Effects of α2-adrenoceptor agonists on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglion neurons
Effects of α2-adrenoceptor agonists on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglion neurons
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DOI：
10.1017/s0265021507000543
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发表时间：
2007-11-01
影响因子：
3.6
通讯作者：
Dohi, S.
中科院分区：
文献类型：
--
作者：
Oda, A.;Iida, H.;Dohi, S.
背景和目的：当鞘内或脑内给药时，α（2）-肾上腺素受体激动剂通过影响初级传入纤维和脊髓神经元的活性产生有效的抗伤害感受。最近的研究表明，在背根神经节神经元中，河豚毒素抗性Na（+）通道在伤害性感觉的传导中起重要作用。因此，我们研究了α（2）-肾上腺素受体激动剂对河豚毒素抗性Na（+）电流的影响。方法：采用全细胞膜片钳技术，记录大鼠背根神经节神经元河豚毒素耐受性Na（+）电流。结果：可乐定和右美托咪定均能降低河豚毒素耐药钠电流的峰值幅度，并呈浓度依赖性和使用依赖性。在保持电位-70 mV下，右美托咪定（58.0 +/- 10.2 μ mol）达到半数最大效应所需的浓度显著低于可乐定（257.2 +/- 30.9 μ mol）。1 μ mol育亨宾（一种α（2）-肾上腺素能受体拮抗剂）不能阻止这些激动剂引起的电流抑制。可乐定和右美托咪定均使河豚毒素抗性Na（+）电流的失活曲线向超极化方向移动。可乐定与利多卡因和右美托咪定与利多卡因的组合对河豚毒素抗性Na（+）电流产生了加性阻断型相互作用。结论：结果表明，直接抑制河豚毒素抗性Na（+）通道可能有助于可乐定和右美托咪定作为区域麻醉添加剂时的抗伤害性作用。
Background and objective: When intrathecally or epidurally administered, alpha(2)-adrenoceptor agonists produce potent antinociception by affecting the activity of primary afferent fibres and spinal cord neurons. Recent reports have indicated that in dorsal root ganglion neurons, tetrodotoxin-resistant Na(+) channels play important roles in the conduction of nociceptive sensation. We therefore investigated the effects of alpha(2)-adrenoceptor agonists on tetrodotoxin-resistant Na(+) currents. Methods: Using the whole-cell patch-clamp technique, we recorded tetrodotoxin-resistant Na(+) currents from rat dorsal root ganglion neurons. Results: Both clonidine and dexmedetomidine reduced the peak amplitude of the tetrodotoxin-resistant Na(+) current concentration- and use-dependently. The concentration required for a half-maximal effect was significantly lower for dexmedetomidine (58.0 +/- 10.2 mu mol) than for clonidine (257.2 +/- 30.9 mu mol) at holding potential -70 mV. The current inhibitions induced by these agonists were not prevented by 1 mu mol yohimbine, an alpha(2)-adrenoceptor antagonist. Both clonidine and dexmedetomidine shifted the inactivation curve for the tetrodotoxin-resistant Na(+) current in the hyperpolarizing direction. The combinations clonidine with lidocaine and dexmedetomidine with lidocaine produced an additive blockade-type interaction on the tetrodotoxin-resistant Na(+) current. Conclusions: The results suggest that a direct inhibition of tetrodotoxin-resistant Na(+) channels may contribute to the antinociceptive effects of clonidine and dexmedetomidine when used as additives to regional anaesthesia.