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Flashcards in Phototransduction Deck (25)
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Anatomy of the eye - Neural components

-optic disk
-optic nerve


Optical components

-aqueous humor
-vitreous humor


Supporting components

-uveal tract
-pigmented epithelium
-ciliary body


Focusing images on the retina

-cornea: provides 80% of the focusing power
-cannot change shape
-lens: provides 20% of focussing power
-thin lens: less light bending (far objects)
-thick lens: more light bending (near objects)

-shape of the lens is controlled by the ciliary muscles
-relax: thin lens (far sight)
-contracted: fat lens (near sight) accommodation


Organization of the retina

-pigment epithelium
-photoreceptor outer segments (rods and cones)
-outer nuclear layer
-outer plexiform layer
-inner nuclear layer
-inner plexiform layer (amacrine, bipolar, horizontal cells)
-ganglion cell layer
-nerve fibre



-transduction=transformation of light energy into neuron activity
-light causes hyperpolarization of photoreceptors
-more intense flash response causes larger hyperpolarization

-dark: Na+ influx, K+ efflux, depolarization
-light: reduced Na+ influx, K+ efflux, hyperpolarization


Light transduction

-outer segment of photoreceptors are filled with stacks of disc membranes
-disc membranes covered with opsins
-Rods have rhodopsin
-cone have opsins (S, M, L)
-vertebrate opsins are closesly relation to metabotropic NT receptors (7TMD)



-rhodopsin has a chromophore called retinal covalently bound to its 7th transmembrane domain
-activation: isomerization of retinal causes conformation change in rhodopsin
-activated rhodopsin has a conformation that exposes a binding pocked which interacts with the G protein Transducin (Gat)


Transducin activation

-transducin is a heterotrimeric G protein
-conformational change in rhodopsin triggers a conformational change in Transducins a subunit
-results in:
1. Decrease in the affinity of the a unit for GDP causing dissociation of GDP from the a subunit, and binding of GTP
2. Dissociation of BY from a subunit
3. Release of G proteins from rhodopsin
-amplification: more than one transducin can be activated during the time the rhodopsin is bound to all-trans retinal


G proteins: conformational changes

-a subunit:
-nucleotide binding site (also the GTPase region) interacts with 3 switch regions
-when GDP is exchanged for GTP the terminal phosphate group of GTP forms hydrogen bones with side chains of switch 1 and 2 to prevent it from interacting with the loops at the bottom of the GY propeller

-BY subunit doesnt change conformation


G protein modulation

-GEFs: facilitate release of GDP
-increases activity due to more Ga-GTP
-ligand bound GPCR acts as a GEF

-GDIs: inhibit release of GDP
-decrease activity: less Ga-GTP

-GAPs: activate intrinsic GTPase activity
-decrease activity: less Ga-GTP

-GIPs: stop intrinsic GTPase from working
-increase activity: more Ga-GTP



-light activated opsin causes Transducin to Exchange GDP for GTP
-transducin dissociates
-a subunit activated phosphodiesterase
-decreased cGMP causes cGMP gated channels to close
-causes hyperpolarization because Na+ and Ca2+ cannot enter cell


Rods can detect a single photon of light

-a single isomerization of retinal starts an enzymatic cascade
-1 activated rhodopsin can close 2% of rods cGMP gated channels
-changes membrane potential by 1mV


Photo-cascade inactivation

-activated rhodopsin (R*) is phosphorylated on 3 different sites by rhodopsin kinase
-multi site inactivation may yield more uniform Tim course of inactivation (less variability = better signal)
-phosphorylated rhodopsin is bound by arresting
-arresting binding causes conformation change in R* so that it cannot active Transducin anymore
-Transducin is inactivated by RGS9-GB5-R9AP complex
-GB5 = Regulatory subunit
-R9AP = membrane anchor


Light adaption

-phototransduction adjusts its magnitude to prevailing light levels
-prevents signal saturation, where all cGMP gated channels are closed


Light adaption mechanism 1

-goal: keep some cGMP gated channels open
-action: make more cGMP

-dark: intracellular Ca2+ inhibits guanylate cyclase activating proteins (GCAPs) (which produces cGMP)
-light: induced closing of cGMP-channels decreases intracellular Ca2+
-drop in Ca2+ up-regulates GCAPs
-GCAPs up regulate guanylate cyclase to produce cGMP
-fastest and most powerful mechanism
-also assists in photo cascade inactivation


Light adaption mechanism 2

-goal: keep some cGMP gated channels open
-action: ensure less PDE activity

-Ca2+ biding protein similar to calmoduin
-dark: Ca2+-Recoverin inhibits rhodopsin kinase from phosphorylation great rhodopsin
-light induced drop in Ca2+ relieves this inhibition
-low Ca2+ = more rapid R* inactivation
-less PDE activation
-more cGMP


Light adaption mechanism 3

-goal: keep some cGMP gated channels open
-action: make channels more sensitive to cGMP


-dark: Ca2+-Calmodulin binds to cGMP gated channels and desensitizes it to cGMP
-light induced drop in Ca2+ = calmodulin dissociates from the channel making it more sensitive to cGMP
-stays open with fewer bound cGMP


Dark adaption

-eyes become more sensitive
-due to replenishing of 11-cis retinal opsins
-retinoids cycle in photoreceptor and pigment epithelium
-interphotoreceptor binding proteins (IRBP) chaperones retinoids between photoreceptors and pigment epithelial cells
-convert all-trans retinal back to 11-cis retinal in pigment epithelium so they can be reactivated by light


Disc maintenance

-photoreceptor disks are continuous being produced
-disks migrate from soma toward end of outer segment
-old disks removed by pigment epithelium


Specialization of rod and cone systems

-rods have high sensitivity, specialized for low intensity vision
-cone have low sensitivity, specialized for high sensitive vision
-cone transduction specialized for bright light
-reduced amplification in their phototransduction cascade
-slower/less effective Gat and PDE
-higher expression of RGS9 (GAP)
-faster inactivation
-cone specific opsin kinase (GRK7)
-more efficient R* inactivation
-much larger changes in Ca2+
-engage in Ca2+ feedback mechanisms more rapidly


Specialization of rod and cone systems continued

-rods send converging inputs to bipolar cells
-pooling of input leads to greater sensitivity and less acuity

-cones have less convergence
-less sensitivity, greater acuity

-only cones at fovea
-less cones everywhere else
-no rods at fovea



-specialized for high acuity
-avascular - no overlaying blood vessels obscuring path of light to the cones
-inner retinal cells (bipolar, ganglion, horizontal, amacrine) swept to side so light has unobstructed path to cones
-foveal cones thinner than elsewhere
-these factors contribute to pit-like structure


Cones and colour vision

-human colour vision is trichromatic
-short, medium and long cones
-short: blue (400 range)
-medium: green-yellow (450-550)
-long: yellow-red (500-600)

S: only 5-10% of cone population
-absent from fovea
-important for circadian rhythms
M & L: predominant rental cone types
-proportions vary between humans yet all have normal colour vision


Cones and colour deficiency

-x linked mutations can cause dichromatism
-protonopia: missing L cones
-deuteranopia: missing M cones
-amino acid sequence of each cone opsin determine the wavelength of light its most sensitive to
-gradual mutation gave rise to Rhodopsin plus 3 cone types

-M and L both on X chromosome and are genetically similar indication recent evolutionary origin - probably from gene duplication
-errors in crossing over during meiosis can produce dichromatism