The General Anesthetic Isoflurane Bilaterally Modulates Neuronal Excitability
Mengchan Ou,
Wenling Zhao,
Jin Liu,
Peng Liang,
Han Huang,
Hai Yu,
Tao Zhu,
Cheng Zhou
Affiliations
Mengchan Ou
Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Wenling Zhao
Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Jin Liu
Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Peng Liang
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Han Huang
Department of Anesthesiology, West China Second Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Hai Yu
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Tao Zhu
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China
Cheng Zhou
Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China; Corresponding author
Summary: Volatile anesthetics induce hyperactivity during induction while producing anesthesia at higher concentrations. They also bidirectionally modulate many neuronal functions. However, the neuronal mechanism is unclear. The effects of isoflurane on sodium channel currents were analyzed in acute mouse brain slices, including sodium leak (NALCN) currents and voltage-gated sodium channels (Nav) currents. Isoflurane at sub-anesthetic concentrations increased the spontaneous firing rate of CA3 pyramidal neurons, whereas anesthetic concentrations of isoflurane decreased the firing rate. Isoflurane at sub-anesthetic concentrations enhanced NALCN conductance but minimally inhibited Nav currents. Isoflurane at anesthetic concentrations depressed Nav currents and action potential amplitudes. Isoflurane at sub-anesthetic concentrations depolarized resting membrane potential (RMP) of neurons, whereas hyperpolarized the RMP at anesthetic concentrations. Isoflurane at low concentrations induced hyperactivity in vivo, which was diminished in NALCN knockdown mice. In conclusion, enhancement of NALCN by isoflurane contributes to its bidirectional modulation of neuronal excitability and the hyperactivity during induction. : Anesthesiology; Neuroscience Subject Areas: Anesthesiology, Neuroscience
