Sensory systems: Transduction
Sensory cells are either
• 1. epithelial cells that are induced to specialize
in performing some type of sensory transduction
or
• 2. neurons that grow into the area where the
stimuli can be detected.
There are a
variety of ways to
categorize
senses: the
visceral afferents
typically do not
provide a
conscious
sensation and
yet provide
information for
reflex responses.
Visual system – Phototransduction
Vertebrate photoreceptors: rods
and cones
Cell types in the primate
retina:
R, rods
C, cones
H, horizontal
A, Amacrine
FMB, IMB, IDB, RB: all are
kinds of bipolar cells
MG, midget ganglion cell
P, parasol cell
Review of anatomy: you may ignore the names of the layers
Why upside
down? During
development, the
eye forms as an
outgrowth of the
brain. The retina
(located at the
back of the
eyeball) is
designed so that
light must pass
through all the
layers of neurons
before reaching
photoreceptors
and finally being
absorbed by the
pigment
epithelium.
Anatomy of rods and cones
Cones have folds and rods have free-floating disks that hold the
photoreceptor pigment. The receptor cell membranes have the highest
proportion of protein to lipid of any membranes analyzed…
Membrane
responses to
light: Cation
channels
(permeable to
Na+, K+ and
Ca++) are closed
in response to
light, which
causes
membrane
hyperpolarization
An individual cell’s
responses to light
are graded: the
more light, the
greater the
response of the
cell, up to a limit, at
which the response
capability of the
cell is saturated.
What is the link between the presence
of light and the cell’s response?
The signal must travel
• 1. from the altered receptor molecule
(rhodopsin-retinal, etc.) which captures
energy from the photon,
• 2. through second messengers in the
cytoplasm
• 3. to the outer membrane, to alter the
open/closed state of the channels.
The chromophore
retinal (retinene) is
a derivative of
Vitamin A. It is
bound to the visual
system’s 7
transmembrane
helix receptors,
rhodopsin and the
cone pigments
The mysterious enzymes will be described later…
The cone pigments have different peak absorbancies,
with Rhodopsin in the middle, at 496nm
Genes for the cone pigments are called S, M and L
Molecular basis of trichromatic vision: The G Protein-coupled 7
transmembrane helix receptor proteins have distinct sequences
Three cone pigments must all
be present to give normal
color discrimination. If one
pigment is defective or absent
(in dichromats) it is most
commonly a problem redgreen discrimination. Both of
these genes are on the X
chromosome, and the genes
are very similar (L vs M). This
explains why distinctions
between red and green are
easily lost, especially in
males, whereas the pigment
for blue is different. All three
cone pigments are equally
different from rhodopsin, the
rod pigment.
Hyperpolarization of rod by light: the cation channel is gated internally
by cyclic GMP, which must bind to open the channel.
Ankyrins organize the rod
membranes
• Ankyrins are intrinsic membrane proteins
involved in organizing a variety of specialized
membrane domains.
• Ankyrin G localizes exclusively to rod outer
segments, where it is necessary for targeting of
the cGMP-gated channel to the outer segment.
• In contrast, ankyrin B is confined to the
membrane of the inner segment, where it serves
to target Na+/K+ ATPase and the Na+/Ca++
exchanger.
• Kizhatil et al., (2009) Science 323: 1614.
Response to
light: rhodopsin
to transducin:
• Cation channels are
open as long as
cyclic GMP is
bound to them.
• “Dark current” (Na+
through cation
channels) is turned
off when cyclic
GMP is converted
to 5’GMP by
phosphodiesterase,
which is activated
by the G protein
Transducin.
Another view of the messages that regulate membrane
channels in the light transduction process
Events from previous slide…
1. In the dark, guanyl cyclase is active, generating cyclic GMP.
In the presence of bound cyclic GMP, the cation channels
are open, admitting both Na+ and, to a lesser extent, Ca++.
2. Photon changes the conformation of the receptor.
3. G protein (transducin) subunit Gα, activates
phosphodiesterase, which catalyzes the degradation of
cyclic GMP to 5’GMP. As the level of cyclic GMP falls,
channels close.
4. Recovery in the dark involves the βγ subunit and a neat
molecule called arrestin, which binds to phosphorylated
rhodopsin and allows the receptor to recover by competing
with the site required for activation of more G proteins
(transducin). The details of adjustment of the sensitivity of
the system (adaptation) that include arrestin are more than
you need to focus on….
What is the effect on synaptic communication if
the photoreceptor cells hyperpolarize in light?
• Hyperpolarization alters the “constitutive” release of
neurotransmitter, which leaks, more or less, from the
receptor, depending on whether the cell is receiving a lot
or a little light.
• Turning off a signal is as good as turning it on, to indicate
a change to the nervous system, as indicated below.
• The transmitter released by the photoreceptors in the
dark is referred to as an inhibitory transmitter – it is
glutamate.
Glutamate is the receptor that the
photoreceptors release in the dark
When light turns off the release of glutamate, the next
cells in the circuit, the bipolar cells, are less
hyperpolarized, i.e., relatively depolarized, and they
release transmitter that excites the ganglion cells
The ganglion cells are
constitutively active, firing
action potentials in the dark –
the level of action potential
generation increases in the
light. The ganglion cell axons
form the optic nerve and their
action potentials relay visual
information to higher levels of
the brain. Note that each cell
type has a graded potential –
the receptor potential, the
synaptic potential of bipolar
cells, and the synaptic
potential on which action
potentials are superimposed
(a recording like this would be
made in the soma).
Conclusions: Visual transduction
• Receptor cells, rods and cones, possess visual
pigments that are 7 transmembrane receptors that
are distorted by reception of light energy
(specifically when 11-cis retinal is converted to the
all trans form). The activation of the associated G
protein leads to changes in the concentration of
cyclic GMP, the ligand for the cation channels that
are open in the dark. The phosphodiesterase that
is activated by the subunit Gα breaks down the
cyclic GMP and so channels that lose their ligand
will close. The βγ subunit is involved in the
recovery process. The (inhibitory) signal relayed to
the postsynaptic cell by the receptor is “off” in the
light and “on” in the dark. Rebound from inhibition
allows the bipolar cells to release transmitter, which
excites the ganglion cells, the first cells in the
pathway to generate action potentials.