FIGURE 1.

Phototransduction feedback loop regulates levels of cGMP and Ca²⁺. Dark levels of cGMP and Ca²⁺ are high in rod and cone photoreceptors. Light activation of rhodopsin initiates rod phototransduction, activated PDE6 rapidly hydrolyzes cytoplasmic cGMP, and cGMP-gated cation channels close. Continued extrusion of Ca²⁺ by the light-insensitive Na⁺-K⁺/Ca²⁺ exchanger (NCKX) lowers free Ca²⁺ which activates guanylate cyclase-activating proteins (GCAPs) and guanylate cyclases (GCs). Restoration of cGMP dark levels re-opens cation channels and Ca²⁺ levels equilibrate to dark levels.