Cardiac Action Potentials

Ever wonder how your heart beats? Or why it beats faster during stressful situations? This is all thanks to cardiac action potentials! The different cardiac action potentials work together to generate a steady heartbeat. The electrical system sends an impulse along the conduction pathway to the ventricle, where the contractile system initiates contraction and pumps blood out into the body. Different inputs can speed up or slow down these systems and impact our heart rate.

 Nodal Cell Action Potential – Electrical System

You have likely studied the action potential profiles of neurons in your previous Human Physiology classes. Studying the action potential profiles help us understand how neural impulses are propagated along a circuit and result in events such as skeletal muscle contractions. In this section, we will investigate the different cell types found in the heart and how these cells differ in their action potential profiles and resulting functions. The first type of cell found within the heart are referred to as nodal cells, which comprise the electrical system. Nodal cells are excitable tissue that undergoes depolarization, which facilitates the subsequent contraction of the heart.

Nodal Cell Action Potential Profile

This diagram illustrates the action potential profile of a nodal cell within the heart, with time plotted against membrane potential. From this diagram, several characteristics of a nodal cell can be noted. For example, there are three distinct stages of the action potential: pre-potential, de-polarization, and re-polarization. In the pre-potential stage, the charge of the membrane is seen to slowly become more positive. This is due to the spontaneous depolarizing characteristic of nodal cells, which is explained later in this subchapter. During this pre-potential stage, there is a slow influx of sodium (Na+) ions into the cell, causing the membrane potential to go from around −60 millivolt (mV) to −40mV. The next phase is de-polarization, characterized by a rapid influx of calcium ions into the cell that causes a sharp spike in membrane potential reaching about +20mV. Finally, re-polarization is the third and final phase in which potassium (K+) ions are removed from the cell, and the membrane potential returns to that starting point of −60mV. The rate of nodal cell firing will depend on the location of these cells in the heart due to the orderly control of electrical activity.

As shown in figure 1, the pre-potential (yellow phase) occurs due to a slow influx of sodium ions until the threshold is reached, followed by a rapid depolarization (red phase) and re-polarization (blue phase) of the cell. The pre-potential accounts for the membrane reaching threshold and initiates the spontaneous depolarization and contraction of the cell. Note the lack of resting membrane potential.

Spontaneous Depolarizer

A spontaneous depolarizer automatically depolarizes to reach threshold without an external stimulus as they do not have a stable membrane potential. Sodium slowly flows into these cells through sodium leak channels making the inside of the cell more positive until threshold is reached and the depolarization phase can begin. The sinoatrial node (SA node) is the spontaneous depolarizer that sets the rhythm of the heart and is often called the pacemaker. In the above diagram, you can see the cell slowly depolarize from −60mV to −40mV through spontaneous depolarization.

Nodal Cell Action Potential Wave Video

This video summarizes the information covered thus far in the subchapter, explaining the process of the nodal cell action potential and how this provides the shape of the profile. The beginning of the video (until 2:15) will focus on the concept of pacemaker cells, otherwise known as nodal cells. The video emphasizes that these cells are spontaneous depolarizers, and therefore, are important for starting a contraction. The video then goes on to describe important terms such as “automaticity“, and “threshold“.

Autonomic Nervous System Impact on Nodal Cell and Heart Rate – Chronotropic Effects

Several factors can influence the firing rate of nodal cells. A key influential factor in these cells’ firing rate is the innervation of the Autonomic Nervous System branches, the Sympathetic Nervous System (SNS), and Parasympathetic Nervous System (PNS). The innervation of these systems allows them to alter the firing rate of nodal cells and therefore alter heart rate. Stimulation of the SNS will increase the firing rate and heart rate, while PNS stimulation will decrease the firing rate and heart rate. The mechanisms of these opposing systems are as follows;

SNS will increase the permeability of nodal cells to sodium (Na+), increasing the Na+ leak rate during the pre-potential phase. This results in the membrane potential reaching threshold and initiates depolarization at a quicker rate. The faster depolarization causes an increase in firing rate, which translates to an increase in heart rate.

PNS will open the ligand-gated potassium (K⁺) channels allowing the positive K⁺ ions from within the cell to flow out. This makes the inside of the cell more negative, bringing the membrane potential further away from threshold. The effect of making the membrane potential more negative and further away from threshold is known as hyperpolarization. The leak rate of Na⁺ is unchanged, however, it will take a longer period of time to accumulate enough Na⁺ to bring the membrane to threshold and spark an action potential. This results in a decrease in firing rate and therefore a decrease in heart rate.

The following diagram illustrates the alteration made to the nodal cell action potential profile as a result of SNS or PNS stimulation. (PNS stimulation is represented through an increase in vagal stimulation).

Cardiac Myocyte Action Potential – Contractile System

Cardiac Myocyte Action Potential Profile 

The second type of cell found in the heart are called cardiac myocytes, and they comprise the contractile system. The cardiac myocytes are responsible for the orderly contraction of the heart to eject blood out and into circulation. The contraction of these cells follows the electrical activity of the nodal cells; therefore, these cell types work together to ensure the efficiency of the heart. There are several distinctions between cardiac myocytes and nodal cells as they serve very different functions. For example, cardiac myocytes do not contain leaky Na⁺ channels and therefore are not spontaneous depolarizers. Another difference lies in the cardiac myocyte permeability to K⁺ as the ions do not enter the cells due to ligand-gated channels. The movement of K⁺ ions out of the cell is a result of concentration and electrical gradients.

The following diagram presents an illustration of the action potential profile of a cardiac myocyte. Similar to nodal cells, there are three distinct phases. These phases are; rapid depolarization, plateau, and re-polarization. Rapid depolarization occurs following the electrical activity of nodal cells that cause the membrane to reach potential and the opening of voltage-gated Na⁺ channels. Na⁺ ions rush into the cell, causing a rapid increase in membrane potential to around +30mV, where the channels become inactive. This signals the plateau phase where voltage-gated Ca²⁺ (calcium) channels open, allowing the slow influx of trigger Ca²⁺ into the cell (recall, Ca²⁺ promotes the actin-myosin interaction and cross-bridge formation required for contraction). The end of the plateau phase occurs when these slow Ca²⁺ channels become inactive. Throughout the process, K⁺ ions flow out of the cells as the inside is becoming increasingly positive due to the influx of Na⁺ and Ca²⁺ , causing K⁺ to move down its concentration. The re-polarization phase includes the continued flux of K⁺ out of the cell, while Ca²⁺ and Na⁺ are no longer fluxing into the cell. This movement imbalance results in the cell becoming more negative and causes the membrane potential to return to the original charge of −90mV. Finally, the end of the re-polarization phase is marked by the closing of these K⁺ channels.

This diagram was included because it is helpful to visualize the flux of ions in and out of a cell as it’s related to membrane potential. The diagram relates action potential stages to refractory periods and compares skeletal muscle action potentials to cardiac muscle action potentials.

When looking at the diagram there are a few concepts to take note of. The long plateau phase is due to the influx of calcium ions. The extended refractory period allows the cell to fully contract before another electrical event can occur. The “absolute” purple arrow in the cardiac muscle action potential should be labeled as the “effective” refractory period.

Absolute/Effective Refractory Period:

The period in which another action potential cannot be generated even if another stimulus is applied. The Na⁺ channels are in the inactive state and cannot be opened even if threshold is reached.

Relative Refractory Period:

The period during which increased stimulation can generate another action potential. The K⁺ channels are open (causing hyper-polarization), but the Na⁺ channels are in the closed state and can be opened if the threshold is reached.

Cardiac Muscle vs. Skeletal Muscle

Now that we have discussed the unique cell types of the heart, we can compare the properties of the contractile cardiac myocytes to the contractile skeletal muscle cells you have likely learned about in past Human Physiology courses. The following diagram is beneficial to use as it clearly labels the differences between cardiac muscle and skeletal muscle action potentials. Additionally, several similarities are displayed in the middle.

Cardiac Myocyte Action Potential Wave Video

This video was included because it explains the previous learning object in more detail and provides more context regarding cardiac myocytes to improve your understanding. The video highlights the differences between Purkinje and nodal cells and describes several important terms. “Automaticity” is described at 1:25, “Conduction” at 6:25, and “Contraction” at 11:08. The video provides interesting context and lots of clinical application examples. Not all of the information is necessary to know so you may benefit from skipping ahead to one of the above definitions if you find yourself struggling. Please note that this learning object is slightly above the level of knowledge required for HK*3810 because it has clinical applications and talks about the vagus nerve.

Summary: Cardiac Cells Comparison

Before we move onto another topic, let’s ensure that you fully understand the differences and similarities between the cardiac cell types. The following graphic compares the characteristics of cell types providing a beneficial learning object to refer to if you are ever in need of a refresher. In the next part of the subchapter, we will apply our knowledge of these cardiac cells to the heart’s electrical conductance and physical contraction in the cardiac cycle.

Conductance and Contraction of the Heart – The Cardiac Cycle

Pathway of Conductance in the Heart

Now that we have covered heart anatomy in the first subchapter and covered the electrical and contractile cells in the first half of the present subchapter, we can apply these concepts to gain a more in-depth understanding of the cardiac cycle. The following diagram provides a simplified illustration of the pathway of electrical conductance in the heart. Note that the purple wave in the diagram depicts the movement of electrical activity.

Summary of the diagram:

1. The SA node and the remainder of the conduction system are at rest.
2. The SA node initiates the action potential, which sweeps across the atria.
3. After reaching the AV node, there is a delay of approximately 100 milliseconds (ms) that allows the atria to complete pumping blood before the impulse is transmitted to the atrioventricular bundle.
4. Following the delay, the impulse travels through the atrioventricular bundle and bundle branches to the Purkinje fibres, and also reaches the right papillary muscle via the moderator band.
5. The impulse spreads to the contractile fibres of the ventricle.
6. Ventricular contraction begins.

Conduction Velocity and Pacemaker Rate

As discussed above, the conductance of electrical activity in the nodal cells of the heart occurs in a pre-determined order. This ensures that the contraction following the depolarization is efficient to push blood throughout the chambers of the heart and into circulation. The nodal cells’ location in the heart will determine their spot in the order, their conduction velocity, and their pacemaker rate. Under normal cardiac conditions, the SA node is the first to depolarize, demonstrating a conduction velocity of 0.05 minutes/second (m/s) and a pacemaker rate of 70-80 beats/minute (beats/min). Since the SA node is the first to depolarize, it is referred to as the pacemaker cell. Note that this learning object is above the level of knowledge required for HK*3810, since specific numbers are not necessary to know.

The different pacemaker cells do not compete, and they go at the pace of the fastest rate (SA node). Therefore, if there is an issue with one structure in the sequence, the conduction rate will move to the next fastest pacemaker rate. This is why the differences in conduction velocity and pacemaker rate can be used as a diagnostic tool to see which pacemaker cell is not working properly in the heart. An artificial cardiac pacemaker is a common medical device that serves the same purpose as a pacemaker nodal cell. It sends an electrical impulse telling the heart when to beat.

Contraction Pattern Cardiac Cycle Diagram 

This diagram was included because it integrates our knowledge on cardiac myocyte action potentials and heart contractions with what we will be learning in the next section about the pressure-volume relationship of the cardiac cycle.

To Summarize…

The cardiac cycle begins in diastole, where the heart is relaxed and the right atria is being passively filled with blood. Next, we see atrial systole in which both atria contract in order to push blood into circulation within the heart. Next, in ventricular systole, we see the blood reach the ventricles before being ejected out of the heart and into circulation of the body. One round of this contraction and circulation is equal to one cardiac cycle.

Cardiac Cycle Video

Here is a video representation of the cycle depicted in figure 7.  Watch as the narrator explains the pathway of blood through the heart with respect to the pressure-volume relationship. The video will also introduce all relevant cardiac output equations (at 10:00) and presents stroke volume, which will also be helpful for next chapter. Please note that this learning object is slightly above the level of knowledge required for HK*3810.

Visualizing Contraction – Putting it All Together

This GIF is a fun addition to provide you a moving representation to visualize how the electrical and contractile systems work together to promote the orderly contraction of the heart. Thinking of the molecular mechanisms behind the contraction can make it seem abstract. Hopefully, the knowledge that you have gained in this section has given you a different perspective when you see this heartbeat. Try thinking about what causes the valves to open and where blood is being pumped to. Next, we will explore the cardiac cycle and then move onto the pressure-volume loop.

Subchapter Quiz

The questions below can be used to assess your knowledge within this chapter. There are five multiple-choice questions that you should attempt without referring to your notes. The questions will provide you with responses to your answers to guide your studying but should not be used as your only resource.