Ion Channels

Question 1

Four important targets of natural products used for predation

Answer 1

1. omega-conotoxin: Ca2+ channels (Conus Geographus)
2. alpha-bungarotoxin: nicotinic AChRs in IMJ (Sea Krait)
3. Ryanodine: RyRs (Ryania speciosa)
4. Tetrodotoxin: Na+ channels (Fugu fish)

Question 2

What are the types of stimuli for gating?

Answer 2

1. Temperature
2. Mechanical deformation
3. Membrane potential
4. Extracellular chemicals (taste, olfaction, neurotransmitters)
5. Intracellular second messengers (ATP, cAMP, Ca2+)
6. Voltage-gated

Question 3

Describe the structure of Nav and Cav channels

Answer 3

1. 4 membrane-spanning domains, linked together as 4 repeats (I, II, III, IV)
2. Each domain has 6 alpha-helices (S1-S6)
3. S4 helices have + charged residues (lys or arg) every 3rd position.
4. S5, S6, and P loop assemble to form the ion conducting pathway and “selectivity filter”

Question 4

How does a Nav and Cav channel sense voltage?

Answer 4

Within each domain there is a S4 helix with + charged residues every 3rd position to sense voltage

Question 5

How do Kv and Nav & Cav channels differ in structure?

Answer 5

Kv: each domain is a separate polypeptide, Nav & Cav: have the four domains linked into a single polypeptide

Question 6

Which section of an ion channel serves as a selectivity filter?

Answer 6

S5 and S6 helices and P loop

Question 7

Are all ion channels the same structure as Kv /Nav/Cav?

Answer 7

No, there are also pentameric and tetrameric receptors

Question 8

Difference between ionotropic and metabotropic receptors. Which can NT activate?

Answer 8

Ionotropic: directly coupled NT receptor to ion channels
Metabotropic: activate 2nd messenger pathways to physically separate ion channels

NT can activate both

Question 9

Describe the structure and give examples of pentameric ligand gated channels

Answer 9

Examples: GABA, GlyRs, nAChRs, 5-HTRs

Structure:

1. 5 subunits with 4 alpha-helices each
2. M2 helices assemble around the ion-conducting pathway
3. Selective for the permeation of chloride or allow permeation of both sodium and potassium

Question 10

Describe tetrameric ligand gated channels and give examples.

Answer 10

Examples: NMDA receptors

Structure:

1. 4 subunits with 3 alpha-helices each
2. In NMDA 2 subunits bind glutamate, 2 bind glycine

Question 11

CLC structure and function. Examples of defects.

Answer 11

Examples: Fainting goats & righting mice

Structure:

1. Dimers in which each subunit has an ion permeation pathway.
2. Each pathway can gate open and close independently of each other
3. Also have a concerted gate which controls both.
4. Controls resting membrane potential

Question 12

Structure of aquaporins. Where are they expressed?

Answer 12

Structure:

1. Tetramers in which each subunit contains a permeation pathway for water molecules.
2. “anti-ion” channels since they exclude all ions including H+

Expressed in cells/tissues where rapid movement of water is important such as the kidney.