Ion Channels in Anesthesia.
Ion Channels in Anesthesia.
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麻醉中的离子通道。
DOI：
10.1007/978-981-16-4254-8_19
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发表时间：
2021
影响因子：
--
通讯作者：
Guan,Zhonghui
中科院分区：
文献类型：
--
作者：
Zhou,Wei;Guan,Zhonghui
离子通道在麻醉中起着关键作用，包括全身麻醉和局部麻醉。两类主要的全身麻醉药（GA）是吸入麻醉药，如异氟烷、七氟烷和一氧化二氮;注射麻醉药，如丙泊酚、依托咪酯和氯胺酮。除催眠药外，还需要肌肉松弛剂用于固定和阿片类药物用于镇痛以实现平衡麻醉。虽然我们对麻醉的理解还远未完成，但最近的研究揭示了麻醉药物与离子通道，特别是配体门控离子通道（LGIC）之间的分子相互作用。离子型GABA A受体（GABAARs）是中枢神经系统（CNS）抑制性信号的主要介质，是全麻药物催眠的关键。在神经肌肉接头和神经系统中表达的离子型胆碱能受体（nAChRs）是肌肉松弛剂的分子靶点。GABAAR和nAChR属于相同的五聚体LGIC家族。离子型谷氨酸受体（iGluR）具有完全不同的结构，在CNS中携带兴奋性信号，并被吸入麻醉剂和氯胺酮靶向。另一个独特的离子通道家族，双孔结构域K+（K2 P）通道，可被吸入麻醉剂激活并引起神经元超极化。在这一章中，我们将讨论最近的进展，通过这些离子通道的分子结构来理解麻醉的分子机制。
Ion channels play a pivotal role in anesthesia, including general and regional anesthesia. Two main classes of general anesthetics (GAs) are inhalational anesthetics, such as isoflurane, sevoflurane, and nitrous oxide; injectable anesthetics, such as propofol, etomidate, and ketamine. Besides hypnotic agents, muscle relaxants for immobility and opioids for analgesia are needed to achieve balanced anesthesia. Although our understanding of anesthesia is far from complete, recent studies have revealed the molecular interactions between anesthetic drugs and ion channels, particularly, the ligand-gated ion channels (LGICs). Ionotropic GABAAreceptors (GABAARs), the main mediators of the inhibitory signals in the central nervous system (CNS), are the key to hypnosis by general anesthetics. Ionotropic cholinergic receptors (nAChRs), expressed at the neuromuscular junction and the nervous system, are the molecular targets of muscle relaxants. GABAARs and nAChRs belong to the same family of pentameric LGICs. With a completely different architecture, ionotropic glutamate receptors (iGluRs) carry the excitatory signals in the CNS and are targeted by inhalational anesthetics and ketamine. Another distinct family of ion channels, two-pore-domain K+(K2P) channels, can be activated by inhalational anesthetics and cause neuron hyperpolarization. In this chapter, we will discuss the recent advance in understanding the molecular mechanisms underlying anesthesia through the molecular structures of these ion channels.