Signaling mechanism underlying the histamine‐modulated action of hypoglossal motoneurons
Signaling mechanism underlying the histamine‐modulated action of hypoglossal motoneurons
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DOI：
10.1111/jnc.13548
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发表时间：
2016-03
影响因子：
4.7
通讯作者：
Zi-long Liu;Xu Wu;Yan-Jia Luo;Lu Wang;W. Qu;Shan-Qun Li;Zhi-Li Huang
中科院分区：
文献类型：
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作者：
Zi-long Liu;Xu Wu;Yan-Jia Luo;Lu Wang;W. Qu;Shan-Qun Li;Zhi-Li Huang
组胺是中枢神经系统觉醒状态的重要调节剂，据报道，组胺在舌下运动核向颏舌肌（GG）提供兴奋驱动，参与阻塞性睡眠呼吸暂停的发病机制。然而，组胺对舌下运动神经元（HMNs）的影响及其潜在的信号传导机制尚不清楚。本研究利用新生大鼠脑切片进行全细胞膜片钳记录，结果显示组胺通过组胺H1受体（H1Rs）在电压箝位下以内向电流和电流箝位下以去极化膜电位激发HMNs。磷脂酶C抑制剂U‐73122阻断了H1Rs介导的兴奋作用，但蛋白激酶A抑制剂和蛋白激酶C抑制剂没有，这表明组胺对HMNs的兴奋作用的信号转导级联是H1R/Gq/11/磷脂酶C/肌醇‐1,4,5‐三磷酸（IP3）。组胺的作用也依赖于细胞外Na+和细胞内Ca2+，这是通过Na+‐Ca2+交换器的激活而发生的。这些结果确定了与组胺对HMNs调节作用相关的信号分子。本研究结果可能为阻塞性睡眠呼吸暂停的治疗方法提供新的见解。
Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole‐cell patch‐clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage‐clamp and a depolarization membrane potential under current‐clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U‐73122 blocked H1Rs‐mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11/phospholipase C/inositol‐1,4,5‐trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na+ and intracellular Ca2+, which took place via activation of Na+‐Ca2+ exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea.