| Summary: | 碩士 === 國立臺灣大學 === 藥理學研究所 === 84 === HF-Ⅴ-15 是合成小分子生物鹼，在大白鼠心臟組織具有稍微增加收縮力
及減慢心跳頻率的作用。本篇論文主要研究 HF-Ⅴ-15 在大白鼠及天竺鼠
心臟組織的電生理學，並研究其抗心律不整的作用機轉。 1、在大白鼠心
房及心室組織，HF-Ⅴ-15 (3∼30μM) 會使收縮力隨濃度增加而略為增強
，並使右心房自發性跳動頻率減慢。 2、在離體天竺鼠心臟組織中，HF-
Ⅴ-15 能使 ouabain 誘發的心律不整，恢復為正常的跳動。 3、HF-
Ⅴ-15 (30μM) 不影響 isoproterenol 的劑量反應曲線。 4、在大白鼠
心室細胞，10μM HF-Ⅴ-15 會延長動作電位，但不影響零期去極化速率
，在 30μM 會使膜電位去極化，動作電位期間更加延長，並且顯著抑制
零期去極化速率。 5、利用全細胞膜電位鉗定法，HF-Ⅴ-15 (3∼100μ
M) 會抑制鈉電流，使鈉電流穩定不活化曲線向負電位方向漂移，並使鈉
電流的恢復時間常數延長。 6、HF-Ⅴ-15 (3∼100μM) 會抑制大白鼠心
室細胞的鈣電流，其抑制作用在 1∼2 分鐘可達穩定，並使穩定不活化曲
線往負電位方向漂移，但不影響鈣管道恢復時間常數(fast component)
。 7、在大白鼠心室細胞，HF-Ⅴ-15 (3∼100μM) 會抑制瞬時外流鉀電
流，其抑制作用在 1∼2 分鐘可達穩定，其抑制程度會隨鉗定時間增加而
增加，並加速其不活化速率，延長恢復時間常數，使穩定不活化曲線向負
電位方向漂移。 8、在大白鼠心室細胞，HF-Ⅴ-15 (10∼100μM) 會抑制
內向整流鉀電流，在 100μM 內向流鉀電流的尖峰電流幾乎完全受抑制，
此內向整流鉀電流之值會隨超極化時間的延長而逐漸恢復。 9、HF-
Ⅴ-15 (10∼100μM) 會抑制天竺鼠心室細胞的遲發性外流鉀電流。 10、
HF-Ⅴ-15 為作用快速的藥物，對上述各種電流的抑制較不具有選擇性，
其抗心律不整的能力來自於鈉、鉀及鈣離子管道的抑制。
HF-V-15 is a synthetic alkaloid found to have slight positive
inotropic and negative chronotropic effect in rat cardiac
tissues . The aim of the study was to examine the
pharmacological effects of HF-Ⅴ-15 on rat and guinea pig
cardiac tissues. The anti- arrhythmic effect of HF-Ⅴ-15 was
also examined. 1.In rat ventricular cells, 10μM HF-Ⅴ-15
prolonged the action potential duration(APD) without any
decrease in (dV/dt)max of the action potential. At 30μM, it
caused depolarization and further increase in APD. 2.In rat
ventricular cells HF-Ⅴ-15(3∼100μM) reduced the sodium
current(INa) and shifted the steady-state inactivation curves
of INa in negative direction and prolonged the recovery time
constant of INa. 3.In rat ventricular cells HF-Ⅴ-15(3∼100μM)
reduced the calcium current(ICa) and reach its steady state
level within 1∼2 minute. The inhibition of ICa was associated
with a negative shift of the steady-state inactivation curve.
4.In rat ventricular cells HF-Ⅴ-15(3∼100μM) reduced the
transient outward curr ent(Ito) time-dependently. This
inhibition of Ito reach its steady state level within 1∼2
minute. HF-Ⅴ-15 accelerated the inactivation rate of Ito and
shifted the steady- state inactivation curve in negative
direction. The recovery time from inactivation state was also
prolonged. 5.HF-Ⅴ-15(10∼100μM ) inhibited the inward
rectifier potassium current(IK1) in rat ventricular cells. The
peak inward current through K1 channels was abolished
completely by 100μM HF-Ⅴ-15. On hyperpolarization , partial
relieve of complete IK1 block was observed. 6.HF-Ⅴ-15 (10∼100
μM) can inhibit delayed rectifier potassium current in guinea
pig ventricular cells. HF-Ⅴ-15 is a fast onset drug. There is
little selectivity of HF-Ⅴ-15 on INa, ICa, Ito and IK1. The
antiarrhythmic effect of HF-Ⅴ-15 can be attributed to its
multiple actions on ion channels.
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