Human CNS sodium channels provide a protein model system for our conti
nuing study of anaesthetic drug interactions at the molecular level. T
he impact of ethanol, an alcohol with general anaesthetic properties,
on sodium channel function and their significance for the overall anae
sthetic effect was quantified. Sodium channels from human brain cortex
tissue were incorporated into voltage-clamped planar lipid bilayers i
n the presence of batrachotoxin and studied at various ethanol concent
rations (0.085 - 0.84 M). Ethanol caused a concentration-dependent and
membrane potential independent reduction of the single channel amplit
ude (major effect) and of the fractional channel open-time (minor effe
ct) with no effect on channel steady-state activation. Severe membrane
perturbing effects at the highest ethanol levels terminated the measu
rements. The weighted computer fit of the concentration-response curve
with an estimate of a maximal conductance block of 40% yielded an EC5
0 Of 1.03 M. The EC50 for the 100% maximal theoretical block was calcu
lated to be 3.3 M. These effects occurred at levels far beyond toxic h
uman serum levels (0.1 M; 0.5%). Thus, the human CNS sodium channel is
not a main target site for the clinical effects of ethanol and other,
more sensitive central receptors are involved in ethanol's mechanism
of action.