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 pre sence of multiple anion binding sites within the channel pore. However, und er steady-state conditions SCN- conductance is very low. Here I show, using patch clamp recording from CFTR-transfected mammalian cell lines, that und er steady-state conditions neither SCN- conductance nor SCN- permeability s how anomalous mole fraction behaviour. Instead, SCN- conductance, permeabil ity, and block of Cl- permeation can all be reproduced by a rate theory mod el that assumes only a single intrapore anion binding site. These results s uggest 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 underst anding the mechanism of anion permeation are discussed.