The sinoatrial (SA) node serves as the heart’s natural pacemaker, and its activity is finely tuned by the autonomic nervous system. Cholinergic fibers of the vagus nerve exert an inhibitory effect on the SA node, modulating heart rate by altering the pacemaker potential and nodal impulse generation through several ion channel mechanisms.

Key Effects of Vagal Stimulation on SA Node Pacemaker Cells

Cholinergic vagal stimulation involves acetylcholine release, which acts primarily via M2 muscarinic receptors on SA node cells, initiating changes in ion channel behavior that decrease heart rate.

Analysis of Proposed Mechanisms

• A. The nodal cell membrane becomes depolarized.
  This is incorrect. Vagal stimulation typically causes hyperpolarization of the membrane, making the inside more negative and less likely to fire an action potential.

• B. The slope of the pacemaker potential is increased.
  This is incorrect. The slope of the pacemaker potential actually decreases during vagal stimulation, meaning it takes longer to reach the threshold for depolarization, slowing the heart rate.

• C. The K+ conductance of nodal cell membrane is decreased.
  This is incorrect. Actually, K+ conductance increases due to activation of acetylcholine-sensitive potassium channels, contributing to hyperpolarization.

• D. The depolarizing effect of ‘h’ current (Ih) on the membrane potential is slowed down due to the opening of G protein-gated K+ channels.
  This is correct. Opening of G protein-activated potassium channels hyperpolarizes the membrane, slowing the inward funny current (Ih) associated with pacemaker potential depolarization.

• E. The opening of Ca++ channels is slowed down due to the decreased cAMP level in the nodal cells.
  This is correct. Activation of M2 receptors via vagal stimulation decreases intracellular cAMP, which reduces Ca++ channel opening, further slowing pacemaker depolarization.

Correct Combination of Statements

Based on the above analysis, the correct statements are D and E, corresponding to option:

(4) D and E.

Overview of Vagal Influence

• Vagal stimulation increases K+ conductance through acetylcholine-regulated channels, causing hyperpolarization.

• The hyperpolarized state reduces the funny current (Ih), delaying the pacemaker potential’s rise to threshold.

• Decreased cAMP from M2 receptor activation slows calcium channel activity, reducing depolarization rate.

• These combined effects slow the SA node firing rate, resulting in decreased heart rate (negative chronotropy).

Summary Table

Conclusion

Cholinergic vagal stimulation inhibits the SA node pacemaker cells primarily through:

• Increased potassium conductance causing hyperpolarization,

• Slowed funny current (Ih) depolarizing effects due to G protein-gated K+ channel activity,

• Reduced intracellular cAMP leading to slower calcium channel opening.

These mechanisms delay the pacemaker potential’s rise to threshold, decreasing heart rate. Therefore, the correct answer to the question is:

(4) D and E

Understanding these mechanisms provides insight into parasympathetic regulation of heart rhythm and informs medical approaches to managing heart rate abnormalities.