Referenced in: none

Automatically associated channels: Slo1

Title: α-conotoxin MrIC is a biased agonist at α7 nicotinic acetylcholine receptors.

Authors: Alexander Mueller, Hana Starobova, Marco C Inserra, Ai-Hua Jin, Jennifer R Deuis, Sébastien Dutertre, Richard J Lewis, Paul F Alewood, Norelle L Daly, Irina Vetter

Journal, date & volume: Biochem. Pharmacol., 2015 Mar 15 , 94, 155-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25646788

Abstract
MrIC is a recently described selective agonist of endogenously expressed α7 nAChR. In this study, we further characterize the pharmacological activity of MrIC using Ca(2+) imaging approaches in SH-SY5Y cells endogenously expressing α7 nAChR and demonstrate that MrIC exclusively activates α7 nAChR modulated by type II positive allosteric modulators, including PNU120596. MrIC was a full agonist at PNU120596-modulated α7 nAChR compared with choline, albeit with slower kinetics, but failed to elicit a Ca(2+) response in the absence of PNU120596. Interestingly, the NMR structure of MrIC showed a typical 4/7 α-conotoxin fold, indicating that its unusual pharmacological activity is likely sequence-dependent. Overall, our results suggest that MrIC acts as a biased agonist that can only activate α7 nAChR modified by type II positive allosteric modulators, and thus represents a valuable tool to probe the pharmacological properties of this important ion channel.