Cardiac Conduction System

In the heart, there are two important types of cells: cells that form the conduction system and cells that form the working myocardium (myocardium = cardiac muscle tissue). The conduction system contains cells that generate and conduct electrical impulses. The working myocardium is composed of cells that respond to these electrical impulses.

Anatomically, the conduction system consists of 5 basic parts. The first part is the sinoatrial node, also called the primary pacemaker, because it generates electrical impulses. When the sinoatrial node has generated the signal, it is then conducted to the atrioventricular node. From there the signal goes to the bundle of His and then through the left and right bundle branches, which are also sometimes called Tawara branches. The last part are the Purkinje fibres, which further transmit the impulses.

The cells of the conduction system are very special in the fact that they don’t have a constant membrane resting potential. After the conduction system cell has generated an action potential, its membrane potential will immediately start to depolarize until it reaches a certain value called threshold. When the membrane potential reaches threshold, another action potential is elicited. And when this action potential potential is over, the membrane potential depolarizes again and so on and so on. That's what we mean by saying that the cells of the conduction system don't have a resting membrane potential: they always spontaneously depolarize.

The mechanism of eliciting an action potential is as follows. The first thing that happens is that sodium ions enter the cell and because they are positively charged, they cause depolarization. When the membrane potential reaches threshold (because of this depolarization), an action potential is elicited and positively charged calcium ions enter the cell. At around 10 millivolts, the membrane potential starts to repolarize as potassium ions leave the cell. Because they are positively charged, the membrane potential becomes more and more negative until it reaches the value of around -70 millivolts and the process repeats again.

All parts of the conduction system don’t have a resting membrane potential and spontaneously depolarize; however, the pacemaker cell is the sinoatrial node. It’s because the sinoatrial node has the highest rhythm in which it depolarizes. It’s around 60 to 100 a minute. The other parts are a bit slower. However, if theoretically the sinoatrial node wasn’t working properly, then the atrioventricular system would become the pacemaker with the frequency of around 40 to 60.

One of the most important characteristics of the heart is automaticity. Automaticity means that the heart is able to generate its own impulses. So, if, hypothetically, you took the heart out of the body but provided enough nutrients, it would still contract regularly. However, the heart also needs to adjust to external circumstances, such as exercise, for example, when we need the heart to beat faster. There are three main substances that help us to modulate heart action and those are acetylcholine, norepinephrine, and epinephrine. These three substances can change what is known as chronotropism and dromotropism. Chronotropism refers to the rate of impulse generation (= how often are the impulse generated) and dromotropism to the velocity of impulse conduction (= how quickly the signal spreads).

Norepinephrine and epinephrine have a positive chronotropic effect which means that they stimulate the heart to generate contraction impulses more frequently. They also have a positive dromotropic effect which simply means that they stimulate faster conduction of the contraction impulse. Simple said, because of norepinephrine and epinephrine our hearts will beat faster. On the other hand, acetylcholine has the opposite effect, decreasing the rate of impulse generation and also the velocity of impulse conduction. This means that it has a negative chronotropic and dromotropic effect. And as a result, our hearts beat more slowly.

Now, let's look at these three substances in more detail. Norepinephrine is released by the sympathetic nerve fibres and epinephrine is found in plasma. When they bind to so-called β1-adrenergic receptors, there's a higher permeability of the cell membrane to sodium. We said that after an action potential the cell starts to depolarize because of sodium ions entering the cell. Now, if the cell membrane is more permeable to sodium, the membrane potential can reach the threshold faster and the same goes for the action potential. This is important in clinical medicine because if you give your patient the so-called beta blockers, you inhibit the binding of epinephrine and norepinephrine to these receptors and then the heart beats more slowly which can help with hypertension (high blood pressure).

Acetylcholine, on the other hand, is released by parasympathetic fibres of the vagus nerve, the tenth cranial nerve. Acetylcholine binds to muscarinic cholinoceptors (M-cholinoceptors), which results in higher permeability of the cell membrane to potassium. Remember when we said that when potassium leaves the cell, the membrane potential repolarizes? Well, if the membrane is more permeable to potassium and more potassium leaves, the membrane potential will become even more negative than usual and then it will be much more difficult for the membrane potential to reach threshold. This essentially means that because it will take more time to elicit an action potential and the heart will beat more slowly.

References:
Costanzo, L. S. (2018). Physiology. Elsevier.
Hall, J. E., Hall, M. E., & Guyton, A. C. (2021). Guyton and Hall Textbook of Medical Physiology. Elsevier.
Silbernagl, S., & Despopoulos, A. (2015). Color atlas of physiology. Thieme.