Rod photoreceptors reliably signal single absorbed photons ( Baylor et al., 1979), but detection threshold is higher in cones. Both these features make cones less light sensitive than rods. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. In nonmammalian rods, in contrast, active PDE lifetime is ∼555 ms. In fish cones, the mean lifetime of active PDE at room temperature is ∼55 ms. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. In cones loaded with high concentration Ca 2+ buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca 2+ that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise).

E current vs dark noise