Neurophysiological process - Visual perception

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

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