CHRM2

CHRM2 Full Name

cholinergic receptor, muscarinic 2

CHRM2 Introduction

The muscarinic acetylcholine receptor M2, also known as cholinergic receptor muscarinic 2, is a muscarinic acetylcholine receptor encoded by the CHRM2 gene in humans. Multiple alternative splicing transcript variants of this gene have been described. It couples with Gi and reduces intracellular cAMP levels. M2 muscarinic receptors act through Gi type receptors, which lead to a decrease in cAMP in cells, typically resulting in inhibitory effects. They seem to typically act as their own receptors. In addition, they regulate the inward rectifying potassium channels of G protein coupling. In the heart, this can lead to a decrease in heart rate. They are achieved through the G β - γ subunit of G protein; G β - γ alters the opening probability of K+channels in the cell membrane of pacemakers, causing potassium to flow outward and effectively hyperpolarize the membrane, thereby slowing down heart rate.

Figure. Structure of CHRM2.

Function
Heart
M2 muscarinic receptors are located in the heart, and after negative stimulation by the parasympathetic nervous system, they slow down depolarization and reduce heart rate to normal sinus rhythm. They also reduce the contractility of the atrial myocardium and decrease the conduction velocity of the atrioventricular node (AV node). However, they have almost no effect on the contraction force of ventricular muscles, with a slight decrease in force.
Smooth Muscle of Airway
Both M2 and M3 muscarinic receptors are expressed in airway smooth muscle, with the majority of receptors being M2 type. The activation of M2 receptors coupled with Gi inhibits β - adrenergic mediated airway smooth muscle relaxation. The synergistic effect is to activate the M3 receptor coupled with Gq, stimulating the contraction of airway smooth muscle.

Signal Mechanism
The activation of M2 receptors triggers a typical Gi/o-mediated cascade of inhibition:
Primary Gi/o pathway: Receptor activation leads to dissociation of Gi/o proteins. The G α i subunit inhibits adenylate cyclase and reduces the production of the second messenger ring AMP (cAMP). This is opposite to the action of excitatory G coupled receptors, such as β 1-adrenergic receptors in the heart.
Ionic channel regulation: The released G β - γ subunit directly binds to and activates a type of inward rectifying potassium channel (GIRK channel, especially Kir3.1/3.4 in the heart). This will increase potassium efflux, hyperpolarize the cell membrane, and reduce excitability.
Inhibition of voltage-gated calcium channels: The G β - γ subunit can also directly inhibit certain voltage-gated calcium channels (such as N-type, P/Q type), especially in neurons, reducing calcium influx and neurotransmitter release.

Alternate Names for CHRM2

CHRM2; cholinergic receptor, muscarinic 2; HM2; muscarinic acetylcholine receptor M2; 7TM receptor; muscarinic M2 receptor; acetylcholine receptor, muscarinic 2; cholinergic receptor, muscarinic 2, isoform a;