MOLECULAR ACTIONS OF PENTOBARBITAL ON SODIUM-CHANNELS IN LIPID BILAYERS - ROLE OF CHANNEL STRUCTURE

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.