Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord
Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord
复制标题
DOI：
10.1111/j.1460-9568.2008.06260.x
复制
发表时间：
2008-06-01
影响因子：
3.4
通讯作者：
Baba, Hiroshi
中科院分区：
文献类型：
--
作者：
Ishii, Hideaki;Kohno, Tatsuro;Baba, Hiroshi
右美托咪定是一种高度特异性、强效和选择性的α（2）-肾上腺素受体激动剂。尽管已发现鞘内和硬膜外给予右美托咪定可产生镇痛，但这种镇痛是否由对脊髓胶状质（SG）神经元的影响引起仍不清楚。在这里，我们使用全细胞膜片钳技术研究了右美托咪定对大鼠脊髓切片SG神经元突触后传递的影响。在检查的92%的SG神经元（n = 84）中，浴中应用的右美托咪定以浓度依赖性方式在-70 mV下诱导外向电流，有效浓度值产生半最大反应（0.62 μ M）。右美托咪定诱导的外向电流被α（2）-肾上腺素受体拮抗剂育亨宾抑制，但不被α（1）-、α（2B）-和α（2C）-肾上腺素受体拮抗剂哌唑嗪抑制。此外，右旋美托咪啶诱导的电流被α（2C）-肾上腺素受体拮抗剂JP-1302部分抑制，而同时应用JP-1302和α（2A）-肾上腺素受体拮抗剂BRL 44408则完全消除了该电流。右美托咪定的作用由α（2A）-肾上腺素受体激动剂羟甲唑啉模拟。电流-电压关系图显示在约-86 mV处的反转电位。通过向移液器溶液中加入GDP-β-S [鸟苷-5 '-O-（2-硫代二磷酸）]或Cs+阻断右美托咪定诱导的电流。这些结果表明，右美托咪定通过G蛋白介导的α（2A）-和α（2C）-肾上腺素受体激活K+通道使SG神经元的膜电位超极化。右美托咪定的这一作用可能至少部分归因于其在脊髓中的抗伤害感受作用。
Dexmedetomidine is a highly specific, potent and selective alpha(2)-adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n = 84), bath-applied dexmedetomidine induced outward currents at -70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 mu M). The outward currents induced by dexmedetomidine were suppressed by the alpha(2)-adrenoceptor antagonist yohimbine, but not by prazosin, an alpha(1)-, alpha(2B)- and alpha(2C)-adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the alpha(2C)-adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the alpha(2A)-adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the alpha(2A)-adrenoceptor agonist oxymetazoline. Plots of the current-voltage relationship revealed a reversal potential at around -86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-beta-S [guanosine-5'-O-(2-thiodiphosphate)] or Cs+ to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K+ channels through alpha(2A)- and alpha(2C)-adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord.