4 - Sensory Systems and G-Proteins; Second Messengers and Effectors Flashcards
How many major families of G proteins are there?
4
What G-proteins are found in class I?
Gs and Golf
What do the G-proteins in class I do?
Activate AC
What G-proteins are found in class II?
Gi, Go, and Gt (transducin)
What do the G-proteins in class II do?
Inhibit AC, activate potassium channels, function in photoreceptors, etc.
What G-proteins are found in class III?
Gq
What do the G-proteins in class III do?
Activate phospholipase C-beta
What G-proteins are found in class IV?
G12/13
What do the G-proteins in class IV do?
Regulate actin cytoskeleton
In which class of G-proteins can the beta/gamma subunit also play a role?
Class II
True or false: our range is vision (in terms of light intensity) is fairly broad
True: we can detect light in many orders of magnitude
What happens in scotopic conditions?
No color vision, poor acuity
What does scotopic mean?
Vision in very low light settings
What cells are active in scotopic conditions?
Rods
What does mesopic mean?
Vision in fairly low light settings
What happens in mesopic conditions?
Start to use cones
What cells are active in mesopic conditions?
Rods and cones
What does photopic mean?
Vision in broad daylight
What happens in photopic conditions?
Good color vision, best acuity
What cells are active in photopic conditions?
Cones
How does perception and interpretation relate to vision?
The background and your expectations influences what we see
What is the path of light in the eye?
Goes through pupil and lens to shine on retina
What are the layers of the retina (in the same order that light would see them)?
Ganglion cells, bipolar cells, photoreceptor cells, endothelial cells
What cells connect to the nerve fiber in vision?
Ganglion cells
Which cells are excited by light?
Photoreceptors (rods and cones)
How does membrane potential change the cell?
Opens ion channels to further change membrane potential
What happens to the membrane potential when ion channels are closed?
Resting potential of the neuron
What happens to the membrane potential when ion channels are open?
Ions rush into or out of the cell, changing the membrane potential
What happens to the membrane potential when ion channels are inactived?
There is no change, since the channel does not open, even in response to a new signal
What is a depolarization?
Membrane potential becomes more positive (positive ions flow in, or negative ions flow out)
What is a hyperpolarization?
Membrane potential becomes more negative (negative ions flow in, or positive ions flow out)
If the membrane potential becomes more positive, what is this called?
Depolarization
If the membrane potential becomes more negative, what is this called?
Hyperpolarization
How does an action potential work in a typical neuron?
- Depolarization leads to influx of sodium
- This leads to a hyperpolarization with an outflux of potassium
- Sodium-potassium pump works to restore membrane potential
What happens when a photoreceptor gets stimulated by light?
It hyperpolarizes (becomes more negative)
What happens to a photoreceptor if there is no stimulus?
It depolarizes (becomes more positive)
How does a photoreceptor stay depolarized with no stimulus?
Leaky Na+ channels (influx of positive charge)
How does a photoreceptor hyperpolarize with a stimulus?
Na+ channels close (stops influx of positive charge)
What molecule is responsible for phototransduction (detects light)?
Retinal
What is the form of retinal in the dark?
11-cis-retinal
What is the form of retinal in the light?
all-trans-retinal
How does retinal transduce the light signal?
The change in conformation (cis -> trans) causes a change in the receptor, thus starting the signal cascade
What is rhodopsin?
An opsin molecule with an embedded retinal molecule
What is opsin?
A GPCR that interacts with retinal to form rhodopsin
What type of signaling is used in vision?
Indirect signaling through the second messenger cGMP
What is similar to rhodopsin (in terms of structure)?
Adrenaline receptor
Who discovered the G-protein associated with vision?
Lubert Stryer
What did Lubert Stryer do?
Discover transducin
What is another name for Gt?
Transducin
What does transducin do?
G-protein for the vision system
What are the levels of cGMP in the dark?
High levels
What are the levels of cGMP in the light?
Low levels
What does transducin do?
Activated cGMP phosphodiesterase (PDE)
What does guanylate cyclase (GC) do?
Converts GTP into cGMP
What does cGMP PDE do?
Converts cGMP into GMP
Why are there high levels of cGMP in the dark?
GC makes cGMP, and PDE is not active to break it down
Why are there low levels of cGMP in the light?
PDE is activated by transducin in light, which breaks down cGMP into GMP
What subunit of transducin activates PDE6?
aGt
What PDE is found in the vision system?
PDE6
What are the subunits of PDE6?
2 regulatory subunits (gamma) and 2 catalytic subunits (alpha and beta)
How does Gt interact with the subunits of PDE6?
2 molecules of aGt bind to the 2 regulatory gamma subunits, thus activating the alpha/beta subunits of PDE6
How does cGMP interact with ion channels?
cGMP binds to ion channels to open them
Why are ion channels opened in the dark?
High levels of cGMP bind to the ion channels to open them
Why are ion channels closed in the light?
Low levels of cGMP prevents many from binding to the ion channels, thus keeping them closed
How is PDE inactivated after starting a signal?
RGS5 and Gbeta5 bind to aGt to increase GTPase activity, thus inactivating it and PDE
What needs to be done (in terms of signaling) to detect rapid movement?
Rhodopsin signaling must be rapidly shut down
How long does the shut down of the vision system take?
~50 ms
How does calcium function in the vision system?
Calcium sensing proteins detect a fall in intracellular concentration, and then stimulate GC to make more cGMP
How is rhodopsin downregulated?
Phosphorylation of rhodopsin by a rhodopsin kinase
How is rhodopsin signaling completely blocked?
Arrestin binds to a tri-phosphorylated rhodospin, stopping signaling
If there are less than three phosophates on rhodopsin, how is the activity changed?
There is less, but some, activity compared to no phosphorylation
What does the photoreceptor cell do when it is depolarized?
Constantly releases neurotransmitter
What does the photoreceptor cell do when it is hyperpolarized?
Stops releasing neurotransmitter
What does the photoreceptor cell do when it is in darkness?
Constantly releases neurotransmitter (depolarized)
What does the photoreceptor cell do when it is in light?
Stops releasing neurotransmitter (hyperpolarized)
What neurotransmitter is released by photoreceptors?
Glutamate
What does glutamate do to bipolar cells?
Inhibits them
When the photoreceptor is in darkness, what happens to the bipolar cells?
Inhibited (glutatmate released by photoreceptor)
When the photoreceptor is in light, what happens to the bipolar cells?
Activated (glutatmate is not released by photoreceptor)
Why use a slow indirect receptor for vision, which needs to be immediate?
Sensitivity and amplification
How is sensitivity achieved in vision?
Driven by the number of ion channels (more ion channels means more light is needed to hyperpolarize cell)
How is amplification achieved in vision?
Each component activates several downstream components
Besides sensitivity and amplification, how can the slow speed of the response be compensated in vision?
Sandwiched discs have a small volume with lots of proteins, so there is reduced distance between signaling components
True or false: rods can respond to one photon of light
True: the amplification in the system allows for a sensitive response
How do the components amplify in response to one photon?
One photon -> 500 Gt activated -> 500 PDE activated -> 10^5 cGMP hydrolyzed -> 250 Na channels close -> 10^6 Na ions over 1 second don’t enter cell -> alter membrane potential by 1 mV -> signal to brain
How does a bipolar cell interact with a ganglion cell?
It is an excitatory synpase (stimulates ganglion cells when it is stimulated, or not inhibited)
When is the bipolar cell hyperpolarized?
When the photoreceptor is depolarized, and releases inhibitory neurotransmitter
When is the bipolar cell depolarized?
When the photoreceptor is hyperpolarized, and stops releasing inhibitory neurotransmitter
When is the ganglion cell activated?
When the bipolar cell is activated (in light) and releases neurotransmitter
When is the ganglion cell inhibited?
When the bipolar cell is inhibited (in darkness) and doesn’t release neurotransmitter
What type of synapse is between a photoreceptor and a bipolar cell?
Inhibitory synapse
What type of synpase is between a bipolar cell and a ganglion cell?
Excitatory synpase
What is visual adaptation?
The change in sensitivity of our eyes to high and low light levels
True or false: rod signaling is reduced after prolonged exposure to bright light?
True: this is part of visual adaptation
How are the proteins in a rod cell distributed in darkness?
Transducin is transported to outer rod segments (where signal transduction happens), while arrestin is transported elsewhere (does not interact)
Why is transducin found in the outer rod segments in darkness?
Transducin activates the signal, which is needed in low light conditions
Why is arrestin found elsewhere in rod cells in darkness?
Arrestin stops the signal, which is not needed in low light conditions
How are the proteins in a rod cell distributed in bright light?
Arrestin is transported to outer rod segments (where signal transduction happens), while transducin is transported elsewhere (does not interact)
Why is transducin found elsewhere in rod cells in bright light?
Transducin activates the signal, which is not needed in bright light conditions
Why is arrestin found in the outer rod segments in bright light?
Arrestin stop the signal, which is needed in bright light conditions
Why does the distrubution of rod proteins change in different light levels?
This allows for high sensitization in low light levels, and low sensitization at high light levels
What is the contrast range of rod cells (due to visual adaptation)?
100,000 fold range
What are the two types of photoreceptors?
Rods and cones
When are rods active?
In low light conditions
When are cones active?
In bright light conditions
Which photoreceptors are responsible for color?
Cones
What does Sidenafil (Viagra) do?
Inhibits PDE
What is the normal signaling pathway for smooth muscle cells (without Viagra)?
Neuronal inputs lead to NO, which activates GC to produce cGMP from GTP. cGMP then activates PKG, which leads to vasodilation (increased blood flow)
What is the effect of Viagra?
Increased blood flow (vasodilation)
Why does Viagra lead to vasodilation (increased blood flow)?
Viagra inhibits PDE, thus keeping cGMP levels high. This stimulates PKG, thus leading to vasodilation
How does Viagra interact with vision?
Viagra also inhibits PDE6 (in the eyes), causing some side effects such as blue aberrations
Why can Viagra cause blue aberrations (and not green or red aberrations)?
Viagra impacts PDE6 in S-cones (blue sensitivity) more than M/L cones
Where does olfaction take place?
In the olfaction bulb
What cells are in the olfaction bulb that receive the signals from receptors?
Glomeruli
How do signals reach the glomeruli?
Oderant bind to odor receptors, which travels through olfactory receptor cells, epithelium, and bone to reach glomeruli
What does the glomeruli do after reciving a signal?
Passes the signal to mitral cells to be sent to the brain
What are glomeruli?
Groups of neurons
How are glomeruli grouped?
The same type of receptor (spread throughout the epithelium) converge at one glomeruli
True or false: One mitral cells codes for one odorant molecule
True: the receptors that recognize a specific odorant all converge on one mitral cell
What is the second messenger in olfaction?
cAMP
What G-protein is associated with olfaction?
Golf
How does Golf work?
Activates AC, which produced cAMP. cAMP then opens ion channels to cause an action potential
What ion channels are present in olfaction?
Sodium, chloride, and calcium
How do the ion channels change when there is an olfaction signal?
Calcium channels open, bringing in calcium and sodium. Calcium binds to chloride channels, moving chloride out. They also bind (with CAM) to calcium/sodium exchangers to move calcium out and more sodium in
What allows for specific odorant detection (in terms of the receptor)?
Variability of amino acid sequence
How does the brain interpret a smell?
Different combinations of signals from glomeruli are processed as a smell
Why is a dog’s smell better than a humans?
More receptors, bigger brain region for processing smells, can smell in 3D (each nostril processes separately)
How do genes evolve with different functions?
Copies of duplicated genes diverge
What is an example of genes with different functions due to duplication?
Lysozyme (enzyme to protect against bacterial infection) and alpha-lactalbumin (helps in milk production)
How can gene evolution occur?
Exon shuffling, and exon duplication (occurs during recombination)
What is a trichromatic view?
Can see reds, blues, and greens
What is a dichromatic view?
Can see blues and greens
What is a monochromatic view?
Can only see shades (no blues, greens, or reds)
What light has the longest wavelength?
Red
What light has the shortest wavelength?
Blue
In old world primates, how are color pigments organized in the genes?
Blue gene is on an autosome, and both red and green genes are on X chromosome
In old world primates, what kind of vision can males see?
Trichromatic (X chromosome has two genes, autosome has 1)
In old world primates, what kind of vision can females see?
Trichromatic (X chromosome has two genes, autosome has 1)
What vision genes are found on the Y chromosome?
None
In new world primates, how are color pigments organized in the genes?
Blue gene is on an autosome, and X chromosome has either one red, one green, or one yellow gene
In new world primates, what kind of vision can males see?
Dichromatic (autosome has 1, X chromsome has 1 of 3 possible options)
In new world primates, what kind of vision can females see?
Either dichromatic or trichromatic, depending on the X chromosomes
If a new world primate female is dichromatic, what can you say about the X chromosomes?
They both have the same color gene (both red, green, or yellow)
If a new world primate female is trichromatic, what can you say about the X chromosomes?
They have two different color genes (from red, green, and yellow)
How did color vision evolve?
Mutations allows for the different color pigments seen in new world primates. A duplication error then causes the two genes to be on one X chromosome, as seen in old world primates
How can the plasticity of the brain be seen in color vision?
A mouse with a new gene can see more and different colors, and can recognize it (can use the new gene)
What is the evolutionary advantage of color vision and being trichromatic?
Better contrast with surroundings (see when food is ripe, etc.)
How can women have tetrachromaticity?
Mutation in one of the X gene shifts the spectrum slightly
If activation of 10% rhodopsin gives a maximal response, how does activation of 90% rhodposin affect the speed of response?
The speed increases
Why does having 90% rhodopsin increase the speed compared to 10% rhodopsin?
More rhodopsin activation leads to more PDE activity, thus reducing cGMP more, and thus closing the ion channels faster
How is the concentration and speed of responses different for rhodopsin?
The concentration to get a max response can be low, and be steady at higher numbers of receptors. The speed will increase with more receptors, since more channels close simultaneously
What is another example of cis/trans signaling?
Proline can be cis or trans, and can be switched by isomerases
Why does the visual system depolarize at a different membrane potential than other neurons?
So there can be less noise, and thus more sensitivity (based on dynamics of the cell)
What phenomena makes vision sensitive to even a single photon?
It’s easier to interrupt a constantly inhibited cell compared to generating a strong enough signal to create response
Do multiple cones and rods share the same pathway?
Both; there are both converging and diverging pathways
What differentiates the three cones cells?
The structure of the opsin, which heavily predominates in a certain cone cell
How is smell and taste processed together?
Through upper brain circuitry
How come you can’t see color in low light conditions?
Cones are not activated under low light
True or false: glutamate is only inhibitory
False: glutamate is primarily excitatory, but can also be inhibitory
Why does imparing the speed of a response get interpreted as blue?
Blue light is filtered as it reaches the retina, while other light isn’t
Why do we have greater acuity in the center of our vision?
Cones are found in the center of the eye
Why does our periphery vision not have color?
Rods are found in the periphery of the eye
Where is the most sensitive opsin found?
In the rod cells
True or false: light is not detected by the photoreceptors when we are asleep
False: light is still detected, but we are not consciously aware of it
True or false: the G-proteins for vision and olfaction are the same, the receptors are different
False: the G-proteins are different between vision (transducin) and olfaction (Golf)
What do mitral cells do?
Take the signal from glomeruli and send it to the brain
What compensates for the vision system having a high metabolic cost?
Very sensitive system of light detection
What mechanisms does visual adaptation use?
Relocation of arrestin / transducin to different segments of rods
What does visual adaptation refer to (in terms of the conditions)?
From bright light to darkness (not from darkness to bright light)
What is the change in photoreceptors in visual adaptation?
From cones to rods (only from bright light to darkness)
