Ion Channels

Question 1

Why do we need ion channels

Answer 1

–> the nervous system relies on ion channels for rapid signaling

• membrane consists of lipids and protein with the core being the phospholipid bilayer
• ion channels are proteins that go across the membrane
• ion channels are involved in AP generation

Question 2

Properties of ion channels

Answer 2

• recognise and select specific ions
• open and close in response to specific electrical, mechanical, or chemical signals
  
  • voltage gated —> in response to
    changes in membrane potential
  • ligand-gated —> in response to chemical
    transmitter
  • mechanical —> in response to pressure
    or stretch
  • some channels are open during resting
    membrane potential, others are closed
• conduct ions across the membrane
  
  • always move down concentration
    gradient
  • cause changes in membrane potential
    which is needed for signaling

Question 3

Ion Channel Selectivity

Answer 3

• How can ion channels be selective?*
• can’t just be selective based on size (e.g. Na+ ions are smaller than K+ but still cannot use K+ channels)

—> depends on the amount of water surrounding an ion

• the smaller an ion the more highly localised its charge, the stronger the electric field —> the smaller the ion the more water it attracts

—> Na+ has larger water shell than K+ which makes it too large to pass through K+ channels

• the smaller the ion, the lower its mobility
• How does a channel select Na+ over K+ if K+ is effectively smaller together with its water shell?*

—> selectivity filters (narrow regions that act as molecular sieves)

• ions must shed most of its water to traverse the channel
• because shedding is energetically unfavourable, ion will only do this if energy of interaction with selectivity filter compensates for loss of energy through losing the water
• Na+ can approach a negative site more closely than K+ and will therefore derive more energy upon binding which compensates for energy loss from losing waters of hydration
• a low negative strength binding site would select K+ over Na+ because Na+ would not provide sufficient free-energy change to compensate for the loss of water BUT would be able to compensate for K+ ion loss are they have less water molecules attached

Question 4

Ion flow is passive

Answer 4

• no metabolic energy is needed by the channels
• direction of flux is determined by electrostatic and diffusional driving forces across the membrane
• select either cations or anions to permeate (most channels are selective to one specific type of ion
• direction determined by two factors*
  1) electrical potential difference across membrane
  2) concentration gradient of the permeant ions across the membrane

—> change in either factor can be the driving force

Question 5

Conformational Changes lead to gating

Answer 5

Gating = transition of channel between open and closed states

• each channel has at least two conformational states that represent different functional states
• some channels open and close through twisting and tilting ox subunits that make up the channel —> this re-arrangement appears to enhance ion conduction through channel not only be creating a wider lumen but also by positioning relatively more polar amino acid constituents at the surface that lines the aqueous pore

Question 6

How do channels open and close?

Answer 6

1) localized conformational change in one region of channel
2) generalized structural change occurs along the length of the channel
3) blocking particle swings into and out of channel mouth

Question 7

What controls opening and closing?

Answer 7

1) ligand binds to receptor site on external surface of channel —> energy from ligand binding causes channel to open
2) protein phosphorylation and dephosporylation —> transfer of high-energy phosphate causes opening
3) changes in electrical potential (voltage-gated channels)

• inactivation via:
  
  • refractory state after opening when membrane is depolarized —> recover from this and return to resting state after membrane potential is restored
  • some Ca2+ inactivate when internal Ca2+ levels increase following channel opening —> internal Ca2+ binds to specific protein

4) stretch or pressure —> mechanical forces passes to channel through cytoskeleton provide energy