INVESTIGADORES
BOUZAT Cecilia Beatriz
congresos y reuniones científicas
Título:
Structural and functional characterization of human heteromeric 5-HT3 receptors
Autor/es:
CORRADI J.; BOUZAT, C .
Lugar:
San Miguel de Tucuman
Reunión:
Congreso; IIILAFeBS, IX Iberoamerican Congress of Biophysics and XLV SAB Meeting; 2016
Resumen:
5-HT3 receptors are members of the Cys-loop receptor family that mediate fast excitatory transmission in central and peripheral nervous system. Genes for five different subunits (A-E) have been identified in humans, and most of the subunits have multiple isoforms. The A subunitis capable of forming functional homomeric (5-HT3A), or heteromeric receptors with the B subunit (5-HT3AB). Here we combine singlechannel and macroscopic current recordings to determine if other 5-HT3 subunits, Br1, Br2, C, D and E (B-E), can combine with the A subunit to form heteromeric receptors. After co-expression of the A subunit with each of the tested subunits, single-channel events with different conductance and kinetic properties with respect to those of 5-HT3A receptorswere detected, except for the Br2 subunit. These results indicate that B-E subunits can assemble into functional heteromeric receptors with the A subunit. From the corresponding recordings, the analysis of the single-channel amplitude of the opening events suggests a possible stoichiometry for each heteromeric receptor, since each subunit (B-E) that is incorporated into the pentamer increases the conductance of the homomeric 5-HT3A receptor in 14 pS. Conversely, the Br2 subunitdoes not appear to form functional receptors with A, since macroscopic currents and single-channel recordings did not differ from those of homomeric 5-HT3A receptors. Our results confirm the incorporation of different 5-HT3 subunits into the receptor, thus leading to a wide varietyof receptors showing different functional properties, such as agonist sensitivity, kinetics and single-channel conductance. The functional characterization of different heteromeric 5-HT3 receptors, which are expressed in different tissues, would contribute to the development of selective therapies targeting this receptor family.