ACTIVATION OF CL- CURRENTS BY INTRACELLULAR CHLORIDE IN FIBROBLASTS STABLY EXPRESSING THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The C1(-) conductance of a mouse fibroblast cell line (LTK(-) cells) t hat was stably transfected with the human CFTR (cystic fibrosis transm embrane conductance regulator) complementary DNA was studied. Single C 1(-) channel activity was observed only after treatment of the cells w ith forskolin, the single-channel conductance being 6.2 +/- 0.2 pS wit h a linear current-voltage relationship. In CFTR(+) cells, the whole-c ell 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 C1(-) concentration to 150 mM activated linear C1(-) currents in the absence of cyclic AMP in CFTR(+) (n = 42) but not in CFTR(-) cells (n = 4). Similar C1(-) curr ent was also activated by high intracellular I- concentration. These r esults indicate that the CFTR-induced C1(-)conductance in LTK(-) cells can be activated by either cyclic AMP or high intracellular halide co ncentrations.