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).{{cite book|last1=Rang|first1=Humphrey P|title=Pharmacology|last2=Dale|first2=M Maureen|last3=Ritter|first3=J M|last4=Moore|first4=Philip Keith|date=2003|publisher=Churchill Livingstone|isbn=978-0-443-07145-4|edition=5th|pages=138|display-authors=etal|name-list-style=vanc}} 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.{{Cite journal|last1=Akk|first1=Gustav|last2=Steinbach|first2=Joe Henry|date=2003-08-15|title=Activation and block of mouse muscle-type nicotinic receptors by tetraethylammonium|journal=The Journal of Physiology|volume=551|issue=Pt 1|pages=155–168|doi=10.1113/jphysiol.2003.043885|issn=0022-3751|pmc=2343137|pmid=12824448}}
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.{{cite journal | vauthors = Alberola-Die A, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A | title = Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine | journal = Frontiers in Molecular Neuroscience | volume = 9 | pages = 12 | date = 2016-02-15 | pmid = 26912995 | pmc = 4753328 | doi = 10.3389/fnmol.2016.00012 | doi-access = free }} 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.{{cite journal | vauthors = Alberola-Die A, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A | title = Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine | journal = Frontiers in Molecular Neuroscience | volume = 9 | pages = 127 | date = 2016-11-24 | pmid = 27932949 | pmc = 5121239 | doi = 10.3389/fnmol.2016.00127 | doi-access = free }}
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.{{Cite journal|last1=Cobo|first1=Raúl|last2=Nikolaeva-Koleva|first2=Magdalena|last3=Alberola-Die|first3=Armando|last4=Fernández-Ballester|first4=Gregorio|last5=González-Ros|first5=José Manuel|last6=Ivorra|first6=Isabel|last7=Morales|first7=Andrés|date=15 July 2020|title=Mechanisms of Blockade of the Muscle-Type Nicotinic Receptor by Benzocaine, a Permanently Uncharged Local Anesthetic|url=https://pubmed.ncbi.nlm.nih.gov/31158437|journal=Neuroscience|volume=439|pages=62–79|doi=10.1016/j.neuroscience.2019.05.043|issn=1873-7544|pmid=31158437|s2cid=171092620|hdl=10045/107949|hdl-access=free}} Tetracaine is a permanently positively charged species. It can bind to the receptor at different sites in both the open and closed conformations.{{Cite journal|last1=Cobo|first1=Raúl|last2=Nikolaeva|first2=Magdalena|last3=Alberola-Die|first3=Armando|last4=Fernández-Ballester|first4=Gregorio|last5=González-Ros|first5=José M.|last6=Ivorra|first6=Isabel|last7=Morales|first7=Andrés|date=2018-08-08|title=Mechanisms Underlying the Strong Inhibition of Muscle-Type Nicotinic Receptors by Tetracaine|journal=Frontiers in Molecular Neuroscience|volume=11|page=193|doi=10.3389/fnmol.2018.00193|issn=1662-5099|pmc=6092513|pmid=30135641|doi-access=free}} Both of these local anesthetics enhance nAChR desensitization.
Ligands
= Agonist =
= Partial Agonists =
- Carbachol
- Suxamethonium{{cite journal | vauthors = Marshall CG, Ogden DC, Colquhoun D | title = The actions of suxamethonium (succinyldicholine) as an agonist and channel blocker at the nicotinic receptor of frog muscle | journal = The Journal of Physiology | volume = 428 | pages = 155–74 | date = September 1990 | pmid = 2133043 | pmc = 1181640 | doi = 10.1113/jphysiol.1990.sp018205 }}
= Antagonists =
- α-Bungarotoxin{{cite web | url = http://www.neurosci.pharm.utoledo.edu/MBC3320/nicotinic.htm | work = Neurosci.pharm, MBC 3320 | title = Acetylcholine | archive-url = https://web.archive.org/web/20071227192643/http://www.neurosci.pharm.utoledo.edu/MBC3320/nicotinic.htm | archive-date=2007-12-27 | url-status = dead }}
- α-Conotoxin
- Hexamethonium
- Pancuronium
- Tubocurarine
See also
References
{{Reflist}}
{{Ligand-gated ion channels}}
{{Nicotinic acetylcholine receptor modulators}}