Muscle-type nicotinic receptor explained

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. 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.

Ligands

Agonist

Partial Agonists

Antagonists

See also

Notes and References

  1. Book: Rang. Humphrey P. Pharmacology. Dale. M Maureen. Ritter. J M. Moore. Philip Keith. 2003. Churchill Livingstone. 978-0-443-07145-4. 5th. 138. etal. vanc.
  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. 10.1113/jphysiol.2003.043885. 0022-3751. 2343137. 12824448.
  3. Alberola-Die A, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A . Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine . Frontiers in Molecular Neuroscience . 9 . 12 . 2016-02-15 . 26912995 . 4753328 . 10.3389/fnmol.2016.00012 . free .
  4. Alberola-Die A, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A . 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 . 27932949 . 5121239 . 10.3389/fnmol.2016.00127 . free .
  5. 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. 10.1016/j.neuroscience.2019.05.043. 1873-7544. 31158437. 171092620. 10045/107949. free.
  6. 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. 10.3389/fnmol.2018.00193. 1662-5099. 6092513. 30135641. free.
  7. Marshall CG, Ogden DC, Colquhoun D . 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 . 2133043 . 1181640 . 10.1113/jphysiol.1990.sp018205 .
  8. Web site: Acetylcholine . Neurosci.pharm, MBC 3320 . https://web.archive.org/web/20071227192643/http://www.neurosci.pharm.utoledo.edu/MBC3320/nicotinic.htm . 2007-12-27 . dead .

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