α-RgIA:: A novel conotoxin that specifically and potently blocks the α9α10 nAChR

The alpha 9 and alpha 10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the alpha 9 alpha 10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition alpha 9 and/or alpha 10 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 alpha 9 alpha 10 channel could be valuable tools for elucidating its role in these diverse tissues. This study describes a novel alpha-conotoxin from the Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is a subtype specific blocker of the alpha 9 alpha 10 nAChR. alpha-RgIA belongs to the alpha 4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity comparisons between alpha-RgIA and previously characterized alpha 4/3 toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are responsible for its preferential inhibition of the alpha 9 alpha 10 nAChR subtype.