Cardiac contractility

Definitions & Key takeaways

Contractility is the ability of the heart muscle to contract and thereby pump blood. Cardiac contractility is determined by the interaction between intracellular calcium concentration, and the myofilament cross-bridge cycling. The Frank-Starling mechanism is a key factor in determining cardiac contractility. This mechanism states that the more stretched (tensed) a heart muscle fiber is, the more calcium it will release from its stores, leading to increased contraction force.

Chapters:

Watch video only

Introduction0:00–0:28

The main job of the heart is to pump blood all over the body to our organs and tissues and keep them oxygenated. It does.
So by contracting around 70 times per minute, the physiological basis of cardiac contractility is the synchronous contraction of heart muscle cells.
AK A cardiomyocytes, cardiac contractility is a measure of the strength of cardiomyocytes to contract. In order for cardiomyocytes to contract, they first need to depolarize.

Depolarization0:28–1:34

Depolarization is when ions move across the membrane of a cell and the membrane potential becomes less negative or even slightly positive.
Think of a really pessimistic negative cell, throwing his hands up and enjoying a moment of joy. When one cell depolarizes enough, it can cause some ions like calcium to flow into neighboring cells and trigger them to depolarize as well.
If one cell after another depolarizes, then there's a depolarization wave which you can imagine would look like a wave moving through a crowd at a football stadium.
Each depolarization wave causes a heart muscle contraction. So the rate at which depolarization waves ripple through the heart actually sets the heart rate.
This depolarization wave starts with the sinoatrial node which sometimes gets called the sa node and then moves through the rest of the heart to cause a contraction.
So if depolarization waves are going through about once per second, that means that your heart beats once per second or 60 times in a minute.

Cardiomyocyte1:34–1:57

Now, let's zoom in on a cardiomyocyte. These hard working cells have branches and intercalated discs along their edges which have small holes called gap junctions that allow ions to flow from one cardiomyocyte to the next.
When ions like calcium move from that cell into a neighboring cell, this triggers depolarization and cardiomyocytes depolarize one after the other, another feature of cardiomyocytes are passageways called transverse tubules or T tubules.

Transverse Tubules1:57–2:50

T tubules are invaginations or tunnels of the cardiomyocyte membrane that increase the surface area of the cardiomyocyte.
And they look like the letter T. So it's easy to remember their name.
One last important element to depolarization and contraction is the sarcoplasmic reticulum, which is an organelle that stores the intracellular calcium.
When a depolarization wavefront hits a cardiomyocyte, a few calcium ions flow through gap junctions. Looking at the cell membrane.
If a threshold membrane potential is reached, then sodium channels start to open up. If there's a depolarization, then calcium and sodium ions start to move across the cell membrane and into the cell.
That's where the t tubules play a key role by bringing calcium deep into the cell. Once this extracellular calcium gets inside, it binds to the ryanodine receptors on the sarcoplasmic reticulum which releases even more calcium into the cell.

Calcium-induced calcium release2:50–3:31

A process called calcium induced calcium release. This process helps to activate two contractile proteins, actin and myosin, which are called myofilaments.
Myosin is able to attach and pull actin with the help of adenosine triphosphate or ATP to form cross bridges that result in shortening of the muscle fiber.
Eventually, calcium ions are removed by iron transporters that rely on ap or concentration ingredients. Now that we understand how a cardiomyocyte contracts.

Cardiomyocyte Contractility3:31–4:24

We can look at the various factors that affect cardiomyocyte contractility, contractility is directly related to the concentration of calcium within the cardiomyocyte.
So, any factors that increase intracellular calcium level will increase cardiac contractility. Since calcium is stored in the sarcoplasmic reticulum, concentrations of calcium will vary with how much calcium there is intracellularly and how much calcium is stored within the sarcoplasmic reticulum that is available to be released.
One of the main methods, intracellular calcium can be changed is with the autonomic nervous system. The heart is innervated by both parasympathetic and sympathetic neurons of the autonomic nervous system.
Sympathetic neurons have a positive inotropic effect where positive means increase and inotropic refers to contractility.
So sympathetic stimulation increases cardiac contractility by releasing catecholamines like norepinephrine, which bind to beta one receptors on cardiomyocytes.

Sympathetic Stimulation4:24–5:30

Activation of the beta one receptors leads to downstream phosphorylation of proteins like sarcolemmal calcium channels on the sarcoplasmic reticulum membrane which increases the sarcoplasmic reticulums ability to release calcium phosphorylation of phospholamban.
A protein found on the sarcoplasmic reticulum membrane regulates calcium ATPase a calcium pump which transports calcium from the cytoplasm into the sarcoplasmic reticulum.
When phosphorylated, these calcium pumps become activated which increases the amount of calcium brought back into the sarcoplasmic reticulum, resulting in greater uptake in storage.
This increases calcium stores for subsequent depolarizations. Finally, phosphorylation of plasma membrane L type calcium channels will increase their permeability to calcium allowing increased amounts of extracellular calcium entry into the cardiomyocyte.
On the other hand, parasympathetic stimulation has a negative inotropic effect. So it decreases contractility mainly due to acetylcholine activating muscarinic m two receptors on cardiomyocytes.

Parasympathetic Stimulation5:30–6:09

This leads to a downstream cascade of intracellular events that ends with inhibition of calcium channels with less working calcium channels.
There is less calcium moving into the cell and less calcium released from the sarcoplasmic reticulum leading to decreased contractility.
In addition, parasympathetic stimulation also acts on the sinoatrial node. Decreasing heart rate.
Heart rate itself can also independently change contractility. For example, with a higher heart rate, there are more action potentials per unit of time and each action potentials inward calcium influx results in an increase in the total calcium that enters the cell with greater amounts of calcium entering the cell.

Contractility6:09–7:12

The sarco plasmic reticulum also accumulates more calcium for subsequent action potentials. Additionally, if the increase in heart rate is due to sympathetic stimulation, phosphorylation of phospholamban and sarcolemmal calcium channels increases release uptake and storage of calcium within the sarcoplasmic reticulum.
This can be seen graphically as the positive staircase effect where an increase in heart rate is shown to increase inotropy gradually.
At first as calcium is not yet accumulated. But with each successive beat more calcium is available for the sarcoplasmic reticulum with a corresponding increase in inotropy.
Until finally, a maximum storage level is reached and a maximum inotropy is seen. This effect can also be seen in post extrasystolic potentiation phenomenon.

Postextrasystolic Potential Phenomenon7:12–8:02

Postextrasystolic means following an additional premature heartbeat. So, a heartbeat that is not commanded by the sign of atrial node.
For whatever reason, this premature beat has a less than normal strength of contraction. As the ryanodine receptors on the sarcoplasmic reticulum have a transient refractory period at this point causing a transient decrease in calcium within the cardiomyocyte.
After this premature beat. Sarcoplasmic calcium load is increased as this premature beat did not allow the sarcoplasmic reticulum to release calcium from the last two beats.
And all of the calcium that's built up gets released together, resulting in an increased contraction. Sometimes that increased forceful contraction can be felt by those who are experiencing an extra systolic beat.

Digoxin8:02–9:29

Another way intracellular calcium can be increased is with a class of drugs called glycosides. They are extracted from the Foxglove plant digitalis purpurea.
The most commonly used glycoside is digoxin and it works by inhibiting the sodium potassium ATPase located in the cell membrane of the cardiomyocyte by binding to the extracellular potassium binding site.
Normally, the sodium potassium ATPase will pump out three sodiums for every two potassiums that it pumps in. With the help of one ap when sodium potassium ATPase is inhibited, less sodium is pumped out of the cell which builds up the intracellular sodium concentration and decreases the sodium gradient across the cell membrane.
This decrease in the sodium gradient affects the function of a calcium sodium exchanger which normally pumps one calcium out of the cell against its electrochemical gradient by using the energy from a sodium moving into the cell down its electrochemical gradient.
Since less sodium is pumped out by the sodium potassium ATPase, less calcium is able to be pumped out by the calcium sodium exchanger.
As a result, the intracellular calcium increases and inotropy increases. The main use of this class of drugs is for patients with congestive heart failure, whose ventricles can't contract hard enough to pump enough blood into the body.
So this class of drug is used to stimulate contractility. All right, as a quick recap cardiomyocyte contractility depends on intracellular calcium concentration.

Review9:29–10:03

This concentration can be modified by autonomic nervous system input where sympathetic activation increases contractility and parasympathetic activation decreases, contractility, contractility can also be increased independently by an increase in the heart rate.
And finally, a class of drugs called glycosides like digoxin can be used by patients who need some extra help with contractility.
Like those with heart failure