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. 2018 Jul 3;13(7):e0199643. doi: 10.1371/journal.pone.0199643

Fig 5. Mediation of lynx1 through α4β2 nAChRs.

Fig 5

(A) Antinociceptive responses in wt and lynx1KO mice after I.P. injection of the non-selective α4β2* nAChR agonist, epibatidine (5 μg·kg-1) (n = 24 wt, 21 KO, p = 0.029, Student’s T-test). Mice were tested on the hot-plate 15 minutes after injection. Epibatidine-mediated antinociception is augmented in lynx1KO mice compared to wt mice. Data presented as mean ± SEM time. *P<0.05 compared to wt controls. wt: wild type, KO: lynx1 knockout. (B) Antinociceptive responses in wt and lynx1KO mice after I.P. injection of the α4β2 nAChRs inhibitor dihydro-β-erythroidine hydrobromide (DHβE) (3.0 mg·kg-1) and nicotine (0.5 mg·kg-1) (nicotine treated lynx1KO mice (n = 8) vs. nicotine+DHβE treated lynx1KO mice (n = 6) using the hot-plate assay. Mice were injected with DHβE 25 minutes and nicotine 15 minutes prior to hot-plate testing. Injections of DHβE blocks the antinociceptive effect of nicotine in lynx1KO mice. Data indicates that lynx1 operates through the α4β2 nAChR to modulate antinociception. Data presented as mean ± SEM time. wt: wild type, KO: lynx1 knockout. (C) Schematic of lynx1 binding to the LS stoichiometry of α4β2 nAChRs preferentially over the HS stoichiometry. α4β2 nAChR pentamers shown in the high sensitivity (HS) and low sensitivity (LS) stoichiometry, made up of (α4)2(β2)3 vs. (α4)2(β2)3 nAChRs respectively. In our model, lynx1 preferentially binds and stabilizes the LS stoichiometry.