Ion Channels

Question 1

What are channelopathies?

Answer 1

Altered ion channel function that causes disease

Can be inherited or acquired (typically autoimmune-mediated

Question 2

What is the function of a patch clamp?

Answer 2

Electrically isolate a small patch of membrane that contains an ion channel

Can control voltage and measure current flow through any channels in the patch

Question 3

What is the molecular mechanism of activation of voltage-gated ion channels?

Answer 3

Movement of voltage sensor within the channel

Cluster of positively charged amino acids

Outward movement - pulls channel open

Inward movement - pulls channel closed

Question 4

How are voltage-gated ion channels inactivated (if they have this feature)?

Answer 4

Ball binds to the inner mouth of the channel, closing the pore

Will remain inactivated until voltage sensors are reset by membrane repolarization

Question 5

What differences would you see between sodium and potassium channel patch clamp experiments?

Answer 5

Sodium - open instantly, close shortly after depolarization (inactivation)

Potassium - delayed opening, will stay open as long as the membrane is depolarized ( can’t inactivate)

Question 6

What are features of voltage-gated ion channels?

Answer 6

Composed of 1 a subunit with four repeats (domains) or 4 separate a subunits

Pore-loop - forms selectivity filter (between S5-6)

Voltage sensor - positively charged amino acids (Arg, Lys)

Question 7

How many transmembrane segments does each subunit of an ion channel contain?

Answer 7

6

S4 segment is the voltage sensor

Question 8

What is the structure of the voltage-gated sodium channel?

Answer 8

4 repeats in one protein molecule

Inactivation particle between domains 3 and 4

Question 9

What is the structure of the voltage-gated K channel?

Answer 9

4 separate proteins assemble to form a complete protein

May contain an inactivation particle at the N-terminal

Question 10

What are the two functional categories of voltage-gated calcium channels?

Answer 10

High voltage activated

Low voltage activated

Question 11

What is the structure of the voltage-gated calcium channel?

Answer 11

4 domains in one protein molecule

Inactivation particle between domains 1 and 2

Question 12

What is characteristic of high voltage activated calcium channels?

Answer 12

Requires strong membrane depolarization for activation

I.e. during action potential

Question 13

What is characteristic of low voltage activated calcium channels?

Answer 13

Activates at more negative membrane potentials

Somewhere between resting potential and action potential

Question 14

How can channelopathies be expressed?

Answer 14

Can be tissue- or organ-specific depending on expression pattern