Identification and functional analyses of CO_2-sensing cells in the central respiratory chemoreceptor

在本研究项目中，我们研究了中枢呼吸化学感受和中枢呼吸控制的神经底物的功能和解剖。为了确定一种重要的神经递质GABA在中枢呼吸控制中的功能作用，我们使用了GABA合成酶(GAD)基因靶向的小鼠，发现GABA在维持稳定的呼吸输出中是必需的(Kuwana等人)。2003年、2004年、2006年)。我们还发现，异丙酚的呼吸抑制是由其GABA样抑制作用诱导的(Kashiwagi等人。我们将电压成像技术应用于体外脑干制备，并成功地绘制了化疗敏感区的功能图谱。我们报道了脑桥A5区域具有内在的化疗敏感性(Ito等人)。在我们假设烟碱型乙酰胆碱受体重要参与中枢呼吸化学感受的基础上，我们在体外分析了非去极化肌松剂对化学反应性的影响。我们首次报道了非去极化肌松剂抑制脑干的呼吸活动(Sakuraba等人。2003；2005)。我们总结了我们的研究结果，并提出了我们的理论，即钾通道在化学感受器细胞中扮演关键角色(Oyamada等人)。2006)，而围绕延髓腹侧浅层细血管的特定小细胞是初级化学感受器细胞(Okada等人。2006)。

In this research project we have studied the function and anatomy of the neural substrate for the central respiratory chemoreception and central respiratory control.In order to identify the functional role of an important neurotransmitter GABA in central respiratory control, we used GABA-synthesizing enzyme (GAD) gene-targeted mice, and found that GABA is necessary in the maintenance of stable respiratory output (Kuwana et al. 2003 ; 2004 ; 2006). We also found that respiratory depression by propofol is induced by its GABA-like inhibitory action (Kashiwagi et al. 2004 ; 2004).We applied a voltage imaging technique to an in vitro brainstem preparation, and succeeded functional mapping of chemosensitive regions. We reported that the pontine A5 region has intrinsic chemosensitivity (Ito et al. 2004).On the basis of our hypothesis that nicotinic acetylcholine receptor is importantly involved in central respiratory chemoreception, we analyzed the effects of non-depolarizing muscle relaxants on chemoresponsiveness in vitro. We first reported that non-depolarizing muscle relaxants inhibit respiratory activity in the brainstem (Sakuraba et al. 2003 ; 2005).We summarized the results of our studies, and have proposed our theories that potassium channels play a key role as the chemosensor in chemoreceptor cells (Oyamada et al. 2006) and that specific small cells surrounding fine vessels in the superficial ventral medulla are primary chemoreceptor cells (Okada et al. 2006).