INVESTIGADORES
PLAZAS Paola Viviana
congresos y reuniones científicas
Título:
FUNCTIONAL PROPERTIES OF AN 910 NICOTINIC RECEPTOR MUTATED IN THE M2 DOMAIN
Autor/es:
GÓMEZ CASATI ME; KATZ E; WEISSTAUB N; PLAZAS P; ELGOYHEN AB1
Reunión:
Congreso; Society for Neuroscience 32nd Annual Meeting; 2002
Resumen:
Nicotinic cholinergic
receptors nAChR are believed to be composed of five membrane spanning subunits
arranged in a ring around the ion permeation pathway, the walls of which are
formed by an a-helical segment, the M2 domain, from each subunit.
Site-directed mutagenesis studies have suggested that the ion channel is
organized into a series of rings of amino acids consisting of the five amino
acids contributed by each subunit and that these rings govern the
pharmacological and ion transport properties of the pore. The a9
and a10
nAChR subunits are the main components of the receptor present at the outer
hair cells of the cochlea. In order to study some structure-function
relationships of the heteromeric a9a10 nAChR, we mutated the aminoacid 263 (Met in a9 and Ileu in a10) in the
extracellular end of the M2 region to Thr in both subunits. Mutated subunits
were co-expressed in Xenopus laevis
oocytes and agonist-evoked currents were measured under two-electrode
voltage-clamp. This mutation altered the desensitization pattern of the a9a10
receptor and increased the apparent affinity for ACh without affecting its Ca++
permeability. Choline, a weak partial agonist of the wild type a9a10
nAChR behaved as a full agonist of the mutant receptor. Nicotine, an antagonist
of the wild type receptor, elicited ionic currents when applied to this mutant.
Serotonin, an antagonist of the wild type receptor, reduced the holding current
in oocytes expressing the mutant receptor. These results suggest that this
mutation might alter the open-close transitions of the channel.
Supported by ANPCyT, Ramón Carrillo-Arturo Oñativia
and HHMI.