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Am J Physiol Cell Physiol 274: C715-C723, 1998;
0363-6143/98 $5.00
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Vol. 274, Issue 3, C715-C723, March 1998

A divergent CFTR homologue: highly regulated salt transport in the euryhaline teleost F. heteroclitus

Thomas D. Singer1, Stephen J. Tucker2, William S. Marshall3, and Christopher F. Higgins1

1 Nuffield Department of Clinical Biochemistry and Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS; 2 University Laboratory of Physiology, Oxford OX1 3PT, United Kingdom; and 3 Department of Biology, Saint Francis Xavier University, Antigonish, Nova Scotia, Canada B2G 2W5

The killifish, Fundulus heteroclitus, is a euryhaline teleost fish capable of adapting rapidly to transfer from freshwater (FW) to four times seawater (SW). To investigate osmoregulation at a molecular level, a 5.7-kilobase cDNA homologous to human cystic fibrosis transmembrane conductance regulator (hCFTR) was isolated from a gill cDNA library from SW-adapted killifish. This cDNA encodes a protein product (kfCFTR) that is 59% identical to hCFTR, the most divergent form of CFTR characterized to date. Expression of kfCFTR in Xenopus oocytes generated adenosine 3',5'-cyclic monophosphate-activated, Cl--selective currents similar to those generated by hCFTR. In SW-adapted killifish, kfCFTR was expressed at high levels in the gill, opercular epithelium, and intestine. After abrupt exposure of FW-adapted killifish to SW, kfCFTR expression in the gill increased severalfold, suggesting a role for kfCFTR in salinity adaptation. Under similar conditions, plasma Na+ levels rose significantly after 8 h and then fell, although it is not known whether these changes are directly responsible for the changes in kfCFTR expression. The killifish provides a unique opportunity to understand teleost osmoregulation and the role of CFTR.

cystic fibrosis transmembrane conductance regulator; chloride channel; killifish; gill; Xenopus expression; osmoregulation; cystic fibrosis; Fundulus heteroclitus


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