Evidence for expression of heteromeric serotonin 5-HT3 receptors in rodents

The gene and cDNAs that encode a novel subunit of rodent serotonin 5-HT3 re ceptors were isolated from mouse and rat tissues. Each of the new rodent su bunits shares 40% amino acid identity with the rat 5-HT3A subunit and 73% i dentity with the human 5-HT3B subunit. Despite a relatively low level of st ructural conservation, sequence analysis and functional studies suggest tha t the new rodent subunits are orthologues of the human 5-HT3B subunit. In c ommon with homologous human receptors, rat heteromeric 5-HT3 receptors disp layed a substantially larger single-channel conductance than homomeric 5-HT 3A receptors. In addition, the rat heteromeric receptors were less sensitiv e to antagonism by tubocurarine. However, in contrast to human heteromeric receptors, those of the rat displayed pronounced inward rectification of bo th the whole-cell and single-channel current amplitudes. Transcripts of the mouse 5-HT3A and 5-HT3B subunits are coexpressed in several cell lines tha t possess endogenous 5-HT3 receptors. in addition, treatment of rat PC12 ce lls with nerve growth factor induced expression of both subunit mRNAs, with a similar time course for accumulation of each transcript. The combination of functional data and expression patterns is consistent with the existenc e of heteromeric 5-HT3 receptors in rodent neurons.