Neurophysiological process - Visual perception

print

Select Species:

Click on a target from the pathway image to view related information. Zoom     View Legend

photo_map
 


Visual perception

Visual phototransduction begins with the light absorption by Rhodopsin in the disk membrane, and culminates in hyperpolarization of the plasma-membrane. The latter causes cis-trans isomerization of 11-cis-Retinal, the chromophoreof Rhodopsin[1]., In less than a millisecond upon the capturing a photon, Rhodopsin starts activating molecules of the Guanine nucleotide binding protein (Transducin). Transducin stimulates phosphodiesterase activity by binding to the gamma subunit of Phosphodiesterase 6G (PDE6G) [2], [3]. PDE6G hydrolyzes cGMP, leading to closure of the cGMP-gated cation channels Cyclic nucleotide gated channel alpha 1 (CNGA1) and Cyclic nucleotide gated channel beta 1 (CNGB1). Thus, in the presence of light cGMP levels decline as a result of PDE6G activation, which causes channels to close and the cell to hyperpolarize. Rapid inactivation of Rhodopsin during the photoresponse is accomplished through the specific mechanism involving phosphorylation of the Rhodopsin by G protein-coupled receptor kinase 1 (Rhodopsin kinase (GRK1) and subsequent binding of S-arrestin. Recoverin binds with high affinity directly to the Rhodopsin kinase in a Ca2+ - dependent manner, and this interaction is essential for Rhodopsin kinase inhibition [4]. The termination of PDE6G activation by Transducin is achieved by a multi-protein complex containing the regulator of G protein signalling 9 binding protein (RGS9), Guanine nucleotide binding protein (G-beta 5) and membrane anchor regulator of G protein signalling 9 binding protein (R9AP)[5], [6]. Complete recovery of the photoresponse requires not only inactivation of components of the cascade, but also restoration of cytoplasmic cGMP concentration to the levels in the dark conditions. This is accomplished by guanylate cyclase. Two isoforms of this enzyme are expressed in the photoreceptors, Guanylate cyclase 2D (RETGC1) and Guanylate cyclase 2F (RETGC2). Guanylate cyclase activation is controlled by guanylate cyclase-activating proteins Guanylate cyclase activator 1A (GCAP1) and Guanylate cyclase activator 1B (GCAP2). GCAPs are sensitive to Ca('2) concentration in the cytosol. Decrease in intracellular calcium leads to activation of the GCAPs and subsequent increase in cGMP production [7], [8], [9]. In its turn, cGMP regulates CNG ion channels CNGA1 and CNGB1 which couple with NCKX channels solute carrier family 24 (SLC24A1 and SLC24A2) proteins and are responsible for Ca2+ inflow in rod cells [10]. The inward ion current through these channels keeps the cell partially depolarized. Ca('2) cytosol concentraction is controlled by the feed back mechanism. Increase in calcium concentration as the result of the activity of the CNG channels causes activation of Calmodullin 3 (Calmodulin)and leads to down-regulation the CNG channels [11], [12].



References

  1. McBee JK, Palczewski K, Baehr W, Pepperberg DR
    Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Progress in retinal and eye research 2001 Jul;20(4):469-529
  2. Neer EJ
    Heterotrimeric G proteins: organizers of transmembrane signals. Cell 1995 Jan 27;80(2):249-57
  3. Arshavsky VY, Lamb TD, Pugh EN Jr
    G proteins and phototransduction. Annual review of physiology 2002;64:153-87
  4. Fain GL, Matthews HR, Cornwall MC, Koutalos Y
    Adaptation in vertebrate photoreceptors. Physiological reviews 2001 Jan;81(1):117-151
  5. Ridge KD, Abdulaev NG, Sousa M, Palczewski K
    Phototransduction: crystal clear. Trends in biochemical sciences 2003 Sep;28(9):479-87
  6. Burns ME, Arshavsky VY
    Beyond counting photons: trials and trends in vertebrate visual transduction. Neuron 2005 Nov 3;48(3):387-401
  7. Polans A, Baehr W, Palczewski K
    Turned on by Ca2+! The physiology and pathology of Ca(2+)-binding proteins in the retina. Trends in neurosciences 1996 Dec;19(12):547-54
  8. Sokal I, Li N, Verlinde CL, Haeseleer F, Baehr W, Palczewski K
    Ca(2+)-binding proteins in the retina: from discovery to etiology of human disease(1). Biochimica et biophysica acta 2000 Dec 20;1498(2-3):233-51
  9. Burns ME, Baylor DA
    Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annual review of neuroscience 2001;24:779-805
  10. Schnetkamp PP
    The SLC24 Na+/Ca2+-K+ exchanger family: vision and beyond. Pflugers Archiv : European journal of physiology 2004 Feb;447(5):683-8
  11. Sallese M, Iacovelli L, Cumashi A, Capobianco L, Cuomo L, De Blasi A
    Regulation of G protein-coupled receptor kinase subtypes by calcium sensor proteins. Biochimica et biophysica acta 2000 Dec 20;1498(2-3):112-21
  12. Trudeau MC, Zagotta WN
    Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. The Journal of biological chemistry 2003 May 23;278(21):18705-8

Target Details

Click on a target from the pathway image to view related information.