Modification of cysteine-substituted CFTR-TM1 mutants by internal MTS reagents. (A) Example time courses of macroscopic currents (measured at +50 mV) carried by cys-less CFTR and Q98C inside-out membrane patches. After patch excision and recording of baseline currents, patches were treated sequentially with 20 nM PKA and 1 mM ATP, 2 mM PPi, and either 200 µM MTSES or 2 mM MTSET. Note that whereas these MTS reagents have no effect on cys-less CFTR current amplitude, they cause rapid inhibition (MTSES) or augmentation (MTSET) of current carried by Q98C. (B) Example leak-subtracted I-V relationships for cys-less CFTR, K95C, Q98C, P99C, L102C, and R104C, recorded from inside-out membrane patches after maximal channel activation with 20 nM PKA, 1 mM ATP, and 2 mM PPi. In each panel, currents recorded before the application of MTS reagents (control) and after full modification by 200 µM of intracellular MTSES or 2 mM MTSET had been achieved.