Biology:Muscle-type nicotinic receptor

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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

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

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

Agonist

Partial Agonists

Antagonists

See also

References

  1. ↑ Rang, Humphrey P et al. (2003). Pharmacology (5th ed.). Churchill Livingstone. pp. 138. ISBN 978-0-443-07145-4. 
  2. ↑ 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. PMID 12824448. 
  3. ↑ 3.0 3.1 "Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine". Frontiers in Molecular Neuroscience 9: 12. 2016-02-15. doi:10.3389/fnmol.2016.00012. PMID 26912995. 
  4. ↑ "Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine". Frontiers in Molecular Neuroscience 9: 127. 2016-11-24. doi:10.3389/fnmol.2016.00127. PMID 27932949. 
  5. ↑ 5.0 5.1 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. ISSN 1873-7544. PMID 31158437. https://pubmed.ncbi.nlm.nih.gov/31158437. 
  6. ↑ 6.0 6.1 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. PMID 30135641. 
  7. ↑ "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. September 1990. doi:10.1113/jphysiol.1990.sp018205. PMID 2133043. 
  8. ↑ "Acetylcholine". Neurosci.pharm, MBC 3320. http://www.neurosci.pharm.utoledo.edu/MBC3320/nicotinic.htm. 



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