Thiocyanate as a probe of the cystic fibrosis transmembrane conductance regulator chloride channel pore

Immediately following exposure to thiocyanate (SCN^-)-containing solutions, the cystic fibrosis conductance regulator Cl^- channel exhibits high unitary SCN^- conductance and anomalous mole fraction behaviour, suggesting the presence of multiple anion binding sites within the channel pore. However, under steady-state conditions SCN^- conductance is very low. Here I show, using patch clamp recording from CFTR-transfected mammalian cell lines, that under steady-state conditions neither SCN^- conductance nor SCN^- permeability show anomalous mole fraction behaviour. Instead, SCN^- conductance, permeability, and block of Cl^- permeation can all be reproduced by a rate theory model that assumes only a single intrapore anion binding site. These results suggest that under steady-state conditions the interaction between SCN^- and the CFTR channel pore can be understood by a simple model whereby SCN^- ions enter the pore more easily than Cl^-, and bind within the pore more tightly than Cl^-. The implications of these findings for investigating and understanding the mechanism of anion permeation are discussed.