K+ channel blocking actions of flecainide compared with those of propafenone and quinidine in adult rat ventricular myocytes.
K+ channel blocking actions of flecainide compared with those of propafenone and quinidine in adult rat ventricular myocytes.
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发表时间：
1994-04
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通讯作者：
M. Slawsky;N. Castle
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作者：
M. Slawsky;N. Castle
用全细胞膜片钳技术比较了Ic类抗心律失常药氟卡尼、普罗帕酮和奎尼丁对离体成年大鼠心室肌细胞K+通道的阻断作用。在大鼠心室肌细胞中，去极化激活失活（ITO）和维持（IK）外向K+电流。氟卡尼、普罗帕酮和奎尼丁都是ITO的有效抑制剂，IC 50分别为3.7、3.3和3.9 μ M。氟卡尼和奎尼丁的IK抑制作用不如普罗帕酮，IC 50为15和14 μ M，而普罗帕酮的IC 50为5 μ M。通过与它们对外向电流的影响相比，这些试剂对内向整流K+电流产生很少或没有抑制，即使在300 μ M时也是如此。所有这三种药物产生的浓度依赖性增加ITO的失活率，但他们只产生轻微的超极化位移（约3 mV）的电压依赖性稳态失活。虽然普罗帕酮对ITO失活的恢复率几乎没有影响，（tau对照= 64 +/- 5 ms; tau普罗帕酮= 84 +/- 9 ms），在氟卡尼和奎尼丁存在下的ITO回收率为双指数;它表现出额外的缓慢组分（氟卡尼的τ FAST = 67 +/- 5 ms，τ SLOW = 2580 +/- 1500 ms;奎尼丁的τ FAST = 55 +/- 5 ms，τ SLOW = 871 +/- 99 ms）。与这些观察结果一致，氟卡尼和奎尼丁，但普罗帕酮，产生使用依赖性块的ITO在1 Hz的刺激频率。（250字处删节）
The K+ channel blocking action of the class Ic antiarrhythmic agent flecainide was compared with that of propafenone and quinidine in isolated adult rat ventricular myocytes by using the whole-cell patch-clamp technique. In rat ventricular myocytes, depolarization activates both an inactivating (ITO) and a maintained (IK) outward K+ current. Flecainide, propafenone and quinidine all were potent inhibitors of ITO with IC50s of 3.7, 3.3 and 3.9 microM, respectively. Flecainide and quinidine were less potent inhibitors of IK than was propafenone with IC50s of 15 and 14 microM compared with an IC50 of 5 microM for propafenone. By contrast with their effects on outward currents, these agents produced little or no inhibition of the inward rectifier K+ current, even when present at 300 microM. All three agents produced a concentration-dependent increase in the rate of inactivation of ITO but they only produced minor hyperpolarizing shifts (approximately 3 mV) in the voltage dependence of steady-state inactivation. Although propafenone had little effect on the rate of ITO recovery from inactivation (tau CONTROL = 64 +/- 5 ms; tau PROPAFENONE = 84 +/- 9 ms), ITO recovery in the presence of flecainide and quinidine was biexponential; it exhibited an additional slow component (tau FAST = 67 +/- 5 ms and tau SLOW = 2580 +/- 1500 ms for flecainide; tau FAST = 55 +/- 5 ms and tau SLOW = 871 +/- 99 ms for quinidine). Consistent with these observations, flecainide and quinidine, but not propafenone, produced use-dependent block of ITO at a stimulation frequency of 1 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)