Monitoring of compound resting membrane potentials of cell cultures with ratiometric genetically encoded voltage indicators.

The cellular resting membrane potential (V) not only determines electrical responsiveness of excitable cells but also plays pivotal roles in non-excitable cells, mediating membrane transport, cell-cycle progression, and tumorigenesis. Studying these processes requires estimation of V, ideally over long periods of time. Here, we introduce two ratiometric genetically encoded V indicators, rArc and rASAP, and imaging and analysis procedures for measuring differences in average resting V between cell groups.