Evento
Stoichiometry for activation of neuronal α7 nicotinic Receptors
Tipo del evento:
Congreso
Nombre del evento:
XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.
Fecha del evento:
30/09/2013
Institución Organizadora:
Sociedad Argentina de Neurociencias;
Título del Libro:
XXVIII Congreso anual de la Sociedad Argentina de Investigación en Neurociencias
Editorial:
Sociedad Argentina de Investigación en Neurociencias
Idioma:
Español
Clasificación temática:
Resumen
Neuronal α7 nicotinic receptors are homopentameric ligand-gated ion channels (LGICs) that participate in cognition, synaptic plasticity and neuroprotection, and have emerged as therapeutic targets for treatment of neurological disorders. α7 often localizes distal to sites of nerve-released ACh, binds ACh with low affinity, and thus elicits its biological response with partial occupancy of its five identical binding sites. We therefore addressed the question of how α7 operates at these physiological conditions. To assess function of α7 when neurotransmitter occupies fewer than five binding sites, we generated α7 receptors with a different number of functional neurotransmitter binding sites. By measuring open-channel lifetime of individual receptors, we found that only one occupied site allows maximal response and that the additional sites allow enhanced agonist sensitivity. In contrast to α7, we found that open-channel lifetime of a receptor formed by the extracellular domain of α7 and the transmembrane region of 5-HT3A (α7-5HT3A) is dependent on the number of functional binding sites. Our results reveal that: i) the agonist binding domain is not sufficient to determine the relationship between agonist occupancy and open-channel stability and, ii) the distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and non-neuronal cells.
Palabras clave:
PATCH-CLAMP
,
RECEPTORS
,
BINDING
Archivos asociados
Licencia
Identificadores
Colecciones
Eventos(INIBIBB)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
Stoichiometry for activation of neuronal α7 nicotinic Receptors; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; Huerta Grande; Argentina; 2013; 285-285
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