Pentobarbital has curare-like effects on adult-type nicotinic acetylcholine receptor channel currents.

UNLABELLED: Pentobarbital (PB) is widely used as a short-term sedative and anticonvulsive drug with a side-effect of relaxing muscle tone. We investigated block of nicotinic acetylcholine receptor (nAChR) channel currents by PB using the patch-clamp technique in combination with an ultrafast system for solution exchange. As a preparation, recombinant rat adult-type nAChR channels transiently expressed in HEK293 cells were used. Appli-cation of 1 mM acetylcholine to small cells or outside-out patches showed a transient current with fast activation and desensitization kinetics. Adding PB to the acetylcholine-containing solution resulted in a decrease of the time constant of current decay and of the peak current amplitude starting at concentrations >0.01 mM PB. Preincubation of nAChR channels with PB led to a decrease of the peak current amplitude without alteration of activation and desensitization kinetics caused by competitive block of nAChR channels. In conclusion, similar to the effect of d-Tubocurarine, block of nAChR channel currents by PB can be explained by a combination of open-channel and competitive block.

IMPLICATIONS: The interaction between adult-type nicotinic acetylcholine receptors, acetylcholine, and pentobarbital was biophysically investigated by using the patch-clamp technique in combination with tools for ultrafast solution exchange. PB elicited open-channel block and competitive block of nicotinic acetylcholine receptor channel currents, whereas the latter seems to be effective in clinically relevant concentrations.