Alpha-RgIA: a novel conotoxin which specifically and potently blocks the alpha9alpha10 nAChR

ELLISON M; HABERLANDT C; GOMEZ CASATI ME; WATKINS M; ELGOYHEN AB; MCINTOSH M; OLINERA BO

BIOCHEMISTRY

Año: 2006 vol. 45 p. 1511 - 1517

0006-2960

The a9 and a10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the a9a10 nAChR subtype.  This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea.  In addition a9 and/or a10 expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes and the pars tuberalis of the pituitary.  Specific antagonists that selectively block the a9a10 channel could be valuable tools for elucidating its role in these diverse tissues.  This study describes a novel a-conotoxin from the Western Atlantic species Conus regius, a-conotoxin RgIA (a-RgIA) that is a subtype specific blocker of the a9a10 nAChR.  a-RgIA belongs to the a4/3 subfamily of the a-conotoxin family; sequence and subtype specificity comparisons between a-RgIA and previously characterized a4/3 toxins indicate that the amino acids in the C-terminal half of a-RgIA are responsible for its preferential inhibition of the a9a10 nAChR subtype.