Atrial fibrillation (AF) is one of the most common arrhythmias in the elderly. In many cases AF is associated with underlying cardiovascular pathology, but AF can also occur in aged individuals with otherwise normal hearts. This suggests that age-dependent modifications of atrial function can cause AF. In preliminary experiments we have established that aged (24 month old) mice are more prone to pacing-induced AF than young mice. As in ventricular myocytes, a rise in intracellular Ca2+ triggers atrial myocyte contraction. While the role of alterations in intracellular Ca2+ in the generation of ventricular arrhythmias has been demonstrated, the impact of altered Ca2+ handling in the genesis of AF has not been firmly established. The central hypothesis of this fellowship application is that alterations in atrial myocyte Ca2+ handling contribute to AF in aging hearts. Specifically, we aim to demonstrate that pathologic diastolic SR Ca2+ release (leak) is a contributing factor in AF and that repairing this dysfunction will provide therapeutic strategies for treating AF in humans.

Public Health Relevance

Atrial fibrillation is the most common cardiac arrhythmia and is a major health concern for the elderly. More than 2 million individuals and 9% of people over the age of 80 suffer from atrial fibrillation in the United States. This project will increase our understanding of the cellular basis for atrial fibrillation in the elderly and provide targets for novel therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL107029-03
Application #
8352101
Study Section
Special Emphasis Panel (ZRG1-F10A-S (20))
Program Officer
Meadows, Tawanna
Project Start
2011-05-01
Project End
2013-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$53,942
Indirect Cost
Name
Masonic Medical Research Laboratory, Inc
Department
Type
DUNS #
077307437
City
Utica
State
NY
Country
United States
Zip Code
13501