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组胺对脊髓α-运动神经元兴奋性的易化作用及其离子机制

伍冠一^1,2, 庄乾兴¹, 张潇洋¹, 李红召¹, 王建军¹, 朱景宁^1,*

¹南京大学医药生物技术国家重点实验室和生命科学学院生理学系，南京 210023；²广西中医药大学基础医学院，南宁 530200

摘要

脊髓α运动神经元直接支配骨骼肌活动，是躯体运动和行为控制的最后公路(final common path)。因此，运动神经元兴奋性调控对于运动行为的执行至关重要。事实上，脊髓运动神经元接受多种神经调质的传入，尤其是单胺能神经调质。然而，组胺和下丘脑组胺能神经系统对脊髓运动神经元的调控作用及其下游离子机制至今仍不清楚。本研究采用大鼠脊髓脑片细胞内记录方法，发现组胺H1和H2受体的激活均能增强脊髓α运动神经元的重复放电行为和兴奋性。钾通道的关闭和钠-钙交换体的激活共同参与了H1受体激活介导的脊髓运动神经元的兴奋，而超极化激活的环核苷酸门控(hyperpolarization- activated cyclic nucleotide-gated, HCN)通道的开放则负责H2受体激活介导的兴奋性效应。以上结果提示，通过切换与组胺受体相耦联的离子通道和交换体的功能状态，组胺可以有效地偏置脊髓α运动神经元的兴奋性，而下丘脑组胺能神经传入很可能以这种方式直接调控最终的运动输出并主动调节脊髓运动反射和运动执行。

关键词： 组胺; 组胺受体; 运动神经元; 脊髓; 钾通道; 钠-钙交换体; HCN通道

分类号：Q25

Facilitation of spinal α-motoneuron excitability by histamine and the underlying ionic mechanisms

WU Guan-Yi^1,2, ZHUANG Qian-Xing¹, ZHANG Xiao-Yang¹, LI Hong-Zhao¹, WANG Jian-Jun¹, ZHU Jing-Ning^1,*

¹State Key Laboratory of Pharmaceutical Biotechnology and Department of Physiology, School of Life Sciences, Nanjing University, Nanjing 210023, China；²College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China

Abstract

Spinal α-motoneurons directly innervate skeletal muscles and function as the final common path for movement and behavior. The processes that determine the excitability of motoneurons are critical for the execution of motor behavior. In fact, it has been noted that spinal motoneurons receive various neuromodulatory inputs, especially monoaminergic one. However, the roles of histamine and hypothalamic histaminergic innervation on spinal motoneurons and the underlying ionic mechanisms are still largely unknown. In the present study, by using the method of intracellular recording on rat spinal slices, we found that activation of either H1 or H2 receptor potentiated repetitive firing behavior and increased the excitability of spinal α-motoneurons. Both of blockage of K+ channels and activation of Na+-Ca2+ exchangers were involved in the H1 receptor-mediated excitation on spinal motoneurons, whereas the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels were responsible for the H2 receptor-mediated excitation. The results suggest that, through switching functional status of ion channels and exchangers coupled to histamine receptors, histamine effectively biases the excitability of the spinal α-motoneurons. In this way, the hypothalamospinal histaminergic innervation may directly modulate final motor outputs and actively regulate spinal motor reflexes and motor execution.

Key words: Histamine; histamine receptors; motoneurons; spinal cord; K+ channels; Na+-Ca2+ exchangers; HCN channels

收稿日期：2019-04-16　　录用日期：2019-07-03

通讯作者：朱景宁　　E-mail: jnzhu@nju.edu.cn

DOI: 10.13294/j.aps.2019.0077

引用本文：

伍冠一, 庄乾兴, 张潇洋, 李红召, 王建军, 朱景宁. 组胺对脊髓α-运动神经元兴奋性的易化作用及其离子机制[J]. 生理学报 2019; 71 (6): 809-823.

WU Guan-Yi, ZHUANG Qian-Xing, ZHANG Xiao-Yang, LI Hong-Zhao, WANG Jian-Jun, ZHU Jing-Ning. Facilitation of spinal α-motoneuron excitability by histamine and the underlying ionic mechanisms. Acta Physiol Sin 2019; 71 (6): 809-823