Activation of Cl- currents by intracellular chloride in fibroblasts stably expressing the human cystic fibrosis transmembrane conductance regulator.

The Cl- conductance of a mouse fibroblast cell line (LTK- cells) that was stably transfected with the human CFTR (cystic fibrosis transmembrane conductance regulator) complementary DNA was studied. Single Cl- channel activity was observed only after treatment of the cells with forskolin, the single-channel conductance being 6.2 +/- 0.2 pS with a linear current-voltage relationship. In CFTR+ cells, the whole-cell current at +90 mV increased from 7.3 +/- 2.7 pA/pF (n = 12) to 46.1 +/- 11.2 pA/pF (n = 5) after addition of dibutyryl-cyclic AMP (10(-4) M) to the bath. Increasing the intracellular Cl- concentration to 150 mM activated linear Cl- currents in the absence of cyclic AMP in CFTR+ (n = 42) but not in CFTR- cells (n = 4). Similar Cl- current was also activated by high intracellular I- concentration. These results indicate that the CFTR-induced Cl- conductance in LTK- cells can be activated by either cyclic AMP or high intracellular halide concentrations.