Four pharmacologically distinct subtypes of alpha4beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes

Nicotinic receptors generally are presumed to consist of two a and three non-a subunits. We varied the relative levels of ex-pression of the neuronal nicotinic a4 and b2 receptor subunits in Xenopus laevis oocytes by nuclear injection of cDNAs coding for these subunits in a:b ratios of 9:1, 1:1, and 1:9. The sensi-tivities of the receptors to acetylcholine and d-tubocurarine were investigated in voltage-clamp experiments. For receptors expressed at the 9:1 and 1:1 a:b ratios, the EC50 value of acetylcholine is;60 mM. For the majority of the receptors expressed at the 1:9 a:b ratio, the sensitivity to acetylcholine is enhanced 30-fold. No evidence for more than one type of acetylcholine binding site in a single receptor is obtained. The sensitivity to d-tubocurarine decreases with decreasing a:b ratio. IC50 values of d-tubocurarine are 0.2, 0.5, and 2 mM for th