CHRM2 — Muscarinic Acetylcholine Receptor M2
<div class="infobox infobox-gene">
<div class="infobox-header">CHRM2</div>
Overview
CHRM1 is a human gene whose product the Muscarinic [Acetylcholine](/entities/acetylcholine) Receptor M2 (CHRM2) is a G protein-coupled receptor (GPCR) that mediates the effects of acetylcholine on slow inhibitory postsynaptic potentials in the heart, smooth muscle, and [neurons](/entities/neurons) [1](https://doi.org/10.1016/j.tips.2012.09.005). CHRM2 is coupled to Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of inwardly rectifying potassium channels (GIRK), and suppression of neuronal excitability [2](https://doi.org/10.1016/j.neuroscience.2014.12.012). Variants in CHRM1 have been implicated in Alzheimer's Disease, Schizophrenia, Cardiac Function. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@power2018]
...CHRM2 — Muscarinic Acetylcholine Receptor M2
<div class="infobox infobox-gene">
<div class="infobox-header">CHRM2</div>
Overview
CHRM1 is a human gene whose product the Muscarinic [Acetylcholine](/entities/acetylcholine) Receptor M2 (CHRM2) is a G protein-coupled receptor (GPCR) that mediates the effects of acetylcholine on slow inhibitory postsynaptic potentials in the heart, smooth muscle, and [neurons](/entities/neurons) [1](https://doi.org/10.1016/j.tips.2012.09.005). CHRM2 is coupled to Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of inwardly rectifying potassium channels (GIRK), and suppression of neuronal excitability [2](https://doi.org/10.1016/j.neuroscience.2014.12.012). Variants in CHRM1 have been implicated in Alzheimer's Disease, Schizophrenia, Cardiac Function. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@power2018]
<div class="infobox-image"> [@cao2017]
<div class="gene-diagram">CHRM2</div> [@cai2019]
</div> [@scarr2016]
<table class="infobox-data"> [@kawata2015]
<tr><th>Gene Symbol</th><td>CHRM2</td></tr>
<tr><th>Full Name</th><td>Cholinergic Receptor Muscarinic 2</td></tr>
<tr><th>Chromosomal Location</th><td>7q31-q36</td></tr>
<tr><th>NCBI Gene ID</th><td>https://www.ncbi.nlm.nih.gov/gene/1128 1128</td></tr>
<tr><th>OMIM</th><td>https://www.omim.org/entry/118510 118510</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000131617</td></tr>
<tr><th>UniProt ID</th><td>https://www.uniprot.org/uniprot/P08172 P08172</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's disease, schizophrenia, cardiac dysfunction</td></tr>
</table>
</div>
Function
The Muscarinic Acetylcholine Receptor M2 (CHRM2) is a G protein-coupled receptor (GPCR) that mediates the effects of acetylcholine on slow inhibitory postsynaptic potentials in the heart, smooth muscle, and neurons [1](https://doi.org/10.1016/j.tips.2012.09.005). CHRM2 is coupled to Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of inwardly rectifying potassium channels (GIRK), and suppression of neuronal excitability [2](https://doi.org/10.1016/j.neuroscience.2014.12.012).
In the central nervous system, CHRM2 is highly expressed in the [hippocampus](/brain-regions/hippocampus), cerebral [cortex](/brain-regions/cortex), and basal ganglia, where it modulates learning, memory, and reward processing [3](https://doi.org/10.1016/j.neuropharm.2018.01.044). The receptor plays a critical role in cholinergic signaling through the septohippocampal pathway, which is essential for spatial memory and attention.
Disease Associations
Alzheimer's Disease
CHRM2 genetic variants are associated with altered risk for Alzheimer's disease [4](https://doi.org/10.1016/j.jad.2017.08.028). The cholinergic hypothesis of AD posits that loss of muscarinic receptor signaling contributes to cognitive decline. CHRM2 agonists have been investigated as potential therapeutics to enhance cholinergic neurotransmission [5](https://doi.org/10.1016/j.pharmthera.2019.04.008).
Schizophrenia
CHRM2 polymorphisms are linked to schizophrenia susceptibility and treatment response [6](https://doi.org/10.1016/j.schres.2016.03.015). Altered CHRM2 expression has been observed in postmortem brain tissue from schizophrenia patients, particularly in the prefrontal cortex.
Cardiac Function
CHRM2 is the primary muscarinic receptor in the heart, mediating vagal slowing of heart rate (negative chronotropy) [7](https://doi.org/10.1016/j.autneu.2015.08.001). CHRM2 activation opens GIRK channels, hyperpolarizing cardiac pacemaker cells.
Expression
CHRM2 exhibits region-specific expression in the nervous system:
- Hippocampus — highest in CA3 region and dentate gyrus
- Cerebral cortex — layers II-III and V-VI
- Basal ganglia — striatum and globus pallidus
- Thalamus — relay nuclei
- Heart — atrial and ventricular myocardium
- Smooth muscle — gastrointestinal tract, bladder
Common Variants
| Variant | Type | Effect | Disease Association |
|---------|------|--------|---------------------|
| rs1824024 | SNP | Altered expression | AD risk |
| rs324640 | SNP | Synonymous | Schizophrenia |
| rs6962022 | SNP | 3' UTR | Substance abuse |
| rs2350780 | SNP | Intronic | Cardiac function |
Therapeutic Implications
Agonists
- Xanomeline — M1/M4 preferring agonist, investigated for AD
- BuT — bitopic ligands with improved efficacy
Antagonists
- Atropine — classic muscarinic antagonist
- Glycopyrrolate — quaternary amine, CNS-impermeant
See Also
- [CHRM1](/genes/chrm1) — Muscarinic receptor M1
- [CHRM3](/genes/chrm3) — Muscarinic receptor M3
- [CHRM4](/genes/chrm4) — Muscarinic receptor M4
- [Acetylcholine](/acetylcholine) — Neurotransmitter
- [Alzheimer's Disease](/diseases/alzheimers-disease) — AD overview
- [GPCR Signaling](/mechanisms/gpcr-signaling) — G protein-coupled receptor pathways
- [Cholinergic Signaling](/mechanisms/cholinergic-signaling) — Acetylcholine neurotransmission
External Links
- [NCBI Gene: CHRM2](https://www.ncbi.nlm.nih.gov/gene/1128)
- [UniProt: CHRM2](https://www.uniprot.org/uniprot/P08172)
- [IUPHAR/BPS Guide to Pharmacology: CHRM2](https://www.guidetopharmacology.org/graphql/receptor/GPCR:1315)
References
[Wess et al., Muscarinic acetylcholine receptors (2013) (2013)](https://doi.org/10.1016/j.tips.2012.09.005)
[Zhang et al., CHRM2 neuronal signaling (2014) (2014)](https://doi.org/10.1016/j.neuroscience.2014.12.012)
[Unknown, Power & Plath, CHRM2 in cognition (2018) (2018)](https://doi.org/10.1016/j.neuropharm.2018.01.044)
[Cao et al., CHRM2 and Alzheimer's disease (2017) (2017)](https://doi.org/10.1016/j.jad.2017.08.028)
[Cai et al., Muscarinic agonists for AD (2019) (2019)](https://doi.org/10.1016/j.pharmthera.2019.04.008)
[Scarr et al., CHRM2 and schizophrenia (2016) (2016)](https://doi.org/10.1016/j.schres.2016.03.015)
[Unknown, Kawata & Koshimizu, Cardiac muscarinic receptors (2015) (2015)](https://doi.org/10.1016/j.autneu.2015.08.001)