Rauchman M I, Nigam S K, Delpire E, Gullans S R
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Am J Physiol. 1993 Sep;265(3 Pt 2):F416-24. doi: 10.1152/ajprenal.1993.265.3.F416.
The terminal inner medullary collecting duct (IMCD) plays an important role in determining the final urinary composition. Currently, there is no continuous cell line derived from this nephron segment. We have developed a cell line derived from the terminal IMCD of mice transgenic for the early region of simian virus SV40 (large T antigen). This cell line, mIMCD-3, retains many differentiated characteristics of this nephron segment including high transepithelial resistance (1,368 +/- 172 omega.cm2), inhibition of apical-to-basal sodium flux by amiloride (41 +/- 7%) and by atrial natriuretic peptide (ANP) (40 +/- 9%), the presence of the amiloride-sensitive sodium channel as determined by Western blot analysis, and accumulation of the major organic osmolytes in response to hypertonic stress. Significantly, mIMCD-3 cells adapted readily and were able to grow in hypertonic medium supplemented with NaCl and urea up to 910 mosmol/kgH2O. These extreme osmotic conditions exist in the renal medulla in vivo but are known to be lethal to most other cells. This cell line should be highly useful for the study of the cellular adaptation to osmotic stress and the cell biology and transport physiology of this nephron segment.
终末内髓集合管（IMCD）在决定最终尿液成分方面起着重要作用。目前，尚无源自该肾单位节段的连续细胞系。我们已经建立了一种源自转基因小鼠终末IMCD的细胞系，该转基因小鼠携有猿猴病毒SV40早期区域（大T抗原）。这个细胞系，即mIMCD - 3，保留了该肾单位节段的许多分化特征，包括高跨上皮电阻（1368±172Ω·cm²）、氨氯吡咪（41±7%）和心房利钠肽（ANP）（40±9%）对顶端到基底钠通量的抑制、通过蛋白质印迹分析确定的氨氯吡咪敏感钠通道的存在以及对高渗应激时主要有机渗透溶质的积累。重要的是，mIMCD - 3细胞很容易适应，并能够在补充有NaCl和尿素、渗透压高达910 mosmol/kgH₂O的高渗培养基中生长。这些极端的渗透条件存在于体内肾髓质中，但已知对大多数其他细胞是致命的。这个细胞系对于研究细胞对渗透应激的适应以及该肾单位节段的细胞生物学和转运生理学应该非常有用。
