Modification of cysteine-substituted CFTR-TM6 mutants by internal MTS reagents. A and B, shown are example time-courses of macroscopic currents (measured at −50 mV) carried by cys-less CFTR, T338C, and M348C in inside-out membrane patches. After patch excision and recording of baseline currents, patches were treated sequentially with PKA (20 nm) and ATP (1 mm), PPi (2 mm), and either MTSES (200 μm) or MTSET (2 mm). Note that whereas these MTS reagents have no effect on cys-less CFTR current amplitude, they cause rapid inhibition or augmentation of current carried by these two mutants. C–E, shown are example leak subtracted I-V relationships for these same three channel variants recorded from inside-out membrane patches after maximal channel activation with PKA (20 nm), ATP (1 mm), and PPi (2 mm). C and D, currents were recorded before (Control) and after application of MTSES (200 μm, C), or MTSET (2 mm, D) to the intracellular (bath) solution. E, shown is the effect of DTT (5 mm) applied after MTSET treatment in T338C and M348C.