Overview

Ventricular resting potential≈ −90 mV

Ventricular AP duration≈250–300 ms

SA node max diastolic potential≈ −60 mV

SA node threshold≈ −40 mV

Ventricular myocyte (fast response). The action potential has five phases.

Phase 4 is the resting potential of about −90 mV. It is maintained by inward-rectifier K⁺ channels (IK1) and the Na⁺/K⁺-ATPase.

Phase 0 is rapid depolarisation to about +20 to +30 mV through fast voltage-gated Na⁺ channels (Nav1.5). How fast this upstroke rises determines conduction velocity. Phase 0 corresponds to the QRS complex. Class I antiarrhythmic drugs act here.

Phase 1 is a brief, partial repolarisation as the Na⁺ channels inactivate and the transient outward K⁺ current (Ito) flows.

Phase 2 is the plateau, held at about 0 mV for about 200 ms. Ca²⁺ flowing in through L-type channels (Cav1.2) balances K⁺ flowing out through delayed-rectifier channels (IKs, IKr). This Ca²⁺ entry triggers Ca²⁺-induced Ca²⁺ release from the sarcoplasmic reticulum. Phase 2 corresponds to the ST segment.

Phase 3 is rapid repolarisation through IKr (hERG), IKs and IK1. It corresponds to the T wave. Class III drugs prolong it.

The whole action potential lasts about 250–300 ms. The effective refractory period covers almost all of it, so the heart cannot be tetanised and contractions cannot summate. Late in phase 3 there is a short vulnerable period, near the peak of the T wave, when an extra stimulus can trigger ventricular fibrillation ("R on T").

SA and AV nodal cells (slow response). These cells have no stable resting potential. In phase 4 they depolarise spontaneously from a maximum diastolic potential of about −60 mV. Three currents drive this: the "funny" current If through HCN channels, a mixed Na⁺/K⁺ inward current that is switched on by hyperpolarisation; T-type Ca²⁺ current late in phase 4; and a declining K⁺ current. Spontaneous Ca²⁺ release from the sarcoplasmic reticulum, through Na⁺/Ca²⁺ exchange, adds to it (the "calcium clock"). At threshold (about −40 mV), phase 0 occurs as a slow upstroke through L-type Ca²⁺ channels. Fast Na⁺ channels are inactivated at these potentials, so conduction is slow. Phase 3 is K⁺ repolarisation. There are no phases 1 or 2.

Function

Generate and conduct the impulse that triggers each heartbeat.
Trigger excitation–contraction coupling through Ca²⁺ entry during the plateau.
Protect against tetany and re-entry through the long refractory period.

Physiology

Plasma potassium has a strong effect on these potentials. Hyperkalaemia makes the resting potential less negative, which inactivates Na⁺ channels and slows conduction. The ECG shows peaked T waves, then flattened P waves, a broad QRS and finally a sine-wave pattern before VF or asystole. Hypokalaemia produces U waves, increases automaticity and makes digoxin toxicity worse.

Calcium mainly affects the QT interval. Hypercalcaemia shortens it and hypocalcaemia lengthens it.

Clinical significance

Antiarrhythmic drug classes (Vaughan Williams)

Class I drugs block Na⁺ channels (for example lidocaine, flecainide). Class II drugs are β-blockers. Class III drugs block K⁺ channels and prolong the QT interval (for example amiodarone, sotalol). Class IV drugs are non-dihydropyridine Ca²⁺ channel blockers (verapamil, diltiazem). Adenosine, digoxin and ivabradine, which blocks If, act through other mechanisms.

Long QT and torsades de pointes

The QT interval can be prolonged by inherited ion-channel disorders. The main types are LQT1 (KCNQ1 gene, IKs), LQT2 (hERG gene, IKr) and LQT3 (SCN5A gene, late Na⁺ current). It can also be acquired, from drugs (macrolides, antipsychotics, ondansetron, methadone) or from low potassium or magnesium. Abnormal depolarisations during phase 3 (early afterdepolarisations) can trigger torsades de pointes, a twisting ventricular tachycardia. It is treated with IV magnesium.

Brugada syndrome

Brugada syndrome is usually caused by a loss-of-function mutation in the Na⁺ channel gene SCN5A. The ECG shows coved ST elevation in V1–V2. Patients are at risk of ventricular fibrillation and sudden death, typically during sleep or fever.

Compiled from standard anatomy and physiology references — see the Cardiovascular System sources. For education only; not medical advice.