Objective: The present study was aimed to investigate the pharmacological modulatory effects of ropivacaine, an amide-type local anesthetic, on rat Nav1.2 (rNav1.2) and rNav1.5, the two Na(+) channel isoforms heterologously expressed in Xenopus oocytes and in HEK293t cell line, respectively.
Methods: Two-electrode voltage-clamp (TEVC) and whole-cell patch-clamp recordings were employed to record the whole-cell currents.
Results: Ropivacaine induced tonic inhibition of peak Na(+) currents of both subtypes in a dose- and frequency-dependent manner. rNav1.5 appeared to be more sensitive to ropivacaine. In addition, for both Na(+) channel subtypes, the steady-state inactivation curves, but not the activation curves, were significantly shifted to the hyperpolarizing direction by ropivacaine. Use-dependent blockade of both rNav1.2 and rNav1.5 channels was induced by ropivacaine through a high frequency of depolarization, suggesting that ropivacaine could preferentially bind to the 2 inactivated Na(+) channel isoforms.
Conclusion: The results will be helpful in understanding the pharmacological modulation by ropivacaine on Nav1.2 subtype in the central nervous system, and on Nav1.5 subtype abundantly expressed in the heart.
目的: 本研究旨在探讨酰胺类局部麻醉药罗哌卡因对外源表达的大鼠脑型(rNav1.2)和心肌型(rNav1.5)电压门控 钠通道电流的药理调制作用。
方法: 运用双电极和膜片钳全细胞记录技术记录全细胞电流。
结果: 罗哌卡因能以浓 度和频率依赖的方式抑制rNav1.2和rNav1.5亚型通道的峰钠电流, 其中Nav1.5亚型通道对罗哌卡因的敏感性相对较 高。 此外, 罗哌卡因能使rNav1.2 和rNav1.5 亚型通道的稳态失活曲线向超极化方向显著偏移, 但对激活曲线没有 影响。 通过重复高频去极化刺激, 罗哌卡因能以使用依赖性的方式抑制rNav1.2 和rNav1.5 亚型通道的电流。
结论: 结果提示罗哌卡因的药理机制体现在对钠通道亚型失活态的调制上。 该结果有助于进一步理解罗哌卡因对脑型和心 肌型电压门控钠通道的药理调制作用。