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- W2089044261 abstract "Muscle-type nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic cholinergic responses at neuromuscular junctions. The adult subtype of the receptor is composed of α1, β1, δ, and e subunits in the ratio 2:1:1:1. Although nicotine is the name-giving agonist for ionotropic acetylcholine receptors, only a few studies investigated its effect of nicotine on this specific nAChR subtype. A comprehensive knowledge of the mechanism underlying the nicotine-induced gating is still missing.For this reason, we had a closer look to macroscopic (α1)2β1δe receptor currents evoked by fast nicotine jumps and compared them with acetylcholine-evoked responses. The receptors were heterologously expressed in HEK293 cells. After lifting and positioning the cells in front of a piezo-driven double-barreled application pipette, whole-cell currents were monitored.Herein, nicotine was found to be an agonist with a relative potency of about 0.60 compared to the full agonist acetylcholine. The efficiency was about 30 times lower than for acetylcholine (EC50 = 97.0 µM versus EC50 = 3.35 µM). When activated by nicotine, (α1)2β1δe receptors desensitize slower than receptors activated by acetylcholine. As expected from single-channel analysis (Akk and Auerbach, Br J Pharmacol. 128:1467-76, 1999; Jadey et al., J Gen Physiol. 141:95-104, 2013), off-currents, occurring after removal of high nicotine concentrations, confirmed the idea of nicotine acting as a channel blocker at concentrations higher than 1 mM.In summary, the data provide new insight into the nicotine-induced gating of adult muscle-type receptors. The differences in comparison to the physiological ligand acetylcholine and the action of nicotine as a partial agonist are discussed." @default.
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- W2089044261 date "2015-01-01" @default.
- W2089044261 modified "2023-09-27" @default.
- W2089044261 title "Stepchild Nicotine: Effect of the Name-Giving Agonist on Muscle-Type Nicotinic Acetylcholine Receptor" @default.
- W2089044261 doi "https://doi.org/10.1016/j.bpj.2014.11.2350" @default.
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