 연구에서는 심장이식 후 거부 반응의 예측 인자로서의 BNP의 역할에 대해 조사하였다. 대상 및 방법: 심장이식을 받은 10명의 환자를 대상으로 하여 2004년 1월부터 2005년 8월까지 BNP측정값, 심내막 생검을 통한 거부반응, 혈역학적 지표, 심초음파 검사 결과 등을 조사하였으며, 57예의 BNP 측정값의 중간값인 290 pg/mL를 기준으로 하여 Low BNP (n=28, $BNP{\le}290$ pg/mL)군, High BNP (n=29, BNP>290 pg/mL)군으로 나누어 거부반응의 정도, 좌심실구혈률, 삼첨판막 폐쇄 부전, 좌심실비대, 폐동맥쐐기압, 평균 폐동맥압, 우심방압을 후향적으로 비교 분석하였다. 결과: BNP값의 차이에 따른 양 군 간심내막생검에 따른 거부반응의 정도, 좌심실구혈률, 삼첨판막 폐쇄 부전, 좌심실비대, 우심방압은 통계학적으로 유의한 차이가 없었다(p>0.05). 그러나, High BNP군에서 폐동맥쐐기압, 평균 폐동맥압이 Low BNP군보다 높았으며(p<0.05), BNP 측정값은 폐동맥쐐기압과 의미 있는 양의 상관관계를 보였다(r=0.590, p<0.001). BNP 측정값 620 pg/mL를 기준으로 했을때, 폐동맥쐐기압은 83.3%의 민감도와 91.1%의 특이도를 보이며 12 mmHg보다 높은 값을 보였다(AUC: $0.900{\pm}0.045$, p<0.001). 결론: 심장이식 후 BNP 측정값은 거부반응의 정도와 의미 있는 상관관계를 보이지는 않았으나, 심실의 이완기 불능 상태를 평가하는 유용한 지표가 될 수 있다.