synapses and neurotransmitters Flashcards
electrical synapses
gap junctions to allow current to pass directly between neurons
cytoplasm becomes continuous through connexons (made of connexins)
large molecules e.g. proteins cannot get through
depolarisations and hyperpolarisations can be transmitted
very fast
chemical synapses
neurotransmitters are packed in vesicles
2 types of vesicle:
synaptic vesicle = small, small molecule neurotransmitters, transporter proteins fill the vesicles, recycled by endocytosis
dense-core secretory granules = large, peptide neurotransmitters, filled by ER and Golgi, used once and not reused
Ca2+ influx causes vesicles to be released into synapse
SNAREs
specialised proteins on vesicle membrane (v-SNAREs) and axon membrane (t-SNAREs)
synaptotagmin underwent confirmational change when Ca2+ binds to it
v and t SNAREs bind to each other and zip together to force vesicle and plasma membrane to fuse
e.g. Botox works by paralysing SNAREs so neurons cannot communicate
ionotropic vs metabotropic receptors
ionotropic = ligand-gated ion channels
directly depolarise or hyperpolarise postsynaptic cell
confirmational change causes channel to open when bound to
metabotropic = G-protein-coupled receptors
more complex effects - confirmational change triggered which activates G-protein and other downstream effects
electrical vs chemical synapses
electrical = both directions, direct signal, fast
chemical = one direction, signals can be transformed (amplified, inverted etc), slower
neuromuscular junction
acetylcholinergic synapses
presynaptic = many active zones
postsynaptic (motor end plate) = has junctional folds (densely filled with NTs) - precisely aligned with active zones
2 type of neurotransmitter
small molecules:
amino acids - GABA (modified amino acids)
amines - 5-HT, DA, acetylcholine, epinephrine
stored in synaptic vesicles
bind to ligand-gated ion channels or G-protein coupled receptors
large molecules:
proteins - smaller proteins
stored in secretory granules
only bind to G-protein coupled receptors
neurons usually only release one of these types
often peptide-releasing neurons also release a small molecule co-transmitter
glutamate - what is it
most common excitatory transmitter in CNS
amino acid - in all neurons
3 ionotropic glutamate receptor subtypes - based on drugs which act as selective agonists
- AMPA, NMDA, Kainate
action is terminated by selective uptake into presynaptic terminals
glutamate - AMPA receptors
mediate fast excitatory transmission
glutamate binding to AMPA triggers Na+ and K+ currents, resulting in EPSP (Na+ in, K+ out)
glutamate - NMDA receptor
often coexist with AMPA receptors
voltage dependent - blocked by Mg2+ - open when neuron is already depolarised
let in Ca2+ and Na+ and K+ out
downstream signalling) from Ca2+
coincidence detector - neuron is activated right after it was already activated - important for learning
glutamate - ionotropic vs metabotropic receptors
ionotropic:
4 subunits form a gated ion channel
e.g. AMPAR, NMDAR
fast (msec)
metabotropic:
G-protein coupled receptor, then downstream signalling cascade
e.g. mGluR1, mGluR2 etc
can allow glutamate to sometimes be inhibitory e.g. in retina
slow (sec-min)
GABA - synthesis, termination
amino acid (doesn’t synthesise proteins)
synthesised from glutamate by glutamic acid decarboxylase
terminate action by selective uptake into presynaptic terminals and glia
GABA - what is it, what it does
most common inhibitory transmitter in CNS
produces IPSPs (inhibitory postsynaptic potentials) via GABA-gated chloride channels (GABAa receptors) — WHEN membrane potential (Vm) is above chloride’s Nernst potential
channels allow Cl- into neuron from synapse
inhibition of GABA – right amount is critical
– too much = coma/loose consciousness
– too little - seizures
GABA - modulation of GABAa receptors
other chemical can bind to GABAa receptor and modulate response to GABA binding
these chemicals have no effects without GABA binding (allosteric):
- ethanol
- benzodiazepine (e.g. diazepam for anxiety)
- barbiturate - sedative and anti-convulsant
- neurosteroids - metabolites of steroid hormones e.g. progesterone
GABA - GABAb receptors
GPCRs (similar to mGluR (glutamate)
act differently in different cells
can open K+ channels, close Ca2+ channels, trigger secondary messengers e.g. cAMP
often presynaptic or autoinhibitory
