Ion channels

Ion Channels Ion channelsare pore-forming membrane proteins which allow the passage of ions in and out of a cell through the plasma membrane.

Ion channels

• Variations
  • selective to various ions
    • Intracellular/extracellular ion concentrations
    • Achieved by the narrowest part of the pore called: selective filter
      • Determine rate of transfer in different ions
    • kinetics of Ion channel
      • can be saturated: Vmax
  • Gating mechanism
    • voltage-gated channels
      • self amplifying oppening
    • mechanically gated channels
      • often have cytoplasmic extensions that link the channel to the cytoskeleton
    • ligand-gated channels
      • Extracellular ligand
        • transmitter-gated channels
          • they produce local permeability changes, and hence changes of membrane potential, that are graded according to how much neurotransmitter is released at the synapse and how long it persists there.
          • An action potential can be triggered from this site only if the local membrane potential increases enough to open a sufficient number of nearby voltage-gated cationchannelsthat are present in the same target cell membrane.
          • When an action potential reaches the nerve terminal in a presynaptic cell, it stimulates the terminal to release its neurotransmitter. The released neurotransmitter binds to and opens the transmitter-gated ion channels concentrated in the plasma membrane of the postsynaptic target cell at the synapse. The resulting ion flows alter the membrane potential of the target cell, thereby transmitting a signal from the excited nerve.
      • Intracellular ligand
        • ion-gated channels
        • nucleotide-gated channels
• Regulations
  • phosphorylation
  • Desensitization
    • when prolonged the stimuli
• examples
  • K+ channel
    • tetramer
      • 4 identical subunits
    • selective filter is
      • diameter for K+ ion
        • 0.133 nm
      • diameter for Na+ ion
        • 0.095 nm
    • Selective filter can give maximum free energy(for dehydration) to K+ but not Na+, this also reduces the conductance rate.
      • The carbonyl oxygen lies on the selective filter to provide binding energy
    • Negatively charged amino acids are concentrated at the cytosolic entrance to the pore
    • Here is a specific structure
      • The pore helix is polar, Because of the polarity of the hydrogen bonds (in red) that link adjacent turns of an α helix, so the negative charged site can stabalize, provide binding energy for the cation in the vestibule.
      • The vestibule response to the openning of the pore, and it sphere structure can keep the ion hydrated
      • Two K+ions occupy sites in the selectivity filter, while a third K+ion is located in the center of the vestibule, where it is stabilized by electrical interactions with the more negatively charged ends of the pore helices...
      • The crystal structure shows two K+ions in single file within the selectivity filter, separated by about 8 Å. Mutual repulsion between the two ions is thought to help move them through the pore into the extracellular fluid.
  • Acetycoline receptor
    • pentamer
    • The pore region is formed by hydrophobic leucinces!
      • not like hydrophylic back bone carbonyl groups in K+ channel
  • TRP superfamily ion channels
    • Specific cases
      • TRPV1
        • activated by
          • Capsasin
            • binding site is intracellular
              • Agonist recognation sites in rodent:
                • residues Arg114and Glu761in the intracellular N-and C-termini
          • Resiniferatoxin(RTX)
          • Evodiamine
          • valtage
          • lipids
          • low pH
          • high temperature(>43)
        • inactivated by
          • PIP2 binding
            • relieved by PLC-mediated PIP2 hydrolysis.
    • Great diversed gatting mechanisms
    • part of the same channel superfamily as the voltage-and ligand-gated potassium channels.
    • Homo/hetero tetramers
      • each subunit is expected to contain six roughly membrane-spanning helical segments
      • 1 to S6—and therefore both the N-and C-terminal extensions are cytosolic.
    • transmembranedomain
      • The sensor
        • S1-S4
      • The pore
        • S5-S6
          • contains selective filter
      • Resemble potassium channel
        • But TRP is less selective
          • TRPV1 can pass Ca2+ > Mg2+ > Na+K+Cs+
          • Some selectivities on selective filter are provided by S5-S6 linker
        • Unlike the voltage gated potassium channel: shacker channel, four positively charged argininesin (Gating charge) in the S4 segment is responsible for voltage sensation, but voltage sensing TRPs do not have the positive charged residue in their sensing domains
    • Ankyrinrepeats
      • TRPA
      • TRPC
      • TRPN
      • TRPV
      • It mediates specific protein-protein interactions
      • 33-residue ankyrinrepeat sequence motif consists of two antiparallel α-helices followed by a long β-hairpin or “finger” loop projecting outward from the helices at a 90°angle.
    • vision, taste, olfaction, hearing, touch, and thermo-andosmosensation.
• How we measure channels' oppenning?
  • • All of those currents are induced by membrane potential, the channel is a voltage gated
  • Patch current: right
    • measure one channel's oppening
  • Aggregate current: left
    • measure the whole cell's average oppening
    • You can see the desensitization
• Prevalance
  • in all animal and plant cells
  • 100 identified
  • response for the neuron firing
• Common
  • pore region
    • Pore regions More likely to be polar residues
    • And non-polar residues interact with lipids
  • passive transport
  • Most are Gated
    • Open&close are all or nothing
      • about 1 millisecond it will close
      • after 20 millisecond of continous stimuli it will desensitized