The Cardiac Action Potential, Pacemakers & the ECG
That steady beep on a hospital monitor is the sound of an electrical wave sweeping through the heart, sixty times a minute, for a lifetime. Understand the ion channels that make that wave — and the natural pacemaker that fires it — and every anti-arrhythmic drug becomes obvious: each one simply blocks one of those channels. This is the wiring diagram behind the entire rhythm section.
In the intensive care unit, a monitor beeps in time with a jagged green line — the ECG, tracing every heartbeat as it happens. Each beat begins as a spark in a tiny cluster of cells, races along a set of electrical wires, and triggers the muscle to squeeze. When that electrical journey goes wrong — too fast, too slow, or chaotic — we call it an arrhythmia, and the drugs that fix it all work on the same handful of ion channels. So before the drugs, we need the circuit: how a single heart cell fires, and how the whole heart keeps its rhythm.
The working-cell action potential
A heart muscle cell fires in five phases. A contracting heart cell produces an action potential in phases, each driven by an ion moving through a channel. Phase 0 is the rapid upstroke: sodium rushes in, depolarizing the cell — this is what antiarrhythmic Class I drugs block. Phase 1 is a brief dip. Phase 2 is the plateau, unique to the heart: calcium flows in and balances potassium flowing out, holding the cell depolarized for a long moment — this sustained calcium entry is what triggers the muscle to contract, and it keeps the cell refractory (unable to re-fire), preventing chaos. Phase 3 is repolarization: potassium exits and the cell resets — Class III drugs block this potassium exit, lengthening the action potential. Phase 4 is the resting membrane. Five phases, a handful of channels — and each channel is a drug target.
Pacemaker cells: the spark
Some heart cells don't wait to be told to fire — they fire themselves, over and over, setting the beat. These pacemaker cells, chiefly in the sinoatrial (SA) node, have an unstable phase 4 that slowly drifts upward on its own (the 'funny current') until it reaches threshold and fires — and in these cells the upstroke is driven by calcium, not sodium. This automatic rhythm is what makes the heart beat without any nerve input. The SA node is the fastest pacemaker, so it sets the pace; the signal then passes to the atrioventricular (AV) node, which deliberately DELAYS it (letting the atria empty into the ventricles) before it races down the conducting fibres to the ventricles. Drugs that slow the SA and AV nodes — beta blockers (Class II) and calcium channel blockers (Class IV) — slow the heart rate and AV conduction.
The ECG is just this electrical journey drawn on paper. The P wave is the atria depolarizing; the QRS complex is the ventricles depolarizing (the big spike, the heartbeat you feel); the T wave is the ventricles repolarizing. The PR interval reflects the AV node's delay. The QT interval reflects how long repolarization takes — and this matters enormously for drugs: anything that blocks the phase-3 potassium exit prolongs the QT, which can trigger a dangerous rhythm called torsades de pointes. That's why 'QT prolongation' is a warning attached to so many drugs.
- Working-cell phases: 0 Na⁺ in (upstroke), 2 Ca²⁺ plateau (contraction), 3 K⁺ out (repolarization).
- Pacemaker (SA node) cells self-fire via an unstable phase 4; their upstroke is Ca²⁺-driven.
- Conduction: SA node → AV node (delay) → His–Purkinje → ventricles.
- ECG: P (atria), QRS (ventricles), T (repolarization); QT = repolarization time.
- Antiarrhythmic classes map to channels: I=Na⁺, II=β/rate, III=K⁺, IV=Ca²⁺.
This diagram IS the antiarrhythmic drug map. The Vaughan-Williams classes are named directly after the channels in these phases: Class I blocks the phase-0 sodium channel, Class II is beta blockers (slowing the pacemaker), Class III blocks the phase-3 potassium channel (prolonging repolarization and the QT), and Class IV blocks the calcium channel (slowing the AV node). Learn the action potential once, and the entire arrhythmia section becomes 'which phase, which channel?' — exactly like the receptor map did for the autonomic drugs.
- Thinking all heart cells fire the same way. Working cells use Na⁺ upstroke; pacemakers use Ca²⁺.
- Ignoring the plateau (phase 2). Its calcium entry is what links electricity to contraction.
- Overlooking QT prolongation. Class III (and many other) drugs can trigger torsades de pointes.
- Forgetting the AV node's protective delay — it's why the atria empty before the ventricles fire.
Which ion drives the rapid upstroke (phase 0) of a working heart-muscle cell?
- Working cells: phase 0 Na⁺ in, phase 2 Ca²⁺ plateau (contraction), phase 3 K⁺ out.
- SA-node pacemakers self-fire (Ca²⁺ upstroke); signal goes SA → AV (delay) → ventricles.
- ECG: P/QRS/T; QT = repolarization time — blocking phase-3 K⁺ prolongs QT (torsades risk).
- Antiarrhythmic classes = channel blockers: I Na⁺, II β, III K⁺, IV Ca²⁺.
- Katzung BG. Basic & Clinical Pharmacology — Agents Used in Cardiac Arrhythmias (electrophysiology).
- Guyton & Hall Textbook of Medical Physiology — Rhythmical excitation of the heart; the ECG.
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Antiarrhythmic drugs.
- Rang HP, Dale MM, et al. Rang & Dale's Pharmacology — The heart: cardiac electrophysiology.
- Lilly LS. Pathophysiology of Heart Disease — The cardiac action potential & conduction.
