Introduction

An action potential is a brief change in the electrical charge across a cell's membrane. In the heart it passes from cell to cell, and in each muscle cell it starts a contraction. A cardiac action potential lasts about 250 to 300 ms, about a hundred times longer than one in a nerve.

The heart has two main types of cell:

• Contractile cells, the muscle cells of the atria and ventricles. They rest at a steady charge, fire quickly, and then hold their charge for a long time (the plateau).
• Pacemaker cells, in the sinoatrial (SA) and atrioventricular (AV) nodes. They never rest: their charge rises slowly by itself until they fire. They are the subject of the next chapter.

This chapter follows a muscle cell of the ventricle.

The resting membrane potential

At rest, the inside of the cell is about 90 mV more negative than the outside. This difference is the membrane potential. It comes from three ions, each kept at a different concentration on each side of the membrane:

Ions cross the membrane only through channels, protein pores that open and close. At rest, most of the open channels let K⁺ through. K⁺ leaks out, carrying positive charge with it, and the inside is left negative.

A pump in the membrane uses energy to push Na⁺ back out and bring K⁺ back in. It keeps the concentrations the same from beat to beat.

The ions that move

The whole action potential comes from three ions crossing the membrane:

• Na⁺ moving in makes the inside positive. It fires the cell.
• Ca²⁺ moving in keeps the inside positive for longer, and starts the contraction.
• K⁺ moving out makes the inside negative again. It holds the cell at rest and brings it back to rest.

Positive charge moving in makes the inside more positive (depolarisation). Positive charge moving out makes it more negative again (repolarisation).

Reading the figures

Each figure shows the same ventricular cell, drawn by the model that builds the ECG elsewhere on this site, at 75 beats a minute: two action potentials, 800 ms apart. The phases are numbered 0 to 4 and keep the same colour in every figure.

Under the first figure, one bar for each ion shows when it moves: dark for the main flow at that moment, grey for a smaller one. The phase figures below each highlight one phase. Phases 0 and 1 last only a few milliseconds, so their figures add a magnified view of the first 40 ms.

Phase 4: the resting membrane potential

Between beats the cell rests at about −90 mV.

• K⁺ channels are open, and a little K⁺ leaks out. This keeps the inside negative.
• Na⁺ and Ca²⁺ channels are closed.
• The pump keeps returning Na⁺ out and K⁺ in.

A healthy ventricular cell does not fire on its own. It waits in phase 4 until a neighbouring cell fires and passes its charge on.

Phase 0: rapid depolarisation

A neighbouring cell's positive charge spreads into this cell and lifts its inside to about −65 mV, the threshold.

• At threshold, the Na⁺ channels open.
• Na⁺ rushes into the cell, because there is much more Na⁺ outside and the inside is negative.
• Each Na⁺ that enters opens more Na⁺ channels, so the rise speeds itself up.
• The inside swings from −90 to about +30 mV in one to two milliseconds.

Within a millisecond or two the Na⁺ channels close and lock shut. They cannot open again until the cell has returned to rest. This is why the cell cannot be fired again straight away.

The more Na⁺ channels a cell has ready, the faster it fires, and the faster it passes the signal on to the next cell.

Phase 1: early rapid repolarisation

At the peak, the Na⁺ channels close, and Na⁺ stops entering.

• A brief set of K⁺ channels opens, and K⁺ moves out.
• The inside becomes a little less positive. This makes a small notch at the top of the action potential.

The notch is deeper in some parts of the heart than others: deepest in the outer layer of the ventricle (the epicardium).

Phase 2: the plateau

This is the phase that makes heart muscle different from nerve and skeletal muscle. For about 200 ms the inside stays near 0 mV.

• Ca²⁺ channels open, and Ca²⁺ moves into the cell. This adds positive charge.
• At the same time, more K⁺ channels open slowly, and K⁺ moves out. This removes positive charge.
• The two flows almost balance, so the charge hardly changes.

The Ca²⁺ that enters also does a second job. It makes the cell release a much larger store of Ca²⁺ from inside it, and this Ca²⁺ makes the cell contract. The plateau links the electrical signal to the heartbeat.

Phase 3: final rapid repolarisation

At the end of the plateau:

• The Ca²⁺ channels close, and Ca²⁺ stops entering.
• More and more K⁺ channels are open, and K⁺ moves out quickly.
• With positive charge now only leaving, the inside falls back to −90 mV.

The cell is back in phase 4, ready for the next beat.

The faster the heart beats, the shorter the action potential becomes, so that each beat has time to finish before the next.

Refractoriness

After it fires, a cell cannot fire again until its Na⁺ channels have unlocked. They unlock only as the cell returns towards rest.

• The absolute refractory period lasts from the upstroke to about −50 mV in phase 3. During it, the cell cannot fire at all, however strong the stimulus.
• The relative refractory period lasts from there to the end of phase 3. Some Na⁺ channels have unlocked: a strong stimulus can fire the cell, but the action potential is weaker and spreads more slowly.

On the ECG, the absolute refractory period of the ventricles ends at about the peak of the T wave, and the relative refractory period matches its downslope. A beat that arrives in this window can start a dangerous rhythm.

The long action potential matters for two reasons:

• The heart cannot stay contracted. Skeletal muscle stimulated fast enough stays contracted. Heart muscle cannot fire again until it has begun to relax, so the chambers always relax and refill between beats.
• Calcium from outside helps the contraction. The Ca²⁺ that enters during the plateau starts the release of the cell's own Ca²⁺ store.

Not every cell is the same

This chapter follows a ventricular cell. Other heart cells have the same phases, with different proportions:

• Atrial cells have a shorter action potential, with a lower, sloping plateau.
• Purkinje fibres, the fast wiring of the ventricles, fire fastest and have the longest action potential. They pass the signal on at 2 to 3 metres a second.
• Across the ventricular wall, the action potential is longest in the middle layer and shortest in the outer layer (the epicardium).

Cardiac AP to ECG shows these tissues together ("All together"), and how each one's action potential contributes to the ECG.

Introduction

An action potential is a brief, self-propagating reversal of the membrane potential. In the heart it spreads from cell to cell through gap junctions, and in each working cell it triggers contraction. A cardiac action potential lasts about 250 to 300 ms at a resting heart rate, a hundred times longer than one in a nerve axon or a skeletal muscle fibre. Its shape also differs between cell types.

The heart has two main types of cell:

• Contractile cells (working cardiomyocytes), in the atria and ventricles. They have a stable resting membrane potential, a fast upstroke and a long plateau.
• Pacemaker cells, in the sinoatrial (SA) and atrioventricular (AV) nodes. They have no stable resting potential. Their potential rises slowly by itself until they fire, with a slow upstroke and no plateau. They are the subject of the next chapter.

This chapter follows a contractile cell of the ventricle, the "typical" action potential from which the five phases are named.

The resting membrane potential

At rest, the inside of a ventricular cell is about 90 mV negative to the outside. Two things set this potential: the concentration gradient of each ion across the membrane, and how permeable the membrane is to each ion.

An ion's equilibrium potential is the membrane potential at which its electrical gradient exactly balances its concentration gradient, so it has no net movement. At rest the membrane is far more permeable to K⁺ than to Na⁺, Ca²⁺ or Cl⁻. The resting potential therefore lies close to the equilibrium potential of K⁺.

Two transporters keep the gradients in place:

• The Na⁺/K⁺-ATPase moves 3 Na⁺ out of the cell for every 2 K⁺ in. Because it moves more positive charge out than in, it also adds a little to the negative resting potential.
• The Na⁺/Ca²⁺ exchanger (NCX) exchanges 3 Na⁺ for 1 Ca²⁺. Its direction depends on the membrane potential and the Na⁺ and Ca²⁺ gradients. During diastole it removes Ca²⁺ from the cell.

The currents

An ionic current is named by its ion: I_Na is the Na⁺ current. An inward current carries positive charge into the cell and depolarises it, making the inside less negative. An outward current carries positive charge out and repolarises it. Four groups of time-dependent currents shape the cardiac action potential:

• I_Na, the fast Na⁺ current. It depolarises contractile cells.
• I_Ca,L, the L-type Ca²⁺ current. It holds the plateau of contractile cells and triggers their contraction. In pacemaker cells it carries the upstroke.
• The K⁺ currents (I_K1, I_to, I_Kr, I_Ks). They set the resting potential and repolarise every type of cardiac cell.
• I_f, the "funny" current. It contributes to the spontaneous depolarisation of pacemaker cells. Contractile cells have little of it.

Reading the figures

Each figure shows the same ventricular cell, drawn by the model that builds the ECG elsewhere on this site, at 75 beats a minute: two action potentials, 800 ms apart. The phases are numbered 0 to 4 and keep the same colour in every figure.

Under the first figure, one bar for each main current shows when it flows. A dark bar means the channels are open; a grey bar means they are opening or closing; a thin line means they are closed. The phase figures below each highlight one phase on both action potentials. Phases 0 and 1 last only a few milliseconds, so their figures add a magnified view of the first 40 ms.

Phase 4: the resting membrane potential

Between action potentials, during diastole, a ventricular cell rests at about −90 mV. The current that holds it there is I_K1, carried by inward rectifier K⁺ channels (Kir). They are open at rest, so the membrane's high K⁺ permeability keeps the potential near the equilibrium potential of K⁺.

Inward rectification means that these channels conduct well near the resting potential but close when the membrane depolarises. As a result, I_K1 holds the resting potential firmly, yet it does not oppose the plateau later.

A healthy ventricular cell does not fire on its own. It stays in phase 4 until current from a depolarised neighbour reaches it.

Phase 0: rapid depolarisation

Current flowing through gap junctions from an activated neighbour depolarises the cell. When the membrane reaches the threshold potential, about −70 to −55 mV, voltage-gated Na⁺ channels open. These are Nav1.5 channels, encoded by the gene SCN5A.

• Na⁺ enters the cell down its electrochemical gradient. This is I_Na.
• The entry of Na⁺ depolarises the membrane further, which opens more Na⁺ channels: a positive feedback.
• The membrane potential rises to about +30 mV in one to two milliseconds. It moves towards the equilibrium potential of Na⁺, but does not reach it.
• I_K1 channels close as the membrane depolarises, which removes their opposing outward current.

Each Na⁺ channel has an activation gate, which opens with depolarisation, and an inactivation gate, which closes a millisecond or two later. Once inactivated, a channel cannot open again until the membrane repolarises. This is the basis of refractoriness.

The rate of rise of phase 0 depends on how many Na⁺ channels are available. It determines how fast the impulse conducts from cell to cell: fewer available channels give a slower upstroke and slower conduction.

Phase 1: early rapid repolarisation

At the peak of phase 0 the Na⁺ channels inactivate, and I_Na stops. At the same time, a transient outward K⁺ current, I_to, flows through Kv4.3 channels, and a Ca²⁺-activated Cl⁻ current adds to it. These outward currents repolarise the membrane a little, which forms a notch.

The depth of the notch depends on the density of I_to channels. It is large in the epicardium, where it gives a "spike and dome" shape, and small in the endocardium. The potential at the end of phase 1 sets the starting level of the plateau, and through it the Ca²⁺ current of phase 2.

Phase 2: the plateau

The plateau is what distinguishes the cardiac action potential from that of nerve and skeletal muscle. For about 200 ms the membrane potential stays near 0 mV, because the inward and outward currents are almost balanced.

The inward current is mainly I_Ca,L, through L-type Ca²⁺ channels (Cav1.2). They activate when the membrane depolarises above about −45 mV. They open and inactivate much more slowly than Na⁺ channels, so they carry current only after the Na⁺ channels have closed, and for much longer. The Na⁺/Ca²⁺ exchanger also carries current during the plateau.

The outward currents are the delayed rectifier K⁺ currents. They activate slowly during the plateau:

• I_Kr, the rapid component, through Kv11.1 channels. Its gene, KCNH2, was formerly called hERG.
• I_Ks, the slow component, through Kv7.1 channels.

Because the net current is small, the potential changes little. The plateau slopes down gently as the Ca²⁺ current wanes and the K⁺ currents grow.

The Ca²⁺ that enters during the plateau has a second role. It opens the ryanodine receptors (RyR2) of the sarcoplasmic reticulum, which release a much larger amount of Ca²⁺ into the cytoplasm. This calcium-induced calcium release starts contraction. The plateau links the electrical event to the mechanical one.

Phase 3: final rapid repolarisation

Towards the end of the plateau, the L-type Ca²⁺ channels inactivate. Their inactivation depends on both voltage and the rising intracellular Ca²⁺. Meanwhile the delayed rectifier currents keep increasing. The outward current now exceeds the inward current, and the membrane repolarises.

• I_Kr, then I_Ks, carry most of the early repolarisation.
• As the potential falls, the inward rectifier channels open again. I_K1 grows as the membrane repolarises, which accelerates the final part of phase 3 and returns the cell to about −90 mV.
• The delayed rectifier channels close again near the resting potential.

Because the resting potential is already close to the equilibrium potential of K⁺, a ventricular action potential has no after-hyperpolarisation.

Several K⁺ currents can repolarise the cell, so the loss of one is partly covered by the others. This redundancy is called the repolarisation reserve.

The action potential shortens as the heart rate rises, so that each beat still has time to repolarise and relax before the next.

Refractoriness

A cell cannot fire again until its Na⁺ channels have recovered from inactivation, and they recover only as the membrane repolarises.

• The absolute refractory period lasts from the start of phase 0 to about −50 mV in phase 3. During it, no stimulus, however strong, can start a new action potential.
• The relative refractory period lasts from there to the end of phase 3. A stimulus stronger than normal can start a new action potential, but its upstroke is slower and smaller, because fewer Na⁺ channels have recovered, and it conducts more slowly.

On the ECG, the absolute refractory period of the ventricles ends at about the peak of the T wave, and the relative refractory period corresponds to its downslope. A premature stimulus in this vulnerable period can start a ventricular arrhythmia.

The long action potential has two important consequences:

• The heart cannot be tetanised. Skeletal muscle stimulated fast enough stays contracted (tetanus). In heart muscle the refractory period lasts almost as long as the contraction, so a second action potential cannot start until the muscle has begun to relax. The chambers relax and refill between beats.
• Extracellular Ca²⁺ contributes to contraction. The Ca²⁺ that enters during the plateau triggers the release of stored Ca²⁺, and the size of the plateau current helps set the force of contraction.

Not every cell is the same

The action potential described here is that of a ventricular cell. Other contractile and conducting cells have the same phases with different proportions:

• Atrial cells have a shorter action potential, with a lower, more sloping plateau.
• Purkinje fibres have the fastest upstroke and the longest action potential. They have many Nav1.5 channels and conduct at 2 to 3 m/s.
• Within the ventricular wall, the action potential is longest in the mid-myocardium, shorter in the endocardium and shortest in the epicardium. The differences come mainly from the density of K⁺ channels, especially Kv4.3 (I_to).

Cardiac AP to ECG shows these tissues together ("All together"), and how each one's action potential contributes to the ECG.