5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems.

Change log
Corradi, Jeremias 
Thompson, Andrew J 
McGonigle, Ian 
Price, Kerry L 
Bouzat, Cecilia 

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.

Serotonin, cys-loop, heteromeric, single channel, Animals, Brain, HEK293 Cells, Humans, Membrane Potentials, Oocytes, Patch-Clamp Techniques, Protein Isoforms, Radioligand Assay, Receptors, Serotonin, 5-HT3, Sequence Homology, Amino Acid, Transfection, Voltage-Sensitive Dye Imaging, Xenopus
Journal Title
ACS Chem Neurosci
Conference Name
Journal ISSN
Volume Title
American Chemical Society (ACS)
Medical Research Council (MR/L021676/1)
Wellcome Trust (081925/Z/07/A)
British Heart Foundation (None)
Supported by grants from Universidad Nacional del Sur (UNS), Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT), and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) to CB, and The Wellcome Trust (81925) and the MRC (MR/L021676) to SCRL.