Muscarinic acetylcholine receptor M2


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. Multiple alternatively spliced transcript variants have been described for this gene.

Function

Heart

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. However, they have little effect on the contractile forces of the ventricular muscle, slightly decreasing force.

IQ

A Dutch family study found that there is "a highly significant association" between the CHRM2 gene and intelligence as measured by the Wechsler Adult Intelligence Scale-Revised. A similar association was found independently in the Minnesota Twin and Family Study.
However, a larger 2009 study attempting to replicate this claim instead found no significant association between the CHRM2 gene and intelligence.

Olfactory behavior

Mediating olfactory guided behaviors.

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.
In addition, they modulate muscarinic potassium channels. 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.

Ligands

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.

Agonists