068 - Arrhythmias - Cardiac Action Potentials

The cardiac action potential represents a sequence of voltage changes across the membrane of cardiac cells, crucial for transmitting electrical signals and triggering myocyte contraction.

1. Myocyte Action Potential (Atrial and Ventricular Myocytes)

This action potential is typically divided into five phases:

  • Resting Potential (Phase 4)

    • Membrane voltage: approximately -85 ext{ millivolts}.

    • Maintained by: Constant outward leak of potassium ions through inward rectifier channels.

    • Channels closed: Sodium and calcium channels.

    • Meaning: More negatively charged molecules inside, more positively charged molecules outside.

  • Cell-to-Cell Transmission

    • Cardiac myocytes are connected by gap junctions.

    • Depolarization (influx of positive ions) in one myocyte transmits to an adjacent myocyte via gap junctions, initiating a new action potential.

  • Phase 0 (Depolarization)

    • Initiated by: Positive ions entering myocyte via gap junctions, raising membrane potential from -85 ext{ millivolts}.

    • When voltage reaches threshold (around -70 ext{ millivolts}): Fast sodium channels open.

    • Result: Rapid inward influx of sodium ions, causing rapid depolarization and positive overshoot of membrane potential.

    • Eventually: Fast sodium channels close.

    • Clinical Correlation: Class I antiarrhythmic drugs block sodium channels, delaying Phase 0.

  • Phase 1 (Initial Repolarization)

    • Event: Potassium channels begin to open.

    • Result: Outward flow of potassium, briefly returning membrane potential close to 0 ext{ millivolts}.

  • Phase 2 (Plateau Phase)

    • Key event: L-type calcium channels open, causing inward movement of calcium ions.

    • Importance: This calcium influx is the trigger for myocyte contraction (excitation-contraction coupling).

    • Concurrent event: Potassium continues to leak out through delayed rectifier channels.

    • Result: Balanced influx of calcium and efflux of potassium creates a sustained plateau.

    • Clinical Correlation: Verapamil and Diltiazem (calcium channel blockers) block L-type calcium channels, slowing conduction and decreasing contractility.

  • Phase 3 (Final Repolarization)

    • Event: Calcium channels inactivate.

    • Main process: Persistent outflow of potassium ions (through delayed rectifier channels).

    • Result: Membrane voltage returns to the resting potential of about -85 ext{ millivolts}.

    • Clinical Correlation: Class III antiarrhythmic drugs block potassium channels, slowing repolarization and impulse propagation.

2. Contrast with Skeletal Muscle Action Potential

  • No Plateau/Phase 2: Calcium is not involved in skeletal muscle depolarization.

  • No Gap Junctions: Each skeletal muscle cell has its own neuromuscular junction and must be individually depolarized by a neuron; depolarization does not spread from cell to cell.

3. Refractory Period

  • Definition: The time from Phase 0 until the myocyte can possibly depolarize again.

  • Function: Determines how fast myocytes can conduct electrical activity.

  • Characteristics: During this period, it is difficult or impossible for the myocyte to conduct another electrical impulse.

  • Clinical Relevance: Many antiarrhythmic drugs prolong the refractory period, making it harder for arrhythmias to spread.

4. Pacemaker Action Potential (SA Node and AV Node)

Cardiac cells in the SA (Sinoatrial) node and AV (Atrioventricular) node exhibit a distinct pacemaker action potential morphology, unlike His bundle, bundle branches, and Purkinje fibers, which have morphology similar to myocyte AP.

  • Key Differences from Myocyte Action Potential

    • Resting Potential: Higher, at about -60 ext{ millivolts} (not -85 ext{ millivolts}).

    • Phases: Only three phases: Phase 4, Phase 0, and Phase 3 (no plateau phase).

    • Phase 4: Membrane voltage is not constant; it slowly drifts upward due to the funny current (slow inward leak of sodium ions).

    • Depolarization Threshold: Reached at about -40 ext{ millivolts}.

    • Depolarization (Phase 0): Primarily due to opening of calcium channels (L-type), resulting in inward calcium ion current.

    • Repolarization (Phase 3): Calcium channels close, potassium channels open, outward potassium current brings voltage back to -60 ext{ millivolts}.

  • SA Node vs. AV Node

    • AV node Phase 4 is slower, meaning it takes longer to reach threshold.

    • SA node is the dominant pacemaker because its Phase 4 rise is quicker.

  • Summary of Pacemaker AP Features

    • Funny Current / Pacemaker Current: Spontaneous inward flow of sodium ions, causing the upward slope of Phase 4.

    • Automaticity: Cells with pacemaker action potential possess automaticity, meaning they can self-initiate depolarization without neural or neighboring cell stimulation.

    • No Fast Sodium Channel Activity: Fewer inward rectifier potassium channels (compared to myocytes) prevent the membrane potential from dropping below -60 ext{ millivolts}, so fast sodium channels (which require -85 ext{ millivolts} to function) have no important role.

  • Drug Effects on Pacemaker Action Potential

    • Drugs that slow the pacemaker action potential cause two effects:

      • Slow heart rate (by slowing sinus node depolarization).

      • Slow AV conduction (by delaying impulse conduction from atria to ventricles).

    • Key Drug Classes Affecting Pacemaker AP:

      • Calcium Channel Blockers (e.g., Verapamil, Diltiazem):

        • Block L-type calcium channels.

        • Slow Phase 0 (where calcium is crucial).

        • Slow sinus depolarization, thus heart rate.

        • Slow conduction through the AV node.

      • Beta Blockers:

        • Modify the slope of Phase 4 (slower slope = longer to reach threshold = lower heart rate).

        • Prolong repolarization (wider AP), slowing conduction in both SA and AV nodes.

  • Factors Changing Phase 4 Slope (in SA Node)

    • Decrease Slope (Slower Heart Rate):

      • Parasympathetic nervous system.

      • Beta blockers.

      • Adenosine (antiarrhythmic drug).

    • Increase Slope (Faster Heart Rate):

      • Sympathetic nervous system (fight or flight response).

      • Sympathomimetic drugs.

  • Other Pacemakers in the Heart

    • Many cardiac cells are capable of automaticity.

    • SA Node: Normally dominant, fastest pacemaker (60-100 ext{ bpm}).

    • If SA node fails, other cells can take over pacing:

      • AV Node: Next fastest (40-60 ext{ bpm}).

      • Bundle of His: Slower (25-40 ext{ bpm}).

      • Purkinje fibers and ventricular myocytes (under certain conditions) can also potentially pace the heart.