We performed photochemical studies to learn if the lightcontrolled isomerization of compound 7 would result in changes of cell morphology as observed with the pharmacological tool compounds during real-time impedance measurements. Therefore, cells were incubated with E-7 and Z-7, as described above, but after an equilibration time of 32 min, LEDs emitting at 505 nm or 400 nm, respectively, were placed above the monolayer to in situ generate the opposite Z-7 or E-7 isomers. The impedance time courses of the in situ isomerization are summarized in Figure . In both diagrams, the unperturbed Zisomer of 7 is colored in blue, while its E-isomer is represented by red curves. After an equilibration time of 20 min, the impedance of the Z-isomer showed no difference to the vehicle control (black), whereas for the E-molecule, the signal dropped to about -1300 Ω. Thus, there is a clear difference between the two isomers. The green curves in the upper panel show the impedance profile during in situ switching of Z → E, while green curves in the lower panel represent switching E → Z. Vertical dashed lines indicate the times when the samples were irradiated with light of the corresponding wavelength for the specified duration (1: 400 nm, t = 1 min; 2: 505 nm, t = 2 min). The first illumination of Z-7 with 400 nm (t = 1 min, vertical line 1) led to an immediate change of the curve, reaching almost the levels of the E-isomer in the dark. At t = 58 min, reforming Z-7 with 505 nm light for 2 min brought back the signal to -500 Ω, not quite reaching the dark control of Z-7. The third isomerization 72 min after compound addition with 400 nm light altered the signal again to drop to -1300 Ω. A similar pattern was observed when the E-isomer (Figure , E-7 irradiated) was subjected to photo-switching. Significant impedance changes were observed after every illumination step (vertical lines 1-3) using the appropriate wavelengths to generate the opposing isomer. Moreover, a separate experiment with several switching cycles with increasingly shorter equilibration times from 3 min to 1 min between individual illuminations can be found in the supporting information (SI, Fig. ). Immediate changes of impedance were observed even for ten individual switching steps. However, some signal drift to lower impedances and some fatigue of the cell response was observed in these experiments, most likely due to the short equilibration times and repeated interference with signaling chains that are presumably transmitted downstream into complex molecular networks. The combination of the photochromic cAMP derivative 7 with real-time ECIS recordings provide a powerful platform technology with reversible photocontrol of cAMP signaling inside living cells. To ensure that the response of the illuminated cell populations was not caused by the light itself, we performed control experiments using the same light intensities and wavelengths but performed the experiments in absence of 7. Upon illumination with either 505 nm or 400 nm for 1 or 2 min, respectively, no significant change of the impedance signal was observed (SI, Fig. ). Similarly, control experiments with culture medium and compound 7 but without cells showed no interaction with the gold-film electrodes or the electrochemical readout, leading to the conclusion that the change in impedance signal results only from the light-induced manipulation of cAMP signaling by the photochromic cAMP mimic 7.