Two different modes of action of pentobarbital at glycine receptor channels

Abstract 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 α 1 β glycine receptor channels. Currents elicited by 0.03 mM glycine were enhanced by pentobarbital showing potentiation of α 1 β 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.