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Sensory Neuroscience 316 > The phototransduction pathway. Lecture 8 > Flashcards

The phototransduction pathway. Lecture 8 Flashcards

1
Q

What is phototransduction?

A

The process of a cell absorbing light and creating a response

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2
Q

What is the response generated by phototransduction?

A

This response is a change in the amount of neurotransmitter released to its target neuron.

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3
Q

What is the first step of the phototransduction pathway?

A

Light interacts with the visual pigment of the photoreceptor. Which is found in the outer segment of the photoreceptors.

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4
Q

What does this lecture go over with regards to the phototransduction pathway?

A
  1. How light is transduced and results in hyperpolarisation.
  2. How this hyper polarisation event also results in low Ca that leads to deactivation of the cascade.
  3. The various possible ways of deactivating the cascade.
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5
Q

What sort of pathway is the phototransduction pathway?

A

A molecular transduction cascade

signalling cascades

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6
Q

What does phototransduction result in?

light on photoreceptors

A

Closure of the Na/Ca channels in the membrane and hyperpolarisation of the membrane.

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7
Q

Do phototransduction result in the generation of an action potential?

A

No action potential is generated by phototransduction regardless of light or dark conditions… however neurotransmitter release can be varied from basal level.

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8
Q

What are the components of the phototransduction pathway in rods?

A
  1. Visual pigment = Rhodopsin (transmembrane protein) CIS-retinal sits in a binding pocket of rhodopsin. (specific form of retinal)
  2. Transducin (intracellular membrane bound protein)
  3. Phosphodiesterase (PDE)
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9
Q

What comprises the transducin protein?

A

alpha, beta and gamma subunits.

In the INACTIVE state G-alpha subunit has GDP bound in its binding site.

Transducin is a G-protein.

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10
Q

What is the activity of the transducin protein?

A

It has GTPase activity.

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11
Q

Whats the function of PDE?

A

Breaks down cGMP to GMP by the PDE enzyme.

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12
Q

Whats the first reaction of the phototransudction pathway?

in light

A

In the presence of light:

  1. Light exposure causes the isomerisation of the CIS-retinal into trans-retinal (causing it to leave the rhodopsin (opsin) protein binding pocket.
  2. This causes a conformational change of rhodopsin into metarhodopsin2 or Rho* (activated form)
  3. Rho* binds transducin
  4. Transducin dissociates from its GDP and binds GTP
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13
Q

Describe the second phototransduction reaction:

In light

A
  1. GTP causes Gα transducin to dissociate from βγ subunit
  2. Gα binds to PDE γ
  3. 2 transducin molecules are required to release inhibitory constraint imposed by PDE γ (activating it)
  4. PDE hydrolyses cGMP to GMP
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14
Q

Whats the third (final) phototransduction step?

IN light

A
  1. The level of cGMP has been reduced by PDE.
  2. low cGMP means that there is insufficient to bind to cGMP gated Na channels therefore there is decreased Na/Ca influx

(lowered Ca levels, means less glutamate release as no Ca to bind to the vesicles and cause vesicle glutamate release.) i.e synaptic transmission.

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15
Q

IN short what is the phototransduction mechanism of rods?

in light

A
  1. LIGHT Activated opsin interacts with
    transducin.
  2. (2) Transducin (Tα-GTP) interact with PDE.
  3. Causes hydrolysis of cGMP.
  4. Low levels of cGMP cause closure of Na+ and Ca2+ channels.
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16
Q

What happens to photoreceptors in the dark at a chemical level that results in increased glutamate release?

A

In the dark:

  1. Activation of guanylate cyclase (GC)
  2. Catalyses the formation of GTP to cGMP 3. Increase in cGMP
  3. Opening of Na+/Ca2+ cGMP gated channels
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17
Q

Describe the location of steps in phototransduction:

A

Steps 1-2 occur in the outer segments optic discs, thus changing cGMP levels.

The step 3 i.e. effects of cGMP change in concentration occurs at the membrane.

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18
Q

Describe signal amplification of photoreceptors.

A

One light activated rhodopsin protein can activate 800 transducin molecules. (RHODOPSIN IS VERY LIGHT SENSITIVE PIGMENT) i.e one photon activates it.

Two transducin molecules are required to activate one PDE

Each PDE can break down 6cGMP

A PDE molecule can break down 800cGMP per second.

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19
Q

How important is the deactivation of the phototransduction cascade?

A

Equally important to activation of signaling is switching the signal off and limiting the duration of this amplifying cascade and restoring molecules to their inactivated state.

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20
Q

What signals for the deactivation of the phototransduction cascade?

A

During the phototransduction cascade i.e light hitting the photoreceptor, Ca is extruded from the outer segment of a photoreceptor and sufficiently low Ca concentration acts as a signalling event partially responsible for the deactivation of the phototransduction cascade.

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21
Q

What exchanger is primarily involved in Ca extrusion from the photoreceptor, during the phototransduction cascade.?

A

Na/ Ca+K exchanger

i.e 4 Na + in for One Ca and One K out.

22
Q

Why is Ca so important?

A

Ca2+ plays a key role in light induced modulation of photoreceptor sensitivity i.e it is partially responsible for phototransduction deactivation.

Low Ca = deactivation!

Ca is a primary deactivation switch

23
Q

What happens to Ca concentrations when light is hitting the photoreceptor and their is phototransduction?

A

Decrease in intracellular Ca2+ due to closing of Ca2+ channels (no cGMP) and extrusion of Ca2+ by the Na+/Ca2+-K+exchanger.

24
Q

What are the three mechanisms that are activated by low Ca?

A

Three

  1. increases the activity of guanylate cyclase
  2. increases the activity of rhodopsin kinase
  3. increases the affinity of cGMP gated channels for cGMP
25
Q

What is the effect of increasing guanylate cyclase activity?

A
  1. increases the activity of guanylate cyclase (i.e. increase in cGMP)
    I. stimulates guanylate cyclase activating proteins (GCAPs).
    II. leads to activation of guanylate cyclase and synthesis of cGMP from GTP, leading to a recovery of the cGMP concentration.

cGMP activates cGMP gated cation channel i.e. Ca influxes.

26
Q

What are the effects of increasing rhodopsin kinase activity?

A
  1. increases the activity of rhodopsin kinase
    i. causes phosphorylation of Rho*
    ii. decreases affinity for binding to transducin
27
Q

How is an increase of cGMP gated ion channels for cGMP achieved?

A
  1. increases the affinity of cGMP gated channels for cGMP
    i. a decrease in intracellular Ca2+ concentration leads to the dissociation of Ca2+ from calmodulin (which binds to closed cGMP channels)
    ii. this in turn results in dissociation of calmodulin from the cGMP-gated channel, which results in an increase in affinity of the cGMP-gated channel for cGMP
28
Q

What is the first pathway that is deactivated?

A

Inactivation of rhodopsin and transducin

29
Q

How are rhodopsin and transducin deactivated and what are the effects of this?

A
  • Activated rhopdopsin is phosphorylated by rhodopsin kinase
  • Arrestin binds to (phosphrylated) rhodopsin
  • Decreases affinity for binding to transducin
  • Transducin is no longer activated
30
Q

What is the second pathway that could deactivate it?

A

Dissociation of all trans retinal from rhodopsin

31
Q

How is trans-retinal dissociated from rhodopsin and what are the effects of this?

A
  • All-trans retinal is reduced to all trans retinol in the photoreceptor cells
  • All-trans retinol is transported to the pigment epithelial cells (RPE)
  • 11 cis retinal is regenerated in three enzymatic steps
  • 11-cis retinal is then transported back to the rods.

This is the visual cycle.

32
Q

What is the visual cycle?

A

The regeneration of CIS retinal.

33
Q

Why is rhodopsin kinase normally not in function?

A

Normally rhodopsin kinase is bound to recoverin and during low Ca levels recoverin dissociates and rhodopsin is activated.

34
Q

What is retinal derrived from?

A

Vitamin A in the diet.

35
Q

Describe visual pigment composition:

A
  1. Found in optic discs of outer segment.
  2. Opsins are g-protein coupled receptors.
  3. 7 transmembrane domains
  4. retinal binding pocket.
36
Q

How does the opsin create the binding pocket?

A

By a lysine residue that is a retinal binding site in the seventh helix.

37
Q

How many opsin are there?

A 
Rods = rhodopsin
Cones = Red, Green, blue photo opsin
38
Q

What is the AA difference between green and red opsin?

A

15 AA difference which changes the sensitivity of photopigment to light.

39
Q

Describe human vision:

A

Trichromatic

40
Q

Whats it called when someone only has two cone receptors are working?

A

Dichromatic.

Sex linked, mainly males.

41
Q

What does a lack of vitamin A lead to?

A

Complete lack of vision due to lack of retinal.

42
Q

What does an opsin mutation lead to?

A

Colour blindness

43
Q

What are the types of colour blindness?

A

Dichromacy (2 colours)
Monochromacy
Anomalous trichromacy

44
Q

What is anomalous trichomromacy?

A

Normal colour vision with slight out of alignment perception of colour

45
Q

What are the types of dichromacy?

A

Protanopia
Deuteranopia
Tritanopia

46
Q

What is propantopia?

A
  1. patients do not have the red cone cells in the retina
  2. most common type of dichromacy
  3. red-green color blindness
  4. impairment in perception of very long wavelengths, such as reds.
47
Q

What is Deuteranopia?

A
  1. patients do not have green cone cells in the retina

2. is an impairment in perceiving medium wavelengths, such as greens.

48
Q

What is tritanopia?

A
  1. Patients do not have the blue cone cells in the retina
  2. A rarer form of colour blindness
  3. An inability to perceive short wavelengths, such as blues.
  4. They tend to confuse greens and blues, and yellow can appear pink.
49
Q

What causes vision difficienies?

A

Normally a change in an AA in the opsin protein leads to deficiencies

50
Q

What is retinitis pigmentosa?

A

A change in an amino acid that causes failure of rhodopsin leading to tunnel vision as peripheral rods are lost.

Sensory Neuroscience 316 (32 decks)

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