Different serotonin type 3 subunit can coassemble into heteromeric receptors

CORRADI, J.; MAZZARINI DIMARCO, A.; BOUZAT, C.

Córdoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Investigación en Neurociencias (SAN)

P.239 - DIFFERENT SEROTONIN TYPE 3 SUBUNITS CAN COASSEMBLE INTO HETEROMERIC RECEPTORS5HT3 receptors are the only serotonin (5 HT) receptors that belong to the Cys loop receptor family. They mediate fast excitatory transmission in central and peripheral nerv ous system. Five different subunits (A E) have been identified in humans. The A subunit is able to form functional homomeric receptors (5 HT3A), and it can also combine with the B subunit to form heteromeric receptors (5 HT3AB). To evaluate the capability of the C, D and E subunits to combine with the A subunit to form heteromeric receptors we performed single channel and macroscopic recordings. After expression of the A subunit, we recorded single channel openings with an amplitude corresponding to the 5 H T3A receptor. However, when this subunit was expressed with one of the C E subunits, opening events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. From macroscopic currents we determined that the EC50 valu es for 5 HT were statistically different when homomeric or heteromeric receptors were expressed. Taking together, our results demonstrate that all the 5 HT3 subunits can combine with the A subunit to form heteromeric receptors. In silico studies provided i nsights into the contribution of the different subunits to the 5 HT binding site. The functional characterization of different heteromeric 5 HT3 receptors will contribute to the development of selective therapies targeting this receptor family.