Muscle-type nicotinic receptor

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.

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. 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.

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. Tetracaine is a permanently positively charged species. It can bind to the receptor at different sites in both the open and closed conformations. Both of these local anesthetics enhance nAChR desensitization.

Ligands

Agonist

• Acetylcholine

Partial Agonists

• Carbachol
• Suxamethonium

Antagonists

• α-Bungarotoxin
• α-Conotoxin
• Hexamethonium
• Pancuronium
• Tubocurarine

References

References

1. (2003). "Pharmacology". Churchill Livingstone.
2. (2003-08-15). "Activation and block of mouse muscle-type nicotinic receptors by tetraethylammonium". The Journal of Physiology.
3. (2016-02-15). "Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine". Frontiers in Molecular Neuroscience.
4. (2016-11-24). "Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine". Frontiers in Molecular Neuroscience.
5. (15 July 2020). "Mechanisms of Blockade of the Muscle-Type Nicotinic Receptor by Benzocaine, a Permanently Uncharged Local Anesthetic". Neuroscience.
6. (2018-08-08). "Mechanisms Underlying the Strong Inhibition of Muscle-Type Nicotinic Receptors by Tetracaine". Frontiers in Molecular Neuroscience.
7. (September 1990). "The actions of suxamethonium (succinyldicholine) as an agonist and channel blocker at the nicotinic receptor of frog muscle". The Journal of Physiology.
8. "Acetylcholine". Neurosci.pharm, MBC 3320.