Activation, Nicotinic acetylcholine receptor leads to Desensitization, Nicotinic acetylcholine receptor

Text from LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:

Desensitizationis a well-studied biological function that occurs upon activation of ligand- gated ion channels, such as the nAChR, with prolonged or repeated exposure to variable concentrations (typically low) of agonist; thus, biological plausibility of activation leading to desensitization is quite strong.However, there are relatively significant uncertainties associated with desensitization of the insect neuronal nAChR, due to incomplete characterization of the subunit combinations that make-up the nAChR in neurons of the honey bee (or other invertebrates), which may affect both chemical binding affinity and available phosphorylation sites involved in recovery from the desensitized state (Hopfield et al., 1988; Thany et al., 2007). Although progress has been made in characterizing the composition of the nAChR subunits, most recombinant hybrid nAChRs evaluated consist of a combination of both insect and vertebrate subunits (Ihara et al., 2007). Therefore, the composition and activity of insect subunits alone have not been elucidated nor evaluated. Further, concentrations and durations of agonist exposure that would lead to a prolonged desensitized state of the receptor, effectively inactivating it, are uncertain. Research focused on characterization of insect nAChR, with evaluation of temporal and dosimetric concordancewould provide greater understanding of the mechanism through which activation of the nAChR can lead to desensitization and subsequent downstream events.