title: Propofol postsynaptically suppresses stellate neuron excitability in the entorhinal cortex by influencing the HCN and TREK-2 channels.
abstract: The entorhinal cortex (EC) provides a majority of the excitatory inputs to the hippocampus and is part of the neural circuitry that is involved in memory formation. Although many studies have investigated the effects of propofol in the hippocampus, the function of propofol in the EC remains unclear. Here, using whole-cell patch clamp recordings, we found that propofol induced a postsynaptic outward current and dramatically suppressed the firing rates in the entorhinal stellate neurons, the axons of which form the perforant pathway and relay the main inputs to hippocampus. Propofol-induced inhibition in the EC was mediated by a dual ionic mechanism, including both HCN channel inhibition and TREK-2 channel activation, which form a subtype of two-pore-domain K(+) channels. The inhibitory action of propofol observed in the EC might provide a mechanism for the anesthetic effect of propofol. Considering the crucial role of the EC in learning and memory, our findings may provide insight into the acute amnesic effect induced by propofol.
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, No. 281 Hospital of People's Liberation Army, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: guocaitaotmmu@163.com.
authors.forename: Guocai
authors.initials: G
authors.lastname: Tao
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D018728:Entorhinal Cortex / Q000187:drug effects* / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology
chemical_list: D018681:Anesthetics, General; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; C503444:Kcnk10 protein, rat; D024683:Potassium Channels, Tandem Pore Domain; D015742:Propofol
keywords: Entorhinal cortex; HCN channels; Propofol; Stellate neurons; TREK-2 channels