Figure 2.

Mutagenesis of positively charged arginine residues induces CFTR channel current rectification. (A) Example leak subtracted macroscopic I-V relationships from different CFTR channel variants in inside-out membrane patches, after maximal channel activation with ATP, PKA, and PPi. In contrast to wild-type CFTR, mutants R303E and, to a lesser extent, R352E showed outward rectification of the I-V relationship with symmetrical 154 mM Cl⁻ solutions. (B) Mutagenesis-induced rectification was specific for these two positions; charge-changing mutations at four other arginine residues did not significantly alter I-V shape. The degree of I-V rectification is quantified as the rectification ratio, as defined in Materials and methods. Mean of data from three to four patches. * indicates a significant difference from wild type (P < 0.0001, two-tailed t test).