A NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR SUBUNIT (ALPHA-7) IS DEVELOPMENTALLY REGULATED AND FORMS A HOMOOLIGOMERIC CHANNEL BLOCKED BY ALPHA-BTX

cDNA and genomic clones encoding alpha-7, a novel neuronal nicotinic acetylcholine receptor (nAChR) alpha subunit, were isolated and sequenced. The mature alpha-7 protein (479 residues) has moderate homology with all other alpha and non-alpha nAChR subunits and probably assumes the same transmembrane topology. Alpha-7 transcripts transiently accumulate in the developing optic tectum between E5 and E16. They are present in both the deep and the superficial layers of E12 tectum. In Xenopus oo-cytes, the alpha-7 protein assembles into a homo-oligomeric channel responding to acetylcholine and nicotine. The alpha-7 channel desensitizes very rapidly, rectifies strongly above -20 mV, and is blocked by alpha-bungarotoxin. A bacterial fusion protein encompassing residues 124-239 of alpha-7 binds labeled alpha-bungarotoxin. We conclude that alpha-bungarotoxin binding proteins in the vertebrate nervous system can function as nAChRs.