The objective is to help satisfy an important need, the need to know the biochemical nature of the different kinds of cells in muscle and nervous system. Brain function depends on the interplay of diverse kinds of cells, grandly entangled with each other. The admixture of the many cell types and the fact that the functional state differs from cell to cell, and from moment to moment, means that macroscopic chemical approaches are limited in usefulness. Muscle is also an intimate mixture of cells which differ greatly in chemical composition. Muscle fibers lying next to each other vary as much as 50-fold in the ratios between particular enzymes, and the differences can be exaggerated in muscle disease. Therefore, here also macroscopic studies are inadequate. To attack this situation an analytical methodology is available which has virtually unlimited sensitivity and which makes it possible to measure nearly any enzyme or metabolite in single nerve cell bodies, in nuclei of large neurons, in other neuronal structures of similar size, and in samll pieces of individual muscle fibers. It is the purpose of this project to exploit this analytical capability in the study of muscle and the nervous system. In some cases, single neurons or portions thereof are examined; in other cases, small groups of cells are studied. Specifically, the retinal layers offer an opportunity to separate for analysis subcellular regions from the same portion of a number of cells. In the case of muscle, the technique is such that the same individual fibers can be analyzed for a great many enzymes, metabolites and cofactors. This approach is proving especially useful when applied to fibers from small biopsy samples from patients with muscle disease. in some cases only a particular fiber type may be affected.
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