Intestinal ion transport in NKCC1-deficient mice
Intestinal ion transport in NKCC1-deficient mice
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DOI：
10.1152/ajpgi.2000.279.4.g707
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发表时间：
2000-10-01
影响因子：
4.5
通讯作者：
Boucher, RC
中科院分区：
文献类型：
--
作者：
Grubb, BR;Lee, E;Boucher, RC
位于肠上皮基底外侧膜上的Na+- k +- 2cl（-）共转运蛋白（NKCC1）被认为是主要的基底外侧Cl-进入途径。通过靶向诱变，产生了缺乏NKCC1蛋白的小鼠。基础短路电流在正常空肠和NKCC1 -/-空肠之间没有差异。在-/-空肠中，forskolin响应（22 μ A/cm(2)）；与正常组织中布美他尼敏感反应（52 μ A/cm(2)）相比，布美他尼不敏感反应明显减弱。离子替代研究表明，在NKCC1 -/-空肠中，福斯克林的反应依赖于HCO3，而在正常空肠中，它不依赖于缓冲液中的HCO3浓度。NKCC1 -/-盲肠表现出福斯克林反应，与正常盲肠没有显著差异，但与正常盲肠不同，它对布美他尼不敏感。离子取代研究表明，基底侧HCO3-和Cl-进入（通过非NKCC1）途径在NKCC1 -/-分泌反应中发挥作用。囊性纤维化小鼠缺乏基础和受刺激的Cl-分泌，并表现出严重的肠道病理，与之相反，NKCC1 -/-小鼠的肠道病理缺失可能反映了肠道通过独立于NKCC1的基底外侧进入机制分泌HCO3-和Cl-的能力。
The Na+-K+-2Cl(-) cotransporter (NKCC1) located on the basolateral membrane of intestinal epithelia has been postulated to be the major basolateral Cl- entry pathway. With targeted mutagenesis, mice deficient in the NKCC1 protein were generated. The basal short-circuit current did not differ between normal and NKCC1 -/- jejuna. In the -/- jejuna, the forskolin response (22 mu A/cm(2); bumetanide insensitive) was significantly attenuated compared with the bumetanide-sensitive response (52 mu A/cm(2)) in normal tissue. Ion-replacement studies demonstrated that the forskolin response in the NKCC1 -/- jejuna was HCO3- dependent, whereas in the normal jejuna it was independent of the HCO3- concentration in the buffer. NKCC1 -/- ceca exhibited a forskolin response that did not differ significantly from that of normal ceca, but unlike that of normal ceca, was bumetanide insensitive. Ion-substitution studies suggested that basolateral HCO3- as well as Cl- entry (via non-NKCC1) paths played a role in the NKCC1 -/- secretory response. In contrast to cystic fibrosis mice, which lack both basal and stimulated Cl- secretion and exhibit severe intestinal pathology, the absence of intestinal pathology in NKCC1 -/- mice likely reflects the ability of the intestine to secrete HCO3- and Cl- by basolateral entry mechanisms independent of NKCC1.