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

Michael Ellison, Christian Haberlandt, María Eugenia Gomez-Casati, Maren Watkins, A. Belén Elgoyhen, J. Michael McIntosh, Baldomero M. Olivera

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

The α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the α9α10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition α9 and/or α10 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 α9α10 channel could be valuable tools for elucidating its role in these diverse tissues. This study describes a novel α-conotoxin from the Western Atlantic species Conus regius, α-conotoxin RgIA (α-RgIA), that is a subtype specific blocker of the α9α10 nAChR. α-RgIA belongs to the α4/3 subfamily of the α-conotoxin family; sequence and subtype specificity comparisons between α-RgIA and previously characterized α4/3 toxins indicate that the amino acids in the C-terminal half of α-RgIA are responsible for its preferential inhibition of the α9α10 nAChR subtype.

Original languageEnglish (US)
Pages (from-to)1511-1517
Number of pages7
JournalBiochemistry®
Volume45
Issue number5
DOIs
StatePublished - Feb 7 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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