The α7 Nicotinic Acetylcholine Receptor Subunit Exists in Two Isoforms that Contribute to Functional Ligand-Gated Ion Channels

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Abstract
Fast synaptic transmission in mammalian autonomic ganglia is mediated primarily by nicotinic receptors, and one of the most abundant nicotinic acetylcholine receptor subtypes in these neurons contains the α7 subunit (α7-nAChRs). Unlike α7-nAChRs expressed in other cells, the predominant α7-nAChR subtype found in rat intracardiac and superior cervical ganglion neurons exhibits a slow rate of desensitization and is reversibly blocked by α-bungarotoxin (αBgt). We report here the identification of an α7 subunit sequence variant in rat autonomic neurons that incorporates a novel 87-base pair cassette exon in the N terminus of the receptor and preserves the reading frame of the transcript. This α7 isoform was detected using reverse transcriptase-polymerase chain reaction techniques in neonatal rat brain and intracardiac and superior cervical ganglion neurons. Immunoblot experiments using a polyclonal antibody directed against the deduced amino acid sequence of the α7-2 insert showed a pattern of expression consistent with α7-2 subunit mRNA distribution. Moreover, the α7-2 subunit could be immunodepleted from protein extracts by solid-phase immunoprecipitation techniques using the anti-α7 monoclonal antibody 319. The α7-2 subunit was shown to form functional homomeric ion channels that were activated by acetylcholine and blocked by α-bungarotoxin when expressed in Xenopus laevis oocytes. This α7 isoform exhibited a slow rate of desensitization, and inhibition of these channels by αBgt reversed rapidly after washout. Taken together, these data indicate that the α7-2 subunit is capable of forming functional αBgt-sensitive acetylcholine receptors that resemble the α7-nAChRs previously identified in rat autonomic neurons. Furthermore, the distribution of the α7-2 isoform is not limited to peripheral neurons.

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