Visualizing the electrical whispering of cells

Mammalian cells can be classified as electrically excitable and non-excitable. While the former are capable of generating electrical action potentials that serve as binary information units, little is known about the electrical signaling of non-excitable cells. The major obstacle is the non-invasive measurement of the electrical membrane potential of many cells in parallel, ideally within a tissue. Here we present rEstus, an enhanced genetically encoded fluorescent voltage indicator with outstanding brightness and voltage sensitivity. Using rEstus, we demonstrate that non-excitable cancer cells are by no means electrically silent. Instead, they exhibit a wealth of minute voltage fluctuations, which can be utilized to analyze the electrical communication between them.