Ion Channel Morphology

Question 1

Typical structure of Na+ ion channels (Nav)

Answer 1

• 24 transmembrane domains
• 4 different voltage-sensing domains
• 4 pore sequences
• Only 1 subunit is needed to form 1 pore
• Groups of 6 domains (4 regions) within the subunit are all slightly different
• Beta subunit interracts with this Alpha subunit (described above) to regulate Po (open probability)

Question 2

Typical structure of K+ ion channels (Kv)

Answer 2

• 6 transmembrane domains
• Domain 4 is the voltage sensor
• Between domains 5 and 6 there is a pore region
• Fully formed channel is made up of 4 subunits to form a multimer
• All 4 of the copies need to be correctly functioning for the channel to form correctly. Having 1 mutant and 3 WT (wildtype) will not have a functioning channel.

Question 3

Typical structure of Kir channels

Answer 3

• 2 transmembrane domains
• NO voltage sensor
• Pore region located between the 2 transmembrane domains
• Fully formed channel is made up of 4 subunits to form a multimer
• Discovered in the kidney through ROMK
• Pore region between Kv and Kir are very similar

Question 4

How are ion channels classified?

Answer 4

Three major classification factors:
1. Selectivity: what ion is allowed through.
2. Structure: recent form of classifying, grouping ion channels into families based off molecular and amino acid structure
3. Gating: how it works, whether its activated through binding, voltage changes, or other sensing molecules like ATP for example.

Question 5

Voltage gated channels versus Ligand dependant channels

Answer 5

Voltage: Po changes with membrane potential, allowing for action potentials to be fired (depolarisation and repolarisation cycle)
- Kv, Nav, Cav, CLC
Ligand: Po changes with the binding of a ligand to the allosteric site.
- Ach, P2X (gated by ATP and allows Ca entry into the cell)

• Other ion presence can change Po with signalling pathways and protein interactions which leads to channels being constitutively open.
• Kir, CFTR

Question 6

Describe the Pore region

Answer 6

• Determines selectivity and permeability
• 4 are needed to make a fully formed pore

Question 7

Reversal potential (VREV)

Answer 7

This is the potential where there is no net movement of the ions, leaving the current at 0.
Vrev is determined by the properties of the ion channel itself.
Graphically, it is seen as where the line crosses the X axis on the IV curve (voltage-current curve: passes through the voltage axis at the ion’s Nernst potential)

Question 8

Nernst potentials

Answer 8

Where there is no net ion movement and the current is 0, similar to Vrev.
Na+ is normally around 60mV, K+ is normally -90mV
If the VREV is close to the Nernst potential, you can use it to see what channel is being studied. It will however not be the EXACT value, as channels are SELECTIVE NOT SPECIFIC. The VREV will be near the middle of both Nernst values for K+ and Na+ if it transports a similar amount of each.

Question 9

Selectivity versus Permeability

Answer 9

Selectivity is what ions can come through, like K+ or Na+ channels, which is determined from VREV.
Permeability is how easily it moves through the pore once its in the pore. This determined the number of ions that can move through the pore at once, and is determined by the current magnitude/size of current.

Question 10

The Goldman Equation

Answer 10

VREV= (RT/zF) . ((lnP[Na]o + P[K]o)/(P[Na]i + P[K]i))
- Used to calculate relative selectivity of the values, and see what structures impact channel selectivity.
- RT/zF for body temperature tends to be 61.5, for room teperature its 58.2