Calcium signaling and fluorescent calcium sensors. (A) Fast calcium signaling regulated by the voltage-gated calcium channels (VGCC) includes EC coupling, cardiac action potential, calcium sparks and neurotransmitter release. (B) Different time scales of calcium signaling. (C) Representatives of calcium dye and genetically encoded calcium indicators. Fura-2 is synthesized calcium dye. Aequorin is used as genetically encoded calcium indicator. Cameleon and TnC sensor are composed by calmodulin and troponin C containing four EF-hands, respectively, flanked with FRET pair. GCaMP, GECO and R-CaMP are single fluorescent protein based sensor with calmodulin. CatchER is the single fluorescent protein with a designed calcium binding site on the surface of EGFP.