Neuropharmacology

Biography

Biography: Frans Vinberg

Abstract

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+, 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) synthetize 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 demonstrate 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.