Grant: Operating Grant

Atrial fibrillation (AF) is a condition of the upper heart chambers in which the normal transmission of electrical signals in the heart is lost. AF is the most common electrical abnormality of the human heart, and is especially common in the aging population (for example 10 % of people in their 80's show signs of AF). The random electrical signals produced during AF result in improper communication (timing of coordinated pumping) between upper and lower heart chambers and impaired upper chamber function (pumping). Thus, long-lasting bouts of AF significantly increase the risk for stroke and other cardiovascular complications. Lastly, a single bout of prolonged AF is believed to reprogram the cells of the upper chambers so that they are more susceptible to future AF events. In other words once you have an AF episode, it becomes much more likely you will have another. Our preliminary work in dog hearts and genetically altered mice and has identified Rgs4 as a key protein that normally protects hearts from AF. Once Rgs4 function is compromised the susceptibility to AF dramatically increases, especially in aging mice. Using the same mouse and dog models described above we have also shown that that AF can expression another protein, Kir6.2 that contributes significantly to the adverse electrophysiology remodeling of upper chambers. This work aims to understand the molecular connections between RGS4 and Kir6.2 function during the development of persistent AF.