Hc. Wartenberg et al., MOLECULAR ACTIONS OF PENTOBARBITAL ON SODIUM-CHANNELS IN LIPID BILAYERS - ROLE OF CHANNEL STRUCTURE, British Journal of Anaesthesia, 72(6), 1994, pp. 668-673
The molecular mechanisms by which anaesthetics interfere with neuronal
function are controversial We have examined the effects of pentobarbi
tone on muscle-derived (eel electroplax) sodium channels incorporated
into planar bilayers under exactly the same experimental conditions th
at we used previously to study the anaesthetic modification of human b
rain channels. This technique allows examination of protein-mediated s
imilarities and differences. Sodium channels from the electroplax (mus
cle-derived) of the electric eel were purified and reconstituted into
planar lipid bilayers containing 4:1 phosphatidylethanolamine :phospha
tidylcholine in the presence of batrachotoxin, a sodium channel activa
tor. Pentobarbitone had similar voltage-independent blocking effects o
n sodium channels from eel electroplax and human brain, as demonstrate
d by similar dose-response curves (IC50 = 613 mu mol litre(-1)). Howev
er, activation of sodium channels from eel electroplax, in contrast wi
th human brain, was relatively insensitive to the concentration of pen
tobarbitone. The only significant effect was a -5.8-mV shift in the ac
tivation midpoint with pentobarbitone 680 mu mol litre(-1). Therefore,
differences in primary structures played no role in the observed volt
age-independent block of channels by pentobarbitone, whereas subunits
or other structural differences between sodium channels from eel elect
roplax and human brain must be responsible for She minimal effect of p
entobarbitone on activation of muscle-derived sodium channels.