Laurikainen E, Lin X, Nuttall A L, Dolan D F
Department of Otolaryngology, Turku University Central Hospital, Finland.
Acta Otolaryngol. 1997 Jul;117(4):523-8. doi: 10.3109/00016489709113432.
Lidocaine was applied to the round window (RW) in order to localize its site of action in the cochlea. Cochlear microphonic (CM), summating potential (SP), and compound action potential (CAP) input/output functions were measured to a 16 kHz tone burst to assess the functional changes of the cochlea. In separate experiments, the effect of lidocaine on the whole cell current of isolated outer hair cells (OHC) was studied. A dose of 2 microliters of 40 mM lidocaine in saline solution, when applied to the RW, caused a small change in all measured variables, indicating a passage of the drug through the RW membrane to sites of action. However, 160 mM of lidocaine further decreased CM, SP, and CAP by a total of 40% from the control. A partial recovery occurred for CM during the 30 min follow-up period. CAP and SP continued to decline. In isolated OHCs, lidocaine decreased the whole cell current in a dose-dependent fashion. The KD for lidocaine effect on OHCs was 7 mM. Our in vivo results indicate that lidocaine affects OHCs and reduces CM, causing a subsequent reduction in SP and CAP. The increased effect of lidocaine on CAP and SP, while CM is recovering, suggests an additional specific effect of lidocaine on the cochlear nerve and/or on inner hair cells. Considering that lidocaine alters OHC current (in isolated hair cells) and that lidocaine does not affect endocochlear potential [Laurikainen et al. Acta Otolaryngol (Stockh) 1991: 112: 800-9], the observed CM changes are most likely due to an in vivo effect on OHCs. Thus, the early effect of lidocaine on the cochlea appears to be due to a significant change in organ of Corti function, rather than to direct anesthesia of the cochlear nerve. Later, an independent effect of the drug may occur on neural tissues in the inner ear.
将利多卡因应用于圆窗，以确定其在耳蜗中的作用部位。测量了16kHz短纯音刺激下的耳蜗微音器电位（CM）、总和电位（SP）以及复合动作电位（CAP）的输入/输出函数，以评估耳蜗的功能变化。在单独的实验中，研究了利多卡因对分离的外毛细胞（OHC）全细胞电流的影响。将2微升40mM利多卡因的盐溶液应用于圆窗时，所有测量变量均有小的变化，表明药物通过圆窗膜到达作用部位。然而，160mM利多卡因使CM、SP和CAP比对照组总共进一步降低了40%。在30分钟的随访期内，CM有部分恢复。CAP和SP则持续下降。在分离的OHC中，利多卡因以剂量依赖的方式降低全细胞电流。利多卡因对OHC作用的解离常数（KD）为7mM。我们的体内实验结果表明，利多卡因影响OHC并降低CM，进而导致SP和CAP随后降低。在CM恢复时利多卡因对CAP和SP的作用增强，提示利多卡因对耳蜗神经和/或内毛细胞有额外的特异性作用。考虑到利多卡因改变OHC电流（在分离的毛细胞中）且利多卡因不影响内淋巴电位[劳里凯宁等人。《耳鼻咽喉头颈外科杂志》（斯德哥尔摩）1991年；112:800 - 9]，观察到的CM变化很可能是由于其在体内对OHC的作用。因此，利多卡因对耳蜗的早期作用似乎是由于柯蒂氏器功能的显著变化，而非耳蜗神经的直接麻醉。之后，该药物可能对内耳的神经组织产生独立作用。
