Il. Reisin et al., THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IS A DUAL ATPAND CHLORIDE CHANNEL, The Journal of biological chemistry, 269(32), 1994, pp. 20584-20591
The cystic fibrosis transmembrane conductance regulator (CFTR) belongs
to a superfamily of proteins implicated in the transport of ions, pro
teins, and hydrophobic substances. Recent studies have demonstrated th
at CFTR is a protein kinase A-sensitive anion channel regulated by ATP
. In the present study, patch-clamp techniques were used to assess the
role of CFTR in the transport of Cl- and ATP. The stable transfection
of mouse mammary carcinoma cells, C127i, with the cDNA for human CFTR
resulted in the appearance of a diphenylamine-2-carboxylate-inhibitab
le Cl- channel, which was activated by cAMP under whole-cell and cell-
attached conditions and by protein kinase A plus ATP under excised, in
side-out conditions. CFTR expression was also associated with the elec
trodiffusional movement of ATP as indicated by the cAMP activation of
ATP currents measured under whole-cell conditions. In excised, inside-
out patches, it was demonstrated that ATP currents were mediated by AT
P-conductive channels, which were also activated by protein kinase A a
nd blocked by the Cl- channel blocker diphenylamine-2-carboxylate unde
r excised, inside-out conditions. Single-channel currents observed in
the presence of asymmetrical Cl-/ATP concentrations indicated that the
same conductive pathway was responsible for both ATP and Cl- movement
. Thus, CFTR is a multifunctional protein with more than one anion tra
nsport capability and may modify signal transduction pathways for Cl-
or other secretory processes by the selective delivery of nucleotides
to the extracellular domain.