An Unlikely Role For The Cystic Fibrosis Gene In The Kidney

Main Category: Urology / Nephrology
Also Included In: Cystic Fibrosis
Article Date: 09 Feb 2006 - 22:00 PDT

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Mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene are known to cause cystic fibrosis (CF) due to impaired fluid and ion transport across cell membranes in the lung. However, little is known about the role of CFTR in the kidney, another important fluid transport organ.

Now, researcher Steven C. Hebert and colleagues at Yale University School of Medicine in Connecticut report that CFTR regulates potassium levels via a functional interaction with a special potassium channel (or pore) known as ROMK (renal outer medullar potassium) specifically in kidney cells.

The study, appearing online on February 9 in advance of print publication in the March issue of the Journal of Clinical Investigation, may help explain the few reports of hypokalemia (low blood potassium) and metabolic alkalosis (increased blood pH) in CF patients.

The authors studied genetically altered mice that either lacked the Cftr gene or had a mutant form of Cftr, and found that, in contrast to wild-type mice, the ROMK activity of these Cftr-deficient mice was not inhibited by the diabetes drug glibenclamide, a potent inhibitor of normal ROMK in kidney cells. The ROMK channels from Cftr-deficient mice also demonstrated an impaired response to a small energy molecule called ATP (adenosine triphosphate). These data suggest that the CFTR protein is a critical component of ROMK function and potassium homeostasis in the kidney. The authors hypothesize that CFTR acts as a functional switch to modulate potassium channel activity between states of water loss and water retention.

TITLE: CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney

AUTHOR:
Steven C. Hebert
Yale University School of Medicine, New Haven, Connecticut, USA
View the PDF of this article at: https://www.the-jci.org/article.php?id=26961

Brooke Grindlinger
bgrindlinger@the-jci.org
Journal of Clinical Investigation
http://www.jci.org