The long term goal of my research program is to understand the design of muscular systems. This involves performing specific experiments that facilitate the integration of information from molecular, cellular and whol animal studies. This approach is unusual and important because scientists generally work either on molecules, cells or whole animals but not on all three. This approach is crucial because there are large gaps in our knowledge of the principles by which animals use their muscles. Further, elucidation of the principles of how healthy motor systems work may be useful in 1) understanding disease/injuries of the motor/cardiovascular systems, 2) designing computer systems for aiding movement in the handicapped, 3) designing pharmacological and genetic interventions for muscle disease states, 4) understanding the functional basis of training/ rehabilitation, 5) chosing appropriate skeletal muscle for heart pumping assist. Muscle must perform mechanical work to power locomotion, pump blood, and produce sound. The frequency at which the work must be produced varies dramatically from less than 1Hz for cardiac muscle (or slow-twitch skeletal muscle) to more than 200 Hz for super-fast sound producing muscles. We have previously found that the contractile properties of the muscle appear to be perfectly matched to the function which the muscle must perform. The question arises, what components set the speed of muscle contraction (i.e. twitch duration), and how at the molecular level i this matching obtained? Although these are fundamental questions in muscle physiology, the answer is unknown. Toadfish represent an excellent model in which to explore these issues because we can examine the function of three different muscle fiber types whose twitch speed and speed of operation in vivo vary about 50 fold. First we will measure the kinetics of the major steps involved in muscle relaxation (Ca2+ -reuptake and crossbridge detachment) as well as individual components which contribute to these processes (parvalbumin, ca2+ pumps, etc). Second, by modelling and empirical approaches we will then determine how these processes interact to set the speed of muscle contraction. Third, we will determine the energetic costs associated with faster relaxation and thus what is the tradeoff between increasing contraction speed and energetic cost. Finally, we will measure how the muscles are actually used in vivo, to better understand the molecular desig for different motor functions.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Physiology Study Section (PHY)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Arts and Sciences
United States
Zip Code
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