Sodium channels from human brain tissue were incorporated into voltage
-clamped planar lipid bilayers in presence of batrachotoxin and expose
d to increasing concentrations of the intravenous anaesthetic drug eto
midate (0.03-1.02 mM). Etomidate interacted with the sodium-conducting
pathway of the channel causing a concentration-dependent block of the
time-averaged sodium conductance (computer fit of the concentration-r
esponse curve: half-maximal blocking concentration, EC50, 0.19 mM; max
imal block, block(max) 38%). This block of sodium-conductance resulted
from two distinct effects (I) major effect: reduction of the sodium-c
hannel amplitude and (II) minor effect: reduction of the fractional ch
annel open-time. These results were observed at concentrations above c
linically-relevant serum concentrations (up to 0.01 mM), suggesting on
ly a limited role for human brain sodium channels in the mechanism of
action of etomidate during clinical anaesthesia. (C) 1998 Elsevier Sci
ence Ireland Ltd. All rights reserved.