• 作者： 陳立; 李志雄; 蘇銘嘉
• 作者服務機構： 台大醫學院藥理研究所; 中山大學化學系
• 中文摘要： S49,CSH087與CSH068均為由香草精合成之阿朴芬鹼，本實驗在單一大鼠心室細胞比較這三種化合物對動作電位與膜電流之影響。在O.1Hz的刺激激下，S49（1.5 μM）, CSH087（3 μM）與CSH068（3μM）均會延長動作電位持續時間。在膜電位鉗定實驗中發現，S49, CSH087與CSH068均會抑制瞬間外流鉀電流，其K值分別為2.0,1.8和5.2μM，但是對鈣電流均無增強作用。另外，對持續外流鉀電流CSH068比其餘兩者有較強之抑制作用。S49，CSH087和CSH068對鈉電流的抑制作用與膜電位有關，對較低的靜止膜電位所引發之鈉電流有較強的抑制，於-80 mV所測得的K值分別為1.2,6.8和7.5μM。另外其還會有使鈉電流的穩定不活化狀態曲線朝負向移動，顯示S49, CSH087與CSH068對鈉管道之不活化狀態有較高的親合力。在測量鈉管道從不活化狀態恢復至靜止狀態的時間時發現，三者均會延長其恢復的時間常數，使得其恢復變慢。S49對鈉電流的作用則較CSH087和CSH068為強。從本實驗的結果發現，S49, CSH087與CSH068的電生理作用類似第一類和第三類的抗心律不整藥。
• 英文摘要： S49, CSH087 and CSH068 are aporphine alkaloids and are synthesized from vanillin. In the presentstudy, the effects of these compounds on the action potential and membrane currents of rat ventricularcells were examined by using the whole cell recording technique with single suction pipettes. At a stimulationfrequency of 0.1 Hz, S49（1.5 μM), CSH087 (3 μM) and CSH068 (3 μM) could prolong the action potentialdurations (APDS and APD). Voltage clamp studies revealed inhibition of the transient outward currentsby S49, CSH087 and CSH068 with K of 2.0, 1.8 and 5.2 μM, respectively, but a lack of enhancement ofcalcium influx. Therefore, the inhibition of the potassium conductance may explain the prolongation ofAPD induced by these compounds. In contrast, the late potassium outward current was more resistant toCSH087 and S49, but was blocked by CSH068 with a K of 6.4 μM．The sodium inward current (I) alsowas inhibited by S49, CSH087 and CSH068 in a dose-dependent manner with Kof 1.2, 6.8 and 7.5 μM,respectively (at a holding potential of-80 mV). The inhibition of I was enhanced at a less negativeholding potential. The voltage-dependent inhibition of I was associated with the shift of the I availabili-ty curve to more negative potentials. These results indicate that these compounds have high affinity forinactivated Na channels. A twin-pulse experiment revealed that these compounds increased the recoverytime constant of I. The potency for the shift of the I availability curve and the retardation of Irecovery from inactivation were S49＞CSH087 and CSH068. The present findings suggest that S49, CSH087and CSH068 may act as class I and class III antiarrhythmic agents.
• 中文關鍵字： isoquinolines; aporphine alkaloids; antiarrhythmic agents; ventricular cells; membrane currents.
• 英文關鍵字： --