S6 Neuro Neurotransmitters and synaptic transmission Flashcards
Gap Junction characteristics
small: 3.0-3.5 nm gap between membranes
cytoplasms connect when channels open
fast (
chemical synapse characteristics
Characteristics
- ) 20-50 nm gap between membranes
- ) No cytoplasmic continuity
- ) Slower (~2 msec)
- ) More common
Key proteins involved in synaptic vesicle fusion
SNAREs and Vesicle trafficking:
- SNAREs: SNAP REceptors
- SNAP: Soluble NSF Attachment Protein
which of the proteins in the synaptic vesicle is the calcium sensor
snaptotagmin
T-snares of interest in synaptic vesicle
syntaxin
SNAP-25
V-snare of NT containing vesicle
snaptobrevin
Synaptic vesicle recycling
Fused vesicle->
clathrin coated->
Dynamic helps pinch vesicle from nerve terminal->
ATPase-> removes clathrin
synopsis binds to cytoskeleton help pull it away from nerve terminal.
other means of synaptic vesicle recycling
endosmoal intermediate
kiss and run
Major classes of neurotransmitters
small-molecule neurotransmitters
neuropeptide
gaseous neurotransmitters
Small molecule NTs
acetylcholine
excitatory AA: glutamate
Inhibitory AA: GABA, Glycine
Biogenic Amines- Catecholamines:
- dompamine
- norepinephrine
3: epinephrine
Indoleamine: Serotonin (5-HT)
imadazole amine: histamine
purine: adenosine
Acetylcholine synthesized in
cytoplasm. by conversion of choline to acetylcholine. packaged into vesicle
Acetylcholine breakdown occurs
in synapse. choline product is recycled into neuron
one of the acetylcholine rich sites in brain
nucleus of meynert
Deficits of acetylcholine in Nucleus of meanest associated with
alzheimer’s disease
boost synaptic acetylcholine to treat AD by
inhibiting enzyme that breaks it down (acetylcholinesterase)
Glutmate can be recycled via
glutmate transporters (reuptake) and it can be scavenged by glia
glia will scavenge glutamate and then
convert it to glutamine
glutmate is
excitatory. as is aspartate
glutamate foci of synthesis
ubiquitous. not specific foci
GABA can be recycled
via GABA transporters (reuptake)
scavenged by glia
GABA in the glia
modified to glutamine and released and then took back up into neuron
GABA is
inhibitory (as is glycine)
GABA foci of synthesis
ubiquitous. no specific foci of synthesis.
Catecholamines
3:
dopamine, norepinephrine and epinephrine
Catecholamines are derived from
tyrosine
rate limiting enzyme in catecholamine synthesis
tyrosine hydroxylase
Catecholamine synthesis path
dopamine-> NE (via DBH) to Epi (via PNMT)
dopamine synthesis site
cytoplasm
NE synthesis site
in vesicle (because DBH is bound to intravesicular membrane)
Epinephrine synthesis site
in cytoplasm. NE leaks out of vesicle and into cytoplasm where PNMT converts it to Epi
catecholamine reuptake
each has own transporter for reuptake.
no glial involement
reuptaken catecholamines
are repackaged into vesicles or degraded by MAO (monoamine oxidase) or catechol-O-methyltransferase (COMT)
High levels of DA found in its 4major pathways
Nigrostriatal (loss of DA Neurons linked to Parkinson’s disease)
Mesocortical
Mesolimbic (significant component of the Reward Pathway)
Tuberoinfundibular
High levels of NE are found in the
locus coeruleus (in pons)
Serotonin derived from
tryptophan
rate limiting enzyme in serotonin synthesis
tryptophan hydroxylase
serotonin pathways emanate from
raphe nuclei
serotonin synthesis occurs in
the cytoplasm
serotonin is packaged into vesicles via
a transporter
serotonin reuptake
by serotonin transporter.
Neuropeptides comprised of
opioid peptides (primarily B-endoprhin and enkephalins) and Substance P.
Neuropeptides mature..
as they migrate to terminal.
start out as pre-propeptides that are converted to propeptides, then the final mature NTs
Neuropeptide reuptake
doesn’t happen. primarily degraded by peptidases.
NO
Not stored in vesicles.
Not released in a calcium dependent manner.
Does not have a specific target (not like a classical NT does, which, when released from a neuron, has the ultimate destination of the postsynaptic cell, although the NT can also affect receptors on the cell from which it was released [these are called autoreceptors, something we did not discuss]).
Released from postsynaptic cell. It can exert effects within the cell where it’s made and/or it can diffuse and affect neighboring neurons, glia, etc. Migrates by diffusion. It is a retrograde messenger if it diffuses back to the pre-synaptic cell and affects the release of NT from that cell.
Affects nearby cells via cGMP coupled mechanisms.
Has role in vasodilation and memory.
Ach receptors
nicotinic (inotropic): Na in, K out
muscarinic: leads to Cl in, K out (hyper polarization)
Glutamate receptors
NMDA (ionotropic)
Kainate inotropic and AMPA (ionotropic): Na, in, K out
mGluR (metabotropic): modulate other receptors
Glutmate NMDA receptor
Calcium and NA in; K out
Glutamate binding site: glumatate must bind
glucose binding site: glycol must bind
Magnesium binding site (Mg must be displaced for Channel to open. for this to happen cell cannot be at resting or at hyper polarized membrane potential- must be sufficient depolarized)
GABA receptors
GABAa (ionotropic): chloride in
- GABA binding site: GABA must bind
- benzodiazepine binding site: inc frequency of opening
- Barbiturate binding site: inc Duration of opening
GABAb (metabotropic)
Glycine receptor
ionotoropic: chloride in
Dopamine receptor
metabotropic
Adnergic receptor
metabotropic. make neurons more excitable
