Study Uncovers Physiological Process Behind Heart Arrhythmias

According to a new study, researchers have determined how heart arrhythmias occur, determining the fundamental biology of calcium waves in relation to this pathophysiology. Scientists at the University of Calgary's and Alberta Health Services' Libin Cardiovascular Institute of Alberta used a combination of molecular biology, electrophysiology, and genetically engineered mice to discover that a calcium-sensing-gate in the cardiac calcium release channel is responsible for initiation of calcium waves and calcium-triggered arrhythmias. Using a genetically modified mouse model, the researchers were able to manipulate the sensor and completely prevent calcium-triggered arrhythmias. The mechanism discovered in this study is an “entirely novel concept,” with the potential to enhance the general understanding of ion channel gating, cardiac arrhythmogenesis, and the treatment of calcium-triggered arrhythmias, according to study authors, who note that this discovery advances the possibilities of new drug intervention. The study findings demonstrate that “genetically suppressing the Ca sensor that is responsible for the initiation of Ca waves completely protects mice from Ca triggered arrhythmias,” says Wayne Chen, PhD, professor in the department of physiology and biophysics and the department of biochemistry and molecular biology at the University of Calgary, and the study’s senior author. Carvedilol, a non-selective beta blocker indicated in the treatment of mild to severe congestive heart failure, “has been known to stabilize this Ca sensor,” says Chen, who notes that carvedilol is the only beta-blocker tested that is able to suppress Ca wave-evoked cardiac arrhythmias. “Therefore,” he says, “drugs that are able to suppress the Ca sensor—like carvedilol—may be superior in the treatment of arrhythmias.” —Mark McGraw Reference Chen W, Wang R, et al. The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias. Nature Medicine. 2014.