Na+-Ca2+ Exchanger, Leak K+ Channel and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Comediate the Histamine-Induced Excitation on Rat Inferior Vestibular Nucleus Neurons
Na+-Ca2+ Exchanger, Leak K+ Channel and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Comediate the Histamine-Induced Excitation on Rat Inferior Vestibular Nucleus Neurons
复制标题
Na-Ca交换器、渗漏K通道和超极化激活的环核苷酸门控通道介导组胺诱导的大鼠前庭下核神经元兴奋
DOI：
10.1111/cns.12451
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发表时间：
2016
影响因子：
5.5
通讯作者：
Jian-Jun Wang
中科院分区：
文献类型：
--
作者：
Lei Yu;Xiao-Yang Zhang;Shu-Liang Cao;Shi-Yu Peng;Deng-Yu Ji;Jing-Ning Zhu;Jian-Jun Wang
目的抗组胺能药物在临床上传统上用于治疗前庭疾病。作为抗组胺能药物的潜在中心靶点，下前庭核（IVN）是前庭中央核复合体中最大的亚核，被认为负责前庭-自主神经反应和前庭、小脑和多感觉信号的整合。然而，组胺在IVN中的作用，特别是潜在的机制，仍然不清楚。方法采用全细胞膜片钳记录大鼠脑切片，研究组胺对IVN神经元的影响及其受体和离子机制。结果我们发现组胺通过组胺H1和组胺H2受体显著地去极化IVN的自发放电神经元和沉默神经元。此外，Na+ -Ca2 +交换器（nxs）和连接H1受体的背景泄漏K+通道以及连接H2受体的超极化激活环核苷酸门控（HCN）通道介导组胺诱导的IVN神经元去极化。结论组胺/中枢组胺系统对IVN神经元的兴奋性调控及其相关的前庭反射和功能存在多种离子机制。这些发现也提示了在前庭中枢核离子通道水平上治疗前庭疾病的潜在靶点。
AimsAntihistaminergic drugs have traditionally been used to treat vestibular disorders in the clinic. As a potential central target for antihistaminergic drugs, the inferior vestibular nucleus (IVN) is the largest subnucleus of the central vestibular nuclear complex and is considered responsible for vestibular‐autonomic responses and integration of vestibular, cerebellar, and multisensory signals. However, the role of histamine on the IVN, particularly the underlying mechanisms, is still not clear.MethodsUsing whole‐cell patch‐clamp recordings on rat brain slices, histamine‐induced effect on IVN neurons and the underlying receptor and ionic mechanisms were investigated.ResultsWe found that histamine remarkably depolarized both spontaneous firing neurons and silent neurons in IVN via both histamine H1 and histamine H2 receptors. Furthermore, Na+–Ca2+exchangers (NCXs) and background leak K+channels linked to H1 receptors and hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels coupled to H2 receptors comediate the histamine‐induced depolarization on IVN neurons.ConclusionThese results demonstrate the multiple ionic mechanisms underlying the excitatory modulation of histamine/central histaminergic system on IVN neurons and the related vestibular reflexes and functions. The findings also suggest potential targets for the treatment of vestibular disorders in the clinic, at the level of ionic channels in central vestibular nuclei.