Synapses and Receptors Flashcards
Time taken between AP of cell 1 and AP of cell 2
2 milliseconds
Describe events of the SNARE hypothesis
Synaptobrevin (VAMP) + SNAP-25 +syntaxin
Synaptotagmin binds to superhelix and conformational change occurs
RIM binds too
Fusion pore opening
NSF, SNAP and ATP bind
NT release
Why is the vesicle-membrane complex so stable?
Synaptobrevin (VAMP), SNAP-25 and syntaxin each have an alpha helix
These 3 bind to form a superhelix
Role of synaptotagmin?
Calcium sensor that can induce the next stage (fusion pore and NT release)
E.g. of G-protein coupled receptors?
DA, NA, ACh-muscarinic, 5HT (5-hydroxytryptamine), enkephalin, substance P
E.g. of ionotropic receptors?
Glutamate, GABA, ACh-nicotinic, glycine
E.g. of amino acid NTs?
glutamate, GABA, glycine
What ion influx is triggered by?
Glutamate:
nACh:
GABA:
Glycine:
What ion influx is triggered by?
Glutamate: Na+
nACh: Na+
GABA: Cl-
Glycine: Cl-
What processes are mediated by glutamate receptors?
Learning and memory, developing and maintaining cellular connections, pain perception
Main glutamate receptors and their roles?
AMPA- mainly mediates fast CNS transmission
NMDA- coincidence detection and synaptic adaptation
Kainate- modulatory role and pre/post synaptic sites. Agonists are potent convulsants and environmental neurotoxins
(Delta- role not established but thought to be related to development)
Why is NMDA not activated from an initial stimulus?
It is blocked by Mg2+
What is the outcome of NMDA receptor activation
- Na+ and Ca2+ influx
- enhanced synaptic activation
What property confers Ca2+ impermeability?
GluR2 subunit
NB: this occurs even when combined with other subunits
What is the mechanism of calcium impermeability within receptors?
Ion conductance is regulated by amino acids
GluR2 in adults have arginine, resulting in Ca2+ impermeability
Most other ionotropic receptors have glutamine instead
How does the mechanism for Ca2+ impermeability arise?
NOTE: Genomic sequence codes for glutamine, NOT arginine
Glutamine is edited by RNA editing to arginine during development, causing Ca2+ impermeability]- this occurs at 100% in adult mammalian brain
Describe the composition of NMDA receptors?
Tetramers: 2 NR1 subunits and 2NR2(A-D) subunits
Describe the features of glutamate coagonists in NMDA receptors
GluN2B binds to glycine mainly
GluN2A binds to D-serine mainly
GluN1 binds to glycine mainly
This is essential before NMDA activation in order to relieve the magnesium block
Feature of NR2B receptor?
Longer phase of memory activation.
Receptors with this subunit stay open for longer (so enhanced coincidence detection)
