RESIDUES 1 TO 80 OF THE N-TERMINAL DOMAIN OF THE BETA-SUBUNIT CONFER NEURONAL BUNGAROTOXIN SENSITIVITY AND AGONIST SELECTIVITY ON NEURONAL NICOTINIC RECEPTORS

Standard two electrode voltage clamp techniques were used to investiga te the response of neuronal nicotinic acetylcholine receptors, express ed in Xenopus oocytes, to various agonists and neuronal bungarotoxin ( NBT). The beta subunit is an important determinant of the receptor's p harmacological profile. Co-expression of alpha4 and beta2 subunits pro duced a receptor that was relatively insensitive to cytisine and nicot ine and inhibited by NBT, whilst the alpha4beta4 combination produced a receptor that was highly sensitive to cytisine and nicotine but resi stant to toxin. The first 80 amino acids of the N-terminal domain of t he beta subunit are implicated in these characteristics, since the com bination of alpha4 with a hybrid beta subunit comprising amino acids 1 --> 80 of beta2 and 81 --> 416 of beta4 became relatively insensitive to nicotine and cytisine and resistant to inhibition by neuronal bung arotoxin.