- Resting potential: -70mV
- Influx of Na+ leads to
- Depolarisation: 30mV
- Na+ channels inactivate, K+ channels open
- Hyper-polarisation: to just below membrane RP
- K+ channels close, Na+/K+ pump restores intra/extra cellular ion balance
- Repolarisation to -70mV.
Simple potassium channel (KcsA)
- Homotetramer: 4 identical protein chains (monomers) make up/enclose the pore
- 2 transmembrane helices per monomer
- Activation: low pH (inactivated by voltage)
- Selectivity: K+ ions lose their hydration shell much easier than Na+ ions because they are larger, less compact
- Backbone carbonyl groups (C=O) substitute for water molecules that otherwise surround K+ ion
- K+ ions can only fit through once they lose some of their HS
- 4 sites in filter where K+ ions bind, not all occupied at once (e.g. Ions occupy 1,3 then 2,4)
Pore structure (K+/Na+)
- 1) Selectivity filter - Size restricted to only allow certain molecules through.
- 2) Central water filled cavity - Water is polarising, lipid bilayer is non-polarising.
- A polarising environment lowers the energetic barrier ions face and allows them to transverse the entire channel.
- 3) Gate - Restriction point opened by Glycine backbone bending helices away in K+ channel and by movement of the S4-S5 linker (due to voltage change) in Na+ channel.
Voltage-gated sodium channel
- Structure: 1 protein chain, w/ 4 domains. Each domain is made up of 6 transmembrane helices
- S5 and S6 helices form the pore, including the selectivity filter, rest face away.
- S4 helix is positively charged - faces downward (towards intracellular domain) during resting state, move outward/upward upon membrane depolarisation due to positive charge in the extra cellular space.
- Movement of S4 helices pulls the S4-S5 linker causing the pore to open in an iris-like dilation
- Inactivate: Domain III - IV intercellular linker contains amino acid (IFM?) puts pressure on S6 linker causing pore to rapidly close.
DEKA selectivity filter
- (In eukaryotic sodium channels)
- Extracellular linkers between S5 and S6 helices form the channel selectivity filter
- DI: aspartate (D) negative
- DII: glutamate (E) negative
- DIII: lysine (K) positive
- DIV: alanine (A) neutral
- Na+ binds to negative charge amino acids on DI, DII, and an extra glutamate side chain on DII. They avoid other amino acid side chains.
Ligand-gated ion channels
- Located: post-synaptic membrane
- Structure: pentameric (homo and hetero) with 4TM helices
- Leucine side chains poke into the side of pore when the channel is closed, repelling ions with hydration shells.
- Activation: binding of neurotransmitters between 2 subunits in the extracellular domain. Ligand binding produces structural change in extracellular domain, pulling leucine side chains from the center of the pore, allowing ions to transverse channel.
- nAChR = Nicotinic acetylcholine receptor
- 5-HT3R = Serotonin receptor
- GABAA/CR = γ-aminobutyric acid (GABA) receptor
- GlyR = Glycine receptor
Transient Receptor Potential channels (TRP)
- Activation: wide array of sensitve input (E.g. mechanosensitive, thermal, volatile
- Produce initial signal
- Structure: 6TM helices. S5 and S6 forms the pore