How the eye sees

Last timeAnatomy of the eyeRods and conesVisual receptorsColor Vision

This timeVisual transductionEye to brain

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Rods and cones have different visual receptorsThe visual receptors are G protein-coupled receptors

• seven transmembrane regions

• hydrophobic/ hydrophilic domains

• conserved motifs• chromophore stably

attached to receptor

(Schiff’s base Lys296 in TM7)• thermostable

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Nomenclature for visual receptorsReceptor == GPCR, opsinLigand == chromophore, retinal, pigmentReceptor bound to ligand == rhodopsin

Light hyperpolarizes the cell

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The visual cascade is a G protein-coupled cascade

Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels

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Signal transduction in the dark

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Signal transduction in the light

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Negative regulation of phototransduction

Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels

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Closing cGMP channels causes a decrease in Ca2+

Decrease in Ca2+ activates

1. Rhodopsin kinase === deactivate receptor

2. Guanylate cyclase === converts GTP to cGMP === opens cGMP channels

Ca2+ independent deactivation also occurs

1. GTPase activating protein

Turning off rhodopsin

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Ca-dependent

Turning ON Guanylate Cyclase

Guanylate cyclase GTP--- cGMP opens cGMP channels GCAP (less Ca)

Phosphodiesterase cGMP--- GMP closes cGMPchannels transducin

ENZYME REACTION ACTION on CHANNELS ACTIVATED BY

Ca-dependent,Decrease in Caactivates GC

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Turning off the G protein

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Mice without GAP cannot turn off light response quickly

no GAP

with GAP (wild-type)

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Rods respond to a single photon of light

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Single photon response is very reproducible

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Dark noise is very low

1 rhodopsin/minute108 rhodopins/ photoreceptor1000 years for all rhodopsins to turn over

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High amplification increases signal size and reliability

Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels

1 100 100 100,000 ~1000

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Properties of phototransduction

• responds to 1 photon of light• responses are extremely reliable• high amplification of signaling• low dark noise

•1000s of discs maximize surface area of light detection• high concentration and thermostability of rhodopsin means high detection, low noise

Photoreceptors are highly specialized to detect light!

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Phototransduction: Differences between rods and cones

Rods ConesVery sensitive to light 30x less sensitive to light

each rhodopsin activates 30x less G proteins

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Drosophila mutants with abnormal light responses

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The signaling pathway for Drosophila phototransduction

Fastest GPCR cascade measuredNo amplification

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Structure of the eye

The Basic Retinal Circuit

1. Receptor Cells(rods and cones)

2. Bipolar Cells

3. Ganglion Cells

Connectivity in the retina

Back of eye

Front of eye

4. Horozontal Cells

5. Amacrine Cells

6. Pigment cells

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View of the retinaRamon y Cajal, Nobel 1906

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Flow of visual information in the retina

Vertical Connections

Back of eye Front of eye back of eyePhotoreceptor Cell---Bipolar Cell---Retinal Ganglion Cell---Brain

Horozontal Connections

Horozontal Cells- connect photoreceptors and bipolar cellsAmacrine Cells- connect bipolar cells and retinal ganglion cells

light

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What happens if all rods and cones are killed?

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Unusual retinal gangion cells

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Retinal ganglion cells express melanopsin, are sensitive to light

and project to the suprachiasmatic nucleus

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