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This invention provides a high throughput screen for measuring the transport of an ion through a cystic fibrosis transmembrane conductance regulator (CFTR) of a cell that endogenously expresses CFTR. The method requires culturing the cell that endogenously expresses CFTR in the presence of an ion-sensitive compound and then contacting the cell with a CFTR activator. After a suitable amount of time after addition of the activator, the test compound is added to the cell culture medium. Thereafter, any change in the ion-sensitive compound is measured by any suitable method that can detect the change in the ion-sensitive compound, i.e. by measuring a change in the light emitted from a fluorescent compound, which can be recorded by an imaging plate reader.