Reduction by sevoflurane of adenosine 5'-triphosphate-activated inward current of locus coeruleus neurons in pontine slices of rats.
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.
Masaki
E
E
Department of Pharmacology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
Kawamura
M
M
Kato
F
F
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
D018685:Anesthetics, Inhalation; D007473:Ion Channels; D008738:Methyl Ethers; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000077149:Sevoflurane; D000255:Adenosine Triphosphate