Cardiac pacemaker

The contractions of the heart are controlled by electrical impulses, these fire at a rate which controls the beat of the heart.

The cells that create these rhythmical impulses are called pacemaker cells, and they directly control the heart rate[?]. Artificial devices also called pacemakers can be used after heart failure to produce these impulses synthetically.

Table of contents 1 Control via the SA node 2 Generation of action potentials 2.1 Phase 4 - Pacemaker potential 2.2 Phase 0 - Upstroke 2.3 Phase 3 - Repolarisation 3 Control of heart rate 3.1 Sympathetic stimulation 3.2 Parasympathetic stimulation 3.3 Hormonal effects

Control via the SA node Although all of the hearts cells possess the ability to generate these electrical impulses, (or action potentials), a specialised portion of the heart, called the sinoatrial node (SA node), is responsible for the whole heart's beat.

The sinoatrial node is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava. These cells are modified cardiac myocytes[?]. They possess some contractile filaments, though they do not contract.

These cells will naturally discharge action potentials at about 70-80 times/minute. Because the sinoatrial node is responsible for the rest of the heart's contractions, it is sometimes called the primary pacemaker.

If, for some reason, the sinoatrial node doesn't function, a group of cells further down the heart will become the heart's pacemaker. These cells form the AV node, which is an area between the atria and ventricles, within the atrial septum.

These cells normally discharge at about 40-60 beats per minute, and are called the secondary pacemaker.

Further down the electrical conducting system of the heart, the Bundle of His, the left and right branches of this bundle, and the Purkinje fibres, will also produce a spontaneous action potential. These tertiary pacemakers fire at a rate between 30-40 per minute.

Even individual cardiac muscle cells will contract rhythmically on their own.

The reason the SA node controls the whole heart, is that its action potentials are released first, this triggers other cells to generate their own action potentials. In the muscle cells, this will produce contraction. The action potential generated by the SA node, passes down the cardiac conduction system, and arrives before the other cells have had a chance to generate their own spontaneous action potential.

Generation of action potentials There are three main stages in the generation of an action potential in a pacemaker cell. Since the stages are analogous to contraction of cardiac muscle cells, they have the same naming system. This can lead to some confusion. There is no phase one or two, just phases zero, three and four.

Phase 4 - Pacemaker potential

The key to the rhythmical firing of pacemaker cells is that, unlike muscle and neurons, these cells will slowly depolarise by themselves.

As in all other cells, the resting potential of a pacemaker cell (-60mV to -70mV) is caused by a continuous outflow or "leak" of potassium ions through ion channel proteins in the membrane that surrounds the cells. The difference is that this potassium permeability decreases as time goes on, partly causing the slow depolarisation. As well as this, there is an slow inward flow of sodium, called the 'funny' current. This all serves to make the cell more positive.

This relatively slow depolarisation continues until the threshold potential is reached. Threshold is between -40mV and -50mV. When threshold is reached, the cells enter phase 0.

Phase 0 - Upstroke

Though much faster than the depolarisation caused by the funny current and decrease in potassium permeability above, the upstroke in a pacemaker cell is relatively slow compared to that in an axon.

The SA and AV node do not have fast sodium channels like neurons, and the depolarisation is mainly caused by a slow influx of calcium ions. (The funny current also increases). The calcium is let into the cell by voltage-sensitive calcium channels, that opened when the threshold was reached.

Phase 3 - Repolarisation

The calcium channels are rapidly inactivated, soon after they opened. Sodium permeability is also decreased.

Potassium permeability is increased, and the efflux of potassium (loss of positive ions) slowly repolarises the cell.

Control of heart rate The heart gets its parasympathetic innervation from the vagus nerve. Signals from this nerve cause the heart rate to decrease.

Sympathetic stimulation comes from the cardiac nerves[?] from the sympathetic chain[?]. Activity in these nerves acts to increase heart rate.

Sympathetic stimulation

When the SA node receives sympathetic stimulation, noradrenaline released from the nerve endings binds to β₁-adrenergic receptors on the pacemaker cell membrane.

This binding causes cyclic AMP production within the cell. This directly increases the funny current, meaning sodium is continually entering the cell more quickly. Cyclic AMP also activates a protein kinase, that phosphorylates the calcium channels, increasing calcium conductance into the cell.

Because both sodium, and calcium can enter the cell more quickly, the continuously natural depolarisation (phase 4) reaches threshold more quickly. So action potentials are generated more frequently.

It takes a while for the heart rate to increase after noradrenaline is released.

Parasympathetic stimulation

Acetylcholine (ACh) is released from the vagus nerve endings, and binds to muscarinic receptors[?] on the pacemaker cells.

In the pacemaker cells, there are ACh sensitive potassium channels. These open in response to ACh binding, potassium ions leak out, and the cell gets hyperpolarised (more negative). The funny current is also reduced by ACh. This means sodium ions enter more slowly, and it takes longer for the cell to reach threshold. Thus the heart rate slows.

Unlike in the sympathetic mechanism, the heart will slow quite soon after vagal stimulation.

Hormonal effects

Noradrenaline and adrenaline are both released into the bloodstream by the adrenal medulla[?].

They have the same action on heart rate as direct sympathetic stimulation.