This application proposes to study the hypothesis that atrial dilatation and acetylcholine alter the properties of ionic channels expressed in pediatric human atrial tissue. Atrial tachyarrhythmias are a common arrhythmias in children and cause morbidity from systemic embolization and stroke. The basis for atrial arrhythmias implicate atrial dilatation and increased vagal tone, but virtually nothing is known about the effects of dilatation and cholinergic agonists on the cellular electrophysiological properties of pediatric human atrial myocardium. The underlying hypothesis is that the action potential, and hence the refractory period, in human atria under these conditions is decreased, as suggested by animal studies and by preliminary data in pediatric human atria. The study will employ patch clamp methods to investigate relevant ion channel function to investigate the mechanisms for this action potential shortening. These will include the transient outward potassium channel, delayed rectifier channel, sustained current, calcium current, and sodium current.
The first aim will measure action potentials to confirm the hypothesis that action potential duration is shortened under these conditions in human pediatric atrium.
The second aim will survey ion currents thought to play a role or potentially play a role in action potential duration. The third through fifth aims will focus on hypotheses involving regulation of transient outward current, and calcium current, two primary suspects behind the cellular mechanisms for action potential shortening in this setting.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL058806-03
Application #
6030849
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1997-08-15
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Tulane University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118