title: Increased sensitivity to halothane but decreased sensitivity to propofol in mice lacking the N-type Ca2+ channel.
abstract: Volatile anesthetics are known to depress excitatory synaptic transmission. Inhibition of voltage-dependent Ca2+ channels is speculated to underlie this mechanism, which remains to be clarified in vivo. We examined the sensitivity to halothane in mice lacking the N-type Ca2+ channel, a major contributor of presynaptic neurotransmitter release. Sensitivity to halothane was significantly increased in the knockout mice compared with the wild-type littermates. Halothane also depressed field excitatory postsynaptic potentials recorded from the Schaffer collateral-CA1 hippocampal synapses more greatly in the knockout mice. We further examined sleep time induced by injection of propofol, an intravenous anesthetic that mainly affects inhibitory synaptic transmission. In contrast, sensitivity to propofol was significantly decreased in the knockout mice. We suggest that inhibition of the N-type Ca2+ channel underlies mechanisms of halothane anesthesia but counteracts propofol anesthesia.
authors.affiliation: Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Takei
authors.forename: Hironao
authors.initials: H
authors.lastname: Saegusa
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zong
authors.forename: Takayuki
authors.initials: T
authors.lastname: Murakoshi
authors.forename: Koshi
authors.initials: K
authors.lastname: Makita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanabe
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006579:Heterozygote; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006720:Homozygote; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D010147:Pain Measurement / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects / Q000235:genetics; D012890:Sleep / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D020864:Calcium Channels, N-Type; D006221:Halothane; D015742:Propofol