Ion Channels: Module 1.9 - 1.13 Flashcards

1
Q

What are the Ion channels grouped into?

A

Superfamilies

Superfamilies thought to evolved from common ancestral gene by gene duplication and divergence.

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2
Q

The transition of a ____ between different conformational states is called ____.

A

The transition of a channel between different conformation states is called gating.

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2
Q

What are the different subunit arragments to form an ion channel?

A
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3
Q

What are the 3 different physical models for the opening and closing of Ion channels?

A
  • Localized conformational change
  • Generalizer structural change
  • Blocking particle
Nicotinic Receptors - Generalized Change Na+ Channels - Blocking Particle
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4
Q

What are 3 major transduction mechanism that control channel opening in neurons?

A
  • Ligand Binding (Extracellular, Intracellular, Phosphorylation)
  • Voltage Changes
  • Mechanical Force(Stretch activated)
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5
Q

How are Inactivation of voltage gated Na and K channels thought to occur?

A

Through a conformational change.

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6
Q

How are voltage gated Ca channels thought to inactivate.

A

Requires influx of Ca to bind to Calmodulin which then binds to the Ion Channel to inactivate.

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7
Q

How many domains does a Alpha sub-unit of a voltage fated K+ channel have?

A

6

S1 - S6

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8
Q

What is the pore forming region of the Alpha subunit of a voltage gated K+ channel?

A

P Domain

Lower Hydropathy Index - Less Hydrophobic

Responsible for Ion Selectivity
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9
Q

What segment acts as the voltage sensor in the Alpha Subunit of voltage gated K+ channel?

A

S4 Segment

Has large number of positively charged lysine and arginine residues.

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10
Q

How many Alpha subunits are required to make a completed Voltage gated K+ ion channel.

A

4

Always need 4 P regions
Can have accessory subunits(Beta etc)

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11
Q

How many Alpha sub units are required to form a complete Na or Ca Channel?

A

1

Single polypeptide with 4 homologous repeats.

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12
Q

Why does Na+ behave as if it is larger than K+?

A

Has more layers of hydration.

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13
Q

Do smaller or larger ions attract more water?

A

Smaller

More localized charge and stronger electric field.

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14
Q

Who was the first to propose that channels have selectivity filters?

A

Bertil Hille (1970 - 1973)

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15
Q

What is the selectivity filter?

A

Narrow region of channel where ions must shed layers of hydration if its energetically favorable to form electrostatic bonds with selectivity filter in order to traverse the channel.

16
Q

Describe the process of the K+ selectivity filter.

A

K+ ions enter the Inner Chamber from the Cytoplasmic side. The ion that was previously in the inner chamber jumps to site 4 moving ions in the outer configuration (site 1 and 3) expelling 1 ion. Now there is 2 ions at site 2 and 4(inner configuration)which jump to the outer configuration.

Higher Dehydration cost than Na
17
Q

Describe the process of the Na+ Selectivity filter.

A

Glutamate and Aspartate Residues(with - charged carboxylic acid groups) attract cations and repel anions at the mouth of the pore. Pore is lined with oxygen and Carboxylic Acid allow Na to temporarily shed layers of hydration and form interactions with them.

Na Channels can allow sever water molecules

18
Q

Why dont K ions cross through the selectivity filter of a Na channel?

A

Size of Partially hydrated K ion is too large for Na selectivity filter.

19
Q

Why dont Na+ ions cross the selectivity filter for K.

A

Electrostatic interactions between Na and K selectivity filter are energetically unfavorable.

Needs to be more favorable than losing hydration layers.

20
Q

What is the distinctive pattern found in the S4 domain?

A

Every third position contains an arginine or lysine residue.

Present in all voltage gated channels - and absent in voltage gated

21
Q

What links the Voltage sensing domain(S1-S4) with the pore domain(S5-P-S6)?

A

Short Coupling Helix (S4-S5)

22
Q

How does a voltage gated K channel close?

A

Membrane repolarization causes the downward movement of the S4-S5 helix, applying force to the S6 inner helix causes it to bend and close the gate of the channel.

23
Q

What type of chart can tell you evolutionary relationship between channels?

A

Dendogram

24
Q

What type of channels are Nav closely related to?

A

Cav

25
Q

How many members are there in the Nav channel family?

A

9(Nav 1.1 - 1.9)

There is a Nax channel however it is not voltage sensitive

Each neuron has all of these, but variable composition differentiates neurons.

26
Q

What channel is the Nax channel most closely related to?

A

Nav 1.7

27
Q

Nav channels can be classified by there sensitivities to TTX

Describe the 2 classes and which Nav channels fall under those classes?

A

TTX Sensitive - Nav 1.1, 1.2, 1.3, 1.4, 1.5, 1.7 - Can be blocked by micromolar concentration of TTX

TTX Resistant - Nav 1.5, 1.8, 1.9 - Can be blocked with Micromolar concentrations of TTX

28
Q

What are the Nav channels that contribute to the AP and what are their role?

A

Nav 1.3 expressed greater in hypersensitive areas.

29
Q

What current precedes current generated from the influx of sodium?

A

Gating current - Brief ouward movement of positive charges within the Nav channels.

30
Q

How does Nav channel gating work?

A

Initial depol causes S4 unites to repel upwards activating the channel. When there is enough depol, all S4 sub units will push upwards initiating the inactivation gate.

31
Q

What is pronase?

A

Pronase is a mixture of several nonspecific endo and exoproteases that digest proteins down to single amino acids. Pronase digests the Nav inactivation gate.

32
Q

How does extracellular calcium concentration affect the open probability of Nav channels?

A

More extracellular calcium will repel S4 movement upwards that cause activation of the channel. You need more depolarization to push S4 up in the presence of more Calcium.

33
Q

What are the 2 types of mutations?

A

Gain of function mutation: mutation that confers new or enhanced activity on a protein.

Loss of function mutation: more common, result in loss/reduced protein function.

34
Q
A
35
Q
A