L2 ion channel gating

Question 1

how does the open probability change with a ligand gated ion channel?

Answer 1

Po changes when ligand binds, e.g. Ach

Po changes further with signalling pathways and protein interactions

Question 2

how does the open probability change with a voltage gated ion channel?

Answer 2

Po changed with changes in membrane potential

Po changes further with signalling pathways and protein interactions

Question 3

what is shape of voltage dependent channel IV graph?

Answer 3

-s shaped
(this is because channel is activated by depolarisation so there is some initial delay)

(not linear)

Question 4

what are the values of conductance?

Answer 4

1= biggest value
0= lowest value (channel closed?)

Question 5

what does boltzman equation describe?

Answer 5

describes the S shaped relationship in voltage gated dependent channel graph

Question 6

give mechanism of ball + chain?

Answer 6

closed - open - inactivated

- is a time delay as channel has to go from inactivated to closed, before being able to become open again

Question 7

what are axis on voltage dependent channel graph?

Answer 7

G/Gmax and potential

modelled by boltzman

Question 8

what is Vo?

Answer 8

where G= 50% of Gmax

Question 9

what is Vm?

Answer 9

membrane potential - the difference between the electrical potential in the cytoplasm and the electrical potential in the EC space

Question 10

what is the resting potential of a cell?

Answer 10

aorund -90mv

Question 11

what are the elements in opening of a voltage dependent channel?

Answer 11

sensor (S4 reigon)
transducer
effector (movement of aa that open/close the channel)

Question 12

how did they try to identify which part of the S4 region causes acitviation?

Answer 12

• did charge neutralising mutations (to see if aa is charge specific)
• did charge conserving mutations - but changed the aa acid (same charge) - see if aa specific?- but charge dependent
• deleted fast inactiviation as this contaminates results/data (IFMQ3????)

Question 13

what is the name of the non-inactivating channel?

Answer 13

IFMQ3 - deletion of fasy inactivation as this contaminates activation results -interfere with ball and change - delete fast actuavtion.

Question 14

what happens when the aa is changed in s4 region?

Answer 14

when aa is changed in s4 region there is a big change in Vo

delay in Vo so delayed ap/depolarisation when aa acid changed e.g to IK4Q

Question 15

what domains/areas of the S4 region are most important shown by mutant studies?

Answer 15

• 4th charge in domains I,II, and IIImost important
• some residues more important than others
• but all S4 regions are inportant

Question 16

where is the linker region Nav?

Answer 16

Nav III-IV linker region

Question 17

what happened when muations were carried out in linker region III-VI?

Answer 17

-charge residue mutation - little impact - charged aa’s not important in linker regions

• when systematically removed sets of aa’s in the linker region - deletion of blocks 1 and 4 - major changes- no/delayed inactivation??
• hydrophobic aa’s are important/key

Question 18

what are the causes of rectification?

Answer 18

1- Voltage dependent Po
2- goldman rectification (all channels)
3- voltage dependent block

Question 19

what does voltage dependent block by Mg2+ on Kir do?

Answer 19

• inward rectification by Vdep block by Mg2+ - K+ goes into the cell but there is no outward current of K+.
• when Mg2+ block isnt there - K+ can move out of the channel
• Mg block if membrane potential is more potisive than Vrev
• Mg not blocking if membrane potential is more negative than Vrev

(aims to have no net flow of K+ - no outward current of K+ (Kir)))