The contractile mechanism of vertebrate striated muscle is activated by the binding of calcium to troponin. Studies relating force to free calcium concentration show that the calcium activating mechanism has the properties of a cooperative system. One aspect of this cooperativity is that calcium-receptor interactions can be modulated by cross-bridge attachments formed between myosin and actin filaments.
The aim of this study will be to analyze and interpret the calcium-troponin interaction as a dynamic property of the working myofilament system. A double isotope technique and EGTA buffers will be used to make simultaneous measurements of bound Ca 2 ion, force development, and ATPase activity in rabbit psoas muscle fibers extracted with detergent and glycerol. Questions to be answered are: 1) what is the quantitative relationship between receptor occupancy, ATPase activity, and the mechanical output?, 2) how do mechanical parameters such as force and length alter calcium receptor properties?, and 3) in the intact myofilament system what is the influence on calcium binding of variations in chemical environment which are known to alter mechanical activity? These studies should enhance our understanding of how calcium mobilization and binding are controlled by the mechanical and chemical conditions which prevail during the contraction cycle of living muscle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR010551-24
Application #
3154714
Study Section
Physiology Study Section (PHY)
Project Start
1978-05-01
Project End
1990-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
24
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Wang, Y P; Fuchs, F (2000) Length-dependent effects of osmotic compression on skinned rabbit psoas muscle fibers. J Muscle Res Cell Motil 21:313-9
Fuchs, F; Wang, Y P (1997) Length-dependence of actin-myosin interaction in skinned cardiac muscle fibers in rigor. J Mol Cell Cardiol 29:3267-74
Bukatina, A E; Fuchs, F; Watkins, S C (1996) A study on the mechanism of phalloidin-induced tension changes in skinned rabbit psoas muscle fibres. J Muscle Res Cell Motil 17:365-71
Fuchs, F; Wang, Y P (1996) Sarcomere length versus interfilament spacing as determinants of cardiac myofilament Ca2+ sensitivity and Ca2+ binding. J Mol Cell Cardiol 28:1375-83
Wang, Y P; Fuchs, F (1995) Osmotic compression of skinned cardiac and skeletal muscle bundles: effects on force generation, Ca2+ sensitivity and Ca2+ binding. J Mol Cell Cardiol 27:1235-44
Bukatina, A E; Fuchs, F; Brandt, P W (1995) Thin filament activation by phalloidin in skinned cardiac muscle. J Mol Cell Cardiol 27:1311-5
Wang, Y P; Fuchs, F (1994) Length, force, and Ca(2+)-troponin C affinity in cardiac and slow skeletal muscle. Am J Physiol 266:C1077-82
Bukatina, A E; Fuchs, F (1994) Effect of phalloidin on the ATPase activity of striated muscle myofibrils. J Muscle Res Cell Motil 15:29-36
Liou, Y M; Fuchs, F (1993) Energy-transfer measurements of the Cys35-Cys84 distance in bovine cardiac troponin C. Biochim Biophys Acta 1202:92-8
Liou, Y M; Fuchs, F (1992) Pyrene-labeled cardiac troponin C. Effect of Ca2+ on monomer and excimer fluorescence in solution and in myofibrils. Biophys J 61:892-901

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