Physiologically, which neurotransmitter and receptor type mediates the effect of parasympathetic stimulation on sinoatrial node automaticity, and what is the ionic mechanism?

• A Acetylcholine on M2 muscarinic receptors; activates IKACh (GIRK channels), hyperpolarizing the SA node and slowing phase 4 depolarization ✓
• B Norepinephrine on beta-1 receptors; increases If (funny current) and ICaL
• C Acetylcholine on M3 muscarinic receptors; reduces intracellular cAMP reducing ICaL
• D Adenosine on A1 receptors; increases K+ conductance identical to acetylcholine mechanism

Explanation

Parasympathetic (vagal) postganglionic fibers release acetylcholine (ACh) onto M2 muscarinic receptors on SA node cells. M2 receptor activation couples to Gi protein, which directly opens GIRK channels (G-protein coupled inwardly rectifying K+ channels, IKACh/IKAdo) via Gbetagamma subunits. Increased K+ conductance hyperpolarizes the SA node maximum diastolic potential (more negative) and reduces the slope of phase 4 spontaneous depolarization, slowing heart rate. Gi also inhibits adenylyl cyclase, reducing cAMP and ICaL (secondary effect). M3 receptors are found on glandular/vascular smooth muscle, not SA node. Adenosine does activate the same GIRK channels via A1 receptors (similar mechanism), but ACh-M2 is the parasympathetic mechanism.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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