title: Desensitization characteristics of the human alpha7nAChR/5HT3A chimera receptor.
abstract: The alpha7-nicotinic acetylcholine receptor (alpha7) is an important ionotropic receptor in the central nervous system, which becomes permeable to cations upon binding of its natural agonist acetylcholine (ACh). alpha7 kinetics are characterized by rapid activation, followed by fast desensitization of the current. As the wild-type (WT) alpha7 is difficult to express heterologously in mammalian cellular systems, frequently a more easily expressible chimera consisting of the extracellular domain of the alpha7 and the transmembrane domain of the 5HT3A receptor is used to study alpha7 pharmacology (chick alpha7/mouse 5HT3A [Eiselé et al., 1993]; human alpha7/mouse 5HT3A [Graig et al., 2004]). Desensitization characteristics of these chimera receptors have been described as intermediate compared with the fast desensitizing alpha7 and the more slowly desensitizing 5HT3A receptors. Here, we describe a fully human chimera receptor (h-alpha7/5HT3A), which is characterized by desensitization, and recovery kinetics that deviate from the human WT alpha7.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica N.V., B-2340 Beerse, Belgium. tdinklo@prdbe.jnj.com
authors.forename: Theo
authors.initials: T
authors.lastname: Dinklo
authors.forename: Anne S
authors.initials: AS
authors.lastname: Lesage
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Grantham
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D005260:Female; D050506:Mutant Chimeric Proteins / Q000378:metabolism; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D050506:Mutant Chimeric Proteins; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000109:Acetylcholine