Satoh H, Hashimoto K
Arch Int Pharmacodyn Ther. 1984 Aug;270(2):241-54.
The ionic mechanism of effect of lidocaine (50-500 micrograms/ml) on the rabbit sino-atrial node was investigated by recording transmembrane potentials and by voltage clamping by means of a two microelectrode technique. Small sino-atrial (SA) node preparations (0.2 X 0.2 mm) were used. At doses larger than 50 micrograms/ml, lidocaine reduced the amplitude of the action potential, the maximum diastolic potential and the maximum rate of depolarization in a dose-dependent manner. At the same time, lidocaine prolonged the action potential duration and the cycle length. At a higher dose, lidocaine induced sinus arrest (in 3 of 17 specimens at 300 micrograms/ml and in 15 of 17 specimens at 500 micrograms/ml). In voltage clamp experiments, lidocaine (50 micrograms/ml) reduced the time-dependent outward current (Ik) but did not affect the slow inward current (Is). At doses larger than 100 micrograms/ml, lidocaine reduced both currents in a dose-dependent manner. The inward current activated by hyperpolarization (Ih) was also reduced. Inactivation of Is (f infinity) and steady-state activation of Ik (p infinity) were unchanged. Lidocaine did not affect the decay time course of Is and Ik. These results suggest that lidocaine decreases Is and Ik and that this decrease is due to a reduction in conductance of these current systems.
采用双微电极技术记录跨膜电位和电压钳制，研究了利多卡因（50 - 500微克/毫升）对家兔窦房结的离子作用机制。使用了小的窦房（SA）结标本（0.2×0.2毫米）。剂量大于50微克/毫升时，利多卡因以剂量依赖性方式降低动作电位幅度、最大舒张电位和最大去极化速率。同时，利多卡因延长动作电位持续时间和周期长度。在较高剂量时，利多卡因诱导窦性停搏（300微克/毫升时17个标本中有3个，500微克/毫升时17个标本中有15个）。在电压钳实验中，利多卡因（50微克/毫升）降低时间依赖性外向电流（Ik），但不影响缓慢内向电流（Is）。剂量大于100微克/毫升时，利多卡因以剂量依赖性方式降低两种电流。超极化激活的内向电流（Ih）也降低。Is的失活（f无穷大）和Ik的稳态激活（p无穷大）未改变。利多卡因不影响Is和Ik的衰减时间进程。这些结果表明，利多卡因降低Is和Ik，且这种降低是由于这些电流系统的电导降低所致。
