title: 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems.
abstract: Genes for five different 5-HT3 receptor subunits have been identified. Most of the subunits have multiple isoforms, but two isoforms of the B subunits, brain-type 1 (Br1) and brain-type 2 (Br2) are of particular interest as they appear to be abundantly expressed in human brain, where 5-HT3B subunit RNA consists of approximately 75% 5-HT3Br2, 24% 5-HT3Br1, and <1% 5-HT3B. Here we use two-electrode voltage-clamp, radioligand binding, fluorescence, whole cell, and single channel patch-clamp studies to characterize the roles of 5-HT3Br1 and 5-HT3Br2 subunits on function and pharmacology in heterologously expressed 5-HT3 receptors. The data show that the 5-HT3Br1 transcriptional variant, when coexpressed with 5-HT3A subunits, alters the EC50, nH, and single channel conductance of the 5-HT3 receptor, but has no effect on the potency of competitive antagonists; thus, 5-HT3ABr1 receptors have the same characteristics as 5-HT3AB receptors. There were some differences in the shapes of 5-HT3AB and 5-HT3ABr1 receptor responses, which were likely due to a greater proportion of homomeric 5-HT3A versus heteromeric 5-HT3ABr1 receptors in the latter, as expression of the 5-HT3Br1 compared to the 5-HT3B subunit is less efficient. Conversely, the 5-HT3Br2 subunit does not appear to form functional channels with the 5-HT3A subunit in either oocytes or HEK293 cells, and the role of this subunit is yet to be determined.
authors.affiliation: †INIBIBB, UNS/CONICET, Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Corradi
authors.affiliation: ‡Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: ‡Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: McGonigle
authors.affiliation: ‡Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Price
authors.affiliation: †INIBIBB, UNS/CONICET, Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bouzat
authors.affiliation: ‡Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Sarah C R
authors.initials: SC
authors.lastname: Lummis
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms; D011869:Radioligand Assay; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D056969:Voltage-Sensitive Dye Imaging; D014981:Xenopus
chemical_list: C509409:HTR3A protein, human; C509410:HTR3B protein, human; D020033:Protein Isoforms; D044406:Receptors, Serotonin, 5-HT3
keywords: Serotonin; cys-loop; heteromeric; single channel