The long term goal of my research program is to understand the design of the muscular system. This involves integrating information from cellular studies and whole animal studies. This approach is unusual and important because scientists generally work either on cells or whole animals but not on both. This approach is crucial because there are large gaps in our knowledge of the integrative principles by which animals use their muscles. Further, I believe that elucidation of the principles of how a healthy motor system works may be useful in 1) diagnosing diseases and injuries of the motor system, 2) understanding function basis of improved performance (training) and 3) designing computer systems for aiding movement in the handicapped. The first goal of this proposal is to test in additional (but functionally different) locomotory systems, the importance of two design constraints we have previously discovered (muscle works at optimal points on the sarcomere length-tension curve and on the force-velocity curve). Then we will evaluate the importance of the kinetics of activation and relaxation in muscle function and design. To do this we must measure the sarcomere length changes, and the duration and phase of the stimulation the muscle undergoes during locomotion and then impose these on isolated muscle. Although our main interest is in understanding muscle function in mammals and man, in this study we use frog and fish as experimental models because their locomotor behavior and muscular anatomies are far simpler allowing us to develop greater insights than we could working directly on mammals. For each of the animals, the sarcomere length changes of the muscle fibers during locomotion will be measured by a combination of high-speed motion picture and anatomical analysis. The duration and phase (with respect to length changes) of the muscle stimulation will be recorded using electromyography. We will then remove the muscle from the animals and impose on it the exact length changes and stimulation pattern that the muscle undergoes in vivo and measure how much work the muscle can perform under these conditions. To determine the relative importance of maximum velocity of shortening (V-max) and rate of relaxation in muscle function, we will pharmacologically slow relaxation (while keeping V-max the same) and then see how well the muscle can still perform its tasks. These approaches will give us new insights into how muscle is designed and the functional importance of the observed variation seen in different fiber types.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR038404-08
Application #
3158542
Study Section
Physiology Study Section (PHY)
Project Start
1989-01-01
Project End
1996-07-31
Budget Start
1993-09-03
Budget End
1994-07-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Harwood, Claire L; Young, Iain S; Tikunov, Boris A et al. (2011) Paying the piper: the cost of Ca2+ pumping during the mating call of toadfish. J Physiol 589:5467-84
Kargo, William J; Ramakrishnan, Arun; Hart, Corey B et al. (2010) A simple experimentally based model using proprioceptive regulation of motor primitives captures adjusted trajectory formation in spinal frogs. J Neurophysiol 103:573-90
Tikunov, Boris A; Rome, Lawrence C (2009) Is high concentration of parvalbumin a requirement for superfast relaxation? J Muscle Res Cell Motil 30:57-65