synapses and neurotransmitters Flashcards
(46 cards)
what is an electrical synapse?
an electrical synapse is where neurons are connected by connexin gap junctions that allow ions and therefore depolarisation (and repolarisation) to pass straight from one neuron to the other
experimentally how can you tell if a synapse is electrical?
fill one neuron with some dye and see if it passes to another (through gap junctions)
or uses electrodes to hyperpolarise/depolarise the first neuron and see if it’s passed along
use a mutation in the connexin to make it inactive and see if the signal is no longer transmitted
what experiment provided the first evidence for a chemical synapse?
the Landendorff experiment on the hear (donor heart stimulated, fluid collected - vagustoff which is acetylcholine, added to recipient heart with nerves removed)
chemical synapses use synaptic vesicles or dense-core granules, compare them
synaptic vesicles are clear and small, around half the size
synaptic vesicles use small molecule NTs whereas dense use peptide NTs
small vesicles get filled by transport proteins at the presynaptic terminal while dense are ‘one and done’, meaning they’re packaged at the golgi, so
aren’t recycled by endocytosis and refilled like synaptic vesicles
what are electrical synapses good for?
fast communication and synchronisation of neurons
how does transmission of an action potential from one neuron to the next work? (snares)
V snares on the vesicle bind with the T snares on the membrane, you’ve also got this protein called synaptotagmin which binds with the docking vesicles
influx of Ca2+ from voltage gated calcium channels
its synaptotagmin that has a conformational change when it binds to Ca2+, snares change too, forcing fusion of vesicle with membrane, NT diffuse across the synapse
what two ways can receptors in neurons work?
they can either cause ligand-gated ion channel to open, or activate a G protein via a GPCR that opens an ion channel
what are three ways NTs are removed?
- diffuse away
- taken up by transporters for recycling in neuron or glia
- destroyed by enzymes
compare electrical and chemical synapses
electrical - signals pass in both directions, chemical is just one direction
electrical - signals are passed directly and can only be attenuated (reduced), chemical signals can be completely transformed/amplified/modulated etc…
electrical are faster, < 0.3 ms, chemical are around 0.3 - 5 ms
in neuromuscular junctions, what happens if the motor neuron produces an action potential?
an action potential will always be produced in the muscle cells, they use ACh
how are NMJs specialised for fast and reliable transmission?
presynaptic has large number of ‘active’ zones
postsynaptic contains folds densely filled with receptors
these active zones and junction folds are very well aligned
how do we know synaptic vesicles are used?
experiments show voltages of uniform increases, because vesicles house the same amount of NT so you can only have like regular levels
are all synapses one to one?
no there are many different kinds, many to one, one to many etc…
what’s the criteria for a molecule to be classed as a neurotransmitter?
- present at the presynaptic terminal, you can check this with immunostaining for the molecule or the proteins involved in it’s production
- released in response to stimulation
- removal of the molecule stops stimulation
- acts on postsynaptic neuron
what types of neurotransmitters are there?
small molecules like amino acids/amines/modified amino acids/catecholamines - act on LGICs and GPCRs, clear vesicles
large molecules - proteins - dense core granules, only act on GPCRs
do NTs do the same thing every time?
no, they can have different effects on different cells and receptors
glutamate - what is it, what receptors does it effect, what are it’s general properties?
amino acid, so present in all neurons, uses clear vesicles, usually excitatory
effects 3 ionotropic receptors (named after drugs that work as agonists) AMPA, NMDA, kainate
effects
also works on metabotropic receptors, mGluRs, for example mGluR1, mGluR2 etc…
action is terminated by selective uptake into presynaptic terminals and glia
what do AMPA receptors do?
mediate fast excitatory transmission
binding of glutamate causes Na+ and K+ currents resulting in EPSP
what do NMDA receptors do?
they often co-exist with AMPA
they have a voltage-dependent Mg2+ block so they actually only open if the neuron is already depolarised, they’re a coincidence detector?
when open they let Ca2+ in leading to downstream signalling
what is GABA etc…?
its an amino acid not used to make proteins, its’s actually made from glutamate by removing the carboxyl group
activation is terminated by selective reuptake into PreST and glia
it is normally an inhibitory NT and is the most common inhibitory NT
what do GABA-A receptors do? explain why opening chloride channels causes hyperpolarisation in terms of Nernst potentials
they are ligand gated chloride channels
they produce IPSPs
Remember that the membrane potential is described by the Goldman equation, which shows that the membrane potential is influenced more by the ions for which the membrane is more permeable. For example, the resting potential is negative because the membrane is most permeable to K+, which has a very negative Nernst potential; the reason that opening Na+ channels depolarises the cell is that it weights the membrane potential more toward the Nernst potential of Na+, which is very positive. So, when you open a chloride channel, you should understand this conceptually as pushing the membrane potential closer to chloride’s Nernst potential. If you are above that, then you will get hyperpolarised
why is the right amount of GABA inhibition so important?
too much = coma/loss of consciousness
too little = siezures
how can GABA-A be modulated and include examples of how we use it?
using allosteric drugs that can bind to the receptor with GABA
examples include benzodiazepines like diazepam used to treat anxiety
barbiturates - sedatives and anti-convulsants
what do GABA-B receptors do?
they are metabotropic
they have diverse effects in different cells so can
1. open K+ channels - brings membrane closer to K+ equilibrium potential = inhibitory (prolonged)
2. close Ca2+
3. trigger second messengers like cAMP
they are often autoinhibitory - present on the presynaptic membrane
