Acetylcholine slows heart rate by activating which mechanism in pacemaker cells?

• A. Opening potassium channels leading to hyperpolarization
• B. Increasing funny current
• C. Inhibiting L-type calcium channels
• D. Increasing threshold rapidly

Answer: (A)

Acetylcholine slows the pacemaker by increasing outward potassium conductance in the sinoatrial node, opening potassium channels and causing hyperpolarization. This makes the pacemaker potential dip more negative and reduces the slope of diastolic depolarization, so it takes longer to reach the threshold for firing another action potential, lowering the heart rate. The binding to muscarinic receptors (via Gi proteins) also reduces cAMP and the funny current, but the direct and principal effect that slows rate is the enhanced K+ efflux leading to hyperpolarization. Increasing the funny current would speed up pacemaker activity, and inhibiting L-type calcium channels would slow conduction more broadly but isn’t the primary vagal mechanism for slowing heart rate. Increasing threshold rapidly isn’t how acetylcholine modulates pacemaker cells.