Muscle-type nicotinic receptor
The muscle-type nicotinic receptor is a type of nicotinic acetylcholine receptor consisting of the subunit combination (α1)2β1δε (adult receptor) or (α1)2β1δγ (fetal receptor).[1] These receptors are found in neuromuscular junctions, where activation leads to an excitatory postsynaptic potential (EPSP), mainly by increased Na+ and K+ permeability.
Activation
[edit]Tetraethylammonium (TEA) is a molecule found to be a weak agonist of the muscle‐type nicotinic receptor. Since receptor activation occurs as isolated bursts, it has been proposed that the receptors have a very low channel‐opening rate constant when bound to TEA.[2]
Inhibition
[edit]Lidocaine, a local anesthetic, has multiple inhibitory actions on the receptor and analysis of the structure of lidocaine has identified the presence of a hydrophobic aromatic ring and a hydrophilic terminal amine.[3] Diethylamine (DEA), a molecule that mimics the hydrophilic moiety of lidocaine by way of a positively charged amine, has been found to block the channel when the receptor is open restricting the flow of Na+ and K+ ions.[3] 2,6-Dimethylaniline (DMA), a molecule that mimics the hydrophobic moiety of lidocaine, has been found to bind the receptor at inter-subunit crevices of the trans-membrane spanning domain thereby causing non-competitive inhibition and restricting the channel from opening.[4]
Benzocaine and tetracaine are also local anesthetics that have an inhibitory effect on the muscle‐type nicotinic receptor. Benzocaine is a permanently uncharged species that inhibits the receptor by plugging the pore of the opened channel.[5] Tetracaine is a permanently positively charged species. It can bind to the receptor at different sites in both the open and closed conformations.[6] Both of these local anesthetics enhance nAChR desensitization.[5][6]
Ligands
[edit]Agonist
[edit]Partial Agonists
[edit]Antagonists
[edit]See also
[edit]References
[edit]- ^ Rang HP, Dale MM, Ritter JM, Moore PK, et al. (2003). Pharmacology (5th ed.). Churchill Livingstone. p. 138. ISBN 978-0-443-07145-4.
- ^ Akk, Gustav; Steinbach, Joe Henry (2003-08-15). "Activation and block of mouse muscle-type nicotinic receptors by tetraethylammonium". The Journal of Physiology. 551 (Pt 1): 155–168. doi:10.1113/jphysiol.2003.043885. ISSN 0022-3751. PMC 2343137. PMID 12824448.
- ^ a b Alberola-Die A, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A (2016-02-15). "Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine". Frontiers in Molecular Neuroscience. 9: 12. doi:10.3389/fnmol.2016.00012. PMC 4753328. PMID 26912995.
- ^ Alberola-Die A, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A (2016-11-24). "Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine". Frontiers in Molecular Neuroscience. 9: 127. doi:10.3389/fnmol.2016.00127. PMC 5121239. PMID 27932949.
- ^ a b Cobo, Raúl; Nikolaeva-Koleva, Magdalena; Alberola-Die, Armando; Fernández-Ballester, Gregorio; González-Ros, José Manuel; Ivorra, Isabel; Morales, Andrés (15 July 2020). "Mechanisms of Blockade of the Muscle-Type Nicotinic Receptor by Benzocaine, a Permanently Uncharged Local Anesthetic". Neuroscience. 439: 62–79. doi:10.1016/j.neuroscience.2019.05.043. hdl:10045/107949. ISSN 1873-7544. PMID 31158437. S2CID 171092620.
- ^ a b Cobo, Raúl; Nikolaeva, Magdalena; Alberola-Die, Armando; Fernández-Ballester, Gregorio; González-Ros, José M.; Ivorra, Isabel; Morales, Andrés (2018-08-08). "Mechanisms Underlying the Strong Inhibition of Muscle-Type Nicotinic Receptors by Tetracaine". Frontiers in Molecular Neuroscience. 11: 193. doi:10.3389/fnmol.2018.00193. ISSN 1662-5099. PMC 6092513. PMID 30135641.
- ^ Marshall CG, Ogden DC, Colquhoun D (September 1990). "The actions of suxamethonium (succinyldicholine) as an agonist and channel blocker at the nicotinic receptor of frog muscle". The Journal of Physiology. 428: 155–74. doi:10.1113/jphysiol.1990.sp018205. PMC 1181640. PMID 2133043.
- ^ "Acetylcholine". Neurosci.pharm, MBC 3320. Archived from the original on 2007-12-27.
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