The muscarinic acetylcholine receptor M₂, also known as the cholinergic receptor, muscarinic 2, is a

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several r ...

that in humans is encoded by the ''CHRM2''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. 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 Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and e ...

down to normal

sinus rhythm A sinus rhythm is any cardiac rhythm in which depolarisation of the cardiac muscle begins at the sinus node. It is characterised by the presence of correctly oriented P waves on the electrocardiogram (ECG). Sinus rhythm is necessary, but not ...

after negative stimulatory actions of the

parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part ...

, by slowing the speed of

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...

. They also reduce contractile forces of the

atrial The atrium ( la, ātrium, , entry hall) is one of two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular valves. There are two at ...

cardiac muscle, and reduce conduction velocity of the

atrioventricular node The atrioventricular node or AV node electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the lower back section of t ...

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

IQ

A Dutch family study "a highly significant association" between the ''CHRM2''

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 The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, i ...

guided behaviors (e.g. odor discrimination,

aggression Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...

mating In biology, mating is the pairing of either opposite- sex or hermaphroditic organisms for the purposes of sexual reproduction. ''Fertilization'' is the fusion of two gametes. '' Copulation'' is the union of the sex organs of two sexually rep ...

Mechanism of action

M₂ muscarinic receptors act via a G_i 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 G protein-coupled inwardly-rectifying potassium channels. In the heart, this contributes to a decreased heart rate. They do so by the G_βγ subunit of the G protein; G_βγ shifts the open probability of K⁺ channels in the membrane of the cardiac pacemaker cells, which causes an outward current of potassium, effectively hyperpolarizing the membrane, 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

* (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide (selective for M₂ but only partial agonist) *

Berberine Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as '' Berberis vulgaris'' (barberry), '' Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), '' H ...

* Iper-8-Naph (alias N-8-Iper, bitopic/dualsteric agonist) *

Methacholine Methacholine (INN, USAN) (trade name Provocholine), also known as Acetyl-β-methylcholine, is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system. Medical uses Methacholine ...

* PAI ( photoswitchable agonist)

Antagonists

AFDX-384 AFDX-384 (BIBN-161) is a drug which acts as a selective antagonist of the muscarinic acetylcholine receptors, with selectivity for the M2 and M4 subtypes. It is used mainly for mapping the distribution of M2 and M4 muscarinic receptors in the b ...

Atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically giv ...

Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

Dicycloverine Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl in the US, is a medication that is used to treat spasms of the intestines such as occur in irritable bowel syndrome. It is taken by mouth or by injection into a muscle. ...

Dimenhydrinate Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chlor ...

Dimethindene Dimetindene , also sold under the brand name Fenistil, is an antihistamine/anticholinergic. It is a first generation selective H1 antagonist. Dimetindene is an atypical first generation H1 antagonist as it only minimally passes across the blood ...

Diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into a v ...

Gallamine Gallamine triethiodide (Flaxedil) is a non-depolarising muscle relaxant. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. Gallamine is a non-depolarising type o ...

Hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including henbane, mandrake, angel's trumpets, jimson ...

Ipratropium Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic (SAMA: short acting muscarinic antagonist) medication which opens up the medium and large airways in the lungs. It is used to treat the symptoms ...

Methoctramine Methoctramine is a polymethylene tetraamine that acts as a muscarinic antagonist. It preferentially binds to the pre-synaptic receptor M2, a muscarinic acetylcholine ganglionic protein complex present basically in heart cells. In normal conditi ...

Otenzepad Otenzepad is a competitive muscarinic receptor antagonist that is relatively selective at the M2 receptor. It was investigated as a treatment for arrhythmia and bradycardia due to its cardioselectivity but research ceased after stage III clinic ...

Oxybutynin Oxybutynin, sold as under the brand names Ditropan among others, is a medication used to treat overactive bladder. It works similar to tolterodine, Darifenacin, and Solifenacin. While used for bed wetting in children, evidence to support thi ...

Thorazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar dis ...

Tolterodine Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth. Common side effects include headach ...

Trimipramine Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of inso ...

References

External links

* * * {{DEFAULTSORT:Muscarinic Acetylcholine Receptor M2 Muscarinic acetylcholine receptors