ions and ion channels

biological importance of ions

• carry signals in the body

• act as energy stores

• interact biochemically with proteins

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

inotropic glutamate receptors

• located in cns

• cation channels

• 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

• transmembrane domain

• gate - controls whether potassium enters and passes through the membrane

• 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

• 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