Courtney K R
Palo Alto Medical Foundation, CA 94301.
J Mol Cell Cardiol. 1988 Jun;20(6):461-4. doi: 10.1016/s0022-2828(88)80073-7.
It has been known for some time now that many antiarrhythmics and local anesthetics block sodium channels especially when they are depolarized. Two major phases of channel blocking occur, one "transient" and one "maintained" during the depolarization. Open channel blocking is thought to occur when intracellular forms of drug access the open channel via an aqueous pathway. This early phase of drug access is transient in the sense that opening of channels occurs for only a brief period of time (a few ms) after a depolarizing stimulus. There is also drug access to the receptor during maintained depolarizations, such as during the plateau phase of cardiac action potentials. New results provided by Kodama et al. regarding these two phases of drug blocking, transient and maintained, have prompted the structural analysis presented here. A surprisingly simple size criterion is developed that explains why certain drugs cannot use the pathway that is available during maintained depolarizations.
目前已知，许多抗心律失常药和局部麻醉药可阻断钠通道，尤其是在通道去极化时。通道阻断主要有两个阶段，一个是去极化过程中的“瞬时”阶段，另一个是“持续”阶段。开放通道阻断被认为是细胞内形式的药物通过水性途径进入开放通道时发生的。药物进入的这个早期阶段是瞬时的，因为在去极化刺激后，通道仅在短时间（几毫秒）内开放。在持续去极化期间，如在心脏动作电位的平台期，也有药物进入受体。儿玉等人关于药物阻断的这两个阶段，即瞬时阶段和持续阶段的新结果，促使了本文所呈现的结构分析。我们得出了一个惊人简单的尺寸标准，它解释了为什么某些药物不能利用持续去极化期间可用的途径。
