Kramer R H, Molokanova E
Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
J Exp Biol. 2001 Sep;204(Pt 17):2921-31. doi: 10.1242/jeb.204.17.2921.
Cyclic-nucleotide-gated (CNG) channels are crucial for sensory transduction in the photoreceptors (rods and cones) of the vertebrate retina. Light triggers a decrease in the cytoplasmic concentration of cyclic GMP in the outer segments of these cells, leading to closure of CNG channels and hyperpolarization of the membrane potential. Hence, CNG channels translate a chemical 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 photoreceptors. Intracellular Ca(2+) is a major signal in light adaptation and, in conjunction with Ca(2+)-binding proteins, one of its targets for modulation is the CNG channel itself. However, other intracellular signals may be involved in the fine-tuning of light sensitivity in response to cues internal to organisms. Several intracellular signals are candidates for mediating changes in cyclic GMP sensitivity including transition metals, such as Ni(2+) and Zn(2+), and lipid metabolites, such as diacylglycerol. Moreover, CNG channels are associated with protein kinases and phosphatases that catalyze changes in phosphorylation state and allosterically modulate channel activity. Recent studies suggest that the effects of circadian rhythms and retinal transmitters on CNG channels may be mediated by such changes in phosphorylation. 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.
环核苷酸门控（CNG）通道对于脊椎动物视网膜光感受器（视杆细胞和视锥细胞）中的感觉转导至关重要。光会引发这些细胞外段中环状GMP胞质浓度的降低，导致CNG通道关闭以及膜电位超极化。因此，CNG通道将环核苷酸浓度的化学变化转化为电信号，该电信号可通过光感受器细胞传播并传递至视觉系统的其他部分。通过光感受器固有的适应过程，将细胞暴露于光下可改变光转导的敏感性。细胞内Ca(2+)是光适应中的主要信号，并且与Ca(2+)结合蛋白一起，其调节的靶标之一是CNG通道本身。然而，其他细胞内信号可能参与了对生物体内部线索做出反应时的光敏感性微调。几种细胞内信号是介导环状GMP敏感性变化的候选信号，包括过渡金属，如Ni(2+)和Zn(2+)，以及脂质代谢产物，如二酰基甘油。此外，CNG通道与催化磷酸化状态变化并变构调节通道活性的蛋白激酶和磷酸酶相关。最近的研究表明，昼夜节律和视网膜递质对CNG通道的影响可能由这种磷酸化变化介导。本文的目的是综述CNG通道调节的分子机制，并将这些调节形式与光敏感性的调节联系起来。
