Abstract: The present invention relates to genetically encoded calcium sensors comprising fluorescent proteins and troponin C as calcium-binding moiety. More specifically, the invention provides a polypeptide comprising a donor moiety for fluorescence resonance energy transfer (FRET), at least two calcium binding moieties derived from the C-terminal domain of troponin C, and an acceptor moiety for FRET. Also, the invention provides nucleic acid molecules, expression vectors, host cells, and transgenic animals. In addition, methods for detecting a change in Ca2+ concentration or Mg2+ concentration, as well as uses of the polypeptides for preparing diagnostic compositions for the detection of changes in the Ca2+-concentration or Mg2+-concentration are provided.