Abstract

Long term objective of this project is to elucidate molecular sources of observed variations in energetic and mechanical properties of striated muscle contraction. Properties to be investigated include: rate of energy liberation during an isometric tetanus and rate of mechanical relaxation. Experiments will be performed on fibers isolated with intact membranes from frog skeletal muscles. Individual fibers will be studied in order to take advantage of naturally occurring variation among fibers in muscles. Hypotheses and specific aims are: I. Isometric energy liberation is a function of composition of the myosin molecule and concentration of parvalbumin (PV). Energy liberation due to cross-bridge cycling at 0 degrees C will be related to heavy and light chain composition of myosin molecule. Correlations will be sought between concentration of PV and magnitude of labile energy liberation. Myosin and PV isoforms will be determined by polyacrylamide gel electrophoresis. II. Parvalbumin is a soluble relaxing factor. Time course of progressive slowing of relaxation and subsequent recovery will be determined as a function of tetanus duration and temperature from 0 to 20 degrees C. Correlations will be sought between concentration of PV and extent of slowing of relaxation at 0 degrees C. Using purified frog PV and stopped-flow techniques at 0 to 20 degrees C, rate of dissociation from PV of: a) Mg2+ will be compared to time course of slowing of relaxation (and evolution of labile energy) and b) Ca2+ will be compared to subsequent recovery of relaxation speed. Ratio of affinities of Ca2+ and Mg2+ for PV will be related to amount of labile energy. Rate of Ca2+ uptake by isolated sarcoplasmic reticulum from 0 to 20 degrees C will be compared to rate of relaxation in prolonged tetani in fibers. PV probably exists in all fast contracting skeletal muscles. Concentration is high in frog, making it useful for study. Proposed experiments provide stringent tests for the putative role of PV in muscle function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR020792-11
Application #
3155136
Study Section
Physiology Study Section (PHY)
Project Start
1978-01-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Liu, Bin; Lee, Ryan S; Biesiadecki, Brandon J et al. (2012) Engineered troponin C constructs correct disease-related cardiac myofilament calcium sensitivity. J Biol Chem 287:20027-36
Lee, Ryan S; Tikunova, Svetlana B; Kline, Kristopher P et al. (2010) Effect of Ca2+ binding properties of troponin C on rate of skeletal muscle force redevelopment. Am J Physiol Cell Physiol 299:C1091-9
Norman, Catalina; Rall, Jack A; Tikunova, Svetlana B et al. (2007) Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities. Am J Physiol Heart Circ Physiol 293:H2580-7
Davis, Jonathan P; Norman, Catalina; Kobayashi, Tomoyoshi et al. (2007) Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophys J 92:3195-206
Swartz, Darl R; Yang, Zhenyun; Sen, Asok et al. (2006) Myofibrillar troponin exists in three states and there is signal transduction along skeletal myofibrillar thin filaments. J Mol Biol 361:420-35
Luo, Ye; Rall, Jack A (2006) Regulation of contraction kinetics in skinned skeletal muscle fibers by calcium and troponin C. Arch Biochem Biophys 456:119-26
Gomes, Aldrin V; Venkatraman, Gayathri; Davis, Jonathan P et al. (2004) Cardiac troponin T isoforms affect the Ca(2+) sensitivity of force development in the presence of slow skeletal troponin I: insights into the role of troponin T isoforms in the fetal heart. J Biol Chem 279:49579-87
Tikunova, Svetlana B; Davis, Jonathan P (2004) Designing calcium-sensitizing mutations in the regulatory domain of cardiac troponin C. J Biol Chem 279:35341-52
Davis, Jonathan P; Rall, Jack A; Alionte, Catalina et al. (2004) Mutations of hydrophobic residues in the N-terminal domain of troponin C affect calcium binding and exchange with the troponin C-troponin I96-148 complex and muscle force production. J Biol Chem 279:17348-60
Davis, Jonathan P; Rall, Jack A; Reiser, Peter J et al. (2002) Engineering competitive magnesium binding into the first EF-hand of skeletal troponin C. J Biol Chem 277:49716-26

Showing the most recent 10 out of 20 publications