The Spark
A threshold is crossed, and a cascade begins. The cardiac action potential — five phases, four major currents, and the entire language of electrophysiology — starts here.
Every revolution starts the same way: a threshold is crossed, and there is no going back. In the cardiac cell, that revolution lasts about 300 milliseconds. In that time, a precise sequence of ion channels opens, conducts, inactivates, and resets — with the timing of a mechanical watch. This sequence is the action potential. It is the fundamental unit of cardiac electricity: the signal that, once triggered, will propagate from cell to cell across the entire heart.
The previous chapter built the battery. This chapter fires it.
The Mechanism: Five Phases of a Single Heartbeat
The action potential is conventionally divided into five phases — numbered 0 through 4, though the cell begins and ends at phase 4. Each phase is defined by which ion channels are open, which are closed, and which direction current flows across the membrane. Each phase corresponds to a specific biophysical event, and each maps onto a recognizable feature of the surface ECG.
In every section below, the logic is the same: membrane voltage (what the electrical field looks like) → electrochemical driving forces on each ion → which channels open or close → net movement of charge → what you see on the cellular trace or the body-surface ECG.
Interactive Action Potential
Click a phase to explore. Toggle cell type. Overlay drug effects.
Phase 0: The Upstroke
Depolarization does not appear from nowhere. A neighbor that has already fired injects current through gap junctions. That current deposits positive charge on the cytosolic side of the membrane here, nudging the local voltage toward threshold (about −70 mV in a working ventricular myocyte). Why does crossing threshold matter? Because the fast Na⁺ channel is built with a voltage sensor: a cluster of positively charged amino acids in its structure. When the inside of the cell becomes less negative, those sensors are pushed outward in the membrane field, mechanically pulling the activation gate open.
Once the pore is open, Na⁺ is driven by both chemistry and electricity: the concentration gradient favors influx (high [Na⁺] outside, low inside), and the electrical gradient favors it too (negative inside attracts positive Na⁺). The result is a violent inward current that flips the membrane from roughly −90 mV to about +20 mV in under 2 milliseconds.
The steepness of that rise — the maximum rate of rise, Vmax — is what sets how quickly the next cell downstream will be brought to threshold. Tall, fast Phase 0 means the wavefront moves quickly through tissue. When Vmax falls — sodium channel block, ischemia, a less negative resting potential leaving channels partly inactivated — the same distance takes longer to excite. Slower propagation lengthens the wavelength of any circulating pattern and is one of the ingredients that can allow reentry.
The Ball-and-Chain: Sodium Channel Inactivation
The sodium channel does not simply open and stay open. Within milliseconds of activation, a separate structural element — the inactivation gate, classically modeled as a "ball and chain" tethered to the intracellular face of the channel — swings into the pore and blocks it. The channel transitions from open to inactivated: closed, but not in the same way it was closed at rest. In this state, the channel cannot reopen, no matter what the voltage does. It must first return to its resting state, which requires the membrane to repolarize fully.
This distinction — between resting-closed (ready to open) and inactivated-closed (locked until reset) — is one of the most important concepts in electrophysiology. It is why the cell has a refractory period. It is why premature stimuli sometimes fail to conduct. It is why certain drugs bind preferentially to one state of the channel over another.
Phase 1: The Notch
At the peak of Phase 0, the electrical world has flipped: the cytosol is now positive relative to the outside. Positive potassium ions sit on both sides of the membrane, so the old story — negative inside pulling K⁺ outward — is no longer the whole picture. Like charges repel: the positive interior now pushes K⁺ toward the extracellular fluid. At the same time, the concentration gradient still favors K⁺ leaving the cell (high [K⁺] inside). Those forces align to drive K⁺ outward.
Specialized channels that activate at depolarized voltages — the transient outward current, Ito — open briefly. A quick slip of K⁺ out of the cell carries positive charge across the membrane, nudging the voltage back down a few millivolts. That small, rapid dip is the notch at the top of the action potential: a pause before the long plateau begins.
This current is not uniform across the heart wall. Epicardial cells express more Ito than endocardial cells, so the outer layer repolarizes slightly faster in early Phase 1 than the inner layer. That voltage difference across the wall — a transmural gradient — shapes what you see at the J point, where the QRS transitions into the ST segment.
When Ito is exaggerated or unevenly distributed — as in Brugada syndrome, where the right ventricular epicardium carries an unusually large early repolarization current — the J point becomes dramatically abnormal. We will return to Brugada in a later chapter. For now, the principle: a single ion current difference between tissue layers can write a visible signature on the surface ECG.
Phase 2: The Plateau
This is what makes the cardiac action potential unlike a nerve or skeletal muscle spike. For 200 milliseconds or more, the voltage lingers near 0 mV instead of collapsing straight back to rest. Why? Because two large currents temporarily balance: inward movement of positive charge through L-type Ca²⁺ channels (ICaL) opposes outward movement of positive charge carried by K⁺ through several potassium pathways that are now open at depolarized voltages.
L-type channels activate slowly compared with Na⁺ channels — they need time to open fully — which is why the plateau begins after the sodium spike, not during it. While they are open, Ca²⁺ enters down its electrochemical gradient: extracellular calcium concentration is much higher than intracellular, and even at 0 mV the driving force still favors inward movement.
Here is the key insight about the plateau: the cell is not electrically quiet during this phase. Enormous numbers of ions cross the membrane every second. But the voltage stays flat because the net current is near zero — inward Ca²⁺ charge roughly equals outward K⁺ charge. It is a dynamic equilibrium, not silence.
The Ca²⁺ that enters is not only a current carrier. It is the trigger for contraction: it binds to ryanodine receptors on the sarcoplasmic reticulum and unleashes a larger Ca²⁺ release (calcium-induced calcium release), which engages the contractile proteins. Electrical plateau and mechanical systole are coupled by that same Ca²⁺ signal.
Skeletal muscle fires a 2–5 millisecond action potential; the heart stretches depolarization across hundreds of milliseconds. That long plateau keeps myocardium refractory while the chamber completes activation — so the organ pumps as a coordinated chamber rather than fibrillating from immediate re-excitation of the same tissue.
Phase 3: Repolarization
The plateau ends when the balance breaks. L-type Ca²⁺ channels inactivate (voltage- and time-dependent closure of the pore), so inward Ca²⁺ current falls. At the same time, delayed rectifier K⁺ channels — IKr and IKs — have been stepping up during depolarization; they now carry a large outward K⁺ current. With less inward Ca²⁺ and more outward K⁺, net current turns outward: positive charge leaves the cytosol faster than it enters, and the membrane voltage marches back toward the K⁺-dominated resting potential (~−90 mV).
On the body surface, that coordinated wave of ventricular repolarization inscribes the T wave. The T wave is normally upright in many leads because repolarization does not unfold identically in every layer — timing differences between epicardium, mid-myocardium, and endocardium vector-sum into a net deflection that varies by lead.
If Phase 3 lengthens (reduced IKr from drugs or mutation, electrolyte shifts, etc.), the QT interval stretches: the tissue stays depolarized longer before the next beat can start safely. If neighboring regions repolarize at different speeds, electrical dispersion appears across the wall — one substrate for re-entrant activity such as torsades de pointes.
Phase 4: Return to Rest
In working myocytes, repolarization completes when the membrane returns near the potassium reversal voltage. The inward rectifier, IK1, dominates resting permeability to K⁺. At negative voltages it carries a strong outward "leak" of K⁺ that stabilizes the resting potential; that same high resting K⁺ conductance is why the cell sits near EK. Fast Na⁺ channels recover from inactivation as the voltage becomes negative again, returning to a closed-but-available state. The cell is ready for the next stimulus.
Pacemaker cells in the SA and AV nodes do not have a flat Phase 4. They lack the strong IK1 "anchor" of working myocardium, so nothing holds the voltage fixed at −90 mV. Instead, a mixed Na⁺/K⁺ current activated by hyperpolarization — the funny current (If) — together with T-type Ca²⁺ channels, slowly drags the diastolic voltage toward threshold. When threshold is reached, Ca²⁺-dependent Phase 0 fires again. That spontaneous diastolic drift is why the sinus node sets rate — and why sympathetic and parasympathetic tone, which shift the balance of those currents, speed or slow the clock.
What the Wavefront Sees
The action potential is the unit of propagation. When one cell depolarizes, its cytosol is momentarily more positive than its neighbor's. That voltage difference drives ionic current through gap junctions (connexons) into the next cell — the same physical principle as local circuit current, just through a specialized pore. That injected current depolarizes the neighbor's membrane; if it reaches threshold, the neighbor fires. Repeat, and the excitation travels at roughly 0.5–4 m/s depending on tissue geometry and gap-junction density.
Ahead of the wavefront lies either excitable tissue (resting potential, Na⁺ channels ready) or refractory tissue (still in plateau or early repolarization, Na⁺ channels largely inactivated). The wavefront cannot re-excite refractory tissue because inactivated channels will not open. The size of the excitable corridor in front of a circulating wave — the excitable gap — will matter when we discuss reentry.
What the ECG Shows
Mass synchronous Phase 0: Na⁺ influx in ventricular myocytes sums into a large net dipole. Narrow QRS means fast, coordinated depolarization; widened QRS means slowed or desynchronized Phase 0.
Phase 2: net transmembrane current ~0 while Ca²⁺ in balances K⁺ out. Little new dipole forms across the wall, so the trace sits on the baseline (injury or ischemia can shift that balance — a later story).
Phase 3: net outward K⁺ current returns the mass to rest. Layers repolarize at slightly different times; the vector sum of those momentary dipoles inscribes the T wave.
The surface ECG is a shadow — it records the sum of all cellular electrical activity projected onto the body surface. It cannot tell you what a single cell is doing. Once you understand the action potential phases, though, you can read the ECG as a timing document: an indirect report of which phase the ventricular mass is in at any given moment.
How the EP Lab Tests It
The effective refractory period (ERP) is the direct electrophysiological measurement of the action potential's protective duration. During programmed stimulation, the EP lab delivers progressively premature extra stimuli (S2, S3) at decreasing coupling intervals. The shortest interval at which S2 still captures the myocardium defines the ERP.
An ERP that is too short means the cell recovers too quickly — and a premature impulse can re-enter tissue that is already re-excitable. An ERP that varies significantly across adjacent regions creates dispersion of refractoriness — one of the key substrates for reentrant arrhythmias. When the EP study measures refractoriness at multiple sites, it is probing the action potential duration — Phase 2 and Phase 3 — indirectly but precisely.
Pharmacology Pearl
Lidocaine: A Sodium Channel Story
Lidocaine is a Class IB sodium channel blocker, but its true utility lies in its mechanism of action.
Lidocaine binds preferentially to the inactivated state of the sodium channel — the state the channel enters after Phase 0 and maintains through the plateau. It has rapid binding and unbinding kinetics (fast on-off). This means lidocaine accumulates in channels that are spending a lot of time in the inactivated state — which happens in two scenarios: rapid heart rates (more time per minute in plateau) and ischemic or depolarized tissue (where channels are chronically partially inactivated because the resting potential is less negative).
The result: lidocaine preferentially suppresses conduction in sick, fast-firing tissue while leaving normal, well-polarized tissue relatively unaffected. This is use-dependence and state-dependence in action — a precision tool that exploits the biophysics of sodium channel gating.
Lidocaine also slightly shortens action potential duration (Phase 2), which is why it is classified as IB rather than IA or IC. The sub-classifications within Class I are defined by their effects on APD and channel kinetics, beyond the shared sodium-blocking property.
Why the Action Potential Matters in the EP Lab
Defining the mechanism and the site of an arrhythmia is the foundation of electrophysiology. A rhythm's name — like "AVNRT" or "VT" — describes what it looks like, but understanding its underlying circuitry explains why it exists and how to intervene.
The action potential is where that discipline begins. If you understand the phases, you understand refractoriness. If you understand refractoriness, you understand why some premature beats conduct and others block. If you understand conduction and block, you can deduce the circuit. And if you can deduce the circuit, you can design the pacing maneuver that proves it — or the ablation that interrupts it.
The EP lab is fundamentally a place for hypothesis testing. Every pacing maneuver asks a question. Every response either confirms or refutes a mechanism. The action potential — its phases, its refractoriness, its response to rate and drugs — is the vocabulary in which those questions are written.
Preview: The Refractory Period
The refractory period deserves its own chapter — and it will get one. But here is the preview: the refractory period is a direct consequence of sodium channel inactivation. During Phases 0 through early Phase 3, the sodium channels are locked in the inactivated state. No stimulus, however strong, can reopen them. This is the absolute refractory period.
During late Phase 3, some channels have recovered, but not all. A very strong stimulus might produce a partial, slow depolarization — but it will conduct poorly. This is the relative refractory period. Full recovery requires complete repolarization to −90 mV.
The clinical importance of this will become clear in Chapter 4 — and will be central to understanding reentry, concealed conduction, and the behavior of the AV node. For now, hold this principle: the action potential's duration is the cell's built-in protection against premature re-excitation. When that protection is compromised — shortened, prolonged unevenly, or disrupted by drugs — arrhythmias become possible.
Clinical Takeaway
The action potential is the mechanism behind every clinical observation in electrophysiology. When you look at a wide QRS, you are seeing slow Phase 0. When you see a long QT, you are seeing prolonged Phase 3. When you see a patient with Brugada syndrome, you are seeing abnormal Phase 1 current in the epicardium. When lidocaine works in ischemic VT but not in normal tissue, you are seeing state-dependent sodium channel kinetics.
The phases of the action potential are the language in which the heart writes its electrical story. Learn the language, and the rhythms become mechanisms you understand — the tracings start to tell you why.
Key Takeaways
- Phase 0 (fast Na⁺ influx) determines conduction velocity. Anything that reduces Phase 0 — depolarized resting potential, sodium channel block, ischemia — slows conduction and widens the QRS.
- Phase 2 (Ca²⁺ plateau) is unique to cardiac cells and links electrical depolarization to mechanical contraction. It also keeps the cell refractory long enough to prevent premature re-excitation.
- Phase 3 (K⁺ repolarization) produces the T wave. Prolongation of Phase 3 lengthens the QT interval and creates risk for torsades de pointes if dispersion of repolarization is present.
- Sodium channel inactivation (the ball-and-chain) is the biophysical basis of the refractory period. The distinction between resting, open, and inactivated channel states explains why some drugs are use-dependent and state-dependent.
- Pacemaker cells have an unstable Phase 4 (funny current, If) that produces spontaneous depolarization. Working myocytes have a stable Phase 4 held by IK1. This difference is why only specialized cells pace.