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Enzyme doesn't act alone in atrial fibrillation
Date:6/17/2009

HOUSTON (June 17, 2009) An overactive enzyme is behind a leaky calcium channel that plays a role in the development of atrial fibrillation, which is the most common cardiac arrhythmia that is responsible for a third of all strokes. However, it doesn't act alone, say researchers at Baylor College of Medicine. The findings can be found online in the current edition of the Journal of Clinical Investigation.

"When the heart pumps properly, the muscle contractions are regulated by waves of calcium. When the heart relaxes, the calcium is stored; when the heart contracts, it is released," said Dr Xander Wehrens, assistant professor of molecular physiology and biophysics, and cardiology at BCM. "In atrial fibrillation, the calcium is released too early. As it leaks out, the heart beats too fast and irregularly."

Researchers knew that an enzyme called calmodulin kinase II is overactive in several heart diseases and believed it played a role in the leaky channels a tiny pore that controls release of calciu through the cell's membrane. In the current study, Wehrens and colleagues were able to show in mouse models that if this enzyme is inhibited, calcium channels normalize and atrial fibrillation is prevented.

To determine if the calcium leak alone was enough to set off atrial fibrillation, researchers bred a mouse with a specific genetic mutation in the calcium channel, making it prone to leaks.

"The mice were fine. They did not develop atrial fibrillation despite the leak," Wehrens said. "There had to be another factor that contributed to arrhythmias."

Wehrens said they discovered that a sudden increase in heart rate is a very specific activator of calmodulin kinase II. The research team found that mice with the mutation were more prone to atrial fibrillation after their heart rate was sped up, activating the enzyme. Mice that lacked the mutation did not suffer from arrhythmias despite having the enzyme activa
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Contact: Graciela Gutierrez
ggutierr@bcm.edu
713-798-4710
Baylor College of Medicine
Source:Eurekalert

Page: 1 2

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