The proposed studies will examine the role of cardiac troponin C (cTnC) in cardiac muscle relaxation.
Specific Aim 1 : Examine factors that control Ca2+ binding and exchange with cTnC in the absence and presence of cTnI by generation of cTnC mutants with dramatically faster or slower Ca2+ dissociation rates from the regulatory site of the cTnC-TnI complex.
Specific Aim 2 : In order to examine the contribution of Ca2+ dissociation from the cTnC-TnI complex to the rate of muscle relaxation, skinned cardiac trabeculae devoid of functional SR will be induced to relax by flash photolysis of a caged Ca2+ chelator diazo-2 after reconstitution with cTnC mutants that exhibit dramatic differences in Ca2+ affinities and dissociation rates.
Specific Aim 3 : In order to examine the contribution of Ca2+ dissociation from the cTnC-TnI complex to the rate of intact cardiac muscle relaxation, contractile properties of electrically stimulated trabeculae will be examined after adenoviral expression of cTnC mutants that exhibit dramatic differences in Ca2+ affinities and dissociation rates. Further insight into the relaxation process will improve understanding of the mechanisms of cardiac muscle diseases that alter relaxation rates.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL073600-01
Application #
6646379
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Commarato, Michael
Project Start
2003-05-01
Project End
2006-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Ohio State University
Department
Physiology
Type
Schools of Medicine
DUNS #
071650709
City
Columbus
State
OH
Country
United States
Zip Code
43210