What do muscarinic M2 receptors do?

• A. Increase heart rate
• B. Decrease smooth muscle contractions
• C. Increase gland secretions
• D. Increase smooth muscle contractions and decrease heart rate

Answer: (D)

Muscarinic M2 receptors are Gi/o-coupled receptors that sit mainly in the heart. When acetylcholine binds to them, they inhibit adenylyl cyclase, lowering cAMP, and open inward-rectifier potassium channels in pacemaker and conduction tissue. This hyperpolarizes those cells and slows SA node firing and AV nodal conduction, producing a decreased heart rate (negative chronotropy) and slower conduction (negative dromotropy). In smooth muscle, M2 has only a minor role compared with M3, which uses a calcium- signaling pathway to drive contraction. Gland secretion is largely driven by M3 as well. So the key takeaway is that M2 activation mainly slows the heart rate; it does not typically cause increased smooth muscle contractions.