Isoflurane inhibits neuronal Ca2+ channels through enhancement of current inactivation.
To help clarify the mechanisms by which volatile anaesthetics act on neuronal Ca2+ channel currents (IBa), the effects of isoflurane were studied on IBa in rat dorsal root ganglion (DRG) cells. Voltage-dependent IBa were pharmacologically subdivided into L-, N- and P/Q-types, and toxin-resistant IBa. At clinically relevant concentrations, isoflurane inhibited the L-, N- and P/Q-types, but not toxin-resistant IBa. The IC50 values for the L-, N- and P/Q-types were 0.7%, 1.3% and 3.0%, respectively (concentrations equivalent to 0.35, 0.68 and 1.46 mmol litre-1 in the aqueous phase). Isoflurane also produced initial transient augmentation of the N-type IBa. Isoflurane shifted the mid-point of the steady-state inactivation curve for the L-, N- and P/Q-type IBa towards negative potentials, and prolonged the time constant of current reactivation. We conclude that isoflurane inhibited L-, N- and P/Q-type IBa in rat DRG neurones by enhancing current inactivation and prolonging recovery time after inactivation. Transient augmentation of the N-type IBa may also form part of the overall actions of isoflurane in DRG neurones.
Kameyama
K
K
Department of Anaesthesiology, Fukuoka Dental College, Japan.
Aono
K
K
Kitamura
K
K
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007530:Isoflurane; D002118:Calcium