INVESTIGADORES
BOUZAT Cecilia Beatriz
congresos y reuniones científicas
Título:
Activation and potentiation of alpha7 receptors with different number of agonist binding sites
Autor/es:
ANDERSEN, N.; CORRADI J.; SINE, S.; BOUZAT, C.
Lugar:
Huerta Grande, Córdoba
Reunión:
Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2012
Resumen:
Neuronal alpha7 nicotinic receptors are homopentameric ligand-gated ion channels, which are emerging as therapeutic targets for treatment of neurological disorders. They are characterized by fast desensitization and brief open-channel lifetime. We studied the relationship between the number of occupied binding sites and alpha7 activation. To generate receptors with different number of functional binding sites we constructed an alpha7 subunit with a mutation that disables the binding site and a reporter mutation that alters conductance, co-expressed mutant and non mutant subunits, and recorded single-channel currents. The current amplitude of each opening reports the number of subunits containing the conductance mutation in the receptor that elicited that opening event, and therefore, the number of functional binding sites. We determined that open-channel lifetime remains constant in receptors with different number of functional binding sites. Lifetime is similarly prolonged by positive allosteric modulators in receptors with 1 or 5 occupied binding sites, indicating that potentiation is independent of the degree of ACh occupancy. Our results reveal a unique feature of alpha7 among other nicotinic receptors: occupancy of only one agonist binding site allows normal activation and potentiation.