The sinoatrial (SA) node, the heart’s natural pacemaker, controls the heartbeat by generating rhythmic electrical impulses. The autonomic nervous system, particularly the vagus nerve, modulates this pacemaker activity to regulate heart rate. When the vagus nerve is stimulated, it inhibits the pacemaker cells, leading to a slower heart rate. Understanding the mechanisms behind this inhibition is key to grasping how the parasympathetic nervous system influences cardiac function.

Key Mechanisms of Vagus Nerve Inhibition on SA Node Pacemaker Cells

When the vagus nerve stimulates the SA node:

• Acetylcholine (ACh) is released and binds to M2 muscarinic receptors on pacemaker cells.

• This binding activates several intracellular pathways leading to changes in ion channel activity that slow down the pacemaker potential.

Details of the Proposed Mechanisms

A. Activation of Acetylcholine-Regulated K+ Channels

• ACh binding opens G-protein coupled acetylcholine-regulated inwardly rectifying potassium channels (GIRK channels).

• Opening these potassium channels allows K+ to flow outward of the cell, increasing K+ conductance.

• This causes the inside of the cell to become more negative (hyperpolarized), making it less likely to reach the threshold for firing the next action potential.

• This mechanism slows the spontaneous depolarization of the SA node pacemaker cells, thus decreasing heart rate.cvphysiology+2

B. Outward K+ Causes Hyperpolarization of Pacemaker Cells

• The increased outward K+ current causes a hyperpolarization of the pacemaker membrane potential.

• This hyperpolarization prolongs the time needed for the membrane potential to reach the threshold for the next action potential, slowing the heartbeat.

• Hyperpolarization makes the cells less excitable and reduces their firing rate.pmc.ncbi.nlm.nih+1

C. Inward “Funny Current” (I_f) is Increased

• The funny current (“h”-channel current) is a mixed Na+ and K+ inward current activated during hyperpolarization.

• However, during vagal stimulation, the intracellular cAMP decreases (due to M2 receptor activity), which reduces the funny current.

• Therefore, the inward funny current does not increase but decreases during vagal inhibition.

• This means statement C is incorrect because vagal stimulation inhibits the funny current.wikipedia+1

D. Increased Intracellular cAMP and Ca++ Channel Opening

• Activation of M2 receptors by acetylcholine through the G-protein pathway decreases intracellular cAMP.

• Lower cAMP results in slower opening of L-type Ca++ channels, reducing inward calcium current.

• This slows depolarization of the pacemaker cells, contributing to reduced heart rate.

• Thus, the correct concept is decreased cAMP, not increased cAMP.

• Hence, statement D mentioning increased cAMP is incorrect.cvphysiology+1

Evaluation of the Given Statements

Therefore, the correct answer is:

(3) A and B

Summary

The vagus nerve inhibits the pacemaker cells of the sinoatrial node primarily by activating acetylcholine-regulated potassium channels that increase outward potassium flow, causing hyperpolarization and slowing the rate of depolarization. This reduces heart rate by delaying the time for the pacemaker cells to reach their firing threshold.

Contrary to statements suggesting an increase in funny current or intracellular cAMP, both actually decrease during vagal stimulation, further contributing to slowed heart rhythm.