BOTH THE WILD-TYPE AND A FUNCTIONAL ISOFORM OF CFTR ARE EXPRESSED IN KIDNEY

The cystic fibrosis transmembrane conductance regulator (CFTR) consist s of five domains, two transmembrane-spanning domains, each composed o f six transmembrane segments, a regulatory domain, and two nucleotide- binding domains (NBDs). CFTR is expressed in kidney, but its role in o verall renal function is not well understood, because mutations in CFT R found in patients with cystic fibrosis are not associated with renal dysfunction. To learn more about the distribution and functional form s of CFTR in kidney, we used a combination of molecular, cell biologic al, and electrophysiological approaches. These include an evaluation o f CFTR mRNA and protein expression, as well as both two-electrode and patch clamping of CFTR expressed either in Xenopus oocytes or mammalia n cells. In addition to wild-type CFTR mRNA, an alternate form contain ing only the first transmembrane domain (TMD), the first NBD, and the regulatory domain (TNR-CFTR) is expressed in kidney. Although missing the second set of TMDs and the second NBD, when expressed in Xenopus o ocytes, TNR-CFTR has cAMP-dependent protein kinase A (PKA)stimulated s ingle Cl- channel characteristics and regulation of PKA activation of outwardly rectifying Cl- channels that are very similar to those of wi ld-type CFTR. TNR-CFTR mRNA is produced by an unusual mRNA processing mechanism and is expressed in a tissue-specific manner primarily in re nal medulla.