Differential effects of isoflurane on A-type and delayed rectifier K channels in rat substantia nigra.
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.
Ishiwa
Dai
D
Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Japan.
Nagata
Isao
I
Ohtsuka
Tatsuo
T
Itoh
Hideki
H
Kamiya
Yoshinori
Y
Ogawa
Kenichi
K
Sakai
Mariko
M
Sekino
Nagaaki
N
Yamada
Yoshitsugu
Y
Goto
Takahisa
T
Andoh
Tomio
T
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
D018685:Anesthetics, Inhalation; D051668:Delayed Rectifier Potassium Channels; D051672:Shal Potassium Channels; D015761:4-Aminopyridine; D007530:Isoflurane; D004298:Dopamine