Arrhythmia in people with no genetic predisposition is an acquired condition

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When encountering a charging predator or participating in a triathlon, the human heart responds by beating faster to increase blood supply to muscles.

It is a natural and well-understood reaction to stress.

However, there are times when emotional or physical stress causes the heart to beat with an irregular or abnormal rhythm, a condition called arrhythmia that is the focus of research by Dr. Filip Van Petegem of the Department of Biochemistry and Molecular Biology at the University of British Columbia.

In a paper published May 8, 2019 in Molecular Cell, Van Petegem sheds new light on how two proteins interact in the heart in cases of stress-induced arrhythmia, and on potential treatment.

“The big picture of our work is to understand how stress signals affect a protein in the heart muscle that is critical for heart contraction,” said Van Petegem.

In a stress situation, that heart protein receives a tag from another protein, and the tag allows more efficient delivery of calcium, key to contraction.

“Normally, the protein is tagged, the heart rate goes up, then the tag is removed and all is fine,” he said.

“This process allows the heart to adapt to the needs of the environment.

“But if the tags stay too long or there are too many tags, calcium can be delivered between heartbeats.

That starts to affect the electrical signals in the hearts and can cause arrhythmia.”

Heart arrhythmia can be acquired by people who are stressed, even with no genetic predisposition
The full Ryanodine Receptor (grey) with the enzyme (blue) and the domain that receives the tag (red). Credit: Canadian Light Source

Arrhythmia in people with no genetic predisposition is an acquired condition, he explained, “and once you have it, it often progresses.”

It serves as a warning signal for more persistent forms of arrhythmia.

“Our research looked at the protein that delivers the tag – how it recognizes the protein on which it has to deliver the tag, and how that tag delivery happens.”

To find the answer, Van Petegem and his colleagues created crystals from the proteins.

They then used X-ray diffraction at the Canadian Light Source (CLS) at the University of Saskatchewan to produce 3-D images that revealed a structure that shows how the tag is delivered.

“The structure was quite a surprise,” he said. “We thought, this is weird, but we tested it in various ways and it was always there.”

With this new understanding of the tag-delivery mechanism between proteins, “we’ve identified a lot of areas where we think a small molecule could be used to interrupt the excessive tagging.

It’s hypothetical but it’s definitely an avenue worth pursuing.”

In addition to identifying the structure between proteins, Van Petegem’s research also found that the structure was subject to genetic mutation, and identified how the tag changes the properties of the protein.

Van Petegem pointed out the published research involved only one of two main proteins that deliver tags.

The second “is equally as important if not more important, and they seem to interfere with each other.”

He hopes to repeat the study on the second protein if crystals can be produced, “but that can sometimes be very tricky.”


The term “arrhythmia” refers to any change from the normal sequence of electrical impulses.

The electrical impulses may happen too fast, too slowly, or erratically – causing the heart to beat too fast, too slowly, or erratically.

When the heart doesn’t beat properly, it can’t pump blood effectively. When the heart doesn’t pump blood effectively, the lungs, brain and all other organs can’t work properly and may shut down or be damaged. 

Types of Arrhythmias

  • Atrial Fibrillation = upper heart chambers contract irregularly
  • Bradycardia = slow heart rate
  • Conduction Disorders = heart does not beat normally
  • Premature contraction = early heart beat
  • Tachycardia = very fast heart rate
  • Ventricular Fibrillation = disorganized contraction of the lower chambers of the heart
  • Other Rhythm Disorders
  • Types of Arrhythmia in Children

The normal heart is a strong, muscular pump a little larger than a fist.

It pumps blood continuously through the circulatory system.

Each day the average heart beats (expands and contracts) 100,000 times and pumps about 2,000 gallons of blood through the body.

In a 70-year lifetime, an average human heart beats more than 2.5 billion times.

Electrical signals control the pump

The heart beat (contraction) begins when an electrical impulse from the sinoatrial node (also called the SA node or sinus node) moves through it. The SA node is sometimes referred to as the heart’s “natural pacemaker” because it initiates impulses for the heartbeat.

The normal electrical sequence begins in the right atrium and spreads throughout the atria to the atrioventricular (AV) node. From the AV node, electrical impulses travel down a group of specialized fibers called the His-Purkinje system to all parts of the ventricles.

This exact route must be followed for the heart to pump properly. As long as the electrical impulse is transmitted normally, the heart pumps and beats at a regular pace. In an adult, a normal heart beats 60 to 100 times a minute.

Electrocardiography (ECG or EKG) is a painless, non-invasive procedure that records the heart’s electrical activity and can help diagnose arrhythmias.

Abnormal heart rhythms (arrhythmias)

Arrhythmias are abnormal beats. The term “arrhythmia” refers to any change from the normal sequence of electrical impulses, causing abnormal heart rhythms. Arrhythmias may be completely harmless or life-threatening.

Some arrhythmias are so brief (for example, a temporary pause or premature beat) that the overall heart rate or rhythm isn’t greatly affected. But if arrhythmias last longer, they may cause the heart rate to be too slow or too fast or the heart rhythm to be erratic – so the heart pumps less effectively.

  • A fast heart rate (in adults, more than 100 beats per minute) is called tachycardia.
  • A slow heart rate (less than 60 beats per minute) is referred to as bradycardia.

Causes

  • Normally, the heart’s most rapidly firing cells are in the sinus (or sinoatrial or SA) node, making that area a natural pacemaker.
  • Under some conditions almost all heart tissue can start an impulse of the type that can generate a heartbeat.
  • Cells in the heart’s conduction system can fire automatically and start electrical activity. This activity can interrupt the normal order of the heart’s pumping activity.
  • Secondary pacemakers elsewhere in the heart provide a “back-up” rhythm when the sinus node doesn’t work properly or when impulses are blocked somewhere in the conduction system.

More information: Omid Haji-Ghassemi et al. The Cardiac Ryanodine Receptor Phosphorylation Hotspot Embraces PKA in a Phosphorylation-Dependent Manner, Molecular Cell (2019). DOI: 10.1016/j.molcel.2019.04.019

Journal information: Molecular Cell
Provided by Canadian Light Source

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