Molecular Neuroscience

  1. Action potentials
    • 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.
    • figure-35-02-03
  2. 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)
    • kcsa-overview-e1320670677407
  3. 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.
  4. 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.
  5. 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.
  6. 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.
    • Image Upload 1
    • nAChR = Nicotinic acetylcholine receptor
    • 5-HT3R = Serotonin receptor
    • GABAA/CR =  γ-aminobutyric acid (GABA) receptor
    • GlyR = Glycine receptor
  7. 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
Author
charl_drogo
ID
344088
Card Set
Molecular Neuroscience
Description
action potentials and ion channels structure and function
Updated