Researchers discover how heart arrhythmia occurs
Researchers have discovered the fundamental biology of calcium waves in relation to heart arrhythmias.
The findings published this month in the January 19 edition of Nature Medicine outlines the discovery of this fundamental physiological process that researchers hope will one day help design molecularly tailored medications that correct the pathophysiology.
Heart arrhythmias cause the heart to beat irregularly, resulting in symptoms such as dizziness and fainting, or in severe cases, sudden arrhythmic death. While many factors contribute to the development of arrhythmias, including genetics, scientists know that a common mechanism of cardiac arrhythmias is calcium overload in the heart, i.e. calcium-triggered arrhythmias that can lead to sudden death. The underlying mechanism of these calcium-triggered arrhythmias has remained a mystery for decades.
Using a combination of molecular biology, electrophysiology, and genetically engineering mice, scientists at the University of Calgary’s and Alberta Health Services’ Libin Cardiovascular Institute of Alberta (Libin Institute)have discovered that a calcium-sensing-gate in the cardiac calcium release channel (ryanodine receptor) is responsible for initiation of calcium waves and calcium-triggered arrhythmias.
Utilizing a genetically modified mouse model they were able to manipulate the sensor and completely prevented calcium-triggered arrhythmias.
“The calcium-sensing- gate mechanism discovered here is an entirely novel concept with potential to shift our general understanding of ion channel gating, cardiac arrhythmogenesis, and the treatment of calcium-triggered arrhythmias,” says SR Wayne Chen, PhD, the study’s senior author and University of Calgary- Libin Institute researcher. “These findings open a new chapter of calcium signaling and the discovery fosters the possibilities of new drug interventions.”
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An arrhythmia is an irregular heartbeat - the heart may beat too fast (tachycardia), too slowly (bradycardia), too early (premature contraction) or too irregularly (fibrillation). Arrhythmias are heart-rhythm problems - they occur when the electrical impulses to the heart that coordinate heartbeats are not working properly, making the heart beat too fast/slow or inconsistently.
Many heart arrhythmias are harmless. We all occasionally experience irregular heartbeats, which may feel like a racing heart or fluttering. Some arrhythmias, however, especially if they veer too far from a normal heartbeat or result from a weak or damaged heart, may cause troublesome and even potentially fatal symptoms.
Rapid arrhythmias are called tachycardias, while slow ones are called bradycardias. Irregular arrhythmias - when the heartbeat is irregular - are called fibrillations, as in atrial or ventricular fibrillation. When a single heartbeat occurs earlier than it should it is called premature contraction.
The English word “arrhythmia” comes from the Greek word rhymos, meaning “rhythm”, the Greek suffix a (letter “a” added to the beginning of a word) means “loss” - put together they mean “loss of rhythm”.
What are the signs and symptoms of arrhythmia?
Some patients may have no symptoms at all. A doctor may detect a sign of arrhythmia during a routine examination. (The patient detects/feels a symptom, and other people, such as the doctor or other members of the household, detect a sign).
This work was supported by research grants from the Canadian Institutes of Health Research, the National Institutes of Health, the Heart and Stroke Foundation of Alberta, and the Canada Foundation for Innovation.
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Marta Cyperli
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University of Calgary