四川大学Cheng Zhou等研究人员合作发现，臂旁外侧核谷氨酸能神经元的漏钠通道有助于在七氟醚麻醉下维持呼吸频率。相关论文于2024年5月20日在线发表在《神经科学通报》杂志上。

研究人员测试了臂旁外侧核（PBL）谷氨酸能神经元中的漏钠通道（NALCN），是否能在全身麻醉下维持呼吸功能。研究结果表明，化学基因激活PBL谷氨酸能神经元会增加小鼠的呼吸频率（RF），而化学基因抑制则会抑制RF。在生理条件下，PBL谷氨酸能神经元中的NALCN敲除会显著降低呼吸频率，而GABA能神经元中的NALCN敲除则不会。

在PBL谷氨酸能神经元中敲除NALCN不会进一步加剧丙泊酚或吗啡引起的呼吸抑制。在七氟醚麻醉状态下，疼痛刺激会迅速增加射频，而PBL谷氨酸能神经元中的NALCN敲除并不会影响射频的增加。这项研究表明，NALCN是PBL谷氨酸能神经元中的一个关键离子通道，它在挥发性麻醉剂七氟醚而非静脉麻醉剂丙泊酚的作用下维持呼吸频率。

据介绍，PBL与呼吸活动的调节有关。NALCN突变会扰乱呼吸节律，并影响啮齿类动物和人类的麻醉敏感性。

附：英文原文

Title: Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia

Author: Wu, Lin, Zhang, Donghang, Wu, Yujie, Liu, Jin, Jiang, Jingyao, Zhou, Cheng

Issue&Volume: 2024-05-20

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.

DOI: 10.1007/s12264-024-01223-0

Source: https://link.springer.com/article/10.1007/s12264-024-01223-0