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Flashcards

Excitatory Amino Acids - Glutamate

Anna mph Neuropharmacology Degree English 56 cards

Cards in this deck (56)

  1. 1What is the principle excitatory amino acid found in all mammalian cells?L-glutamate
  2. 2What can L-glutamate not cross?Blood brain barrier
  3. 3Which conditions are associated with a malfunction in glutamate transmission?Epilepsy, schizophrenia, parkinsons and alzheimers
  4. 4What are the two subtypes of glutamate receptors?Ionotropic and metabotropic
  5. 5What are the group 1 metabotropic receptors?mGlu1,5
  6. 6What are the group 2 metabotropic receptors?mGlu2,3,
  7. 7What are the group 3 metabotropic receptors?mGlu4,6,7,8
  8. 8What is the glutamate transporter located on the postsynaptic membrane?EAAT3
  9. 9What are the transporters located on the astrocyte for the up take of glutamate? Which ions are required?EAAT1 and EAAT2
    3Na+ and H+ in, K+ out
  10. 10What substances and which enzyme is required for the conversion of glutamate to glutamine?Glutamine synthetase
    ATP+NH4
  11. 11Which transporter transports glutamate from the cytosol into vesicles?VGLUT
  12. 12What is the most likely transporter located on pre synpatic terminal?EAAT2
  13. 13Which enzyme converts glutamine to glutamate?Glutanimase
  14. 14How many subunits are in an NMDA receptor and what are they?4
    2GluN1 and 2GluN2
  15. 15How many transmembrane domains does each subunit have?4
  16. 16Which transmembrane domains make up the ligand binding domain?S1S2
  17. 17What is S1?Extracellular peptide chain extending from TM1
  18. 18What is S2?Extracellular peptide chain extending join TM3 and TM4
  19. 19Which transmembrane chain makes a re-entrant loop forming the pore of the channel?TM2 - loop points in towards channel
  20. 20Which ions can pass through an NMDA channel?Na+ and Ca2+ flow inwards
    K+ flows outwards
  21. 21What are the three important properties of NMDA channels regarding Calcium, glycine and magnesiumNMDA channels have a high Ca2+ permeability
    Mg2+ blocks the pore
    Glycine is a co-agonist
  22. 22Which subunit binds the glycine?GluN1
  23. 23Which subunit binds the glutamate?GluN2
  24. 24What are the sub categories of GluN2 receptors?GluN2A, GluN2B, GluN2C and GLUN2D
  25. 25At what membrane potential is the magnesium block removed?~ -35mV
  26. 26How does the pore open?Binding of glutamate and glycine causes a conformational change
  27. 27Which other type of receptor is usually present where NMDAR are found? What is the purpose of this?AMPA
    Sufficiently depolarise the membrane to remove the Mg2+ block
  28. 28In terms of neuroplasticity what is the NMDA receptor and why?Coincidence detector
    Ca2+ entry depends on both the membrane being sufficiently depolarised and glutamate release.
  29. 29What type of drugs can block an NMDA receptor?Voltage dependent (positively charged)
  30. 30Explain the shape of a NMDAR - I/V curveMagnesium block is progressively lost (downwards U shape) then at -35mV block is completely removed and current becomes completely voltage dependent.
  31. 31What is eliprodil? Where does it bind? Which subunit is it selective for?Negative allosteric modulator
    Site E (interface between GluN1 and GluN2B)
    GluN2B
  32. 32What are D-AP5 and D-CPPene?Glutmatergic antagonists - bind at S1S2 on GluN2B
  33. 33What are Kynuernate and 5-7 dichlorokynurenic acid?Competitive antagonists of glycine - bind at S1S2 site on GluN1
  34. 34Where do ketamine, memantine, PCP and MK-801 all bind? What does this make them?Binding site C - Use dependent blocks
  35. 35What does NMDA stand for?N-Methyl-D-Aspartate
  36. 36Which binds with more affinity, R-AP5 or R-CPPene?R-CPPene
  37. 37What is an agonist for the glycine binding site?D-Serine
  38. 38What determines the affinity of Glycine to the Glu1 subunit?The type of GluN2 subunit present
  39. 39What is D-serine released from?Astrocytes
  40. 40Where is kynurenate produced from? What more potent drug has been developed from it?Glial cells
    5,7-dichlorokynurenate
  41. 41What is memantine used to treat? What is its affinity like?Memory impairment in moderate/severe alzheimers, vascular dementia and dementia in parkinsons
    low affinity channel blocker (same for ketamine)
  42. 42Which are the two high affinity channel blockers?PCP (phencyclidine) and MK-801
  43. 43How much higher is MK-801 affinity than ketamines? what is its dissociaton rate like?150-fold
    much slower dissociation rate
  44. 44What causes the tonic activation of NMDARs in alzheimer's disease?soluble B-amyloid plaques
  45. 45How do solid B-amyloid plaques cause tonic activation of NMDARs?Increase of glutamate in synapse by inhibition of glutamate transporters. Also removal of Mg2+ block.
  46. 46What is the effect of tonic background noise and what effect does this have on normal physiological signals?Background noise - hard to detect normal physiological responses - impaired cognition.
  47. 47In terms of membrane potentials why is memantine effective?Blocks NMDAR at tonic activation at -50mV but not under physiological conditions when a signal causes a depolarisation of around -20mV.
    BLOCKS PATHOLOGICAL NOT PHYSIOLOGICAL SIGNAL
  48. 48Why is MK-801 not useful clinically in terms of membrane potentials?Remains bound to (and blocks) channel in pathological and physiological conditions. Blocks signal transmission.
  49. 49What effect might memantine have on neurodegeneration?Preventative - may reduce neurodegeneration by preventing neurotoxicity (alzheimer's causes increased synaptic glutamate which would cause increased inward calcium current through over active NMDAR)
  50. 50What are the 2 main physiological roles of NMDARs?1) Mediate slow EPSP via Ca2+ and Na+
    2)Synaptic plasticity - change strength of synaptic pathways and consolidate new path ways)
  51. 51What are the two processes within synaptic plasticity mediated by NMDARs?1) LTP - long term potentiation of synaptic transmission
    2) LTD - Long term depression of synaptic transmission
  52. 52Which two factors determine whether LTP or LTD are induced?1) Frequency of stimulation
    2) Duration of stimulation
  53. 53What happens when you stimulate the Schaffer collateral pathway in the hippocampus at 100Hz for 1 sec? Why?LTP - increased amplitude of current, last for hours
    AMPA receptors inserted into membrane
  54. 54What happens when you stimulate the schaffer collateral pathway in the hippocampus at 1Hz for 15 mins? Why?1) LTD - current decreases
    2) Down regulation of AMPA receptors at membrane
  55. 55How can you test that NMDAR are involved in LTD and LTP induction?D-AP5 (NMDAR antagonist) blocks induction.
  56. 56What are the four main pathophysiological roles of NMDA receptors?1) Excitotoxicity
    2) Epilepsy
    3) Transmission of pain responses
    4) Schizophrenia

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Degree Neuropharmacology Flashcards on Excitatory Amino Acids - Glutamate , created by Anna mph on 18/12/2015.
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