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BMS2002 Cell Biology and Disease > Strand 1 - Membrane transport and ion channels > Flashcards

Strand 1 - Membrane transport and ion channels Flashcards

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1
Q

what do ion channels regulate?

A

membrane potential

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2
Q

what is the membrane potential the difference between?

A

electrical potential/voltage inside and outside of the cell

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3
Q

where does this difference in charge exist in the cell?

A

plasma membrane

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4
Q

what happens to the potential when K+ efflux out of the cell?

A

it gets more negative (as K are positive)

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5
Q

what happens to the potential when Cl- efflux out of the cell?

A

gets more positive

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6
Q

what is a technique used to measure changes in membrane potential?

A

patch clamp electrophysiology

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7
Q

what is the resting membrane potential of most cells?

A

-50 mV

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8
Q

In the Nernst equation what do the letters stand for?

R
T
z
F

A

R = gas constant
T = temp
z = valence of ion (if it’s + or 2+)
F = faraday constant

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9
Q

What is the human homologue of the “shaker” K+ channel?

A

KCNA3

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10
Q

What is gating involving in ion channels?

A

opening/closing in response to stimuli

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11
Q

which animal toxin (puffer fish) is an Na+ blocker?

A

tetradotoxin

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12
Q

which animal toxin (scorpion) is a K+ blocker?

A

charybdotoxin

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13
Q

which animal toxin (funnel web spider) is a Ca2+ blocker?

A

w - agatoxin

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14
Q

what are the polar hydrophillic regions for in ion channels?

A

ligand binding

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15
Q

which two techniques are used to investigate ion channel structure?

A

electron microscopy

x ray crystallography

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16
Q

why are ion channels hard to crystallise?

A

they are large, dyanmic proteins

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17
Q

between which two domains of the 6 transmembrane proteins on an alpha subunit does the pore form?

A

domains 5 and 6

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18
Q

how many domains does a typical K+ channel have?

A

4

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19
Q

what do amino acids occlude at the N terminus of the channel?

what does this cause?

A

the intracellular side of the channel pore

channel inactivation

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20
Q

what happens to the selectivity filter during C type inactivation?

A

conformational change

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21
Q

where does C type inactivation occur?

A

extracellular entrance to channel

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22
Q

what is the difference in transmission in chemical vs electrical synapses?

A

chemical - intermittent transmission

electrical - continuous transmission

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23
Q

a sudden reverse of membrane polarity is also known as an …..

A

action potential

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24
Q

which channels are open during depolarisation?

A

Na+ and K+

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25
Q

Which channels open more slowly in depolarisation?

A

K+

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26
Q

at what voltage is depolarisation?

A

-55mV

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27
Q

which channels are open and then close slowly in repolarisation?

A

K+

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28
Q

which channels are closed in repolarisation?

A

Na+

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29
Q

the voltage gated Na+ channel has 3 states what are they?

A

Open, closed and inactive

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30
Q

are both the Na and K + channels open or closed in hyperpolarisation?

A

closed

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31
Q

what is open during hyperpolarisation?

A

Na/K pump

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32
Q

which channels recover during the relative refractory period?

A

Na+

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33
Q

which channels are still open during the relative refractory period?

A

K+

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34
Q

what does tetradotoxin prevent being fired? in what type of neuron?

A

action potentials in motor neurons

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35
Q

what stage of an action potential does tetradotoxin affect?

A

depolarisation

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36
Q

if a cell cannot repolarise what is the likely cause of this?

A

voltage gated Na+ channels cannot close

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37
Q

what are nociceptors?

where in nociceptors, are noxious stimuli transduced to electrical activity?

A

sensory receptors for painful stimuli

at the peripheral terminals

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38
Q

where are signals from nociceptors sent to for processing, what must they go through first however?

A

to the CNS via dorsal root ganglions

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39
Q

what are the four stage of nociception?

A

transduction
transmission
modulation
perception

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40
Q

what is transmission achieved by?

A

primary afferent nociceptors

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41
Q

what is modulation achieved by?

A

interneurons

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42
Q

what type of stimuli do AB fibers detect?

A

non noxious mechanical (light touch)

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43
Q

what type of stimuli do Ad fibers detect?

A

noxious thermal and mechanical

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44
Q

what type of stimuli do C fibers detect?

A

noxious mechanical, thermal and chemical

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45
Q

which fibers are myelinated?

which is more thickly myelinated?

A

AB, Ad

AB more myelinated

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46
Q

which fiber is lightly myelinated?

A

Ad

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47
Q

which fiber is not myelinated?

A

C

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48
Q

after primary afferent neurons, where does the signal travel to ?

A

dorsal root ganglions

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49
Q

after dorsal root ganglions where do signals travel to?

A

the CNS/spinal cord

50
Q

which fiber type has the largest diameter?

A

AB

51
Q

what is the thermal threshold of type 1 Ad fibers?

A

53 degrees C

52
Q

what is the thermal threshold of type 2 Ad fibers?

A

43 degrees C

53
Q

which fiber type has no thermal threshold?

A

AB

54
Q

What do TRPA1, TRPM8, TRPC5 detect?

A

noxious cold

55
Q

What do TRPV4, TRPV3, TRPV2, TRPV1 detect?

A

noxious heat

56
Q

what do chillies contain which binds TRPV1 and gives a sensation of heat?

A

capsaicin

57
Q

what does menthol bind to to give a cold sensation?

A

TRPM8

58
Q

Which two TRPs does cannabidiol bind to?

A

TRPA1, TRPV1

59
Q

where in the body does somatic pain come from?

A

muscles, joints

60
Q

is somatic pain localised?

A

yes

61
Q

which 2 types of fibers are responsible for somatic pain?

A

Ad and C

62
Q

give 3 examples of places where visceral pain can originate from

A

uterus, kidneys, intestine, liver etc

63
Q

which 2 types of fibers are responsible for visceral pain?

A

Ad and C

64
Q

is visceral pain responsive to pain relief?

A

no

65
Q

what are exmples of inflammatory mediators produced from APCs and binds to nociceptors?

A

TNF alpha, histamine, IL, prostaglandins

66
Q

what type of pain is carpal tunnel syndrome?

A

neuropathic

67
Q

which stage of nociception is lost due to neuropathic pain?

A

the first stage - transduction

68
Q

which types of drugs are commonly used to treat neuropathic pain?

A

opiods, antidepressants

69
Q

which voltage gated ion channel does lidocaine block?

A

Na+

70
Q

what does lidocaine bind to reversibly?

A

inner pore of Na+ channel

71
Q

is lidocaine non selective or selective?

A

non selective

72
Q

does lidocaine have greater affinity for resting or inactive channels?

A

inactivated

73
Q

which voltage gated Na+ channel subtype is found on the gene SCN9A

A

1.7

74
Q

what does a channelopathy arise from?

A

ion channel dysfunction

75
Q

give an example of a genetic channelopathy?

A

cystic fibrosis

76
Q

is cystic fibrosis monogenic or polygenic?

A

monogenic

77
Q

what does the dysfunction of Cl- ion influx lead to in the airways in a person with CF?

A

mucus accumulation

78
Q

Class 1 CFTR mutation is:

A

failure to create a CFTR from mRNA

79
Q

Class 2 CFTR mutation is:

A

failure in protein trafficking

80
Q

Class 3 CFTR mutation is:

A

mutation in ion gating

81
Q

Class 4 CFTR mutation is:

A

faulty CFTR channel

82
Q

Class 5 CFTR mutation is:

A

mutation of amount of protein

83
Q

Class 6 CFTR mutation is:

A

failure to anchor to the plasma membrane

84
Q

autosomal recessive conditions involve both parents to be……

A

carriers

85
Q

what percentage of children are affected if 2 parents are carriers for an autosomal recessive disease?

A

25%

86
Q

if one parent is affected by the disease and the other is not, then the condition is ……… ……….

A

autosomal dominant

87
Q

is autosomal recessive associated with LOF or GOF?

A

Loss of Function

88
Q

what % of children will be affected if one of their parents is affected by a autosomal dominant disease?

A

50%

89
Q

which gene is highly expressed by sensory neurons of the DRG?

A

SCN9A

90
Q

which subunit is associated with the voltage gated Na+ channel subtypes?

A

alpha

91
Q

which phase of an action potential does NaV 1.7 contribute to ?

A

rising phase

92
Q

what does Nav 1.7 do subthreshold stimuli?

A

amplifies them

93
Q

Inherited Erythromelalgia (IEM) is an autosomal ……… condition

A

autosomal dominant

94
Q

IEM involves burning episodes in which areas of the body?

A

hands and feet

95
Q

what are attacks triggered by in IEM?

A

exercise and / or heat

96
Q

when does onset of IEM begin?

A

childhood

97
Q

which domain does the first mutation (L858H) in IEM occur?

A

second domain

98
Q

what do mutations in IEM do to the activation threshold? (long process)

A
  • lower it, channels open more easily in response to smaller depolarizations
  • make the channel activate at more hyperpolarized potentials

= prolonged channel opening times

99
Q

Paroxysmal extreme pain disorder (PEPD) is an …………….. disorder

A

autosomal dominant

100
Q

PEPD causes pain in which 3 areas?

A

rectal, ocular and mandibular

101
Q

what are PEPD attacks triggered by?

A

chewing and or heat

102
Q

when does PEPD onset occur?

A

childhood

103
Q

what happens to the threshold for channel activation in PEPD?

A

it is lowered

104
Q

In PEPD the channel stays open for …… than usual?

A

longer

105
Q

CIP is an autosomal ….. condition?

A

recessive

106
Q

in IEM the L858H mutation means what?

A

leucine is converted to histidine

107
Q

CIP, IEM, PEPD all have mutations in which gene ?

A

SCN9A

108
Q

mutations for CIP occur within which two domains?

A

1 and 2

109
Q

mutations in CIP cause the protein to become…….

A

truncated

110
Q

Which ions usually contribute most significantly to the resting membrane potential?

A

Potassium

111
Q

The ____________ pump is an electrogenic ion channel with a stoichiometry of 3:2

A

sodium/potassium

112
Q

When looking at protein sequence of an ion channel alpha subunit, you would predict that a long stretch of hydrophobic amino acids would be most likely correspond to which domain?

A

transmembrane

113
Q

regions involved in voltage gating have mainly hydro…… amino acids

A

hydrophillic

114
Q

alpha subunits of ion channels have 4 homologue domains each with….. transmembrane regions

A

6

115
Q

how many beta and alpha subunits are in the shaker ion channel?

A

2 beta, 4 alpha

116
Q

what is continuous transmission in neurons achieved by?

A

hemichannels

117
Q

charybdotoxin affects which phase of an AP?

A

repolarisation

118
Q

After an action potential fires, which **ion channel pump **is primarily responsible for returning the cell to resting membrane potential?

A

sodium-potassium pump

119
Q

what does lidocaine prevent the DRG axon from propagating?

A

an action potential

120
Q

Genetic variation in the SCN9A gene is thought to influence pain perception in humans commonly through …… in ……. regions

A

SNPs in coding regions

BMS2002 Cell Biology and Disease (6 decks)

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