Questions: Cardiac Electrophysiology and Action Potentials

Question 1

A pharmacologist administers a drug that selectively blocks L-type voltage-gated calcium channels in cardiac muscle. Which effect on the ventricular action potential and cardiac function would you predict?

• A. Phase 0 (rapid depolarization) is abolished because L-type Ca²⁺ channels drive the initial depolarization
• B. The plateau phase is shortened or eliminated, weakening contraction and reducing the refractory period
• C. The action potential duration is unchanged; only heart rate is affected because Ca²⁺ controls the SA node
• D. Repolarization is slowed because Ca²⁺ efflux normally helps restore the negative resting potential

Answer: (B)

L-type Ca²⁺ channels are the key inward current sustaining the Phase 2 plateau. Blocking them removes the inward Ca²⁺ current that balances outward K⁺ current, collapsing the plateau. Two consequences follow: (1) Contraction weakens because Ca²⁺ entry triggers calcium-induced calcium release from the SR, which drives actin-myosin cross-bridging — less Ca²⁺ entry means weaker contraction. (2) The refractory period shortens because it depends on the long plateau, and a shorter AP allows premature re-excitation and risk of arrhythmia. Option A is the key misconception: Phase 0 is driven by fast Na⁺ channels, not Ca²⁺.

Question 2

Why does the cardiac action potential last roughly 200–300 milliseconds while a neuronal action potential lasts only 1–2 milliseconds?

• A. Cardiac Na⁺ channels inactivate much more slowly than neuronal Na⁺ channels, prolonging Phase 0
• B. L-type voltage-gated Ca²⁺ channels open during Phase 2 and sustain an inward current that balances outward K⁺ current, holding the membrane near 0 mV for hundreds of milliseconds
• C. The cardiac muscle cell has a much larger surface area, requiring more time to fully depolarize
• D. Delayed rectifier K⁺ channels are absent in cardiac muscle, so repolarization must rely on slow Ca²⁺ channel inactivation alone

Answer: (B)

The plateau is the defining feature of the cardiac action potential. After Phase 0 (fast Na⁺-driven depolarization, identical in principle to neurons), L-type Ca²⁺ channels open. Their inward Ca²⁺ current is balanced by outward K⁺ current through delayed rectifier channels, holding the membrane potential near 0 mV — this is Phase 2, lasting 200–300 ms. No comparable plateau exists in neurons because neurons lack this sustained Ca²⁺ influx after depolarization. The plateau is not a side effect; it is functionally essential for both contraction and rhythm.

Question 3

The long plateau of the cardiac action potential creates an extended refractory period that prevents the heart from entering sustained tetanic contraction.

• T. True
• F. False

Answer: True

The refractory period — during which cardiac muscle cannot be re-excited — lasts nearly as long as the plateau, because fast Na⁺ channels remain inactivated until repolarization nears completion. This means the heart cannot receive another stimulus and contract again until the current contraction cycle is almost complete. In skeletal muscle, the brief action potential and short refractory period allow repeated stimuli to summate into tetanus. The cardiac design deliberately prevents this: tetanus would lock the heart in systole, blocking ventricular filling and eliminating cardiac output.

Question 4

Calcium influx into the cardiac cell is greatest during Phase 0 (rapid depolarization), which is why Phase 0 triggers the contractile machinery.

• T. True
• F. False

Answer: False

Phase 0 is driven by fast voltage-gated Na⁺ channels, not Ca²⁺ channels. Calcium influx occurs primarily during Phase 2 (the plateau), when L-type Ca²⁺ channels open. This Ca²⁺ then binds ryanodine receptors on the sarcoplasmic reticulum, triggering a much larger Ca²⁺ release (calcium-induced calcium release) that activates the contractile apparatus. The plateau phase, not Phase 0, is the trigger for contraction.

Question 5

The Phase 2 plateau of the cardiac action potential serves two distinct physiological functions. What are they, and how does each protect the heart?

Model answer: First, the plateau creates an extended refractory period: fast Na⁺ channels remain inactivated throughout the plateau, making the cardiac muscle unexcitable until repolarization is nearly complete. This prevents tetanic contraction and ensures the ventricle can refill between beats. Second, the plateau delivers the Ca²⁺ signal for contraction: L-type Ca²⁺ channel opening during Phase 2 triggers calcium-induced calcium release from the SR, providing the cytoplasmic Ca²⁺ that drives actin-myosin cross-bridge cycling.

These two functions are inseparably linked by the plateau's duration. Shortening the plateau (e.g., by L-type Ca²⁺ channel blockers, hypokalemia, or ischemia) simultaneously weakens contraction (less Ca²⁺ trigger) and increases arrhythmia risk (shorter refractory period allows premature re-excitation and re-entrant circuits). This dual role explains why antiarrhythmic drugs that modulate cardiac Ca²⁺ channels must be used carefully — the same channel that prevents arrhythmia when open is the same one that drives contraction.