Visual cycle
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The visual cycle is the process where light impacting on the photosensitive cells of the retina is converted into electrical polarisation that generates nerve stimulation[1]. It is linked to the phototransduction cascade.
Phototransduction Initiation:In all visual pigment opsins 11-cis retinal is joined to a lysine in the 7th transmembrane region of the opsin by a Schiff base linkage. Light forms an all-trans retinal which actuates a cascade of events leading to cell polarisation change. The opsin is regenerated via the visual cycle. If this Schiff base is proteated the pigment has an absortion maxima > 440nm. Such positively charged Schiff bases are modulated by a counterion which is a glutamate residue from the 3rd transmembrane region of the opsin. A weak interaction delocalises the positive charge through the π system of the retinal causing more red shift Further modification of the electronic dipolar environment is possible by neutral side chains of the opsin. In man the spectral shift between the red and green cone opsins is 95% accounted for by the aminoacid differences at AA180 (alanine/serine) in the 4th transmembrane segment and at AA277(tyrosine/phenylalanine) and AA285 (alanine/threonine) in the 6th transmembrane segment.[2]
In rod cells:
- Rhodopsin(opsin bound to 11-cis retinal) + Photon (λ) → activated metarhodopsin II* containing all-trans retinal
- The all-trans ligand forces a conformational change in rhodopsin to metarhodopsin II
- Metarhodopsin II* → α-transducin in the trimer complex α-β-γ-transducin
- α-transducin-GDP → α-transducin-GTP
- α-transducin-GTP activates photoreceptor phosphodiesterase
- Activated photoreceptor phosphodiesterase hydrolyses cyclic GMP → 5'GMP.
- Lower levels of cyclic GMP decrease cyclic GMP binding to photoreceptor cGMP-gated cation channels
- This closes the cation channels → membrane hyperpolarization
- Reduces entry of Ca2+ and Na+ into the photoreceptor
- Activated photoreceptor phosphodiesterase hydrolyses cyclic GMP → 5'GMP.
- α-transducin-GTP activates photoreceptor phosphodiesterase
- α-β-γ-transducin→ α-transducin-GTP and β-γ-transducin
- Regeneration of α-transducin-GDP
- Metarhodopsin II* + rhodopsin kinase → Metarhodopsin II (phosphorylated at at least 3 opsin C terminus residues)
- Metarhodopsin II capped by arrestin
- Hydrolysis of Metarhodopsin II → retinal + opsin
- All-trans retinol leaves photoreceptor, binds an extracellular binding protein (IRBP)
- IRBP-retinal complex transferred to retinal pigment epithelium
- All-trans retinol + lecithin retinol acyl transferase → all-trans retinyl esters
- All-trans retinyl esters + RPE65 (an isomerohydrolase) → 11-cis retinol
- 11-cis retinol storage in retinal pigment epithelium
- 11-cis retinol + NAD+ + 11-cis retinol dehydrogenase → 11-cis retinal +NADH
- IRBP-retinal complex transferred to retinal pigment epithelium
- 11-cis retinal leaves retinal pigment epithelium, binds IRBP and IRBP-11-cis retinal is delivered back to the photoreceptor outer segment
- α-transducin-GDP → α-transducin-GTP
- Calcium is a key intracellular signal ion in the photoreceptor. Ca2+:
- Binds to GCAP thus inhibiting cyclic GMP production by guanylyl cyclase
- Stimulates binding of calmodulin to the cGMP-gated cation channels
- Reduces channel affinity to cyclic GMP
- Binds to recoverin
- Recoverin* inhibits rhodopsin kinase
This article is a work in progress. Please feel free to contribute to it.
External Links
References
- ↑ Cornwall MC, Ala-Laurila P. A perfect marriage: molecular genetics ties the knot with electrophysiology in studies of visual transduction. The Journal of general physiology. 2007 Jul; 130(1):7-10.(Link to article – subscription may be required.)
- ↑ Nathans J. The evolution and physiology of human color vision: insights from molecular genetic studies of visual pigments. Neuron. 1999 Oct; 24(2):299-312.
