L1 - Introduction

Question 1

What are the two types of ion channel?

Answer 1

Conductive 
- Ions flow 
- Current
Non-conductive
- No flow 
- No current

Question 2

What are the four ways ion channels can be classified?

Answer 2

Selectivity
Gating
Regulation
Molecular structure

Question 3

What is the selectivity of ion channels?

Answer 3

What is the main ion that moves through the pore

Question 4

What is the gating of ion channels?

Answer 4

What is needed to open the channel

Voltage dependent, ligand dependent

Question 5

What is the regulation of ion channels?

Answer 5

What regulates the channel

ATP, G-proteins, Ca

Question 6

What is the function of the ion channel?

Answer 6

When open they drive membrane potential towards the Nernst potential for the channel
Eion = potential when no net flow of ions across the membrane
Always use 61.5K as this is body temperature

Question 7

Why do Ks membrane potential sit slightly away from Ek?

Answer 7

K channels not only selective for K – they have Na leak
- This is vice versa for Na channels
Other channels also open

Question 8

What are the changes in membrane selectivity during an action potential?

Answer 8

At start at -70 mV - K+ > Na+ around 50 times more selective
At peak of action potential - Na+ > K+ around 5 times more selective
Exact values depend on the tissue and the ionic concentrations

Question 9

What is an example of two channels with similar Nernst potentials?

Answer 9

Cl and K channels

Both drive membrane potential in the negative direction

Question 10

If two channels have similar Nernst potentials how do you work out which channel is present?

Answer 10

Look at the currents present

Use equation I = N.Po.g.(Vm-Ei)

Question 11

What does everything stand for in I = N.Po.g.(Vm-Ei)

Answer 11

I = total current carried by population channels
N = no of channels
Po = open probability
g = single channel conductance
Vm = membrane potential
Ei = Nernst potential ion

Question 12

How can the number of channels be regulated?

Answer 12

Membrane shuttling

Question 13

How can the open probability of channels be regulated?

Answer 13

Phosphorylation
Ca
G proteins
ATP

Question 14

How can the membrane potential of a channel be regulated?

Answer 14

Activation or inhibition of other channels

Question 15

What are the two ways to measure total current flow across the whole membrane?

Answer 15

Use whole cell patch technique or two electrode voltage clamp technique

Question 16

What equation would you use to measure Itotal if just Na and K channels open in membrane?

Answer 16

Itotal = INa + IK 
Very small contribution from ATPase
Then use 
- INa = N.Po.g.(Vm-Ei)
- IK = N.Po.g.(Vm-Ei)

Question 17

How can you identify ion channel currents?

Answer 17

Using whole cell patch clamp technique you can clamp to a specific Vm potential and measure total current flow across the membrane
Each line represents the current recorded at a range of different potentials

Question 18

What does pharmacological dissection involve?

Answer 18

Add a blocker of an ion channel and see if the current decreases

Question 19

What happens when Ba2+ is added to an ion channel?

Answer 19

Currents very close to zero

So Ba2+ (K+ channel blocker) is inhibiting the channels that mediate the current – K+ channels

Question 20

What are the 3 configurations of Na channels?

Answer 20

Closed – at negative potentials
Open
Inactivated – pore blocked by ball and chain mechanism

Question 21

What happens to Na channels upon depolarisation?

Answer 21

Activate quickly with depolarisation, giving an increase in current
Close and inactivate slowly with depolarisation

Question 22

What happens to Na channels if you depolarise the potential you hold your cell at?

Answer 22

1. Na channels will first open – increase in current
2. Na channels then close – decrease in current
3. Channel inactivation then occurs

Question 23

What is the role of tetrodotoxin?

Answer 23

Na channel blocker
Smaller currents are seen as the channels are inactivated
If you can tell how much the current has dropped can work out the % of channels that are tetrodotoxin sensitive

Question 24

What symptoms does the FHEIG disease cause?

Answer 24

Bi-temporal narrowing, hypertrichosis, thin upper lip, bushy eyebrows, overgrowth of mouth tissue
Delayed development of intellectual ability and motor skills
Seizures and EEG anomalies

Question 25

What mutation causes FHEIG?

Answer 25

Mutations in a K channel – KCNK-4

Mutants have larger currents – gain of function

Question 26

Where is KCNK-4 expressed?

Answer 26

In CNS and PNS

Question 27

In KCNK-4 wildtype is interstitial space high or low in K?

Answer 27

Low

Question 28

Impact of KCNK-4 mutant on K concentrations?

Answer 28

K+ loss into interstitial space high
Increased K+ accumulation
Depolarised EK
Neighbouring cells depolarised