This is a Program to study the cell biology of striated muscle (cardiac and skeletal). Seven project leaders collaborate in investigations using biochemical, morphological, physiologic and immunologic tools. The Unifying theme of the Program is muscle, its growth, activation and contraction. There are four subthemes. One effort focusses on RNA and DNA control of synthesis of cell constituents during embryologic development and work hypertrophy, especially myosin synthesis. These studies require monospecific antibody development and reverse transcription. A second subtheme is correlation of biochemical and physiological steps in contractile protein interaction and cross-bridge movement. This includes contractile protein kinetics in solutions and force-velocity studies in skinned fibers. A third subtheme is excitation-contraction coupling, with studies of the regulation of intracellular calcium using skinned fibers, ion-selective microelectrodes and morphologic study of the specialized membrane system. Finally, structure-function studies are made of factors controlling excitation and conduction in complex tissues, such as multi-cellular heart muscle, especially the gap junction. This is a proposal for continuation of support for this Program for an additional five years. It is comprised of eight continuation projects and three new projects.
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