title: Reduction by sevoflurane of adenosine 5'-triphosphate-activated inward current of locus coeruleus neurons in pontine slices of rats.
abstract: Increasing evidence indicates that volatile general anesthetics exert their effects by affecting various types of membrane conductance expressed in the central nervous system (CNS), such as ligand-gated receptor-channels. The most recently identified family of the receptor-channels in the CNS are the extracellular ATP-gated channels (P2X purinoceptors). In the present study, we tested whether volatile anesthetics can affect P2X receptor function in the CNS network. We recorded whole-cell currents of locus coeruleus (LC) neurons in pontine slices from young rats. Adenosine 5'-triphosphate (ATP) sodium (0.03-3 mM) evoked a rapidly rising and moderately desensitizing inward current (50-200 pA) in a dose-dependent manner in LC neurons at a holding potential of -80 mV. Perfusion with clinically relevant concentration of sevoflurane (0.1-0.5 mM) reduced the ATP-induced inward current in a dose-dependent manner (to 56.8+/-5.9% of control with 0.5 mM sevoflurane; mean+/-S.E.M., n=13). Estimated IC(50) of sevoflurane was 0.59 mM. We conclude that the attenuation of extracellular ATP-mediated signaling in the central nervous system might be one of the multiple actions of volatile anesthetics.
authors.affiliation: Department of Pharmacology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Masaki
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
authors.forename: F
authors.initials: F
authors.lastname: Kato
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D007473:Ion Channels; D008738:Methyl Ethers; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000077149:Sevoflurane; D000255:Adenosine Triphosphate