From Light to Vision: Demystifying the PHOTOTRANSDUCTION CASCADE and VISUAL CYCLE
Summary
TLDRThis lecture by Dr. Amrit delves into the intricate process of phototransduction, the conversion of light into electrical signals in the retina. It explains how light activates rhodopsin, triggering a cascade involving transducin and phosphodiesterase, leading to changes in membrane potential and ultimately vision. The video also covers the roles of sodium channels, calcium channels, and the importance of signal amplification and regulation in maintaining visual acuity.
Takeaways
- ๐ Phototransduction is the process of converting light energy into electrical signals in the retina, leading to vision.
- ๐ Phototransduction occurs in the discs of the outer segments of rods and cones, which contain photosensitive pigments.
- ๐ฌ Rhodopsin, a visual pigment in rods, is a G-protein coupled receptor with opsin and a carotenoid derived from vitamin A.
- ๐ Light exposure triggers a series of photochemical changes in rhodopsin, converting 11-cis retinal to all-trans retinal, initiating the visual cycle.
- ๐ The activation of rhodopsin leads to the activation of transducin, a GDP/GTP exchange protein, which is a key step in the signal transduction pathway.
- โก๏ธ Phosphodiesterase (PDE) is activated by transducin and is responsible for converting cGMP to GMP, affecting the opening and closing of sodium channels.
- ๐ก Sodium channels are open in the dark and close in the light due to the decrease in cGMP levels, causing hyperpolarization of the photoreceptor cells.
- ๐ The inner segment of the rod contains a sodium pump that maintains the negative charge inside the cell, part of the process known as dark current.
- ๐ Phototransduction involves signal amplification, where a single photon can activate multiple transducin molecules and lead to the closure of many sodium channels.
- ๐ The process is regulated by calcium channels, guanylate cyclase, and the protein arrestin, which help to halt and control phototransduction.
- ๐ Photoregeneration is the process of converting all-trans retinal back to 11-cis retinal, facilitated by the retinal pigment epithelium and isomerase enzymes.
Q & A
What is phototransduction?
-Phototransduction is the process by which light energy is converted into electrical changes in the retina, ultimately leading to vision. It involves a series of photochemical changes in the rods and cones of the retina after light absorption by photosensitive pigments.
Where does phototransduction occur in the structure of rods and cones?
-Phototransduction occurs in the discs present in the outer segment of the rods and cones.
What is the role of rhodopsin in phototransduction?
-Rhodopsin, a photosensitive visual pigment found in the disks of the outer segments of rods, plays a crucial role in phototransduction. It is a G-protein coupled receptor that undergoes a conformational change upon light absorption, initiating a series of reactions that lead to the generation of an electrical signal.
What happens during the isomerization of 11-cis retinal to all-trans retinal in rhodopsin?
-Upon light absorption, 11-cis retinal in rhodopsin undergoes isomerization to all-trans retinal, causing a conformational change in the rhodopsin molecule, which then activates a series of downstream reactions.
What is the function of transducin in the phototransduction process?
-Transducin is a G-protein that gets activated by the conformational change in rhodopsin. It exchanges GDP for GTP and activates the phosphodiesterase enzyme, which is involved in the hydrolysis of cyclic GMP.
How does the activation of phosphodiesterase affect sodium channels?
-The activation of phosphodiesterase leads to a decrease in cyclic GMP levels, causing the sodium channels to close. This results in hyperpolarization of the cell membrane in response to light.
What is the significance of the sodium channels' state in dark and light conditions?
-In dark conditions, sodium channels are open due to high levels of cyclic GMP, allowing sodium ions to enter and causing depolarization. In light conditions, the decrease in cyclic GMP levels causes the sodium channels to close, leading to hyperpolarization.
What is the role of the sodium-potassium pump in the inner segment of the rod cells?
-The sodium-potassium pump in the inner segment of the rod cells actively transports sodium ions out of the cell, maintaining the negative charge inside the cell and contributing to the dark current.
How does the neurotransmitter release at the synaptic terminals change between dark and light conditions?
-In dark conditions, depolarization of the photoreceptors leads to the release of neurotransmitters, such as glutamate. In light conditions, hyperpolarization results in a decrease in the rate of neurotransmitter release due to the closure of sodium and calcium channels.
What is the purpose of signal amplification in phototransduction?
-Signal amplification in phototransduction allows a single photon absorbed by a rhodopsin molecule to activate multiple transducin molecules, leading to the closure of many sodium channels and a significant change in the membrane potential, enhancing the sensitivity of the visual system.
What is the role of guanylate cyclase in the visual cycle?
-Guanylate cyclase is an enzyme activated by a decrease in internal calcium concentration. It catalyzes the production of cyclic GMP, which helps to reopen the sodium channels and allows sodium and calcium to enter the cells, thus regulating the phototransduction process.
What is the function of arrestin in the phototransduction process?
-Arrestin is a protein that blocks the ability of rhodopsin to activate transducin and facilitates the breakdown of activated rhodopsin. It helps to regulate and terminate the phototransduction process after it has been initiated.
Outlines
๐ Introduction to Phototransduction
Dr. Amrit introduces the concept of phototransduction, the process by which light energy is converted into electrical signals to initiate vision. This process begins when light hits the retina and is absorbed by photosensitive pigments in the rods and cones, leading to a series of photochemical changes. The focus is on the outer segment of rods and cones where phototransduction occurs in the discs. Key characters in this process include rhodopsin, transducin, and phosphodiesterase, which are activated in sequence. Rhodopsin, a G-protein coupled receptor, is composed of opsin and a light-sensitive molecule derived from vitamin A, known as 11-cis retinal. The absorption of light triggers a series of isomerization steps, converting 11-cis retinal to all-trans retinal, which activates the rhodopsin and initiates the visual cycle.
๐ The Activation of Transducin and Phosphodiesterase
This section delves into the activation of transducin, a GDP-GTP exchange protein that switches from an inactive to an active form upon binding with the activated opsin. The active form of transducin then interacts with phosphodiesterase, an enzyme that, when activated, converts cyclic GMP (cGMP) to GMP. The decrease in cGMP levels is pivotal as it leads to the closure of sodium channels, which are crucial for the generation of electrical signals in the retina. The sodium channels' stateโopen in the dark due to high cGMP levels and closed in the light due to low cGMP levelsโdirectly influences the cell's polarization state, leading to depolarization in the dark and hyperpolarization in the light.
๐ก The Role of Sodium and Calcium Channels in Phototransduction
The script explains the inner workings of the rod's inner segment, where a sodium pump actively maintains the cell's negative charge by pumping sodium out. In contrast, the outer segment's sodium channels allow sodiumโand a smaller amount of calciumโto enter, contributing to the cell's depolarization in the dark. This results in a 'dark current' due to the depolarization of photoreceptors and the release of neurotransmitters like glutamate. The calcium channels at the synaptic terminals are also highlighted, showing how their openness in the dark leads to increased neurotransmitter release, which is reduced in the light due to hyperpolarization and decreased calcium influx.
๐ Signal Amplification and Regulation in Phototransduction
The concept of signal amplification is introduced, where a single photon can activate multiple transducin molecules, leading to the closure of numerous sodium channels and a significant change in membrane potential. The importance of calcium levels in regulating phototransduction is discussed, with the calcium-activated guanylate cyclase enzyme playing a role in the production of cGMP, which in turn opens sodium channels. The presence of arrestin is also mentioned as a means to inhibit further activation of transducin by rhodopsin, thus controlling the phototransduction process.
๐ The Visual Cycle and Phototransduction Summary
The final paragraph wraps up the lecture by summarizing the key photochemical reactions in the rods: rhodopsin bleaching, where light converts 11-cis retinal to all-trans retinal, and rhodopsin regeneration, where all-trans retinal is converted back to 11-cis retinal by the retinal pigment epithelium. The balance between these reactions, known as the visual cycle, is essential for maintaining vision. The video concludes with a recap of the importance of phototransduction and its regulation for proper vision.
Mindmap
Keywords
๐กPhototransduction
๐กRhodopsin
๐กTransducin
๐กPhosphodiesterase
๐กSodium Channels
๐กDepolarization
๐กHyperpolarization
๐กCalcium Channels
๐กSignal Amplification
๐กGuanylate Cyclase
๐กArrestin
Highlights
Photo transduction is the process of converting light energy into electrical changes in the retina, leading to vision.
Photo transduction occurs in the discs of the outer segments of rods and cones.
Rhodopsin, a photosensitive pigment in the rod cells, plays a crucial role in the visual cycle.
The 11-cis retinal in rhodopsin undergoes a conformational change to all-trans retinal upon light exposure.
Rhodopsin bleaching or photo decomposition is the separation of opsin from all-trans retinal induced by light.
Transducin is a GDP-GTP exchange protein that gets activated by the conformational change in opsin.
Phosphodiesterase enzyme, activated by transducin, converts cyclic GMP to GMP, affecting sodium channels.
Sodium channels' opening and closing are regulated by the levels of cyclic GMP and GMP, influencing the cell's polarization state.
Depolarization in the dark and hyperpolarization in the light are key to the functioning of photoreceptors.
The inner segment of the rod contains a sodium pump that maintains the cell's negative charge.
Dark current is the result of depolarization and the release of neurotransmitters like glutamate in the synaptic terminals.
Differences between rods and cones and other sensory cells include the release of neurotransmitters and the generation of graded potential changes.
Voltage-gated calcium channels at the synaptic terminals regulate neurotransmitter release based on light conditions.
Signal amplification in phototransduction allows a single photon to activate multiple transducin molecules.
The guanylate cyclase enzyme helps regulate phototransduction by producing cyclic GMP when internal calcium concentration decreases.
Arrestin protein blocks rhodopsin's ability to activate transducin, facilitating the breakdown of activated rhodopsin.
Rhodopsin regeneration involves the conversion of all-trans retinol back to 11-cis retinal by retinal isomerase enzyme.
The visual cycle, including rhodopsin bleaching, regeneration, and the balance between light and dark processes, is essential for vision.
Transcripts
hello and welcome to Insight oftalmology
this is Dr Amrit welcoming you to
another lecture today we are studying
photo transduction or the visual cycle
first is what is photo transduction
light falls on retina and it is absorbed
by the photosensitive pigments which are
present in the rods and cones this will
cause a series of photochemical changes
in the rods and Cone finally leading to
the electrical changes in their membrane
potential and this process of changing
of light energy into electrical changes
finally leading to vision is called
photo
transduction we know that the rods and
the cones they basically have the outer
segment an inner segment and a synaptic
region now the question is where does
photo transduction occur it basically
occurs in the discs which are present in
the outer segment of the rods and also
in the cones we know the outer segment
of Rod actually have this arrangement of
several discs stacked on each other now
now if we actually Zoom this dis of the
outer segment let me now introduce to
you the various characters of this video
in this video we shall be studying about
the ropin and how ropin affects another
character that is the transducin and we
have the phosphor Diest which is
affected by the transducin however you
should know that phosphor Diest always
exist with its two gamma subunits apart
from that we shall be talking about
another important character and that is
the sodium channels so first of all what
is ropson ropin is actually a
photosensitive visual pigment which is
present in the disk of the outer
segments of the rod it is actually a g
protein coupled receptor it is one of
those Serpentine receptors it has two
subunits the one basic one is a protein
and apart from the protein which is
called opsin we have a carotenoid this
carotenoid is derived from vitamin A and
therefore it is also called vitamin a
alide or also called retinene apart from
that the name with which it is famous is
the 11 Cy retinol so here you can see in
Orange is the option and we have a small
component of the vitamin A which is the
11 CIS retina very important component
now going a step further so let us see
what exactly happens when light strikes
the retina inside the ropson molecule
where we have the 11 Cy retina at the
carbon 11 and carbon 12 Bond there will
be a confirmational change such that we
get from 11 C retinol all trans
retinol so these two are actually
isomers that means the 11 C retinol and
the all trans retinol if you carefully
observe they have similar chemical
composition that mean the same number of
carbon atoms the same number of hydrogen
atoms however their shapes are
different so ropson will be actually
converted that means the 11 CIS retinol
in the the adoption will finally be
converted into the all trans retinal
through a series of steps so the steps
are as follows the ropin is first
converted into the Bor ropin then we get
Lumi ropin then we get meta ropin one
and finally we get meta ropin 2 which is
the active ropin containing the all
trans retinol remember all this happens
in the presence of
light so as I told you that activated
ropin and how was the rops in activated
by the presence of life it basically has
all trans retinol in it now as the
confirmational change occurs and it
becomes metod opsin to they cannot live
together opsin and all trans retinal
will now have to separate from each
other and this process which is induced
by light that is the separation of the
opsin from the ultan retinal is called
ropson bleaching or the photo
decomposition are you with me so we
completed the character adoption next we
have the transducer okay this guy in red
color so basically our activated ropin
has the all trans retina right now this
is called active ropin because it is
going to go and activate our next
protein that is the
transducin so our next character that is
a transducin is a GDP GTP exchange
proteins now it has two forms it has an
inactive form and an active form the
active form basically has the GTP
attached to it and the inactive form has
a GDP attached to it the question is how
will it be activated so it is our
activated opsin which will go and bind
to transducin and activate the
transducin so our activated opsin
molecule we know how it gets activated
from the dosin to metaoption 2 metop
adoption 2 actually has all trans
retinol the option will now separate
from the all trans retinal and this
option will now develop this binding
site on it and now what happens is that
with this binding site this option is
going to go and bind to your inactive
transduc which had GDP before and that
GDP will now be exchanged with GTP and
therefore we will get an active
transducin now once we have an active
ropion an active transducin let us now
introduce the Third character and that
is the phosphor diestra enzyme so our
phosphor diestra enzyme is also present
in the membrane and the thing is that in
its inactive form it has these two gamma
units attached on the either side and
obviously once you remove these gamma
units from the phosphor diestra you will
have an active molecule of phosphor
diestra
enzyme again the question is what will
activate phosphor diast so you might
have guessed it by now it is our
activated transducin which has a GTP in
it so that will come and activate your
inactive phosphor diestra okay so what
happens is it basically your transducin
is actually a trimeric protein that
means it has three parts so one part of
your transducin which has GTP attached
to it is going to come down to your
gamma unit of the phosphor destr and it
will actually attach to the gamma unit
of the phospho diay and subsequently it
will try to separate that gamma unit
from your phosphor diestra gamma complex
but the thing is we still have this
phosphor diestra as inactive because of
the presence of one more gamma unit to
it so what will happen next one more
transducin which is activated by your
opsin will come forth and try to remove
this gamma unit and therefore finally
the gamma units from both the sides of
the phosphor dry stay will be removed
and you will will get an activated
phosphor diestra so now we got our
activated phosphor diestra molecule but
did I tell you what is the function of
this phosphor Diest the function is that
it will convert your cyclic GMP to the
normal gine mono phosphate or the GMP so
the cyclic GMP will represent in brown
color and the GMP will represent in the
blue
color now what happens is as you can see
as your phosphor G will get activated
all your cyclic GMP is getting converted
to your GMP so obviously the cyclic GMP
concentration is coming down and there
will be a decrease in the level of
cyclic GMP so remember that cyclic GMP
is also very important component and you
will understand it better when I
introduce to you the next character of
the story which is the sodium channels
your sodium channels can either be
opened or it could be closed so the the
top one is a open sodium Channel and the
bottom one is a closed sodium Channel
now if you see carefully I have drawn a
brown color ball near the open sodium
Channel and that brown color is nothing
but it is a cyclic GMP whereas the blue
color is a normal GMP so you can say
that the sodium channels will open in
the presence of your cyclic GMP and they
will close Whenever there is a normal
GMP around that channel so basically in
dark what happens is these channels will
be open and therefore the sodium
channels will be open in dark because of
the increased level of cyclic GMP
however in the presence of light do you
remember all the characters what was
happening light was bringing all those
characters and activating them whether
it was ropin transducin and then the
phosphor diestra enzyme so this phosphor
di enzyme then led to decrease in the
cyclic GMP concentration and ultimately
what will happen as the cyclic GMP goes
down the GMP increases and therefore the
channels will remain closed and
therefore in light the channels will
actually close so that's very important
Point regarding this
character so basically what is happening
in our dark is that we have cyclic GMP
we have open sodium channels and because
of the increased level of cyclic GMP
more and more amount of sodiums is
actually entering the cell the cell is
becoming relatively positive and this is
called deol ization which occurs in the
dark
phase whereas in light what happens we
have our active character of phosphor
diestra which is actually converting
your cyclic GMP to your GMP and the GMP
concentration is rising and therefore
the channels are closed and therefore
the sodium is going to start
accumulating outside the cell the inside
of the cell is going to become more and
more negative and this is called
hyperpolarization which occurs in the
light phase so do you know that some
changes also occur in the inner segment
of the rod so in the inner segment of
the rod we have a sodium pump which will
actively keep on pumping the sodium out
so obviously the inside of the cell in
the inner segment will become negative
because all the positives are coming out
and obviously in the outer segment we
know we have seen that the sodium from
outside is entering inside through those
sodium channels right this is what we
already saw and these channels are going
to open induct so because of this
variable ionic conduction inside the
cell that means the outer segment is
relatively positive in the dark because
of the sodium entering and the inner
segment is relatively negative because
the sodium is exiting through the pump
we get a particular type of current
flowing from the outer segment inner
segment and going up to your CTIC
Terminals and this current is called the
dark current okay and this dark current
is basically basically because of the
depolarization of the photo receptor I
already told you what is depolarization
as the receptor gets depolarized we will
have the release of the neurotransmitter
from the synaptic Terminals and mostly
this neurotransmitter is
glutamate there are some changes between
other sensory cells and the rods and
cones in the other sensory cell the
receptor will get activated by
depolarization and then we will have an
action potential generation and finally
we will have the release of the
neurotransmitter however in rods and
cones you saw that in dark the receptor
was depolarized however when light came
about there was actually receptor
hyperpolarization and then that leads to
generation of graded change in the
potential and not action potential
moreover the neurotransmitter was being
released in the dark and let me tell you
it is also released in the light also
however there's a graded change in the
amount of neurotransmitter that is being
released at the post synaptic neurons so
that is some important differences
between the sensory cells and the rods
and cones so basically what happens in
dark there is some amount of negativity
inside that is called the resting
membrane potential and that is about 40
molts and obviously when light strikes
there is a progressive increase in the
negativity inside and you will see the
the membrane potential reaching minus 65
m volts because of the
hyperpolarization so this over here is
actually an introduction to another
character of the story and that is the
calcium channels okay understanding this
character is very important if you want
to understand how this entire process of
photor transduction will actually come
to a halt okay so the volted Gated
calcium channels are actually present at
the preoptic terminals okay so you can
see that here I've drawn them in pink
color the these recycles are actually
containing your
neurotransmitters now I already told you
that in the outer segment in the dark
what is happening the sodium channels
are open and the sodium is entering the
outer segment now let me tell you that
along with sodium a little bit amount of
calcium is also going to enter into the
outer segment to keep the photo
receptors depolarized because the amount
of calcium in the rods is more IND dark
the number of calcium channels in the
synaptic terminal will also be more will
be open more and this will lead to more
amount of neurotransmitter release so
the rate of neurotransmitter release is
correspondingly great in compared to
dark compared to light so in the light
what happens again we know that in light
what happens the sodium channels will
close so even the calcium enters to the
sodium channels the amount of calcium
will also be less the rods are
hyperpolarized the number of open
calcium channels will therefore be
reduced and the rate of neurotransmitter
will also be reduced at the synaptic
terminal so in dark we have
depolarization that ultimately causes an
increased neurotransmitter release
however in light we have
hyperpolarization and that causes a
decreased neurotransmitter release okay
so this is what you can actually
understand here through this diagram so
in the dark what is happening the sodium
is able to enter even the calcium is
able to enter the cyc GMP level AB are
more and what do we see we see that the
this arrow is actually towards the de
rise take that means the inside of the
cell is not as negative as compared to
the light so in light what happens the
cyclic GMP levels will be less the uh
GMP levels will be more and therefore
the sodium channels will be closed the
inside of the cell will become more
negative see the arrow is tilting more
towards the negative side and there will
be hyperpolarization therefore in the
presence of Darkness there is
depolarization and in light there is
hyperpolarization of the receptor now I
think this would be a right time to
introduce you to the signal
amplification concept we know that in
the disc segment or in the dis of the
outer segment we have these various
discs and all these dis individually
also have so many molecules of
transducin sitting on that a single
light activated adoption can actually
activate about 800 transducin molecules
which is about 8% of the total molecules
which are sitting on the disk surface so
just look at that number now either one
or two translucent molecules will go and
activate one phosphor Diest molecule
okay now actually there's a controversy
about it that some sources say that we
need two translucent molecules to
activate one phosphor di enzyme and some
sources say that we need only one
translucent molecule to activate one
phosphor di molecule okay so what do you
think about it just let me know in the
comment section now each phosphor Diest
can actually break down about six cyclic
GMP molecules okay so this there's so
much amount of signal amplification that
a single Photon by a ropson molecule can
actually lead to closure of about 200
sodium ion channels and that is about 2%
of the number of channels in each Rod
that are actually open in the duck right
and this this amount of Channel closure
will cause a net change in the membrane
potential of about 1 million volt okay
so this light amplification the
magnitude of this amplification actually
varies with the prevailing level of
Illumination you change the level of
Illumination and you can change the
amplification signal now this is called
light adaptation so the concentration of
calcium in the outer segment is very
very important the cyclic GMP gated
channels in the outer segment as I told
you they are permeable to both sodium as
well as calcium and therefore when the
light causes closure of these Channel
there will be a net decrease in the
internal calcium concentration as well
now as the internal calcium
concentration goes down what happens is
that there's another protein which gets
activated another enzyme gets activated
and that enzyme is the galate cycles and
it will now leads to production of the
cyclic GMP and we know what happens when
the cyclic GMP increases so when the
cyclic GMP will increase the sodium
channels will now open apart from that
the cyclic GM this Guan Cycles will also
increase the Affinity of the cyclic GMP
gated channels for the
cgmp this will cause the sodium channels
to open and sodium and calcium will now
enter the cells the calcium
concentration will now increase and the
photo ructions U amplification whatever
we saw will now start decreasing okay so
that is how the photot transduction is
actually control okay now there's
another protein which is called arrestin
so this arrestin basic basically what
what it does is that it actually blocks
the ability of ropin to activate
transducin and facilitates the breakdown
of activated adoption so this arrestin
is going to arrest the adoption and
prevent this red option for further
activating transducin so definitely
photot transduction is an important
process but everything needs to be
controlled after some time and we have
this important calcium channels we have
this gal cyclist that we studied about
and also we have this important protein
molecule which is called a Restin which
will regulate our photo
transduction so after this photo
transduction stops the red option will
undergo regeneration which is nothing
but the all trans retinol will be
converted to 11 set retinol again which
is called which is done by the retinal
isomerase enzyme the 11 say retinal will
again join with opsin and leads to
formation of R opsin this occur in the
retinal Pig pment epithelium by the
way so now let us join all these dots
together so there are basically three
main photochemical reactions which are
occurring in the rods we have a rops and
bleaching rops and regeneration and the
visual cycle now it'll become very easy
for you the first step is redops and
bleaching we saw that when light strikes
the retina the 11 C retinol will undergo
isomerization change and gets converted
into Old trans retinol to a series of
changes of course now this process is
called ropion bleaching or photo
decompression the next step is the
redops and regeneration we know how it
occurs all trans retinal gets converted
back to its original form ropson which
was broken down again forms a new ropson
this is called ropson regeneration so
degeneration basically is dependent on
light however the Regeneration occurs
equally in light as well as dark that's
important point so the first process by
which 11 says retinol is converted into
all trans retinol is called photo
bleaching or photo decomposition and the
second process by which it is
regenerated back to 11 say retinol is
called photo regeneration and there is
always a balance in the eye between the
two now this balance and this cycle is
called the vault's visual
cycle so that was a detailed video on
photo transduction I hope you were able
to follow it I hope it was useful thank
you and have a nice day
[Music]
yeah
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