Synaptical Transmission Flashcards
Electrical Signal Transmission
Via gap junctions → Induces voltage changes in postsynaptic cell
Gap junction formation: 6 connexin subunits = 1 connexon, 2 connexon = 1 gap junction channel, multiple channels = 1 gap junction
Without gap junction delay in signal transmission
Chemical synapse (Synaptic release)
AP → CV open → Ca2+ enters axon terminal → Vesicle release → NT binds ligand-gated ion channels → Graded potentials
Reuptake by pre-synapse & followed by enzymatic degradion
Neurotransmitter Classes
Biogenic Amines: Adrenaline, NA, dopamine, serotonin
AA transmitters: GABA, glutamate, glycine
Neuropeptides: e.g. Endorphins, cholecystokinin, dynorphin, enkephalins, NPY, somatostatin, substance P, VIP
Acetylcholine
Properties of a Neurotransmitter
Synthesis in the presynaptic nerve terminal
Storage in secretory vesicles
Regulated release in the synaptic space between the pre- & postsynaptic neurons
Presence of specific receptors for the NT on postsynaptic membrane
Means for termination of the action of the released NT
Neurotransmitter Packaging
Vesicles produced in soma (ER & Golgi) → Active transport in vesicles along microtubules
VMATs: Vesicular monoamine transporters (2 H+ out; pH>psi)
VACht: Vesicular ACh transporters (2H+ out, pH >psi)
VGAT: Vesicular GABA & glycine transporters (nH+ out, pH=Psi)
VGLUTs: Vesicular glutamine transporters (nH+ out, pH< Psi)
Vesicle Fusion
Interaction of SNARE proteins
vSNARE: Expressed on vesicles with synaptotagmin
TSNARE: Expressed on (trans-)membrane
Involvement of Syntaxin, SNAP-25 & Munc
Ca2+ binds on negative SNAREs → Conformation change → Movement → SNAREs are twisting each other → Vesicles come closer → Fusion & NT release
Methods to Study Neurotransmitter release
Styryl dye: Vesicle takes up fluorescent dye upon fusion with membrane
SV-pHluain: GFP coupled & pH dependent → Fusion = physiological pH = Green signal
Quantum dots
Transporters for Neurotransmitter Reuptake
NSS NT sodium symporter type transporters → Co-transport 1-3 Na+ in exchange to K+, H+ & Cl-
LeuT: Homologue of NT transporters for biogenic amines & GABA & Glycine
EAAT: Excitatory AA transporter (Glutamate)
Microglia necessary for reuptake of GABA & Glutamate → Increase/Shrink in size due to AQP transport → Different distances to synapse
EAAT
Depends on Na+/K+-ATPase gradient
Glutamate binds in outward open confirmation when Na+ is bound → Conformational change → Release of glutamate → Exchange of Na+ for K+ → Return to outward open confirmation
Glutamate synthesis
From alpha-ketoglutarate
Glutamate hydroxylase & Glutamate oxalacetate transaminase → No suitable markers for glutamatergic neurons (Due to GABA synthesis)
GABA synthesis
From glutamate through glutamate decarboxylase
Dopamine
L-Tyrosine to L-DOPA via Tyrosine hydroxylase
L-DOPA to Dopamine via DOPA-Decarboxylase
Main dopaminergic neurons in Substantia nigra & ventral tegmental area
Adrenaline & Noradrenaline synthesis
Dopamine to NA via Dopamine-beta-hydroxlase and further to Adrenaline
NA system: From Locus coerueus (Pons) in multiple brain regions (including spinal cord) → Affects incoming sensatory stimulation (e.g. Pain)
Serotonin synthesis
L-Trypotphan to 5-Hydroxy-Tryptophan via oxidation
5-Hydroxy-Tryptophan to Serotonin via decarboxylation
Serotonin system: From Raphe nuclei (Brain stem) to multiple other brain regions
Acetylcholine synthesis
Acetyl-CoA + Choline → Through ChAT to ACh
Main ACh population: Ncl. Basalis Meynert, Pedunculopontine nucleus (PPN), Laterodorsal tegmental neurons
Interneurons in Striatum & Ncl. Accumbens
