Cardiac Action Potential Phases 0 4

The cardiac action potential represents the electrical heartbeat of the human body, a precisely choreographed sequence of ion movements that transforms a chemical gradient into a mechanical contraction. Consider this: unlike the rapid, triangular spikes seen in skeletal muscle or nerves, the cardiac action potential is distinguished by a prolonged plateau phase, a feature essential for preventing tetany and ensuring the heart has time to refill with blood between beats. Understanding the five distinct phases—numbered 0 through 4—provides the foundational knowledge required to grasp cardiac physiology, pharmacology, and the mechanisms underlying arrhythmias.

Phase 4: The Resting Membrane Potential

Before the storm of depolarization begins, the cardiac myocyte sits in Phase 4, the resting state. On top of that, in working myocardial cells (ventricular and atrial myocytes), this potential is stable, typically resting near -90 mV. This negative voltage is established and maintained primarily by the Na⁺/K⁺-ATPase pump, which actively transports three sodium ions out of the cell and two potassium ions into the cell against their concentration gradients, consuming ATP in the process It's one of those things that adds up..

The membrane is highly permeable to potassium (K⁺) at rest due to open inward rectifier potassium channels (I_K1). Potassium leaks out of the cell down its concentration gradient, dragging the membrane potential toward the equilibrium potential for K⁺ (E_K, approx. Consider this: -96 mV). The slight difference between the resting potential (-90 mV) and E_K is due to a small, steady "leak" of sodium ions into the cell.

It is critical to distinguish working myocardial cells from pacemaker cells (SA and AV nodes). In pacemaker cells, Phase 4 is not stable; it exhibits spontaneous diastolic depolarization (the "pacemaker potential"). A funny current (I_f, mixed Na⁺/K⁺ influx) and decaying K⁺ efflux slowly drive the membrane potential toward threshold, initiating the next heartbeat automatically Nothing fancy..

Quick note before moving on.

Phase 0: Rapid Depolarization (The Upstroke)

Phase 0 is the explosive beginning of the action potential. In working myocardial cells (fast-response cells), this phase is mediated by the rapid influx of sodium ions (Na⁺) through voltage-gated fast Na⁺ channels (I_Na) No workaround needed..

When the membrane potential reaches a threshold (approx. In real terms, the massive electrochemical gradient—high Na⁺ outside, low Na⁺ inside, and a negative interior—drives Na⁺ into the cell at a staggering rate. -70 mV), these channels snap open. This creates a maximum upstroke velocity (dV/dt_max) of 200–300 V/sec, rocketing the membrane potential from -90 mV to approximately +20 to +30 mV.

This rapid depolarization serves two vital functions:

1. Propagation: The strong current flow depolarizes adjacent membrane segments, allowing the action potential to spread rapidly through the ventricles via gap junctions.
2. Trigger: The positive voltage opens the voltage-gated L-type Calcium channels required for the next phase.

In pacemaker cells (slow-response cells), Phase 0 looks different. Day to day, because the resting potential is less negative (approx. -60 mV), the fast Na⁺ channels are largely inactivated (in a "closed-but-unavailable" state). So depolarization here is carried by L-type Calcium channels (I_Ca,L), resulting in a much slower upstroke (dV/dt_max ~ 10 V/sec). This slower conduction velocity is a protective feature, delaying AV nodal transmission to allow atrial contraction to finish before ventricular contraction begins Still holds up..

Phase 1: Early Rapid Repolarization (The Notch)

Immediately following the sodium-driven spike, the membrane potential takes a brief, sharp dip downward. This is Phase 1, caused by the transient outward potassium current (I_to) That's the part that actually makes a difference..

As the cell becomes positive, two things happen almost simultaneously: the fast Na⁺ channels inactivate (slamming shut), and the I_to channels open. Worth adding: a burst of K⁺ rushes out of the cell, creating a distinct "notch" or "spike-and-dome" morphology on the voltage trace. This phase is much more prominent in epicardial cells than in endocardial or mid-myocardial (M-cells) cells Not complicated — just consistent. Practical, not theoretical..

It sounds simple, but the gap is usually here.

This heterogeneity in Phase 1 magnitude across the ventricular wall creates a transmural voltage gradient during early repolarization. This gradient is the cellular basis for the J-wave (Osborn wave) on the ECG and plays a role in the genesis of early repolarization syndromes and Brugada syndrome But it adds up..

Not the most exciting part, but easily the most useful.

Phase 2: The Plateau Phase (The Cardiac Signature)

Phase 2 is the defining characteristic of the cardiac action potential. While nerve and skeletal muscle action potentials last 1–5 milliseconds, the cardiac action potential lasts 200–400 milliseconds. This prolonged plateau is a delicate tug-of-war between inward (depolarizing) currents and outward (repolarizing) currents That alone is useful..

The Inward Current: L-Type Calcium (I_Ca,L)

As the membrane potential hovers around 0 to +10 mV, voltage-gated L-type Calcium channels open slowly. Calcium enters the cell down its massive electrochemical gradient. This influx serves a dual purpose:

1. Electrical: It provides the inward current necessary to balance K⁺ efflux, maintaining the plateau voltage.
2. Mechanical (Excitation-Contraction Coupling): The entering Ca²⁺ triggers Calcium-Induced Calcium Release (CICR) from the Sarcoplasmic Reticulum (SR) via Ryanodine Receptors (RyR2). This flood of cytosolic calcium binds troponin C, initiating contraction.

The Outward Currents: Delayed Rectifier Potassium (I_Kr and I_Ks)

Simultaneously, delayed rectifier K⁺ channels begin to open. These are voltage-gated but activate slowly.

• I_Kr (Rapid delayed rectifier): Encoded by hERG (KCNH2). Activates quickly during the plateau but inactivates at positive voltages; recovers during repolarization to drive the final push down.
• I_Ks (Slow delayed rectifier): Encoded by KCNQ1/KCNE1. Activates very slowly throughout the plateau and does not inactivate. It acts as a "repolarization reserve," becoming critical when I_Kr is blocked (e.g., by drugs or Long QT Syndrome type 2).

The Balance

During the plateau, I_Ca,L ≈ I_Kr + I_Ks. The membrane potential stays relatively stable because the inward positive charge (Ca²⁺) perfectly cancels the outward positive charge (K⁺). This electrical stability maintains the contraction long enough for effective ejection of blood.

Clinical Relevance: Drugs that block I_Kr (many antiarrhythmics, antibiotics, antipsychotics) prolong Phase 2, lengthening the QT interval and risking Torsades de Pointes. Conversely, ischemia opens ATP-sensitive K⁺ channels (I_K,ATP), shortening Phase 2 to conserve ATP, but creating electrical heterogeneity that predisposes to ventricular fibrillation.

Phase 3: Rapid Repolarization

Eventually, the balance tips. Phase 3 begins when the inward Calcium current inactivates (Ca²