ORGANIZATION OF THE MOUSE 5-HT3 RECEPTOR GENE AND FUNCTIONAL EXPRESSION OF 2 SPLICE VARIANTS

The structure of the mouse 5-HT3 receptor gene, 5-HT(3)R-A, is most si milar to nicotinic acetylcholine receptor (nAChR) genes, in particular to the gene encoding the neuronal nAChR subunit alpha(7). These genes share among other things the location of three adjacent introns, sugg esting that 5-HT(3)R-A and nAChR genes arose from a common precursor g ene. The alternative use of two adjacent splice acceptor sites in intr on 8 creates, in addition to the original 5-HT(3)R-A cDNA (5-HT(3)R-A( L)), a shorter isoform (5-HT(3)R-A(S)) which lacks six codons in the s egment that translates into the major intracellular domain. This splic e consensus sequence is not found in human genomic DNA. In mouse, we d emonstrate by mRNA in both neuroblastoma cell lines and neuronal tissu es. We used the Semliki Forest virus expression system for electrophys iological characterization of 5-HT(3)R-A(S) and 5-HT(3)R-A(L) in mamma lian cells. No differences in electrophysiological characteristics, su ch as voltage dependence, desensitization kinetics, or unitary conduct ance were found between homomeric 5-HT(3)R-A(S) and 5-HT(3)R-A(L) rece ptors. Their properties are very similar to those of 5-HT3 receptors i n mouse neuroblastoma cell lines.