M2 - muscarinic Receptors (Ach)

Transmembrane topology and action of a M2-muscarinic receptor..
The receptor's amino (N) terminal is extracellular (above the plane of the membrane), and its carboxyl (C) terminal intracellular. The terminals are connected by a polypeptide chain that traverses the plane of the membrane seven times. The hydrophobic transmembrane segments (light color) are designated by roman numerals (I-VII). Acetylcholine (Ach) approaches the receptor from the extracellular fluid and binds to a site surrounded by the transmembrane regions of the receptor protein. G proteins (G) interact with cytoplasmic regions of the receptor, especially with portions of the third cytoplasmic loop between transmembrane regions V and VI. The receptor's cytoplasmic terminal tail contains numerous serine and threonine residues whose hydroxyl (-OH) groups can be phosphorylated. This phosphorylation may be associated with diminished receptor-G protein interaction.
M2-muscarinic receptor activation is coupled to opening of K+ channels causing potassium to flow outside the cell producing hyperpolarization. The heart becomes more refractory to contraction and the rate slows.
M2-muscarinic receptors cause action in the heart in the following manner:

• Heart SA node: decrease in heart rate.
• Heart AV node: decrease in conduction velocity
• Heart Atria: decrease in contractility

Adapted from Figure 2-14: StatRef Online Library: Basic and Clinical Pharmacology 8th ed. (2001)
by Michael Bolger, 8/26/01
Copyright(c) 2001 The McGraw Hill Companies, Inc. All rights reserved