Baba H, Goldstein P A, Okamoto M, Kohno T, Ataka T, Yoshimura M, Shimoji K
Department of Anesthesiology, Niigata University School of Medicine, Japan.
Anesthesiology. 2000 Feb;92(2):485-92. doi: 10.1097/00000542-200002000-00031.
It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic."
A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied.
In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM).
The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.
先前已有报道称，去甲肾上腺素作用于脊髓背角时，可兴奋背角神经元的一个亚群，推测为抑制性中间神经元。在本研究中，作者测试了去甲肾上腺素是否能激活抑制性中间神经元，特别是那些“γ-氨基丁酸能”的中间神经元。
从成年雄性Sprague-Dawley大鼠分离的腰段脊髓获取横切片。使用盲法膜片钳技术对胶状质神经元进行全细胞膜片钳记录。研究了去甲肾上腺素对自发性γ-氨基丁酸能抑制性突触后电流的影响。
在大多数测试的胶状质神经元中，去甲肾上腺素（10 - 60微摩尔）显著增加了γ-氨基丁酸能抑制性突触后电流的频率和幅度。这些增加被河豚毒素（1微摩尔）阻断。去甲肾上腺素的作用被α1受体激动剂苯肾上腺素（10 - 80微摩尔）模拟，并被α1受体拮抗剂WB - 4101（0.5微摩尔）抑制。苯肾上腺素（40微摩尔）也减弱了深背角宽动态范围神经元的初级传入诱发多突触兴奋性突触后电位或兴奋性突触后电流。
这些观察结果表明，γ-氨基丁酸能中间神经元具有体细胞树突状α1受体，这些受体的激活可兴奋抑制性中间神经元。本文报道的α1作用可能有助于鞘内注射苯肾上腺素的镇痛作用。
