Biography
Biography: Teresa Duda
Abstract
As the eye flicks about a scene, a photoreceptor, rod and cone, sees an alternating pattern of light and dark. This pattern is transduced by the photoreceptor outer segment into electrical signals (a mechanism termed phototransduction), and these signals are processed first by the retina, then by the visual cortex, and finally are decoded as the perceived image. In the phototransduction cascade of rods and cones, the second messenger cyclic GMP is generated by membrane-bound guanylate cyclases (ROS-GCs). In darkness, cyclic GMP opens cyclic nucleotide-gated (CNG) channels and a steady influx of Na+ and Ca2+ enters the outer segment and keeps the photoreceptor depolarized. Photons trigger hydrolysis of cyclic GMP, closing the channels and hyperpolarizing the photoreceptor. The recovery phase occurs when the Na+/Ca2+,K+ exchanger reduces intracellular concentration of Ca2+. Guanylate cyclase-activating proteins (GCAPs) sense this fall and stimulate ROS-GCs to synthesize cyclic GMP at a faster rate, leading to recovery of the photoreceptor dark current. The basic phototransduction components of rods and cones are similar, but important differences render rods more sensitive and cones faster with a larger dynamic range. While rods express ROS-GC1, ROS-GC2, GCAP1, and GCAP2, cones express only ROS-GC1 and GCAP1. We have discovered that cone photoreceptors, but not rods, express another Ca2+ sensor, S100B. This protein stimulates cyclic GMP synthesis as intracellular concentration of Ca2+ increases, and this modulation is specific to ROS-GC1, the only guanylate cyclase expressed in cones. Thus ROS-GC1 functions as a Ca2+-bimodal switch that increases its rate of cyclic GMP synthesis when intracellular Ca2+ rises to higher levels or falls to very low levels. We hypothesize that this bimodal feature serves cone function to better operate during daytime when cones are continuously light adapted and their function is to convey both light increments and decrements. While GCAP unimodal modulation of ROS-GC1 in rods provides negative feedback and is responsible primarily for accelerating response recovery, the GCAP/S100B bimodal feature can provide both negative and positive feedback, accelerating both the recovery and the rising phases.