Loss of epithelial polarity: A novel hypothesis for reduced proximal tubule Na+ transport following ischemic injury |
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Authors: | Bruce A Molitoris Laurence K Chan Joseph I Shapiro John D Conger Sandor A Falk |
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Institution: | (1) Division of Nephrology and Department of Medicine, Veterans Administration Medical Center, University of Colorado School of Medicine, 80262 Denver, Colorado |
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Abstract: | Summary Ischemia results in the marked reduction of renal proximal tubule function which is manifested by decreased Na+ and H2O reabsorption. In the present studies the possibility that altered Na+ and H2O reabsorption were due to ischemia-induced loss of surface membrane polarity was investigated. Following 15 min of renal ischemia and 2 hr of reperfusion, proximal tubule cellular ultrastructure was normal. However, abnormal redistribution of NaK-ATPase to the apical membrane domain was observed and large alterations in apical membrane lipid composition consistent with loss of surface membrane polarity were noted. These changes were associated with large decreases in Na+ (37.4vs. 23.0%,P<0.01) and H2O (48.6vs. 36.9%,P<0.01) reabsorption at a time when cellular morphology, apical Na+ permeability, Na+-coupled cotransport, intracellular pH and single nephron filtration rates were normal. We propose that the abnormal redistribution of NaK-ATPase to the apical membrane domain is in part responsible for reduced Na+ and H2O reabsorption following ischemic injury. |
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Keywords: | renal ischemia epithelial polarity NaK-ATPase Na+ transport |
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