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 CHRM2gene.[1] Multiple alternatively spliced transcript variants have been described for this gene.[1]
The M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after positive 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 found that there is "a highly significant association" between the CHRM2gene and intelligence as measured by the Wechsler Adult Intelligence Scale-Revised.[2] A similar association was found independently in the Minnesota Twin and Family Study.[3][4]
However, a larger 2009 study attempting to replicate this claim instead found no significant association between the CHRM2 gene and intelligence.[5]
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.[7]
In addition, they modulate muscarinic potassium channels.[8][9] In the heart, this contributes to a decreased heart rate. They do so by the Gβγ subunit of the G protein; Gβγ opens K+ channels in the parasympathetic notches in the heart, which causes an outward current of potassium, 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.
↑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. PMID17081262.
↑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/sj.mp.4001095. PMID12556901.
↑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. PMID17160701.
↑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. PMID19418213.
↑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. PMID11714883.
↑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. PMID3436364.
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