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Membrane Excitability > Ion channel diversity > Flashcards

Ion channel diversity Flashcards

1
Q

why study ion channel diversity?

A
  • important physiological roles e.g. muscle contraction
  • can do a lot of things e.g. sense environment
  • potential therapeutic targets
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2
Q

how are APs in heart generated and deactivated?

A
  • depolarisation from influx of sodium ions
  • plateau sustained by calcium ion influx
  • opening of slow K+ channels to start repolarising
  • opening of fast K+ channels to cause fast repolarization
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3
Q

what do regulators of excitability affect?

A

size, shape, frequency and pattern of APs

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4
Q

what’s the most diverse ion channel?

A

Potassium channel

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5
Q

what does the a-subunit of the potassium channel do?

A

forms majority of the channel

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6
Q

what does the B-subunit of the potassium channel do?

A

modulates a- subunit properties

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7
Q

what are the 4 types of K+ channel?

A
  • calcium-activated
  • inward rectifying
  • 2- P domain
  • voltage- gated
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8
Q

how does diversity arise in Na+ channels?

A

different accessory units

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9
Q

what are the 3 types of voltage gated Ca2+ channels?

A
  • high voltage activated/ DHP sensitive - L type
  • high voltage activated/ DHP insensitive
  • low voltage activated- T-type
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10
Q

what 4 factors are used to differentiate ion channels?

A
  • electrophysiology
  • pharmacology
  • modulation by regulatory molecules
  • structure
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11
Q

what are the 3 ligand gated ion-channel alpha subunits?

A

Nicotinic Ach superfamily
glutamate family
P2X family

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12
Q

how many subunits does the nicotinic Ach superfamily have?

A

5- pentamer

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13
Q

how many subunits does the glutamate receptor family have?

A

4- tetramer

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14
Q

how many subunits does the P2X receptor family have?

A

3- trimer

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15
Q

what is the minimal motif requirement for a pore loop so it’s considered a channel?

A

S5- P- S6

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16
Q

what’s Kv channel made up of?

A

4 a-subunits (tetramer) forms functional channel

B-subunit- enhances cell surface expression, modulates channel gating (inactivation)

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17
Q

draw a voltage- gated potassium channel

A

https://www.google.com/search?safe=active&rlz=1C1CHBF_en-gbGB767GB767&biw=1280&bih=616&tbm=isch&sxsrf=ACYBGNSD27-HatrrtGR_uD-TMWXMefgiVA%3A1579451624151&sa=1&ei=6IQkXr76CKqEhbIP5Je-qAw&q=voltage+gated+potassium+channel+diagram&oq=voltage+gated+potassium+channel+diagram&gs_l=img.3..0.7409.8743..8926…0.0..0.194.982.8j3……0….1..gws-wiz-img…….35i39j0i7i30.lZnlnx0Yeus&ved=0ahUKEwi-jv3ni5DnAhUqQkEAHeSLD8UQ4dUDCAc&uact=5#imgrc=nN4hSmYgsdVrYM:

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18
Q

what part of the potassium channel has a voltage sensor?

A

S4

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19
Q

what is C-type gating?

A

localized inactivation

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20
Q

what is N-type gating?

A

particle inactivation

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21
Q

what speed is C-type gating?

A

slow

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22
Q

what speed is N-type gating?

A

rapid

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23
Q

what, evolutionarily are the most recent voltage-gated channels?

A

Na+ channels

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24
Q

what’s the main purpose of voltage gated sodium channels?

A

initiation and propagation of APs in excitable cells

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25
Q

what drugs target voltage gated sodium channels?

A

local anaesthetics, anticonvulsants and antiarrhythmics

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26
Q

what’s the structure of Na+ voltage gated channels?

A

pseudotetramer (4 TM domains)

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27
Q

do voltage gated sodium channels have rapid or slow activation?

A

rapid

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28
Q

what types of inactivation do voltage gated sodium channels have?

A

N and C

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29
Q

what do different Nav subunits have?

A

different biophysical properties

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30
Q

do Nav drugs tend to target 1 or many types of Nav channels?

A

many- hard to target just 1

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31
Q

what do drugs affecting Na 1.1 tend to treat?

A

epilepsy

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32
Q

what do drugs affecting Na 1.5 tend to treat?

A

cardiac arrythmias

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33
Q

what do drugs affecting Na 1.7,8,9 tend to treat?

A

Pain

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34
Q

what are the 2 types of Nav current?

A

Tetrotoxin sensitive

tetrotoxin resistant

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35
Q

what is a tetrotoxin sensitive current?

A 
blocked by TTx in nM range
rapid activation/ inactivation
low activation threshold
aromatic
e.g. nerve/ skeletal muscle
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36
Q

what is a tetrotoxin resistant current?

A 
blocked by tetrotoxin in micromolar range
slow activation/ inactivation
higher threshold
polar
e.g. cardiac/ sensory neurons
37
Q

what has greater inward current flow, TTx sensitive or resistant?

A

sensitive

38
Q

what peaks earlier TTx sensitive or resistant?

A

resistant

39
Q

what do Nav TM B-subunits do (3)?

A
  • modulate channel gating
  • regulate cell surface expression
  • function as cell adhesion molecules
40
Q

where in Nav channel a-subunit do local anaesthetics bind?

A

TM 1,3 and 4

41
Q

how many states are Nav channels in?

A

3

42
Q

what are the 3 states of Nav channels?

A

closed- resting
open- activated
inactivated- closed

43
Q

what can a mutation on Nav 1.7 cause?

A

Inherited Erythromelalgia

44
Q

what does inherited erythromelalgia do?

A

hyper excitation of neurons

45
Q

what are the symptoms of erythromelalgia

A

intense burning pain, redness, warmth

46
Q

When do voltage-gated calcium channels open?

A

in response to cell depolarisation

47
Q

in what direction does the calcium travel through voltage gated calcium channels?

A

inwards- influx

48
Q

what do voltage gated calcium channels do that no other channels do?

A

convert electrical signals directly into biochemical work

e.g muscle contraction, gene expression etc.

49
Q

what are the 5 types of Cav channels?

A 
L type
P/Q type
R type
N type
T type
50
Q

which a1- subunits do L-type have?

A
  1. 1
  2. 2
  3. 3
51
Q

which a1- subunits do Q/P-type have?

A

2.1

52
Q

which a1- subunits do N-type have?

A

2.2

53
Q

which a1- subunits do R-type have?

A

2.3

54
Q

which a1-subunits do T-type have?

A
  1. 1
  2. 2
  3. 3
55
Q

what are L-type Cav channels used for?

A

skeletal/cardiac muscle contraction

secretion from glands

56
Q

what are P/Q type channels used for?

A

transmitter release (CNS)

57
Q

what are N- type channels used for?

A

transmitter release (PNS + CNS)

58
Q

what are R- type channels used for?

A

transmitter release

59
Q

what are T-type channels used for?

A

excitability

60
Q

what else gives diversity to Cav channels (other than a-subunit)?

A

different B and a2delta

61
Q

what Cav type do classical Cav antagonists target?

A

L-type

62
Q

what are the 3 L-type channel blockers?

A

1,4- dihydropyradines
phenylalkylamines
benzothiazepines

63
Q

what are 1,4 dihydropyradines?

A

anti- hypertensives

64
Q

what are phenylalkylamines?

A

anti- arrhythmics

65
Q

what are benzothiazepines?

A

anti- hypertensives and arrhythmics

66
Q

what are the 4 main types of K+ channels?

A

Kv- voltage-gated
Kca- calcium gated
Kir -inward rectifiers
K2P- twin pore domain

67
Q

what are the 2 voltage gated potassium channels?

A

delayed outward rectifiers

transcient A-type current

68
Q

what are the 3 calcium gated potassium channels?

A

BKca- big conductance
IKca- intermediate conductance
SKca- small conductance

69
Q

what do K+ channels in excitable cells do? (function) (6)

A

set RMP
stabilise MP
regulate repolarisation
terminate intense electrical activity
set time between spike intervals during repetitive AP firing
reduce potency of excitatory inputs on cells

70
Q

what is RMP for most cells = ?

A

Ek (-90mV)

71
Q

which K+ channels have 2 TMs ?

A

inward rectifier

72
Q

which K+ channels have 4 TMs?

A

K2P

73
Q

which K+ channels have 6TMs?

A

Kv, SKca, IKca

74
Q

which K+ channels have 7TMs?

A

BKca

75
Q

why is tetramer formation important?

A

enables channels have diversity

76
Q

what are the 2 types of tetramer?

A

homomeric

heteromeric

77
Q

what’s different between homoremic and heteroremic dimers?

A

homo- slower time to peak, larger depolarisation, less powerful repolarisation, small current
hetero- fast peak, smaller depolarisation, more powerful repolarisation, large current

78
Q

what do delayed outward rectifiers do?

A

control AP duration

short neurons, long heart

79
Q

what block outward rectifiers?

A

quaternary ammonium ions

80
Q

what do transcient A-type currents do?

A

control AP interspike interval
if current is small- short interval
if current is large- long interval

81
Q

what blocks transcient A-type currents?

A

dendrotoxins

82
Q

what do Kcas do?

A

act to oppose calcium overload

AP repolarisation/after polarisation

83
Q

are Kcas voltage sensitive and why?

A

no

they have no +ve AAs in S4

84
Q

what activates Kcas?

A

IC calcium, binds to calmodulin on C-region
pore opens
calcium efflux

85
Q

are inward rectifiers physiologically relevant?

A

no

86
Q

what are the 2 types of Inward rectifier?

A

strong and weak

87
Q

what do strong inward rectifiers do?

A

reduce threshold for excitation of neurons, skeletal and cardiac muscle

88
Q

what do weak inward rectifers do?

A

more outward K+ current- reduces excitability

89
Q

How does Kir affect Magnesium?

A

increases Mg2+, less K+ outward/efflux

stronger inward rectification

Membrane Excitability (9 decks)

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