Fichas
Excitatory amino acids - AMPA and Kainate receptors subtypes
Fichas del conjunto (50)
- 1How does the topology and amino acid sequence vary between NMDAR and AMPA/Kainate receptors?Topology is the same - amino acid sequence different.
- 2Where is the Q/R site and what does it determine?Located on the TM2 loop, determines permeability to Ca2+
- 3What is the structure of the AMPA receptors? What are the constitutional subunits?Tetrameter - GluA1-4
- 4What is the endogenous agonist which binds to AMPAR and Kainate receptors?Glutamate
- 5What are the subunits which make up a kainate receptor? Which subunits can not form a functional receptor if they are the sole subunit?GluK1-5
GluK4 and GluK5 can't form a functional receptor on their own >> receptor won't make it to the surface. - 6What shape is the Amino terminal domain in an GluA2 tetramer? And the LBD?Clam shell (V), same but at 90 degrees to each other (<
- 7What is the structure of the transmembrane domain similar to?Inverted K+ channel pore
- 8What type of synaptic transmission do AMPA receptors mediate?fast
- 9Which ions pass through an AMPA receptor?Na+ in (Ca2+ in sometimes)
K+ out - 10Why do GluA2 receptors have relatively low Ca2+ permeability?Positively charged arginine (R) residue is expressed rather than neutral glutamine (Q)
- 11What percentage of GluA2 receptors are edited to express the arginine (R) residue?99%
- 12What are the molecules on the Q/R site? What effect do they have?Q - Spermidine, +ve charge, blocks the channel
R - Arginine residue, +ve charge inhibits spermidine block - 13What type of current is seen in a GluA2Q/GluK2Q (neutral glutamine at Q/R site). What happens at positive membrane potentials up to 80mV?1)Inwardly rectifying - more inward current than outward.
2)Little outward current as channel is blocked on the inside by polyamines - outward current increases around +80mV because large +tive current unblocks channel. - 14What is the current like through GluA2R or GluK2R (R edited +charge at Q/R site)? Why?Straight line current - no rectification.
Charged arginine prevents polyamine (spermidine) from causing a block. - 15Name three endogenous AMPA agonists - which is the partial?Glutamate
AMPA
Kainate (partial) - 16What is NBQX?Competitive AMPAR antagonist
- 17What does AMPA cause at at AMPARs?Fast desnsitisation
- 18What is perampanel?AMPAR negative allosteric modulator
- 19What type of drug is Cyclothiazide? What does it do?1) Amapkine
2) Positive allosteric modulator - inhibits glutamate-induced fast desnsitisation - 20What are the differences in terms of current/desensitisation induced by Kainate and 5-fluorowillardine (or AMPA)?Kainate produces small steady current with no desensitisation.
F-W or AMPA produce large peak current which rapidly desensitises. - 21Explain the structure of the ligand binding zone (S1S2) in terms of dimers.S1 and S2 are both made up of a set of D1 and D2. D1 sits on top of D2. The two pairs face each other so D1 faces D1 and D2 faces D2.
- 22Through which part of the dimer that makes up S1 and S2 is the majority of the dimer assembled?D1
- 23What happens when glutamate binds in between D1 and D2?D2 moves up towards D1, causing the linkers holding D2 to the membrane to open outwards in scissor like motion allowing the pore to open.
- 24How does desensitisation occur regarding the dimer?The dimer undergoes a conformational change causing the bonds between D1 to change. A rotation of one of the paris of the subunits around the axis relieves the strain on the linkers causing the pore to close.
- 25Which is more potent: LY404187 or cyclothiazedine?LY404187
- 26How do positive allosteric modulators (AMPAKINES) enhance the effect of agonists?Block desensitisation of AMPARs.
- 27Where do ampakines bind? What effect does this have?LBD interface - Between D1 units of the dimer. Stabilises reactions between D1 regions and prevents the conformational change which leads to desensitisation.
- 28What affect do ampakines have on NMDARs?Increase recruitment of NMDARs by increasing current through AMPARs (because that removes the Mg2+ block)
- 29What other effect does increased current through AMPARs have?Leads to greater depolarisation of membrane which can activate voltage-dependent calcium channels.
- 30What are the potential therapeutic uses of ampakines? What is this based on?1) Improve cognitive impairment caused by neurodegenerative diseases (parkinson's, alzheimer's), schizophrenia and sleep deprivation
2) Ampakines facilitate LTP. Showed improvement in animal models of learning and memory. - 31Where is it thought that NAMs bind to AMPARs? How do they work?Bind between TM1 and TM4 adjacent to the peptide linker which connect the Transmembrane region to the ligand binding region. 'Clamps' the ion channel shut.
- 32What is a therapeutic use of perampanel?anti-convulsant - treatment for partial seizures.
- 33Where are Kainate receptors expresses? (3) (GluK1?)1)Dorsal root fibres
2) GluK1 expressed in C nociceptive fibres (involved in pain transmission)
3) Hippocampus - 34What type of transmission are kainate receptors involved in in the hippocampus?High frequency
- 35What ions are kainate receptors permeable to and what does this depend on?Na+ in, Ca2+ in (depending on Q/R editing state), K+ out.
- 36Where are kainate receptors located in the hippocampus?pre synaptically on CA3 mossy fibres
- 37What does activation of the kainate receptors in the CA3 mossy fibres lead to? (2)1) Increased glutamate release
2) Induction of NMDAR independent LTP synaptic transmission - 38What effect does kainate have at kainate receptors?Agonist - desensitizing.
- 39What is Domoate? What effect does it have at AMPAR?Domoate is a desensitizing agonist at kainate receptors. At AMPAR it is a partial agonist with no desensitising effect.
- 40What are CNQX and ACET? How do they differ in terms of selectivity?Competitive antagonists at kainate receptor. ACET is selective for GluK1 subunit. CNQX is also an competitive antagonist at NMDAR and AMPAR.
- 41Where can Kainate be extracted from and what can it be used for?Red algae and anthelmintic (expels worms)
- 42What does lectin concanavalin A (con A) do? What is it?Blocks kainate induced desensitization. Plant
- 43How has it been shown in CA3 mossy fibres that KAR are responsible for LTP?D-AP5 (NMDAR antag.) didn't block LTP
ACET (Gluk1 antag) blocked LTP - 44How might the KAR (Gluk1) be involved in glut release and why is this a positive feedback loop?Calcium permeable > Influx calcium leads to glutamate release> Increased glutamate leads to further activation of KAR > More calcium current more glutamate release and so on.
- 45What might the Ca2+ induced release of glutamate via KAR underly?Long-term synaptic potentiation of synaptic transmission in the MF-CA3 pathway.
- 46What are the 3 potential therapeutic uses of Kainate receptor antagonists?1) Epilepsy
2) Neuropathic pain
3) Migraines - 47How might KAR antagonists work to prevent epilepsy?Prevent epileptogenesis. Blocks convulsions in animal models of epilepsy.
- 48How might KAR antagonists work in neuropathic pain?GluK1 is expressed in C nociceptive fibres - block them with antagonist to prevent transmission.
- 49How might KAR antagonists work to treat migraines?Gluk1 receptors present on trigeminal neurons (major part of pathway). Antagonists block pain responses in animal models of migraine.
- 50What is sumatriptan? What does it treat?5-HT agonist, reduces vascular inflammation associated with migraine.
Información
- Descripción
- Degree Neuropharmacology Fichas sobre Excitatory amino acids - AMPA and Kainate receptors subtypes, creado por Anna mph el 18/12/2015.
- Creado por
- Anna mph
- Visitas
- 94
- Valoración