L1 - Introduction Flashcards
What are the two types of ion channel?
Conductive - Ions flow - Current Non-conductive - No flow - No current
What are the four ways ion channels can be classified?
Selectivity
Gating
Regulation
Molecular structure
What is the selectivity of ion channels?
What is the main ion that moves through the pore
What is the gating of ion channels?
What is needed to open the channel
Voltage dependent, ligand dependent
What is the regulation of ion channels?
What regulates the channel
ATP, G-proteins, Ca
What is the function of the ion channel?
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
Why do Ks membrane potential sit slightly away from Ek?
K channels not only selective for K – they have Na leak
- This is vice versa for Na channels
Other channels also open
What are the changes in membrane selectivity during an action potential?
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
What is an example of two channels with similar Nernst potentials?
Cl and K channels
Both drive membrane potential in the negative direction
If two channels have similar Nernst potentials how do you work out which channel is present?
Look at the currents present
Use equation I = N.Po.g.(Vm-Ei)
What does everything stand for in I = N.Po.g.(Vm-Ei)
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
How can the number of channels be regulated?
Membrane shuttling
How can the open probability of channels be regulated?
Phosphorylation
Ca
G proteins
ATP
How can the membrane potential of a channel be regulated?
Activation or inhibition of other channels
What are the two ways to measure total current flow across the whole membrane?
Use whole cell patch technique or two electrode voltage clamp technique
What equation would you use to measure Itotal if just Na and K channels open in membrane?
Itotal = INa + IK Very small contribution from ATPase Then use - INa = N.Po.g.(Vm-Ei) - IK = N.Po.g.(Vm-Ei)
How can you identify ion channel currents?
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
What does pharmacological dissection involve?
Add a blocker of an ion channel and see if the current decreases
What happens when Ba2+ is added to an ion channel?
Currents very close to zero
So Ba2+ (K+ channel blocker) is inhibiting the channels that mediate the current – K+ channels
What are the 3 configurations of Na channels?
Closed – at negative potentials
Open
Inactivated – pore blocked by ball and chain mechanism
What happens to Na channels upon depolarisation?
Activate quickly with depolarisation, giving an increase in current
Close and inactivate slowly with depolarisation
What happens to Na channels if you depolarise the potential you hold your cell at?
- Na channels will first open – increase in current
- Na channels then close – decrease in current
- Channel inactivation then occurs
What is the role of tetrodotoxin?
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
What symptoms does the FHEIG disease cause?
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
What mutation causes FHEIG?
Mutations in a K channel – KCNK-4
Mutants have larger currents – gain of function
Where is KCNK-4 expressed?
In CNS and PNS
In KCNK-4 wildtype is interstitial space high or low in K?
Low
Impact of KCNK-4 mutant on K concentrations?
K+ loss into interstitial space high
Increased K+ accumulation
Depolarised EK
Neighbouring cells depolarised
