Activation of M2 muscarinic receptors on the heart causes which effect?

• A. Lower heart rate
• B. Increased heart rate
• C. Increased conduction velocity
• D. No change

Answer: (A)

M2 receptor activation slows the heart by engaging Gi proteins that blunt the heart’s pacemaker activity. When acetylcholine binds these receptors in the SA and AV nodes, it inhibits adenylate cyclase, lowering cAMP. This reduces the funny current (If) and L-type calcium currents, slowing diastolic depolarization and AV conduction. At the same time, GIRK channels open, causing potassium efflux and hyperpolarization of pacemaker cells. The combined effect is a slower heart rate, with a notable decrease in AV nodal conduction; sympathetic stimulation would be needed to raise rate or conduction, not parasympathetic activation.