Cardiomyocytes (Cardiac Muscle Cells)- Structure, Function & Histology

In this article, we are going to talk about cardiomyocytes which are cardiac muscle cells that make up the heart of most living things.

We are going to take an in-depth drip exploring what these cells are, what their function is, how they are structured, and how to view them. 

So, without further ado, let us begin by taking a moment to go over what these cells are and what some of their main characteristics are.

A Bit About What Cardiomyocytes Are

Cardiomyocytes which also go by the name myocardiocytes are cells that are found in the heart and even make up the cardiac muscle.

They are one of the most important and predominant cells in the heart and are mostly responsible for the contractile function of the heart.

Which basically means that they help to pump blood all around the body. The heart is an amazing organ that is essential for life.

In many animals and even humans, these cardiomyocyte cells are among the first cells to terminally differentiate which means that the heart is one of the first organs that is formed when a fetus is developing. 

If we take a look at a mouse, for example, the embryo will start to develop cells that make up the cardiac muscle after just six days after the egg has been fertilized.

So, what are the main characteristics of Cardiomyocytes? Let’s take a look below before we move on:

• Cardiomyocytes are elongated cylindrical cells striated
• Cardiomyocytes tend to have only one nucleus
• Cardiomyocytes tend to have contractile proteins
• Cardiomyocytes are connected to each other by intercalated discs.

Now that we have a better idea of what exactly a cardiomyocyte cell is we can finally take a closer look at their structure and function. 

What Is The Ultrastructure Of Cardiomyocytes?

Cardiomyocytes are muscle cells, however, they are actually inherently different from other muscle cells around the body. Most other muscle cells within the body are prone to fatigue after a short while of work.

But the cardiomyocyte cells are highly resistant to fatigue, which is a good thing. Can you imagine if your heart got tired? That wouldn’t be good!

The fact that cardiomyocyte cells do not get tired easily means that your heart can contract and relax without ever stopping which means that your body can get good circulation all around the body. 

This whole process is possible because of the components of this cell type. So, let us take an in-depth look at the components of cardiomyocyte cells:

Let’s Talk About The Basement Membrane

In simple terms, the basement membrane of myocytes is the wall that separates the intracellular section of the cell from the extracellular environment.

This part of the cardiomyocyte is made up of glycoproteins laminin, fibronectin, type IV collagen, and proteoglycans.

All of these components work together to make up the basement membrane which is only about fifty nanometers.   

This membrane is made up of two layers known as the lamina densa and the lamina lucida. The basement membrane gives the cardiomyocyte cell an interface for continuity with the extracellular environment.

This process then makes it so that the membrane can crap calcium and ions while still acting as a barrier which allows many macromolecules to be exchanged. 

Let’s Talk About The Sarcolemma

This component is a specialized structure which is also an important shell that covers the cardiomyocyte cell. Sarcolemma is made up of glycocalyx, plasmalemma, and collagen.

This component can control what kinds of molecules enter the cell, this is due to the fact that it is largely composed of lipid bilayer.

Because of the hydrophobic core in the lipid bilayer, the sarcolemma is impregnable to certain types of molecules. 

In addition to that, this particular component is a part of the intercalated discs and the transverse tubular system within the cardiac muscle itself.

The sarcolemma is essentially a mechanical link between the cardiac cells throughout the specialized intercalated discs. On top of that, this component helps with excitation and contraction coupling within the transverse tubules.

These T-Tubules work to organize all the cardiomyocyte cells in the cardiac muscle into pairs which helps to create striated muscle strands

Let’s Talk About The Desmosomes

This component of cardiomyocyte cells is a part of the sarcolemma and works to anchor the ends of cardiac muscle fibers together.

This process stops the cells from pulling apart when the muscle contracts and relaxes. The desmosomes are unlike Gap Junctions which are also a part of the sarcolemma.

Gap junctions are channels between fibers of the cardiac muscle which allow the depolarizing current to flow through the cardiomyocyte cells.

This current moves from one cell to another and helps with the relaxation and contraction of the cells.  

Through study, desmosomes have been thought to be able to resist mechanical stress due to the fact that this component is hyper-adhesive. Due to this feature, desmosomes are able to resist chelating agents. 

Let’s Talk About The Sarcomeres

This component is basically a functional unit that lines the myofibrils.

They are split into two very important components called the contractile proteins which help with the contraction of the myofilament and the cytoskeleton proteins which work to maintain the shape of the cell while stabilizing the proteins of the sarcomere and maintaining the mechanical integrity and resistance of this part of the cardiomyocyte cells.

Let’s Talk About The Myofilaments

This component is essentially a contractile protein that contains myosin as well as actin proteins. Within the cell, myosin is an integral part of the motor proteins which make the muscle contract.

In the cardiomyocyte cells, the presence of myosin II has an important role to fill. It is responsible for the contraction of the muscle and makes it possible for blood to get pumped all around the body. 

This special type of myosin contains two heavy chains and two light chains.

When this component gains energy from ATP or adenosine triphosphate, the head of the myosin will bind to the actin which then results in the muscle contracting. 

Acting is made up of globular actin or G-Actin which are single units of actin. The filament is then joined and bound to regulatory proteins including the following: 

• Troponin-T
• Troponin-C
• Troponin-I
• Tropomyosin

The protein known as troponin is located between the grooves between the actin filaments and covers the areas where the actin is bound with myosin.

This process controls the binding of myosin to actin and by extension affects the contraction and relaxation of the cardiac muscle itself. 

Let’s Talk About The Mitochondria

Cardiomyocytes are chock-full of various types of organelles that are there to keep the cell alive and help it to function as it should. But, cardiomyocyte cells have more mitochondria than other cells.

In fact, about forty percent of the cell is occupied by mitochondria which helps to maintain the high levels of adenosine triphosphate that the cell needs to function as it should. 

 As we now know, cardiac muscles are always contracting and relaxing so that blood is able to be pumped everywhere it is needed.

This process takes place around the clock and never stops which is why this muscle needs a high amount of energy.

The high number of mitochondria helps the cells to get all the energy that it needs in order to keep up the taxing job that the heart must do in order to keep humans and animals alive. 

Other Important Parts Of The Cardiomyocyte Cells

We have talked about the majority of the important parts of cardiomyocyte cells, but there are actually several more that play an important role in making sure that these cells work as they should.

Below is a short list of some of the other essential components of cardiomyocytes cells: 

• Nucleus
• Golgi Apparatus
• Alpha Tubulins
• Beta Tubulins
• Endoplasmic Reticulum

Let’s Talk About The Function Of Cardiomyocytes

As we now know cardiomyocytes are constantly contracting and relaxing in a cycle that makes it possible for the cardiovascular system to pump blood all around the body without ever stopping.

This whole process is possible as a result of excitation-contraction coupling which is then used to convert an action potential for example an electric stimulus which then results in the muscle contraction. 

We have talked about the structure of cardiomyocytes in relatively high detail. At this point, you should have a basic understanding of these cells and what they do.

So, in this section, we are going to go over the mechanism of cardiomyocytes and how they function. So, without further ado, let us get started!

What Is The Mechanism Of Contraction?

When an electric stimulus or action occurs the membrane depolarization will result in an influx of calcium ions into the cardiomyocyte cell.

This influx of calcium then binds to the reception within the cell which then results in the release of more calcium into the cell.

This process will then shorten the actin-myosin fibrils inside the cell and by extension, the contraction of the cell is affected. 

Below we have written a simple step-by-step guide on how this process may happen: 

Step 1 – The cells of the pacemaker within the sinoatrial and atrioventricular nodes induce an action potential or electric stimulus. This first happens to the cardiomyocytes within the gap junctions otherwise known as the intercalated discs. 

Step 2 – The second thing to happen is the calcium channels within the T-tubules are then activated by this electrical stimulus when it goes between the sarcomeres of the myofibril in order to release calcium ions into the wall of the cell. 

Step 3 – Within the cardiomyocyte cell, calcium will bind to cardiac troponin-C, and then it will move the troponin complex to the place where the actin was being bound. This all happens within the cytoplasm of the cardiomyocyte. Because of this, the actin is then free to bind myosin which then initiates contraction. 

Step 4 – When the myosin starts to be bound to the ATO molecules the actin filaments are then pulled to the center of the sarcomere which then makes it possible for the muscle to contract. 

Step 5 – Calcium is then taken away from the cytoplasm of the cell which then allows the troponin complex to come back to its usual spot and this will then stop the contraction. This process is known as the repolarization phase. 

What About Cardiomyocytes Renewal?

There have been many studies on cardiomyocyte renewal. These studies have shown that these cells have a tendency to renew at a much slower rate throughout the life of a person or animal.

If we take a look at someone aged twenty-five we will see that the annual turnover of cardiomyocytes will be about one perfect. This number will drop to under half a percent for people that are seventy-four and older. 

In the lifetime of a person, there will be less than fifty percent of these cells renewed. This indicates that cardiomyocytes have a much longer lifespan when compared to other types of cells.

But, when the cardio muscle has sustained damage through injury or myocardial infarction, there will be monocytes that will then remove the damaged or necrotic cardiomyocytes.

Do Cardiomyocytes Regenerate?

There are only a select few types of animals such as the Zebrafish that have the ability to regenerate parts of the heart muscle that has been injured.

Us humans do not have the ability to regenerate sufficiently or to the extent that the heart would be able to heal itself.

It is because of this flaw that those of us that have experienced physical heart injuries or had heart attacks are prone to developing heart failure which can often lead to our demise. 

There has been research into this topic, studies have found that after a week of being alive it becomes impossible for humans to regenerate injured parts of the heart.

This is why people that have heart damage can only be helped through the implantation of a mechanical ventricular device or by way of a heart transplant.

Both of which are big and risky surgeries that do not always work out. 

Cardiac cells within the body do not have the capacity to regenerate fast enough to repair damage or injuries.

However, through many studies, scientists have found that progenitor cells in human adults actually have the ability to create new cells.

These cardiac stem cells are located within the heart and to this day scientists and medical professionals are attempting to isolate them in the hopes of creating a way for the heart to regenerate. 

There are a few suggested methods that have been thought to lead to the regeneration of cardiomyocyte cells. 

Below we have listed a few of these methods: 

A Direct Reprogramming of Fibroblasts

Within the total of cardiac cells cardiac fibroblasts make up about fifty percent of that total. They have the ability to live for long periods of time and also join cells next to them.

Fibroblasts are ideal for direct reprogramming in order to convert themselves into a cell that is similar to cardiomyocytes. Over the last several years there have been countless studies into this process that have been successful and managed to reprogram fibroblasts to become similar to cardiomyocytes.

In a study that took place in 2012 by someone named Olson, this process of reprogramming was successful due to the fact that the cells had improved performance and also helped to reduce scars from forming after myocardial infarction.

The Implantation of an iPSC Cardiomyocytes

This method involves induced pluripotent stem cells or iPSC technology. Researchers have been able to find a function in cardiomyocytes which then gets rid of the requirement of human embryos for this purpose.

When these cardiomyocytes are transplanted through the iPSC method into a heart that has been damaged there has been a relative success in helping the cardiac muscles to work normally. 

Viewing Cardiomyocytes Under A Microscope

If you want to see cardiomyocytes under a microscope you will firstly need to mount the cells in a way that is visible by the microscope.

When you have fixed and permeabilized them on a slide you will be able to view them easily.

But, what will you need to be able to do this? Below is a short list of all the requirements to view cardiomyocytes under a microscope:

• Cardiomyocytes Sample, you will most likely get this sample from small animals like rats or mice. This may prove to be a tricky thing to obtain if you do not know where or how to get a sample. 
• Paraformaldehyde
• Phosphate buffered saline with a pH of 7.4.
• A tissue adhesive will be needed to stick the sample to the slide. 
• 0.1M sodium bicarbonate with a pH of 8.0
• Nutator
• Centrifuge with controlled temperature
• Cover glass with chamber
• A slide for your microscope
• A culture medium that has five percent of fetal bovine serum, 47.5 percent MEM, 10mM pyruvic acids, Tyrode’s solution, 6.1mM glucose, and finally, 4.0 mM HEPES
• A blocking solution with 0.01 percent BSA in PBS

Stains You Will Need

Because you will be observing something so small, you will need a cell stain which will help you to see the sample better.

Different types of stains will make it easier for you to see different parts of a cell such as the nucleus or cell wall. 

Below is a short list of what kinds of stains you will need to view your cardiomyocyte cells:

• Bovine Serum Albumin
• MitoTracker Deep Red 633
• SYTO 11 Green-Fluorescent Nucleic Acid
• Alexa Fluor 568 Phalloidin

How To Prepare Your Sample

You will of course need to prepare the sample you intend to observe. Below is a brief guide on what you can expect to do to prepare your sample before you view it: 

Step 1 – The first thing you will need to do is suspend the cell in a medium with five percent carbon dioxide and it should be kept suspended at eighty-six degrees Fahrenheit. 

Step 2 – Now you need to label your sample by using MitoTracker Deep Red 633 and allow your sample to incubate for at least thirty minutes in a CO2 incubator. This whole process will stain the mitochondria.

Step 3 – Now you will need to wash your sample by using PBS twice in a dark room. You can do this by simply covering the tube with aluminum foil while you wash. 

Step 4 – You will now need to use a low G Force at eighty-six degrees Fahrenheit. Make sure to pellet isolated cells for a few seconds before you suspend the cells in four percent paraformaldehyde in PBS. After this has happened make sure to mix the contents with a nutating mixer for at least thirty minutes so that it can fix. 

Step 5 – The next step is to pellet the cells for a minute at a low G Force and resuspend the cell using the PBS.

Step 6 – Now you need to layer the cardiomyocytes on the chambered cover glass, make sure to do this with a tissue adhesive, and Call-Tak Cell 

Step 7 – Now your chamber will need to stand for two hours at room temperature. Make sure that the cell is not disturbed for this time period. 

Step 8 – Next, you will need to wash the cells with the PBS on the glass surface. 

Step 9 – Now, you will need to use a 0.1 percent Triton X-100 in PBS to help permeabilize the cells. This should be done at room temperature for three minutes. 

Step 10 – The next thing you will need to do is wash the cells with PBS twice for two minutes. 

Step 11 – using the blocking solution you will need to treat the sample for thirty minutes. This should be done at room temperature. 

Step 12 – In a dark room at room temperature, you can label your sample for the next thirty minutes. 

Step 13 – The next step is to stain the actin using the Alexa Fluor 568 Phalloidin. 

Step 14 – You will now need to stain the nucleus by using SYTO 11 Green-Fluorescent Nucleic Acid. 

Step 15 – Wash the sample with PBS three times for three minutes per wash. 

Step 16 – Using PBS you will need to maintain the cells containing antibiotics. 

Step 17 – Now you are ready to view your slide under the microscope. 

Final Thoughts 

We hope that you enjoyed reading our article on cardiomyocytes and how they work and function. Have a fantastic day and don’t forget to keep learning!

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