FLIPR(R) membrane potential dye measures changes of charges across the cell membrane, upon activation of SLC6A8. The assay allows the detection of ion channel and transporter modulation by increasing or decreasing the fluorescent signal as cellular membrane potential changes. When cells are depolarized dye enters the cells, causing an increase in fluorescent signal, conversely, cells hyperpolarization results in dye exit and decreased fluorescence. SLC6A8 is a Na+/Cl- coupled electrogenic cotransporter, with a 2 Na+:1 Cl-:1 creatine stoichiometry, thus determining dye signal increase upon activation. It mediates creatine uptake into a variety of cells, including neuronal cells, skeletal and cardiac muscle cells and intestinal and kidney epithelial cells and it is important in the maintenance of ATP homeostasis in tissues that have high energy requirement.