A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found tha...
A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.
A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.
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대상 데이터
moellendorffii Hance was collected in July 2002 at Soonchang, Chonbuk, Korea. A voucher specimen was deposited in the herbarium of the College of Pharmacy, Woosuk University (WSU-02-015).
데이터처리
The results are expressed as mean ± S.E.M. The student's Mest and analysis of variance (ANOVA) were used for statistical analysis of data. A value of p<0.
이론/모형
Steady-state currents taken at the end of the depolarizing puse of +60 mV were normalized to the control to construct the dose-response curve. Data were fitted with the Hill equation. Each point of the vertical bar denotes the mean ± S.
Kv currents were recorded by using the whole cell configuration of the gigaohm-seal patch clamp technique (Kwak et al., 1999). Electric기 signals were amplified with a patch clamp amplifier (Axopatch-1D, Axon Instruments, Foster).
성능/효과
5 channel. Fourth, the effects of psoralen were use-dependent. These phenomena are also cited as evidences of an open-channel blocking mechanism.
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