Neurotransmitters Flashcards
How are NTs packaged into vesicles?
Energy dependent process.
- against conc gradient.
Vesicular conc is 100mM…
VGluT antiporter - negatively charged glutamate exchanged fro H+.
ATPase proton pump pumps protons into vesicle.
Criteria for classical NT?
Local synthesis - enzyme present at nerve terminals.
Storage - secretory vesicles.
Regulated release into synaptic space.
Post-synaptic cell receptors.
Means for terminating the action
Termination and regulated release provide temporal control.
Release into synaptic space - spatial control
How is Glutamate synthesised?
Mitochondrial-associated Glutaminase produces Glutamate.
Active process of VGluT uptake (ATPase proton pump and VGluT antiporter).
Glutamine-Glutamate shuttle:
EAAT2 is abundantly expressed on astrocytes and uptakes glutamate.
Glutamine synthase converts to glutamine.
GLutamine exported from astrocyte by SN, and uptaken by SA in neurone.
= Then Glutaminase, then uptake.
Highly energetically expensive due to ATP requirement = brain little stored glycogen, so ischaemia will lead to excitotoxicity.
Excessive gutamate release - can deplete energy stores of pre-synaptic cell, but also excessive glutamate signalling for proteasesllike calpain and endonucleases, release of ROS - cytoskeletal damage, DNA etc. = cell death!
How is GABA synthesised?
Other products of glutamate?
GAD present in GABAergic cells converts glutamaet into GABA.
Glutathione is synthesised from glutamte - major neuronal anti-oxidant to mop up free radicals…
Catecholamines, Indolamnes and Imidazolamines?
NA, A, Dopamine - tyrosine/
5-HT - tryptophan
Histamine. - histidine
