Human color vision is based on three light-sensitive pigments. The isolation and sequencing of genomic and complementary DNA clones that encode the apoproteins of these three pigments are described. The deduced amino acid sequences show 41 +/- 1 percent identity with rhodopsin. The red and green pigments show 96 percent mutual identity but only 43 percent identity with the blue pigment. Green pigment genes vary in number among color-normal individuals and, together with a single red pigment gene, are proposed to reside in a head-to-tail tandem array within the X chromosome.

https://science.sciencemag.org/content/sci/232/4747/193.full.pdf

Molecular genetics of human color vision: the genes encoding blue, green, and red pigments

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila, and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.

Cyclic Nucleotide-Gated Ion Channels

Cyclic GMP is central to visual excitation in vertebrate retinal rod cells. Sodium channels in the plasma membrane of the outer segment are kept open in the dark by a high level of cGMP. Light closes these channels by activating an enzymatic cascade that leads to the rapid hydrolysis of cGMP. Photoexcited rhodopsin triggers transducin by catalyzing the exchange of GTP for bound GDP. The activated GTP-form of transducin then switches on the phosphodiesterase by overcoming an inhibitory constraint. The overall gain of this cascade is about 10(5). The cascade is turned off by the GTPase activity of transducin and by the action of rhodopsin kinase and arrestin. One of the challenges now is to delineate the interplay of cGMP, calcium ion, and phosphoinositides in excitation and adaptation. Transducin belongs to a family of signal-coupling proteins that includes the G proteins of the hormone-regulated adenylate cyclase cascade. The initial events in visual excitation in molluscs and arthropods are probably similar to those of vertebrates. The triggering of transducin by photoexcited rhodopsin is a recurring motif in visual transduction. The coming together of electrophysiology, biochemistry, and molecular genetics affords new opportunities in unraveling the molecular mechanism of visual transduction.

Cyclic GMP cascade of vision.

Olfactory transduction is thought to be initiated by the binding of odorants to specific receptor proteins in the cilia of olfactory receptor cells (reviewed in refs 1–3). The mechanism by which odorant binding could initiate membrane depolarization is unknown, but the recent discovery of an odorant-stimulated adenylate cyclase in purified olfactory cilia4,5 suggests that cyclic AMP may serve as an intracellular messenger for olfactory transduction. If so, then there might be a conductance in the ciliary plasma membrane which is controlled by cAMP. Here we report that excised patches of ciliary plasma membrane, obtained from dissociated receptor cells, contain a conductance which is gated directly by cAMP. This conductance resembles the cyclic GMP-gated conductance that mediates phototransduction in rod and cone outer segments6,7, but differs in that it is activated by both cAMP and cGMP. Our data provide a mechanistic basis by which an odorant-stimulated increase in cyclic nucleotide concentration could lead to an increase in membrane conductance and therefore, to membrane depolarization. These data suggest a remarkable similarity between the mechanisms of olfactory and visual transduction and indicate considerable conservation of sensory transduction mechanisms.

A cyclic nucleotide-gated conductance in olfactory receptor cilia

Understanding of the organization and function of a newly identified neuronal messenger molecule, nitric oxide, has progressed rapidly. Nitric oxide synthase has been purified and molecularly cloned from brain. Its localization is exclusively neuronal and endothelial. The catalytic activity of nitric oxide synthase accounts for the NADPH diaphorase staining of neurons that are uniquely resistant ot toxic insults and neurodegenerative disorders. Nitric oxide has diverse functions. In platelets it inhibits their aggregation, in macrophages it mediates cytotoxicity, and in blood vessels it acts as a vasodilator. In the nervous system nitric oxide may be the retrograde transmitter in long-term potentiation. It is the “neurotransmitter” of cerebral vasodilator nerves and the inhibitory “neurotransmitter” of the motor neurons of the intestines. Nitric oxide in situations of excessive production may function as neurotoxin, suggesting a role for nitric oxide in neurodegenerative disorders.

A novel neuronal messenger molecule in brain: the free radical, nitric oxide.

Vertebrate rod photoreceptors hyperpolarize when illuminated, due to the closing of cation-selective channels in the plasma membrane. The mechanism controlling the opening and closing of these channels is still unclear, however. Both 3′, 5′-cyclic GMP1,2 and Ca2+ ions3 have been proposed as intracellular messengers for coupling the light activation of the photopigment rhodopsin to channel activity and thus modulating light-sensitive conductance. We have now studied the effects of possible conductance modulators on excised ‘inside-out’ patches from the plasma membrane of the rod outer segment (ROS), and have found that cyclic GMP acting from the inner side of the membrane markedly increases the cationic conductance of such patches (EC50 30 µM cyclic GMP) in a reversible manner, while Ca2+ is ineffective. The cyclic GMP-induced conductance increase occurs in the absence of nucleoside triphosphates and, hence, is not mediated by protein phosphorylation, but seems rather to result from a direct action of cyclic GMP on the membrane. The effect of cyclic GMP is highly specific; cyclic AMP and 2′, 3′-cyclic GMP are completely ineffective when applied in millimolar concentrations. We were unable to recognize discrete current steps that might represent single-channel openings and closings modulated by cyclic GMP. Analysis of membrane current noise shows the elementary event to be 3 f A with 110 mM Na+ on both sides of the membrane at a membrane potential of −30 mV. If the initial event is assumed to be the closure of a single cyclic GMP-sensitive channel, this value corresponds to a single-channel conductance of 100 fS. It seems probable that the cyclic GMP-sensitive conductance is responsible for the generation of the rod photoresponse in vivo.

Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2895%2900002-Q

Dual effects of microwaves on single Ca2+-activated K+ channels in cultured kidney cells Vero

THE molecular basis of photoreception has been extensively studied, but it is not yet clear which of the photolysis products of rhodopsin has the key role in receptor potential generation. Penn and Hagins1 have shown that the effect of an absorbed photon persists for about 0.1 s at 33 °C (rat retina). If metarhodopsin II is the key product, as most workers assume it to be, then the result of Penn and Hagins can be explained as follows. On formation of metarhodopsin II a visual pigment molecule undergoes a transformation with time constant 0.1 s, which ‘cuts-off’ the process of visual excitation. Metarhodopsin II persists for dozens of seconds at 33 °C (as determined from spectral characteristics2) so if the suggested transformation takes place it should not result in variations of the absorption spectrum of metarhodopsin II, and thus could not be detected by spectroscopy. As the artificial lipid membrane (ALM) is a good detector of changes in functionating protein molecules3–5, we attempted to detect the above process by examining the photoeffect on ALM, modified by photoreceptor membrane components.

Evgeniy E. Fesenko

Papers

Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment

Dual effects of microwaves on single Ca2+-activated K+ channels in cultured kidney cells Vero

Effect of light on artificial lipid membranes modified by photoreceptor membrane fragments

Single anion channels of frog rod plasma membrane.

Growth characteristics of human bone marrow mesenchymal stromal cells at cultivation on synthetic polyelectrolyte nanofilms in vitro.