Amino acid transmitters Flashcards
Glutamate - key facts!
Main excitatory NT in the brain - synthesised in the brain from glucose metabolism or glutamine from astrocytes.
Storage of glutamate?
Vesicles, electrical gradient (from ATP proton pump), VGluT1-3 have high affinity for glut, Km = 1mM.
Release and reuptake of glutamate?
Exocytosis - receptors…reuptake by glial, high affinity, keep conc down…15-20,000 transporters (EAAT) per bouton. Can diffuse away and act at a different synapse.
Explain ionotropic glutamate receptors.
Ionotropic - 3…
- Kainate
- NMDA - 2NR1 and 2 NR2 subunits - permeable to Na+, K+ and Ca++.
- AMPA - GluR1-4…2 of 1, 2 of another. Permeable to Na and K.
NMDA and AMPA colocalise at functional excitatory synapses…both have 3TMF, tetramer.
AMPA - fast synaptic current, fast decay (low affinity of glu for AMPA)
NMDA - slow onset due to Mg block <-50mV…slow decay, glut high affinity for NMDA.
Explain metabotropic glutamate receptors.
Metabotropic receptors:
3 groups due to aa homology, agonist pharmacology and signal transduction pathway.
Group I: mGluR1, mGluR5 - Activate PLC, IP3 and DAG.
IP3 - Ca+ release…increase intracellular calcium,
DAG - activates KC - protein phosphorylation.
Also modify ion channels via BY.
Group II - mGluR2, mGluR3
Group III - mGluR4, mGluR6-8
Inhibit adenylate cyclase…decrease cAMP.
Also modify ion channels - BY.
Explain the modulatory effects of the mGluRs.
Variety effects on different types of Ca and K channels.
Presynaptic (by IIand III) - inhibit VOCC…decrease NT release from other terminals
Postsynaptic - mainly I…either inhibit of increase activity of K+ channels depending on cell type involved.
GABA - key facts.
major inhibitory NT in brain.
Synthesised from glutamine…glutamate…GABA.
Glutamic acid decarboxylase - GAD - only in GABA neurones.
GABA storage?
vesicles due to H+ gradient.
GABA reuptake
Na Cl dependant…reutilised presynaptically and degraded postsynaptically,
GABAa receptor?
Ionotropic - pentameric, 2A1, 2B2, 1Y2.
4TMD each
GABA binds between alpha and beta subunits.
Cl- channel - IPSPs.
GABAb receptor?
metabotropic.
Presynaptically - inhibit VOCC
Postsynaptically - inhibit opening of K channels.
7TMD, GPCR
Coupled to Gi - inhibit ad cyc
Coupled to ion channel via BY.
Glycine - key facts.
inhibitory
made from serine by serine hydroxymethyl transferase.
Glycine storage?
Vesicles, H grad.
Glycine reuptake?
glia (terminate action)
presynaptically (replenish vesicles)…driven by Na and Cl grads.
Glycine receptor?
Pentameric, 3alpha, 2 beta - each with 4TMD.
Ion channel permeable to Cl-.
Glycine binds alpha subunit.
