A classification of antiarrhythmic drugs based on the Na^+ channel blocking properties directly assessed by the cardiac Na^+ current recordings

根据评估药物作用的方法、不同的制剂和个别记者的不同，I类抗心律失常药物的次级分类有相当大的差异。作为上述混淆的一个可能原因，大多数报道都是通过测量动作电位的V&lt；max和gt；来评估Na~+通道阻滞剂的，动作电位是Na~+通道可用性的间接指标，而不是当前的测量。因此，我们尝试用膜片钳技术直接通过记录心肌Na~+电流来探讨I类抗心律失常药物对Na~+通道的阻断模式，并在此基础上对药物进行新的分类。我们用胶原酶处理的豚鼠心脏分离的心室肌细胞。用膜片钳全细胞构型、细胞贴附和内向外膜片构型、异丙吡胺、I_a试剂记录Na~+电流，产生快和慢两个指数函数的用药依赖的钠电流阻断。不同外在pH条件下的实验进一步表明，慢阻断过程是由与Na~+通道激活状态具有亲和力的药物的电离形式引起的，而快过程是由非电离形式的药物对通道激活状态产生的。快的和慢的阻塞分数组成几乎相同的程度。Ib试剂利多卡因也引起两次指数级阻滞发展，而大部分阻滞发展是由快成分引起的，小部分是由慢成分引起的。快速阻断是由非电离药物结合通道的失活状态，慢阻断是由电离药物引起的通道激活状态。与利多卡因相似，美施莱汀也引起两个指数阻滞发展。电离美西律压片

There have been considerable variation as to the subclassification of the class I antiarrhythmic drugs depending on the methodology to assess the drug actions, different preparations and individual reporters. As a possible reason for the above confusion, most of the reports dealt with the Na^+ channel block as assessed by measuring V_<max> of action potentials, an indirect index of the Na^+ channel availability rather than the current measurement. Therefore we tried to explore the modes of the Na^+ channel block by class I antiarrhythmic drugs directly assessed by the recordings of the cardiac Na^+ current using the patch-clamp technique and to obtain a new classification of the drugs based on the results. We used isolated ventricular myocytes from guinea-pig hearts by collagenase treatment. The Na^+ currents were recorded by the patch-clamp technique of whole-cell configuration, cell-attached and inside-out patch configurations, Disopyramide, I_a agent, produced used-dependent block of the Na^+ current with two exponential functions, fast and slow component. It was further shown by the experiments conducted under different external pH that the slow block process was caused by ionized form of the drug having affinity to bind the activated state of the Na^+ channel, while the fast process was produced by the non-ionized form to the activated state of the channel. The fast and slow block fractions consisted nearly equal degrees. Lidocaine, I_b agent, also caused two exponential block developments, while the major portion of the block development was brought by the fast fraction with small part by the slow component. The fast block was made by the non-ionized drug to bind the inactivated state of the channel and the slow block was caused by the ionized drug to the activated state of the channel. Mexyletine also caused two exponential block development as similar to lidocaine. The ionized mexiletine pr