关附甲素对豚鼠乳头肌动作电位最大除极速度的频率依赖性抑制作用

应用标准微电极技术，研究了关附甲素对豚鼠右心室乳头肌动作电位最大除极速率(V_max)的频率依赖性抑制作用(RDB)，并与美西律，奎尼丁，劳卡尼进行了比较. 在相同刺激间隔(300 ms)，产生50%左右RDB的药物浓度下，美西律的RDB开始最快，其第2个V_max所产生的抑制已占RDB的64%，奎尼丁，劳卡尼和关附甲素的RDB开始速率常数分别为每个动作电位0.165, 0.076和0.136. 美西律，奎尼丁，劳卡尼和关附甲素产生RDB的恢复时间常数分别为1.4, 9.0, 18.2和44.0 s，而且它们的恢复时间常数是不依赖于药物浓度而变化的，结果提示，关附甲素是一个慢动力学钠通道阻滞剂.

Rate-dependent block of maximum velocity of depolarization by Guan- fu base A in guinea pig papillary muscle action potentials

The rate-dependent decrease in maximum velocity of depolarization (V_max) caused by Guan-fu base A (GFA) was analyzed and compared with those caused by three class I antiarrhythmic agents with different binding kinetics (mexiletine, quinidine and lorcainide) in guinea pig papillary muscles using standard microelectrode technique with computerization. In the presence of GFA, quinidine and lorcainide, trains of stimuli at various interstimulus intervas (ISI) of 200-4800 ms led to an exponential decline in V_max to a new steady state level (rate-dependent block, RDB). The RDB was augmented at higher stimulation frequencies and at higher drug concentrations. The onset rate constants of RDB of V_max (at ISI of 300 ms) were 0.136, 0.165 and 0.076 per action potential for GFA (64 μmol·L^-1), quinidine (16 μmol·L^-1) and lorcainide (1 μmol·L^-1), respectively giving approximately 50% decrease in V_max. Mexiletine exhibited the fastest response in the onset rate of RDB. V_max reached 64% of its final fall by the second beat of train. The time constants of the recovery of V_max (τ_re) from the RDB were 44.0, 18.2, 9.0 and 1.4 s, respectively in the presence of GFA (64 μmol·L^-1), lorcainide (1 μmol·L^-1), quinidine (16 μmol·L^-1) and mexiletine (25 μmol·L^-1). The time constants of recovery were independent of the drug concentration. These results suggest that GFA may be a sodium channel blocker with slow kinetics.