Acetylcholine is applied experimentally to a sinoatrial node pacemaker cell. Which ionic mechanism primarily accounts for the hyperpolarization and slowing of phase 4 depolarization?
- A Activation of GIRK (G protein-coupled inwardly rectifying K+) channels increasing K+ conductance ✓
- B Blockade of L-type calcium channels reducing inward Ca2+ current
- C Inhibition of HCN channels reducing the funny current (If)
- D Stimulation of the Na+/K+ ATPase increasing outward current
Correct answer: A. Activation of GIRK (G protein-coupled inwardly rectifying K+) channels increasing K+ conductance
Explanation
Acetylcholine binds M2 muscarinic receptors on SA node cells, activating the Gi beta-gamma subunit which directly opens GIRK channels (IK,ACh). This increases K+ conductance, hyperpolarizing the cell and slowing phase 4 depolarization, thus reducing heart rate. While acetylcholine also modestly inhibits If via reduced cAMP, the dominant bradycardic effect in humans is mediated by GIRK channel activation. L-type calcium channel block is a minor contributor.
Reference: Berne & Levy Principles of Physiology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.