MT - Ion Channels Flashcards

1
Q

The thalamocortical neuron has similar channel properties to the ______ in the ______.

A

Sa node (funny current) channels in the heart.

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2
Q

How many proteins are required to make a voltage-gated K+ channel? How many transmembrane domains do each of these proteins have?

A

Need 4 proteins, each with 6 transmembrane domains.

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3
Q

How many proteins are required to make an inward rectifier K+ channel? How many transmembrane domains do each of these proteins have?

A

Need 4 proteins, each with 2 transmembrane domains and a pore loop..

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4
Q

How many proteins are required to make a two pore K+ channel? How many transmembrane domains do each of these proteins have?

A

Need 2 proteins, each of which have 4 transmembrane domains and 2 pore loops.

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5
Q

Imagine a single protein from a K+ channel. Which transmembrane domain contains the voltage-sensor? What amino acids are common here.

A

S4. Contains many arginine residues.

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6
Q

Where in the body are GIRK channels found? What kind of channel are they?

A

They are inward rectifier K+ channels found in the heart.

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7
Q

What differentiates the membrane potential trace of a voltage-gated K+ channel from that of an inward rectifier K+ channel?

A

Vgated: rapid peak with relatively fast repolarization.
Rectifier: Slower activation but little/no repolarization.

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8
Q

What are the BK, IK, and SK channels (think about a specific ion/ions)?

A

Big (BK), intermediate (IK, and small (SK) conductance Ca2+-activated K+ channel

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9
Q

What toxin is capable of blocking big conductance Ca2+-activated K+ channels (BKs)(KCa1.x)?

A

Scorpion toxins charybdotoxin and iberiotoxin.

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10
Q

What channels are Scorpion toxins charybdotoxin and iberiotoxin known to block?

A

Big conductance Ca2+-activated K+ channels (BKs).

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11
Q

What toxin is capable of blocking small conductance Ca2+-activated K+ channels (SKs)(KCa2.x)?

A

Apamin, a component of bee venom.

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12
Q

What toxin is capable of blocking intermediate conductance Ca2+-activated K+ channels (IKs)(KCa3.1)?

A

Scorpion charybdotoxin.

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13
Q

How many transmembrane domains do big conductance Ca2+-activated K+ channels (BKs) have? Any pore loops?

A

7 (one extra!). 1 pore loop.

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14
Q

How many transmembrane domains do small/intermediate conductance Ca2+-activated K+ channels (SKs/IKs) have?

A
  1. 1 pore loop.
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15
Q

Why do bee stings hurt?

A

Bee venom contains aptamin. This blocks the Ca2+-activated K+ channels from repolarizing the membranes, causing perpetuated firing.

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16
Q

What is the K+ channel “signature sequence”? Where is it in the channel?

A

TVGYG. It is contained in the selectivity filter.

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17
Q

Each subunit in a K+ channel has _ transmembrane ______, a _______, a pore helix, and a _______ ________.

A

… 2 transmembrane α-helices, a turret, a pore helix, and a selectivity filter.

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18
Q

Are both openings of the K+ channel the same charge? What charge(s) are they?

A

They are both negatively charged.

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19
Q

How many possible locations could we find a K+ ion in the K+ channel selectivity filter?

A

There are 4 potential locations.

20
Q

How many K+ ions are likely passing through the K+ channel filter selectivity at a given time? What else is in the channel during this time?

A

Only 2. 2 water molecules occupy the other 2 potential locations.

21
Q

What feature of the K+ channel pore helices helps to stabilize the hydrated K+ through the channel?

A

They all point with their carboxyl ends towards the central cavity. This partial negative charge interacts with the cation.

22
Q

How do the subunits move to open/close the K+ channel? When does this happen?

A

With membrane depolarization, the S4-S5 linker moves upward (closed) or downward (open), twisting the channel proteins closed/open.

23
Q

How are the structures of the Na+ and Ca2+ channels similar to the K+ channels? How are they different?

A

They have the same general structure with 6 transmembrane domains, but instead of having these on 4 different proteins they just have one long protein with 4 of these “K+-like” 6 domain motifs. (24 TM domains total).

24
Q

What toxin is known to block Na+ channels? What else?

A

Tetrodotoxin from pufferfish. Also lidocaine (local anesthetic) as well as phenytoin and carbamazapine (anticonvulsants).

25
Q

Nav1.1-Nav1.4, Nav1.6-Nav1.7 are ____ to tetrodotoxin (TTX).

A

Highly sensitive (<30 nM).

26
Q

Nav1.5 are ____ to tetrodotoxin (TTX).

A

Intermediately sensitive (2 microM).

27
Q

Nav1.8 and Nav1.9 are ____ to tetrodotoxin (TTX).

A

Insensitive (unaffected).

28
Q

How many Na+ ions will be in the Na+ channel selectivity filter at any time?

A

2-3.

29
Q

How many pore helices per domain in a K+ channel? What about an Na+ channel? Also give the total # per channel.

A

K+: 1 (so 4 per channel)

Na+: 2 (so 8 per channel)

30
Q

Why are K+ channels not permeable to Na+ ions, even though Na+ is slightly smaller?

A

K+ is dehydrated as it passes through the channel, but dehydration of Na+ is unfavourable. Hydrated Na+ is too large to fit.

31
Q

Are AAs in the K+ channel charged? What about in the Na+ channel? Why?

A

In Na+ channels, the -vely charged AAs are needed to strip the hydration shell off the Na+ ions. No charged AAs in K+ channels.

32
Q

What differentiates an α-helix from a 3₁₀ helix?

A

α-helix: 3.6 residues/turn

3₁₀: 3 residues/turn (they line up!)

33
Q

How are 3₁₀ helices leveraged in the Na+ channel?

A

Contain -vely charged AAs which stabilize the Na+ ion as it passes through the membrane.

34
Q

What differentiates the inactivation of K+ channels and Na+ channels?

A

K+: just close normally

Na+: have an inactivation gate which blocks the pore on the cytosolic side.

35
Q

Where is the inactivation gate of an Na+ channel located on a diagram of topographic structure?

A

On the cytoplasmic loop between domains 3 an 4.

36
Q

How can we determine the reversal/equilibrium potential for an Na+ current from a graph?

A

It’s just the x-intercept of the graph.

37
Q

What are the 4/5 types of voltage-gated Ca2+ channels?

A
  1. L
  2. P/Q
  3. N
  4. R
  5. T
38
Q

What toxin inhibits the N-type voltage-gated Ca2+ channels?

A

ω-conotoxin from that crazy underwater snail.

39
Q

What toxin inhibits the P-type voltage-gated Ca2+ channels?

A

ω-agatoxin from the funnel web spider.

40
Q

What toxins inhibit the L-type voltage-gated Ca2+ channels?

A

Dihydropiridines (ex: nimodipine and nifedipine)

41
Q

What is the general role of HCN channels?

A

To act as pacemakers (produce funny currents).

42
Q

How are HCN channels activated?

A

By hyperpolarization.

43
Q

What ions do HCN channels flux?

A

Na+ and K+ (mostly).

44
Q

What must bind to the C-terminal region of an HCN channel?

A

cAMP.

45
Q

Which types of Ca2+ channels are involved in producing the funny current in the SA node of the heart?

A

T-type and L-type Ca2+ channels.