Ion Channels in Anesthesia

Abstract

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 GABA_A receptors (GABA_ARs), 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. GABA_ARs 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.

Keywords: Anesthetics; Cholinergic receptors; Etomidate; GABAA receptors; Glutamate receptors; Isoflurane; Ketamine; Nitrous oxide; Propofol; Sevoflurane; Two-pore-domain K+ channels.