Part of the TeachMe Series

Cardiac Pacemaker Cells

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Original Author(s): Chloe Hill
Last updated: 17th July 2023
Revisions: 31

Original Author(s): Chloe Hill
Last updated: 17th July 2023
Revisions: 31

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In the heart, electrical impulses are generated by specialised pacemaker cells and spread across the myocardium in order to produce a co-ordinated contraction in systole. An action potential generated is generated by a change in the potential difference between the inside and outside of the cell. The particular action potential generated by cardiac pacemaker cells is very different from that of ventricular myocardial cells. In this article, we will discuss cardiac pacemaker cells and the action potential they generate in more detail.

Pacemaker Cells

Cardiac pacemaker cells are mostly found in the sinoatrial node (SAN), which is situated in the upper part of the wall of the right atrium. These cells have natural automaticity, meaning they can generate their own action potentials.

Fig 1 – The conduction system of the heart.

The atrioventricular node (AVN) and the Purkinje fibres also latent pacemaker cells, meaning they have cells capable of pacemaker activity. However, the pacemaker cells with the fastest pacing rate dictate the rate for all other cells, so as their natural rate is much slower than the SAN’s, they are normally overridden.

Action potential in sinoatrial node

The action potential in the SA node occurs in three phases which are discussed below.

Phase 4 – Pacemaker potential

The pacemaker potential occurs at the end of one action potential and just before the start of the next. It is the slow depolarisation of the pacemaker cells e.g. cells of the sinoatrial node, towards the membrane potential threshold. This is sometimes referred to as the ‘funny’ current, or If.

The pacemaker potential is achieved by activation of hyperpolarisation activated cyclic nucleotide gated channels (HCN channels). These allow Na+ entry into the cells, enabling slow depolarisation. These channels are activated when the membrane potential is lower than -50mV. Once the membrane potential gets depolarised to reach the threshold, an action potential can be fired.

Phase 0 – Depolarisation

Once the HCN channels have brought the membrane potential to around -40mV, voltage-gated calcium channels open. This allows an influx of Ca2+  which produces a faster rate of depolarisation to reach a positive membrane potential (responsible for the upstroke of the action potential). HCN channels then start to inactivate. At the peak of the action potential, Ca2+ channels inactivate, and K+ channels open.

Phase 3 – Repolarisation

Once the Ca2+ channels inactivate, and the K+ channels open, there is an efflux of K+ ions out of the cells. This results in the repolarisation of the membrane, which is seen as the downstroke of the action potential.  

Unlike the ventricular action potential, the opening of Ca2+ channels is not sustained, and there is no ‘plateau’ stage. Therefore, the action potential is triangular in shape. After the action potential, repolarisation must occur and the membrane potential must reach negative values. This allows the HCN channels to be reactivated again, enabling another action potential to be generated (phase 4).

Fig 2 – Diagram showing the action potential in cardiac pacemaker cells and the main ion movements at each stage.

Control by the Autonomic Nervous System

The autonomic nervous system (ANS) alters the slope of the pacemaker potential, in order to alter heart rate.

Heart rate is affected by both the parasympathetic and sympathetic branches of the ANS, which innervate both the SAN and AVN.

  • Parasympathetic activity is mediated via acetylcholine acting on M2 muscarinic receptors at the SAN. This lengthens the interval between pacemaker potentials, hence slowing heart rate.
  • Sympathetic activity is mediated via noradrenaline acting on B1 adrenoceptors. This shortens the interval between impulses by making the pacemaker potential steeper, hence increasing the heart rate.

If all autonomic inputs are blocked, the intrinsic heart rate is about 100 beats per minute (bpm). The normal resting rate of about 60bpm is produced because the parasympathetic system dominates at rest. Initial increases in heart rate are brought about by a reduction in the parasympathetic outflow. Increasing sympathetic outflow allows for further increases in heart rate.

Clinical Relevance – Arrhythmias

Disturbance to the natural pacemaker activity of the heart can lead to arrhythmias i.e. a heartbeat with an irregular rate and/or rhythm.

Causes of arrhythmias include:

  • Ectopic Pacemaker Activity: This is when another area of myocardium becomes spontaneously active and its depolarisations dominate over the SAN. Latent pacemaker regions can become activated due to ischaemic damage.
  • After-Depolarisations: This is when abnormal depolarisations follow the action potential – thought to be caused by high intracellular Ca2+.
  • Re-entry loop: This occurs when the normal spread of excitation across the heart is disrupted due to a damaged area. When the conduction damage is incomplete, it allows the impulse to spread the wrong way through the damaged area and create a circle of excitation. Multiple small re-entry loops can occur in the atria, leading to atrial fibrillation.

Arrhythmias are particularly dangerous as they allow blood to collect in the heart chamber and form clots, leading to an increased risk of strokes or MIs. Additionally many arrhythmias, particularly in the ventricles, can lead to cardiac arrest. The treatments for arrhythmias is often DC cardioversion, which tries to shock the heart back into a regular rhythm, or rhythm-controlling drugs such as amiodarone.