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Glutamate neurotransmitter

Glutamate neurotransmitter. The metabolic roles of Glu. Glutam ate (aspart a t e ). The most important excitator y neurotransmitters Learning Neuronal development Epilepsy Ischemia Non essential aa-s – do not penetrate the BBB Metabolites + neurotransmitters – separate pool.

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Glutamate neurotransmitter

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  1. Glutamate neurotransmitter

  2. The metabolic roles of Glu

  3. Glutamate (aspartate) The most important excitatory neurotransmitters Learning Neuronal development Epilepsy Ischemia Non essential aa-s – do not penetrate the BBB Metabolites + neurotransmitters – separate pool

  4. Glutamatergic neurotransmission GLT-1 GLAST

  5. NDMA – N-metil-D-aspartate AMPA – a-amino-3-hidroxi-5-metil-4-izoxazol propionic acid

  6. Synaptic AMPA & NMDA receptors • Az AMPA & NMDA receptors colocalization • AMPA activation → depolarization→ • inhibition by Mg2+ onNMDA receptor↓ →NMDA activation

  7. The synaptic AMPA & NMDA receptors AMPA activation à depolarizátion â Mg2+ inhibition NMDA â â NMDA activation Fast desensitization

  8. NMDA receptor (Glu & Asp receptor) Strictly controlled Activators: Gluand Gly co-agonists Poliamines Inhibitors: Mg2+ Zn2+ H+ inhibit ion-flux èVoltage-dependent block of the open channel èpH 6 complet inhibition Ha van GluR2 subunit Nincs Ca2+ permeabilitás

  9. NMDA receptor Activation à Na+, K permeability Ca2+ influx ↓↓ transient activation of Ca2+-dependent enzymes Ca2+-CAM dep. prot. kináz II. Calcineurin PKC Phospholipase A2 PLC NO synthase Endonuclease Synaptic plasticity Hippocampus LTP LTD

  10. Metabotrop glutamatergic receptors mGluR- pre- and postsynaptic localization Modulation Ionic channels L-N type Ca2+ channelsâ K+-channel – â Receptors (NMDA, AMPA, DA, GABA, NA) á or â Presynaptic GABA, Glu transzm â (Ca2+channel inhibition)

  11. Increased glutamateergic activity è neurotoxic Ischemia Neurodegeneration Epileptiform seizures

  12. Neurotransmitter uptake systems in the presyzinaptic glutamatergic neurons

  13. Neurotransmitter symport systems Na-dependent reuptake in the axon terminál (secondary active transport) Two subfamilies *GABA, glicin, noradrenalin, dopamin, serotonin transporters 12 transzmembrane regions Na (Cl-) dependent transporter *Na+-(-K+) dependent glutamate transporter (5 isoforms) GLAST (glutamate-aspartate transporter) GLT-1 Astrocytes ââ Glu clearance – from the synapse Hiányuk: [Glu]eá Lethal convulsions (mice)

  14. Neurotransmitter symports Many isoforms in neurons 1 < Na+ influx - depolarization anion efflux – intracellular acidification [Glu]szinapszis < 0,6 uM (10 mM brain, 2-3 uM extracellular) Anoxia, long-lasting depolarization – reversal of function Glu release Toxic

  15. AMPA & NMDA receptors in synapses

  16. Initial steps of ischemic brain damage

  17. Excitotoxic effect of Glu in ischemia

  18. Ca2+homeostasis In mitochondria Ca2+ physiological effects PDH ICDH KGDH activation ↓ NADH ↑ ↓ increased ATP productioin Ca2+ pathological effects : - decrease in m ↓ decreased ATP production - increased ROS prodn - permeability tranzition pore opening -180 mV

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