Week 1- Neurotransmitters and Pharmacology Flashcards
What is synaptic transmission?
The release of neurotransmitters and their interaction with postsynaptic receptors
Describe the movement of signals down a neuron
- Information reception
- Integration of signal
- Rapid transmission
What type of transmission occurs in a synapse?
Chemical
How large is a synaptic cleft?
20-100nm
What are the 3 stages of synaptic transmission?
- Biosynthesis, packaging and release of neurotransmitter
- Receptor action
- Inactivation of neurotransmitter
What are some examples of neurotransmitters?
Amino acids, amines and neuropeptides
Describe the activation of a CNS synapse
- AP arrives and causes depolarisation
- Na+ influx
- K+ efflux
- Ca 2+ influx
- Exocytotic release of transmitter
- Transmitter has contact w post synaptic receptors
- Excitatory receptors causes Na+ influx triggering AP
- Once over, Na/K pump retains ionic balance
How much intracellular Ca 2+ is required?
200 micro m
How fast is transmission?
Very quick, within milliseconds
What is electromechanical transduction?
Ca2+ influx, vesicle fusion, vesicle exocytosis, transmitter release
How does neurotransmitter exocytosis work?
- Vesicles are pumped with transmitter
- Vesicles dock on presynaptic membrane (needs protein complex formation between vesicle, membrane and cytoplasmic proteins)
- Vesicles are primed
- Further Ca2+ influx causes fusion of vesicles w membrane
- Neurotransmitter is released
- Vesicles are pinched off via endocytosis and recycled
NOTE: vesicular proteins help with docking
What do neurotoxins target?
Vesicular proteins
Whats does neurotoxin alpha latrotoxin do?
Stimulates transmitter release to depletion
Whats does neurotoxin Zn 2+ dependant endopeptidases do?
Inhibit transmitter release
Whats does neurotoxin tetanus toxin C tetani do?
Causes paralysis
Whats does neurotoxin C botulinum do?
Cause flaccid paralysis
What are the 2 main classes of receptors that transmitters work on?
Ion channel receptors (fast excitatory and inhibitory responses i.e. milliseconds) and G protein coupled receptors (slow responses i.e. secs/mins, effectors may be enzymes or channels)
Describe ion channel receptors
They have multiple subunits which can be rearranged to give slightly different receptors with different functional properties
Describe the different between excitatory and inhibitory neurotransmitter receptors
Excitatory: membrane potential increases
Inhibitory: membrane potential decreases, reducing chances of going over threshold and generating APs
What are the 2 main glutamate receptors?
AMPA (fast excitatory synapses with rapid onset and offset, only allows sodium in) and NMDA (slow component of excitatory transmission, allow calcium and sodium in)
Describe the process occurring at an excitatory synapse
- Glutamate is synthesized from vous ose via TCA cycle and transamination
- Glutamate irreversibly binds post synaptic NMDA receptors (linked to ion channels)
- Rapid reuptake of glutamate by glial cells and presynaptically into nerve terminal where it can be reused
- Glutamate in glial cells is modified by glutamine synthetase to glutamine
What happens if there is an excessive amount of glutamate in synapses?
Usually GABA neurons bring excitation back down to a normal level after which there should be an increase in glutamine levels, if GABA fails to do so there is increased EEG activity which can increase seizures.
What is epilepsy?
Reccurent seizures due to abnormal neuronal excitability
Describe the GABA CNS synapse
- GABA formed by decarboxylation of glutamate by glutamic acid decarboxylase
- GABA reversible binds to post synaptic receptors
- Rapid reuptake of GABA by GABA transporters (GATs) into glial cells and presynaptic terminals
- In glial cells and presynaptic terminal GABA is converted to succinate semialdehyde by GABA transaminase
What is the structure of GABA receptor?
Has 5 subunits, drugs like benzodiazepines they enhance the receptor function.
