University of Washington, USA
Scientific Tracks Abstracts: Neurochem Neuropharm
Absorption of a photon by visual pigment molecule in the photoreceptor outer segment (OS) triggers a G protein signaling cascade that leads to accelerated rate of cGMP hydrolysis, decline in cGMP concentration and reduced Na+ and Ca2+ influx via cGMP-gated cation channels (CNG channels). However, Ca2+ extrusion from the OS by Na+/Ca2+ and K+ exchangers persists; causing photoactivation-induced decrease in Ca2+ concentration. The resulting Ca2+ dependent modulation of cGMP synthesis is critical for the ability of photoreceptors to adapt to background light. Retinal guanylate cyclases (RetGC) synthesize cGMP in both rod and cone photoreceptors. The activity of RetGCs is regulated by guanylate cyclase activating proteins (GCAP) in calcium-dependent manner. As background light intensity increases and Ca2+ concentration decreases, the active EF hand binding sites of GCAPs become occupied by Mg2+ instead Ca2+. These Mg2+-GCAPs activate RetGCs, thus accelerating the synthesis of cGMP. Recent studies have shown that both GCAP1 and GCAP2 are involved in modulating rod phototransduction. However, the distinct contributions of GCAP1 and GCAP2 to the physiology of mammalian cones have not been studied. Here we used electrophysiological recordings from mouse retina to investigate how Ca2+ feedbacks via GCAP1 and GCAP2 regulate cGMP and CNG channel current as well as phototransduction and light adaptation in intact mammalian cones. Our results demonstrated that, unexpectedly, GCAP2 can contribute significantly to the regulation of cGMP concentration and light adaptation in mammalian cones at least in the absence of GCAP1.
Frans Vinberg has received his MSc and PhD in Biomedical Engineering from Aalto University School of Science in Finland. He is currently a Postdoctoral Fellow at Washington University in Dr. Kefalov’s Laboratory. He recently received an NIH/NEI Pathway to Independence K99 Award. He is interested in understanding the molecular mechanisms that could explain the differences in the physiology of rod and cone photoreceptors mediating our nighttime and daytime vision, respectively. Furthermore, he wants to understand how defects in the function of retinal cells lead to blinding diseases. Specifically, he is focused on determining how Ca2+ feedback and regulation mechanisms contribute to the biology and pathobiology of mammalian photoreceptors.