Ventricular action potential: phases 0 to 4 and their ion currents
A ventricular muscle cell takes about a quarter of a second to fire. Match each phase to its ion current, then to the antiarrhythmic class that acts on it.
Chapters (10)
Relate phases 0–4 of the ventricular myocyte action potential to the ion currents responsible and to the antiarrhythmic classes that target them (class I phase 0, class IV the plateau, class III phase 3).
The short version
- Membrane voltage is pulled towards the equilibrium potential of the ion with the highest conductance; each phase is a change in which ion is winning.
- Phase 0 is fast sodium in, 1 a little potassium out (Ito), 2 calcium in, 3 potassium out, 4 rest.
- The plateau (about 175 ms) is calcium entry, and that calcium triggers further calcium release from the sarcoplasmic reticulum, which makes the cell contract.
- Fast sodium channels are inactivated from the end of phase 0 through phase 3 and into early phase 4, so no new action potential can start: this is the effective refractory period.
- Class I drugs flatten the slope of phase 0, class IV acts on the plateau, and class III delays phase 3 and lengthens the refractory period.
Why is the ventricular action potential so long?
A skeletal muscle fibre fires an action potential in two to five milliseconds. A ventricular muscle cell takes about a quarter of a second.[1][2]
This lesson on the ventricular action potential explains why the heart makes its cells wait so long. The aim is to match phases 0 to 4 to the ion currents behind them, and to the drugs that target each one.
The tug of war: which ion is winning
The membrane voltage is pulled towards the equilibrium potential of whichever ion has the highest conductance, meaning the most open channels.[1]
- Potassium pulls towards about −96 mV.
- Sodium pulls towards about +50 mV.
- Calcium pulls towards well above that (about +134 mV).
Every phase of the action potential is just a change in which ion is winning.[1]
Ventricular action potential phases 0–4, one by one
| Phase | What happens | Main current |
|---|---|---|
| 4 (rest) | K⁺ channels open; the cell sits near −90 mV. Fast Na⁺ and L-type Ca²⁺ channels are closed. | Resting K⁺ conductance |
| 0 | Threshold about −70 mV; Na⁺ rushes in and the voltage shoots up to about +30 mV in 3–5 ms. | Fast Na⁺ current |
| 1 | Na⁺ channels inactivate; a brief outward K⁺ current takes a small notch off the peak. | Transient outward K⁺ (Ito) |
| 2 (plateau) | L-type Ca²⁺ channels open at about −40 mV; Ca²⁺ flows in while K⁺ flows out, and the voltage barely moves (about 175 ms). | L-type Ca²⁺ current |
| 3 | Ca²⁺ channels inactivate and delayed rectifier K⁺ channels, including the rapid one, take over; K⁺ pours out and the voltage falls back to rest. | Delayed rectifier K⁺ (IKr) |
Phase 0 is the sodium current, and its slope sets how fast the impulse conducts.[1] The peak, about +30 mV, stays short of the sodium equilibrium potential because the sodium channels inactivate.[1]
The plateau is calcium entry, and that calcium triggers more calcium release from the sarcoplasmic reticulum, which makes the cell contract.[3]
The refractory period: why the long plateau protects the ventricle
The whole event lasts about 250–300 ms. From the end of phase 0 through phase 3 and into early phase 4, the fast sodium channels are inactivated or only just recovering.[1][2]
So no new action potential can start. This is the effective refractory period. It gives the ventricle time to relax and fill, and stops it locking into tetany.[1][2]
Antiarrhythmic drugs by phase: classes I, IV and III
Classes I, IV and III each target one phase of the ventricular action potential.[1][3]
| Class | Target | Effect on the action potential |
|---|---|---|
| I | Sodium channels | Flatten the slope of phase 0 |
| IV | L-type calcium channels (verapamil, diltiazem) | Block L-type Ca²⁺ entry, which acts on the plateau |
| III | Potassium channels | Delay phase 3 and lengthen the refractory period |
Slower repolarization shows up as a longer QT interval, and too much of it risks torsades de pointes.[3]
Three things to keep
- The five phasesZero sodium in, one potassium out, two calcium in, three potassium out, four rest.
- The long plateauIt gives a long refractory period that protects the ventricle.
- The drug classesClass I hits phase 0, class IV the plateau, class III phase 3.
Next in the series: how sinoatrial node cells fire without a push, in the heart's own pacemaker.
Practice question
Original · USMLE styleA 61-year-old man with recurrent sustained ventricular tachycardia is started on an experimental antiarrhythmic drug in a clinical pharmacology study. Intracellular recordings from an isolated ventricular myocyte are made before and after exposure to the drug. The resting membrane potential, peak potential and maximum upstroke velocity are unchanged. The plateau is longer, and the action potential duration increases from 270 ms to 350 ms.
Common questions
What are the phases of the ventricular action potential?
Phase 0 is fast sodium in, phase 1 a brief transient outward potassium current, phase 2 the calcium plateau, phase 3 delayed rectifier potassium out, and phase 4 the resting state near −90 mV.
Why is the cardiac action potential so much longer than in skeletal muscle?
Skeletal muscle fires in about 2–5 ms; the ventricular event lasts about 250–300 ms. The difference is the plateau, about 175 ms, where calcium entering balances potassium leaving.
What is the effective refractory period?
It is the stretch from the end of phase 0 into early phase 4 when fast sodium channels are inactivated or only just recovering, so no new action potential can start. It lets the ventricle relax and fill, and stops tetany.
Which antiarrhythmic class acts on which phase?
Class I drugs block sodium channels and flatten phase 0, class IV calcium channel blockers act on the plateau, and class III drugs block potassium channels, delaying phase 3.
Transcript
Read the full narration, by chapter687 words
0:00Why does the heart wait so long?
A skeletal muscle fibre fires an action potential in two to five milliseconds. A ventricular muscle cell takes about a quarter of a second. Why would the heart make its cells wait so long? Today: match phases zero to four of the ventricular action potential to the ion currents behind them, and to the drugs that target each one.
0:21The tug of war: which ion is winning
Start with the tug of war. The membrane voltage is pulled towards the equilibrium potential of whichever ion has the highest conductance, the most open channels. Potassium pulls towards about minus 96 millivolts. Sodium pulls towards plus 50. Calcium pulls towards well above that. Every phase of the action potential is just a change in which ion is winning.
0:46Phase 4: the resting state
Phase four is the resting state. Potassium channels are open, so the cell sits near minus 90 millivolts. Fast sodium channels and L-type calcium channels are closed.
0:58Threshold and phase 0: fast sodium in
Now a neighbouring cell depolarizes ours to threshold, about minus 70 millivolts. Phase zero: fast sodium channels open, sodium rushes in, and the voltage shoots up to about plus 30 millivolts in three to five milliseconds. Phase zero is the sodium current, and its slope sets how fast the impulse conducts.
1:20Phases 1 and 2: Ito and the calcium plateau
Phase one: the sodium channels inactivate, and a brief transient outward potassium current takes a small notch off the peak. Phase two is the plateau, lasting about 175 milliseconds. L-type calcium channels open at about minus 40 millivolts, and calcium flows in while potassium flows out. Inward and outward currents balance, so the voltage barely moves. The plateau is calcium entry, and that calcium triggers more calcium release from the sarcoplasmic reticulum, which makes the cell contract.
1:57Phase 3: delayed rectifier potassium out
Phase three: the calcium channels inactivate, and delayed rectifier potassium channels, including the rapid one, take over. Potassium pours out, and the voltage falls back to the resting level. Zero, sodium in. One, a little potassium out. Two, calcium in. Three, potassium out. Four, rest. Now back to our puzzle.
2:24The effective refractory period
The whole event lasts about 250 to 300 milliseconds. Through phases zero to three, and early phase four, the fast sodium channels stay inactivated. So no new action potential can start. This is the effective refractory period. That long refractory period gives the ventricle time to relax and fill, and stops it locking into tetany.
2:48Antiarrhythmic classes I, IV and III by phase
Now the drugs. Each class of antiarrhythmic targets one phase. Class one drugs block sodium channels and flatten the slope of phase zero. Class four calcium channel blockers, such as verapamil and diltiazem, act on the plateau. Class three drugs block potassium channels, delay phase three, and lengthen the refractory period. Slower repolarization shows up as a longer QT interval, and too much of it risks torsades de pointes.
3:18Practice question
Your turn. A 61-year-old man has recurrent sustained ventricular tachycardia, and starts an experimental drug. Recordings from a ventricular myocyte, before and after, show the same resting potential, the same peak and the same upstroke velocity. The plateau is longer: action potential duration rises from 270 to 350 milliseconds. Which current is most likely inhibited? A, the fast sodium current. B, the funny current. C, the rapid delayed rectifier potassium current. D, the L-type calcium current. E, the inward rectifier potassium current. Pause here and decide. A is out: blocking sodium slows the upstroke of phase zero, and the upstroke did not change. B is out: the funny current drives pacemaker cells in the sinoatrial node, and does not set the ventricular plateau. D is out: blocking calcium entry would shorten the plateau, not lengthen it. E is out: the channels that hold the resting potential were not the target, because the resting potential was unchanged. So the answer is C: blocking the rapid delayed rectifier delays phase three, which lengthens the action potential, the class three effect.
4:45Recap and next lesson
Three things to keep. One: zero sodium in, one potassium out, two calcium in, three potassium out, four rest. Two: the long plateau gives a long refractory period that protects the ventricle. Three: class one hits phase zero, class four the plateau, class three phase three. Next, we look at the heart's own pacemaker: how SA node cells fire without a push.
Sources
Numbers in the text, e.g. [1], point here- Klabunde RE. CV Physiology: Non-Pacemaker Action Potentials (A006); Cardiac Electrophysiology pages A003, A004, A009 and A010. cvphysiology.com/Arrhythmias/A006 · cvphysiology.com/Arrhythmias/A003 · cvphysiology.com/Arrhythmias/A004 · cvphysiology.com/Arrhythmias/A009 · cvphysiology.com/Arrhythmias/A010
- OpenStax. Anatomy and Physiology 2e, 19.2 Cardiac Muscle and Electrical Activity. openstax.org/books/anatomy-and-physiology-2e/pages/19-2-cardiac-muscle-and-electrical-activity
- EHRA practical compendium of antiarrhythmic drugs (2025), Europe PMC PMC12367031. europepmc.org/article/PMC/PMC12367031
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Thumbnail plate: Servier Medical Art (smart.servier.com), "Heart (sagittal overview)", licensed under CC BY 4.0, recoloured and resized. No licensed art or 3D model is used in the lesson video itself. The action potential traces, ion arrows, cell sketch, refractory-period band, class overlays, question card, pocket card and all handwriting are drawn in code (original). Ghost curves for the drug classes are schematic. Previous: EP 03 · HOCM vs Aortic Stenosis at the Bedside · Next: EP 05 · Pacemaker Cells and Autonomic Control of Heart Rate
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-CARD-013.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01S2 splitting and heart sounds S1–S4, explained5:26
- EP 02Heart murmurs and dynamic manoeuvres, from preload and afterload5:15
- EP 03HOCM vs aortic stenosis murmur: telling them apart at the bedside5:31
- EP 04Ventricular action potential: phases 0 to 4 and their ion currents5:15
- EP 05SA node pacemaker potential: phase 4 sets the heart rate5:17
- EP 06ECG waves and intervals: what P, PR, QRS, ST and QT mean5:29