Isoflurane inhibits neuronal Ca2+ channels through enhancement of current inactivation

To help clarify the mechanisms by which volatile anaesthetics act on neuron al Ca2+ channel currents (I-Ba), the effects of isoflurane were studied on Iga in rat dorsal root ganglion (DRG) cells. Voltage-dependent I-Ba were ph armacologically subdivided into L-, N- and P/Q-types, and toxin-resistant I -Ba. At clinically relevant concentrations, isoflurane inhibited the L-, N- and P/Q-types, bur nor toxin-resistant I-Ba. The IC50 Values for the L-, N - and P/Q-types were 0.7%, 1.3% and 3.0%, respectively (concentrations equi valent to 0.35, 0.68 and 1.46 mmol litre(-1) in the aqueous phase). Isoflur ane also produced initial transient augmentation of the N-type I-Ba. Isoflu rane shifted the mid-point of the steady-state inactivation curve for the L -, N- and P/Q-type Iga towards negative potentials, and prolonged the time constant of current reactivation. We conclude that isoflurane inhibited L-, N- and P/Q-type I-Ba in rat DRG neurones by enhancing current inactivation and prolonging recovery time after inactivation. Transient augmentation of the N-type I-Ba may also form part of the overall actions of isoflurane in DRG neurones.