Kamiya K, Takikawa R, Singh B N
Department of Medicine, UCLA School of Medicine.
J Cardiovasc Pharmacol. 1989 Apr;13(4):630-7.
The effects of recainam (Wy 42,362) on transmembrane action potentials were examined in isolated rabbit right ventricular papillary muscles. Recainam (3 x 10(-5) to 3 x 10(-4) M) caused a concentration-dependent decrease in the Vmax of the action potential. At 3 x 10(-4) M, there was a slight decrease in the amplitude of the action potential. The resting potential and the action potential duration were not affected. Use-dependent block of Vmax was tested over a wide range of pacing frequencies (from 0.1 to 3.0 Hz). At 1.0 Hz, recainam 10(-4) M produced exponential decreases in Vmax with a rate constant of 0.17 per action potential and 39.8% reduction at steady state. This use-dependent block was augmented at the higher stimulation frequencies. The time constant for the recovery of Vmax from use-dependent block (offset) was 17.2 s. In papillary muscles depolarized with 10 mM [K+]0, the use-dependent block was augmented but tonic block and the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations in 4 mM [K+]0. The curves relating membrane potential and Vmax in preparations stimulated at a low frequency (0.01 Hz) were not shifted by 10(-4) M recainam. These findings suggest that recainam is a specific sodium-channel blocker and has kinetically slow but potent affinity for the channel during action potentials. This selective binding during action potential was further augmented by depolarization and is likely to play a significant role in the control of ventricular arrhythmias by the drug.
在离体兔右心室乳头肌中研究了瑞卡南（Wy 42,362）对跨膜动作电位的影响。瑞卡南（3×10⁻⁵至3×10⁻⁴M）引起动作电位Vmax呈浓度依赖性降低。在3×10⁻⁴M时，动作电位幅度略有降低。静息电位和动作电位持续时间未受影响。在很宽的起搏频率范围（从0.1至3.0Hz）测试了Vmax的使用依赖性阻滞。在1.0Hz时，10⁻⁴M瑞卡南使Vmax呈指数下降，每个动作电位的速率常数为0.17，稳态时降低39.8%。这种使用依赖性阻滞在较高刺激频率时增强。Vmax从使用依赖性阻滞恢复（抵消）的时间常数为17.2秒。在用10mM [K⁺]₀使乳头肌去极化时，使用依赖性阻滞增强，但强直阻滞以及使用依赖性阻滞的起始和抵消速率与在4mM [K⁺]₀的正常极化标本中相似。在低频（0.01Hz）刺激的标本中，10⁻⁴M瑞卡南未使膜电位与Vmax的关系曲线发生移位。这些发现提示瑞卡南是一种特异性钠通道阻滞剂，在动作电位期间对通道具有动力学缓慢但强效的亲和力。动作电位期间的这种选择性结合在去极化时进一步增强，并可能在该药物控制室性心律失常中起重要作用。
