NDLI: Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA–regulated apical chloride channels in cortical collecting duct

Content Provider	PubMed Central
Author	Lu, Ming Dong, Ke Egan, Marie E. Giebisch, Gerhard H. Boulpaep, Emile L. Hebert, Steven C.
Abstract	The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in many segments of the mammalian nephron, where it may interact with and modulate the activity of a variety of apical membrane proteins, including the renal outer medullary potassium (ROMK) K+ channel. However, the expression of CFTR in apical cell membranes or its function as a Cl− channel in native renal epithelia has not been demonstrated. Here, we establish that CFTR forms protein kinase A (PKA)-activated Cl− channels in the apical membrane of principal cells from the cortical collecting duct obtained from mice. These Cl− channels were observed in cell-attached apical patches of principal cells after stimulation by forskolin/3-isobutyl-1-methylxanthine. Quiescent Cl− channels were present in patches excised from untreated tubules because they could be activated after exposure to Mg-ATP and the catalytic subunit of PKA. The single-channel conductance, kinetics, and anion selectivity of these Cl− channels were the same as those of recombinant mouse CFTR channels expressed in Xenopus laevis oocytes. The CFTR-specific closed-channel blocker CFTRinh-172 abolished apical Cl− channel activity in excised patches. Moreover, apical Cl− channel activity was completely absent in principal cells from transgenic mice expressing the ΔF508 CFTR mutation but was present and unaltered in ROMK-null mice. We discuss the physiologic implications of open CFTR Cl− channels on salt handling by the collecting duct and on the functional CFTR–ROMK interactions in modulating the metabolic ATP-sensing of ROMK.
Related Links	http://dx.doi.org/10.1073/pnas.0902661107
Starting Page	6082
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-03-30
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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