Acetylcholine-activated channels couple to which G-protein?

• A. Gs
• B. Gi
• C. Gq
• D. G12/13

Answer: (B)

Acetylcholine-activated channels in the heart are the GIRK channels that are opened by the beta-gamma subunits of Gi/o proteins after a muscarinic receptor is stimulated. When acetylcholine binds the M2 receptor, the G protein splits into Gαi and Gβγ; the Gβγ subunits directly gate the GIRK channels, increasing potassium efflux, hyperpolarizing pacemaker cells, and slowing heart rate. The Gαi subunit also inhibits adenylyl cyclase, reducing cAMP, but the channel opening that slows conduction comes from the Gβγ effect. Other G-protein families would drive different paths: Gs raises cAMP and does not open GIRK; Gq activates phospholipase C with IP3/DAG signaling; G12/13 links to RhoA and cytoskeletal pathways. So the acetylcholine-activated channel coupling is with Gi.