Ion Channels

Question 1

NaV ion channel structure

Answer 1

4 identical membrane spanning repeats with 6 alpha helices (S1-6) strung together
S4 is voltage sensor with arg/lys at every 3rd position
S5 and S6 connected by P loop which is selective conducting pathway

Question 2

Kv ion channel strucutre

Answer 2

4 separate membrane spanning repeats with 6 alpha helices (S1-S6)
S4 is voltage sensor with arg/lys at every 3rd position
S5 and S6 have connecting P loops which forms selective conducting pathway

Question 3

Factors of channel selectivity (3)

Answer 3

Size of ion, Charge of ion, Hydration

Channel specificity varies among channels

Question 4

Hydration

Answer 4

Ions stabilized by water molecules which must be removed to pass through pore. Loss of stability replaced with weak interactions with AAs within pore. These interactions are also selective.

Question 5

Activation Gates

Answer 5

Both K and Na have activation gates. Positive residues on activation gate keeps it closed when cytosol is negative. When depolarization occurs, positive cytosol repels activation gate and it swings open. It closes when cytosol is negative again (deactivation)

Question 6

Inactivation Gates

Answer 6

Na channels have inactivation gate formed by loop between III and IV linker fold which binds to part of channel that is blocked by closed activation gate so it remains open at rest. When activation gate opens, inactivation gate is able to close by binding its target.

Question 7

Sidedness

Answer 7

Location of selectivity filter near extracellular side and location of activation gates near intracellular side cause agents to bind with specific sidedness

ex. Tetrodotoxin is unable to cross membrane so it interacts extracellularly with Na channels and binds outside of selectivity fileter
Lidocaine can cross membrane and binds from cytoplasmic side when activation and inactivation gates are open

Question 8

State-dependence

Answer 8

Because lidocaine binding requires Na inactivation and activation gates to be open to reach its binding target, this is called state-dependence.

Question 9

Other types of channels? (4)

Answer 9

Pentamer Ligand-gated

Tetrameric Ligand-Gated

CLC Chloride Channels

Aquaporins

Question 10

Pentamer Ligand-gated

Answer 10

GABA-R, GlyR, nAChR

Heteropentamers, 4 membrane spanning alpha helices per subunit
M2 is conducting pathway

Question 11

NMDA Rs

Answer 11

2 units bind glutamate, 2 units bind glycine

Inhibited at negative membrane potential because magnesium blocks

Question 12

Tetrameric Ligand gated

Answer 12

4 subunits w/ 3 alpha helices each

Question 13

CLC Chloride channels

Answer 13

Dimer, independent gates in each, one shared gate too.

Question 14

Aquaporin

Answer 14

Tetramer, each unit with water pore.