Muscle activity is regulated by the cytoplasmic Ca2+ concentration. Contraction initiated by Ca2+ release from the sarcoplasmic reticulum while relaxation follows the reaccumulation of the Ca2+ by the sarcoplasmic reticulum. Ca2+ release is activated by an unknown mechanism following depolarization of the action potential. Ca2+ transport into the sarcoplasmic reticulum is mediated by the Ca2+, Mg2+-ATPase. The purpose of this research project is to investigate several functional properties of isolated sarcoplasmic reticulum vesicles and T-tubule vesicles in order to increase our understanding of how the cytoplasmic Ca2+ concentration is regulated in the muscle fiber. We would like to investigate: 1. The relationship between Ca2+ and H+, K+ and potential gradients across the sarcoplasmic reticulum membrane. 2. The mechanism by which calsequestrin (a Ca2+-bindidng protein in the sarcoplasmic reticulum lumen) aggregates. 3. The mechanism of Ca-induced Ca release. 4. The structure and function of the voltage-gated Ca2+ channel of the T-tubule. The ultimate goal of this research is to establish an in vitro system to study excitation-contraction coupling.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM029300-05
Application #
3276858
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1981-04-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. Uniformed Services University of Health Science
Department
Type
Schools of Medicine
DUNS #
City
Bethesda
State
MD
Country
United States
Zip Code
20814