Sympathetic nerve stimulation plays a crucial role in increasing heart rate, especially during fight-or-flight situations. It does so by modulating ionic currents in the pacemaker cells of the sinoatrial (SA) and atrioventricular (AV) nodes, which are responsible for initiating the heartbeat.

Mechanism of Sympathetic Stimulation on Nodal Cells

Sympathetic nerves release norepinephrine (NE) which binds to β1-adrenergic receptors on the surface of pacemaker cells. This activates the G-protein-cAMP-protein kinase A (PKA) signaling cascade, resulting in several key changes in ion channel activity:

1. Facilitation of “funny” (If) channels

   • The funny current increases due to direct binding of cAMP to HCN channels, raising the inward sodium and potassium current during diastolic depolarization.

   • This speeds up the pacemaker potential, thereby increasing heart rate.pmc.ncbi.nlm.nih

2. Increased opening of L-type calcium channels (LTCC)

   • PKA phosphorylates L-type Ca²⁺ channels, increasing their opening probability.

   • This enhances the inward calcium current during the action potential upstroke, contributing to faster depolarization and stronger contractions.pmc.ncbi.nlm.nih

3. Potassium conductance generally decreases during sympathetic stimulation, allowing faster depolarization

   • Potassium channels tend to be inhibited, not increased, to allow quicker progression toward threshold potential.pmc.ncbi.nlm.nih

4. Fast sodium channels do not play a major role in nodal pacemaker cells

   • Unlike in ventricular myocytes, fast sodium channels are sparse or inactive in the SA/AV node cells.pmc.ncbi.nlm.nih

Evaluating the Options

• (1) Opening of sodium channels is facilitated
  Incorrect. Fast sodium channels are not significant in nodal cells for pacemaking.

• (2) Potassium conductance is increased
  Incorrect. Potassium conductance usually decreases to speed up depolarization.

• (3) Opening of L-type calcium channels is facilitated
  Correct. Enhanced L-type Ca²⁺ channel opening is a key step in increasing heart rate through faster AP upstroke.

• (4) ‘h’ channels are inhibited
  Incorrect. Sympathetic stimulation facilitates the funny (If) channels rather than inhibiting them.

Summary

The main change in the nodal tissue membrane that results in increased heart rate due to sympathetic stimulation is:

(3) Opening of L-type calcium channels is facilitated.

This, combined with increased funny current, accelerates diastolic depolarization and action potential firing rate in pacemaker cells, thus increasing heart rate.

Additional Insights

These effects support the sympathetic nervous system’s role in:

• Positive chronotropy (increased heart rate)

• Positive inotropy (enhanced myocardial contractility)

• Positive dromotropy (faster conduction through the AV node)

These changes optimize cardiac output during stress or exercise.