INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Functional characterization of a4b2 recombinant nicotinic receptors with point mutations in the TM2 domain.
Autor/es:
LIPOVSEK, M; ELGOYHEN, AB; KATZ, E
Lugar:
Buenos Aires
Reunión:
Congreso; XXXIX Asociación Argentina de Farmacología Experimental; 2007
Resumen:
The most abundant heteromeric neuronal nicotinic receptor, is formed by the a4 and b2 subunits. Mutations in these subunits are linked to a monogenic familial epilepsy known as ADNFLE. To reproduce the human phenotype of ADNFLE, Klaasen et al. generated ‘knock in’ mice that carry one of the two most extensively characterized mutations in the a4 subunit: S248F and 776ins3. Both mutations are located within the second transmembrane domain. The goal of the present work was to study, using the two electrode voltage clamp technique, the functional properties of the recombinant receptors that result from the expression, in Xenopus oocytes, of mouse clones with the S248F or 776ins3 mutations in the a4 subunit. Both mutations affected the sensitivity of the receptor for acetylcholine (ACh). The pronounced effect caused by the S248F mutation allowed the discrimination in the ACh dose response curve of three different populations of receptors present in the membrane. The S248F mutant receptors desensitized more than wild type and 776ins3 mutant receptors. Responses to ACh were potentiated by the increase in extracellular calcium in both wild type and mutant receptors. The results presented here are in agreement with published data for human wild type and mutant receptors. These results support the use of the knock-in mice as an animal model for the study of ADNFLE.