5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
ACS Chemical Neuroscience
American Chemical Society
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Corradi, J., Thompson, A., McGonigle, I., Price, K., Bouzat, C., & Lummis, S. (2015). 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems. ACS Chemical Neuroscience, 6 1158-1164. https://doi.org/10.1021/acschemneuro.5b00080
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.
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.
Wellcome Trust (081925/Z/07/A)
British Heart Foundation (PG/13/39/30293)
External DOI: https://doi.org/10.1021/acschemneuro.5b00080
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248207
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/