Modulation of cyclic-nucleotide-gated channels and regulation of vertebrate phototransduction

Cyclic-nucleotide-gated (CNG) channels are crucial for sensory transduction in the photoreceptors (rods and cones) of the vertebrate retina. Light tri ggers a decrease in the cytoplasmic concentration of cyclic GMP in the oute r segments of these cells, leading to closure of CNG channels and hyperpola rization of the membrane potential. Hence, CNG channels translate a chemica l change in cyclic nucleotide concentration into an electrical signal that can spread through the photoreceptor cell and be transmitted to the rest of the visual system. The sensitivity of phototransduction can be altered by exposing the cells to light, through adaptation processes intrinsic to phot oreceptors. Intracellular Ca2+ is a major signal in light adaptation and, i n conjunction with Ca2+-binding proteins, one of its targets for modulation is the CNG channel itself. However, other intracellular signals may be inv olved in the fine-tuning of light sensitivity in response to cues internal to organisms. Several intracellular signals are candidates for mediating ch anges in cyclic GMP sensitivity including transition metals, such as Ni2+ a nd Zn2+, and lipid metabolites, such as diacylglycerol. Moreover, CNG chann els are associated with protein kinases and phosphatases that catalyze chan ges in phosphorylation state and allosterically modulate channel activity. Recent studies suggest that the effects of circadian rhythms and retinal tr ansmitters on CNG channels may be mediated by such changes in phosphorylati on. The goal of this paper is to review the molecular mechanisms underlying modulation of CNG channels and to relate these forms of modulation to the regulation of light sensitivity.