Differential Block of Fast and Slow Inactivating Tetrodotoxin-sensitive Sodium Channels by Droperidol in Spinal Dorsal Horn Neurons
Differential Block of Fast and Slow Inactivating Tetrodotoxin-sensitive Sodium Channels by Droperidol in Spinal Dorsal Horn Neurons
复制标题
氟哌利多对脊髓背角神经元中河豚毒素敏感钠通道的快速和慢速失活的差异阻滞
作者：
A. Olschewski;M. Bräu;G. Hempelmann;W. Vogel;B. V. Safronov
研究背景脊髓背角神经元参与神经元痛觉传递。在脊髓和硬膜外麻醉期间，背角神经元暴露于局部麻醉剂和阿片类药物。氟哌利多通常与阿片类药物一起使用，以避免恶心和呕吐。最近发展的“全索马分离法”使直接研究氟哌利多对背角神经元Na ~+电流不同成分的作用成为可能。方法采用全细胞膜片钳记录和全索马体分离相结合的方法，研究氟哌利多对幼年大鼠背角神经元两种Na+电流的直接作用。结果河豚毒素敏感性Na+电流由快失活成分（F，0.5 ~ 2 ms，占总振幅的80-90%）和慢失活成分（S，6-20 ms，占总振幅的10-20%）组成。氟哌利多，在浓度相关的脊髓和硬膜外麻醉，选择性和可逆性抑制快的组成部分，半最大抑制浓度（IC 50）为8.3 m。缓慢失活组分对氟哌利多的敏感性低得多;估计的IC 50值为809 m。结论氟哌利多选择性地阻断快Na+通道，背角神经元Na+电流的快、慢成分通过不同类型的Na+通道传递，其作用不同于局麻药和河豚毒素对快、慢成分的等效抑制。氟哌利多可作为分离不同类型的灭活河豚毒素敏感性Na+通道的药理学工具。
Background Dorsal horn neurons of the spinal cord participate in neuronal pain transmission. During spinal and epidural anesthesia, dorsal horn neurons are exposed to local anesthetics and opioids. Droperidol is usually given with opioids to avoid nausea and vomiting. A recently developed method of “entire soma isolation” has made it possible to study directly the action of droperidol on different components of Na+ current in dorsal horn neurons. Methods Using a combination of the whole-cell patch-clamp recording from spinal cord slices and the entire soma isolation method, we studied the direct action of droperidol on two types of Na+ currents in dorsal horn neurons of young rats. Results The tetrodotoxin-sensitive Na+ current in isolated somata consisted of a fast inactivating (&tgr;F, 0.5–2 ms; 80–90% of the total amplitude) and a slow inactivating (&tgr;S, 6–20 ms; 10–20% of the total amplitude) component. Droperidol, at concentrations relevant for spinal and epidural anesthesia, selectively and reversibly suppressed the fast component with a half-maximum inhibiting concentration (IC50) of 8.3 &mgr;m. The slow inactivating component was much less sensitive to droperidol; the estimated IC50 value was 809 &mgr;m. Conclusions Droperidol selectively blocks fast Na+ channels, the fast and slow components of the Na+ current in dorsal horn neurons are carried through pharmacologically distinct types of Na+ channels, and the effects of droperidol differ from those of local anesthetics and tetrodotoxin, which equipotently suppress both components. Droperidol may be suggested as a pharmacologic tool for separation of different types of inactivating tetrodotoxin-sensitive Na+ channel.
影响因子：
2.5
作者：
HUGUENARD, JR;HAMILL, OP;PRINCE, DA
通讯作者：
PRINCE, DA