neurotransmitters Flashcards
neurotransmitters: define the components required for neurotransmitter release, explain the difference between excitatory and inhibitory transmission, identify mechanisms of termination of neurotransmitter action at the synapse, and explain the clinical application of synaptic modulation (for example GABA and epilepsy)
properties of synaptic transmission
rapid timescale (2ms), diversity, adaptability, plasticity, learning and memroy
3 stages of synpatic transmission pathway
transmitter released from 1st cell → synaptic activation of 2nd cell → signal integration and signal conduction by 2nd cell
pathway of action potential in neurone
dendrites on spines → soma → axon → nerve endings/terminals
what happens at dendrites
information reception
what happens in the soma
integration of signals
what happens in the axon
rapid transfer of action potential
what happens at nerve terminals
synapse onto next body using neurotransmitter release
main components of synapse
presynaptic nerve ending, synaptic cleft, postsynaptic region (dendrite/soma)
how large is the synaptic cleft
20-100nm
synaptic pathway process
action potential reaches presynaptic terminal → causes depolarisation → Na+ influx → K+ outflux → Ca2+ voltage-gated channels open → Ca2+ influx → synaptic vesicles containing neurotransmitters to fuse with membrane → neurotransmitters released by exocytosis → diffuse across synaptic cleft → bind to receptors on postsynaptic region → cause depolarisation → new action potential generated → neurotransmitters removed by transporter into cytosol → Na+/K+ balance restored by Na+/K+ ATPase pump
why are there lots of mitochondria in the presynaptic terminal
lots of energy required to produce and release neurotransmitters
is the synapse symmetrical or asymmetrical
asymmetrical
properties of neurotransmitters
enormous diversity in variety of transmitters and receptors, mediate or slow effects, vary in abundance
what makes up neurotransmitters
amino acids, amines, neuropeptides
examples of amino acid neurotransmitters
glutamate, GABA, glycine
properties of glutamate
most important and potent
what is GABA
major inhibitory transmitter in CNS
examples of amine neurotransmitters
noradrenaline, dopamine
example of neuropeptide neurotransmitters
opioid peptides
essential components of synaptic transmission
restricted to specialised asymmetric synapse, fast, Ca2+ influx essential, synaptic vesicles as source of neurotransmitter
how does rapid release occur
synaptic vesicles filled with neurotransmitter and docked in synaptic zone “primed” → Ca2+ influx activates Ca2+ sensor in protein complex → interaction between synaptic vesicle and synaptic membrane proteins allow rapid response → exocytosis → neurotransmitter endocytosis → restart
what do neurotoxins such as tetanus target
vesicular proteins
components required for neurotransmitter release
transmitter containing vesicles to be docked on presynaptic membrane, protein complex formation between vesicle, membrane and cytoplasmic proteins (enable docking and rapid response), ATP and vesicle recycling
receptors on postsynaptic membrane
ion channel and G-protein coupled
relative speed and function of ion channel receptors
fast; mediate all fast excitatory and inhibitory transmission
relative speed and function of G-protein coupled receptors
slow; activate effector: enzyme (e.g. adenyl cyclase) or channels (e.g. Ca2+)
ion channel receptor in CNS
GABA
ion channel receptor in NMJ (neuromuscular junction)
acetylcholine
G-protein coupled receptor in CNS and PNS
acetylchonline, dopamine, noradrenaline, 5HT, neuropeptides
properties of ion channel-linked receptors
rapid activation, diversity and rapid information flow, multiple subunit combinations for distinct functional properties
GLUR
excitation (Na+ influx - depolarise membrane)
GABAR
inhibitory (Cl- influx - hyperpolarise membrane)
where is GLUR usually found
dendrites
where is GABAR ususally found
soma so acts downstream of GLUR
excitatory receptor (e.g. GLUR)
depolarises membrane
inhibitory receptor (e.g. GABAR)
hyperpolarises membrane
glutamate receptors
AMPA and NMDA
AMPA receptor
Na+ influx; only acts on cell which has already been depolarised; majority of fast excitatory synapses
NMDA receptor
Na+ and Ca2+ influx; Ca2+ modifies recepor, activates protein synthesis which modifies synapse formation; slow component of excitatory transmission; serve as coincidence detectors which underlie learning mechanisms
excitatory synapse mediated by glutamate and inhibition
mediated by depolarising membrane; EAAT (transporter) takes glutamate into glial cell; conversion of glutamate to glutamine by glutamine synthetase
what does abnormal cell firing associated with excess glutamate in synapse lead to
epileptic seizures
epilepsy characterisation
recurrent seizures due to abnormal neuronal excitability
GABA structure vs glutamate structure
GABA is glutamate without COOH group; catalysed by glutamic acid decarboxylase
inhibitory synapse mediated by GABA and inhibition
mediated by hyperpolarising membrane; GAT (transporter) takes GABA into glial cell; conversion of GABA to succinate semialdehyde by GABA-T
treating epilepsy
drugs dampen down excitatory activity and target pentameric organisation of GABA, enhancing enhance transmission and influx of Cl- (e.g. increases frequency of Cl- channel opening)
