Enhanced voltage-dependent inhibition in cell-attached patches in S1141K-CFTR. (A) Example macroscopic currents carried by E1371Q and S1141K/E1371Q-CFTR in cell-attached patches (left panels) after excision into the inside-out patch configuration (middle panels) and after the addition of 10 µM CFTR_inh-172 to the intracellular solution (right panels). Currents were recorded with either a high (154-mM) or low (4-mM) Cl⁻ concentration in the extracellular solution as noted. No PKA, ATP, or PPi was added to the bath solution during these experiments. With 154 mM Cl⁻ outside, currents were recorded during voltage steps from a holding potential of 0 mV to between −100 and +100 mV, whereas with 4 mM Cl⁻, voltage steps were from a holding potential of +60 mV to between −100 and +60 mV. In each case, the 0 current level is indicated by a dotted line. (B) Corresponding I-V relationships during cell-attached (●) and inside-out patch recording (○) after the subtraction of leak currents recorded after the addition of CFTR_inh-172. (C and D) Quantification of the voltage-dependent inhibition of currents during cell-attached recording by plotting the macroscopic current amplitude in cell-attached patches as a fraction of current in the same patch after excision into the inside-out patch configuration for both E1371Q (●) and S1141K/E1371Q (○), with 154 mM Cl⁻ (C) or 4 mM Cl⁻ (D) in the extracellular solution. Mean of data from four to six patches. Asterisk indicates the voltage range over which there was a significant difference between these two channel variants (P < 0.05).