Exam 2 Koh- Retina Biochem 1 Flashcards Preview

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Flashcards in Exam 2 Koh- Retina Biochem 1 Deck (69):
1

How is vision started?

Photon absorption by the visual pigments in cone and rods

2

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

Graded, ganglion

3

What are the 2 laminar structures of the retina?

Outer retinal pigment epithelium (RPE) and inner neural retina

4

What is the origination of the laminar structures?

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

5

How thick are photoreceptors?

~200 micrometers thick

6

The photoreceptors transduce light into an _______ signal

Electrical

7

Amacrine cells are ______ interneurons

Inhibitory

8

How many amacrine cells are there?

>50 types

9

How many morphological types of ganglion cells are there?

>10-15 types

10

Mammals other than primates have what types of cones?

Only 2 types (L and S cones)

11

What is the function of photoreceptors?

Detect food source, mate, predator/prey, orientation

12

What are opsins?

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

13

How are signals transduced?

Signal via heterotrimeric G proteins

14

How many opsins are in the animal kingdom?

>1000

15

What are opsins structurally similar to?

Bacteriorhodopsin and channelopsins

16

What are the 2 major groups of opsins?

R and C

17

Rhabdomeric photoreceptors _______ to light

Depolarize

18

What motif does r-opsin use for phototransduction?

Phospholipase C

19

Ciliary vertebrate rods and cones _________ to light

Hyperpolarize

20

What motif does c-opsin use for phototransduction?

Cyclic-nucleotide

21

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

Olfaction and taste

22

Where does rod phototransduction take place?

In the cell's ciliary outer segment

23

How many rhodopsins?

1 billion rhodopsins per ROS

24

Retinitis pigmentosa is caused by mutations in the gene for ______

Rhodopsin

25

What leads to autosomal dominant retinitis pigmentosa?

Improperly folded or constitutively activated protein

26

What leads to autosomal recessive retinitis pigmentosa?

Impaired activation or reduced opsin level

27

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

Opsin mutations

28

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

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

29

When do cone photoreceptors disappear?

3 months of age

30

What light does rhodopsin absorb best?

Green, insensitive to red light

31

Rod rhodopsins are _______ and cone reodopsins are ______

Scotopsins, photopsins

32

What does rod rhodopsin consist of?

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

33

What does cone rhodopsin consist of?

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

34

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

All-trans-retinal

35

Metarhodopsin II activates _____, the G protein of phototransduction

Transducin

36

How is dark current maintained?

By cGMP-gated cation channels at night

37

How does the dark current depolarize the cell?

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

38

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

100:10:1

39

One activated rhodopsin activates how many transducins?

20

40

20 transducins activate how many PDE molecules?

20

41

Each PDE hydrolyzes cyclic GMP at what?

4000/s

42

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

10^4, several hundred sodium channels are closed

43

What happens when rods are deactivated in the dark?

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

What is rhodopsin desensitisation?

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

How many phosphorylation sites are on rhodopsin?

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

46

What happens in dephosphorylation and reactivation?

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

47

How long is the slowest step of transducin?

~200 ms in mouse

48

What is CNG?

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

49

CNG is ______ to monovalent and divalent cations

Nonselective

50

What is the affinity for cGMP?

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

Why are only 1% open of cGMP channels?

Providing a fast response to light

52

How much does Ca2+ carry?

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

53

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

Na/Ca, K exchanger

54

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

Lowering

55

Calcium decrease leads to what 3 things?

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

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

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

57

What is GRK1 modulated by?

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

What happens to Ca2+ in brighter light?

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

59

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

Increase

60

Calcium decrease leads to what 2 things?

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

61

Cone phototransduction is less _____ but faster in ______

Sensitive, kinetics

62

Does cone or rod phototransduction have faster adaptation?

Cone

63

What is the difference between rod phototransduction and cone phototransduction?

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

What proteins are located in the sac?

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

65

What proteins are located in the rim of the sac?

Peripherin, ROM-1, ABC transporter

66

What proteins are located in the membrane?

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

67

What proteins are located in the sac and cytoplasm?

Ca-dependent GCAP and calmodulin

68

What protein is located in the inner segment?

Na, K-ATPase

69

How long does isomerisation take?