Demonstration That CFTR Is a Chloride Channel by Alteration of Its Anion Selectivity

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Abstract
Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3′,5′-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide > chloride > iodide > fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide > bromide > chloride > fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.