PHYSIOLOGY AND PHARMACOLOGY OF EXTRAOCULAR MUSCLES

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Extraocular muscles (EOM's) are unique in mammales because they contain two main populations of fibers: singly innervated (SIF's) and multiply innervated (MIF's). MIF's are absent in limb muscles. The two fiber types have been subdivided into several categories distributed in two layers: orbital and global. Our long term objective is to explore the physiological and morphological properties of EOM fibers with the hope of establishing the cellular basis of ocular motility. Morphological studies indicate that orbital MIF's display two types of nerve junctions. The same fiber has a single endplate ending localized in the central portion of the fiber and numerous, small and superficial endings concentrated in the distal region. The development of sarcoplasmic reticulum markedly changes from the central region of the fiber, where it is well developed, to the distal portion where it is sparse. These observations suggest that corresponding differences in the physiological properties of the fiber may exist between these two regions. The ability to generate action potential in these two areas will be tested. The distribution of fast and slow myosins and different ATPases, along the fiber will be studied. The effects of denervation on the electrical properties of EOM fibers will be examined. The process of reinnervation of fibers also will be investigated to determine whether it is specific for fiber type. The metabolic requirements of the tension produced by MIF's will be investigated by analyzing the effects of different metabolic inhibitors. The role of extracellular Ca in the excitation-contractin coupling mechanism of MIF's will be explored. The effects will be studied of Ca-free salines and of agents that decrease cr increase membranes permeability to Ca (Cd and nifedipine; nitrate and thiocyanate). The functional changes that extraocular muscles undergo in early postnatal development will be analyzed. The structure of SIF's and MIF's will be examined in serial cross-sections with emphasis on the location and appearance of endings and on the distribution of mitochondria and sarcoplasmic reticulum. Morphometirc techniques will be employed for this purpose.