Nicotinic acetylcholine receptors assembled from the alpha 7 and beta 3 subunits

Intracellular recordings were performed in voltage-clamped Xenopus oocytes upon injection with a mixture of cDNAs encoding the beta 3 and mutant alpha 7 ((L247T)alpha 7) neuronal nicotinic acetylcholine receptor (nAChR) subun its. The expressed receptors maintained sensitivity to methyllycaconitine a nd to alpha-bungarotoxin but exhibited a functional profile strikingly diff erent from that of the homomeric (L247T)alpha 7 receptor, The heteromeric ( L247T)alpha 7 beta 3 nAChR had a lower apparent affinity and a faster rate of desensitization than L247Ta7 nAChR, exhibited nonlinearity in the I-V re lationship, and was inhibited by 5-hydroxytryptamine, much like wild type a lpha 7 ((WT)alpha 7) nAChR. Single channel recordings in cell-attached mode revealed unitary events with a slope conductance of 19 picosiemens and a l ifetime of 5 ms, both values being much smaller than those of the homomeric receptor channel. Upon injection with a mixture of (WT)alpha 7 and beta 3 cDNAs, clear evidence was obtained for the plasma membrane assembly of hete romeric nAChRs, although ACh could not activate these receptors. It is conc luded that beta 3, long believed to be an orphan subunit, readily co-assemb les with other subunits to form heteromeric receptors, some of which may be negative regulators of cholinergic function.