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Anatomy and Biochemisty > Exam 2 Koh- Retina Biochem 1 > Flashcards

Exam 2 Koh- Retina Biochem 1 Flashcards

1
Q

How is vision started?

A

Photon absorption by the visual pigments in cone and rods

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2
Q

Retinal circuit integrates ____ analog info of photoreceptors into a digital signal at the ______ cell level

A

Graded, ganglion

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3
Q

What are the 2 laminar structures of the retina?

A

Outer retinal pigment epithelium (RPE) and inner neural retina

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4
Q

What is the origination of the laminar structures?

A

Laminar structures arise from an invagination of the embryonic optic cup that folds an ectodermal layer into apex-to-apex contact with itself

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5
Q

How thick are photoreceptors?

A

~200 micrometers thick

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6
Q

The photoreceptors transduce light into an _______ signal

A

Electrical

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7
Q

Amacrine cells are ______ interneurons

A

Inhibitory

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8
Q

How many amacrine cells are there?

A

> 50 types

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9
Q

How many morphological types of ganglion cells are there?

A

> 10-15 types

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10
Q

Mammals other than primates have what types of cones?

A

Only 2 types (L and S cones)

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11
Q

What is the function of photoreceptors?

A

Detect food source, mate, predator/prey, orientation

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12
Q

What are opsins?

A

Visual pigments, a vitamin A-based chromophore, a seven-transmembrane-helix apoprotein, prototypical G protein-coupled receptors

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13
Q

How are signals transduced?

A

Signal via heterotrimeric G proteins

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14
Q

How many opsins are in the animal kingdom?

A

> 1000

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15
Q

What are opsins structurally similar to?

A

Bacteriorhodopsin and channelopsins

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16
Q

What are the 2 major groups of opsins?

A

R and C

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17
Q

Rhabdomeric photoreceptors _______ to light

A

Depolarize

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18
Q

What motif does r-opsin use for phototransduction?

A

Phospholipase C

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19
Q

Ciliary vertebrate rods and cones _________ to light

A

Hyperpolarize

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20
Q

What motif does c-opsin use for phototransduction?

A

Cyclic-nucleotide

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21
Q

Rod phototransduction is good for understanding other sensory transduction in _____ and _____

A

Olfaction and taste

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22
Q

Where does rod phototransduction take place?

A

In the cell’s ciliary outer segment

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23
Q

How many rhodopsins?

A

1 billion rhodopsins per ROS

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24
Q

Retinitis pigmentosa is caused by mutations in the gene for ______

A

Rhodopsin

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25
Q

What leads to autosomal dominant retinitis pigmentosa?

A

Improperly folded or constitutively activated protein

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26
Q

What leads to autosomal recessive retinitis pigmentosa?

A

Impaired activation or reduced opsin level

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27
Q

Supplementation with natural or synthetic retinoids may slow photoreceptor degeneration owing to _____ _____

A

Opsin mutations

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28
Q

What happens to mice with a knockout mutation in the rod opsin gene?

A

Fail to form rod OS and have no rod electroretinographic (ERG) response, but show a cone response early in life

29
Q

When do cone photoreceptors disappear?

A

3 months of age

30
Q

What light does rhodopsin absorb best?

A

Green, insensitive to red light

31
Q

Rod rhodopsins are _______ and cone reodopsins are ______

A

Scotopsins, photopsins

32
Q

What does rod rhodopsin consist of?

A

A combination of opsin (apoprotein), 11-cis-retinal (prosthetic group), and Lys 296

33
Q

What does cone rhodopsin consist of?

A

In cone outer segments with opsin-like apoproteins and 11-cis-retinal

34
Q

Upon photon absorption, 11-cis-retinal isomerizes to ________

A

All-trans-retinal

35
Q

Metarhodopsin II activates _____, the G protein of phototransduction

A

Transducin

36
Q

How is dark current maintained?

A

By cGMP-gated cation channels at night

37
Q

How does the dark current depolarize the cell?

A

To ~30 mV to sustain synaptic-transmitter (glutamate) release, neural signals for vision

38
Q

In rods, what is the proportion of Rh:Gt: PDE?

A

100:10:1

39
Q

One activated rhodopsin activates how many transducins?

A

20

40
Q

20 transducins activate how many PDE molecules?

A

20

41
Q

Each PDE hydrolyzes cyclic GMP at what?

A

4000/s

42
Q

How many cyclic GMP hydrolyzed per activated rhodopsin? How many sodium channels are closed?

A

10^4, several hundred sodium channels are closed

43
Q

What happens when rods are deactivated in the dark?

A

For complete deactivation, each active component must shut down, Rh* (corresponding to the meta-II state of Rh, decays over a minute into an inactive state (meta-III). Long before this decay Rh* is phosphorylated by a rhodopsin kinase (G protein-coupled- receptor- kinase 1)

44
Q

What is rhodopsin desensitisation?

A

Followed rapidly by the binding of another protein, arrestin (Arr), which recognizes phosphorylated Rh* (Rh-P). Rh-P still has perhaps some activity, but the Rh*~P-Arr loses all activity

45
Q

How many phosphorylation sites are on rhodopsin?

A

6-7 C terminal phosphorylation sites, many need to be phosphorylated for the normal decay of the response

46
Q

What happens in dephosphorylation and reactivation?

A

Regenerated rhodopsin loses its bound arrestin and is dephosphorylated by phosphatase 2A

47
Q

How long is the slowest step of transducin?

A

~200 ms in mouse

48
Q

What is CNG?

A

A tetrameric complex composed of A and B subunits, each with a single cGMP-binding site

49
Q

CNG is ______ to monovalent and divalent cations

A

Nonselective

50
Q

What is the affinity for cGMP?

A

With free cGMP at ~1 micrometer in darkness, only ~1% of the channels, or ~10^4 out of an overall 10^6 channels are open

51
Q

Why are only 1% open of cGMP channels?

A

Providing a fast response to light

52
Q

How much does Ca2+ carry?

A

~15% of the dark inward current, the rest being carried largely by Na+

53
Q

In darkness, steady Ca2+ influx is balanced by an equal Ca2+ efflux via a ________

A

Na/Ca, K exchanger

54
Q

In the light, the closure of cGMP-gated channels stops the Ca2+ influx, but the Ca2+ efflux continues, thus _____ the intracellular free Ca2+

A

Lowering

55
Q

Calcium decrease leads to what 3 things?

A

GC activity increase, GC activity requires 2 quanylate cyclase activating proteins, GCAP1 and GCAP2 which are Ca2+- binding proteins that are negatively modulated by Ca2+ binding

56
Q

What happens to guanylate cyclase with high calcium in the dark?

A

~600 nM keeps GC in check, in the light, the Ca2+ decrease disinhibits the GCAPs, thus activating GC, producing negative feedback

57
Q

What is GRK1 modulated by?

A

Negatively modulated by Ca2+ through another Ca2+ binding protein: recoverin or S-modulin so that Rh* phosphorylation (arrestin binding) is moderately slow in dim light

58
Q

What happens to Ca2+ in brighter light?

A

Accelerates when Ca2+ progressively decreases in brighter light, reducing the active lifetime of Rh*

59
Q

Calcium decrease leads to _____ in affinity of CNG channels to cGMP

A

Increase

60
Q

Calcium decrease leads to what 2 things?

A

High Ca2+ reduces the affinity of cGMP for the channel, so some channels initially closed by light reopen as Ca2+ falls

61
Q

Cone phototransduction is less _____ but faster in ______

A

Sensitive, kinetics

62
Q

Does cone or rod phototransduction have faster adaptation?

A

Cone

63
Q

What is the difference between rod phototransduction and cone phototransduction?

A

Gt is less efficiently activated by Rh, the effective lifetime of cone R is also much shorter, GRK7 has a much higher specific activity and more abundant than GRK1, GTPase activity of Gtalpha- GTP and hence its deactivation are more rapid in cones, Ca2+ feedback is also faster in cones

64
Q

What proteins are located in the sac?

A

Rhodopsin, transducin, PDE, rhodopsin kinase, arrestin, recoverin, guanylate cyclase, dehydrogenase

65
Q

What proteins are located in the rim of the sac?

A

Peripherin, ROM-1, ABC transporter

66
Q

What proteins are located in the membrane?

A

cGMP gated channel, glucose transporter, Na/K, Ca exchanger

67
Q

What proteins are located in the sac and cytoplasm?

A

Ca-dependent GCAP and calmodulin

68
Q

What protein is located in the inner segment?

A

Na, K-ATPase

69
Q

How long does isomerisation take?

A

Anatomy and Biochemisty (15 decks)

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