Neurotransmission and Pharmacology Flashcards
What does information transfer across a synapse require?
Release of neurotransmitter
Interaction of neurotransmitter with postsynaptic receptors
What 3 processes are neurones adapted to do?
Information reception
Integration
Rapid transfer (AP)
What does communication between cells require?
Neurotransmitter release
Describe the structure of a neurone.
Spines
Dendrites
Soma
Axon
Synaptic terminal
How many synapses do each neurone make?
several hundred or thousands
Where is neurotransmission restricted to?
the synapses (they are specialized structures)
How big is the gap of a synapse?
roughly 20-100nm
What are the 3 stages of synaptic transmission?
- biosynthesis, packaging and release of neurotransmitter
- receptor action
- inactivation
How do transmitters vary?
Enormous diversity in variety of transmitters and their receptors including Amino acids (e.g. glutamate, γ-aminobutyric acid [GABA], glycine [Gly]), Amines (e.g. noradrenaline [NA] and dopamine [DA]) and Neuropeptides (e.g. opioid peptides)
Vary in abundance from nM to mM CNS tissue concentrations
May mediate rapid (micros- ms) or slower effects (secs)
What are the essential features of synaptic transmission?
Restricted to specialised structures - the synapses
Calcium is essential - transmitter release requires an increase in intracellular Ca2+ (200 microM)
Transmission is fast - within ms
Synaptic vesicles (SVs) provide the source of neurotransmitter (4,000-10,000 molecules per SV)
What is transmitter release dependent on?
calcium dependent
and requires RAPID transduction
Describe the process of neurotransmitter release.
Membrane depolarisation-> Ca2+ channels open-> Ca2+ influx-> Vesicle fusion-> vesicle exocytosis-> transmitter release
What are the stages of the neurotransmitter vesicle in the pre-synaptic neurone?
Budding-> forms endosome->?
Budding->
Docking->
Priming->
Fusion->
Neurotransmitter release
How do rapid release rates occur?
Synaptic vesicles are filled with neurotransmitter (T) and docked in the synaptic zone
Special proteins on the vesicle and presynaptic membrane enable fusion & exocytosis
What is an example of a target for neurotoxins?
vesicular proteins
Give 2 examples of neurotoxins affecting vesicles and how they work?
Alpha latrotoxin (from spider)
- lots of stimulation
- promotes Ca2+ influx
- excess sweating
- too much neurotransmitter
- constant spasm
Botulinum toxin (C botulinum)
- most potent toxin in the world
- prevent neurotransmitter release= paralysis of skeletal muscle
What are the transmitter release requirements?
- Calcium-dependent (Ca2+)
- Transmitter-containing vesicles to be docked on the presynaptic membrane
- Protein complex formation between vesicle, membrane and cytoplasmic proteins to enable both vesicle docking and a rapid response to Ca2+ entry leading to membrane fusion and exocytosis
(ATP and vesicle recycling)
What is neurotransmitter action defined by?
receptor kinetics
What is the difference between ion channel-linked receptor and G-protein-coupled receptors?
Give examples of ion channel linked receptors and g-protein-coupled receptors.
Describe ion-channel linked receptors.
What causes excitatory postsynaptic potential?
Na+ entering the cell
What causes inhibitory postsynaptic potential?
Cl- entering the cell
What are the type of glutamate receptors?
AMPA and NMDA
Describe AMPA and NMDA receptors?
What happens in an excitatory Glu synapse?
What happens in an inhibitory GABA synapse?
What leads to seizures?
Abnormal cell firing leads to seizures associated with excess GLUTAMATE in the synapse
?Aetiology uncertain – Glutamine synthetase?
What is an EEG?
Electroencephalography (EEG) measures electrical activity in the brain
What converts glutamate to something else?
Glutamine synthetase to glutamine in glial cells
What is epilepsy?
One of the common neurological conditions affecting 50 million people worldwide
Characterised by recurrent seizures due to abnormal neuronal excitability
Despite advances in modulating seizure generation and propagation the disease can be disabling
25-30% don’t respond to treatment
What are symptoms of epilepsy?
Loss of consciousness
Weakness
Anxiety
Staring
Contracting and jerking of muscles
Confused speech
What is a possible treatment for epilepsy?
The synaptic properties of GABA may be modulated pharmacologically as an approach to treating epilepsy
How do you monitor seizures?
With EEG (electroencephalography)
excessive activation in the brain, associated with excess glutamate
