2.5: Neurotransmitters & pharmacology Flashcards
What is synaptic transmission?
Information transfer across synapse requiring release of neurotransmitters and their interaction with postsynaptic receptors
List 4 characteristics of synaptic transmission
Rapid timescale
Diversity
Plasticity
Learning and memory
4 basic structures of neurones
Dendrites
Soma
Axon
Synaptic terminal
Purpose of spines present on surface of dendrites
Protein molecules that increase the surface area for information reception
What neuronal structure integrates all information coming into a neurone
Soma (cell body)
3 steps that occur when a dendrite of one neurone receives an electrical impulse form another neurone
Information reception at dendrites
Integration (occurs at soma)
Rapid transfer (AP) - impulse passed along axon towards synaptic terminals
What type of neurotransmission occurs at the synapse
Chemical neurotransmission
What structures is neurotransmission restricted to?
Synapses
3 things synapse consists of
Presynaptic nerve ending/terminal
Gap(synaptic cleft) ~ 20-100nm
Postsynaptic regions (dendrite or cell soma)
3 stages of synaptic transmission
Biosynthesis, packaging and release of neurotransmitter stored in vesicles
Receptor action- activation of post-synaptic receptors
Inactivation - NT inactivated once it’s activated receptors on post synaptic terminal
3 types of molecules that can be neurotransmitters + examples
Amino acids - glutamate, gamma-aminobutyric acid (GABA)
Amines - noradrenaline and dopamine
Neuropeptices -opioid peptides
Single-most important excitatory neurotransmitter in the brain
Glutamate
Single-most important inhibitory neurotransmitter in the brain
GABA
Where is glycine most active (2)
Is glycine excitatory or inhibitory?
Spinal cord and brain stem
Inhibitory
2 methods by which neurotransmitters are returned to the pre-synaptic terminal
Re-uptake via protein transport channel
Enzymatic degradation within synaptic cleft
What is the source of neurotransmitter
Synaptic vesicles
Outline process of neurotransmitter release
Membrane depolarisation lead to opening of Ca2+ channels
Ca2+ influx leading to docking of synaptic vesicles onto pre-synaptic membrane
Neurotransmitter released by exocytosis in synaptic cleft
Vesicle buds off and recycles forming new vesicles that can be reused
2 things required for neurotransmitter release
Calcium influx
Rapid transduction
What type of proteins on the vesicles and presynaptic membrane enable fusion and exocytosis?
SNARE proteins (vesicular proteins e.g. synapsin)
Vesicular proteins are targets for
Neurotoxins (esp. those that interfere with NT release process)
What does alpha larotoxin (neurotoxin) do?
(From black widow spider)
Stimulate NT release until depletion of NT leading to muscular paralysis
Function of Zn2+ dependent endopeptidases
Inhibit transmitter release
What does tetanus toxin cause ?
What bacteria produce it
Spasms and paralysis as GABA and glycine inhibited
Produced by Clostridium tetani
What does botulinum toxin cause and how does this come about?
Flaccid paralysis - complete muscle relaxation
Cleaves peptide bonds of vesicular proteins leading to inactivation - docking, fusion, release of NT cannot occur
What bacteria produces botulinum toxin (one of most powerful toxins)
Clostridium botulinum
How can drug toxicity be measured
Minimum dosage required to kill a mouse
What repossessed do ion channel linked receptors mediate?
All fast excitatory and inhibitory transmission
What type of responses do G-protein coupled receptors mediate?
SLOWer than ion channel linked receptors
What can the effectors of the response generated by G-protein coupled receptors be?
Enzymes or ion channels
2 examples of responses where ion channel linked receptors are used
CNS - glutamate, GABA
NMJ - ACh at nicotinic receptors
Give examples of responses where G-protein coupled receptors are used
CNS and PNS - ACh at muscarinic receptors (heart)
Dopamine, noradrenaline, serotonin and neuropeptides
What does opening of Na+ channels via a glutamate molecule do to postsynaptic membrane potential
Increase for short time
repolarisation
What postsynaptic potential does an inhibitory NT (e.g GABA A) cause ?
IPSP ( inhibitory postsynaptic potential) caused by GABA A receptor —> Cl- influx
hyperpolarisation
2 types of ion-channel linked glutamate receptors and what they mediate
AMPA - FAST excitatory synapses, only Na+ permeable
NMDA - SLOW component of excitatory transmission, coincidence detectors which underline learning mechanisms - permeable to Na+ and Ca2+ (HIPPOCAMPUS high density )
Outline the process that occurs at an excitatory glutamate synapse
1) Glutamate synthesised from glucose via TCA cycle and transamination
2)Loaded into vesicles- released into synaptic cleft via exocytosis
Glutamate reversibly binds postsynaptic receptors (AMPA and NMDA)
3) Rapid uptake of glutamate by excitatory amino acid transporters (EAATs)
OR
4) Glutamate enzymatically modified by glutamine synthetase to glutamine in glial cells
What does an EEG (electroencephalogram) measure
Electrical activity in brain
Abnormal cell firing associated with excess glutamate leads to
Seizures
Spikes on EEG
What is epilepsy characterised by?
Recurrent seizures due to abnormal neuronal excitability
Process that occurs at an inhibitory GABA synapse
1) GABA synthesised (pre-synaptic terminal) by decarboxylation of glutamate by glutamic acid decarboxylase [GAD]
2) GABA Reversibly binds to post-synaptic receptors (Cl- channels open, influx leading to hyperpolarisation)
3) Rapid uptake of GABA by GABA transporters (GATs)
OR
4) GABA enzymatically modified by GABA-T (GABA transaminase) to succinic semialdehyde (glial cells and GABA nerve terminals)
6 drugs facilitating GABA transmission.
Barbiturates
Benzodiazepines
Steroids
Convulsants
Zn 2+
Ethanol
4 properties of drugs facilitating GABA transmission
Antiepileptic
Anxiolytic
Sedative
Muscle relaxant
How many subunits does the GABA A receptor have?
5 - pentameric
4 examples of neurotoxins
Alpha latrotoxin
Zn2+ dependent endopeptidases
Tetanus toxin (C tetani)
Botulinum toxin (C botulinum)
Two types of neurotransmitter receptors
Ion channel-linked receptors
G-protein-coupled receptors
Two types of ion channel linked receptors
GABA receptor - Na+
glutamate receptor - Cl-
