Influence of Y151F mutation in loop B on the agonist potency in insect nicotinic acetylcholine receptor

Abstract

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, which mediate fast cholinergic synaptic transmission in insect and vertebrate nervous systems. The nAChR agonist-binding site is present at the interface of adjacent subunits and is formed by loops A-C present in α subunits together with loops D-F present in either non-α subunits or homomer-forming α subunits. Although Y151 in loop B has been identified as important in agonist binding, various residues at the 151-site are found among vertebrate and invertebrate nAChR α subunits, such as F151. In Xenopus oocytes expressing Nlα1 or Nlα1Y151F plus rat β2, Y151F mutation was found to significantly change the rate of receptor desensitization and altered the pharmacological properties of acetylcholine, but not imidacloprid, including the decrease of Imax, the increase of EC50 (the concentration causing 50% of the maximum response) and the fast time-constant of decay (τf). By comparisons of residue structure, the hydroxyl group in the side chain of Y151 was thought to be important in the interaction between Nlα1/β2 nAChRs and acetylcholine, and the phenyl group to be important between Nlα1/β2 nAChRs and imidacloprid. © Institute of Zoology, Chinese Academy of Sciences.