Excitatory effect of histamine on rat spinal motoneurons by activation of both H1 and H2 receptors in vitro
Excitatory effect of histamine on rat spinal motoneurons by activation of both H1 and H2 receptors in vitro
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DOI：
10.1002/jnr.22730
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发表时间：
2012-01
影响因子：
4.2
通讯作者：
Guan-Yi Wu;Xiao‐Hu Han;Q. Zhuang;Jun Zhang;W. Yung;Y. Chan;Jing-Ning Zhu;Jian-jun Wang
中科院分区：
文献类型：
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作者：
Guan-Yi Wu;Xiao‐Hu Han;Q. Zhuang;Jun Zhang;W. Yung;Y. Chan;Jing-Ning Zhu;Jian-jun Wang
中枢组胺能神经系统起源于下丘脑的结节乳头核，广泛支配几乎整个大脑和脊髓。然而，组胺对脊髓运动神经元（运动控制的最终共同途径）的影响尚不清楚。通过8 ~ 14天大的大鼠脊髓切片和细胞内记录，研究了组胺对腰椎运动神经元的影响及其机制。组胺（30-300 μM）在脊髓运动神经元中引起膜去极化（78/ 90,86%）。用河豚毒素或低Ca2+/高Mg2+培养基灌注的薄片不能阻断组胺诱导的兴奋，这表明组胺对运动神经元有直接的突触后作用。单独应用选择性组胺H1受体拮抗剂甲胺或选择性组胺H2受体拮抗剂雷尼替丁部分抑制组胺诱导的兴奋，而雷尼替丁和甲胺联合使用则完全阻断组胺对运动神经元的兴奋作用。另一方面，选择性组胺H1受体激动剂2‐吡啶乙胺和选择性组胺H2受体激动剂地马匹利都能模拟组胺对脊髓运动神经元的兴奋作用。这些激动剂诱导的兴奋也被甲皮拉米或雷尼替丁阻断。此外，组胺影响膜输入阻力，增强脊髓运动神经元的重复放电行为。这些结果表明，组胺通过组胺H1和H2受体刺激大鼠脊髓运动神经元并增加其兴奋性，表明下丘脑脊髓组胺能纤维可能直接调节最终运动输出并积极调节正在进行的运动执行和脊髓运动反射。©2011 Wiley期刊公司
The central histaminergic nervous system, originating from the tuberomammillary nucleus of the hypothalamus, widely innervates almost the whole brain as well as the spinal cord. However, the effect of histamine on spinal motoneurons, the final common path for motor control, is still unknown. By using 8–14‐day‐old rat spinal slice preparations and intracellular recordings, the effect of histamine on motoneurons in lumbar spinal cord and the underlying mechanisms were studied. Bath application of histamine (30–300 μM) induced a membrane depolarization in the majority of recorded spinal motoneurons (78/90, 86%). Perfusing slices with tetrodotoxin or low‐Ca2+/high‐Mg2+ medium did not block the histamine‐induced excitation, indicating a direct postsynaptic action of histamine on motoneurons. Separate application of the selective histamine H1 receptor antagonist mepyramine or the selective histamine H2 receptor antagonist ranitidine partially suppressed the histamine‐induced excitation, whereas a combination of ranitidine and mepyramine totally blocked the excitatory effect of histamine on motoneurons. On the other hand, both the selective histamine H1 receptor agonist 2‐pyridylethylamine and the selective histamine H2 receptor agonist dimaprit mimicked the excitation of histamine on spinal motoneurons. These agonist‐induced excitations were also blocked by mepyramine or ranitidine. Furthermore, histamine affected membrane input resistance and potentiated repetitive firing behavior of spinal motoneurons. These results demonstrate that histamine excites rat spinal motoneurons via the histamine H1 and H2 receptors and increases their excitability, suggesting that the hypothalamospinal histaminergic fibers may directly modulate final motor outputs and actively regulate ongoing motor execution andspinal motor reflexes. © 2011 Wiley Periodicals, Inc.