During parasympathetic (vagal) activation, acetylcholine binds to which receptor subtype to slow heart rate?

• A. Muscarinic M2 receptors
• B. Nicotinic Nn receptors
• C. Muscarinic M1 receptors
• D. Beta1 adrenoreceptors

Answer: (A)

Parasympathetic input to the heart slows rate by acetylcholine acting on the muscarinic M2 receptors in the SA and AV node. When ACh binds M2, it activates Gi proteins, which inhibits adenylate cyclase and lowers cAMP. The βγ subunits open GIRK potassium channels, causing hyperpolarization and a decrease in the pacemaker current If, plus reduced calcium influx. This slows automaticity in the SA node and conduction through the AV node, producing a slower heart rate. Other receptor types don’t produce this direct cardiac slowing: nicotinic receptors are at autonomic ganglia, M1 receptors are mainly CNS/peripheral and not the primary cardiac mediator, and beta1 adrenoceptors drive sympathetic, not parasympathetic, effects.