Ion Channels

Question 1

What stimuli can control the gating of ion channels?

Answer 1

temperature
mechanical deformation
membrane potential
extracellular chemicals
intracellular 2nd messengers

some respond to more than 1

Question 2

What pathologies are caused by ion channel mutations?

Answer 2

severe chronic pain
lack of pain
periodic paralysis
familial hemiplegic migrane
arrhythmias
DM
immunodeficiency
congenticla catracts 
nephrogenic diabetes insipidus

Question 3

What are some natural products that target ion channels?

Answer 3

conotoxin -> Ca2+ channels - cone snails
alpha-bunarotoxin -> nicotinicAChRs - sea krait
Ryanodine -> RyRs - ryania speciosa plant
tetrodotoxin -> Na+ channels - fugu

Question 4

What are the common patterns in ion channel formation?

Answer 4

4 membrane spanning domains

• each with 6 alpha-helices
• S4 helices have + residues at every 3rd position -> voltage sensors
• S5, S6 ^ p-loop form ion conductiong pathway

Question 5

How are K channels different from Na & Ca channels?

Answer 5

in K each domain is a separate polypeptide

in Na & Ca -> 4 domains from a single polypeptide

Question 6

What are ionotropic receptors?

Answer 6

neurotransmitter receptors directly coupled to ion channels (receptor and channel are part of the same protein)

Question 7

What are metabotropic receptors?

Answer 7

neurotransmitters that activate a second messenger pathway and can affect physically separate ion channels

Question 8

What are pentameric ligand gated channels?

Answer 8

heteropentamer -> 4 transmembrane alpha helicies (M1-M4)
M2 assembles around central ion-conducting pathway
- selective for permeation of Cl
OR
- allow both Na and K with preference for Na

Question 9

What are ionotropic glutimate receptors?

Answer 9

tetrameric ligand gated channels

-NMDA: 2 bind glutamate, 2 bind glycine

Question 10

How are chloride channels formed & regulated?

Name 1 important function.

Answer 10

dimers
Each subunit has ion permeability pathway
- each can open and close independently of the other
- separate gate can control both

Include: H+/Cl- exchangers -> stabilize resting membrane potential

Question 11

Why are aquaporins anti-ion channels?

Answer 11

exclude all ions, including protons

Question 12

Where are aquaporins expressed?

Answer 12

tissues where rapid movement of water is important => i.e. kidneys

Question 13

Are all channels equally selective?

Answer 13

No
K channels: 1/10,000 is not K
AChr: 1.3 preference for Na over K

Question 14

How does charge affect ion channels

Answer 14

only let cations OR anions through

**ionic valance also important **

Question 15

How is size important in ion channel selectivity?

Answer 15

substances larger than narrowest part of pore cannot pass
BUT
wrong ion cannot go through even if smaller than narrowest part

Question 16

How doew dehydration affect ion channel selectivity?

Answer 16

ions must dehydrate to pass

- difficult energetically-> interact with aa. in pore to stabilize during travel - not too much -> would stick!

Question 17

How is the gating of Na and K channels controlled?

Answer 17

membrane potential

Question 18

When is the K activation gate closed? open?

Answer 18

controlled by voltage sensing charge

CLOSED
when inside of cell is - relative to outside

OPEN
When inside is + relative to outside
=> rotates (activation)

Once inside is - again rotates closed => deactivation

Question 19

When is the activation gate of the Na channel open? Closed?

what about theI INACTIVATION GATE?

Answer 19

activation gate
OPEN: during depolarization, as cell becomes +
CLOSED: when inside negative

Inactivation gate is in place after activation gate opens- after depolarization-> must be “removed”
- inactivation open when activation gate closed

Question 20

On which side of the plasma membrane is the inactivation gate located?

Answer 20

cytoplasmic (intracellular)

Question 21

How is the lidocaine block state dependent?

Answer 21

protonated form is dominant at physiological pH

• cannot cross membrane
• no effect outside - but can block Na channel intracellularly

Activation gate must be open, and inactivation gate not closed for protonated form to access vestibule (cytoplasm) and have an effect

only de-protinated form can cross membrane