Researchers find cause of calcium-triggered arrhythmias

Date: Jan-20-2014A new study published recently in Nature Medicine describes how researchers

in Canada have discovered the underlying biological mechanism of calcium waves in the heart and

how they trigger a type of arrhythmia that can lead to sudden death.

The researchers, led by senior author Dr. SR Wayne Chen, an electrophysiologist at the University of

Calgary's Libin Institute, hope their discovery will lead to new "molecularly tailored" drugs

to treat this type of arrhythmia.

Heart arrhythmia means something is not right with the rate or rhythm of the heartbeat -

it is either too fast, too slow or irregular. This disrupts blood flow, and while most

arrhythmias are harmless, some can be serious and even life threatening.

While many factors contribute to the development of heart arrhythmias, including genetics,

scientists know that one mechanism is calcium overload in the heart. This disrupts the finely

controlled electrical activity that governs contraction of heart muscle.

Calcium-triggered arrhythmias can lead to sudden death, but exactly how they arise has been

a mystery for decades, until now.

For their study, the team focused on how calcium ions are released from cells' internal

stores to help regulate the electrical activity behind heart rhythm. They looked at one part of this system in particular - the ryanodine receptor, a key

mechanism for the release of calcium ions.

Manipulating calcium sensor prevented calcium-triggered arrhythmias

Working with genetically engineered mice, and bringing together expertise in molecular

biology and electrophysiology, they discovered that a calcium-sensing gate in the ryanodine

receptor is responsible for generating calcium waves and calcium-triggered arrhythmias.

In their study report they describe manipulating the calcium sensor in the mice, and how

doing so completely prevented calcium-triggered arrhythmias.

Dr. Chen says:

"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.

These findings open a new chapter of calcium signaling and the discovery fosters the

possibilities of new drug interventions."

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 helped

finance the study.

In January 2013, researchers from the Massachusetts General Hospital in Boston reported that

some antidepressants may increase

arrhythmia risk. Writing in the British Medical Journal, they said SSRIs

(selective serotonin reuptake inhibitors) are associated with a long QT interval - the duration

of electrical activity of the heart muscle, and a marker for heart rhythm abnormalities.

Written by Catharine Paddock PhD




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