Introduction

Pacemaker cells fire on their own. They do not wait for a neighbouring cell: each one charges up slowly by itself, fires, resets, and starts again. This is called automaticity. The fastest pacemaker cells are in the sinoatrial (SA) node. They fire about 70 times a minute at rest, so they set the heart rate.

A pacemaker action potential has only three phases: 4, 0 and 3. It has no phase 1 and no plateau. And it never rests: as soon as the cell has reset, its charge starts to rise again.

How it differs from a ventricular cell

Because a pacemaker cell's lowest point is only −60 mV, most of its fast Na⁺ channels stay locked shut. It fires with Ca²⁺ instead, which is slower.

Reading the figures

Each figure shows a cell of the SA node, drawn by the model that builds the ECG elsewhere on this site. The dashed line is the threshold, about −40 mV: the cell fires when its charge reaches it. The phases keep the same colours as in the cardiac action potential: 4 grey, 0 amber, 3 pink. 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.

Phase 4: diastolic depolarisation

After each beat the cell's charge is at its lowest, about −60 mV. Then it starts to rise by itself. This slow rise is the pacemaker potential. It is what makes the heart beat on its own.

• Special channels, the funny channels, open when the cell resets. They are unusual: most channels open when the charge rises, these open when it falls.
• Na⁺ leaks in through them, slowly, and the inside becomes less negative.
• Near the end of phase 4, some Ca²⁺ channels open as well, and the rise speeds up.

The funny channels are how the nerves of the heart change its rate: the more of them open, the steeper the rise.

Phase 0: depolarisation

When the charge reaches the threshold, about −40 mV:

• Ca²⁺ channels open, and Ca²⁺ flows into the cell.
• The inside rises to about +10 mV.

Ca²⁺ channels open much more slowly than the Na⁺ channels of a ventricular cell, so the upstroke takes tens of milliseconds, not one or two. This is also why nodal cells pass the signal on slowly. In the AV node, this slowness makes the pause between the atria and the ventricles.

Phase 3: repolarisation

• The Ca²⁺ channels close.
• K⁺ channels open, and K⁺ flows out of the cell.
• The inside falls back to about −60 mV.

At the bottom, the K⁺ channels close, the funny channels open again, and the next phase 4 begins. The cycle repeats with no outside signal.

What sets the heart rate

The heart rate is how often the SA node fires. That depends on how long phase 4 takes to reach the threshold. The steeper the rise, the sooner the cell fires.

The nerves of the heart change the slope:

• Sympathetic nerves (the "fight or flight" system) release noradrenaline. More funny channels open, phase 4 rises faster, and the heart speeds up.
• The vagus nerve releases acetylcholine. Fewer funny channels open, phase 4 rises more slowly, and the heart slows down. Acetylcholine also opens extra K⁺ channels, which lower the starting point, so the cell has further to climb.

In the figure the sympathetic cell fires at 129 a minute, the resting cell at 75, and the vagal cell at 55.

Pacemakers below the sinoatrial node

The SA node is not the only pacemaker. Other cells of the heart's wiring can fire on their own too, but more slowly. Normally the slower pacemakers do not fire on their own: the impulse from the SA node reaches each one first and fires it. Their rates below are the rates at which each would take over if that impulse stopped arriving.

Normally the SA node fires first, and its signal fires the slower pacemakers before they reach their own threshold. Each beat resets them. This is overdrive suppression: the fastest pacemaker is in charge. If the SA node stops, the next fastest takes over at its own slower rate, as an escape rhythm.

Cardiac AP to ECG shows the AV node being fired before its own phase 4 reaches threshold.

Introduction

Pacemaker cells generate action potentials spontaneously and rhythmically: they need no stimulus from a neighbouring cell. This property is called automaticity. In the healthy heart the pacemaker cells of the sinoatrial (SA) node fire fastest, about 70 times a minute at rest, and so set the heart rate. Their impulse spreads through the atria to the atrioventricular (AV) node and on to the ventricles.

A pacemaker action potential has only three phases: 4, 0 and 3. There is no phase 1 and no plateau (phase 2). Above all, there is no stable resting membrane potential. As soon as the cell has repolarised, its membrane potential begins to depolarise again, slowly, until it reaches threshold and the cell fires.

How it differs from a ventricular cell

The less negative potential has a reason. Nodal cells have few inward rectifier K⁺ channels (I_K1), which hold a ventricular cell near the equilibrium potential of K⁺. Without them the membrane potential is less negative, and at about −60 mV most fast Na⁺ channels are inactivated. The upstroke therefore has to be carried by Ca²⁺.

Reading the figures

Each figure shows a cell of the SA node, drawn by the model that builds the ECG elsewhere on this site. The dashed line is the threshold, about −40 mV. The phases keep the same colours as in the cardiac action potential: 4 grey, 0 amber, 3 pink. Under the first figure, one bar for each main current shows when it flows: dark when the channels are open, grey when they are opening or closing.

Phase 4: diastolic depolarisation

Phase 4 starts at the maximum diastolic potential, about −60 mV, the most negative point of the cycle. From there a small net inward current depolarises the membrane slowly towards threshold. This diastolic depolarisation, or pacemaker potential, is the basis of automaticity: without it, the heart would not beat spontaneously.

The main current early in phase 4 is the funny current, I_f:

• It flows through HCN channels (hyperpolarisation-activated, cyclic nucleotide-gated), mainly HCN4 in the SA node.
• Unlike other voltage-gated channels, HCN channels open when the membrane repolarises, at the end of the previous action potential. Their unusual behaviour gave the current its name.
• They are permeable to Na⁺ and K⁺. At diastolic potentials the influx of Na⁺ exceeds the efflux of K⁺, so the net current is inward and depolarising.
• cAMP binds directly to the channel and makes it open more easily (at less negative potentials). This is how the autonomic nerves change the slope of phase 4.

Late in phase 4, as the potential approaches threshold, T-type Ca²⁺ channels (Cav3.1) activate, from about −60 mV, and their inward current, I_Ca,T, accelerates the depolarisation. T-type channels are found in nodal and conducting cells, but not in the adult working myocardium.

A second mechanism also contributes: the calcium clock. Late in diastole the sarcoplasmic reticulum releases Ca²⁺ spontaneously, in small local releases. The Na⁺/Ca²⁺ exchanger removes this Ca²⁺ from the cell, exchanging 3 Na⁺ for each Ca²⁺, and so carries a net inward current, I_NCX, that adds to the depolarisation. How the membrane currents ("membrane clock") and the Ca²⁺ cycling ("calcium clock") work together is still debated. Current evidence supports a coupled system of the two.

Phase 0: depolarisation

When the membrane reaches threshold, about −40 mV, the depolarisation, helped by the T-type current, activates L-type Ca²⁺ channels (Cav1.3 and Cav1.2). They open from about −30 mV, Cav1.3 at slightly more negative potentials than Cav1.2. Ca²⁺ enters the cell, and this current, I_Ca,L, carries the upstroke to a peak of about +10 mV.

Ca²⁺ channels activate much more slowly than the fast Na⁺ channels of a ventricular cell. The upstroke takes tens of milliseconds instead of one or two, and its peak is rounded. Because the upstroke is slow, nodal cells also conduct slowly. In the AV node, this slow conduction is the delay between atrial and ventricular activation.

Phase 3: repolarisation

The L-type Ca²⁺ channels inactivate, and delayed rectifier K⁺ channels open. The efflux of K⁺, I_K, repolarises the membrane to the maximum diastolic potential.

As the membrane repolarises, two things set up the next cycle:

• The K⁺ channels deactivate, so their outward current falls.
• The HCN channels open again, and I_f starts the next diastolic depolarisation.

The cycle repeats without any external stimulus.

What sets the heart rate

The heart rate is the rate at which the SA node fires. It depends on how long phase 4 takes to reach threshold, which depends on three things:

• The slope of the diastolic depolarisation. A steeper slope reaches threshold sooner.
• The maximum diastolic potential. The more negative it is, the further the membrane has to travel.
• The threshold. The less negative it is, the further the membrane has to travel.

The autonomic nervous system changes the rate mainly through the slope:

• Sympathetic stimulation releases noradrenaline, which acts on β₁-adrenergic receptors and raises intracellular cAMP. More HCN channels open at each potential, so I_f increases and phase 4 becomes steeper. cAMP also increases the L-type Ca²⁺ current and the Ca²⁺ release of the calcium clock. The heart rate rises.
• Parasympathetic (vagal) stimulation releases acetylcholine, which acts on M₂ muscarinic receptors and lowers cAMP. I_f decreases and phase 4 becomes flatter. At higher concentrations, acetylcholine also opens acetylcholine-activated K⁺ channels (I_K,ACh), which hyperpolarise the membrane and make the maximum diastolic potential more negative. The heart rate falls.

In the figure the model changes only the slope: the sympathetic cell fires at 129 a minute, the resting cell at 75, and the vagal cell at 55.

Pacemakers below the sinoatrial node

Other cells of the conduction system also have automaticity, at slower intrinsic rates. Normally the slower pacemakers do not fire on their own: the impulse from the SA node reaches each one first and fires it. Their rates below are the rates at which each would take over if that impulse stopped arriving.

Normally the SA node fires first, and its impulse depolarises the slower pacemakers before their own phase 4 can reach threshold. Each beat resets them. This is overdrive suppression: the fastest pacemaker controls the heart. If the SA node fails, or its impulse is blocked, the next fastest pacemaker reaches threshold first and takes over as an escape rhythm, at its own slower rate.

Cardiac AP to ECG shows the AV node's action potential being fired before its phase 4 reaches threshold.