Alpha-RgIA: a novel conotoxin that specifically and potently blocks the alpha9alpha10 nAChR.
The alpha9 and alpha10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the alpha9alpha10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition alpha9 and/or alpha10 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 alpha9alpha10 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 alpha9alpha10 nAChR. alpha-RgIA belongs to the alpha4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity comparisons between alpha-RgIA and previously characterized alpha4/3 toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are responsible for its preferential inhibition of the alpha9alpha10 nAChR subtype.
Ellison
Michael
M
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA. michael.ellison@m.cc.utah.edu
Haberlandt
Christian
C
Gomez-Casati
María Eugenia
ME
Watkins
Maren
M
Elgoyhen
A Belén
AB
McIntosh
J Michael
JM
Olivera
Baldomero M
BM
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D020916:Conotoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013045:Species Specificity; D014981:Xenopus / Q000235:genetics
C470699:Chrna10 protein, rat; C498541:Chrna9 protein, rat; D020916:Conotoxins; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C510079:conotoxin alpha-RgIA, Conus regius