ATP-LINKED EFFECTORS OF NA,K-ATPASE AND CATARACT

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Changes in lenticular Na+ and K+ concentrations have been correlated with increasing lens color and increasing cortical opacity. Na,K-ATPase is inhibited in epithelium in 37% of the cataract population. Inhibition of the Na,K-ATPase of the lens cortex is more general, occurring in 80-90 percent of the lenses. The purpose of the proposed studies is to characterize the Na,K- ATPase of the epithelium and cortex of normal and cataractous lenses. Since human cataract lenses are not available for study, animal models and in vitro model systems will be employed. During the next five years, the sites of glucosylation, carbamylation, and oxidation of lens epithelial cell Na,K-ATPase will be located. The interaction of Na+,K+,Mg2+,ATP,ADP,Pi, and ouabain with the three modified Na,K-ATPase preparations will be determined. This will be accomplished using steady state kinetics techniques, lens organ culture and lens epithelial cell culture techniques as well as non steady state kinetics techniques with purified renal Na,K-ATPase in synthetic membrane vesicles. Studies will be initiated to characterize the Na,K-ATPase of the superficial cortical fibers. The isozyme(s) present in the cortex will be determined using specific antisera to the three major sequenced heavy subunit isozymes. The fate of the Na,K-ATPase in the lens cortex of selected model cataracts will be determined.