PDF(Pubmed)
Abstract：
The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.
摘要：
臂旁外侧核（PBL）与呼吸活动的调节有关。钠泄漏通道（NALCN）突变会破坏啮齿动物和人类的呼吸节律并影响麻醉敏感性。这里,我们研究了PBL谷氨酸能神经元中的NALCN是否在全身麻醉下维持呼吸功能。我们的结果表明，PBL谷氨酸能神经元的化学遗传激活增加了小鼠的呼吸频率（RF）；而化学遗传抑制抑制了RF。在生理条件下，PBL谷氨酸能神经元而不是GABA能神经元中的NALCN敲低显著降低RF，并在七氟醚麻醉下引起更多的呼吸抑制。PBL谷氨酸能神经元中的NALCN敲低并没有进一步加剧丙泊酚或吗啡诱导的呼吸抑制。七氟醚麻醉下,疼痛刺激迅速增加射频，PBL谷氨酸能神经元中不受NALCN敲低的影响。这项研究表明，NALCN是PBL谷氨酸能神经元中的关键离子通道，在挥发性麻醉剂七氟醚而不是静脉麻醉剂异丙酚下维持呼吸频率。
