+ All Categories
Home > Documents > Glutamate neurotransmitter

Glutamate neurotransmitter

Date post: 13-Jan-2016
Author: belle
View: 74 times
Download: 7 times
Share this document with a friend
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. - PowerPoint PPT Presentation
Embed Size (px)
of 27 /27
Glutamate neurotransmitter
  • Glutamate neurotransmitter

  • The metabolic roles of Glu

  • Glutamate (aspartate)The most important excitatory neurotransmittersLearningNeuronal developmentEpilepsyIschemiaNon essential aa-s do not penetrate the BBBMetabolites + neurotransmitters separate pool

  • Glutamatergic neurotransmissionGLT-1GLAST

  • NDMA N-metil-D-aspartateAMPA a-amino-3-hidroxi-5-metil-4-izoxazol propionic acid

  • Synaptic AMPA & NMDA receptorsAz AMPA & NMDA receptors colocalization AMPA activation depolarization inhibition by Mg2+ on NMDA receptor NMDA activation

  • The synaptic AMPA & NMDA receptors

    AMPA activation depolariztion Mg2+ inhibition NMDA NMDA activation Fast desensitization

  • NMDA receptor (Glu & Asp receptor)Strictly controlledActivators:Glu and Gly co-agonistsPoliaminesInhibitors: Mg2+Zn2+H+inhibit ion-fluxVoltage-dependent block of the open channelpH 6 complet inhibitionHa van GluR2 subunitNincs Ca2+ permeabilits

  • NMDA receptorActivation Na+, K permeability Ca2+ influxtransient activation of Ca2+-dependent enzymesCa2+-CAM dep. prot. kinz II.CalcineurinPKCPhospholipase A2PLCNO synthaseEndonucleaseSynaptic plasticityHippocampusLTPLTD

  • Metabotrop glutamatergic receptorsmGluR- pre- and postsynaptic localizationModulationIonic channels L-N type Ca2+ channels K+-channel Receptors(NMDA, AMPA, DA, GABA, NA) or PresynapticGABA, Glu transzm (Ca2+channel inhibition)

  • Increased glutamateergic activity neurotoxicIschemiaNeurodegenerationEpileptiform seizures

  • Neurotransmitter uptake systems in the presyzinaptic glutamatergic neurons

  • Neurotransmitter symport systemsNa-dependent reuptake in the axon terminl (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 Glu clearance from the synapseHinyuk: [Glu]e Lethal convulsions (mice)

  • Neurotransmitter symportsMany isoforms in neurons

    1 < Na+ influx - depolarizationanion 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

  • AMPA & NMDA receptors in synapses

  • Initial steps of ischemic brain damage

  • Excitotoxic effect of Glu in ischemia

  • Ca2+ homeostasisCa2+ pathological effects :

    - decrease in m decreased ATP production - increased ROS prodn- permeability tranzition pore openingIn mitochondriaCa2+ physiological effects

    PDH ICDH KGDH activation

    NADH increased ATP productioin-180 mV