ions and ion channels

biological importance of ions

• carry signals in the body

• act as energy stores

• interact biochemically with proteins

how many alpha subunits proteins contribute to the channel lining in voltage gated sodium channels and calcium channels

• 1

difference between nicotinic receptor pore and voltage gated calcium channels

• pore is formed from amino acids from multiple subunit proteins

• in voltage gated the pseudosubunits are linked together, not separate

which subunit is non pore forming found in sodium and calcium

beta

how many subunits contain voltage sensing segment in potassium channel

• tetramer

• voltage sensor found in 4th transmembrane domain

• → 4

which ion channels have alpha 2 delta subunits

calcium voltage gated ion channels

what percentage of drugs target ion channels

11%

how many membrane spanning domains for ionotropic ligand gated ion channels (ampa, nmda, kainate)

• 3

example of rectifying channel

inward rectifier potassium channel

rectification

• ion channel can flow across membrane better in one direction than the other

which ions interact biochemically with proteins

• calcium 2+ with troponin in muscle contraction

• magnesium 2+ and ATP

classes of ions

• physiologically useful

• biochemically useful

• physiologically and biochemically useful

which class of ion is Ca2+

• physiologically and biochemically useful

what happens to ions in aqueous solution

• forms hydration shell

• pos ions will attract the partial neg charge of oxygen in water

relationship between ionic size and hydration shell

• smaller ions have larger hydration shells due to higher charge density

• as the size increases the hydration shell decreases

how do hydration shells affect mobility

• larger the hydration shell the slower the mobility

• K+ most mobile

soidium potassium atpase pump

• 3 sodium ions move from in cell to outside

• 2 potassium ions move from outside of cell to inside

• use atp

• low sodium in cytoplasm

• high potassium in cytoplasm

• generates electrochemical gradient

use of ion gradients

• source of energy

• signalling via ion channels

• powers secondary active transport

two types of proteins in secondary active transport

• antiporter/exchanger

• symporter

sodium calcium exchanger

• sodium gradient used to power movement of calcium

• 3 sodium ions into cell for every 1 calcium ion out

• more effective than sodium pump

properties of ion channels

• transmembrane

• selectively permeable

• gate controlled

• diverse

how are ion channels selectively permeable

• selectivity filter

• ring of charged amino acids

• opp charge to the ion it is selective for

what does cryo-electron microscopy visualise

• ion channel structure

• 3 different staes

• resting, activated and closed

cys loop receptors

• neurotransmitter ion gated channels

• cys loop protein loop in the extracellular domain with a disulfide bridge between two cysteine residues

nicotinic AChR

• ligand gated ion channel

• cys loop receptor

• gated by acetylcholine

• cation channel

• important in nerve signalling

examples of cys loop receptors ligand gated ion channels

• nicotinic AChR

• GABAa

• 5HT3 receptor

• inhibitory glycine receptor

ionotropic glutamate receptors

• ligand gated ion channel located in cns

• for glutamate

• structurally distinct

• operate in a similar way

characteristics of ligand gated channels

• pore lets ions through

• ligand binding site

• coupling mechanism

• desensitisation mechanisms - closes channel if ligand binds for too long

structure of nicotinic acetylcholine receptor

• pentamer of similar subunits

• half of protein is outside of the cell

• alpha helix structures

• halfway through the structure is the gate

voltage gated ion channels

cation channels selective for calcium(Cav) , sodium (Nav), potassium (Kv)

Kv structure

• tetramer

• symmetrical

• 6 transmembrane domains - alpha helices

• between 5th and 6th has a membrane dipping domain

  • forms lining of the pore

• voltage sensor in the middle

evolution of cav and nav

• two pore channel

• gene duplication event

• overtime became mutated

structure of cav

• alpha subunit

• pseudosubunit - kv

• joined together to form one long peptide chain

• 10 different cav subunits

• also have beta, gamma, alpha 2 delta accessory subunit proteins

• 24 transmembrane domains

structure of nav

• alpha subunit

• pseudosubunit - kv

• joined together to form one long peptide chain

• 9 different nav subunits

  • 4 beta accessory subunits

  • one alpha or two beta subunits associated

  • 24 transmembrane domains

alpha 2 delta subunits

• single peptide chain cut and held together by disulfide bond

how was AChBP discovered

• snail lymnae stagnalis

does AchBP have an N terminus

• yes, like the nicotinic receptor

synaptic role of AChBP

• helps to understand ligand gated ion channels

• glial cells release AChBP into synapse

• acts as a molecular sponge for acetylcholine, lowering levels in the synapse

ELIC

• found in bacteria

• contains cys loop

• pentameric cation ligand gated ion channel

• gated by amines such as GABA

• 4 transmembrane domains per subunit

GLIC

• bacterial cation channel protein

• gated by protons

• homopentamer proteins

• no cys loop

• 4 transmembrane domains per subunit

how many proteins are present in native voltage gated calcium channel comples

3 or 4

• alpha, beta, alpha 2 delta

• sometimes gamma