Abstract: The present invention relates to methods of identifying drug-resistant and/or drug-sensitive cells, for example, breast cancer and brain tumor cells, on the basis of different ion and/or second messenger dynamics between a drug-sensitive and drug-resistant cell. For example, the invention provides measuring the comparative decay rates of a cellular ion, such as calcium, released into the intracellular compartment of drug sensitive and/or drug resistant cells. The present invention also provides methods for screening compounds that modulate the ionic dynamics of a cell as well as methods of determining drug resistance/sensitivity of cancer cells from cancer patients and/or designing cancer therapy based on of the ionic dynamics of cancer cells from a particular patient.

Abstract: 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.