Residues from ICL2 and ICL4 in close proximity were targeted, and their involvement in the functioning of CFTR was studied by whole cell patch clamp recording.
We identified 2 pairs of amino acids, at the extremity of the bundle formed by the four intracellular loops, whose mutation i) decreases the Cl鈭?/sup> current of CFTR (couple E267-K1060) or ii) increases it with a change of the electrophysiological signature (couple S263-V1056). These results highlight the critical role of these ICL residues in the assembly of the different domains and/or in the Cl鈭?/sup> permeation pathway of CFTR.Conclusions