A DIVERGENT CFTR HOMOLOG - HIGHLY REGULATED SALT TRANSPORT IN THE EURYHALINE TELEOST FUNDULUS-HETEROCLITUS

The killifish, Fundulus heteroclitus, is a euryhaline teleost fish cap able of adapting rapidly to transfer from freshwater (FW) to four time s seawater (SW). To investigate osmoregulation at a molecular level, a 5.7-kilobase cDNA homologous to human cystic fibrosis transmembrane c onductance regulator (hCFTR) was isolated from a gill cDNA library fro m SW-adapted killifish. This cDNA encodes a protein product (kfCFTR) t hat is 59% identical to hCFTR, the most divergent form of CFTR charact erized to date. Expression of kfCFTR in Xenopus oocytes generated aden osine 3',5'-cyclic monophosphate-activated, Cl--selective currents sim ilar to those generated by hCFTR. In SW-adapted killifish, kfCFTR was expressed at high levels in the gill, opercular epithelium, and intest ine. After abrupt exposure of FW-adapted killifish to SW, kfCFTR expre ssion in the gill increased severalfold, suggesting a role for kfCFTR in salinity adaptation. Under similar conditions, plasma Na+ levels ro se significantly after 8 h and then fell, although it is not known whe ther these changes are directly responsible for the changes in hfCFTR expression. The killifish provides a unique opportunity to understand teleost osmoregulation and the role of CFTR.