“…However, only the advent of imaging technologies first by fluorescence (Tsien and Tsien, 1990) and later by FRET (Miyawaki, 2003) allowed the discovery of the full spectrum of spatiotemporal patterns in second-messenger concentrations. These studies revealed not only that concentrations in calcium as well as cAMP can show complex patterns of oscillations but that these may be interlinked by various intracellular mechanisms such as Ca 2ϩ -regulated phosphodiesterases and adenylyl cyclases (Zaccolo and Pozzan, 2003;Landa et al, 2005;Harbeck et al, 2006;Willoughby and Cooper, 2006;Kim et al, 2008;von Hayn et al, 2010;Ni et al, 2011;Werthmann et al, 2011). Oscillations have also been de- 326 scribed for the activity of protein kinase C (Violin et al, 2003).…”