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Articles in PresS, published online ahead of print March 5, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00038.2002
Submitted on January 29, 2002
Accepted on February 25, 2002
1 Laboratory of Kidney and Electrolyte Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA
2 Laboratory of Kidney and Electrolyte Metabolism, National Heart Lung and Blood Institute, Bethesda, MD, USA; Laboratory of Cellular and Molecular Physiology, Universidad de los Andes, Santiago, Chile
3 Department of Cell Biology, Georgetown University Medical Center, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: maurice_burg{at}nih.gov.
Renal inner medullary (IM) cells survive interstitial osmolality that ranges from 600 to 1700 mosmol/kg, or more. In contrast, much smaller acute changes killed the cells previously studied in tissue culture, such as mIMCD3 which are immortalized with SV40 and proliferate rapidly. Proliferation and DNA replication sensitize mIMCD3 to hypertonicity. In the present studies we observed that proliferating cells are scarce in rat IM. Then, we prepared passage 2 mouse IM epithelial (p2mIME) cells. They have a much lower incidence of DNA replication than mIMCD3 cells. p2mIME cells survive much greater acute increases of NaCl than do mIMCD3 cells and also tolerate significantly greater acute increases of urea and of NaCl plus urea, but still not to levels as high as occur in vivo. We conclude that immortalization and continued DNA replication account for part of the previously observed difference in osmotic tolerance between IM cells in vivo and in cell culture, but that other factors must also be involved.
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