title: Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics.
abstract: General anesthesia is a relatively safe medical procedure, which for nearly 170 years has allowed life saving surgical interventions in animals and people. However, the molecular mechanism of general anesthesia continues to be a matter of importance and debate. A favored hypothesis proposes that general anesthesia results from direct multisite interactions with multiple and diverse ion channels in the brain. Neurotransmitter-gated ion channels and two-pore K+ channels are key players in the mechanism of anesthesia; however, new studies have also implicated voltage-gated ion channels. Recent biophysical and structural studies of Na+ and K+ channels strongly suggest that halogenated inhalational general anesthetics interact with gates and pore regions of these ion channels to modulate function. Here, we review these studies and provide a perspective to stimulate further advances.
authors.affiliation: Department of Neuroscience and Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: manuel.covarrubias@jefferson.edu.
authors.forename: Manuel
authors.initials: M
authors.lastname: Covarrubias
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Annika F
authors.initials: AF
authors.lastname: Barber
authors.affiliation: Institute for Computational Molecular Science, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carnevale
authors.affiliation: Laboratorio de Biologia Teorica e Computacional, Universidade de Brasilia, Brazil.
authors.forename: Werner
authors.initials: W
authors.lastname: Treptow
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
mesh_terms: D000595:Amino Acid Sequence; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D024642:Potassium Channels, Voltage-Gated; D061566:Voltage-Gated Sodium Channels