A pharmacologist studies a drug that activates M2 muscarinic receptors in the sinoatrial node. Which intracellular mechanism directly mediates the negative chronotropy produced by this drug?
- A Increased cAMP via Gs protein activation
- B Activation of GIRK channels via Gi-released Gβγ subunits ✓
- C Decreased IP3 production via Gq suppression
- D Opening of voltage-gated L-type calcium channels
Correct answer: B. Activation of GIRK channels via Gi-released Gβγ subunits
Explanation
M2 receptors couple to Gi proteins; the released Gβγ subunits directly open G-protein-coupled inwardly rectifying potassium (GIRK) channels in the SA node, hyperpolarising the pacemaker cells and slowing heart rate. Gs-cAMP activation is the mechanism of sympathetic positive chronotropy, not M2. Gq/IP3 is the pathway of M1 and M3 receptors, not M2.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.