Transcript like a previous Lecture

BBE/CNS 150 Lecture 13
Wednesday, October 29, 2014
Vision 1: Phototransduction and the Retina
Bruce Cohen
Kandel Chapter 26
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Organization of the retina
•Glutamate is the major
transmitter
Rod
Cone
•Some neurons make dopamine &
acetylcholine (amacrine cells)
•Inhibitory neurons release GABA.
.
Synapses of outer plexiform layer
Horizontal cells
Bipolar cells
Synapses of inner plexiform layer
Ganglion cell is unique in firing impulses
optic nerve
Like Fig. 26-2
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Photoreception
•Photoreceptor organs have evolved independently at least 40
times, each time responding to the visible spectrum and near-UV.
•How do we explain the use of a limited part of the spectrum?
•Infrared light is not sufficiently energetic to drive photochemical
reactions such as the cis-trans isomerization of retinal.
•Shorter-wavelength ultraviolet light is too energetic and would
destroy organic molecules.
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Outer segment of photoreceptors contains the visual pigment
Rhodopsin
Free-floating discs
Rhodopsin
hn
hn
Like Figs.
26-5, 26-7
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There are 3 types of opsin in human color-sensitive cones.
Each opsin interacts distinctly with retinal, producing a distinct absorption spectrum.
Absorption spectra of cone pigments
Blue-
greenabsorbing
red-
Mutations that change the spectrum
Like Fig. 26-8, 26-9
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Rods dominate the visual response at low light levels
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Detection of light by retinal bound to opsin
Enzymes
From Darnell et al., Mol. Cell Biology
Like Fig. 26-8
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membrane
receptor
G protein
i q s t
cytosol
effector
channel enzyme
intracellular
messenger
cAMP
Ca2+ cGMP
channel
The GPCR pathway in photoreceptors
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Phototransduction
•Starts with photon absorption by
rhodopsin
•Transducin binds to activated
rhodopsin , exchanges GTP for
GDP
•Activated transducin dissociates
into  and  subunits
•The  subunit binds to, and
activates, phosphodiesterase
•Intracellular cGMP concentration
decreases
•Reduction in cGMP closes
cGMP-gated cation channels in
the plasma membrane
•Membrane potential
hyperpolarizes
•Closing of cGMP-gated channel
reduces intracellular calcium
•Reduced calcium counteracts the
effects of light absorption
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like a previous Lecture
receptor
Rods and Cones have
cGMP-activated Na+/Ca2+ Channels
G protein
i q s t
effector
channel enzyme
Excised
“inside-out” patch
allows access
to the inside surface
of the membrane
+cGMP*
intracellular
messenger
cAMP
Ca2+ cGMP
channel
no cGMP
no channel openings
open
+cGMP*
closed
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The “ribbon synapse” facilitates the tonic high rate of transmitter release
Photoreceptor to horizontal cell synapse
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The Phototransduction Cascade:
1. Amplification
2. Adaptation
1. When fully dark-adapted, many species can detect ~1 photon
per photoreceptor cell
2. When fully light-adapted, many species can accurately analyze
light at intensities ~1010 fold brighter
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The Phototransduction Cascade:
1. Amplification
1a. When the rod is dark adapted, the activated Receptor (O*) can activate
500 transducin proteins.
1b. The phosphodiesterase has a turnover number of 4200/sec, near the
diffusion limit for catalysis.
1c. Each millisecond that the cGMP-dependent cation channel in the rod
outer segment plasma membrane is open,10,000 ions flow through it.
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The Phototransduction Cascade:
(1. Amplification)
2. Adaptive mechanisms
2a. Transducin hydrolyses GTP to GDP and thus inactivates itself.
2b. The activated receptor (O* or R*) must also be deactivated.
(1) Rhodopsin kinase phosphorylates the carboxyl tail of the receptor
(2) The phosphorylation permits binding of the inhibitory protein, arrestin
3c. Guanylate cyclase must synthesize new cGMP from GTP
(1) Guanylate cyclase is partially inhibited by [Ca2+] >
~75 nM.
(2) Ca2+ influx through the tonically open cation
channel sets the cytosolic level of Ca2+ to ~ 500 nM.
(3) When the cation channel closes upon light
stimulation, Ca2+ continues to be pumped out via the
usual processes, lowering cytosolic Ca2+ to ~50 nM
and activating guanylate cyclase
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Visual excitation is followed by Recovery and Adaptation
Light
Cyclic GMP
hydrolysis
Channel
Closure
Lowered
cytosolic
Ca2+
Increased
cyclic GMP
synthesis
Channel
opening
Dark
State
The role of Ca2+ in adaptation also appears to be important, but this
process is not understood in molecular detail yet.
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•Visual information flows from photoreceptors
to ganglion cells through the bipolar neurons
•There are two types of bipolar cells, “on” and
“off”
•On bipolar cells are depolarized by light at
the center of their receptive field
•Off bipolar cells are hyperpolarized by light at
the center of their field
• Off bipolars have glutamate-gated ion
channels that shut off when the photoreceptor
stops releasing glutamate
•On bipolars have glutamate GPCRs that
activate phosphodiesterase and inhibit cGMPgated channels from opening in the dark
• When the photoreceptor stops releasing
glutamate, the cGMP channels open and
depolarize the on bipolar cell
Information flow in the
retina
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Retinal ganglion cells have centersurround receptive fields
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BBE/CNS 150
End of Lecture 13
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