While the efficiency of cardiac excitation-contraction (E-C) coupling in heart failure undergoes a defective down-regulation, that in hibernating mammals is up-regulated. The long-term objective of the proposed research is to find the cellular and molecular mechanism of E-C coupling regulation in hibernators, and seek to apply them in rescuing failing hearts.
The specific aims, hypotheses and research designs are: 1) to test the hypothesis that the Ca2+ influx tends to activate more Ca2+ release from sarcoplasmic reticulum hibernating than awake hibernators such that the E-C coupling efficiency can be increased. This will be achieved by combining electrophysiological recording and confocal Ca2+ imaging. 2) to test the hypothesis that, in a single E-C coupling unit, Ca2+ release channels become more responsive to single-channel Ca2+ trigger during hibernation, but less in impaired E-C coupling during heart failure. The intermolecular coupling fidelity and latency and signal mass of Ca2+ sparks in failing and hibernating models will be analyzed using our recently developed loose-patch confocal imaging. 3) to test the hypothesis that different changes in the unitary properties of Ca2+ underlie the opposite alternation of E-C coupling efficiency in hibernation and heart failure. The strength and kinetics of single-channel Ca2+ release and micro-recruitment of release channels in failure and hibernation models will be assessed by analyzing the quantal property of Ca2+ sparks recently found by this PI. The above study will reveal the molecular details underlying the opposite modifications of E-C coupling occurred in hibernation and heart failure. This will provide necessary and important basis for further studies to rescue failing heart with strategies employed by hibernators.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Project (R01)
Project #
5R01TW007269-02
Application #
7127735
Study Section
Special Emphasis Panel (ZRG1-BDA-E (50))
Program Officer
Liu, Xingzhu
Project Start
2005-09-27
Project End
2010-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$52,731
Indirect Cost
Name
Peking University
Department
Type
DUNS #
653934935
City
Beijing
State
Country
China
Zip Code
10087-1
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