Irregular Heart Beat: Support for Controversial Theory
Atrial fibrillation, the most common form of human heart beat irregularity, can be fatal if left untreated. Some clinicians believe it is caused, in part, by calcium leaking from a cellular store in heart cells, potentially through the RyR2 channel, although this mechanism remains controversial.
Now, a team of researchers at Baylor College of Medicine, Houston, and Dresden University of Technology, Germany, has provided support for this hypothesis by showing that the protein CaMKII can enhance RyR2-mediated calcium leak, promoting atrial fibrillation in mice.
The team, led by Xander Wehrens and Dobromir Dobrev, studied mice engineered to express a mutant form of RyR2 associated with calcium leak. Although they did not spontaneously develop atrial fibrillation, these mice were more likely to develop atrial fibrillation than normal mice if their heart rate was forced up.
The development of atrial fibrillation in these mice was related to the functional interaction of CaMKII with RyR2. Blocking CaMKII function in these mice prevented them from developing atrial fibrillation when their heart rate was forced up.
As a functional link between CaMKII and RyR2 was observed in heart biopsies from patients with chronic atrial fibrillation, the authors suggest that enhanced CaMKII function might increase calcium leakage via RyR2 and initiate clinical atrial fibrillation.
SOURCE: Journal of Clinical Investigation, June 15, 2009