title: Mutation of alpha1G T-type calcium channels in mice does not change anesthetic requirements for loss of the righting reflex and minimum alveolar concentration but delays the onset of anesthetic induction.
abstract: BACKGROUND
  T-type calcium channels regulate neuronal membrane excitability and participate in a number of physiologic and pathologic processes in the central nervous system, including sleep and epileptic activity. Volatile anesthetics inhibit native and recombinant T-type calcium channels at concentrations comparable to those required to produce anesthesia. To determine whether T-type calcium channels are involved in the mechanisms of anesthetic action, the authors examined the effects of general anesthetics in mutant mice lacking alpha1G T-type calcium channels.
  
  
  METHODS
  The hypnotic effects of volatile and intravenous anesthetics administered to mutant and C57BL/6 control mice were evaluated using the behavioral endpoint of loss of righting reflex. To investigate the immobilizing effects of volatile anesthetics in mice, the minimum alveolar concentration (MAC) values were determined using the tail-clamp method.
  
  
  RESULTS
  The 50% effective concentration for loss of righting reflex and MAC values for volatile anesthetics were not altered after alpha1G channel knockout. However, mutant mice required significantly more time to develop anesthesia/hypnosis after exposure to isoflurane, halothane, and sevoflurane and after intraperitoneal administration of pentobarbital.
  
  
  CONCLUSIONS
  The 50% effective concentration for loss of righting reflex and MAC values for the volatile anesthetics were not altered after alpha1G calcium channel knockout, indicating that normal functioning of alpha1G calcium channels is not required for the maintenance of anesthetic hypnosis and immobility. However, the timely induction of anesthesia/hypnosis by volatile anesthetic agents and some intravenous anesthetic agents may require the normal functioning of these channel subunits.
authors.affiliation: Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Department of Integrated Neuroscience, Center for Integrated Human Brain Science, Brain Research Institute, Niigata University, Japan. abpetr@med.niigata-u.ac.jp
authors.forename: Andrey B
authors.initials: AB
authors.lastname: Petrenko
authors.forename: Mika
authors.initials: M
authors.lastname: Tsujita
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kohno
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Baba
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018345:Mice, Knockout; D012018:Reflex / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018686:Anesthetics, Intravenous; D020747:Calcium Channels, T-Type