Neurotransmitters Flashcards
What is the basic structure of the of the neurone?
axon- rapid signal transfer dendrites- information comes here via spines on dendrites soma- where all different signals coming into the cell integrate synaptic terminal
What biological molecules are common neurotransmitter?
Amino Acids e.g. glutamate Amine e.g. noradrenaline neuropeptides e.g. opiod peptides
What happens to neurons when they receive multiple signals?
all the signals are integrated to produce diverse functional responses
Describe the activation of the CNS synapse?
Action potential causes VGCC tho open = influx down concentration gradient into the pre-syaptic neuron. This causes the transmitter to be released and diffuse across cleft and then bind to receptors on post synaptic neuron. If they are excitary neurotransmitters this causes VGSC to open there Na+ influx into post synaptic neurone and can cause action potential.
What does the sodium potassium pump do?
Causes the resting membrane potential to be reset after action potential has occured in pre-synaptic neuron
How are neurotransmitters released from the vesicles?
1- membrane depolarised 2-Ca2+ channels open 3- Ca2+ influx into presynaptic neurone 4- This causes vesicles be docked(move onto memebrane) primed, and then to fuse with membrane 5-vesicle exocytosis 6-transmitter release
What is electrochemical transduction?
For the process of neurotransmitter release it includes everything for the Calcium influx to the neurotransmitter being released
How does the rapid release process occur?
1- vesicles are filled with neurotransmitter due to pump in vesicle membrane 2- vesicle is the docked in the SYNAPTIC ZONE 3- Vesicles and pre-synaptic membrane have proteins put on surface (vesicular proteins), enabling fusion and exocytosis
What do neurotoxins do?
They target vesicular proteins
Give examples of some neurotoxins?
Alpha latrotoxin (from black widow spiders) stimulates transmitter release to depletion Zn2+ dependent endopeptidases inhibit transmitter release Tetanus toxin C tetani causes paralysis Botilinum toxin C botulinum causes flaccid paralysis and food poisoning
What are the requirements for transmitter release?
Calcium influx Transmitter containing vesicles must be docked on the presynaptic membrane Protein complex formation between the vesicle membrane and the cytoplasmic proteins to enable both vesicle docking and a rapid response to the Ca2+ entry leading to membrane fusion and exocytosis ATP needed Vesicles must be recycled so they can be reused
What are the 2 main classes of receptors?
Ion channel receptor - Fast response (miliseconds) - mediate all fast excitatory and inhibitory transmission response(secs G-protein coupled receptors- slow (secs and minutes)
Examples of G-protein coupled receptors ?
Muscarinic receptors- type of ACh recepetor on the heart
What do inhibitory and excitatory receptors do?
Excitatory- depolarisation Inhibitory-hyperpolarisation
What are the 2 main types of glutamate receptors?
AMPA receptors: -Linked to Na+ channels so that when glutamate binds VGSC open causing influx into post synaptic neurone -Majority are fast excitatory synapses -Have a rapid onset so they open and close very quickly and desensitise quickly NMDA receptors: -Slow component of excitatory transmission -LINKED TO Na+/Ca2+ channels so allow both to pass into the cell -serve as coincidence detectors as they are only activated due to another input elsewhere on cell. The NMDA receptors detect this signal and became activated as a result. -underlie learning mechanisms
describe glutamate synapse?
1- glutamate synthesised from glucose via TCA Cycle and transamination 2- when it is released into synaptic cleft it is reversibly binded to the post synaptic receptors (linked to ion channels) 3- glutamate inactivated by being taken up by GLIAL CELLS or uptaken by excitatory amino acid transporters (EAATs) in pre-synaptic neuron to be used again 4- the glutamate taken up into the glial cells is modified by the enzyme glutamine sythetase and glutamate is broken down into glutamine (inactivated)
What happens if there’s an excessive amount of glutamate in synapses?
If GABA doesnt kick in this leads to increased electrical activity in the brain=increased abnormal cell firing which can lead to seizures e.g those seen in epilepsy
What does GABA do?
counteracts glutamate to bring excitation levels down to a normal amount
What percentage of people with epilepsy don’t respond well to any of the drugs used to treat it?
25-30%
Describe what happens at a GABA synapse?
1- GABA is formed by decarboxylation of glutamate by enzyme Glutamic acid decarboxylase (GAD) 2- GABA is released due to influx of calcium ions into per synaptic neuron and then it binds to post synaptic receptors linked to ion channels on the post synaptic neuron. 3- GABA is inhibitory so when it binds it cause influx of chloride ions into the post synaptic neuron which prevents action potential 4-Rapid uptake of GABA by GABA transporters and it is enzymatically modified by GABA transaminase to succinate semialdehyde in glial cells. Both these methods = GABA inactivated
What is the structure of a GABA receptor?
Pentameric organisation and pharmacologically important binding domains e.g. barbituates and benzodiazepines bind to certain domains to enhance the activity of GABA 5 SubunitsGABA binds to the beta subunit
which drugs facilitate GABA transmission?
Antiepileptic Anxiolytic Sedatve Muscle relaxant
