Questions: Heart Rate Control and Autonomic Modulation

Question 1

A researcher administers a drug that completely blocks all vagal (parasympathetic) input to the SA node while sympathetic tone remains at its normal resting level. What change in heart rate would you predict?

• A. Heart rate drops to around 40 bpm because sympathetic tone alone is insufficient
• B. Heart rate increases toward or above 100 bpm, approaching the SA node's intrinsic firing rate
• C. Heart rate remains at roughly 65 bpm because sympathetic tone is unchanged
• D. Heart rate becomes dangerously irregular because the pacemaker requires both inputs to function

Answer: (B)

The SA node's intrinsic firing rate in a denervated heart is about 100 bpm. The resting heart rate of 60–70 bpm exists because vagal tone continuously holds the rate below the intrinsic rate. Removing vagal input releases this 'brake,' and the heart accelerates toward its intrinsic rate. This demonstrates that resting bradycardia relative to intrinsic rate is an active, maintained inhibition, not a neutral baseline.

Question 2

Acetylcholine released by vagal fibers slows heart rate at the SA node primarily by:

• A. Blocking beta-1 adrenergic receptors, preventing sympathetic acceleration
• B. Opening GIRK (IKACh) potassium channels, hyperpolarizing the pacemaker cell and slowing Phase 4 depolarization
• C. Directly inhibiting L-type calcium channels in ventricular cardiomyocytes, reducing contractility
• D. Increasing acetylcholinesterase concentration at the synapse, speeding up ACh degradation

Answer: (B)

ACh binds M2 muscarinic receptors, activating Gi protein which opens GIRK channels (IKACh). The resulting K⁺ efflux hyperpolarizes the pacemaker cell, so each cycle begins from a more negative membrane potential. Combined with reduced If and ICa,L (via decreased cAMP), this slows the slope of Phase 4 depolarization and increases the time to threshold, decreasing heart rate.

Question 3

During sudden standing (orthostasis), the observed increase in heart rate is caused largely by increased sympathetic nerve activity to the SA node.

• T. True
• F. False

Answer: False

The increase in heart rate during orthostasis involves both vagal withdrawal AND sympathetic activation. When blood pressure drops upon standing, baroreceptors signal the brainstem to reduce parasympathetic outflow (releasing the vagal brake) and increase sympathetic outflow. The initial rapid component of heart rate rise largely reflects vagal withdrawal, since parasympathetic responses are faster (milliseconds, due to quick ACh hydrolysis) than sympathetic responses (seconds).

Question 4

A person's resting heart rate of 62 bpm is below the intrinsic SA node firing rate of approximately 100 bpm because the vagus nerve provides continuous inhibitory tone to the SA node even at rest.

• T. True
• F. False

Answer: True

This is a fundamental point in cardiac physiology. The SA node does not fire at its intrinsic rate under normal resting conditions because the vagus nerve is tonically active, continuously releasing ACh that hyperpolarizes pacemaker cells. This 'vagal tone' actively suppresses heart rate below the intrinsic rate. Atropine (a muscarinic blocker) administered at rest dramatically increases heart rate by removing this brake.

Question 5

Explain why a rise in heart rate is often better described as 'releasing the brake' rather than 'pressing the accelerator.' What is the physiological basis of this analogy, and under what conditions does it best apply?

Model answer: At rest, vagal tone actively holds heart rate below the SA node's intrinsic rate (~100 bpm). Because heart rate is already being suppressed, it can increase simply by reducing parasympathetic output — no increase in sympathetic activity required. This 'releasing the brake' mechanism is especially prominent during mild to moderate increases in heart rate (e.g., standing up, light exercise), where much of the rise comes from vagal withdrawal. The analogy is most apt at rest and during moderate activity; at higher intensities, when vagal tone has been fully withdrawn, further increases do require 'pressing the accelerator' via increased sympathetic drive.