Scheme of inhibitory optoGPCRs that couple via the G i/o pathway. A dark, inactive optoGPCR bound to the heterotrimeric Gabg protein is shown. Once the optoGPCR is activated by light, the heterotrimeric G protein separates into the active Ga and Gbg subunits. Gbg activates GIRK channels, inhibits VGCCs and may interfere with the SNARE vesicle fusion apparatus. The Ga subunit inhibits ACs, thus reducing production of cAMP. OptoGPCRs can relax thermally ( k B T ) to the non-signaling ground state. If their active state is spectrally separated from the ground state (see inset: absorption), absorption of a second photon with longer wavelength ( l ) can terminate the signaling activity. hv, light energy.