LABORATORY INVESTIGATIONS Isoflurane inhibits neuronal Ca2F channels through enhancement of current inactivation

To help clarify the mechanisms by which volatile anaesthetics act on neuronal Ca21 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-, Nand P/Q-types, and toxin-resistant IBa. At clinically relevant concentrations, isoflurane inhibited the L-, Nand P/Q-types, but not toxin-resistant IBa. The IC50 values for the L-, Nand 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-, Nand P/Qtype IBa towards negative potentials, and prolonged the time constant of current reactivation. We conclude that isoflurane inhibited L-, Nand 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.