Muscarinic acetylcholine receptor M2

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Muscarinic receptor M2 coupled to protein G - 6OIK.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesCHRM2, HM2, cholinergic receptor muscarinic 2
External IDsOMIM: 118493 MGI: 88397 HomoloGene: 20190 GeneCards: CHRM2
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 7: 136.87 – 137.02 MbChr 6: 36.37 – 36.51 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor that in humans is encoded by the CHRM2 gene.[5] Multiple alternatively spliced transcript variants have been described for this gene.[5]



The M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of the parasympathetic nervous system, by slowing the speed of depolarization. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node (AV node). However, they have little effect on the contractile forces of the ventricular muscle, slightly decreasing force.


A Dutch family study "a highly significant association" between the CHRM2 gene and intelligence as measured by the Wechsler Adult Intelligence Scale-Revised.[6] A similar association was found independently in the Minnesota Twin and Family Study.<rfound that there isef name="pmid12556901">Comings DE, Wu S, Rostamkhani M, McGue M, Lacono WG, Cheng LS, MacMurray JP (January 2003). "Role of the cholinergic muscarinic 2 receptor (CHRM2) gene in cognition". Molecular Psychiatry. 8 (1): 10–1. doi:10.1038/ PMID 12556901. S2CID 22314941.</ref>[7]

However, a larger 2009 study attempting to replicate this claim instead found no significant association between the CHRM2 gene and intelligence.[8]

Olfactory behavior

Mediating olfactory guided behaviors (e.g. odor discrimination, aggression, mating).[9]

Mechanism of action

M2 muscarinic receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects. They appear to serve as autoreceptors.[10]

In addition, they modulate muscarinic potassium channels.[11][12] In the heart, this contributes to a decreased heart rate. They do so by the Gαi subunit of the G protein; Gαi opens K+ channels in the membrane of the cardiac myocytes, which causes an outward current of potassium, effectively hyperpolarizing the membrane, which slows down the heart rate.


Few highly selective M2 agonists are available at present, although there are several non-selective muscarinic agonists that stimulate M2, and a number of selective M2 antagonists are available.



See also


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000181072 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045613 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: CHRM2 cholinergic receptor, muscarinic 2".
  6. ^ Gosso MF, van Belzen M, de Geus EJ, Polderman JC, Heutink P, Boomsma DI, Posthuma D (November 2006). "Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families". Genes, Brain and Behavior. 5 (8): 577–84. doi:10.1111/j.1601-183X.2006.00211.x. PMID 17081262.
  7. ^ Dick DM, Aliev F, Kramer J, Wang JC, Hinrichs A, Bertelsen S, Kuperman S, Schuckit M, Nurnberger J, Edenberg HJ, Porjesz B, Begleiter H, Hesselbrock V, Goate A, Bierut L (March 2007). "Association of CHRM2 with IQ: converging evidence for a gene influencing intelligence". Behavior Genetics. 37 (2): 265–72. doi:10.1007/s10519-006-9131-2. PMID 17160701. S2CID 9353852.
  8. ^ Lind PA, Luciano M, Horan MA, Marioni RE, Wright MJ, Bates TC, Rabbitt P, Harris SE, Davidson Y, Deary IJ, Gibbons L, Pickles A, Ollier W, Pendleton N, Price JF, Payton A, Martin NG (September 2009). "No association between Cholinergic Muscarinic Receptor 2 (CHRM2) genetic variation and cognitive abilities in three independent samples". Behavior Genetics. 39 (5): 513–23. doi:10.1007/s10519-009-9274-z. PMID 19418213. S2CID 2523697.
  9. ^ Smith RS, Hu R, DeSouza A, Eberly CL, Krahe K, Chan W, Araneda RC (July 2015). "Differential Muscarinic Modulation in the Olfactory Bulb". The Journal of Neuroscience. 35 (30): 10773–85. doi:10.1523/JNEUROSCI.0099-15.2015. PMC 4518052. PMID 26224860.
  10. ^ Douglas CL, Baghdoyan HA, Lydic R (December 2001). "M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse". The Journal of Pharmacology and Experimental Therapeutics. 299 (3): 960–6. PMID 11714883.
  11. ^ a b c d e f Rang HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.
  12. ^ Boron WF, Boulpaep EL (2005). Medical Physiology. Philadelphia: Elsevier Saunders. p. 387. ISBN 1-4160-2328-3.
  13. ^ Scapecchi S, Matucci R, Bellucci C, Buccioni M, Dei S, Guandalini L, Martelli C, Manetti D, Martini E, Marucci G, Nesi M, Romanelli MN, Teodori E, Gualtieri F (March 2006). "Highly chiral muscarinic ligands: the discovery of (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonist". Journal of Medicinal Chemistry. 49 (6): 1925–31. doi:10.1021/jm0510878. PMID 16539379.
  14. ^ Matera C, Flammini L, Quadri M, Vivo V, Ballabeni V, Holzgrabe U, Mohr K, De Amici M, Barocelli E, Bertoni S, Dallanoce C (March 2014). "Bis(ammonio)alkane-type agonists of muscarinic acetylcholine receptors: synthesis, in vitro functional characterization, and in vivo evaluation of their analgesic activity". European Journal of Medicinal Chemistry. 75: 222–32. doi:10.1016/j.ejmech.2014.01.032. PMID 24534538.
  15. ^ Cristofaro, Ilaria; Spinello, Zaira; Matera, Carlo; Fiore, Mario; Conti, Luciano; De Amici, Marco; Dallanoce, Clelia; Tata, Ada Maria (2018). "Activation of M2 muscarinic acetylcholine receptors by a hybrid agonist enhances cytotoxic effects in GB7 glioblastoma cancer stem cells". Neurochemistry International. 118: 52–60. doi:10.1016/j.neuint.2018.04.010. ISSN 0197-0186. PMID 29702145. S2CID 207125517.
  16. ^ Bock A, Merten N, Schrage R, Dallanoce C, Bätz J, Klöckner J, Schmitz J, Matera C, Simon K, Kebig A, Peters L, Müller A, Schrobang-Ley J, Tränkle C, Hoffmann C, De Amici M, Holzgrabe U, Kostenis E, Mohr K (2012-09-04). "The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling". Nature Communications. 3: 1044. Bibcode:2012NatCo...3.1044B. doi:10.1038/ncomms2028. PMC 3658004. PMID 22948826.
  17. ^ Riefolo, Fabio; Matera, Carlo; Garrido-Charles, Aida; Gomila, Alexandre M. J.; Sortino, Rosalba; Agnetta, Luca; Claro, Enrique; Masgrau, Roser; Holzgrabe, Ulrike; Batlle, Montserrat; Decker, Michael; Guasch, Eduard; Gorostiza, Pau (2019). "Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist". Journal of the American Chemical Society. 141 (18): 7628–7636. doi:10.1021/jacs.9b03505. hdl:2445/147236. ISSN 0002-7863. PMID 31010281. S2CID 128361100.
  18. ^ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), "ED-SPAZ- hyoscyamine sulfate tablet, orally disintegrating", DailyMed, U.S. National Library of Medicine, retrieved January 13, 2013
  19. ^ Melchiorre C, Angeli P, Lambrecht G, Mutschler E, Picchio MT, Wess J (December 1987). "Antimuscarinic action of methoctramine, a new cardioselective M-2 muscarinic receptor antagonist, alone and in combination with atropine and gallamine". European Journal of Pharmacology. 144 (2): 117–24. doi:10.1016/0014-2999(87)90509-7. PMID 3436364.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.