Novel genetically encoded fluorescent probes enable real-time detection of potassium in vitro and in vivo

Changes in intra- and extracellular potassium ion (K(+)) concentrations control many important cellular processes and related biological functions. However, our current understanding of the spatiotemporal patterns of physiological and pathological K(+) changes is severely limited by the lack of practicable detection methods. We developed K(+)-sensitive genetically encoded, Förster resonance energy transfer-(FRET) based probes, called GEPIIs, which enable quantitative real-time imaging of K(+) dynamics. GEPIIs as purified biosensors are suitable to directly and precisely quantify K(+) levels in different body fluids and cell growth media. GEPIIs expressed in cells enable time-lapse and real-time recordings of global and local intracellular K(+) signals. Hitherto unknown Ca(2+)-triggered, organelle-specific K(+) changes were detected in pancreatic beta cells. Recombinant GEPIIs also enabled visualization of extracellular K(+) fluctuations in vivo with 2-photon microscopy. Therefore, GEPIIs are relevant for diverse K(+) assays and open new avenues for live-cell K(+) imaging.