McNicholas C M, Guggino W B, Schwiebert E M, Hebert S C, Giebisch G, Egan M E
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520-8026, USA.
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):8083-8. doi: 10.1073/pnas.93.15.8083.
We demonstrate here that coexpression of ROMK2, an inwardly rectifying ATP-sensitive renal K+ channel (IKATP) with cystic fibrosis transmembrane regulator (CFTR) significantly enhances the sensitivity of ROMK2 to the sulfonylurea compound glibenclamide. When expressed alone, ROMK2 is relatively insensitive to glibenclamide. The interaction between ROMK2, CFTR, and glibenclamide is modulated by altering the phosphorylation state of either ROMK2, CFTR, or an associated protein, as exogenous MgATP and the catalytic subunit of protein kinase A significantly attenuate the inhibitory effect of glibenclamide on ROMK2. Thus CFTR, which has been demonstrated to interact with both Na+ and Cl- channels in airway epithelium, modulates the function of renal ROMK2 K+ channels.
我们在此证明，内向整流型ATP敏感性肾钾通道（IKATP）ROMK2与囊性纤维化跨膜传导调节因子（CFTR）共表达可显著增强ROMK2对磺脲类化合物格列本脲的敏感性。单独表达时，ROMK2对格列本脲相对不敏感。通过改变ROMK2、CFTR或相关蛋白的磷酸化状态可调节ROMK2、CFTR和格列本脲之间的相互作用，因为外源性MgATP和蛋白激酶A的催化亚基可显著减弱格列本脲对ROMK2的抑制作用。因此，已证明在气道上皮细胞中与Na+和Cl-通道均有相互作用的CFTR可调节肾ROMK2钾通道的功能。
