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The 7 Nicotinic Acetylcholine Receptor Subunit Exists in Two Isoforms that Contribute to Functional Ligand-Gated Ion Channels

Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa, Florida

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 7 subunit (7-nAChRs). Unlike 7-nAChRs expressed in other cells, the predominant 7-nAChR subtype found in rat intracardiac and superior cervical ganglion neurons exhibits a slow rate of desensitization and is reversibly blocked by -bungarotoxin (Bgt). We report here the identification of an 7 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 7 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 7-2 insert showed a pattern of expression consistent with 7-2 subunit mRNA distribution. Moreover, the 7-2 subunit could be immunodepleted from protein extracts by solid-phase immunoprecipitation techniques using the anti-7 monoclonal antibody 319. The 7-2 subunit was shown to form functional homomeric ion channels that were activated by acetylcholine and blocked by -bungarotoxin when expressed in Xenopus laevis oocytes. This 7 isoform exhibited a slow rate of desensitization, and inhibition of these channels by Bgt reversed rapidly after washout. Taken together, these data indicate that the 7-2 subunit is capable of forming functional Bgt-sensitive acetylcholine receptors that resemble the 7-nAChRs previously identified in rat autonomic neurons. Furthermore, the distribution of the 7-2 isoform is not limited to peripheral neurons.

Address correspondence to: Dr. Javier Cuevas, Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, 12901 Bruce B. Downs Boulevard, MDC 9, Tampa, FL 33612-4799. E-mail: jcuevas{at}hsc.usf.edu

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