Which receptor mediates parasympathetic slowing of the heart rate?

• A. Alpha-1 adrenergic receptor
• B. Beta-1 adrenergic receptor
• C. Muscarinic (M2) acetylcholine receptor
• D. Nicotinic receptor

Answer: (C)

Parasympathetic control of heart rate works through acetylcholine binding to muscarinic receptors in the heart, especially the M2 subtype on pacemaker cells of the SA node and, to a lesser extent, the AV node. When ACh activates M2 receptors, it engages Gi proteins that inhibit adenylyl cyclase, lowering cAMP levels and slowing the heart’s pacemaker activity. This also opens certain potassium channels, increasing K+ efflux and hyperpolarizing the cells, which further slows the rate of spontaneous depolarization and reduces conduction velocity. The net result is a slower heart rate (negative chronotropy) and slower conduction through the AV node.

Other receptor types listed don’t mediate this slowing. Alpha-1 adrenergic receptors are part of sympathetic responses, mainly causing vascular constriction; beta-1 adrenergic receptors, when activated, increase heart rate and contractility; nicotinic receptors are present at autonomic ganglia and neuromuscular junctions and don’t directly slow heart rate.