Disclosed are novel compositions and methods employing cyclic
nucleotide-gated channels and fluorescence dyes and other indicators in
detecting changes of intracellular cAMP levels, for instance in response
to the stimulation of G-protein-coupled receptors. CNG mutants comprising
one or more pore mutations that enhance sensitivity to cAMP and decrease
divalent cation-mediated blockage are used in a variety of assays,
including detection of the G-protein-coupled receptor activity. Also
disclosed are novel dye quencher formulations that are particularly
suited for cell-based assays of protein interactions.