Download Heart Cells Made Easy

Heart Cells Made
Easy
Cardiology Made Easy
T.M.I. Publishing
1st Edition
Preface
I have to say that explaining heart cells through the written word is no easy challenge. The
biggest challenge is knowing what order to teach the different concepts. I have ordered the book
in a way that will hopefully make sense, though I have a feeling this book should be flicked
through a second time to help glue the pieces of the jigsaw together.
Good Luck
Carl R.
How the Heart Beats....................................................................8
The Order of Play and The ECG........................................................................9
Shortening of Multiple Cells and Contraction............................1
Cardiomyocytes and Desmosomes.......................................................................1
How The Shortening Of Multiple Cells Causes A Heartbeat.............................4
How Individual Heart Cells Shorten...........................................1
The Squeezing Cell...............................................................................................1
What Puts the ‘Muscle’ in Heart Muscle?............................................................1
Actin and Myosin..........................................................................................................................5
Sliding Filament Theory.......................................................................................5
Intercalated Discs, T-Tubules and Sarcoplasmic Reticulum........1
Intercalated Discs..................................................................................................1
Shared Cytoplasm..........................................................................................................................1
T-Tubules and The Sarcoplasmic Reticulum.......................................................4
T-Tubules..............................................................................................................4
Sarcoplasmic Reticulum........................................................................................5
Heart Cells and Electrical Charge...............................................1
How Can a Cell have an Electrical Charge?........................................................1
Types of Ion.................................................................................................................................6
Quite interestingly and just to confuse things, particular ions can often move
freely in and out of cells........................................................................................2
Action Potentials...........................................................................1
The Heartbeat Nightclub......................................................................................1
Phase 4..................................................................................................................1
Phase 0..................................................................................................................2
Phase 1..................................................................................................................2
Phase 2..................................................................................................................2
Phase 3..................................................................................................................2
Phase 4..................................................................................................................2
The Heart Cell Contraction.................................................................................3
Phase 4..................................................................................................................3
Phase 0..................................................................................................................3
Phase 1..................................................................................................................4
Phase 2..................................................................................................................4
Phase 3..................................................................................................................4
Phase 4..................................................................................................................5
Pacemaker Cells...........................................................................1
The Role Of Pacemaker Cells..............................................................................1
Automaticity..................................................................................................................................1
Action Potential of a Pacemaker Cell...................................................................2
Phase 4..................................................................................................................2
Phase 0..................................................................................................................3
Phase 3..................................................................................................................3
Why Phase 4,0 and 3?...........................................................................................4
How Do Pacemaker Cells Trigger a Heartbeat?..................................................4
S.A. Node, A.V. Node and the Bundles of His.....................................................6
Awaiting Their Turn.............................................................................................6
Escape Beats..........................................................................................................7
Nucleus, Mitochondria and Other Bits and Bobs........................1
Nucleus.................................................................................................................1
Deoxyribonucleic Acid (DNA)..............................................................................1
Ribonucleic Acid (RNA).......................................................................................2
Messenger Ribonucleic Acid (mRNA)..................................................................2
Ribosomes.............................................................................................................2
Transfer Ribonucleic Acid tRNA..........................................................................2
Mitochondria........................................................................................................2
Other Available Titles..................................................................2
Dedication.............................................................................................................3
Cardiomyocyte - The Heart Muscle Cell
Mitochondria
Intercalated Discs
Nucleus
Desmosomes
T-Tubule
Openings
Myofibrils
Sarcoplasmic
Reticulum
Gap Junctions
Sarcolema
(Membrane)
Intracellular = Within The Cell Membrane
Extracellular = The Cell’s External Environment
Introduction
The heart is made up of many different types of cell that all play a role in making the heart a
successful pump, capable of maintaining blood flow around the body. The following chapters
focus on the cells responsible for making the heart beat and the properties unique to them.
The heart muscle cells (cardiomyocytes) are responsible for the mechanical squeezing. They
pass an electrical signal to one another as they contract, which triggers a contraction in all
neighbouring cells. This causes a large scale synchronised contraction of all connected cells that
we commonly know as a heartbeat.
Pacemaker cells are also specialists in passing on electrical signals but more importantly they
are able to initiate their own electrical signal. They are responsible for starting each healthy
heartbeat.
Pacemaker cells are also part of the conduction system, a network of specialist tissue vital in
the control and order of each contraction. It is not always appreciated that the heart has an order
to each contraction, so it seems that would be a good place to start before we dive deeper into
cardiac cells.
Chapter 1
How the Heart Beats
The heart beats and most of us take it for granted. You can be sure that your heart is beating
right now, if not please call a doctor.
Even though so many of us have a heartbeat, very few people know the basics behind how it
beats. It is regulated by the electrical conduction system, which controls when different parts of
the heart contract.
The Heart's Electrical Conduction System Simplified
Every healthy heart comes fitted with its very own pacemaker, a cluster of cells called the
Sino Atrial Node (SA Node) (Picture 1). This natural pacemaker lets of an electric charge
intermittently and when it does that initiates a heartbeat. If your heart rate is 60bpm you can be
sure this little bugger is going off every second. It can be found in the top left of the heart as you
look at it (anatomically this is the right atrium).
Image 1 S.A. Node (The Sinoatrial Node)
When the SA node fires it initiates a chain of events. Picture one domino, in front of it two
dominoes, in front of those 3 dominoes and so on and so forth. The SA Node is pushing over the
first 'domino' and the knock on effect causes all the cells to contract in order. The main muscle
cells in your heart are all like dominoes lined up next to each other. If you push one then that will
star a chain event (Contraction)
THE ORDER OF PLAY AND THE ECG
The contraction of all the cells in the top part of your heart (left and right atrium) can be
seen on an ECG and is known as the P wave. Image 2 shows the chain of cell contraction started
by the SA Node and Image 3 is an ECG of a heart beat with the P Wave circled.
Image 2. The Atria Contract
Image 3 The P Wave on an ECG
This works well for the top of the heart. The order of contraction from the top down to the
middle will push the blood into the bottom of the heart filling the ventricles with blood (which is
desired). However when the bottom of the heart contracts, we would like it to squeeze from the
bottom upwards. This will push the most blood, up, out and around the body.
This is demonstrated in Image 4, it shows a cross section of the heart to illustrate the desired
direction of blood flow.
Image 4. Atria Pump Downwards, Ventricles Pump Upwards.
This optimal direction of blood flow is the reason that the atria contract from top to bottom
and the ventricles contract from bottom to top.
So how does the heart manage to make the ventricles pump from bottom to
top?
The heart uses some clever electrical circuitry to get the bottom of the heart to contract
before the rest. Knocking the ‘dominoes’ at the bottom of the heart over first will ensure that the
chain reaction moves upwards. Firstly there is a barrier of non conductive tissue that separates the top chambers and the
bottom chambers in the heart which is shown in Image 5.
Image 5. Non Conductive Barrier Between Atria and Ventricles and the A.V. Node
There is a bundle of cells that traverses this barrier called the Atrioventricular Node (A.V.
Node). This cluster of cells is part of the chain reaction but passes on the electrical energy very
slowly in relation to the other heart cells, a bit like a sprinter having to suddenly run through
treacle - the electrical signal is deliberately slowed down. The non-conductive barrier means that
the electrical signal can only reach the ventricles through this node.
Whilst the electrical signal is passing through this ‘treacle’ there is an absence of muscle
activity (neither the atria or the ventricles are contracting). This lack of activity can be noted on
an ECG rhythm strip circled here in Image 6 and is referred to as the PR interval.
The PR Interval As Seen On an ECG Rhythm Strip
There is good reason why we want a pause between the top and the bottom sections of the
heart contracting. That is to allow time for all the blood possible to be squeezed out of the atria
and pushed into the ventricles.
So perfect! The Ventricles are now really full and ready to forcefully push all the blood
required to the lungs and the rest of your body. Time to tell the bottom of the heart to contract
first.
The electrical energy eventually passes through the sticky AV Node and arrives the other side
at some more specialist conductive tissue called the bundle of His (Image 7).
Image 7 The Bundle of His (and Left and Right Bundles)
This bundle of cells carries electrical energy incredibly quickly much quicker than the
majority of cells in the heart (like the electrical signal just got a speed boost!). The bundle of His
carries the electrical signal from the A.V. node to the Purkinje Fibres.
Image 8. The Purkinje Fibres Intertwined into the Ventricles
Easier to pronounce than to spell, the Purkinje fibres (Image 8.) are also specialised at
carrying the the electrical impulse that makes heart muscle cells contract. The fibres are entwined
in abundance through the lower part of the ventricles. As the electrical signal passes through the
Purkinje fibres it triggers a mass contraction of the muscle cells that they are in contact with. This
triggers a rapid contraction of the ventricular heart muscle cells that moves like a wave from
bottom to top (Image 9.)
Image 9. A Ventricular Contraction From Bottom to Top.
This maximises the blood ejected up and out around the body by the heartbeat. This mass
contraction of cells is visible on the ECG as the 'QRS complex' which is circled in Image 11.
Image 11. The QRS Complex As Seen on an ECG Rhythm Strip.
Finally on the ECG is the 'T' Wave (Image 12.) this is all the cells in the bottom of the heart
recharging ready to do it all again!
Image 12. The Recharging of Ventricular Heart Muscle Cells.
Chapter 2
Shortening of Multiple Cells
and Contraction
How The Heart Pumps.
CARDIOMYOCYTES AND DESMOSOMES
Most of the heart’s mass is made up of cardiomyocytes (or myocardiocytes), these are the
heart’s muscle cells and are attached to one another by desmosomes (a cell structure
specilialised for cell to cell adhesion). This creates a community of cells, separate cells that work
as one unit.
Cardiomyocytes and Desmosomes
These cells have the ability to suddenly shorten in length during a change in the electrical
properties of the cell (electrophysiology). This process will be explained in detail later in the book.
For now, just understand that these cell’s can shorten and when they do, they release ions.
Cells Shorten and Release Ions
Ions
Cell Shortens
Released
Ions are atoms or molecules with either a negative or positive electrical charge and as these
ions leak into neighbouring cardiomyocytes, they cause them to shorten too. This causes a knock
on effect and a wave of contraction moves incredibly quickly through all connected
cardiomyocytes.
Now because the cardiomyocytes are all attached to one another by the desmosomes, this
sudden shortening of cells causes an overall contraction of the structure as a whole - the basis for
a heartbeat.
Wave of Contraction Moving Through The Heart Cells.
HOW THE SHORTENING OF MULTIPLE CELLS CAUSES A
HEARTBEAT
It may still be unclear how a shortening of individual cells could be responsible for the heart’s
pumping ability. The cells shortening decreases the size of the heart’s chambers, causing an
increase in pressure, forcing blood out and around the body.
The Heart Pumping
To help visualise this concept, picture yourself as part of a giant circle of people holding
hands. You represent one of these heart muscle cells and abide two similar principles.
• When the person you are in contact with is ‘activated’ you are triggered.
• When triggered you shorten (pull your arms inwards next to your body)
One ‘cell’ being triggered will start a wave through the circle which will lead to an overall
contraction.
This can be seen in the following illustration.
A Knock on Effect and Contraction
This is how the shortening of cells causes a decrease in chamber size pumping blood around
the body.
Chapter 3
How Individual Heart Cells
Shorten
Calcium, Actin and Myosin
THE SQUEEZING CELL
Now you instinctively know that the heart muscle is not always pumping. It pumps, relaxes,
pumps, relaxes, so on and so forth. So something must be changing on a cellular level to make it
beat. From the previous chapter you may have started to realise that it is the movement of ions
that is responsible.
It is actually the movement of multiple different ions that are responsible for the entire
process of contacting cells, and we will come on to this later in the book. Before we get on to that,
I just want to focus on one particular link in the chain. The mechanics behind how a cell
physically becomes shorter when calcium ions enter through the membrane (cell skin).
WHAT PUTS THE ‘MUSCLE’ IN HEART MUSCLE?
Actin and Myosin
Actin and Myosin are hugely abundant stringy proteins that are interlinked within the
cardiomyocyte.
Actin and Myosin as Part of a Heart Cell (Cardiomyocyte)
ACTIN
MYOSIN
If you zoom in even closer you can see that the actin is a helical structure with lots of ‘craters’
along it. Myosin on the other hand has two ‘heads’ protruding from each protein. There are
more than one myosin protein in each myosin filament and as a result their are numerous heads
along one myosin filament.
Actin Filament
‘Nooks and Crannies’
Myosin Filament
Multiple Heads of Multiple Myosin Proteins
These two proteins are the main protagonists in a contraction (shortening of the cell). To
shorten the cell’s length, the myosin protein pulls the actin proteins closer together when the cell
is contracting and releases the actin when cell relaxes.
Myosin Pulls The Actin Together Shortening the Cell
Relaxation
Contraction
How the myosin pulls the actin together is known as the sliding filament theory.
SLIDING FILAMENT THEORY.
There are two main principles behind sliding filament theory. One is that the heads of the
myosin proteins are actually able to change shape and use the nooks and crannies of the actin
proteins to pull them closer.
The second factor is that whilst myosin heads are able to do this, the actin proteins do not
always allow them to.
The Movement of Myosin Heads
This movement involves the heads of the myosin proteins being straightened out (which puts
them under tension) and when released they spring back to their resting form. In a contracting
muscle, one myosin head pulling on an actin protein may look like this (ignore the additions to
the actin filament, this will be explained very shortly).
The ‘Cocking’ and ‘Firing’ of the Myosin Heads
Myosin Bound to Actin
Myosin Releases Actin
Myosin Head
Straightens
Under Tension
Myosin Head
Springs Back With
Force
Pulling the Actin
Closer
When you have multiple myosin heads working in conjunction the muscle cell is able to
shorten very quickly.
The straightening of the myosin head is caused by the ‘energy’ currency of biological cells
ATP. I do not want to go in to any more detail in this book, however if you are particularly
interested in this process please google hydrolysis of ATP and myosin.
The second factor is that the actin proteins are not always viable.
The Viability of Actin Proteins
The actin protein is actually not alone, it is entwined with another protein called tropomyosin
that has troponin complexes attached to it. This tropomyosin prevents the myosin heads from
binding with the actin protein as they ‘cock and fire’.
Tropomyosin Blocks Myosin From Binding with Actin
Troponin Complexes
Blocked
From
Binding
Tropomyosin
It is only when the tropomyosin is moved out the way that the myosin heads are able to grab
on to the actin.
How is Tropomyosin Moved Out of the Way?
Calcium Ions! When there are an abundance of calcium ions in the cell they bind with the
troponin complex. When this happens it pulls the tropomyosin out of the way, exposing all of the
delightful nooks and crannies that myosin heads are attracted to. This allows for the binding of
myosin and actin to occur, causing the muscle cell to shorten (contract).
Calcium Ions Binding to the Troponin Complex Pulls The Tropomyosin Out of the Way
Calcium Binds
to the
Troponin
Pulling the
Tropomyosin
Out of the Way
Now the Myosin
Can Bind to the
Actin
Drawing the
Actin Closer
Without having stated it directly, you should now see that heart muscle cells contract in the
presence of calcium ions. In plain terms, when there are a lot of calcium ions in the cell, the cell
contracts. A scarcity of calcium ions will mean that the tropomyosin slips back into its resting
position, preventing the binding of myosin to actin once more, causing the muscle cell to relax.
Analogy Time - The Third Wheel
I enjoy an analogy and did not want to leave this topic without one to help you to remember
the concept. This next analogy is slightly adult in its content. However I feel if you are reading
about contracting cardiac cells you are probably old enough to handle it, if indeed you are under
16 then I encourage you to put down my book and go and play playstation or football or
something.
Myosin and actin are essentially on a date in a poorly lit bar. They are desperate to pull each
other closer and get physical with some public displays of attraction. Unfortunately actin has
brought her friend called tropomyosin along who is a real drag and is getting in the way.
Just when myosin feels like all hope is lost, in walks his friend calcium ion.
Calcium ion knows the drill and takes tropomyosin by the arm (troponin complex) and leads
her away for a boogie. Now alone actin and myosin are free to act out their desires and pull one
and other as close as they can, I will spare you the details.
Calcium ions are the ultimate wingman.
A wingman is a friend or acquaintance that will keep the third wheel entertained so that you and your date can
enjoy some time alone.
When calcium ion leaves the bar, tropomyosin returns to be with actin and myosin and the
public displays of attraction have to stop.
NB. Tightly bound bundles of these ‘contracting’ proteins are called
myofibrils.
Chapter 4
Intercalated Discs, T-Tubules
and Sarcoplasmic Reticulum
Cell Communication and Efficiency
So far we have learned how the heart muscle cells shorten and how a communication of ions
between cells leads to a wave of contraction. There are other physical properties belonging to
cardiomyocytes that help with both of these processes.
INTERCALATED DISCS
The point at which one cardiomyocyte joins to another is called the intercalated disc. Whilst
this disc is the point where the desmosomes (cell glue) is anchored, it is also the point where
numerous gap junctions exist. These gap junctions are an open pathway from one cell to the
next, through which certain ions can freely pass.
Ions Moving Through Gap Junctions in the Intercalated Disc
Shared Cytoplasm
This connection between all cells means that the cells share a singular cytoplasm. Cytoplasm
is the thick solution that usually fills an individual cell. This shared cytoplasm means that the
heart can be described as a functional syncytium. This is a rather posh word that essentially
means a group of cells that function as one.
At the point where there is large amounts of ions in one cell, they will diffuse through the
cytoplasm and ultimately end up in adjacent cells (we will learn a little more about diffusion
later). This influx of positive ions will cause that cell to contract and to release even more ions.
Those ions then filter through into their adjacent cells and so on and so forth.
Ions Flowing Through Gap Junctions In the Shared Cytoplasm Causing Cells to Contract
Relaxed Cells
Increase in
Ions
Moving
Through Gap
Junctions
Contracting Cell
Cells Share a
Cytoplasm
The Knock On Effect a Functional Syncytium
T-TUBULES AND THE SARCOPLASMIC RETICULUM
As we now know cell contraction is dependent on calcium binding with the troponin
complex. For this to occur there actually needs to be a relatively large amount of calcium
mingling amongst the myofibrils (tightly bound actin and myosin). The required amount is
actually far in excess of that which will enter the cell from external sources. If the cell was
dependent on the calcium entering from the extracellular fluid, there would neither be enough
calcium, nor would it infiltrate through the cell quickly enough to be of any real use.
So the two problems the cell faces is to supply the myofibrils with sufficient calcium and to
deliver it very quickly. Step forward T-tubules and the sarcoplasmic reticulum.
T-Tubules and Sarcoplasmic Reticulum in a Cardiomyocyte
T-Tubules
Sarcoplasmic
Reticulum
Myofibrils
T-TUBULES
According to wikipedia; T-tubules are a “deep invagination of the sarcolemma, which is the
plasma membrane cardiac muscle cells.” I personally would require a thesaurus to decode this
statement. I view T-tubules as deep craters in the surface of the cardiomyocyte. Like diamond
mines that penetrate deep underground.
T-tubules increase the surface area of a cell and despite penetrating deeply in to the cell, they
belong to the external environment. A bit like how the inside of a snorkel has air in it as opposed
to water... despite being inside the ocean.
The T-Tubules Are Part of the External Environment Just Like A Snorkel
The t-tubules are rich in calcium voltage gated ion channels, these are doorways through
which calcium can pass but only at certain times. We will come on to when and why these
doorways open later, but for now it is just important that you know they exist. When calcium
doorways open they allow calcium to enter the cell along the entire length of the t-tubule. This
means that calcium very quickly penetrates deeply into the cell. Phase one complete!
Phase 2 of saturating the myofibrils with calcium involves the sarcoplasmic reticulum.
SARCOPLASMIC RETICULUM
The sarcoplasmic reticulum is a network of tubes that surrounds the myofibrils, it is essential
in delivering large amounts of calcium to the actin and myosin. It is not just tubing though, it is a
store and pump for large amounts of calcium ions..
Sarcoplasmic Reticulum (in blue) Wrapped Around One Myofibril
The sarcoplasmic reticulum has a property known as calcium induced calcium release or
CICR. In short, the trigger for the sarcoplasmic reticulum to release and pump it’s stored calcium
ions... is calcium ions themselves. By binding to receptors (ryanodine receptors) on the membrane
of the sarcoplasmic reticulum, calcium ions act as a signal for mass calcium release amongst the
muscle cell.
So in sequence, calcium voltage gated ion channels open in the t-tubules, calcium enters the
cell binds to the sarcoplasmic reticulum triggering a mass pumping of calcium ion throughout
the cells myofibrils. The extra ions bind with the troponin complexes on the tropomyosin causing
an extremely rapid and proficient contraction of the cell.
In summary, cells contract following an influx of calcium ions from external sources. Thus for
cells to contract there will need to be a mechanism through which calcium ions enter the cell.
Calcium ions enter and leave the cell in response to a change in the cells electrical properties.
This relationship between electrical stimulation and mechanical movement of the cell is
sometimes referred to as the excitation-contraction coupling. To understand this relationship
further it is time to look at the electrical properties of heart cells.
Chapter 5
Heart Cells and Electrical
Charge
Cells have a Resting Electrical Charge.
Cells in the human body have an electrical charge. By an electrical charge I am referring to
that physics class at school where you learned that opposites attract. So something with a positive
charge and something with a negative charge will be attracted (pulled) towards one another.
Things of the same charge (both negative or both positive) will be repelled from one another!
These forces have a huge affect on how the cells in our bodies work.
HOW CAN A CELL HAVE AN ELECTRICAL CHARGE?
There are many molecules/atoms (tiny building blocks of matter) in the body. If these atoms
have a charge then they are called an ion (ion just means a variation of an atom or molecule that
carries a net positive or negative charge). If there are more electrons than protons in an atom it
will have a negative charge (negative ion) and if there are more protons than electrons it will have
a positive charge (positive ion). Types of Ion
So there are many types of ions in the human body and human cells. Below is a list of the
most plentiful and whether they are a positive ion or a negative ion.
Na+
K+
CL-
Ca2+
Mg2+
Na+! !
CL-! !
Mg2+ !!
Ca2+ ! !
K+ ! !
Sodium Ion
Chloride Ion
Magnesium Ion
Calcium Ion
Potassium Ion
Each ion has it’s own rules, and body
movement is a result of the function of
these ions.
Each cell type contains a varying number and type of ions. It is the number and ratio of
these ions within a cell that dictates its overall charge. If you have a cell made up entirely of
chloride ions then the net charge of the cell would be negative. If a cell contains a mixture of
positive and negative ions the charge of the cell will depend on whether the charge of the
negative ions or the positive ions is more dominant. For example if you had a cell with 20 x
Sodium Ions (+'ve) and 10 x Calcium Ions (-'ve) then the net charge of the cell will be positive.
Quite interestingly and just to confuse things, particular ions can often move freely
in and out of cells.
So What Decides the Number and Type of Ions in Different Cells?
Well the amount of ions in cardiac cells has many factors. The body actually uses a lot of
energy powering ‘pumps’ that keep some ions in the cell and other ions outside the cell in
extracellular fluid.
One particularly useful pump is the sharply named sodium-potassium adenosine
triphosphatase pump. This pump is located in the membrane the heart muscle cells and actively
moves sodium out of the cell and draws potassium into the cell.
Sodium-Potassium Adenosine Triphosphatase Pump In Action
1.
6.
2.
Pump
Sodium
Potassium
5.
3.
4.
Working alongside these pumps are ‘passive’ factors. These involve the physical properties of
the cell membrane and also some laws of physics.
This is really cool stuff... Lets start with a simple one.
Permeability of the Membrane
The Membrane of the cell is like a clever skin, keeping everything in that it wants and
everything out that it doesn't. It does this through special 'door ways' in the cell membrane that
will allow only certain ions to pass. A calcium ion channel for example would allow calcium ions
to pass through it but other ions, such as potassium, would be unable to make it through. Like a
doorman outside a nightclub the cell membrane controls which particles can pass through. If
your name isn't on the list then you are not coming through.
Unsurprisingly these 'gateways' in the cell membrane are called ion channels and these
channels have a huge influence on ion concentrations.
Diffusion
Diffusion is something you are familiar with, even if you don't realise it. What happens if you
urinate in a swimming pool? Does a cloud of yellow water follow you around for the rest of the
day? No. The particles in the water diffuse. They spread out so they are equally distributed
around the pool. They become so diffused that you can no longer see your shameful act. This
principle is at work within cells and their extracellular fluid (the fluid that they float around in). If
there is a large concentration of ions on the outside of a cell they will try and diffuse to the area
with a low concentration (into the cell) and vice versa. Anyway the pictures explains this better
than I do. This process is obviously dependent on the membrane permeability that I just
discussed.
Electromagnetic Forces
We touched on this earlier but basically the ions that are happy to be contained within the
cell, have an electrical charge. This electrical charge may be ‘binding’ to ions with an opposite
electrical charge inside the cell, that would otherwise be looking to leave.
Think of magnets pulling ions into the cell that would otherwise be happy outside of it.
In Summary
We have a few different forces all trying to influence the movement of ions, the only solution
is that a compromise has to be reached. The compromise between these forces decides how
many ions of different types are inside and outside the cell. Here is a fictional example of a cell.
3 Passive Factors that Influence Ion Concentrations
A Compromise of Forces in Real Life
In actual fact you are familiar with forces working along side one another during every day
life! It happens everywhere.
Think of a plane staying in the air - gravity wants the plane to come down, propulsion wants
it to move forward and the force of the air passing the wings pushes the plane upwards. None of
the 'forces' really get totally what they want. It is the compromise of the forces keeps the plane in
a state of linear motion through the air.
I Drew a Pretty Fantastic Plane
So there we have an explanation of how a cell can have and sustain an electrical charge.
I just want to familiarise you with two terms that will be important in the next chapter,
membrane potential and action potential.
Membrane Potential and Action Potential
The difference between the electrical charge inside the cell and the electrical charge outside
the cell (in the extracellular fluid) is what is known as the membrane potential. This is because the
cell has a potential to release energy based on this imbalance.
Think of an inflated ballon, this has a 'membrane potential'. A potential energy caused by the
difference in number of atoms held inside the balloon and that on the outside. This potential
energy is not released until there is a change in circumstance (i.e. the membrane permeability is
changed by a child and a large sharp pin!) at which point the energy is released! BANG!
The electrical ‘charge’ of a heart muscle cell (cardiomyocyte) is able to change (alter its
membrane potential) very quickly. This fast change in membrane potential is known as action
potential.
Chapter 6
Action Potentials
What is an Action Potential?
In cells an action potential is the sudden changing of the cells membrane potential (electrical
charge). This change in the cells electrical charge is important as it helps manipulate which ions
(electrically charged particles) can pass in and out of the cell. As we read earlier, particular ions
(calcium) entering the cell are the trigger that make it contract, so keep your eye out for the influx
of calcium ions.
Here is how the charge of the heart muscle cell (cardiomyocyte) is able to alter over and over
again.
Action Potentials
I have read and listened to so many explanations of action potentials and it is not a nice topic
and the subject is very dull and explained in a very similar way all the time. If you do want a
more clinical explanation then just google action potentials and you will be inundated. I am
going to attempt to use an analogy to explain the cycle the heart cells go through and hopefully
this will make things a little more digestible and memorable.... wish me luck. The heart cell cycle
has 4 stages.
I invite you to join me inside the Heart Cell Nightclub.
THE HEARTBEAT NIGHTCLUB
Phase 4
The empty night club. There is the potential for a lot of energy and dancing and music to
happen the building, bar and speakers are all in place. But without outside influences the
nightclub would just sit there doing nothing.
Luckily there are some staff (cleaners, barman, dj's) with keys that slowly filter into the
nightclub via the staff entrances and slowly set about getting the nightclub ready for business.
Phase 0
Thanks to the staff preparing the nightclub the main doors are ready to be opened. This is a
very popular nightclub and the hype is huge so there are crowds of people outside waiting to
come in. So many in fact that several sets of main doors are required. The crowds flood in filling
the club very quickly.
Phase 1
The club gets so full that the main doors are all closed and no more people are allowed to
enter. In fact it is so busy that some back door exits are opened and some people have already
had enough and start to leave. Phase 2
The doormen notice that people are leaving and decide they can start to let a few people in at
a time using a side entrance. For those that have ever queued at a nightclub, this is your classic
"one in one out" scenario. As people leave more people come in so the head count of people in
the nightclub remains pretty constant.
Phase 3 The club is ever so slightly starting to empty so the manager decides its time to close. No
more people are allowed in the nightclub and those remaining continue to leave through the
exits.
The process repeats every night;
Phase 4
Staff filter in and ready the nightclub.
Etcetera etcetera.
The Heartbeat Nightclub on a Graph.
This cycle of events that happens day in day out are all dependent on the preceding
eventuality. Believe it or not this is uncannily like how heart cells operate.
THE HEART CELL CONTRACTION
Phase 4.
Sodium and Calcium ions filter into the cardiomyocyte via gap junctions. These are
doorways where only particular ions can pass and in relatively small numbers. Sodium and
calcium ions have a positive electrical charge, therefore as they enter the cell they have an affect
on the its overall charge, making it more positive. Numerically, these ions alter the membrane potential of the cell from -90mV to -70mV.
Phase 0.
When the membrane potential of the cell is -70mV the main doors swing open. These are
voltage-gated ion channels, doors that are only open during particular voltages for particular
ions. In this phase the doorways that open are specific to sodium ions. Through the main doors
the sodium is able to flood into the cell. It does this because of diffusion, the concentrations of
sodium are high outside the cell and low inside the cell.
This very quickly changes the overall charge of the cell even further from -70mV to
around +20mV. We call this depolarisation because the cell has gone from a negative net charge
to a slightly positive net electrical charge.
Phase 1.
At around 20mV the sodium voltage-gated ion channels (main doors) close. At this point
another voltage-gated door opens specific to potassium. However this time there is large amounts
of potassium ions inside the cell so it flood outwards because of diffusion. Potassium ions have a
positive charge so as it leaves through these doors the overall charge of the cell becomes less
positive. 20mV to around 5mV.
Phase 2.
As the charge of the cell nears around 5mV a third set of voltage-gated doors open. These
allow calcium to enter the cell (because of diffusion). Calcium ions are positively charged so make
the cell more positive.
However...
The potassium ions leaving the cell and the calcium ions entering the cell cancel each other
out. The overall charge of the cell hovers around 5mV for a relatively long period of time.
Phase 3.
Eventually the charge of the cell does become less positive. This causes the calcium specific
voltage-gated ion channels to close, and the calcium ions no longer pass through them. The
potassium ions however continue to exit through their voltage-gated ion channels taking their
positive charge with them. The cell gradually becomes more negatively charged once more
reaching -90mV... seeing as the cell has regained its polarity, we call this repolarisation.
Once repolarised at around -90mV the potassium specific voltage-gated ion channels also
close.
The process repeats every heartbeat;
Phase 4
Sodium and Calcium filter into the cardiomyocyte via gap junctions.
Etcetera etcetera.
Heart Cell Action Potential on a Graph
In Summary
I know from experience that learning about action potentials, depolarisation and
repolarisation of cardiomycytes may be dull. More so the subject matter is often very alien and
hard to get your head around and remember. I hope that this nightclub analogy shows that the
change in 'state' of the cell is down to movement of ions (people), in and out of the cell
(nightclub) via channels (different doorways) that are only open at specific times.
Chapter 7
Pacemaker Cells
Starting a heartbeat.
THE ROLE OF PACEMAKER CELLS
The main bulk of the heart is made up from cardiomyocytes, so it is understandable that we
have focused on them and how an electrical signal moves like a wave through these cells causing
the heart to beat. Cardiomyocytes rely on an influx of ions from neighbouring cells to trigger
their action potential, without the influence of other cells, they would not contract. So what we
are yet to look at is how the electrical signal begins in the first place. Heartbeats start from cells
that are able to trigger their own action potential. This property is known as automaticity and is a
feature of pacemaker cells.
Pacemaker Cells can be found in the sinoatrial node, the atrioventricular node and the
bundles of His.
Where Pacemaker Cells Can Be Found
Sinoatrial Node
Atrioventricular
Node
Bundles of His
Automaticity
If we consider what we have learned about other heart cells, we know that membrane
potentials and action potentials are influenced by a few factors. These factors can be broken up
into categories; the cell structure, the cell’s environment and laws of physics.
• Membrane Permeability/Gap Channels ( Cell Membrane Structure)
• Ion Pumps (Cell Membrane Structure)
• Voltage Gated Ion Channels (Cell Membrane Structure)
• Diffusion (Laws of Physics)
• Magnetic Fields (Laws of Physics)
• Extracellular Fluid (Environment)
The environmental factors and the laws of physics are constants within the heart and do not
alter. However if a cell had a different membrane structure, it would change the cell’s membrane
potential and action potential (by affecting the movement of ions in and out of the cell).
If a man jumped from a plane without a parachute, he would plummet to the ground and
probably be annoyed that he had been written in to doing so. If that man had jumped from the
same plane with a parachute then he would drift gently to the earth and survive to tell the tale.
Gravity, terminal velocity, wind resistance, air pressure and weather would all have remained
constant. It is the change in the mans ‘structure’ that was able to changed the series of events.
Evolution has lead to pacemaker cell’s having a different structure which alters their
behaviour too. Through variations in their structure, pacemaker cell’s have the ability to ‘self
trigger’ or in other words, they can bring on their own action potential (automaticity).
This will probably make more sense if we look at the action potential of a pacemaker cell.
ACTION POTENTIAL OF A PACEMAKER CELL
The cell membrane is less permeable to potassium through gap junctions. Less potassium
leaks into the extracellular fluid which means that the cell’s ‘lowest’ membrane potential is less
negative than a cardiomyocyte’s, around -70mv.
Phase 4
Sodium from the extracellular fluid enters the pacemaker cells through gap junctions.
Sodium ions are positive and bring the cell’s voltage up to -40mV. This is the threshold for the
action potential to begin.
Phase 0
At -40mV calcium voltage gated ion channels open. Remember there is lots of calcium in the
extracellular fluid compared to the intracellular fluid, so as a result of the concentration gradient,
calcium pours into the cell. Calcium ions are also positive and therefore continue to make the
voltage of the cell more positive. Quickly reaching a voltage of around +10mV.
Phase 3
At this voltage the calcium voltage gated ion channels close and the potassium voltage gated
ion channels open. This has two effects, firstly the voltage of the cell no longer becomes more
positive as positive ions are no longer entering the cell. Instead positive ions are leaving the cell.
As a result of there being many more potassium ions inside the cell compared to the extracellular
fluid. The potassium ions pour outwards taking their positive charge with them. With these
positive ions leaving the cell the electrical charge of the cell becomes more negative. Eventually
the cell reaches -60mV, at this point the potassium voltage gated ion channels close and the
process is repeats itself.
Pacemaker Cell Action Potential on a Graph
Overall Electrical Charge
10mV
Calcium Voltage
Gated Ion
Channels Open.
Calcium Floods in.
0
Calcium Voltage Gated
Ions Close Potassium
Gates Open.
Potassium Floods Out
of the Cell.
3
0
3
Sodium
Filters
into the Cell.
4
4
-60 mV
Potassium Voltage Gated
Ion Channels Close
Time
4
WHY PHASE 4,0 AND 3?
When labeling the phases in pacemaker cells, scientists looked at the phases of a
cardiomyocyte and drew comparisons. The 3 phases of the pacemaker cell looked most similar to
phases 4, 0 and 3 of the cardiomyocytes action potential. I have not decided if this is more or less
confusing yet but it doesn’t really matter as I do not think I get a say.
Where the Phase Phase Numbers Came From
Action Potential In
a Cardiomyocyte
1
2
0
3
4
Action Potential In
a Pacemaker Cell
0
3
4
HOW DO PACEMAKER CELLS TRIGGER A HEARTBEAT?
The pacemaker cells are connected to cardiomyocytes in a very similar way to how they are
connected to one another. Through the intercalated discs there are gap junctions through which
ions can pass. During phase 0, where calcium ions flood in to the pacemaker cells, these ions will
diffuse through the shared cytoplasm, via the gap junctions and into the neighbouring
cardiomyocytes. The influx of calcium ions (and some sodium ions too) makes the cardiomyocyte
membrane potential become more positive. The cell reaches threshold and the action potential
begins. This starts the contraction and knock on affect within the connected cardiomyocytes.
Image of Pacemaker Cells Amongst Cardiomyocytes.
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S.A. NODE, A.V. NODE AND THE BUNDLES OF HIS.
At the beginning of the chapter I mentioned that there are a few places in the heart where
pacemaker cells can be found. These clusters of cells actually have slightly different properties to
one another. As a result they have differing lengths of phase 4. The phase of ‘rest‘ before they
reach threshold and their action potential begins. This means that were we to have a race
between the clusters of cells. The S.A. node cells would self trigger first, then the A.V. node cells
and finally the clusters of pacemaker cells found in the his bundles.
Relative Time Pacemaker Cells Take to Self Trigger
SA Node
AV Node
His Bundles
Time to Self Triggering (Automaticity)
There is good reason that we have more than one set of pacemaker cells, they start our
heartbeats so if one lot fails we do have a back up.
If, for example, the S.A. node was the only cluster of cells in the heart that could 'start' a
heart beat, the heart would be totally reliant on this cluster of cells working perfectly. If the S.A.
node failed, then your heart wouldn't beat and your long term health prospects would be hugely
affected.
AWAITING THEIR TURN
Quite a simple mechanism stops the other groups of pacemaker cells competing with one
another in the triggering of heartbeats. As the wave of ions moves through the hearts muscle
cells, all the following clusters of pacemaker cells are also triggered. This causes them to trigger
as part of a natural heartbeat, ‘resetting’ their own timer in the process.
So, apart from the S.A. node (which is the first in the series), the other clusters of pacemaker
cells do not get the opportunity to self trigger provided they are stimulated by cells that go before
them.
Other Pacemaker Cells Reset By Wave of Depolarisation (resting heart rate around 60bpm)
S.A. node self activates around
once per second. The wave of
depolarisation activates the A.V.
node and His bundles. These
pacemaker cells do not get a
chance to self activate.
ESCAPE BEATS
When cells other than the S.A. node are initiating a heart beat, this is called escape beats or
escape rhythm. A prolonged escape rhythm is often a result of a significant break down in the
conduction system where the electrical signal is not making it all the way through the heart.
How, When and Why Escape Beats and Rhythms Occur
S.A. node fails. The A.V. node is not
activated by a wave of
depolarisation. After around 1.5-2s
the A.V. node self activates. The
subsequent wave of depolarisation
activates the His bundles.
The His bundle cells do not get a
chance to self activate.
S.A. node activates but the A.V.
node fails. The wave of
depolarisation does not reach the
His bundles. After 2-3 seconds the
His bundles self activate. The
subsequent wave of depolarisation
activates the rest of the His
bundles and the Pirkinje fibres.
Escape rhythms are nearly always a precursor to pacemaker implant. Generally speaking, the
lower down the conduction system that the escape rhythm is being produced, the less ‘safe’ a
person is. I have never shared this analogy, but in my head I have always likened escape rhythms
to the people you would want flying your plane.
You Wouldn’t Want A Passenger Flying Your Plane... But You May Just Survive
Sinoatrial Node
Pilot
Atrioventricular Node
Co-Pilot
His Bundles
Flight Attendant
Pirkinje Fibres
Passenger
Chapter 8
Nucleus, Mitochondria and
Other Bits and Bobs
Mitochondria
Nucleus
Cells are incredibly complex structures, you could write entire books on each part of the cell
and what they are responsible for. So far I have stuck to the components and structure of heart
cells that make them different to other cells, enabling the heart to beat.
Just before you finish the book, I wanted to quickly mention some components of heart cells
that can be found in the majority of animal cells.
NUCLEUS
The cell nucleus is a membrane that encapsulates the cells DNA. For those of you that are
interested, cells that have a nucleus are known as eukaryotes, these include plant cells, animal
cells and fungi.
DEOXYRIBONUCLEIC ACID (DNA)
DNA is something that we are all familiar with. Inherited from our parents, DNA are
macromolecules that contain the genetic information required for the production of all the other
components of the cell. In essence DNA is the instruction manual used in the development and
functioning of all known living organisms (and many viruses too).
RIBONUCLEIC ACID (RNA)
RNA is a nucleic acid much like DNA and is also an essential component for all known forms
of life. RNA has a few different purposes in the human body some of which are covered below.
Structurally, RNA differs from DNA as it tends to be a single strand folded in on itself as opposed
to DNA which consists of a paired double strand.
MESSENGER RIBONUCLEIC ACID (MRNA)
mRNA is a specific type of RNA used as a messenger to carry the instructions for cell
structure and function to the ribosomes. Mature mRNA is a more refined version of mRNA with
some non essential regions called introns having now been removed. Think of this as a fully
edited video compared to RNA the pre-edited footage. The mRNA needs to be fully edited
before it is of any use to the ribosomes.
RIBOSOMES
Ribosomes are the sites of protein synthesis. That means that the ribosomes link amino acids
together to form proteins. They build proteins following the instructions delivered to them by the
mRNA.
TRANSFER RIBONUCLEIC ACID TRNA
tRNA is responsible for delivering amino acids to the ribosomes. Amino acids are the
ingredients that the ribosomes require to make specific proteins.
MITOCHONDRIA
Mitochondria are responsible for creating the cells energy currency ATP. One example use of
ATP is in sliding filament theory where ATP is involved in straightening out a myosin head
allowing it to reach further along the actin protein.
This is in no way a comprehensive list and many of the components listed have multiple
functions not mentioned. I just wanted to give a very brief overview of the most well known
structures. If you are interested in general cell structure there is plenty on google and youtube to
keep you busy.
You may also want to search:
• Nucleolus
• Vesicle
• Rough endoplasmic reticulum
• Golgi apparatus (or "Golgi body")
• Cytoskeleton
• Smooth endoplasmic reticulum
• Vacuole
• Lysosome
• Centrosome
Disclaimer
Although the author and publisher have made every effort to ensure that the information in
this book was correct at press time, the author and publisher do not assume and hereby disclaim
any liability to any party for any loss, damage, or disruption caused by errors or omissions,
whether such errors or omissions result from negligence, accident, or any other cause.
Other Available Titles
Other Books Coming/Available in this Series:• Heart Cells Made Easy
• Pacemakers Made Easy
• The Heart Made Easy
• Arrhythmia Made Easy
• The ICD Expansion Pack
DEDICATION
To my two hamsters both named Theodore. I am sorry that the family cat
was so prolific.
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