WHOLE-CELL CL- CONDUCTANCES IN MOUSE CHOROID-PLEXUS EPITHELIAL-CELLS DO NOT REQUIRE CFTR EXPRESSION

Whole cell patch-clamp studies were performed with tissue isolated fro m the cystic fibrosis (CF) transgenic Cftr(m1cam) mouse, to determine whether anion currents in choroid plexus epithelial cells require the expression of cystic fibrosis transmembrane conductance regulator (CFT R). Inclusion of 0.25 mM adenosine 3',5'-cyclic monophosphate (cAMP) a nd 375 nM protein kinase A (PKA) in the pipette solution caused a sign ificant activation of a Cl--selective, inward-rectifying conductance i n cells from wild-type and CF mice. The small, outward currents observ ed in wild-type and CF animals, however, were not activated by cAMP-PK A. There were no significant differences in the size of currents betwe en wildtype, heterozygote, and CF cells in the presence or absence of cAMP-PKA. A second whole cell conductance was activated when cells fro m wild-type mice were swollen. These volume-activated currents were Cl - selective and exhibited outward rectification. They were Ca2+ indepe ndent and ATP dependent and blocked by 4,4'-diisothiocyanostilbene-2,2 '-disulfonic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid. The volume-activated channels were also activated in CF mutant cells, and there was no significant difference in the size of the volume-activat ed currents between wild-type, heterozygote, and CF cells. It is concl uded that CFTR neither contributes to the whole cell conductance nor r egulates the other anion conductances in choroid plexus epithelial cel ls.