Muscarinic acetylcholine receptor M2
Encyclopedia
The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor
.
down to normal sinus rhythm
after stimulatory actions of the sympathetic 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 no effect on the contractile forces of the ventricular muscle.
and intelligence. The study concluded that there was an association between the CHRM2 gene on chromosome 7 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised. The Dutch family study used a sample of 667 individuals from 304 families.
A similar association was found independently in the Minnesota Twin and Family Study (Comings et al. 2003) and by the Department of Psychiatry at the Washington University.
However, a larger 2009 study attempting to replicate this claim instead found no significant association between the CHRM2 gene and intelligence in a Scottish cohort
of 2,091 individuals over age 50, nor an English sample of 758 non-cognitively-impaired elderly individuals, nor an Australian family-based sample of 1,537 adolescents.
type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects.
In addition, they modulate muscarinic potassium channels. In the heart, this contributes to a decreased heart rate.
Multiple alternatively spliced transcript variants have been described for this gene.
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
.
Heart
The M2 muscarinic receptors are located in the heart, where they act to slow the heart rateHeart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
down to normal sinus rhythm
Sinus rhythm
In medicine, sinus rhythm is the normal beating of the heart, as measured by an electrocardiogram . It has certain generic features that serve as hallmarks for comparison with normal ECGs.- ECG structure :...
after stimulatory actions of the sympathetic nervous system, by slowing the speed of depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...
(AV node). However, they have no effect on the contractile forces of the ventricular muscle.
IQ
A 2006 Dutch family study found that there is "a highly significant association" between the CHRM2 geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
and intelligence. The study concluded that there was an association between the CHRM2 gene on chromosome 7 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised. The Dutch family study used a sample of 667 individuals from 304 families.
A similar association was found independently in the Minnesota Twin and Family Study (Comings et al. 2003) and by the Department of Psychiatry at the Washington University.
However, a larger 2009 study attempting to replicate this claim instead found no significant association between the CHRM2 gene and intelligence in a Scottish cohort
Cohort (statistics)
In statistics and demography, a cohort is a group of subjects who have shared a particular time together during a particular time span . Cohorts may be tracked over extended periods in a cohort study. The cohort can be modified by censoring, i.e...
of 2,091 individuals over age 50, nor an English sample of 758 non-cognitively-impaired elderly individuals, nor an Australian family-based sample of 1,537 adolescents.
Mechanism
M2 muscarinic receptors act via a GiGi alpha subunit
Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors...
type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects.
In addition, they modulate muscarinic potassium channels. In the heart, this contributes to a decreased heart rate.
Gene
Muscarinic acetylcholine receptor M2 is encoded by the gene .Multiple alternatively spliced transcript variants have been described for this gene.
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
- BethanecholBethanecholBethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action. Bethanechol does not involve...
(nonselective muscarinic agonist) - (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)
Antagonists
- Dimethindene - N,N-Dimethyl-3-[(1S)-1-(2-pyridinyl)ethyl]-1H-indene-2-ethanamine, CAS# 121367-05-3, mixed M2 / histamine H1 antagonist
- Otenzepad - 11-([2-[(Diethylamino)methyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one, CAS# 102394-31-0
- AQRA-741 - 11-([4-[4-(Diethylamino)butyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one, CAS# 123548-16-3
- AFDX-384AFDX-384AFDX-384 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 brain, and studying their involvement in the development and...
(mixed M2/M4 antagonist) - N-[2-[2-[(Dipropylamino)methyl]-1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4]benzodiazepine-11-carboxamide, CAS# 118290-27-0