The long-term objective of this work is to relate the physiological properties of muscle fibers to their biochemical composition. A special feature of the proposed work is that it will be carried out on single muscle fibers (skeletal) or small bundles of muscle fibers (cardiac). This approach is necessary because it is now known that whole muscles are heterogeneous with respect to their biochemical and structural properties. Previous work in this laboratory has established considerable expertise in the area of muscle fiber physiology. More recent work has advanced this laboratory's capability in the biochemical domain to the level at which is now possible to carry out subsequent biochemical analysis of the same small piece of muscle sample used to obtain physiological measurements. The major problem to be addressed concerns the influence of myosin isozyme heterogeneity, or myosin """"""""polymorphism"""""""", on the contractile properties of muscle samples. There has been a rapid increase in the number of known myosin isozymes, and, furthermore, it is now known that even individual fibers and muscles within a given species can have a broad spectrum of myosin types. Moreover, it is now also known that a considerable """"""""plasticity"""""""" exists in myosin isozymes reflected in a succession of different phenotypes during development and response to altered """"""""loading"""""""". However, a fundamental problem is now revealed concerning the physiological relevance of these various myosin isozymes. In order to solve this crucial problem, it is proposed to carry out physiological measurements on small muscle samples and then subject these same samples to biochemical analysis consisting of both native and SDS gel electrophoresis in order to determine the myosin isozyme pattern present. In this way, it will be possible to correlate directly physiological properties with myosin isozyme content. A further novel and important feature of the proposed work is the intent to use human muscle samples in the proposed work. This is necessary, not only for health relatedness considerations, but also because it is becoming increasingly clear that extrapolation of human muscle properties from animal work is not always possible, as is now apparent from recent work on myosin isozymes in animal and human hearts.
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