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Cell Membranes > Lecture 12: Ion Channels > Flashcards

Lecture 12: Ion Channels Flashcards

1
Q

How fast do ions get transported through channels?

A

Fast 10^8

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2
Q

What generates differences in ion concentration across the PM and using what?

A

pumps and ATP.

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3
Q

What do passive channels do in response to Na/K channels?

A

Leak some K out the cell. Na/K channel does 3 Na out, 2K in.

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4
Q

Which ions move inwards and which outwards?

A

Na, Ca, cl inwards, K outwards.

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5
Q

How many putative ion channels are there?

A

over 400

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6
Q

What are the two types of ion channels in humans?

A

voltage and ligand gated

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7
Q

What do they play key roles in?

A

The transmission of noxious stimuli from the env to the brain.

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8
Q

What is the most diverse channel family?

A

The K channel

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9
Q

What can K channels respond to?

A

Voltage, ligand or heat

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10
Q

What are the four types of K channel?

A
  1. 2 TM domains with a P-loop between
  2. 6 TM domains. S4 has a role in voltage sensing in the voltage gated K channels and lots of Arg here (charged) for action potential transmission, and S1-4 is the gating mechanism
  3. 8TM and 2 P loops
  4. 4TM and 2 P loops. 2 repeats of type 1. Are leakage channels and targets of anaesthetics.
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11
Q

What is the basic structure of a K+ channel?

A

4 identical subunits

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12
Q

What does each subunit of the Kcsa (normal) channel have?

A

2 TM domains s5,6 and a p (pore) segment

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13
Q

What forms the selectivity filter and how long is it?

A

The 4 P segments from each subunit which partly penetrate the lipid bilayer from the exoplasmic surface. 12 A long.

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14
Q

What happens in the bacterial K+ channel, compare to AQP?

A

8TM domains form an inverted cone generating a water filled cavity called the vestibule which allows ions to go fairly deep before selectivity like AQP. The ions are channeled 1 at a time like AQP.

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15
Q

How was crystallisation of Kcsa achieved?

A

Removed flexible c terminal by cleavage with chymotrypsin to 3.2 A and then improved to 2A by binding with monoclonal Fab fragment.

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16
Q

Explain the structure of the K + pore

A

Formed by P loops forming a vestibule in the middle of the membrane. The K+ remain hydrated and 4 CO groups are spaced at exact distances to act as transient binding sites for the dehydrated K+.

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17
Q

Why can’t Na+ pass through?

A

the carbonyl oxygens are two far away for the smaller Na+ to compensate for the energy expense associated with dehydration required for entry. Not good interactions

18
Q

How many ions are located in the selectivity filter and where is the other one and why?

A

2 and the third is in the centre of the vestibule where is is stabilised by the more negatively charged end of the pore helix.

19
Q

What enhances the cation recruitment?

A

More negatively charged AAs at the cytosolic side

20
Q

What is the selectivity of K+ over Na+?

A

10,000:1

21
Q

Why can’t ca2+ pass through?

A

Bind water more tightly so harder to dehydrate

22
Q

Describe the bacterial Na/K channel and how it differs to Kcsa

A

is non-selective and allows Na and Ca to pass through. Similar structure to Kcsa but lacks the S1 and S2 and has a wider vestibule. The Na remains hydrated in the selectivity filter which differs to K+ in Kcsa.

23
Q

What is highly conserved across species? What do mutations here cause?

A

The P-segment. Inability to channel K+. Replacing the AA sequence of P-segment of bacterial K+channel with mammalian makes no difference.

24
Q

What is the knock-on mechanism?

A

The filter is packed with K+ ions in direct contact and repulsion between them is key to efficient movement

25
Q

What causes a conformational change?

A

Glycine gating hinge in the inner helix of K+ channels which allows opening and closing of the pore.

26
Q

Compare AQPs and K+ channels

A

AQPs have hydrophilic side chains, CO groups, NPA motifs, electrostatic repulsion by R195 and H180 and size restriction at core of pore. K+ channels have CO backbone, P-loop and selectivity filter.

27
Q

How many TM segments do voltage gated channels have and how may P loops? Which parts line the pore? Wich parts form the voltage sensor?

A

6, S1-6 and 1. S5 and 6. S1-4.

28
Q

Voltage differences across the membrane cause what in voltage gated channels?

A

Conformational changes

29
Q

How does the channel open in the voltage gated Kvap tetramer?

A

Upward movement of the S3-4 paddle pulls on S4-5 linker helix to trigger opening of the channel formed by S5,6.

30
Q

What senses the membrane potential?

A

Arg R1-R4 on S4 in the voltage sensor.

31
Q

What are the three types of neurotransmission ion channels?

A

Transducer ion channels, conduction ion channels, neurotransmission channels

32
Q

What do transducer ion channels do?

A

Detect noxious stimuli and convert to an electrical current eg TRPV1

33
Q

What do conduction ion channels do?

A

communicate noxious signals by way of action potentials over long distances eg Nav1.7

34
Q

What do neurotransmission channels do?

A

Release and modulate neurotransmitters in to the synapse to signal to the post synaptic spinal neurons

35
Q

What activates TRPV1 channels?

A

Membrane current activated in a heat sensitive and insensitive neurone in response to a temperature change from 25 to 9 degrees c. Capsaicin, the main ingredient in chilli peppers elicits a sensation of burning by activating sensory neurones.

36
Q

What is Nav1.7 essential in?

A

human pain

37
Q

What is channelopathy associated with?

A

insensitivity to pain and loss of function of the voltage gated Na channel gene SCN9A.

38
Q

What mutations can you get in Nav1.7 family?

A

Of the form AX eg I167X. in family 2.

39
Q

What is not happening with mutated type in patc clamping experiments?

A

Action potentials

40
Q

What happens if you have gain of function mutations of Nav1.7? What is it caused by?

A

Extreme pain disorders. A point mutation

41
Q

What diseases are ion channels associated with?

A

Cardiac disorders, neurological disease, kidney failure, pain perception

42
Q

How many channelopathies have been identified?

A

Over 60

Cell Membranes (17 decks)

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