title: Differential effects of isoflurane on A-type and delayed rectifier K channels in rat substantia nigra.
abstract: The authors previously demonstrated that isoflurane, a widely used volatile anesthetic, induced depolarization and increased the frequency of spontaneous action potentials in principal dopamine neurons in rat substantia nigra pars compacta. We studied the effects of isoflurane on voltage-dependent K channels to clarify the mechanisms of the increase in excitability in these neurons. Voltage-clamp whole-cell recordings were made in rat midbrain slices. We recorded the outward membrane currents in response to depolarizing voltage steps from -120 mV and -25 mV and isolated the transient outward current mediated through A-type K channels by subtraction. Isoflurane at clinically relevant concentrations accelerated the decay of the A-type K current and delayed the recovery from inactivation without changing the steady-state inactivation curves. Isoflurane did not affect the non-inactivating outward current. Addition of 4-aminopyridine partially occluded the excitatory effects of isoflurane in current-clamp recordings. These results demonstrate that isoflurane accelerated the inactivation and delayed the recovery from inactivation of A-type K channels in principal neurons in rat substantia nigra pars compacta without affecting delayed rectifier K channels. These effects may contribute in part to excitation of these neurons and the isoflurane-induced increases in dopamine release reported in vitro and in vivo.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ishiwa
authors.forename: Isao
authors.initials: I
authors.lastname: Nagata
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Hideki
authors.initials: H
authors.lastname: Itoh
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ogawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakai
authors.forename: Nagaaki
authors.initials: N
authors.lastname: Sekino
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takahisa
authors.initials: T
authors.lastname: Goto
authors.forename: Tomio
authors.initials: T
authors.lastname: Andoh
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D051668:Delayed Rectifier Potassium Channels; D051672:Shal Potassium Channels; D015761:4-Aminopyridine; D007530:Isoflurane; D004298:Dopamine