EXPRESSION AND MOLECULAR REGULATION OF NA-K+-ATPASE AFTER RENAL ISCHEMIA()

Renal ischemia causes redistribution of Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) to the apical membrane of proximal tubules. We determ ined the time course of regeneration of Na+-K+-ATPase polarity and sou ght evidence of increased enzyme production during recovery as a means to restore polarity. Anesthetized rats underwent 45 min renal ischemi a and reflow of 15 min, 2 h, 6 h, and 24 h. Immunofluorescent and elec tron microscopy showed loss of strict basolateral localization of Na+- K+-ATPase at 15 min reflow with repolarization by 24 h in sublethally injured cells. Both alpha(1)- and beta-subunits were only in microsoma l fractions at all reflow intervals. Immunodetectable levels of both s ubunits declined to 60-70% of control by 24 h reflow. Levels of mRNA f or each subunit declined in parallel through 24 h to 55% of control. O verall transcription was profoundly depressed through 6 h but had reco vered to near control by 24 h. Specific transcription of alpha(1)- and beta-subunit mRNA was markedly decreased after ischemia and only part ially recovered by 24 h. These results suggest that recycling of mispl aced units rather than new Na+-K+-ATPase production is the means by wh ich renal epithelia initially repolarize after ischemic injury.