Two different modes of action of pentobarbital at glycine receptor channels.

Glycine receptor channels are pentameric ligand-gated ion channels which respond to the binding of inhibitory transmitters by opening of a chloride-selective central pore. Pentobarbital is widely used as an anticonvulsive, hypnotic and anaesthetic drug. In the present study, the interaction between pentobarbital and glycine receptor channels was studied on outside-out patches of human embryonic kidney (HEK) 293 cells expressing alpha(1)beta glycine receptor channels. Currents elicited by 0.03 mM glycine were enhanced by pentobarbital showing potentiation of alpha(1)beta glycine receptor channels. In the presence of 1 mM glycine+pentobarbital (1 and 3 mM), desensitization was faster and the peak current amplitude decreased. After the end of glycine+pentobarbital pulses, off-currents occurred suggestive for a channel block mechanism. Pentobarbital had no agonistic effects at glycine receptor channels.