INVESTIGADORES
BOUZAT Cecilia Beatriz
congresos y reuniones científicas
Título:
Functional and structural characterization of human heteromeric 5-ht3 receptors
Autor/es:
MAZZARINI DIMARCO, A.; BOUZAT, C.B.; CORRADI, J.
Lugar:
Villa Carlos Paz
Reunión:
Congreso; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2019
Resumen:
5 HT3 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 nervous system. Five different subunits (A-E) have been identified in humans. The A subunit is able to form homomeric receptors (5-HT3A), and it can combine with the B subunit to form heteromeric receptors. We here evaluated if the C-E subunits can combine with the A to form heteromeric receptors. To this end, we constructed a high-conductance A subunit (AHC) that allowed to obtain single-channel events. After expression of the AHC we observed events with an amplitude of ~4.7 pA corresponding to the 5 HT3AHC receptor. However, when AHC was expressed in combination with one of the C-E subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. From macroscopic currents we observed an increase in the 5-HT EC50 value for each of the heteromeric receptors with respect to that for the 5 HT3AHC receptor. In-silico studies provided insights into the contribution of the different subunits to the 5-HT binding site. Our results demonstrate that C-E subunits can combine with the A subunit to form heteromeric receptors. These results bring structural and functional details about the different human 5-HT3 receptors and will contribute to the development of selective therapies targeting this receptor family.