The mechanism of steroid anaesthetic (alphaxalone) block of acetylcholine-induced ionic currents.

The effects of the steroid anaesthetic alphaxalone on acetylcholine (ACh)-induced ionic channels were studied in voltage clamped 'myoballs' in culture. Alphaxalone produced a reversible blockade of the ACh-evoked inward current, ED50 = 6.0 microM. The ACh reversal potential (-5.0 mV), the single channel conductance (13.5 pS) and mean open time (3.6 ms) were unchanged by the drug. Thus, alphaxalone produced an 'all or none' block of the ionic channel. In double pulse conditioning experiments, alphaxalone produced an additional inhibition with a time constant of recovery (550 ms) much longer than the time constant of recovery of the normal desensitization (250 ms). It was concluded that alphaxalone blocks active (open) ionic channels.