Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats
Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats
复制标题
组胺对大鼠内侧前庭核神经元兴奋作用的突触后机制
DOI：
10.1111/bph.12256
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发表时间：
2013-09-01
影响因子：
7.3
通讯作者：
Wang, Jian-Jun
中科院分区：
文献类型：
--
作者：
Zhang, Xiao-Yang;Yu, Lei;Wang, Jian-Jun
背景与目的抗组胺能药物已广泛应用于前庭疾病的临床治疗，多数研究集中于其突触前作用。本研究旨在探讨组胺对前庭内侧核(MVN)神经元的突触后作用及其机制。实验方法采用大鼠脑片全细胞膜片钳记录方法，检测组胺对MVN神经元的突触后作用及其受体和离子机制。用免疫双标和单标记法定位突触后组胺H-1、H-2和H-4受体的分布。用实时定量RT-PCR法检测H-1、H-2、H-4受体、Na+-Ca~(2+)交换器(NCX)和超极化激活环核苷酸门控(HCN)通道的mRNAs的表达。突触后H-1和H-2而不是H-4受体共同定位于相同的MVN神经元。NCXs参与由H-1受体介导的内向电流，而HCN通道负责激活H-2受体所引起的兴奋。此外，NCX1和NCX3而不是NCX2，以及HCN1而不是HCN2-4mRNAs在MV中大量表达。结论与H-1受体和与H-2受体相连的HCN通道连接的NCXs共同介导了组胺对MVN神经元的强烈突触后兴奋作用。这些结果强调了突触后机制在中枢组胺能系统调节前庭功能中的积极作用，并为临床治疗前庭疾病提供了潜在的靶点。
Background and Purpose Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms.Experimental Approach Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-clamp recordings on rat brain slices. The distribution of postsynaptic histamine H-1, H-2 and H-4 receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H-1, H-2 and H-4 receptors and for subtypes of Na+-Ca2+ exchangers (NCXs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was assessed by quantitative real-time RT-PCR.Key Results A marked postsynaptic excitatory effect, co-mediated by histamine H-1 and H-2 receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H-1 and H-2 rather than H-4 receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H-1 receptors, whereas HCN channels were responsible for excitation induced by activation of H-2 receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN.Conclusion and Implications NCXs coupled to H-1 receptors and HCN channels linked to H-2 receptors co-mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders.