FUNCTIONALITY CORE

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For striated muscles, functionality is defined as the capability of an organ, the heart or a muscle, or a cell, muscle fibers, to develop force and power during isometric, shortening, or lengthening contractions. Our working hypothesis is that functionality of striated muscles is a complex phenomenon and the provision of reliable and valid measurements requires sophisticated equipment and highly trained muscle mechanists to make the measurements and analyze and interpret the results. Consequently, to test rigorously hypotheses related to the underlying mechanisms of the reduced functionality of striated muscles in diseased and old animals, a Functionality Core is a necessity. The specific aims of the Functionality Core are: (1) the provision of valid, state-of-the-art, functional measurements: (1a) for Project #1 of single permeabilized fibers of limb muscles and whole limb muscles of wild type, dystrophic, transgenic and mutant adult and old mice, and in mice after vector-based gene transfer; (1b) for Project #2 of single cardiac myocyte function and whole heart hemodynamics of adult and old, wild type and mutant mice, and in young and old mice and rats after vector-based gene transfer in vitro and in vivo; (1c) for Project #3 of single permeabilized fibers from flight muscles, force and power of flight muscles during tethered flight, and whole heart muscle functionality of wild type, transgenic and mutant Drosophila; (2) continuous up-dating of the design, development, and construction of innovative experimental protocols and apparatus to measure specific mechanical properties of striated muscles; (3) consultation and training of trainees and faculty to make measurements of functionality and maintain the apparatus used to measure functional properties of striated muscles of rodents and Drosophila. The significance of the Functionality Core lies in the critical role that functional properties play in the interpretation of the structure-function relationships with natural aging of the organism and following any genetic manipulation of skeletal or cardiac muscles of rodents or Drosophila. Impairments in functionality of striated muscles may occur at any age due to injury or disease or as an intractable concomitant of aging. The impairments in functionality, whether due to injury, disease, or old age, limit the activities of daily living and reduce the quality of life.