Meneton P, Schultheis P J, Greeb J, Nieman M L, Liu L H, Clarke L L, Duffy J J, Doetschman T, Lorenz J N, Shull G E
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
J Clin Invest. 1998 Feb 1;101(3):536-42. doi: 10.1172/JCI1720.
Previous studies using isolated tissues suggest that the colonic H, K-ATPase (cHKA), expressed in the colon and kidney, plays an important role in K+ conservation. To test the role of this pump in K+ homeostasis in vivo, we generated a cHKA-deficient mouse and analyzed its ability to retain K+ when fed a control or K+-free diet. When maintained on a control diet, homozygous mutant (cHKA-/-) mice exhibited no deficit in K+ homeostasis compared to wild-type (cHKA+/+ greater, similar mice. Although fecal K+ excretion in cHKA-/- mice was double that of cHKA+/+ mice, fecal K+ losses were low compared with urinary K+ excretion, which was similar in both groups. When maintained on a K+-free diet for 18 d, urinary K+ excretion dropped over 100-fold, and to similar levels, in both cHKA-/- and cHKA+/+ mice; fecal K+ excretion was reduced in both groups, but losses were fourfold greater in cHKA-/- than in cHKA+/+ mice. Because of the excess loss of K+ in the colon, cHKA-/- mice exhibited lower plasma and muscle K+ than cHKA+/+ mice. In addition, cHKA-/- mice lost twice as much body weight as cHKA+/+ mice. These results demonstrate that, during K+ deprivation, cHKA plays a critical role in the maintenance of K+ homeostasis in vivo.
以往使用分离组织进行的研究表明，在结肠和肾脏中表达的结肠H⁺，K⁺-ATP酶（cHKA）在钾离子保存中起重要作用。为了测试该泵在体内钾离子稳态中的作用，我们培育了一种cHKA缺陷型小鼠，并分析了其在喂食对照饮食或无钾饮食时保留钾离子的能力。当维持对照饮食时，与野生型（cHKA⁺/⁺）小鼠相比，纯合突变体（cHKA⁻/⁻）小鼠在钾离子稳态方面没有缺陷。虽然cHKA⁻/⁻小鼠的粪便钾离子排泄量是cHKA⁺/⁺小鼠的两倍，但与两组相似的尿钾排泄量相比，粪便钾离子损失较低。当维持18天无钾饮食时，cHKA⁻/⁻和cHKA⁺/⁺小鼠的尿钾排泄量均下降了100倍以上，且降至相似水平；两组的粪便钾离子排泄量均减少，但cHKA⁻/⁻小鼠的损失是cHKA⁺/⁺小鼠的四倍。由于结肠中钾离子的过度流失，cHKA⁻/⁻小鼠的血浆和肌肉钾离子水平低于cHKA⁺/⁺小鼠。此外，cHKA⁻/⁻小鼠的体重减轻是cHKA⁺/⁺小鼠的两倍。这些结果表明，在钾离子缺乏期间，cHKA在体内维持钾离子稳态中起关键作用。
