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Membrane Excitability > Ion channel diversity > Flashcards

Ion channel diversity Flashcards

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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
what drugs target voltage gated sodium channels?
local anaesthetics, anticonvulsants and antiarrhythmics
26
what's the structure of Na+ voltage gated channels?
pseudotetramer (4 TM domains)
27
do voltage gated sodium channels have rapid or slow activation?
rapid
28
what types of inactivation do voltage gated sodium channels have?
N and C
29
what do different Nav subunits have?
different biophysical properties
30
do Nav drugs tend to target 1 or many types of Nav channels?
many- hard to target just 1
31
what do drugs affecting Na 1.1 tend to treat?
epilepsy
32
what do drugs affecting Na 1.5 tend to treat?
cardiac arrythmias
33
what do drugs affecting Na 1.7,8,9 tend to treat?
Pain
34
what are the 2 types of Nav current?
Tetrotoxin sensitive | tetrotoxin resistant
35
what is a tetrotoxin sensitive current?
``` blocked by TTx in nM range rapid activation/ inactivation low activation threshold aromatic e.g. nerve/ skeletal muscle ```
36
what is a tetrotoxin resistant current?
``` blocked by tetrotoxin in micromolar range slow activation/ inactivation higher threshold polar e.g. cardiac/ sensory neurons ```
37
what has greater inward current flow, TTx sensitive or resistant?
sensitive
38
what peaks earlier TTx sensitive or resistant?
resistant
39
what do Nav TM B-subunits do (3)?
- modulate channel gating - regulate cell surface expression - function as cell adhesion molecules
40
where in Nav channel a-subunit do local anaesthetics bind?
TM 1,3 and 4
41
how many states are Nav channels in?
3
42
what are the 3 states of Nav channels?
closed- resting open- activated inactivated- closed
43
what can a mutation on Nav 1.7 cause?
Inherited Erythromelalgia
44
what does inherited erythromelalgia do?
hyper excitation of neurons
45
what are the symptoms of erythromelalgia
intense burning pain, redness, warmth
46
When do voltage-gated calcium channels open?
in response to cell depolarisation
47
in what direction does the calcium travel through voltage gated calcium channels?
inwards- influx
48
what do voltage gated calcium channels do that no other channels do?
convert electrical signals directly into biochemical work | e.g muscle contraction, gene expression etc.
49
what are the 5 types of Cav channels?
``` L type P/Q type R type N type T type ```
50
which a1- subunits do L-type have?
1. 1 1. 2 1. 3
51
which a1- subunits do Q/P-type have?
2.1
52
which a1- subunits do N-type have?
2.2
53
which a1- subunits do R-type have?
2.3
54
which a1-subunits do T-type have?
3. 1 3. 2 3. 3
55
what are L-type Cav channels used for?
skeletal/cardiac muscle contraction | secretion from glands
56
what are P/Q type channels used for?
transmitter release (CNS)
57
what are N- type channels used for?
transmitter release (PNS + CNS)
58
what are R- type channels used for?
transmitter release
59
what are T-type channels used for?
excitability
60
what else gives diversity to Cav channels (other than a-subunit)?
different B and a2delta
61
what Cav type do classical Cav antagonists target?
L-type
62
what are the 3 L-type channel blockers?
1,4- dihydropyradines phenylalkylamines benzothiazepines
63
what are 1,4 dihydropyradines?
anti- hypertensives
64
what are phenylalkylamines?
anti- arrhythmics
65
what are benzothiazepines?
anti- hypertensives and arrhythmics
66
what are the 4 main types of K+ channels?
Kv- voltage-gated Kca- calcium gated Kir -inward rectifiers K2P- twin pore domain
67
what are the 2 voltage gated potassium channels?
delayed outward rectifiers | transcient A-type current
68
what are the 3 calcium gated potassium channels?
BKca- big conductance IKca- intermediate conductance SKca- small conductance
69
what do K+ channels in excitable cells do? (function) (6)
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
what is RMP for most cells = ?
Ek (-90mV)
71
which K+ channels have 2 TMs ?
inward rectifier
72
which K+ channels have 4 TMs?
K2P
73
which K+ channels have 6TMs?
Kv, SKca, IKca
74
which K+ channels have 7TMs?
BKca
75
why is tetramer formation important?
enables channels have diversity
76
what are the 2 types of tetramer?
homomeric | heteromeric
77
what's different between homoremic and heteroremic dimers?
homo- slower time to peak, larger depolarisation, less powerful repolarisation, small current hetero- fast peak, smaller depolarisation, more powerful repolarisation, large current
78
what do delayed outward rectifiers do?
control AP duration | short neurons, long heart
79
what block outward rectifiers?
quaternary ammonium ions
80
what do transcient A-type currents do?
control AP interspike interval if current is small- short interval if current is large- long interval
81
what blocks transcient A-type currents?
dendrotoxins
82
what do Kcas do?
act to oppose calcium overload | AP repolarisation/after polarisation
83
are Kcas voltage sensitive and why?
no | they have no +ve AAs in S4
84
what activates Kcas?
IC calcium, binds to calmodulin on C-region pore opens calcium efflux
85
are inward rectifiers physiologically relevant?
no
86
what are the 2 types of Inward rectifier?
strong and weak
87
what do strong inward rectifiers do?
reduce threshold for excitation of neurons, skeletal and cardiac muscle
88
what do weak inward rectifers do?
more outward K+ current- reduces excitability
89
How does Kir affect Magnesium?
increases Mg2+, less K+ outward/efflux | stronger inward rectification

Membrane Excitability (9 decks)

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