Synaptic Transmission Flashcards
synaptic transmission
electrical and chemical means that neuron use to signal between cells
neuron strcuture
4 regions: cell body, dendrites, axon, presynaptic termini (some have no dendrites others no axon most have all 4 though)
synapse
site of interaction between neurons in nervous system and target cells (transmits information from one neuron to next)
types synaptic contact that can occur
axosomatic, axodendritic, axoaxonic
axosomatic
axon terminating on cell soma of another neuron
axodenderitic
axon terminating on dendrite of another neuron
axoaxonic
axon terminates on another axon
presynaptic terminal
where upstream axon talks to downstream axon
types of synaptic transmission
electrical or chemical
synaptic structure
synapse involves apposition of presynaptic neuron and postsynaptic cell
- compartments of synapse: presynaptic terminal and postsynaptic site, synaptic cleft (chemical synapses only)
presynaptic termmial
where axondendritic synapses would be at end of axon
postsynaptic site
on dendrite opposite presynaptic terminal on receiving neuron
synaptic cleft
chemical synapses which separate presynaptic terminal and postsynaptic site
electrical synapses
- gap junctions
- present in heart and NS but mostly in heart most NS synapses are chemical
gap junction structure
multipliers of connexin protein which will form pore connecting cells -
- facilitate v fast transmission from one cell to next
what can be transmitted across gap junction
- action potential passively transmitted as current
- small molecules like cAMP and some neurotransmitters can also be passed from one cell to next
- gap jnxs can coordinate actions of number cells by electrically connecting them
chemical vs electrical synapses
electrical are faster but chemicals are more flexible
chemical synapse
gap between neuron bridged by release of chemical signal called neurotransmitter from presynaptic ternimal
neurotransmitter classical criteria
- classical neurotransmitters produced and stored (and therefore, can be localized) within a neuron
- When a neuron is stimulated (depolarized) a neurotransmitter is released by neuron. Release is dependent upon calcium
- Neurotransmitters must be inactivated
- When neurotransmitter released it acts upon post-synaptic receptor to cause biological effect
general categories neurotransmitters
small molecules (includes small molecules, monoamines, animo acids, catecholamines) and neuropeptides
small molecules
acetylcholine
animo acids
glutamate, GABA, Glycine
monoamines
serotonin, histamine
catecholamines
dopamine, norepinephrine, epinephrine
small molecules synthesized where transported how
enzymes that make them made in cell body then enzymes transported via slow axonal transport from cell body to presynaptic terminal; small molecule neurotransmitters synthesized from component parts at presynaptic terminal vesicles loaded at synaptic terminal where small molecules are made
what enzyme is made to use acetylcholine
choline acetyl transferase
neuropeptide synthesized wehre transported how
synthesized in cell body and packaged into vesicles here then transported by fast axonal transport
acetylcholine synthesized from
Acetyl-coA and choline by choline acetyltransferase in presynaptic terminal (these component parts aren’t sitting around presynaptic terminal they are sitting in vesicles docked at cleft waiting for release)
small molecule vs neuropeptide synthesis location
small molecules synthesized in presynatic terminal neuropeptide synthesis occurs in cell body
vesicles small molecules vs vesicles neuropeptides
vesicles containing small molecules can be docked at presynaptic terminal membrane and primed for release; vesicles containing neuropeptides are not docked
what is being moved in fast vs slow axonal transport
enzymes that make small molecules transported in slow axonal transport while neuropeptides are transported by fast axonal transport (neuropeptides are in vesicles when they’re being transported by fast axonal transport)
how is neurotransmitter released
Chemical synapses defined by presence of synaptic vesicles which are filled with neurotransmitter which gets released when vesicle fuses with terminal membrane
- action potential travels down axon and enters presynaptic terminal, voltage-gated calcium channels ion terminal open -> calcium flows into terminal -> calcium triggers fusion vesicle with membrane -> release neurotransmitter into cleft
vesicle fusion
dependent upon SNARE proteins and calcium
major v snares
synaptobrevin and synaptotagmin
major t snares
syntaxin and SNAP-25
what leads to fusion
interaction synaptobrevin with vesicle and syntaxin and SNAP-25 on terminal membrane brings each vesicle loaded with neurotransmitter in contact with release site, fusion and release occur if synaptotagmin binds calcium which requires voltage gated calcium channels open in terminal bc action potential
after neurotransmitter release
vesicles recycled using other proteins and refilled
toxins and vesicular fussion
natural toxins can:
prevent fusion of vesicles:
including tetanus toxin and botulinum toxins B, D, F G (cleave synaptobrevin) Botulinum toxins C1 and A/E (cleave syntaxin and SNAP-25), Conotoxins (block calcium channels necisary for vesicular release)
Medite fusion and release of vesicles even in absence of calcium
= Latrotoxin (black widow spider)
Cotransmitters
most neurons secrete more than one neurotransmitter providing additional flexibility and modulation of signal
- single actin potential produces transient rise in Ca2+ -> immediate release docked small molecule vesicles into cleft
- series action potentials in close temporal order -> prolonged elevated level calcium -> release vesicles containing neuropeptides (this allows strength of signal to be passed on to next neuron via use multiple transmitters)
neurotransmitter inactivation
- necessary because once signal passed onto post-synaptic cell must be turned off so cycle can begin again
- usually involves one or more of:
1. Removal by specific transport proteins
2. Diffusion
3. Degredation by transmitter-specific enzymes
acetylcholine inactivation
removal of acetylcholine in cleft mediated by acetylcholinesterase (enzyme) which produces acetate and choline
- choline diffusies away from cleft and recycled into presynaptic terminal by high-affinity choline transporters; this lets cell inactivate neurotransmitter and avoid having to synthesize new one
what happens once choline in terminal
choline acetyl transferase adds acetyl group to choline to regenerate acetylcholine which is imported into vesicles so cycle can repeat
glutamate inactivation
- no enzymes specifically for degradation glutamate in synaptic cleft
- diffusion and uptake via glutamate transporters remove glutamate and recycle it into presynaptic terminal
- glutamate can also be removed by glutamate transporters on glia surrounding synapse w/in glial cell glutamate converted -> glutamine -> released -> glutamine taken up into presynaptic terminal via transporters -> glutamine converted -> glutamate -> vesicles refilled with glutamate
agents affecting neurotransmitter inhibition
- acetylcholinesterase inhibitors (acetylcholinesterase mediates removal acetylcholinesterase in cleft)
- Ache inhibitors (nerve agents Sarin and VX1), Malathione
- Anti-Depressants affect neurotransmitter transporers
neurotransmitter receptor diversity
more varieties receptors than specific neurotransmitters; this variety provides additional ways of regulating information flow
2 general classes neurotransmitter receptors
- ionotropic
- metabotropic
inotropic receptors
- ligand gated ion channels
- direct effect
- binding of neurotransmitter -> opening channel -> ions flowing in or out of cell
Major neurotransmitter of neuromuscular junction
Ach
Ach
mediates fnx at neuromuscular junction via inotropic receptor (aka nicotinic Ach receptor)
What happens when Ach released by presynaptic motoneuron onto muscle fiber
Ach diffuses across cleft -> binds to inotropic Ach receptor -> opening channel -> depolarization (excitatory response) -> muscle fiber contraction
ligand gated channel Ach
Ligand gated channel opens when Ach binds this is non-selective cat ionic channel so when it opens cations like Na+ and K+ can flow through so Na+ influxes K+ effluxes -> cell depolarizing
** these channels are not activated by depolarization they are activated by binding of ligand**
GABA effect on target neurons ionotropic receptor
usually mediates inhibitory (hyperpolarization) effect on target neurons
How does GABA -> inhibition with ionotropic recceptor
GABA released by presynaptic neuron onto post synaptic neuron -> binds GABA specific ionotropic receptor ->channels open allowing chloride to enter cell -> inhibition
Metabotropic receptors
- G protein coupled receptors
- indirect effect
- neurotransmitter binds -> activation effector protein class (G proteins) -> activate variety other intracellular effects
- post synaptic effects can take longer than inotropic receptors but changes an last longer and this process can amplify signal
Ach effect on heart
- due to metabotropic acetylcholine receptor (Ach receptor)
- slows down heart rate
metabotropic acetylcholine receptor in heart aka
muscarinic Ach receptors
ionophore acetylcholine receptor smooth muscle aka
nicotinic Ach receptor
how does Ach effect heart steps
- Bind Ach to metallic receptor -> activation G protein complex
- beta-gamma subunit Gprotein activates G-protein inward rectifying potassium channel (GIRK) (specfilzied form of K+ channel)
- openning channel -> efflux K+ -> inhibitory post-synaptic potential
ALSO
- binding Ach to muscarinic receptor -> affect L-type Ca2+ channels through alpha (Gi) subunit which has additional inhibitory effect
Other metabotropic Ach receptors
- couple to different G-protein (Gq)
- ex. smooth muscle: release Ach by parasympathetic neurons -> Ach binds receptor -> activation phospholipase C -> release Ca2+ -> muscle contraction
Synapses/ neuron
individual neuron can have MANY synapses (in brain can have 1000s -> 100,000s)
- synapses are from neighboring neurons
- can be inhibitory, excitatory, modulatory
- neurons have to integrate varied synaptic inputs and in turn produce action potential that influences other neurons
dxs affecting synaptic transmission
- myasthenia gravis
- storage dx
- LEMs
- Epilepsy
- ALS
drugs affecting synaptic transmission
- anti-psycotics
- anti-depressants
- barbiturates
- all affect receptors/ enzymes/ transporters involved in transmission; many drugs bing GABA receptor
epilepsy
loss inhibitory control in brain -> inappropriate excitation by gluatmate
equinte motoneuron dx
vet equivalent ALS; influenced by distribution glutamate transporters in glial cells, affects slow axonal transport
Myastenia Gravis
body attacks nicotinic Ach receptors; vet med correlate paraneoplatsic syndrome (thymoma -> autoimmune response)
storage dx
affects neotramistter synthesis and release
LEMs
produces autoimmune response against voltage-sensitive Ca2+ channels needed for vesicle fusion
propagation of information in NS one way or two ways
it is two ways there is feedback
autoreceptors
- autoreceptors for released neurotransmitters often on presynaptic terminal as well as postsynaptic cells
- these provide feedback to regulate amount of secreted enurotransmitter
metabotropic glutamte receptors expressed on
presynaptic terminals and postsynaptic cells
effect metabotropic glutamate receptors on presynaptic terminals
- sense secreted amounts glutamate present in cleft
- if levels too high activate autorceptors -> produce second messengers -> affect Ca2+ channels (reduce calcium input into terminal) or K+ channels (increasing repolarization following an action potential) via phosphorylation (both of these actions -> reduced amount secreted glutamate)
- mGLuR’s also expressed on postsynaptic cells
